Complex magnetic orders in small cobalt-benzene molecules.

Organometallic clusters based on transition metal atoms are interesting because of their possible applications in spintronics and quantum information processing. In addition to the enhanced magnetism at the nanoscale, the organic ligands may provide a natural shield against unwanted magnetic interactions with the matrices required for applications. Here we show that the organic ligands may lead to non-collinear magnetic order as well as the expected quenching of the magnetic moments. We use different density functional theory (DFT) methods to study the experimentally relevant three cobalt atoms surrounded by benzene rings (Co3Bz3). We found that the benzene rings induce a ground state with non-collinear magnetization, with the magnetic moments localized on the cobalt centers and lying on the plane formed by the three cobalt atoms. We further analyze the magnetism of such a cluster using an anisotropic Heisenberg model where the involved parameters are obtained by a comparison with the DFT results. These results may also explain the recent observation of the null magnetic moment of Co3Bz3+. Moreover, we propose an additional experimental verification based on electron paramagnetic resonance.

Comienzo del hábito tabáquico en la adolescencia y factores relacionados / Beginning smoking habit in adolescence and related factors

Estudio: Estudio descriptivo del consumo de tabaco en la adolescencia, que forma parte de un estudio más amplio sobre un estilo de vida saludable en la adolescencia temprana e intermedia. Personas y métodos. Profesores de educación física estudiaron a 1.112 adolescentes de 10 a 17 años de edad de los centros educativos mediante una encuesta de hábitos saludables y pruebas objetivas antropométricas y de condición física. Resultados. El 9% (IC-95%: 7,4% a 10,8%) de los adolescentes han fumado alguna vez, solo el 4,7% cuando no fuma ninguno de sus padres, el 12,6% cuando solo fuma uno de ellos y el 15,4% (IC-95%: 10,7% a 21,8%) cuando fuman ambos padres. El contacto con el tabaco empieza al inicio de la adolescencia, va aumentando hasta el 40,9% en los varones de 17 años y el 50,0% en las mujeres de igual edad. Las mujeres empiezan algo más tarde (13,8 años, IC-95%: 13,3 a 14,3) que los varones (12,7 años, IC-95%: 11,8 a 13,6), pero fuman más (5,1 cig/día, DE = 2,6) que los varones (4,4 cig/día, DE = 2,9). Actualmente fuma el 7,7% (IC-95%: 6,3% a 9,5%), unos ocasionalmente y otros habitualmente, con un consumo medio de 4,7 (DE = 2,74) cigarrillos diarios, dedicando las mujeres una media de 7,3 euros/sem (DE = 4,56) mientras que los varones solo 6,1 euros/sem (DE = 5,15). El 65,1% de los adolescentes piensan que el tabaco limita su actividad física, aunque no se evidencia en las pruebas de condición física, excepto en la prueba de course-navette en la que los varones fumadores rinden menos. Los fumadores duermen significativamente menos que los no fumadores (casi una hora menos los días laborables). Los fumadores valoran peor su satisfacción corporal, tanto los chicos (p = 0,013) como las chicas (p < 0,001). Otro hallazgo en este estudio es el distinto patrón en el test EnKid de alimentación sana, en el que los fumadores toman más bollería industrial, más alcohol, más comidas en fast-food y más chucherías, mientras que los no fumadores desayunan, desayunan un lácteo y un cereal, toman frutas a diario y toman verduras. No se observó asociación entre el estado nutricional y el hábito tabáquico y sí con el hábitat urbano. Conclusiones. El hábito tabáquico empieza en la primera etapa de la adolescencia, se consolida en la etapa intermedia y se caracteriza por su mayor predominio en las mujeres. Dicho hábito se asocia con dormir menos y cambios hacia una alimentación menos saludable y con una menor resistencia en las pruebas anaerobias en los varones

Aims: To analyze tobacco consumption, by age and sex, in primary and secondary school adolescents in Cantabria. Methodology. A cross-sectional study was carried out, analyzing a sample of 1,112 adolescents: 574 (51.6%) were men and 538 (48.4%) were women, aged between 10 and 17, attending 16 different primary and secondary education public centres in Cantabria, by means of a health habit questionnaire, objective anthropometric and physical condition trials. Results. 9% of adolescents from 10 to 17 years old have smoked sometime; only 4.7% of them do it when their parents are non-smokers, but this percentage rises to 12.6% when one of the two parents is a smoker and to 15.4% when both parents are smokers. The first contact with tobacco is at the beginning of adolescence and it is increases to 40.9% in 17 years old males and to 50.0% in females of the same age. The 7.7% of adolescents are current smokers, some of them are occasional users, but others are frequent users with an average consumption of 4.7 cigarettes per day. This consumption means an average expense of 7.3 euros per week in females and 6.1 euros in males. 65% of adolescents think tobacco limit their physical activity. Smokers sleep less than non-smokers; moreover, those have a worse valuation of their self-image. Finally, smokers eat more factory-produced cakes, rolls and buns, fast food and sweet candy, and consume more alcohol than non-smokers. Conclusions. The tobacco habit begins in the first stage of adolescence. It is consolidated at the intermediate stage and it is characterized by its greater predominance in females. This habit is associated with fewer hours of sleep and with changes towards a less healthy nutrition and less anaerobic trials resistance in males

Prácticas alimentarias de los adolescentes de Cantabria / Eating practices of adolescents of Cantabria

Objetivo: Analizar determinadas prácticas alimentarias en adolescentes escolarizados en centros de educación pública de Cantabria, participantes en el Proyecto 'Promoción de Hábitos Saludables en Adolescentes desde el Ámbito Educativo'. Sujetos: Se realizó un estudio transversal, analizando una muestra de 1.101 adolescentes: 568 (51,6%) varones y 533 (48,4%) mujeres, de edades comprendidas entre los 10 y los 17 años, escolarizados en dieciséis centros de enseñanza primaria y secundaria, mediante un cuestionario autocumplimentado. Resultados: Los adolescentes suelen realizar entre cuatro (41,5%) y cinco (31,6%) ingestas diarias. Durante los días de colegio, el 34% emplea entre diez y quince minutos en desayunar, y entre 30 y 35 minutos en comer (33,5%) y cenar (23%). Un elevado porcentaje (49,4%) de adolescentes desayunaba en soledad durante los días lectivos. Las principales ingestas alimenticias se realizan en el hogar. Las bebidas no alcohólicas (53,6%) y los dulces (42%) son los principales destinos de su dinero de bolsillo. En la casi totalidad de los hogares, es la madre la que se encarga de la compra de los alimentos, de la preparación de las comidas y de decidir tanto el almuerzo como la merienda. La pizza (72,6%) y las patatas fritas (70,8%) son los alimentos considerados más ricos entre los analizados, mientras que el perrito caliente (49,4%) y la hamburguesa (48,5%) son considerados como los menos sanos. El 58,6% de los encuestados cena viendo la televisión. Conclusión: En el estudio del comportamiento alimentario es necesario analizar la influencia de otros factores que, en muchas ocasiones, están detrás de las recomendaciones dietéticas y que casi siempre son ignorados. Prácticas alimentarias como las analizadas en el presente estudio, permiten, cuando estas se desarrollan de forma adecuada, una mejora sustancial en la salud alimentaria y nutricional de las personas

Objetive: To analyse some food practices, by age and sex, in primary and secondary schools adolescents in Cantabria, who are participating in the "Adolescents Health Habits Promotion since Education field" project. Methodology: A cross-sectional study was carried out, analysing a sample of 1101 adolescents: 568 (51.6%) were men and 533 (48.4%) were women, aged between 12 and 17, attending 16 different primary and secondary education centers in Cantabria, by means of questionnaire. Results: Adolescents usually eats between 4 and 5 times a day. They use between 10 to 15 minutes in having breakfast, between 30 to 35 minutes in having lunch and dinner on school days. A high percentage have breakfast alone on school days. The main eats were carried on at home. Soft drinks and sweet are the main purchase with their pocket money. Almost always, the mother is charged of buying the foods, preparing the meals and decide the morning and the afternoon snacks. Pizza and fried potatoes are considerated as most taste, whereas hot dog and hamburger are considerated as less healthy. The 58.6% of adolescents having dinner watching television. Conclusions: In the food behavior study, it is necessary to analyse the influence of other factors which, in many occasions, are behind of dietetic recommendations and the almost always are ignored. Food practices as we have analysed permit, when these are carry out in a right way, an important improve in the people nutritional health

[Assessment of nutritional risk among in-school adolescents from Cantabria]. / Evaluación del riesgo nutricional de los adolescentes escolarizados en Cantabria.

OBJECTIVE: To analyse nutritional risk, by age and sex, among primary and secondary education adolescents from Cantabria. METHODOLOGY: a cross-sectional study was carried out, analysing a sample of 1101 adolescents: 568 (51.6%) were men and 533 (48.4%) were women, aged 12 to 17, attending 16 different primary and secondary education centres in Cantabria, by means of a Krece Plus questionnaire. RESULTS: A high percentage of adolescents with a high nutritional risk (35%) can be observed. Men show a high nutritional risk slightly higher than women (37.8% male vs 32.1% female). Moreover, the high nutritional risk experiences a notable increase as young people get older. Significant statistical differences can be seen both in male and female groups, and as a global group. In all three cases, the nutritional risk distribution in the youngest group is very similar (35.2-35.8% in male, 27.9-29.7% in female, 31.7-32.7% in the global group); whereas in elder adolescents, those values are practically doubled (57.1% in male, 69.0% in female, y 62.2% in the global group). CONCLUSIONS: Results are alarming mainly given the high percentage of adolescents with a high nutritional risk. Men and older adolescents are the groups in which high nutritional risk is more evident.

Objetivo: Evaluar el riesgo nutricional, por edad y sexo, que presentan los adolescentes escolarizados en la Comunidad Autónoma de Cantabria. Sujetos: Se realizó un estudio transversal, analizando una muestra de 1101 adolescentes, de los que 51,6% eran varones y 48,4% fueron mujeres de edades comprendidas entre los 10 y los 17 años, escolarizados en centros de enseñanza pública, mediante el cuestionario Krece Plus. Resultados: Se observa un elevado porcentaje de adolescentes que presentan un riesgo nutricional elevado (35%). Los varones presentan un riesgo nutricional alto en un porcentaje ligeramente superior a las mujeres (37,8 % vs 32,1%). Además, el riesgo nutricional alto sufre un notable incremento a medida que la edad de los jóvenes aumenta. Se aprecian diferencias estadísticamente significativas tanto en los grupos de edad de los varones (p = 0,024), de las mujeres (p < 0,001) como en el grupo global (p = 0,001). En los tres casos, la distribución del riego nutricional en los grupos de menor edad es muy similar (entre 35,2 y 35,8% en los h, entre 27,9 y 29,7% en las m, y entre 31,7 y 32,7% en el grupo total). Mientras que en el grupo de mayor edad estos valores prácticamente se duplican (57,1% en los h, 69,0% en las m, y 62,2 % en el grupo total). Conclusión: Los resultados obtenidos muestran una realidad preocupante debido, principalmente, al elevado porcentaje de adolescentes que presentan un riesgo nutricional elevado. Siendo los varones y los adolescentes de mayor edad los sectores en los que este riesgo nutricional elevado es superior.

Evaluación del riesgo nutricional de los adolescentes escolarizados en Cantabria / Assessment of nutritional risk among in-school adolescents from Cantabria

Objetivo: Evaluar el riesgo nutricional, por edad y sexo, que presentan los adolescentes escolarizados en la Comunidad Autónoma de Cantabria. Sujetos: Se realizó un estudio transversal, analizando una muestra de 1101 adolescentes, de los que 51,6% eran varones y 48,4% fueron mujeres de edades comprendidas entre los 10 y los 17 años, escolarizados en centros de enseñanza pública, mediante el cuestionario Krece Plus. Resultados: Se observa un elevado porcentaje de adolescentes que presentan un riesgo nutricional elevado(35%). Los varones presentan un riesgo nutricional alto en un porcentaje ligeramente superior a las mujeres (37,8% vs 32,1%). Además, el riesgo nutricional alto sufre un notable incremento a medida que la edad de los jóvenes aumenta. Se aprecian diferencias estadísticamente significativas tanto en los grupos de edad de los varones (p =0,024), de las mujeres (p < 0,001) como en el grupo global(p = 0,001). En los tres casos, la distribución del riego nutricional en los grupos de menor edad es muy similar(entre 35,2 y 35,8% en los h, entre 27,9 y 29,7% en las m, y entre 31,7 y 32,7% en el grupo total). Mientras que en el grupo de mayor edad estos valores prácticamente se duplican (57,1% en los h, 69,0% en las m, y 62,2 % en el grupo total).Conclusión: Los resultados obtenidos muestran una realidad preocupante debido, principalmente, al elevado porcentaje de adolescentes que presentan un riesgo nutricional elevado. Siendo los varones y los adolescentes de mayor edad los sectores en los que este riesgo nutricional elevado es superior (AU)

Objective: To analyse nutritional risk, by age and sex, among primary and secondary education adolescents from Cantabria. Methodology: a cross-sectional study was carried out, analysing a sample of 1101 adolescents: 568 (51.6%) were men and 533 (48.4%) were women, aged 12 to 17,attending 16 different primary and secondary education centres in Cantabria, by means of a Krece Plus questionnaire. Results: A high percentage of adolescents with a high nutritional risk (35%) can be observed. Men show a high nutritional risk slightly higher than women (37.8% h vs32.1% m). Moreover, the high nutritional risk experiences a notable increase as young people get older. Significant statistical differences can be seen both in male and female groups, and as a global group. In all three cases, the nutritional risk distribution in the youngest group is very similar (35.2-35.8% in h, 27.9-29.7% in m, 31.7-32.7% in the global group); whereas in elder adolescents, those values are practically doubled (57.1% in h, 69.0% in m, y62.2% in the global group).Conclusions: Results are alarming mainly given the high percentage of adolescents with a high nutritional risk. Men and older adolescents are the groups in which high nutritional risk is more evident (AU)

Autoimagen en las dos primeras fases de la adolescencia y factores ralacionados / Self-image in two first stages of the adolescence and related factors

Se trata de la descripción de la imagen corporal en un amplio grupo de alumnos escolarizados en Cantabria (n=1179 adolescentes), de 10 a 17 años de edad (adolescencia temprana e intermedia) dentro de un estudio más amplio encaminado a evidenciar un estilo de vida saludable en estos adolescentes, llevado a cabo por profesores de universidad y profesores de educación física de los centros educativos. Los principales hallazgos consisten en que los adolescentes tienen, en general, una buena imagen de sí mismos y, aunque no reconocen la elevada prevalencia de sobrepeso y obesidad, desean adelgazar y el grado de satisfacción que tienen con su imagen corporal va empeorando conforme avanza la adolescencia, significativamente más en las del sexo femenino. Esta insatisfacción debe ser tenida en cuenta en el abordaje de los adolescentes con obesidad

This paper describes the body image in an large group of students from Cantabria, Spain (n=1179 adolescents), 10 to 17 years old (early and intermediate adolescence) within a ampler study directed to demonstrate a healthful lifestyle in these adolescents carried out by professors of university and professors of physical education of the educative centers. The main findings are that the adolescents have, generally, a good self-image, and although they do not recognize the high prevalence of overweight and obesity, they wish to become thin and the satisfaction degree that they have with his body image is getting worse as advances the adolescence, significantly more in girls. This dissatisfaction must be considered in the boarding of the adolescents with obesity

Effective analysis of rotundone at below-threshold levels in red and white wines using solid-phase microextraction gas chromatography/tandem mass spectrometry.

Rotundone is an oxygenated sesquiterpene belonging to the family of guaianes, giving the 'peppery' aroma to white and black pepper and to red wines. Here we describe a novel, convenient protocol for the synthesis of rotundone, starting from a commercially available compound and requiring only two reaction steps, and an improved, faster method of GC separation (30 min) with selective quantisation of rotundone using tandem mass spectrometry in multiple reaction monitoring (MRM) mode with d(5)-rotundone as internal standard. With limits of detection (LODs) of 1.5 ng/L in white wine and 2.0 ng/L in red wine, intraday repeatability CV values of 6% and 5% at 50 ng/L and 500 ng/L and interday repeatability CV values of 13% and 6% at 50 ng/L and 500 ng/L, respectively, the improved protocol provides the desired sensitivity and selectivity for routine analysis of rotundone in both white and red wines. Initial application of this method highlighted the presence of unexpectedly high concentrations of rotundone, thus explaining the origin of the distinctive peppery aroma in Schioppettino and Vespolina red wines and in Gruener Veltliner white wines.

In vitro and in vivo metabolism of a novel cannabinoid-1 receptor inverse agonist, taranabant, in rats and monkeys.

The metabolism and excretion of taranabant (MK-0364, N-[(1S,2S)-3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2{[5-(trifluoromethyl)pyridine-2-yl]oxy}propanamide), a potent cannabinoid-1 receptor inverse agonist, were evaluated in rats and rhesus monkeys. Following administration of [¹4C]taranabant, the majority of the radioactivity was excreted within 72 h. In both rats and rhesus monkeys, taranabant was eliminated primarily via oxidative metabolism, followed by excretion of metabolites into bile. Major pathways of metabolism that were common to rats and rhesus monkeys included hydroxylation at the benzylic carbon adjacent to the cyanophenyl ring to form a biologically active circulating metabolite M1, and oxidation of one of the two geminal methyl groups of taranabant or M1 to the corresponding diastereomeric carboxylic acids. Oxidation of the cyanophenyl ring, followed by conjugation with glutathione or glucuronic acid, was a major pathway of metabolism only in the rat and was not detected in the rhesus monkey. Metabolism profiles of taranabant in liver microsomes in vitro were qualitatively similar in rats, rhesus monkeys and humans and included formation of M1 and oxidation of taranabant or M1 to the corresponding carboxylic acids via oxidation of a geminal methyl group. In human liver microsomes, metabolism of taranabant was mediated primarily by CYP3A4.

Importance of mechanistic drug metabolism studies in support of drug discovery: A case study with an N -sulfonylated dipeptide VLA-4 antagonist in rats.

N-(1-(3,5-dichlorobenzenesulfonyl)-2S-methyl-azetidine-2-carbonyl)-L-4-(2',6'-dimethoxyphenyl)phenylalanine (1) is a potent antagonist of the very late activating (VLA) antigen-4. During initial screening, 1 exhibited an apparent plasma clearance (CL) of 227 ml min(-1) kg(-1) in Sprague-Dawley rats following an intravenous bolus dose formulated in an aqueous solution containing 40% polyethylene glycol. Such a high CL value led to speculation that the elimination of compound 1 involved extra-hepatic tissues. However, the apparent plasma CL was reduced to 97 ml in(-1) kg(-1) when a 2-min time point was added to sample collections, and further decreased to 48 ml min(-1) kg(-1) after the dose was formulated in rat plasma. The lung extraction of 1 in rats was negligible whereas the hepatic extraction was > or =90%, based on comparison of area under the curve (AUC) values derived from intra-artery, intravenous, and portal vein administration. In rats dosed intravenously with [(14)C]-1, approximately 91% of the radioactivity was recovered in bile over 48 h, with 85% accounted for in the first 4-h samples. The biliary radioactivity profile consisted of approximately 30% intact parent compound, 20% 1-glucuronide, and 50% oxidation products resulting from O-demethylation or hydroxylation reactions. When incubated with rat liver microsomes, oxidative metabolism of 1 was inhibited completely by 1-aminobenzotriazole (ABT), whereas the oxidation and glucuronidation reactions were little affected in the presence of cyclosporin A (CsA). In contrast, the hepatic extraction of 1 in rats was unperturbed in animals pre-dosed with ABT, but was reduced approximately 60% following treatment with CsA. In vitro, 1 was a substrate of the rat organic anion transporter Oatp1b2, and its cellular uptake was inhibited by CsA. In addition, the hepatic extraction of 1 was approximately 30% lower in Eisai hyperbilirubinaemic rats which lack functional multidrug resistant protein-2 (MRP2). Collectively, these data suggest that the clearance of 1 in rats likely is a result of the combined processes of hepatic oxidation, glucuronidation and biliary excretion, all of which are facilitated by active hepatic uptake of parent compound and subsequent active efflux of both unchanged parent and its metabolites into bile. It was concluded, therefore, that multiple mechanisms contribute to the clearance of 1 in rats, and suggest that appropriate pharmacokinetic properties might be difficult to achieve for this class of compounds. This case study demonstrates that an integrated strategy, incorporating both rapid screening and mechanistic investigations, is of particular value in supporting drug discovery efforts and decision-making processes.

[Nutritional aversions and preferences of 14-18 years old adolescents, schooled at the city of Santander]. / Aversiones y preferencias alimentarias de los adolescentes de 14 a 18 años de edad, escolarizados en la ciudad de Santander.

OBJECTIVE: To describe the nutritional aversions and preferences of 14-18 years old adolescents schooled at Santander and analyze the changes taking place within the last decade. SUBJECTS: A cross-sectional study was carried out analyzing a sample of 1134 adolescents: 549 males (48.4%, 95% CI: 45.5%-5.3%) and 585 females (5.6%, 95% CI: 48.7%-54.5%), ages comprised between 14 and 18 years, and schooled at centers of secondary educational level from Santander, by means of a questionnaire. RESULTS: vegetables (54.7%) and legumes (18.7%) represent the main nutritional aversions of adolescents. On the other hand, grains (53.3%) and meats (14.6%) are the preferred foods. Lentils, lettuce, strawberry, water, and pasta generally were the best-valued foods within the groups of foods and drinks to which they belong. CONCLUSION: nutritional aversions and preferences of adolescents from Santander generally are very similar to those observed in other studies and we have not observed important changes within the last decade. The data obtained may be useful to observe future trends on nutritional preferences that, together with other parameters, may help characterized the nutritional behavior of our adolescents.

Aversiones y preferencias alimentarias de los adolescentes de 14 a 18 años de edad, escolarizados en la ciudad de Santander / Nutritional aversions and preferences of 14-18 years old adolescents, schooled at the city of Santander

Objetivo: Describir las aversiones y preferencias alimentarias de los adolescentes, de 14 a 18 años de edad, escolarizados en Santander y analizar los cambios ocurridos en las mismas en la última década. Sujetos: Se realizó un estudio transversal, analizando una muestra de 1.134: 549 varones (48,4%, IC-95%:45,5% a 51,3%) y 585 mujeres (51,6%, IC-95%: 48,7%a 54,5%), de edades comprendidas entre los 14 y los 18años, escolarizados en siete centros de enseñanza secundaria de Santander, mediante un cuestionario. Resultados: Las verduras y hortalizas (54,7%) y las legumbres (18,7%) constituyen las principales aversiones alimentarias de los adolescentes. Por otro lado, los cereales (53,3%) y la carne (14,6%) son los grupos de alimentos preferidos. Las lentejas, la lechuga, la fresa, el agua y la pasta en general fueron los alimentos más valorados dentro de sus respectivos grupos de alimentos y bebidas. Conclusión: Las aversiones y preferencias alimentarias de los adolescentes santanderinos son, en líneas generales, bastante similares a las observadas en otros estudios, y no han sufrido cambios sustanciales a lo largo de la última década. Los datos obtenidos pueden ser útiles para observar las futuras tendencias sobre preferencias alimentarias, que conjuntamente con otros parámetros permitan caracterizar el comportamiento alimentario de nuestros adolescentes

Objective: To describe the nutritional aversions and preferences of 14-18 years old adolescents schooled at Santander and analyze the changes taking place within the last decade. Subjects: A cross-sectional study was carried out analyzing a sample of 1134 adolescents: 549 males(48.4%, 95% CI: 45.5%-5.3%) and 585 females (5.6%,95% CI: 48.7%-54.5%), ages comprised between 14 and18 years, and schooled at centers of secondary educational level from Santander, by means of a questionnaire. Results: vegetables (54.7%) and legumes (18.7%) represent the main nutritional aversions of adolescents. On the other hand, grains (53.3%) and meats (14.6%) are the preferred foods. Lentils, lettuce, strawberry, water, and pasta generally were the best-valued foods within the groups of foods and drinks to which they belong. Conclusion: nutritional aversions and preferences of adolescents from Santander generally are very similar to those observed in other studies and we have not observed important changes within the last decade. The data obtained may be useful to observe future trends on nutritional preferences that, together with other parameters, may help characterized the nutritional behavior of our adolescents

Insight into molecular changes of the FIX protein in a series of Italian patients with haemophilia B.

Deficiency or dysfunction of factor IX FIX leads to haemophilia B (HB), an X-linked, recessive, bleeding disorder. On a molecular basis, HB is due to a heterogeneous spectrum of mutations spread throughout the F9 gene. In several instances, a cause-effect relation has been elucidated, in others predicted possibilities have been offered by crystallography inspection and by software-constructed models of the protein. The aim of this study was to contribute to the understanding of HB molecular pathology. The F9 missense mutations we identified in 21 unrelated Italian HB patients by direct sequencing of the whole F9 coding regions were inspected for the causative effect they provoked on the ensuing transcript, and on the protein structure. Each alteration was studied in order to: (i) characterize the defect on the basis of the nature of the mutation; (ii) identify the predicted defect that is induced in the gene and (iii) speculate about the potential, detrimental effects which upset the protein functionality through an idealized FIX model. The resulting data may further contribute to the comprehension of the mechanisms underlying the disease.

[Breakfast and snack of schooled adolescents in Santander]. / Desayuno y almuerzo de los adolescentes escolarizados de Santander.

OBJECTIVE: To study the breakfast model and food intake at mid-morning (snack) in schooled adolescents at Santander city. SUBJECTS: A cross-sectional study was performed analyzing a sample of 403 adolescents: 232 girls (58%; 95% CI: 52%-62%) and 171 boys (42%; 95% CI: 38%-48%), with ages between 12 and 19 years, schooled at 12 second degree education centers of Santander, by means of a closed questionnaire and a recall 24 hours later. RESULTS: Five percent (95% CI: 3.1%-7.6%) of the adolescents referred neglecting breakfast. The most consumed foods were milk (47%; 95% CI: 42%-52%), chocolate milk (40%; 95% CI: 36%-45%), and cookies (45%; 95%CI: 36%-45%). On the other hand, 63% of adolescents consume whole milk (95% CI: 58%-70%), 21% semi-skimmed milk (95%CI: 17%-26%), and 11% skimmed milk (95% CI: 8%-15%). A decreasing lineal tendency in whole milk consumption is observed and a parallel increase in consumption of milks with a lower fat content as the academic year of adolescents advances (Armitage's chi-square test for lineal tendency = 2.32; p = 0.02). Boys consume an average of 3.0 (SD = 1.35) different foods during breakfast and girls 2.4 (SD = 1.20). Forty-three percent (95% CI: 38%-48%) of adolescents have a snack, which means that 2% of adolescents do not have breakfast or a snack (95% CI: 1%-4%). Breakfast represents 18% (95% CI: 16%-19%) of the total daily energy intake, whereas for snack, this percentage is 16% (95% CI: 14%-17%). CONCLUSION: it is necessary to promote consumption of a healthy breakfast and snack that provide an appropriate quantitative and qualitative intake.

Desayuno y almuerzo de los adolescentes escolarizados de Santander / Breakfast and snack of schooled adolescents in Santander

Objetivo: Estudiar el modelo de desayuno e ingesta alimentaria de media mañana (almuerzo) de los adolescentes escolarizados de la ciudad de Santander. Sujetos: Se realizó un estudio transversal, analizando una muestra de 403 adolescentes: 232 mujeres (58%; IC-95%:52%-62%) y 171 varones (42%; IC-95%: 38%-48%), de edades comprendidas entre los 12 y los 19 años, escolarizados en 12 centros de enseñanza secundaria de Santander, mediante un cuestionario cerrado y un recuerdo de 24 horas. Resultados: El 5% (IC-95%: 3,1%-7,6%) de los jóvenes manifestó no desayunar. Los alimentos más consumidos son la leche (47%; IC-95%: 42%-52%), la leche chocolateada (40%: IC-95%: 36%-45%) y las galletas (45%; IC-95%: 36%-45%). Por otro lado, el 63% (IC-95%:58%-70%) de los jóvenes consume leche entera, el 21% (IC-95%:17%-26%) leche semidesnatada y el 11% (IC-95%:8%-15%) leche desnatada. Se aprecia una tendencia lineal decreciente en el consumo de leche entera, y un aumento paralelo en el consumo de leches con menos fracción grasa conforme aumenta el curso académico de los adolescentes (test r2 de tendencia lineal de Armitage = 2,32; p = 0,02). Los varones consumen una media de 3,0 (DE=1,35) alimentos diferentes en el desayuno y las mujeres 2,4 (DE=1,20). El 43% (IC-95%:38%-48%) de los adolescentes almuerza, lo que implica que un 2% (IC-95%: 1%-4%) de los jóvenes ni desayuna ni almuerza. El desayuno representa el 18% (IC-95%: 16%-19%) del total de la ingesta energética diaria, mientras que para el almuerzo este porcentaje es del 16% (IC-95%:14%-17%). Conclusión: Es necesario fomentar el consumo de un desayuno y almuerzo saludables que proporcionen una ingesta cuantitativa y cualitativa adecuadas (AU)

Objective: To study the breakfast model and food intake at mid-morning (snack) in schooled adolescents at Santander city. Subjects: A cross-sectional study was performed analyzing a sample of 403 adolescents: 232 girls (58%; 95%CI: 52%-62%) and 171 boys (42%; 95%CI: 38%-48%), with ages between 12 and 19 years, schooled at 12 second degree education centers of Santander, by means of a closed questionnaire and a recall 24 hours later. Results: Five percent (95%CI: 3.1%-7.6%) of the adolescents referred neglecting breakfast. The most consumed foods were milk (47%; 95%CI: 42%-52%), chocolate milk (40%; 95%CI: 36%-45%), and cookies (45%; 95%CI: 36%-45%). On the other hand, 63% of adolescents consume whole milk (95%CI: 58%-70%), 21% semi-skimmed milk (95%CI: 17%-26%), and 11% skimmed milk (95%CI: 8%-15%). A decreasing lineal tendency in whole milk consumption is observed and a parallel increase in consumption of milks with a lower fat content as the academic year of adolescents advances (Armitage's r2 test for lineal tendency = 2.32; p = 0.02). Boys consume an average of 3.0 (SD = 1.35) different foods during breakfast and girls 2.4 (SD = 1.20). Forty-three percent (95%CI: 38%-48%) of adolescents have a snack, which means that 2% of adolescents do not have breakfast or a snack (95%CI: 1%-4%). Breakfast represents 18% (95%CI: 16%-19%) of the total daily energy intake, whereas for snack, this percentage is 16% (95%CI: 14%-17%). Conclusion: it is necessary to promote consumption of a healthy breakfast and snack that provide an appropriate quantitative and qualitative intake (AU

Germ-line origin of intron 1 inversion in two haemophilia A families.

Factor VIII gene inversion of intron 1 has recently been reported to be the mutation responsible for haemophilia A in about 5% of severe cases. In our series of patients, which is made up of 77 Italian cases negative for intron 22 inversion, the mutation was found in three sporadic and in one familial patients, with an overall frequency of 5.2%. The carrier status of the patients' female relatives was assessed by mutation analysis and showed that only two-thirds of cases could be considered truly sporadic. The germ-line origin of the mutation was investigated in the two sporadic families by haplotype analysis on genomic DNA of the patients' maternal grandparents. These studies indicated that both mutation events had occurred in the germ cell lines of the patients' healthy grandfather, suggesting that, as already demonstrated for the inversion of intron 22, the male germ cell line is more susceptible to the intrachromosome recombination which leads to the inversion of intron 1.

The discovery of sulfonylated dipeptides as potent VLA-4 antagonists.

Directed screening of a carboxylic acid-containing combinatorial library led to the discovery of potent inhibitors of the integrin VLA-4. Subsequent optimization by solid-phase synthesis afforded a series of sulfonylated dipeptide inhibitors with structural components that when combined in a single hybrid molecule gave a sub-nanomolar inhibitor as a lead for medicinal chemistry. Preliminary metabolic studies led to the discovery of substituted biphenyl derivatives with low picomolar activities. SAR and pharmacokinetic characterization of this series are presented.

Detection of T cell receptor delta gene rearrangements in childhood B and T lineage acute lymphoblastic leukaemia by southern blot and PCR: technical comparison of two methods of analysis.

Molecular analysis of antigen receptor genes (Ig and TCR) has been useful for clonal studies in acute lymphoblastic leukaemia (ALL) patients. Rearrangements of these genes can be used to track the persistence of the leukaemic clone during the therapy. The purpose of our study was to analyse the percentage and the pattern of the rearrangements at the TCR D locus in a series of ALL patients, comparing the results obtained by Southern blot and PCR. Genomic DNA was extracted from mononuclear BM cells of 40 paediatric ALL cases, digested with different restriction enzymes and hybridized to TCRDJ1 probe to study the TCR delta locus. Amplification of the rearranged TCR delta genes was performed by PCR to define the gene segments involved. The junctional region was deduced from the sequence to obtain patient-specific primers. Among the 31 B lineage ALL samples, one or two TCR delta alleles proved to be rearranged in 53% of cases. Two different types of rearrangements were chiefly detected: Vdelta2Ddelta3 and Ddelta2Ddelta3. In T-ALL patients, the predominant rearrangement involved the Vdelta1 and the Jdelta1 gene segments.

Substituted 2-aminopyridines as inhibitors of nitric oxide synthases.

A series of substituted 2-aminopyridines was prepared and evaluated as inhibitors of human nitric oxide synthases (NOS). 4,6-Disubstitution enhanced both potency and specificity for the inducible NOS with the most potent compound having an IC50 of 28 nM.