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INTRODUCTION: The high prevalence of musculoskeletal disorders in pathologists, together with the current trend towards the digitization of pathology, prompted us to study the different types of input devices employed during the revision of whole slide images, in order to investigate the pattern and extent of muscle activity involved in their use. MATERIAL AND METHODS: A comparative study was made of 10 input devices (conventional and vertical mouse, three trackballs, the Ergopointer™, the Rollermouse™, an optical pen mouse, a touchpad, and the Leap Motion™). Six medical students performed a standardized circuit using a Fitts' Law based tissue array, digitized. The electrical activity of seven upper limb muscles (adductor pollicis, extensor pollicis longus, extensor digitorum, flexor digitorum, middle deltoid, upper trapezius, and middle trapezius) was measured using surface electromyography. RESULTS: Statistically significant differences in the overall electrical activity among the different input devices, both absolute values in mV as well as normalized values to the upper limb at rest, were observed (p

A massive release of platelet-derived CD9(+) microvesicles occurs during HIV infection, regardless of virologic control or antiretroviral therapy administration. Some of these microvesicles contain mitochondria, but their prevalence and mitochondrial density are reduced in HIV infection. Background The role of extracellular vesicles (EVs) in human immunodeficiency virus (HIV) pathogenesis is unknown. We examine the cellular origin of plasma microvesicles (MVs), a type of ectocytosis-derived EV, the presence of mitochondria in MVs, and their relationship to circulating cell-free mitochondrial deoxyribonucleic acid (ccf-mtDNA) in HIV-infected patients and controls. Methods Five participant groups were defined: 30 antiretroviral therapy (ART)-naive; 30 ART-treated with nondetectable viremia; 30 elite controllers; 30 viremic controllers; and 30 HIV-uninfected controls. Microvesicles were quantified and characterized from plasma samples by flow cytometry. MitoTrackerDeepRed identified MVs containing mitochondria and ccf-mtDNA was quantified by real-time polymerase chain reaction. Results Microvesicle numbers were expanded at least 10-fold in all HIV-infected groups compared with controls. More than 79% were platelet-derived MVs. Proportions of MVs containing mitochondria (22.3% vs 41.6%) and MV mitochondrial density (706 vs 1346) were significantly lower among HIV-infected subjects than controls, lowest levels for those on ART. Microvesicle numbers correlated with ccf-mtDNA levels that were higher among HIV-infected patients. Conclusions A massive release of platelet-derived MVs occurs during HIV infection. Some MVs contain mitochondria, but their proportion and mitochondrial densities were lower in HIV infection than in controls. Platelet-derived MVs may be biomarkers of platelet activation, possibly reflecting pathogenesis even in absence of HIV replication.

HIV-1 infection remains incurable despite the efficient combined antiretroviral therapy (cART) due to the formation of long-lived viral reservoirs that are mostly settled in CD4+T cells and maintained by homeostatic proliferation. The use of cytostatic drugs such as tyrosine kinase inhibitors (TKIs) as adjuvants to cART could be helpful to avoid the reservoir establishment and replenishment. We determined previously that TKI dasatinib, which is successfully used for treating chronic myeloid leukemia (CML), shows antiviral effect against HIV-1 infection of CD4 + T cells in vitro. HIV-infected subjects that developed CML may safely combine long-term treatment with TKIs and cART but there is no information about the effect of dasatinib on HIV-1 reservoir in vivo. Therefore, we analyzed the ability of dasatinib to protect NSG mice engrafted with human CD34 + hematopoietic stem cells from HIV-1 infection. Mice were randomly assigned to two groups that received dasatinib or placebo daily by oral gavage. After five days, all mice were infected intraperitoneally with HIV-1 and followed up for 21?days in the absence of cART. Daily administration of dasatinib decreased viral and proviral load in all treated mice, showing in 40% of these mice undetectable viral RNA or DNA in blood. Proviral HIV-1 DNA in gut-associated lymphoid tissue (GALT) was also reduced in all dasatinib-treated mice and under the limit of detection in one of these mice. Finally, treatment with dasatinib modified the distribution of CD4 + and CD8 + T-cell subpopulations, delaying their differentiation into memory T-cell subsets that are a major component of the viral reservoir. In conclusion, dasatinib afforded protection of NSG mice from HIV-1 intraperitoneal infection in the absence of cART.

En la primera mitad del siglo V, Nono de Panópolis se sirve del griego homérico para parafrasear en cerca de 3700 hexámetros dactílicos el Evangelio de san Juan. En el presente trabajo tratamos de descubrir, mediante el análisis de los títulos cristológicos empleados en el poema, qué significa para Nono de Panópolis la figura de Jesús de Nazaret. Tras examinar los pasajes que presentan a Jesús como enviado y revelador del Padre, se analizan los títulos cristológicos que hacen referencia más directa a la esencia de Jesús: Logos, Dios verdadero, Hijo unigénito de Dios, sabio Hijo del hombre y Cristo verdadero. A continuación, se estudian los títulos relacionados con dos de los tria munera (rey y profeta) y se analizan los «Yo soy» de Jesús. Nono, a la vez que reconstruye el relato evangélico paso a paso y lo adorna con un lenguaje y una técnica literaria muy elaborados, va perfilando en la mente del lector una figura de Cristo en la que destacan su poder, su realeza y, sobre todo, su divinidad. El poeta evita las polémicas cristológicas que salpican el entorno alejandrino durante el siglo V, pues su obra no es un comentario del texto evangélico, sino una relectura que mantiene, aunque con cierta ambigüedad, la ortodoxia, y procura hacer más atractivo el mensaje del Evangelio para un público culto. Con el objetivo de hacer más asequible el estudio de la obra y facilitar futuras investigaciones, se ofrece también la primera traducción completa en castellano de la Paráfrasis. In the first half of the fifth century, Nonnus of Panopolis uses Homeric Greek to paraphrase the Gospel of Saint John in about 3700 dactylic hexameters. In the present work we try to discover, through the analysis of the Christological titles used in the poem, what the figure of Jesus of Nazareth means to Nonnus of Panopolis. After examining the passages that present Jesus as sent and revealed by the Father, the Christological titles that refer more directly to the essence of Jesus are analyzed: Logos, true God, only begotten Son of God, wise Son of man and true Christ. Next, the titles related to two of the tria munera (king and prophet) are studied and the «I am» of Jesus are analyzed. Nonnus, while rebuilding the Gospel story step by step and decorating it with a very elaborate language and literary technique, is shaping in the mind of the reader a figure of Christ in which are highlighted his power, his royalty and especially his divinity. The poet avoids the Christological polemics affecting the Alexandrian environment during the fifth century, because his work is not a commentary on the Gospel text, but a rereading that maintains, although with some ambiguity, orthodoxy, and seeks to make the message of the Gospel more attractive for a cultured public. In order to make the study of the work more accessible and facilitate future research, the first complete translation in Spanish of the Paraphrase is also offered.

BACKGROUND: The role of extracellular vesicles (EVs) in HIV pathogenesis is unknown. We examine the cellular origin of plasma microvesicles (MVs), a type of ectocytosis-derived EV, the presence of mitochondria in MVs, and their relationship to circulating cell-free mitochondrial DNA (ccf-mtDNA) in HIV-infected patients and controls. METHODS: Five participant groups were defined: 30 ART-naive; 30 ART-treated with non-detectable viremia; 30 elite controllers; 30 viremic controllers; and 30 HIV-uninfected controls. MVs were quantified and characterized from plasma samples by flow cytometry. MitoTrackerDeepRed identified MVs containing mitochondria and ccf-mtDNA was quantified by real-time PCR. RESULTS: MV numbers were expanded at least 10-fold in all HIV-infected groups compared to controls. More than 79% were platelet-derived MVs. Proportions of MVs containing mitochondria (22.3% vs. 41.6%) and MV mitochondrial density (706 vs. 1346) were significantly lower among HIV-infected subjects than controls, lowest levels for those on ART. MV numbers correlated with ccf-mtDNA levels that were higher among HIV-infected patients. CONCLUSIONS: A massive release of platelet-derived MVs occurs during HIV infection. Some MVs contain mitochondria, but their proportion and mitochondrial densities were lower in HIV infection than in controls. Platelet-derived MVs may be biomarkers of platelet activation, possibly reflecting pathogenesis even in absence of HIV replication.