Suprachoroidal and Subretinal Injections of AAV Using Transscleral Microneedles for Retinal Gene Delivery in Nonhuman Primates.

Retinal gene therapy using adeno-associated viruses (AAVs) is constrained by the mode of viral vector delivery. Intravitreal AAV injections are impeded by the internal limiting membrane barrier, while subretinal injections require invasive surgery and produce a limited region of therapeutic effect. In this study, we introduce a novel mode of ocular gene delivery in rhesus macaques using transscleral microneedles to inject AAV8 into the subretinal or suprachoroidal space, a potential space between the choroid and scleral wall of the eye. Using in vivo imaging, we found that suprachoroidal AAV8 produces diffuse, peripheral expression in retinal pigment epithelial (RPE) cells, but it elicited local infiltration of inflammatory cells. Transscleral subretinal injection of AAV8 using microneedles leads to focal gene expression with transduction of RPE and photoreceptors, and minimal intraocular inflammation. In comparison, intravitreal AAV8 shows minimal transduction of retinal cells, but elicits greater systemic humoral immune responses. Our study introduces a novel mode of transscleral viral delivery that can be performed without vitreoretinal surgery, with focal or diffuse transgene expression patterns suitable for different applications. The decoupling of local and systemic immune responses reveals important insights into the immunological consequences of AAV delivery to different ocular compartments surrounding the blood-retinal barrier

The role of clinically significant antiphospholipid antibodies in systemic lupus erythematosus

The objective is to investigate the role of clinically significant antiphospholipid antibodies (aPL) in a cohort of systemic lupus erythematosus (SLE) patients. All SLE patients followed for at least 5 years and with available aPL profile at the beginning of the follow-up in our center were studied. Clinically significant aPL were defined as: positive lupus anticoagulant test, anti-cardiolipin and/or anti- β2Glycoprotein I IgG/IgM >99th percentile on two or more occasions at least 12 weeks apart. Patients with and without clinically significant aPL were compared by univariate (Chi square or Fisher's exact test for categorical variables and Student's t or Mann-Whitney test for continuous variables) and multivariate analysis (logistic regression analysis). P values <0.05 were considered significant. Among 317 SLE patients studied, 117 (37%) had a clinically significant aPL profile at baseline. Such patients showed at univariate analysis an increased prevalence of deep venous thrombosis, pulmonary embolism, cardiac valvular disease, cognitive dysfunction and antiphospholipid syndrome (APS), but a reduced prevalence of acute cutaneous lupus and anti-extractable nuclear antigens (ENA) when compared with patients without clinically significant aPL. Multivariate analysis confirmed the association between clinically significant aPL and reduced risk of acute cutaneous lupus [p=0.003, odds ratio (OR) 0.43] and ENA positivity (p<0.001, OR 0.37), with increased risk of cardiac valvular disease (p=0.024, OR 3.1) and APS (p<0.0001, OR 51.12). Triple positivity was the most frequent profile and was significantly associated to APS (p<0.0001, OR 28.43). Our study showed that one third of SLE patients had clinically significant aPL, and that this is associated with an increased risk, especially for triple positive, of APS, and to a different clinical and serological pattern of disease even in the absence of APS

The gastrointestinal parasite community of wild guanacos (Lama guanicoe) from La Payunia Provincial Reserve, Mendoza, Argentina

Los vertebrados silvestres albergan comunidades parasitarias compuestas por varias especies, pero la estructura natural de estas comunidades se está viendo afectada en la actualidad por la fragmentación de hábitat e introducción de especies exóticas. El objetivo de este trabajo fue identificar a las especies de parásitos gastrointestinales presentes en la población migratoria de guanacos silvestres de la Reserva Provincial La Payunia (Mendoza), mediante la identificación de las formas evolutivas presentes en la materia fecal. Se analizaron las heces de 756 individuos, colectadas entre los años 2009 y 2012. La comunidad parasitaria gastrointestinal de esta población de guanacos estuvo compuesta por al menos 11 especies. Los parásitos pertenecieron a 5 especies de nematodes: 2 de Nematodirus, 1 de Trichuris, 1 de Capillaria y 1 de Strongyloides; 1 especie de cestode correspondiente a Moniezia benedeni, y 5 especies de protozoos del género Eimeria (E. lamae, E. alpacae, E. punoensis, E. macusaniensis y E. ivitaensis). Nematodirus spp., Strongyloides sp., y Moniezia benedeni son parásitos propios de rumiantes domésticos y su presencia refleja la susceptibilidad del guanaco, por lo que se recomienda realizar monitoreos parasitológicos periódicos, a fin de poder anticiparse ante incrementos importantes en este tipo de parasitismo en los guanacos silvestres.The parasite community of wild vertebrate hosts is composed of several species, but the natural structure of these communities is currently being affected by habitat fragmentation and the introduction of exotic species. The aim of this work was to identify, through the recognition of immature stages in feces, the gastrointestinal parasite species present in the migratory wild guanaco population from La Payunia Reserve (Mendoza). Feces of 756 individuals, collected between 2009 and 2012, were analyzed. The gastrointestinal parasite community of this guanaco population consisted of at least 11 species. Parasites belonged to 5 nematode species: 2 of Nematodirus, 1 of Trichuris, 1 of Capillaria, and 1 of Strongyloides; 1 cestode species corresponding to Moniezia benedeni; and 5 protozoan species of the genus Eimeria (E. lamae, E. alpacae, E. punoensis, E. macusaniensis, and E. ivitaensis). Nematodirus spp., Strongyloides sp., and the detected spe­cies of Moniezia are typical parasites of livestock, and their presence reflects the guanaco susceptibility to be parasitized by them. We suggest conducting parasitological surveys periodically to be able to anticipate to an important rise in this type of parasitism in wild guanacos.Fil: Moreno, Pablo Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Shroeder, Natalia M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Taraborelli, Paula Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Gregorio, Pablo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Carmanchahi, Pablo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Beldomenico, Pablo Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentin

Macrophage activation syndrome in adult systemic lupus erythematosus: report of seven adult cases from a single Italian rheumatology center.

The aim was to describe the macrophage activation syndrome (MAS), a life-threatening syndrome characterized by excessive immune activation that can be triggered by conditions affecting immune homeostasis, in a cohort of adult Italian patients with systemic lupus erythematosus (SLE). This was a monocentric retrospective evaluation. The utility of the H-score, developed to estimate the individual risk of having reactive MAS in adult patients, was assessed. Among 511 patients with SLE, 7 cases (1.4%) of MAS (all females) were identified and their medical records reviewed. In all cases, MAS was simultaneous to the onset of SLE. All patients had fever, lymphadenopathy, hematological involvement, and high titer of anti-dsDNA antibodies. Workup for infections and malignancies was negative. In all cases, the H-score was higher than the cut-off suggested for the classification of reactive MAS. All cases required hospital admission, and 2 patients were admitted to the intensive care unit. Most patients were treated successfully with high doses of corticosteroids and with immunosuppressive drugs, whereas the full therapeutic regimen developed for primary hemophagocytic lymphohistiocytosis HLH was used only in one case. No death from MAS was observed. MAS is a rare and severe disorder that complicated the onset of SLE in our cohort. The H-score may be useful in the classification of these patients

Termotratamiento en madera de álamo como alternativa de mejora de su resistencia al biodeterioro

El interés por el uso del termotratamiento como técnica de mejora de las propiedades físicas, mecánicas y de durabilidad de la madera, data desde hace varias décadas y actualmente ha cobrado interés debido principalmente a la escasez de maderas resistentes al biodeterioro y con características tecnológicas (físico-mecánicas) apropiadas, como así también a la demanda de procedimientos alternativos y amigables con el medio ambiente para la mejora de dichas propiedades. Esto además, sumado a la creciente demanda de materiales constructivos sostenibles en general. Objetivo del trabajo: aplicar tratamientos de termo-modificación a la madera de Populus x canadensis ‘I-214’ como alternativa menos nociva para mejorar su resistencia al ataque de agentes bióticos de deterioro. Se trabajó con probetas dimensionadas según lo establecido en la norma UNE 56528:1978. Los ensayos de biodeterioro fueron realizados atendiendo a los procedimientos indicados en las normas CEN/TS 15083-1:2005 (durabilidad frente a hongos xilófagos) y EN 117:2012 (durabilidad frente a termitas). De acuerdo con ello, fue evaluada la resistencia del material expuesto a la cepas de pudrición castaña: Coniophora puteana; pudrición blanca: Trametes versicolor y a la acción de termitas: Reticulitermes grassei. Para la realización del termotratamiento se trabajó con 4 temperaturas (80, 120, 160 y 200°C) combinadas con 4 tiempos (45, 90, 135 y 180 minutos); paralelamente se trabajó con madera sin termotratar como material testigo. Resultados obtenidos: frente a hongos de pudrición castaña, la madera experimentó un porcentaje de pérdida de peso, Pp (%), descendente con el aumento de la temperatura. En cuanto al tiempo de exposición, las Pp (%) fueron estadísticamente inferiores cuando el material estuvo expuesto durante 135 minutos. Frente a hongos de pudrición blanca y de termitas, el único factor influyente en la bioresistencia fue la temperatura. Asimismo, para los hongos de pudrición blanca no pudo evidenciarse un comportamiento homogéneo en la evolución de las Pp (%) con los rangos de temperaturas empleados, mientras que para termitas, a 80°C se evidenció una tasa de supervivencia TS (%) superior con respecto a las otras temperaturas. En términos generales estos comportamientos podrían estar vinculados a la degradación de la lignina en el caso de los hongos de pudrición blanca, a la menor concentración de grupos hidroxilos con capacidad de absorber agua en el caso de los hongos de pudrición castaña y a la mayor disponibilidad de humedad que presenta la madera a bajas temperaturas, para la supervivencia de las termitas.Laboratorio de Investigaciones en Mader

Dynamics in online social networks

An increasing number of today's social interactions occurs using online social media as communication channels. Some online social networks have become extremely popular in the last decade. They differ among themselves in the character of the service they provide to online users. For instance, Facebook can be seen mainly as a platform for keeping in touch with close friends and relatives, Twitter is used to propagate and receive news, LinkedIn facilitates the maintenance of professional contacts, Flickr gathers amateurs and professionals of photography, etc. Albeit different, all these online platforms share an ingredient that pervades all their applications. There exists an underlying social network that allows their users to keep in touch with each other and helps to engage them in common activities or interactions leading to a better fulfillment of the service's purposes. This is the reason why these platforms share a good number of functionalities, e.g., personal communication channels, broadcasted status updates, easy one-step information sharing, news feeds exposing broadcasted content, etc. As a result, online social networks are an interesting field to study an online social behavior that seems to be generic among the different online services. Since at the bottom of these services lays a network of declared relations and the basic interactions in these platforms tend to be pairwise, a natural methodology for studying these systems is provided by network science. In this chapter we describe some of the results of research studies on the structure, dynamics and social activity in online social networks. We present them in the interdisciplinary context of network science, sociological studies and computer science.Comment: 17 pages, 4 figures, book chapte

Anti-cyclic citrullinated peptide antibodies in systemic lupus erythematosus patients with articular involvement: a predictive marker for erosive disease?

summary A small number of systemic lupus erythematosus (SLE) patients develops an erosive disease. Some studies have suggested an association between anti-cyclic citrullinated (anti-CCP) antibodies and this pattern of arthritis, but their exact significance in SLE patients remains unclear. The aim of this study was to evaluate the prevalence of anti-CCP antibodies in SLE patients with different subsets of articular disease. Among 521 SLE patients followed in this center from 1976 to 2011, those with articular involvement (n=298) were selected to take part in the study. We searched for anti-CCP2 IgG antibodies in 198 patients using a commercial enzyme linked immunosorbent assay (Immunoscan RA, Eurodiagnostica). In 174 patients the results for rheumatoid factor (RF) by nephelometry were retrospectively collected. C reactive protein (CRP) was obtained from clinical records. Patients were classified into 3 groups: erosive, non-erosive deforming, non-erosive non-deforming arthritis. Results of the different tests were compared among the groups. P<0.05 was considered statistically significant. Anti-CCP antibodies were significantly associated with erosive disease. We also found that RF positivity and increased CRP were more frequent in erosive arthritis and erosive or non-deforming arthritis, respectively, than in non-erosive non-deforming arthritis. This study supports the evidence that anti-CCP antibodies could be a useful marker of erosive disease in SLE patients. Increase in RF and CRP could be an additional means of identifying lupus patients with arthritis at risk of a worse prognosis