Importancia del equilibrio del índice omega-6/omega-3 en el mantenimiento de un buen estado de salud: recomendaciones nutricionales

The modification of dietary patterns has led to a change in fatty acid consumption, with an increase in the consumption of -6 fatty acids and a markerd reduction in the consumption of -3 fatty acids. This in turn has given rise to an imbalance in the -6/ -3 ratio, which is now very different from the original 1:1 ratio of humans in the past. Given the involvement of -6 and -3 essential fatty acids in disease processes, the present article examines changes in dietary patterns that have led to the present reduction in the consumption of -3 essential fatty acids, and to study the importance of the -6/ -3 balance in maintaining good health. In addition, an assesement is made of the established recommendations for preventing a poor intake of -3 essential fatty acids, and the possible options for compensating the lack of these fatty acids in the dietLa modificación de los hábitos alimentarios ha llevado a un cambio en el consumo de ácidos grasos, con una aumento de los ácidos grasos -6 y una marcada reducción en el consumo de los ácidos grasos -3. Esto a su vez ha dado lugar a un desequilibrio en la relación -6/ -3, muy diferente de la proporción original 1:1 que tenían los seres humanos en el pasado. Dada la importancia de la relación entre los ácidos grasos esenciales -6 y -3 en el desarrollo de diferentes enfermedades, en el presente artículo se examinan los cambios en los hábitos alimentarios que han llevado a la reducción en el consumo de ácidos grasos esenciales -3, y se estudia la importancia de este equilibrio en el mantenimiento de la salud. Además, se realiza una evaluación de las recomendaciones establecidas para prevenir una deficiencia en la ingesta de ácidos grasos esenciales -3, y las posibles opciones para compensar la falta de esos ácidos grasos en la diet

Hormonal an inflammatory biomarkers in a group of overweight and obese women

Introducción y Objetivos: Recientemente se ha descubierto que la obesidad es una patología caracterizada por un estado crónico de inflamación leve. El objetivo de este estudio fue describir la situación hormonal e inflamatoria de un colectivo de mujeres con sobrepeso/obesidad. Pacientes y métodos: se incluyeron mujeres > 18 años, con IMC ≥ 25 < 40 kg/m2. Se recogieron datos socio-sanitarios, presión arterial, parámetros antropométricos, de actividad física, estudio bioquímico, hormonal e inflamatorio para determinar la situación hormonal e inflamatoria de un colectivo de mujeres antes del inicio de un tratamiento para el control de peso corporal. Resultados: participaron 104 mujeres con edad media de 48,4 ± 9 años y un IMC de 29,8 ± 3,5 kg/m2. Un 48% de las mujeres estudiadas se encontraba en etapa de menopausia. Un 8,9% presentó hiperinsulinemia. El valor medio obtenido de grhelina fue 38,8 ± 33,6 pg/ml, no se encontró correlación entre sus concentraciones y las variables antropométricas y bioquímicas estudiadas. Los valores medios de PCR, leptina, adiponectina, resistina, IL 6, IL 10 y PAI 1 fueron 3,0 ± 2,7 mg/dl, 36,3 ± 19,5 ng/ml, 8,3 ± 4,5 μg/ml, 24,3 ± 23,2 ng/ml, 51,6 ± 93,6 pg/ml, 10,0 ± 34,2 pg/ml y 22,3 ± 30,6 ng/ml, respectivamente. Estas concentraciones correlacionaron significativamente con diferentes variables antropométricas y bioquímicas, sin embargo, estas correlaciones fueron débiles. Variables como la edad y presencia o no de menopausia o la práctica de actividad física de forma regular no influyeron en los valores medios obtenidos. Las pacientes con obesidad tuvieron valores medios significativamente más elevados que aquellas con sobrepeso, aunque sólo en el caso de la resistina y PAI 1. Conclusión: El grupo de mujeres estudiadas presentó cifras de adipoquinas alteradas en relación a otros estudios realizados en población con situación nutricional normal. Esto pone en evidencia la situación inflamatoria presente en estos pacientes y los valores obtenidos pueden contribuir a establecer unos rangos normalizados de estos marcadores para el colectivo de personas con sobrepeso y obesidadBackground and objectives: The aim of this study was to describe the hormonal and inflammatory status of a group of overweight/obese women. Patients and methods: The sample studied was a crosssectional cohort of women > 18 years of age, BMI ≥ 25 < 40 kg/m2, prior to starting a weight control program. Data collected were: demographic characteristics, blood pressure, anthropometric parameters, physical activity data, and biochemical, hormonal and inflammatory biomarkers. Results: The study involved 104 women with a mean age of 48.4 ± 9 years and a BMI of 29.8 ± 3.5 kg/m2. Some 48% of the women studied were in menopause. Some 8.9% had hyperinsulinemia. The mean ghrelin value was 38.8 ± 33.6 pg/ml; there was no correlation between ghrelin levels and anthropometric and biochemical variables. CRP, leptin, adiponectin, resistin, IL6, IL10, and PAI1 were 3.0 ± 2.7 mg/dl, 36.3 ± 19.5 ng/ml, 8.3 ± 4.5 mg/ml, 24.3 ± 23.2 ng/ml, 51.6 ± 93.6 pg/ml, 10.0 ± 34.2 pg/ml and 22.3 ± 30.6 ng/ml, respectively. Obese patients had significantly higher mean values of resistin and PAI 1 than those who were overweight. These levels correlated significantly with anthropometric and biochemical variables; however, the correlations were weak. Age, menopause or the regular practice of physical activity had no effect on mean values. Conclusions: The group of women studied had altered inflammatory biomarkers in relation to people of normal weight. The study shows the inflammatory status of overweight/ obese individuals, and the values obtained may help to establish standard ranges for these markersEste trabajo ha sido posible gracias a un proyecto de investigación obtenido por concurso y subvencionado por la campaña “Pan cada día” promovida por el Comité Científico del Pan y el Incerhpan (Interprofesional Agroalimentaria de la cadena Cereales-Harina- Pan

Eficacia de un programa para el tratamiento del sobrepeso y la obesidad no mórbida en atención primaria y su influencia en la modificación de estilos de vida

Introducción y Objetivos: la modificación de conductas no saludables es fundamental para tratar la obesidad. El objetivo de este estudio fue evaluar los efectos de un programa basado en dieta, ejercicio y apoyo psicológico en la modificación conductual de pacientes con sobrepeso y obesidad tratados en Atención Primaria. Métodos: 60 pacientes con sobrepeso grado II y obesidad grado I-II fueron incluidos en este ensayo piloto. Edad entre 18-50 años. Los pacientes recibieron un programa que combinaba educación nutricional, actividad física y apoyo psicológico. Formato grupal, periodicidad quincenal. Los principales resultados medidos al inicio y 6 meses fueron parámetros antropométricos (índice de masa corporal, porcentaje de masa grasa, perímetro cintura) y de estilos de vida usando el Cuestionario para la valoración de hábitos de vida relacionados con el sobrepeso y la obesidad. Consta de 5 dimensiones: contenido calórico de la dieta (CC), alimentación saludable (AS), ejercicio físico (EF), comer por bienestar psicológico (BP) y consumo de alcohol (CA). La mayor puntuación indica mejores hábitos para CC, AS y EF y peores para BP y CA. Resultados: al final de la intervención mejoraron las escalas CC (2,60± 0,5 vs 3,49± 0,7, p<0,001), EF (2,19± 0,9 vs 3,17± 1,0, p<0,001) y AS (3,04± 0,4 vs 3,43± 0,4, p<0,05) del cuestionario; CA (3,98± 0,7 vs. 4,25± 0,7, p<0,05) y BP (2,82± 1,0 vs. 3,34± 0,7, p<0,001) empeoraron. Conclusión: el programa basado en moderada restricción de la dieta, aumento de actividad física y apoyo psicológico puede mejorar parámetros antropométricos y estilos de vida en pacientes obesos tratados en un centro de Atención PrimariaBackground: Lifestyle intervention is fundamental for obesity treatment. The aim of this study was to evaluate the effects of a program focused on diet, exercise and psychological support on Lifestyle Modification in overweight and obese patients treated in Primary Health Care setting. Methods: 60 patients with grade II overweight and non-morbid grade I-II obesity were included in this pilot clinical trial. Ages ranged from18 to 50 years. They were provided with a program combining nutritional education, physical activity and psychological support. Subjects attended group sessions every 2 weeks. The main outcome measures at baseline and 6 months were body composition parameters (BMI, body fat percentage, waist circumference) and lifestyle intervention using the Questionnaire for the assessment of overweight and obesity related lifestyles at baseline and six months. This questionnaire yields an five dimensions: diet caloric intake (CC), healthy eating (AS), physical activity (EF), searching for psychological well-being eating (BP) and alcohol intake (CA). The higher score indicates better lifestyles for CC, AS, EF and worse for BP y CA. Results: At the end of the intervention the program achieved improvements in Questionnaire related lifestyles subscales: CC (2,60± 0,5 vs. 3,49± 0,7, p<0,001), EF (2,19± 0,9 vs. 3,17± 1,0, p<0,001) and AS (3,04± 0,4 vs. 3,43± 0,4, p<0,05); CA (3,98± 0,7 vs. 4,25± 0,7, p<0,05) and BP (2,82± 1,0 vs. 3,34± 0,7, p<0,001) has got worse. Conclusion: The Program focused on balanced and moderate energy-restricted diets, increased physical activity and psychological support may improve the anthropometric parameters and the Lifestyle intervention in obese patients treated in a primary healthcare center.Este proyecto ha sido becado por el Ministerio de Ciencia e Innovación, a través del Instituto de Salud Carlos III y la Subdirección General de Evaluación y Fomento de la Investigación, en el marco del «Subprograma de Proyectos de Investigación de Evaluación de Tecnologías Sanitarias e Investigación en servicios de salud». Convocatoria 2008 de ayudas de la Acción Estratégica en Salud, en el marco del Plan Nacional de I+D+I 2008-2011 (PI08/90357). Y por la Fundación MAPFRE, a través del programa de Ayudas a la Investigación (2009

Predictor variables for low adherence to a lifestyle modification program of overweight treatment in primary health care

Objetivos: Identificar variables predictoras de baja adherencia a un programa piloto de Modificación de Estilos de Vida (MEV) para el tratamiento del exceso de peso en Atención Primaria (AP). Material y métodos: Se reclutaron 60 sujetos con IMC > 27 kg/m². Profesionales sanitarios dirigieron el programa, en formato grupal y con una periodicidad quincenal, basado en educación nutricional, pautas dietéticas individualizadas, promoción de actividad física y apoyo motivacional. Para identificar las variables relacionadas con la adherencia al programa se utilizó un cuestionario validado sobre Hábitos de Vida de personas con Sobrepeso y Obesidad y se midieron variables antropométricas al inicio y a los seis meses del tratamiento. Una baja adherencia al programa fue considerada cuando los sujetos del estudio acudían a menos del 80% de las visitas quincenales. Resultados: Se adhirieron al programa 27 sujetos (45%). Las variables asociadas a baja adherencia estuvieron relacionadas al inicio del estudio con IMC ≥ 35 kg/m2 (p < 0,05); período de exfumador ≤ 4 meses (p < 0,01); mayor contenido calórico de la dieta (p < 0,01) y menor práctica de ejercicio físico (p < 0,05). A los 6 meses los sujetos que finalizaron el programa presentaron una disminución significativa de: peso (86,0 ± 15,6 vs 79,2 ± 13,4 kg; p < 0,001);% de masa grasa (41,6 ± 4,6 vs 38,8 ± 5,4%; p < 0,001) y glucemia (108 ± 45,48 vs 94,38 ± 11,97 mg/dl; p < 0,01). Además mejoró el perfil calórico de su dieta, disminuyendo sobretodo el porcentaje de grasa sobre el valor calórico total (39,6 ± 4,8 vs. 35,5 ± 5,6%; p < 0,01). Conclusión: Haber dejado de fumar recientemente, padecer obesidad de grado dos o superior, el alto contenido calórico de la dieta y la menor práctica de ejercicio físico fueron las variables basales identificadas como predictoras de una baja adherencia a un programa de MEV para el tratamiento de sobrepeso y obesidad en AP. Esta experiencia piloto una vez evaluada no la consideramos satisfactoria y otras nuevas estrategias están en fase de desarrolloObjectives: To identify predictive variables of low adherence to a pilot Lifestyle Modification Program (LMP) for overweight and obesity treatment in primary health care (PC ). Material and methods: Sixty subjects with BMI > 27 kg/m² were recruited. Health professionals directed the program in a group structure and biweekly, based on nutrition education with individualized dietary guidelines, promotion of physical activity and motivational support. A validated questionnaire on lifestyle habits for overweight and obesity subjects was used to identify variables related with program adherence and anthropometric variables were measured before and 6 months after intervention. Low adherence was considered when patients attended to less than 80% of visits. Results: Twenty-seven subjects (45%) presented high adherence to the program. The variables associated to low adherence were related to baseline with IMC ≥ 35 kg/m2 (p < 0.05); ex smoker period ≤ 4 months (p < 0.01); high caloric diet (p < 0.01) and scarce physical activity (p < 0.05). At 6 months the subjects who finalized the program presented a significant decrease of weight (86.0 ± 15.6 vs 79.2 ± 13.4 kg; p < 0,001); fat mass percentage (41,6 ± 4,6 vs 38.8 ± 5,4%; p < 0.001), blood glucose (108 ± 45.48 vs 94.38 ± 11.97 mg/dl; p < 0.01). It also improved caloric diet profile, above all decreasing the percentage of fat (39.6 ± 4.8 vs 35.5 ± 5.6%; p < 0.01). Conclusion: Have recently left smoking, obesity degree two or higher, a high caloric diet and scarce physical activity were basal variables identified as predictive of a low adhesion to a LMP for the treatment of overweight and obesity in primary health care. We do not consider this pilot experience as satisfactory and other new strategies are under developmentEste proyecto ha sido subvencionado a través del “Subprograma de Proyectos de Investigación de Evaluación de Tecnologías Sanitarias e Investigación en servicios de salud” de la convocatoria 2008 de ayudas de la Acción Estratégica en Salud, en el marco del Plan Nacional de I+D+I 2008-201

Nutritional composition assessment of 3000 individualized parenteral nutrition bags in a tertiary referral hospital: Current prescribing patterns

Individualized parenteral nutrition is the most specialized type of nutritional support in the hospital setting. The composition and prescribing patterns for parenteral nutrition have evolved due to new emerging scientific evidence. In the last few years, there has been a tendency to increase the nitrogen and lipid content and decrease the carbohydrate content. To assess the prescribing pattern in a tertiary referral hospital in Spain, the nutritional composition of individualized parenteral nutrition was evaluated retrospectively from January to December of 2016. A total of 3029 parenteral nutrition units were analysed, corresponding to 257 hospitalized adult patients. Medical specialists in General Surgery and Haematology were the most common petitioners. The three most frequently prescribed parenteral nutrition formulae contained 13.4 (28.8%), 15.7 (19.54%) and 17.9 (17.79%) g of nitrogen. The quantity of carbohydrates and lipids showed a mean non-protein calories-to-nitrogen ratio of approximately 78:1 and a carbohydrate-to-lipid ratio that was near 50:50 in most cases. These results suggest a trend towards the administration of parenteral nutrition with a high content of nitrogen and smaller proportion of the non-protein components

Regular consumption of LIPIGO® promotes the reduction of body weight and improves the rebound effect of obese people undergo a comprehensive weight loss program

Obesity is a global public health problem. Objective: To evaluate the effect of the regular consumption of the product Lipigo® on body weight and rebound effect on overweight/obese subjects undergoing a comprehensive weight loss program. Methods: A randomized, parallel, double-blind, placebo-controlled clinical trial was conducted with male and female subjects presenting a BMI 25–39.9 kg/m . All subjects underwent a comprehensive weight loss program (WLP) for 12 weeks, which included an individualized hypocaloric diet, physical activity recommendations, nutritional education seminars, and three times a day consumption of the product Lipigo® or Placebo. After-WLP, subjects continued the treatment for 9 months to assess rebound effect. Body weight (BW), BMI, and body composition were measured at the beginning and the end of the WLP, and in the follow-up. Results: A total of 120 subjects (85% women) 49.0 ± 9.5 years old and with a BW of 81.57 ± 13.26 kg (BMI 31.19 ± 3.44 kg/m ) were randomized and 73 subjects finished the study. At the end of the WLP, there was a tendency toward reduced BW (p = 0.093), BMI (p = 0.063), and WC (p = 0.059) in the treated group. However, subjects with obesity type 1 (OB1) from the treated group significantly reduced body weight (−5.27 ± 2.75 vs. −3.08 ± 1.73 kg; p = 0.017) and BMI (−1.99 ± 1.08 vs. −1.09 ± 0.55 kg/m ; p = 0.01) compared with placebo. They also presented a minor rebound effect after 9 months with product consumption (−4.19 ± 3.61 vs. −1.44 ± 2.51 kg; p = 0.026), minor BMI (−1.61 ± 1.43 vs. −0.52 ± 0.96 kg/m ; p = 0.025) and tended to have less fat-mass (−3.44 ± 2.46 vs. −1.44 ± 3.29 kg; p = 0.080) compared with placebo. Conclusions: The regular consumption of the product Lipigo® promotes the reduction of body weight and reduces the rebound effect of obese people after 52 weeks (12 months), mainly in obesity type 1, who undergo a comprehensive weight loss program. 2 2 2 2This study was supported by the DAMM S.A. group through the project RTC-2016-5317-1 from the RETOS COLABORACIÓN 2016 program of Economy and Competitiveness Ministry of Spain (MINECO

Usual Dietary Intake, Nutritional Adequacy and Food Sources of Calcium, Phosphorus, Magnesium and Vitamin D of Spanish Children Aged One to <10 Years. Findings from the EsNuPI Study

Bone problems in the population begin to be establish in childhood. The present study aims to assess the usual calcium, phosphorus, magnesium, and vitamin D intakes, along with the food sources of these nutrients, in Spanish children participating in the EsNuPI (Estudio Nutricional en Población Infantil Española) study. Two 24 h dietary recalls were applied to 1448 children (1 to <10 years) divided into two sub-samples: one reference sample (RS) of the general population [n = 707] and another sample which exclusively included children consuming enriched or fortified milks, here called “adapted milks” (AMS) [n = 741]. Estimation of the usual intake shows that nutrient intake increased with age for all nutrients except vitamin D. Using as reference the Dietary Reference Values from the European Food Safety Authority (EFSA), calcium and magnesium intakes were found to be below the average requirement (AR) and adequate intake (AI), respectively, in a considerable percentage of children. Furthermore, phosphorus exceeded the AI in 100% of individuals and vitamin D was lower than the AI in almost all children studied. The results were very similar when considering only plausible reporters. When analyzing the food sources of the nutrients studied, milk and dairy products contributed the most to calcium, phosphorus, magnesium, and vitamin D. Other sources of calcium were cereals and vegetables; for phosphorus: meat, meat products, and cereals; for magnesium: cereals and fruits; and, for vitamin D: fish and eggs. These results highlight the desirability of improving the intake concerning these nutrients, which are involved in bone and metabolic health in children. The AMS group appeared to contribute better to the adequacy of those nutrients than the RS group, but both still need further improvement. Of special interest are the results of vitamin D intakes, which were significantly higher in the AMS group (although still below the AI), independent of ageThis research was funded by Instituto Puleva de Nutrición (IPN)S

Usual dietary intake, nutritional adequacy and food sources of calcium, phosphorus, magnesium and vitamin D of spanish children aged one to dagger

Bone problems in the population begin to be establish in childhood. The present study aims to assess the usual calcium, phosphorus, magnesium, and vitamin D intakes, along with the food sources of these nutrients, in Spanish children participating in the EsNuPI (Estudio Nutricional en Población Infantil Española) study. Two 24 h dietary recalls were applied to 1448 children (1 to <10 years) divided into two sub-samples: one reference sample (RS) of the general population [n = 707] and another sample which exclusively included children consuming enriched or fortified milks, here called “adapted milks” (AMS) [n = 741]. Estimation of the usual intake shows that nutrient intake increased with age for all nutrients except vitamin D. Using as reference the Dietary Reference Values from the European Food Safety Authority (EFSA), calcium and magnesium intakes were found to be below the average requirement (AR) and adequate intake (AI), respectively, in a considerable percentage of children. Furthermore, phosphorus exceeded the AI in 100% of individuals and vitamin D was lower than the AI in almost all children studied. The results were very similar when considering only plausible reporters. When analyzing the food sources of the nutrients studied, milk and dairy products contributed the most to calcium, phosphorus, magnesium, and vitamin D. Other sources of calcium were cereals and vegetables; for phosphorus: meat, meat products, and cereals; for magnesium: cereals and fruits; and, for vitamin D: fish and eggs. These results highlight the desirability of improving the intake concerning these nutrients, which are involved in bone and metabolic health in children. The AMS group appeared to contribute better to the adequacy of those nutrients than the RS group, but both still need further improvement. Of special interest are the results of vitamin D intakes, which were significantly higher in the AMS group (although still below the AI), independent of age

Very few frequent syndromes

Dismorfología, Citogenética y Clínica: Resultados sobre los datos del ECEMCThis section is based on two facts: First, that the majority of the malformation syndromes are very few frequent. Second, the progressive generalization in our country of the prenatal diagnosis with a high resolution echography performed to all women between 18-20 weeks of gestation as a Service of the National Health System, together with the possibility of voluntary interruption of gestation if fetal anomalies are detected. Thus, the impact of prenatal diagnosis is that the frequency at birth of these syndromes shows an important and progressive decreasing trend. For these reasons, in addition to the difficulty for pediatricians and geneticists or our population to diagnose these usually rare syndromes, the impact of prenatal diagnosis increases the usual difficulties that the young pediatricians and geneticists have to identify these pathologies. This increases the possibility that some affected patients can remain undiagnosed for a long time, or even never be diagnosed. As started last year in this section of the "Boletín del ECEMC", we present other six syndromes of low frequency in our country.N

Macrophages direct cancer cells through a LOXL2-mediated metastatic cascade in pancreatic ductal adenocarcinoma

[Objective]: The lysyl oxidase-like protein 2 (LOXL2) contributes to tumour progression and metastasis in different tumour entities, but its role in pancreatic ductal adenocarcinoma (PDAC) has not been evaluated in immunocompetent in vivo PDAC models.[Design]: Towards this end, we used PDAC patient data sets, patient-derived xenograft in vivo and in vitro models, and four conditional genetically-engineered mouse models (GEMMS) to dissect the role of LOXL2 in PDAC. For GEMM-based studies, K-Ras +/LSL-G12D;Trp53 LSL-R172H;Pdx1-Cre mice (KPC) and the K-Ras +/LSL-G12D;Pdx1-Cre mice (KC) were crossed with Loxl2 allele floxed mice (Loxl2Exon2 fl/fl) or conditional Loxl2 overexpressing mice (R26Loxl2 KI/KI) to generate KPCL2KO or KCL2KO and KPCL2KI or KCL2KI mice, which were used to study overall survival; tumour incidence, burden and differentiation; metastases; epithelial to mesenchymal transition (EMT); stemness and extracellular collagen matrix (ECM) organisation.[Results]: Using these PDAC mouse models, we show that while Loxl2 ablation had little effect on primary tumour development and growth, its loss significantly decreased metastasis and increased overall survival. We attribute this effect to non-cell autonomous factors, primarily ECM remodelling. Loxl2 overexpression, on the other hand, promoted primary and metastatic tumour growth and decreased overall survival, which could be linked to increased EMT and stemness. We also identified tumour-associated macrophage-secreted oncostatin M (OSM) as an inducer of LOXL2 expression, and show that targeting macrophages in vivo affects Osm and Loxl2 expression and collagen fibre alignment.[Conclusion]: Taken together, our findings establish novel pathophysiological roles and functions for LOXL2 in PDAC, which could be potentially exploited to treat metastatic disease.JCL-G received support from a 'la Caixa' Foundation (ID 100010434) fellowship (LCF/BQ/DR21/11880011). This study was supported by ISCIII FIS grants PI18/00757 and PI21/01110 (BSJ) and PI18/00267 (LG-B), and grants from the Spanish Ministry of Economy and Innovation SAF2016-76504-R (ACan and FP), PID2019-111052RB-I00 (FP), PID2019-104644RB-I00 (GM-B), a Ramón y Cajal Merit Award RYC-2012–12104 (BSJ) and ISCIII, CIBERONC, CB16/12/00446 (ACar) and CB16/12/00295 (ACan and GM-B), all of them co-financed through Fondo Europeo de Desarrollo Regional (FEDER) 'Una manera de hacer Europa'; a Fero Foundation Grant (BSJ); a Coordinated grant (GC16173694BARB) from the Fundación Científica Asociación Española Contra el Cáncer (FC-AECC) (BSJ); a Miguel Servet award (CP16/00121) (PS); a DFG, German Research Foundation Grant—Project no: 492 436 553 (KG); and a Max Eder Fellowship of the German Cancer Aid (111746) (PCH