Necrosis aséptica de astrágalo: presentación de un caso en la infancia

Se presenta un caso de necrosis aséptica de astrágalo en la infancia de origen idiopático que, hasta donde sabemos, resulta único en la literatura mundial. Se trata de una niña con un síndrome de Klippel-Trenaunay que debuta a la edad de 8 años con un cuadro de dolor e inflamación intermitente en tobillo derecho. Se realiza estudio mediante radiografías simples, RNM y gammagrafía con "Tc, llegando al diagnóstico de necrosis avascular de astrágalo. Se trata mediante descarga del miembro durante 3 meses, realizando la paciente vida normal con mínimas molestias a los 3 años del diagnósticoWe present one case of idiopathic avascular necrosis of the talus in a child.To our knowledge, this is the first case reported in the literature. The patient is a girl diagnosed of Klippel-Trenaunay syndrome of the ipsilateral limb. When she was 8 years old began with pain and swelling in the right ankle. Simple X-ray, isotopic bone scan and MRI were done, and she was diagnosed of avascular necrosis of the talar dome. The treatment was no weight bearing for three months. She has no sympthoms three years after diagnosis

Immunotherapeutic targeting of LIGHT/LTβR/HVEM pathway fully recapitulates the reduced cytotoxic phenotype of LIGHT-deficient T cells.

Tumor necrosis factor (TNF)/TNF receptor (TNFR) superfamily members play essential roles in the development of the different phases of the immune response. Mouse LIGHT (TNFSF14) is a type II transmembrane protein with a C-terminus extracellular TNF homology domain (THD) that assembles in homotrimers and regulates the course of the immune responses by signaling through 2 receptors, the herpes virus entry mediator (HVEM, TNFSFR14) and the lymphotoxin β receptor (LTβR, TNFSFR3). LIGHT is a membrane-bound protein transiently expressed on activated T cells, natural killer (NK) cells and immature dendritic cells that can be proteolytically cleaved by a metalloprotease and released to the extracellular milieu. The immunotherapeutic potential of LIGHT blockade was evaluated in vivo. Administration of an antagonist of LIGHT interaction with its receptors attenuated the course of graft-versus-host reaction and recapitulated the reduced cytotoxic activity of LIGHT-deficient T cells adoptively transferred into non-irradiated semiallogeneic recipients. The lack of LIGHT expression on donor T cells or blockade of LIGHT interaction with its receptors slowed down the rate of T cell proliferation and decreased the frequency of precursor alloreactive T cells, retarding T cell differentiation toward effector T cells. The blockade of LIGHT/LTβR/HVEM pathway was associated with delayed downregulation of interleukin-7Rα and delayed upregulation of inducible costimulatory molecule expression on donor alloreactive CD8 T cells that are typical features of impaired T cell differentiation. These results expose the relevance of LIGHT/LTβR/HVEM interaction for the potential therapeutic control of the allogeneic immune responses mediated by alloreactive CD8 T cells that can contribute to prolong allograft survival

Osteocondritis disecante de primera cuña en la infancia: presentación de 1 caso

Se presenta un caso de osteocondritis disecante de la primera cuña en la infancia, patología no descrita hasta el momento en la literatura mundial. Se trata de una niña de 11 años que se estudió por dolor de 1 año de evolución y tras llegar al diagnóstico se trató mediante artrodesis de la primera articulación escafocuneana, encontrándose la paciente asintomática tras 10 meses de seguimiento.We report a case of osteochondritis dissecans of the first cuneiform bone in a child. We have not found a similar case in world literature. She is an 11 years old girl with 1 year of pain in her foot. After the diagnosis was made, the treatment was an arthrodesis of the first naviculo-cuneiform joint. The patient is now asympthomatic after 10 months of follow-u

Fracturas de estrés en la infancia

Aportamos 13 casos de fracturas de estrés diagnosticadas en nuestro centro en los últimos 5 años ocurridas en niños entre 4 y 15 años de edad. Encontramos una mayor incidencia en el sexo masculino (9 de los 13 casos), así como un claro predominio de la localización en el tercio proximal de la diáfisis tibial (7 casos), hallazgos que concuerdan con los referidos en la literatura. Uno de los aspectos más interesantes de este tipo de fracturas es su similitud tanto clínica como radiológica con procesos de origen infeccioso y neoplásico, por lo que la realización de un correcto diagnóstico diferencial, apoyado en las radiografías simples, tomografías, gammagrafía, TAC y, más recientemente, RMN, resulta crucial.We present 13 cases of stress fractures in children, collected in our center during the last 5 years. The age of patients ranged from 4 to 15 years old. In agreement with literature, we found a greater incidence on males (9 of 13 cases), and a predominant location on the proximal shaft of the tibia (7 cases). One of the most interesting aspects of this type of fractures is their clinical and radiological similarity with infections and tumors. Therefore, it is essential to achieve a right diagnosis based on standard radiographs, tomography, radionuclide bone scan, CT-scan and, most recently, MRI

Therapeutic implications of NK cell regulation of allogeneic CD8 T cell-mediated immune responses stimulated through the direct pathway of antigen presentation in transplantation.

Natural killer (NK) cells are a population of innate type I lymphoid cells essential for early anti-viral responses and are known to modulate the course of humoral and cellular-mediated T cell responses. We assessed the role of NK cells in allogeneic CD8 T cell-mediated responses in an immunocompetent mouse model across an MHC class I histocompatibility barrier to determine its impact in therapeutic clinical interventions with polyclonal or monoclonal antibodies (mAbs) targeting lymphoid cells in transplantation. The administration of an NK cell depleting antibody to either CD8 T cell replete or CD8 T cell-depleted naïve C57BL/6 immunocompetent mice accelerated graft rejection. This accelerated rejection response was associated with an in vivo increased cytotoxic activity of CD8 T cells against bm1 allogeneic hematopoietic cells and bm1 skin allografts. These findings show that NK cells were implicated in the control host anti-donor cytotoxic responses, likely by competing for common cell growth factors in both CD8 T cell replete and CD8 T cell-depleted mice, the latter reconstituting in response to lymphopenia. Our data calls for precaution in solid organ transplantation under tolerogenic protocols involving extensive depletion of lymphocytes. These pharmacological biologics with depleting properties over NK cells may accelerate graft rejection and promote aggressive CD8 T cell cytotoxic alloresponses refractory to current immunosuppression

Sucrose digestion capacity in birds shows convergent coevolution with nectar composition across continents

The major lineages of nectar-feeding birds (hummingbirds, sunbirds, honey-eaters, flowerpiercers, and lorikeets) are considered examples of convergentevolution. We compared sucrose digestion capacity and sucrase enzymatic activ-ity per unit intestinal surface area among 50 avian species from the New World,Africa, and Australia, including 20 nectarivores. With some exceptions, nectari-vores had smaller intestinal surfaces, higher sucrose hydrolysis capacity, andgreater sucrase activity per unit intestinal area. Convergence analysis showedhigh values for sucrose hydrolysis and sucrase activity per unit intestinal surfacearea in specialist nectarivores, matching the high proportion of sucrose in thenectar of the plants they pollinate. Plants pollinated by generalist nectar-feedingbirds in the Old and New Worlds secrete nectar in which glucose and fructose arethe dominant sugars. Matching intestinal enzyme activity in birds and nectarcomposition in flowers appears to be an example of convergent coevolution be-tween plants and pollinators on an intercontinental scale.Todd J. McWhorter, Jonathan A. Rader, Jorge E. Schondube, Susan W. Nicolson, Berry Pinshow, Patricia A. Fleming, Yocelyn T. Gutie, rrez-Guerrero, and Carlos Martı, nez del Ri

One Health contributions towards more effective and equitable approaches to health in low- and middle-income countries

This research was supported by the UK Biotechnology and Biological Sciences Research Council (BB/J010367/1) and the UK Zoonoses and Emerging Livestock Systems Initiative (BB/L017679/1, BB/L018926/1 and BB/L018845/1) (S.C., J.E.B.H., J.S., J.B., A.D., J.A.C., W.A.d.G., R.R.K., T.K., D.T.H., B.T.M., E.S.S., L.W.). The Wellcome Trust provided supported for K.H. and A.L. (095787/Z/11/Z) and K.J.A. (096400/Z/11/Z). The US National Institutes of Health provided support for J.A.C. (R01AI121378) and M.P.R. (R01AI121378, K23AI116869).Emerging zoonoses with pandemic potential are a stated priority for the global health security agenda, but endemic zoonoses also have a major societal impact in low-resource settings. Although many endemic zoonoses can be treated, timely diagnosis and appropriate clinical management of human cases is often challenging. Preventive ‘One Health’ interventions, e.g. interventions in animal populations that generate human health benefits, may provide a useful approach to overcoming some of these challenges. Effective strategies, such as animal vaccination, already exist for the prevention, control and elimination of many endemic zoonoses, including rabies, and several livestock zoonoses (e.g. brucellosis, leptospirosis, Q fever) that are important causes of human febrile illness and livestock productivity losses in low- and middle-income countries. We make the case that, for these diseases, One Health interventions have the potential to be more effective and generate more equitable benefits for human health and livelihoods, particularly in rural areas, than approaches that rely exclusively on treatment of human cases. We hypothesize that applying One Health interventions to tackle these health challenges will help to build trust, community engagement and cross-sectoral collaboration, which will in turn strengthen the capacity of fragile health systems to respond to the threat of emerging zoonoses and other future health challenges. One Health interventions thus have the potential to align the ongoing needs of disadvantaged communities with the concerns of the broader global community, providing a pragmatic and equitable approach to meeting the global goals for sustainable development and supporting the global health security agenda.Publisher PDFPeer reviewe

Caracterización de la púrpura trombótica trombocitopénica congénita mediante técnicas inmunológicas y moleculares: resultados de la colección nacional del GEPTT

CO-093 Introducción: La Púrpura Trombótica Trombocitopénica congénita (PTTc) es una enfermedad ultra-rara caracterizada por un déficit severo de la enzima ADAMTS13 como consecuencia de mutaciones heredadas de forma autosómica recesiva en el gen ADAMTS13 (9q34). En este estudio, desarrollado dentro del Grupo Cooperativo Español de PTT (GEPTT), se ha llevado a cabo la creación de una colección centralizada de muestras biológicas y su caracterización inmunológica y molecular para mejorar el diagnóstico y el manejo clínico de los pacientes. Métodos: Se incluyeron en este estudio seis pacientes con diagnóstico clínico o sospecha de PTTc de diferentes hospitales españoles. Se estudió la actividad de ADAMTS13 e inhibidores mediante la técnica ELISA con el kit “TECHNOZYM® ADAMTS-13 Activity e INH” (Technoclone). Además, se realizó test Bethesda para descartar la presencia de inhibidores no IgG. Para el estudio genético, se implementó un panel de captura (SureSelect, Agilent) dirigido a la región genómica completa, incluyendo también las regiones no codificantes, del gen ADAMTS13 (chr9: 136278459 - 136325025, hg19). Las librerías de DNA se secuenciaron con la plataforma MiSeq (Illumina®) y el posible efecto patogénico de las variantes identificadas se estudió a nivel de i) proteína, utilizando predictores de cambio de aminoácido (SIFT) y de estructura de la proteína (SwissModel) y ii) splicing, con herramientas de análisis in silico (HSF) y validación funcional in vitro mediante minigenes. En 3 casos se realizó un cariotipo molecular utilizando array de SNPs (CytoScan HD, Affymetrix) para detectar regiones de pérdida de material genético y/o de heterocigosidad (LOH). Resultados: La mediana de actividad de ..

The energy spectrum of cosmic rays beyond the turn-down around 10^17 eV as measured with the surface detector of the Pierre Auger Observatory

We present a measurement of the cosmic-ray spectrum above 100 PeV using the part of the surface detector of the Pierre Auger Observatory that has a spacing of 750 m. An inflection of the spectrum is observed, confirming the presence of the so-called second-knee feature. The spectrum is then combined with that of the 1500 m array to produce a single measurement of the flux, linking this spectral feature with the three additional breaks at the highest energies. The combined spectrum, with an energy scale set calorimetrically via fluorescence telescopes and using a single detector type, results in the most statistically and systematically precise measurement of spectral breaks yet obtained. These measurements are critical for furthering our understanding of the highest energy cosmic rays