Comparación entre la videografía y el método Sit and Reach para la valoración de la flexibilidad isquiotibial en deportistas escolares

Existen diferentes test para evaluar la flexibilidad articular. El objetivo de nuestro estudio era el de comparar el test de sit and reach y el de goniometría de la rodilla en extensión, mediante videografía para la valoración de la flexibilidad isquiotibial en una muestra de 139 deportistas escolares, de edades comprendidas entre los 7 y los 16 años. El coeficiente de Kappa muestra una concordancia muy débil entre las dos pruebas (0,022 (I.C. 95% -0,07 – 0,12)). Demostrando que el sit and reach no es un test válido para la evaluación de la flexibilidad isquiotibial.

Teoría de la comunicación y paisaje. Las geografías del sujeto y la perspectiva interpretativa de la comunicación

El estudio de las implicaciones comunicativas presentes en el paisaje tangible e intangible circundante abre un amplio abanico de posibilidades para el tratamiento de la denominada comunicación en el paisaje. El análisis de los efectos que el entorno genera en los procesos de comunicación humana, el seguimiento de los procesos comunicativos mediante los cuales se mercadea con el paisaje, la construcción de imaginarios individuales y colectivos a partir de la interacción ciudadanía-territorio, el tránsito de espacio a lugar y, más recientemente, la habilitación de identidades territoriales a partir de la construcción de una imagen de marca de ciudad o de país –léase promoción turística, citymarketing y/o branding, entre otros– presentan, en todos los casos, amplias connotaciones de alcance comunicativo. La búsqueda del mensaje presente en el paisaje plantea, en este mismo sentido, el tratamiento del espacio a modo de sistema de comunicación. En cualquier caso, parece claro que, en los últimos tiempos, asistimos a una cierta eclosión de procesos de comunicación concebidos desde la realidad existente en el espacio y más aún, en el paisaje, por lo que se hace necesario avanzar hacia un tratado comunicativo del paisaje.

Qualitative modeling identifies IL-11 as a novel regulator in maintaining self-renewal in human pluripotent stem cells.

Pluripotency in human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) is regulated by three transcription factors-OCT3/4, SOX2, and NANOG. To fully exploit the therapeutic potential of these cells it is essential to have a good mechanistic understanding of the maintenance of self-renewal and pluripotency. In this study, we demonstrate a powerful systems biology approach in which we first expand literature-based network encompassing the core regulators of pluripotency by assessing the behavior of genes targeted by perturbation experiments. We focused our attention on highly regulated genes encoding cell surface and secreted proteins as these can be more easily manipulated by the use of inhibitors or recombinant proteins. Qualitative modeling based on combining boolean networks and in silico perturbation experiments were employed to identify novel pluripotency-regulating genes. We validated Interleukin-11 (IL-11) and demonstrate that this cytokine is a novel pluripotency-associated factor capable of supporting self-renewal in the absence of exogenously added bFGF in culture. To date, the various protocols for hESCs maintenance require supplementation with bFGF to activate the Activin/Nodal branch of the TGFβ signaling pathway. Additional evidence supporting our findings is that IL-11 belongs to the same protein family as LIF, which is known to be necessary for maintaining pluripotency in mouse but not in human ESCs. These cytokines operate through the same gp130 receptor which interacts with Janus kinases. Our finding might explain why mESCs are in a more naïve cell state compared to hESCs and how to convert primed hESCs back to the naïve state. Taken together, our integrative modeling approach has identified novel genes as putative candidates to be incorporated into the expansion of the current gene regulatory network responsible for inducing and maintaining pluripotency.

Derechos emergentes en regiones emergentes: el derecho al agua potable y al saneamiento en Asia Central

El derecho humano al agua potable y al saneamiento viene afirmándose de manera cada vez más rotunda en el plano internacional. Supone la capacidad de cada ser humano de acceder a agua limpia y segura de manera asequible, y la obligación correlativa de los Estados de garantizar y proteger este derecho. Los Estados de Asia Central disponen de agua suficiente para garantizar este derecho a todos sus ciudadanos, pero la mala gestión y el despilfarro hace que algunas zonas, sobre todo rurales, tengan importantes carestías. Las mejoras en tarificación, servicio y cooperación transfronteriza se apuntan como posibles vías de solución.

La responsabilidad social de las multinacionales y el respeto de los derechos humanos a propósito de los informes presentados por el representante especial del Secretario General de Naciones Unidas (RESG) sobre derechos humanos y corporaciones transnacionales y otras empresas.

Este artículo se plantea como una revisión del proceso que se inició a partir de las“Normas sobre las responsabilidades de las transnacionales y otras empresascomerciales respecto a los derechos humanos” que aunque fueron aprobadas en el 55ºperíodo de sesiones de Naciones Unidas de agosto de 2003, finalmente no fueronadoptadas quedando de momento sin entrar en vigor. Se realiza una presentación del papel jugado por el profesor John Ruggie en el proceso posterior a la emisión de las normas, y del informe “Protect, respect and remedy” junto con el informe sobre líneas estratégicas de abril de 2009. Las normas finalmente fueron aprobadas el 16 de junio de 2011 siguiendo la pauta establecida en el informe anteriormente citado.

A novel approach to characterize clonality and differentiation of human melanoma-specific T cell responses: spontaneous priming and efficient boosting by vaccination.

Despite major progress in T lymphocyte analysis in melanoma patients, TCR repertoire selection and kinetics in response to tumor Ags remain largely unexplored. In this study, using a novel ex vivo molecular-based approach at the single-cell level, we identified a single, naturally primed T cell clone that dominated the human CD8(+) T cell response to the Melan-A/MART-1 Ag. The dominant clone expressed a high-avidity TCR to cognate tumor Ag, efficiently killed tumor cells, and prevailed in the differentiated effector-memory T lymphocyte compartment. TCR sequencing also revealed that this particular clone arose at least 1 year before vaccination, displayed long-term persistence, and efficient homing to metastases. Remarkably, during concomitant vaccination over 3.5 years, the frequency of the pre-existing clone progressively increased, reaching up to 2.5% of the circulating CD8 pool while its effector functions were enhanced. In parallel, the disease stabilized, but subsequently progressed with loss of Melan-A expression by melanoma cells. Collectively, combined ex vivo analysis of T cell differentiation and clonality revealed for the first time a strong expansion of a tumor Ag-specific human T cell clone, comparable to protective virus-specific T cells. The observed successful boosting by peptide vaccination support further development of immunotherapy by including strategies to overcome immune escape.

Implicaciones de derechos humanos en el tratado de libre comercio entre Colombia y la Unión Europea

[spa] Tras largas y complejas negociaciones, la Unión Europea celebró un acuerdo comercial con Colombia en 2010 que ha empezado a aplicarse provisionalmente el 1 de agosto de 2013. El artículo se centra en las relaciones entre Colombia y la Unión y analiza el impacto que dicho acuerdo pueda tener en el marco de las obligaciones de las partes de respetar los derechos humanos universalmente reconocidos, incluyendo derechos sociales y los derechos de los pueblos indígenas. De dicho análisis se deriva que la presencia de cláusulas democráticas o de derechos humanos en el Acuerdo es insuficiente, habida cuenta los antecedentes del SGP+ vigente hasta la entrada en vigor del nuevo acuerdo, mientras que algunos aspectos sustantivos del Acuerdo permiten augurar consecuencias negativas respecto de los sectores sociales más desfavorecidos en la República de Colombia.

Combined radioimmunotherapy and chemotherapy of human colon carcinoma grafted in nude mice, advantages and limitations.

In order to determine if 5-fluorouracil (5FU) could potentiate the effect of radioimmunotherapy (RIT), nude mice bearing subcutaneous human colon carcinoma xenografts were treated by 1 or 2 intravenous injection(s) of subtherapeutic doses of 131I labeled F(ab')2 from anti-carcinoembryonic antigen monoclonal antibodies combined with 5 daily intraperitoneal injections of 5FU. Control mice received either 131I F(ab')2 alone, 5FU alone or no treatment. RIT alone induced significant tumor regression, while 5FU alone gave only minimal tumor growth inhibition. The combined treatment group also resulted in long-term tumor regression with tumors remaining significantly smaller than in the RIT alone group. There was however, no significant difference in tumor recurrence time between the groups treated with RIT alone or with RIT + 5FU. Myelotoxicity, the major side effect of RIT, detected by the decrease of peripheral white blood cells (WBC), was shown to be almost identical between the groups receiving only RIT or only 5FU. Surprisingly, there was no cumulative bone marrow toxicity in animals which received 5FU before RIT. Furthermore, in the latter group, the WBC levels after RIT were significantly higher than in the control group receiving only RIT. Taken together, the results demonstrate the higher therapeutic efficiency of RIT as compared to 5FU in this model. They do not show, however, that the combination of the two forms of treatment can induce longer tumor remission. Interestingly, the WBC results suggest that 5FU given before RIT can have a radioprotective effect on bone marrow, possibly by selecting radioresistant bone marrow stem cells.

Simulando una vía de comunicación: el tramo de la vía romana entre el Coll de Panissars y Girona

Mediante programa informático es posible simular las vías de comunicación existentes entre asentamientos humanos, siendo muchos los trabajos publicados y varias las formas de aproximación al problema. El objetivo del trabajo que nos ocupa ha consistido en la generación de un nuevo modelo a partir del cual fuera posible simular una vía de comunicación, con la salvedad de que en este caso ya existía una idea aproximada de cual sería su trayectoria a partir de trabajos de otros autores. Esta vía de comunicación es la vía Augusta, en el tramo que une el Coll de Panissars y la ciudad de Girona.

Evolución de la agregación y separación de sexos: ¿Qué hemos aprendido de las poblaciones ibéricas de Mercurialis annua?

Most plant species are hermaphrodites, with both male and female functions performed by the same individuals. However, separate sexes (dioecy) have evolved on numerous independent occasions, probably either in response to selection for inbreeding avoidance, or because it pays individuals to specialize in one gender or the other. Although the evolution of dioecy from hermaphroditism tends to be thought of as a one-way path, dioecy has broken down to yield hermaphroditic populations on several occasions. One such case is found in the mainly dioecious genus Mercurialis (Euphorbiaceae). In the species complex M. annua, diploids are dioecious, but polyploid populations are variously monoecious or androdioecious (where males co-exist with functional hermaphrodites). This species complex offers rich material for addressing questions concerning the evolution and ecology of combined versus separate sexes, the evolution of secondary sexual dimorphism, which likely contributes to the stability of dioecy in the genus, and the evolution and genetics of sex determination and sex chromosomes. The species also offers itself as a valuable teaching tool for addressing topics ranging from sex-ratio selection to inter-sexual competition.

Concept of fat balance in human obesity revisited with particular reference to de novo lipogenesis.

The measurement of fat balance (fat input minus fat output) involves the accurate estimation of both metabolizable fat intake and total fat oxidation. This is possible mostly under laboratory conditions and not yet in free-living conditions. In the latter situation, net fat retention/mobilization can be estimated based on precise and accurate sequential body composition measurements. In case of positive balance, lipids stored in adipose tissue can originate from dietary (exogenous) lipids or from nonlipid precursors, mainly from carbohydrates (CHOs) but also from ethanol, through a process known as de novo lipogenesis (DNL). Basic equations are provided in this review to facilitate the interpretation of the different subcomponents of fat balance (endogenous vs exogenous) under different nutritional circumstances. One difficulty is methodological: total DNL is difficult to measure quantitatively in man; for example, indirect calorimetry only tracks net DNL, not total DNL. Although the numerous factors (mostly exogenous) influencing DNL have been studied, in particular the effect of CHO overfeeding, there is little information on the rate of DNL in habitual conditions of life, that is, large day-to-day fluctuations of CHO intakes, different types of CHO ingested with different glycemic indexes, alcohol combined with excess CHO intakes, etc. Three issues, which are still controversial today, will be addressed: (1) Is the increase of fat mass induced by CHO overfeeding explained by DNL only, or by decreased endogenous fat oxidation, or both? (2) Is DNL different in overweight and obese individuals as compared to their lean counterparts? (3) Does DNL occur both in the liver and in adipose tissue? Recent studies have demonstrated that acute CHO overfeeding influences adipose tissue lipogenic gene expression and that CHO may stimulate DNL in skeletal muscles, at least in vitro. The role of DNL and its importance in health and disease remain to be further clarified, in particular the putative effect of DNL on the control of energy intake and energy expenditure, as well as the occurrence of DNL in other tissues (such as in myocytes) in addition to hepatocytes and adipocytes.

TLR3 and Rig-like receptor on myeloid dendritic cells and Rig-like receptor on human NK cells are both mandatory for production of IFN-gamma in response to double-stranded RNA.

Cross-talk between NK cells and dendritic cells (DCs) is critical for the potent therapeutic response to dsRNA, but the receptors involved remained controversial. We show in this paper that two dsRNAs, polyadenylic-polyuridylic acid and polyinosinic-polycytidylic acid [poly(I:C)], similarly engaged human TLR3, whereas only poly(I:C) triggered human RIG-I and MDA5. Both dsRNA enhanced NK cell activation within PBMCs but only poly(I:C) induced IFN-gamma. Although myeloid DCs (mDCs) were required for NK cell activation, induction of cytolytic potential and IFN-gamma production did not require contact with mDCs but was dependent on type I IFN and IL-12, respectively. Poly(I:C) but not polyadenylic-polyuridylic acid synergized with mDC-derived IL-12 for IFN-gamma production by acting directly on NK cells. Finally, the requirement of both TLR3 and Rig-like receptor (RLR) on mDCs and RLRs but not TLR3 on NK cells for IFN-gamma production was demonstrated using TLR3- and Cardif-deficient mice and human RIG-I-specific activator. Thus, we report the requirement of cotriggering TLR3 and RLR on mDCs and RLRs on NK cells for a pathogen product to induce potent innate cell activation.

Human papilloma virus type and recurrence rate after surgical clearance of anal condylomata acuminata

Résumé : Le condylome acuminé anal (CAA), transmis par contact sexuel, résulte d'une infection par Human Papilloma Virus (HPV). Son traitement chirurgical est grevé d'un taux de récidive de 4-29%. Le but de cette étude était d'identifier une éventuelle corrélation entre type d'HPV présent dans les CAA excisés chirurgicalement et taux de récidive de la maladie, Cette étude rétrospective porte sur 140 patients opérés au Centre Hospitalier Universitaire Vaudois de CAA, entre 1990 et 2005. Le diagnostic lésionnel a été confirmé par un examen histomorphologique. Le(s) type(s) d'HPV présent(s) dans ces lésions a été déterminé par Polymerase Chain Reaction (PCR). Les patients ont donné leur accord à cette analyse et complété un questionnaire. Une éventuelle corrélation entre récidive de CAA, type d'HPV et status HIV a été recherchée. HPV 6 et 11 sont les virus les plus fréquemment découverts (51% et 28%, respectivement) chez les 140 patients (123H/17F). Trente-cinq (25%) d'entre eux ont présenté une récidive. HPV 11 était present chez 19 (41%) sujets. Ceci est statistiquement significatif (P<0.05), en comparaison aux autres HPVs. Il n'y a par contre pas de différence significative entre la fréquence de récidive des 33 (24%) patients HIV-positifs et le reste du collectif. HPV 11 est donc associé à un taux de récidive de CAA significativement élevé. Un suivi strict des patients atteints est nécessaire pour identifier une récidive et la traiter sans délai, notamment lorsque HPV 11 est present. Ces résultats innovateurs soulèvent la question de la nécessité de pratiquer une typisation virale systématique sur les lésions excisées. La justification d'une telle attitude demande toutefois encore d'être confirmée.

Efficacy of Canakinumab (ACZ885), a Fully Human Anti-Interleukin (IL)-1beta Monoclonal Antibody, in the Prevention of Flares in Gout Patients Initiating Allopurinol Therapy

Background: Gout patients initiating urate lowering therapy have an increased risk of flares. Inflammation in gouty arthritis is induced by IL-1b. Canakinumab targets and inhibits IL-1b effectively in clinical studies. This study compared different doses of canakinumab vs colchicine in preventing flares in gout patients initiating allopurinol therapy.Methods: In this 24 week double blind study, gout patients (20-79 years) initiating allopurinol were randomized (1:1:1:1:1:1:2) to canakinumab s.c. single doses of 25, 50, 100, 200, 300 mg, or 150 mg divided in doses every 4 weeks (50+50+25+25 mg [q4wk]) or colchicine 0.5 mg p.o. daily for 16 weeks. Primary outcome was to determine the canakinumab dose giving comparable efficacy to colchicine with respect to the number of gout flares occurring during first 16 weeks. Secondary outcomes included number of patients with gout flares and C-reactive protein (CRP) levels during the first 16 weeks.Results: 432 patients were randomized and 391 (91%) completed the study. All canakinumab doses were better than colchicine in preventing flares and therefore, a canakinumab dose comparable to colchicine could not be determined. Based on a negative binomial model, all canakinumab groups, except 25 mg, reduced the flare rate ratio per patient significantly compared to colchicine group (rate ratio estimates 25 mg 0.60, 50 mg 0.34, 100 mg 0.28, 200 mg 0.37, 300 mg 0.29, q4wk 0.38; p<=0.05). The percentage of patients with flares was lower for all canakinumab groups (25 mg 27.3%, 50 mg 16.7%, 100 mg 14.8%, 200 mg 18.5%, 300 mg 15.1%, q4wk 16.7%) compared to colchicine group (44.4%). All patients taking canakinumab were significantly less likely to experience at least one gout flare than patients taking colchicine (odds ratio range [0.22 - 0.47]; p<=0.05 for all). The median baseline CRP levels were 2.86 mg/L for 25 mg, 3.42 mg/L for 50 mg, 1.76 mg/L for 100 mg, 3.66 mg/L for 200 mg, 3.21 mg/L for 300 mg, 3.23 mg/L for q4wk canakinumab groups and 2.69 mg/L for colchicine group. In all canakinumab groups with median CRP levels above the normal range at baseline, median levels declined within 15 days of treatment and were maintained at normal levels (ULN=3 mg/L) throughout the 16 week period. Adverse events (AEs) occurred in 52.7% (25 mg), 55.6% (50 mg), 51.9% (100 mg), 51.9% (200 mg), 54.7% (300 mg), and 58.5% (q4wk) of patients on canakinumab vs 53.7% of patients on colchicine. Serious AEs (SAE) were reported in 2 (3.6%; 25 mg), 2 (3.7%, 50 mg), 3 (5.6%, 100 mg), 3 (5.6%, 200 mg), 3 (5.7%, 300 mg) and 1 (1.9%, q4wk) patients on canakinumab and in 5 (4.6%) patients on colchicine. One fatal SAE (myocardial infarction, not related to study drug) occurred in colchicine group.Conclusion: In this large randomized, double-blind active controlled study of flare prevention in gout patients initiating allopurinol therapy, treatment with canakinumab led to a statistically significant reduction in flares compared with colchicine (standard of care), and was well tolerated.