Cardiometabolic and Cardiovascular Complications of Obesity in Children

The rise in obesity in both children and adults has made obesity one of the biggest public health problems of this century. Obesity along with other factors such as hypertension, insulin resistance, dyslipidemia and diabetes mellitus are risk factors for the development of cardiovascular diseases. Overweight and/or obesity during childhood and its maintenance until adult life has been associated with early stages of cardiovascular disease. For this reason, the aim of this study is to revise the state of the art of cardiometabolic and cardiovascular complications related with overweight and/or obesity in children and adolescents. The first consequence of weight gain is an increase in adipose tissue, with different distribution depending on the sex. The excess of fat mass entails dysfunction of adipose tissue with an altered secretion of adipokines and instauration of a proinflammatory environment, which may derive in metabolic syndrome condition. The increase of adipose tissue along with an increase in sympathetic nervous system, triggers an increased left ventricular mass and with a reduced diastolic function. Therefore, obesity should be prevented from the early stages of life, in order to avoid obesity itself and the metabolic disturbances that could undermine quality of life further on

Challenges and improvement needs in the care of patients with central diabetes insipidus

Central diabetes insipidus (CDI) is a rare condition, with significant impact on patient health and well-being. It is a chronic condition which usually requires meticulous long-term care. It can affect both children and adults. There is limited literature considering the needs and challenges inherent in providing high quality care to patients with CDI, across the care pathway. This paper seeks to address this gap by providing a unique and well-rounded understanding of clinical and healthcare systems-related challenges. It draws on insights from the literature, from direct clinical experience contributed by five clinicians as co-authors (providing insights from France, Ireland, Italy, Spain and the United Kingdom), and from patient perspectives provided through interviews with patient representatives from three patient organisations. We identify clinical challenges related to the diagnosis of CDI, including differentiating between other similar conditions and determining the underlying aetiology. Treatment is challenging, given the need to tailor medication to each patient’s needs and ongoing management is required to ensure that patients continue to respond adequately to treatment. Ongoing support is required when patients switch between formulations. We also identify healthcare systems challenges related to limited awareness of CDI amongst primary care physicians and general paediatricians, and the need for highly skilled specialist care and appropriate workforce capacity. There is also a significant need for raising awareness and for the education of both healthcare professionals and patients about different aspects of CDI, with the aim of supporting improved care and effective patient engagement with healthcare professionals. We reflect on this information and highlight improvement opportunities. These relate to developing guidance to support patients, carers, primary care physicians and general paediatricians to identify clinical features earlier, and to consider CDI as a possible diagnosis when a patient presents with suggestive symptom

Ovulation rate and early embryonic survival rate in female rabbits of a synthetic line and a local Algerian population

[EN] A higher litter size at birth has been reported in female rabbits from a Synthetic line than in those of the Local Algerian population. The aim of this work was to analyse whether this difference in litter size was due to a higher ovulation rate and/or embryonic survival rate in Synthetic line than in Local Algerian population. In total, 24 multiparous female rabbits from Synthetic line and 23 from Local population were used in this experiment. Litter size at birth was recorded up to the first 3 parities. Litter size was 20% higher in Synthetic line than Local population. At their 4th gestation, the females were euthanized at 72 h post coitum. Synthetic line females had 50% more ova and embryos than those of Local population (+4.42 ova and +3.92 embryos, respectively). Synthetic line displayed a lower percentage of normal embryos and a larger number of unfertilized oocytes than Local population (–2.81% and +0.64 oocytes, respectively), but differences were not relevant. Synthetic line showed a lesser embryonic stage of development at 72 h post coitum, showing a higher percentage of early morulae (31.50 vs. 8.50%) and a lower percentage of compact morulae (51.45 vs. 78.65%) than Local population. No relevant difference was found for early embryonic survival rate between Synthetic line and Local population. In conclusion, the difference in litter size was mainly due to a higher ovulation rate in the Synthetic line, allowing more embryos to develop in this line.Belabbas, R.; García, M.; Ainbaziz, H.; Berbar, A.; Zitouni, G.; Lafri, M.; Bouzouan, M.... (2016). Ovulation rate and early embryonic survival rate in female rabbits of a synthetic line and a local Algerian population. World Rabbit Science. 24(4):275-282. doi:10.4995/wrs.2016.5301.SWORD275282244Argente, M. J., Santacreu, M. A., Climent, A., & Blasco, A. (2003). Relationships between uterine and fetal traits in rabbits selected on uterine capacity1. Journal of Animal Science, 81(5), 1265-1273. doi:10.2527/2003.8151265xBelabbas R., AinBaziz H., Ilès I., Zenia S., Boumahdi Z., Boulbina I., Temim S. 2011. Study of prolificacy and its main biological components in rabbits of local Algerian population (Oryctolagus cuniculus). Livest. Res. Rur. Dev., 23: 61.Brun J.M., Baselga M. 2004. Analysis of reproductive performances during the formation of a rabbit synthetic strain. In Proc.: 8th World Rabbit Congress, September 7-10, 2004, Puebla, Mexico, 32-37.Bolet, G., & Theau-Clément, M. (1994). Fertilisation rate and preimplantation embryonic development in two rabbit strains of different fecundity, in purebreeding and crossbreeding. Animal Reproduction Science, 36(1-2), 153-162. doi:10.1016/0378-4320(94)90062-0Buhi, W. C., & Alvarez, I. M. (2003). Identification, characterization and localization of three proteins expressed by the porcine oviduct. Theriogenology, 60(2), 225-238. doi:10.1016/s0093-691x(03)00027-xGacem M., Lebas F. 2000. Rabbit husbandry in Algeria. Technical structure and evaluation of performances. World Rabbit Sci., 8(Suppl. 1): B75-80.Gacem M., Zerrouki N., Lebas F., Bolet G., 2008. Strategy of developing rabbit meat in Algeria: creation and selection of a synthetic strain. In Proc.: 9th World Rabbit Congress, June 10-13, 2008, Verona, Italy, 85-89.Nancarrow C.D., Hill J.L. 1995. Oviduct proteins in fertilization and early embryo development. J. Reprod. Fertil., (Suppl) 49: 3-13.Salvetti P., Guérin P., Theau-Clément M., Hurtaud J., Beckers J.F., Joly T. 2007. Essais d'amélioration de la production d'embryons chez la lapine. In Proc.: 12èmes Journées de la Recherche Cunicole, 27-28 Novembre 2007, Le Mans, France, 41-44.Xie, S., Broermann, D. M., Nephew, K. P., Bishop, M. D., & Pope, W. F. (1990). Relationship between oocyte maturation and fertilization on zygotic diversity in swine. Journal of Animal Science, 68(7), 2027. doi:10.2527/1990.6872027xYoussef Y.K., Iraqi M.M., El-Raffa A.M., Afifi E.A., Khalil M.H., García M.L., Baselga M. 2008. A joint project to synthesize new lines of rabbits in Egypt and Saudi Arabia: emphasis for results and prospects. In Proc.: 9th World Rabbit Congress, June 10-13, 2008, Verona, Italy, 1637-1642

Building quests for online games with virtual institutions

Abstract. This document describes how to re-purpose an existing agent technology called Virtual Institutions as a mechanism to define new "quest" elements in Massively Multiplayer Online Games based on MultiAgent Systems. Quests are a very important part of most Massive Online Games as they wield to flow and narrative of the game in a linear or nonlinear manner

RhIGF-1 treatment increases bone mineral density and trabecular bone structure in children with PAPP-A2 deficiency

KARGER: "This is the peer-reviewed but unedited manuscript version of the following article: Hormone Research in Paediatrics 89.3 (2018): 200-204 DOI: 10.1159/000486336. The final, published version is available at http://www.karger.com/. http://doi.org/10.1159/000486336]."Aim: Our objective was to determine changes in bone mineral density (BMD), trabecular bone score (TBS), and body composition after 2 years of therapy with recombinant human insulin-like growth factor-1 (rhIGF-1) in 2 prepubertal children with a complete lack of circulating PAPP-A2 due to a homozygous mutation in PAPP-A2 (p.D643fs25∗) resulting in a premature stop codon. Methods: Body composition, BMD, and bone structure were determined by dual-energy X-ray absorptiometry at baseline and after 1 and 2 years of rhIGF-1 treatment. Results: Height increased from 132 to 145.5 cm (patient 1) and from 111.5 to 124.5 cm (patient 2). Bone mineral content increased from 933.40 to 1,057.97 and 1,152.77 g in patient 1, and from 696.12 to 773.26 and 911.51 g in patient 2, after 1 and 2 years, respectively. Whole-body BMD also increased after 2 years of rhIGF-1 from baseline 0.788 to 0.869 g/cm2in patient 1 and from 0.763 to 0.829 g/cm2in patient 2. After 2 years of treatment, both children had an improvement in TBS. During therapy, a slight increase in body fat mass was seen, with a concomitant increase in lean mass. No adverse effects were reported. Conclusion: Two years of rhIGF-1 improved growth, with a tendency to improve bone mass and bone microstructure and to modulate body composition.The authors are funded by Fondos de Investigación Sanitaria and FEDER (Grants PI1302195 and PI1600485 to J.A.), Ministerio de Ciencia e Innovación (BFU2014-51836-C2-2-R to J.A.C.), Centro de Investigación Biomédica en Red Fisiopatología de Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (J.A.), and Fundación Endocrinología y Nutrició

Response to growth hormone in patients with RNPC3 mutations

Peer reviewe

Designing normative open virtual enterprises

This is an Accepted Manuscript of an article published by Taylor & Francis Group in Enterprise Information Systems on 23/03/2016, available online: http://www.tandfonline.com/10.1080/17517575.2015.1036927.[EN] There is an increasing interest on developing virtual enterprises in order to deal with the globalisation of the economy, the rapid growth of information technologies and the increase of competitiveness. In this paper we deal with the development of normative open virtual enterprises (NOVEs). They are systems with a global objective that are composed of a set of heterogeneous entities and enterprises that exchange services following a specific normative context. In order to analyse and design systems of this kind the multi-agent paradigm seems suitable because it offers a specific solution for supporting the social and contractual relationships between enterprises and for formalising their business processes. This paper presents how the Regulated Open Multiagent systems (ROMAS) methodology, an agent-oriented software methodology, can be used to analyse and design NOVEs. ROMAS offers a complete development process that allows identifying and formalising of the structure of NOVEs, their normative context and the interactions among their members. The use of ROMAS is exemplified by means of a case study that represents an automotive supply chain.This work was partially supported by the projects [PROMETEOII/2013/019], [TIN2012-36586-C03-01], [FP7-29493], [TIN2011-27652-C03-00] and [CSD2007-00022], and the CASES project within the 7th European Community Framework Programme [grant agreement number 294931].Garcia Marques, ME.; Giret Boggino, AS.; Botti Navarro, VJ. (2016). Designing normative open virtual enterprises. Enterprise Information Systems. 10(3):303-324. https://doi.org/10.1080/17517575.2015.1036927S303324103Cardoso, H. L., Urbano, J., Brandão, P., Rocha, A. P., & Oliveira, E. (2012). ANTE: Agreement Negotiation in Normative and Trust-Enabled Environments. Advances on Practical Applications of Agents and Multi-Agent Systems, 261-264. doi:10.1007/978-3-642-28786-2_33Chu, X. N., Tso, S. K., Zhang, W. J., & Li, Q. (2002). Partnership Synthesis for Virtual Enterprises. The International Journal of Advanced Manufacturing Technology, 19(5), 384-391. doi:10.1007/s001700200028Davidsson, P., & Jacobsson, A. (s. f.). Towards Norm-Governed Behavior in Virtual Enterprises. Studies in Computational Intelligence, 35-55. doi:10.1007/978-3-540-88071-4_3DeLoach, S. A., & Ojeda, J. C. G. (2010). O-MaSE: a customisable approach to designing and building complex, adaptive multi-agent systems. International Journal of Agent-Oriented Software Engineering, 4(3), 244. doi:10.1504/ijaose.2010.036984DI MARZO SERUGENDO, G., GLEIZES, M.-P., & KARAGEORGOS, A. (2005). Self-organization in multi-agent systems. The Knowledge Engineering Review, 20(2), 165-189. doi:10.1017/s0269888905000494Dignum, V. 2003. “A Model for Organizational Interaction: Based on Agents, Founded in Logic.” PhD diss., Utrecht University.Dignum, V., and F. Dignum. 2006.A Landscape of Agent Systems for the Real World. Technical Report 44-CS-2006-061. Utrecht: Institute of Information and Computing Sciences, Utrecht University.Dignum, V., Meyer, J.-J. C., Dignum, F., & Weigand, H. (2003). Formal Specification of Interaction in Agent Societies. Lecture Notes in Computer Science, 37-52. doi:10.1007/978-3-540-45133-4_4Garcia, E. 2013. “Engineering Regulated Open Multiagent Systems.” PhD diss., Universitat Politecnica de Valencia.Garcia, E., Giret, A., & Botti, V. (s. f.). Software Engineering for Service-Oriented MAS. Lecture Notes in Computer Science, 86-100. doi:10.1007/978-3-540-85834-8_9Garcia, E., Giret, A., & Botti, V. (2013). A Model-Driven CASE tool for developing and verifying regulated open MAS. Science of Computer Programming, 78(6), 695-704. doi:10.1016/j.scico.2011.10.009Garcia, E., Giret, A., & Botti, V. (2011). Evaluating software engineering techniques for developing complex systems with multiagent approaches. Information and Software Technology, 53(5), 494-506. doi:10.1016/j.infsof.2010.12.012Garcia, E., Giret, A., & Botti, V. (2011). Regulated Open Multi-Agent Systems Based on Contracts. Information Systems Development, 243-255. doi:10.1007/978-1-4419-9790-6_20Garcia, E., Giret, A., & Botti, V. (2014). ROMAS Methodology. Handbook on Agent-Oriented Design Processes, 331-369. doi:10.1007/978-3-642-39975-6_11Hollander, C. D., & Wu, A. S. (2011). The Current State of Normative Agent-Based Systems. Journal of Artificial Societies and Social Simulation, 14(2). doi:10.18564/jasss.1750HORLING, B., & LESSER, V. (2004). A survey of multi-agent organizational paradigms. The Knowledge Engineering Review, 19(4), 281-316. doi:10.1017/s0269888905000317Julian, V., Rebollo, M., Argente, E., Botti, V., Carrascosa, C., & Giret, A. (2009). Using THOMAS for Service Oriented Open MAS. Lecture Notes in Computer Science, 56-70. doi:10.1007/978-3-642-10739-9_5Luck, M., Barakat, L., Keppens, J., Mahmoud, S., Miles, S., Oren, N., … Taweel, A. (2011). Flexible Behaviour Regulation in Agent Based Systems. Lecture Notes in Computer Science, 99-113. doi:10.1007/978-3-642-22427-0_8Meneguzzi, F., Modgil, S., Oren, N., Miles, S., Luck, M., & Faci, N. (2012). Applying electronic contracting to the aerospace aftercare domain. Engineering Applications of Artificial Intelligence, 25(7), 1471-1487. doi:10.1016/j.engappai.2012.06.004Presley, A., Sarkis, J., Barnett, W., & Liles, D. (2001). International Journal of Flexible Manufacturing Systems, 13(2), 145-162. doi:10.1023/a:1011131417956Saeki, M., & Kaiya, H. (2008). Supporting the Elicitation of Requirements Compliant with Regulations. Active Flow and Combustion Control 2018, 228-242. doi:10.1007/978-3-540-69534-9_18Such, J. M., García-Fornes, A., Espinosa, A., & Bellver, J. (2013). Magentix2: A privacy-enhancing Agent Platform. Engineering Applications of Artificial Intelligence, 26(1), 96-109. doi:10.1016/j.engappai.2012.06.009Telang, P. R., & Singh, M. P. (2009). Enhancing Tropos with Commitments. Lecture Notes in Computer Science, 417-435. doi:10.1007/978-3-642-02463-4_22Wooldridgey, M., & Ciancarini, P. (2001). Agent-Oriented Software Engineering: The State of the Art. Lecture Notes in Computer Science, 1-28. doi:10.1007/3-540-44564-1_

Activated Lymphocytes and Increased Risk of Dermatologic Adverse Events during Sorafenib Therapy for Hepatocellular Carcinoma

Altres ajuts: Asociación Española Contra el Cáncer PI044031Hepatocellular carcinoma is the second cause of cancer-related death worldwide. Of those advanced-stage patients who are treated with sorafenib, those who develop early dermatologic adverse events have a better prognosis. These events are possibly immune-related. Therefore, we analyzed the phenotype of 52 sorafenib-treated patients' circulating lymphocytes throughout treatment. We found that different co-stimulatory and immune exhaustion markers, such as Programmed cell death protein 1 (PD-1) and DNAX accessory molecule 1 (DNAM-1) amongst others, correlate with the probability of developing these adverse events, both before and during the treatment. We also compared the phenotype of those lymphocytes expressing DNAM-1 with those that do not, and while NK DNAM-1-expressing cells have a co-stimulatory phenotype, T DNAM-1-expressing cells are immune-suppressors. Overall, we set a rationale for the combination of sorafenib and immune-targeted therapies; and for the use of immune markers (such as DNAM-1) for patients' prognosis evaluation. Advanced hepatocellular carcinoma patients treated with sorafenib who develop early dermatologic adverse events (eDAEs) have a better prognosis. This may be linked to immune mechanisms, and thus, it is relevant to assess the association between peripheral immunity and the probability of developing eDAEs. Peripheral blood mononuclear cells of 52 HCC patients treated with sorafenib were analyzed at baseline and throughout the first eight weeks of therapy. T, B, Natural Killer cells, and their immune checkpoints expression data were characterized by flow cytometry. Cytokine release and immune-suppression assays were carried out ex vivo. Cox baseline and time-dependent regression models were applied to evaluate the probability of increased risk of eDAEs. DNAM-1, PD-1, CD69, and LAG-3 in T cells, plus CD16 and LAG-3 in NK cells, are significantly associated with the probability of developing eDAEs. While NK DNAM-1 + cells express activation markers, T DNAM-1 + cells induce immune suppression and show immune exhaustion. This is the first study to report an association between immune checkpoints expression in circulating immune cells and the increased incidence of eDAEs. Our results support the hypothesis for an off-target role of sorafenib in immune modulation. We also describe a novel association between DNAM-1 and immune exhaustion in T cells

Heterozygous rare genetic variants in non-syndromic early-onset obesity

BACKGROUND: Obesity is a very heterogeneous disorder at both the clinical and molecular levels and with high heritability. Several monogenic forms and genes with strong effects have been identified for non-syndromic severe obesity. Novel therapeutic interventions are in development for some genetic forms, emphasizing the importance of determining genetic contributions. OBJECTIVE: We aimed to define the contribution of rare single-nucleotide genetic variants (RSVs) in candidate genes to non-syndromic severe early-onset obesity (EOO; body mass index (BMI) >+3 standard deviation score, <3 years). METHODS: Using a pooled DNA-sequencing approach, we screened for RSVs in 15 obesity candidate genes in a series of 463 EOO patients and 480 controls. We also analysed exome data from 293 EOO patients from the "Viva la Familia" (VLF) study as a replication dataset. RESULTS:Likely or known pathogenic RSVs were identified in 23 patients (5.0%), with 7 of the 15 genes (BDNF, FTO, MC3R, MC4R, NEGR1, PPARG and SIM1) harbouring RSVs only in cases (3.67%) and none in controls. All were heterozygous changes, either de novo (one in BDNF) or inherited from obese parents (seven maternal, three paternal), and no individual carried more than one variant. Results were replicated in the VLF study, where 4.10% of probands carried RSVs in the overrepresented genes. RSVs in five genes were either absent (LEP) or more common in controls than in cases (ADRB3, LEPR, PCSK1 and PCSK2) in both obese datasets. CONCLUSIONS: Heterozygous RSVs in several candidate genes of the melanocortin pathway are found in ~5.0% patients with EOO. These results support the clinical utility of genetic testing to identify patients who might benefit from targeted therapeutic intervention.Clara Serra-Juhé, Gabriel Á. Martos-Moreno, Francesc Bou de Pieri, Raquel Flores, Julie A. Chowen, Luis A. Pérez-Jurado, Jesús Argent