Treatment of an aneurysmal bone cyst in a young dog: A case report

Background: An aneurysmal bone cyst (ABC) is a rare benign lytic lesion affecting the medullary canal of long bones. It has been widely reported in human medicine, but rarely described in domestic animals. Objective: To report the surgical treatment and long term follow-up of a dog affected by ABC. Methods: An 8-month-old, intact female Weimaraner was presented with lameness affecting the left front limb and progressive swelling of the mid-distal radius. Survey radiographs revealed a mid-distal diaphyseal radial lesion. Fine needle aspirates, biopsy, CT scan and histopathology results supported the diagnosis of ABC. Treatment consisted of partial corticotomy of the affected radius, filling of the cystic cavity with demineralised bone matrix and autologous bone graft and stabilisation using lag screws and a neutralisation plate. Results: The long-term follow-up, at 36 post-operative months, showed no recurrence of the cyst and bone modelling. Comparing preoperative radiographs with those at 36 months, bone modelling reduced the radial area by 23.3% in the craniocaudal radiographic view and 30% in the mediolateral projection. Conclusions: This treatment was sucessful in the case here described, with a 3 years follow-up

Drug design and synthesis of first in class PDZ1 targeting NHERF1 inhibitors as anticancer agents

Targeted approaches aiming at modulating NHERF1 activity, rather than its overall expression, would be preferred to preserve the normal functions of this versatile protein. We focused our attention on the NHERF1/PDZ1 domain that governs its membrane recruitment/displacement through a transient phosphorylation switch. We herein report the design and synthesis of novel NHERF1 PDZ1 domain inhibitors. These compounds have potential therapeutic value when used in combination with antagonists of β-catenin to augment apoptotic death of colorectal cancer cells refractory to currently available Wnt/β-catenin-targeted agents

Human Wharton’s jelly-derived mesenchymal stem cells express several immunomodulatory molecules both in their naïve state and hepatocyte-like differentiated progeny: prospects for their use in liver diseases.

Wharton’s jelly (WJ), the main constituent of umbilical cord, is a reliable source of mesenchymal stem cells (MSC). WJ-MSC show unique ability in crossing lineage borders. As other extraembryonic mesenchymal populations (placenta and amnionderived cells), WJ-MSC express several immunomodulatory molecules, essential during the initial phases of human development. Indeed, our recent work pointed out the expression of non-classical HLA molecules as HLA-G in such cells, together with a favorable combination of B7 costimulators. Very few data in literature suggest that some of the immune features of the naïve cells are maintained after performing differentiation. The aim of this work was extending the knowledge on the expression of immunomodulatory molecules by naïve and differentiated WJ-MSC. To this purpose, WJMSC underwent differentiation to osteoblasts, adipocytes and hepatocyte-like cells. Differentiated cells were characterized, by both RT-PCR, ICC and histological stains for the acquisistion of the desired phenotypical features. RT-PCR and ICC were used to investigate the differential expression of immune-related molecules in control and differentiated cells. WJ-MSC resulted expressing diverse immunomodulatory molecules which spans from non-classical type I HLAs (i.e. HLA-E, -F, -G) , to further members of the B7 family, and of the CEA superfamily, for all of which in vivo immunomodulating functions are known. In addition, we demonstrated for the first time that the expression of these molecules is maintained after performing osteogenic, adipogenic or hepatogenic differentiation. Further experiments are undergoing to better evaluating the implications of these findings in the evolving field of liver regenerative medicine

Inteligencia emocional y estrés académico en adolescentes de tercero de secundaria de una institución educativa policial de Huancayo, 2022

El estudio titulado inteligencia emocional y estrés académico en adolescentes de tercero de secundaria de una institución educativa policial de Huancayo, 2022, el cual tuvo como finalidad indicar la relación que existe entre inteligencia emocional y estrés académico en adolescentes de tercero de secundaria de una institución educativa policial de Huancayo, 2022. Por lo cual se construyó el siguiente problema: ¿existe relación entre inteligencia emocional y estrés académico en adolescentes de tercero de secundaria de una institución educativa policial de Huancayo, 2022? Seguidamente se planteó la hipótesis: sí, existe relación inversa entre inteligencia emocional y estrés académico en adolescentes de tercero de secundaria de una institución educativa policial de Huancayo, 2022. Asimismo, la investigación es de diseño correlacional transversal, tipo básica, nivel correlacional, lográndose trabajar con una muestra de 80 adolescentes, a los que se aplicó los instrumentos Inventario de Inteligencia Emocional de BarOn Ice-Forma Abreviada e Inventario Sistémico Cognoscitivista de estrés académico- SISCO. El análisis de resultados y la contrastación de hipótesis se realizaron con el estadígrafo prueba rho de Spearman, llegando a concluir que existe relación inversa y moderada entre inteligencia emocional y estrés académico en adolescentes de tercero de secundaria de una institución educativa policial de Huancayo, 2022. Donde el 28,7 % de la muestra tienen inteligencia emocional medio y estrés académico moderado, empleando rho de Spearman rs= - .497, situándose en relación inversa y moderada, de la misma manera se obtuvo p = .008 < .05 corrobora la relación

Surgical findings and outcomes after unilateral adrenalectomy for primary hyperaldosteronism in cats: a multi-institutional retrospective study

Case series summary: Twenty-nine cats from different institutions with confirmed or highly suspected primary hyperaldosteronism treated by unilateral adrenalectomy were retrospectively included in this study. The most frequent clinical signs were lethargy (n = 20; 69%) and neck ventroflexion (n = 17; 59%). Hypokalaemia was present in all cats, creatinine kinase was elevated in 15 and hyperaldosteronism was documented in 24. Hypertension was frequently encountered (n = 24; 89%). Preoperative treatment included potassium supplementation (n = 19; 66%), spironolactone (n = 16; 55%) and amlodipine (n = 11; 38%). There were 13 adrenal masses on the right side, 15 on the left and, in one cat, no side was reported. The median adrenal mass size was 2 × 1.5 cm (range 1-4.6 × 0.4-3.8); vascular invasion was present in five cats, involving the caudal vena cava in four cats and the renal vein in one. Median duration of surgery was 57 mins. One major intraoperative complication (3%) was reported and consisted of haemorrhage during the removal of a neoplastic thrombus from the caudal vena cava. In 4/29 cats (14%), minor postoperative complications occurred and were treated medically. One fatal complication (3%) was observed, likely due to disseminated intravascular coagulation. The median duration of hospitalisation was 4 days; 97% of cats survived to discharge. The potassium level normalised in 24 cats within 3 months of surgery; hypertension resolved in 21/23 cats. Follow-up was available for 25 cats with a median survival of 1082 days. Death in the long-term follow-up was mainly related to worsening of comorbidities. Relevance and novel information: Adrenalectomy appears to be a safe and effective treatment with a high rate of survival and a low rate of major complications. Long-term medical treatment was not required

El arte de lo diáfano

En este trabajo analizaremos el corto Diáfano realizado en el marco de la cursada de la materia Realización 1 en el año 2008 de la Facultad de Artes, UNLP con los conceptos desarrollados en la materia Estética, de la misma Facultad. Esto puede ser posible debido a que la estructura del cortometraje remite directamente a lo simbólico, a aquello que muestra y que oculta, dejando en nosotros, como espectadores, la oportunidad de re-significarlo, de interpretarlo y adherirlo según nuestros recuerdos. Pero, en base a su contenido y forma no convencional, surge el interrogante de si Diáfano puede ser considerado una obra de arte. El eje fundamental es intentar responder a la pregunta ¿se puede representar los sentimientos? ¿Esto es una obra de arte? ¿Es un medio de comunicación? Para esto elegimos a los autores Gadamer (1998), Grüner (2000 y 2004) y de Gyldenfeldt (2008).Facultad de Arte

Mishkinchando la creatividad y la autonomía al estilo Shimishanga : sistematización de la experiencia de la I.E. 18214, Cochamal, Rodríguez de Mendoza, Amazonas

En la Institución Educativa (I.E.) 1814 San Marcos de Cochamal se marcó un hito en nuestra labor docente al promover espacios de reflexión en los cuales se formuló estas preguntas: ¿cuántas veces hemos usado verbos en modo imperativo para pedir a nuestros alumnos escribir un cuento, un poema o que dibujen? ¿Cuántas veces no hemos dado importancia a espacios acogedores para la germinación de ideas y la consolidación de propuestas creativas y originales dentro de la escuela? ¿Hemos respetado los puntos de vista o intereses de los niños como elementos fortalecedores de su autonomía? ¿Hemos considerado sus situaciones de vida en familia y sociedad como factores influyentes en su creatividad y autonomía? Dichas interrogantes nos ponen de cara ante uno de los problemas que enfrenta la educación pública en nuestro país, que es la carencia de autonomía en el proceso creativo de los estudiantes. Frente a esta realidad, se implementó el proyecto “Dejad que los niños nos cuenten”. Esta experiencia fue movilizada a través de la estrategia Shimishanga, la cual ha permitido a los docentes proponer técnicas para la escritura de cuentos y poemas en el taller “Libertad para crear”; los textos producidos fueron compartidos de manera oral con la comunidad educativa en diversos espacios pedagógicos dentro y fuera de la escuela, entre ellos, el “Paraje Cultural”. Los escritos de los niños fueron editados y publicados a nivel institucional en la revista “Llovizna” y en el libro “Cuentos no contados”, en sus diversas ediciones. La sistematización del proyecto innovador da cuenta del proceso de reflexión dinámico de los diversos actores, quienes desarrollaron sinergias para que los estudiantes expresen sus pensamientos, emociones e impresiones a través de narraciones y poemas llenos de matices que recogen la esencia de la flora, la fauna, sus costumbres, creencias y aspiraciones sociales. Su finalidad es dar a conocer el funcionamiento de la estrategia Shimishanga en el desarrollo de la creatividad y el fortalecimiento de la autonomía de los estudiantes para ser ciudadanos proactivos y éticos. Con este aporte, se deja abierta la oportunidad para profundizar en el desarrollo de la estrategia y su contextualización, con el objetivo de constituirse en una propuesta pedagógica inspiradora para las instituciones multigrado de nivel primario orientadas a la formación integral de los niños

Binding hotspots of BAZ2B bromodomain: Histone interaction revealed by solution NMR driven docking.

Bromodomains are epigenetic reader domains, which have come under increasing scrutiny both from academic and pharmaceutical research groups. Effective targeting of the BAZ2B bromodomain by small molecule inhibitors has been recently reported, but no structural information is yet available on the interaction with its natural binding partner, acetylated histone H3K14ac. We have assigned the BAZ2B bromodomain and studied its interaction with H3K14ac acetylated peptides by NMR spectroscopy using both chemical shift perturbation (CSP) data and clean chemical exchange (CLEANEX-PM) NMR experiments. The latter was used to characterize water molecules known to play an important role in mediating interactions. Besides the anticipated Kac binding site, we consistently found the bromodomain BC loop as hotspots for the interaction. This information was used to create a data-driven model for the complex using HADDOCK. Our findings provide both structure and dynamics characterization that will be useful in the quest for potent and selective inhibitors to probe the function of the BAZ2B bromodomain.This is the final published version of the article. It has been published by the American Chemical Society in Biochemistry. The article can be accessed on their website here: http://pubs.acs.org/doi/abs/10.1021/bi500909d. It is freely available under a CC BY licence

USP18-Based Negative Feedback Control Is Induced by Type I and Type III Interferons and Specifically Inactivates Interferon α Response

Type I interferons (IFN) are cytokines that are rapidly secreted upon microbial infections and regulate all aspects of the immune response. In humans 15 type I IFN subtypes exist, of which IFN α2 and IFN β are used in the clinic for treatment of different pathologies. IFN α2 and IFN β are non redundant in their expression and in their potency to exert specific bioactivities. The more recently identified type III IFNs (3 IFN λ or IL-28/IL-29) bind an unrelated cell-type restricted receptor. Downstream of these two receptor complexes is a shared Jak/Stat pathway. Several mechanisms that contribute to the shut down of the IFN-induced signaling have been described at the molecular level. In particular, it has long been known that type I IFN induces the establishment of a desensitized state. In this work we asked how the IFN-induced desensitization integrates into the network built by the multiple type I IFN subtypes and type III IFNs. We show that priming of cells with either type I IFN or type III IFN interferes with the cell's ability to further respond to all IFN α subtypes. Importantly, primed cells are differentially desensitized in that they retain sensitivity to IFN β. We show that USP18 is necessary and sufficient to induce differential desensitization, by impairing the formation of functional binding sites for IFN α2. Our data highlight a new type of differential between IFNs α and IFN β and underline a cross-talk between type I and type III IFN. This cross-talk could shed light on the reported genetic variation in the IFN λ loci, which has been associated with persistence of hepatitis C virus and patient's response to IFN α2 therapy

A2ML1 and otitis media : novel variants, differential expression, and relevant pathways

A genetic basis for otitis media is established, however, the role of rare variants in disease etiology is largely unknown. Previously a duplication variant within A2ML1 was identified as a significant risk factor for otitis media in an indigenous Filipino population and in US children. In this report exome and Sanger sequencing was performed using DNA samples from the indigenous Filipino population, Filipino cochlear implantees, US probands, Finnish, and Pakistani families with otitis media. Sixteen novel, damaging A2ML1 variants identified in otitis media patients were rare or low-frequency in population-matched controls. In the indigenous population, both gingivitis and A2ML1 variants including the known duplication variant and the novel splice variant c.4061 + 1 G>C were independently associated with otitis media. Sequencing of salivary RNA samples from indigenous Filipinos demonstrated lower A2ML1 expression according to the carriage of A2ML1 variants. Sequencing of additional salivary RNA samples from US patients with otitis media revealed differentially expressed genes that are highly correlated with A2ML1 expression levels. In particular, RND3 is upregulated in both A2ML1 variant carriers and high-A2ML1 expressors. These findings support a role for A2ML1 in keratinocyte differentiation within the middle ear as part of otitis media pathology and the potential application of ROCK inhibition in otitis media.Peer reviewe