Upregulation of retinal VEGF and connexin 43 in murine nonarteritic anterior ischemic optic neuropathy induced with 577 nm laser.

Nonarteritic anterior ischemic optic neuropathy (NAION) is a common acute optic neuropathy and cause of irreversible vision loss in those older than 50 years of age. There is currently no effective treatment for NAION and the biological mechanisms leading to neuronal loss are not fully understood. Promising novel targets include glial cells activation and intercellular communication mediated by molecules such as gap junction protein Connexin 43 (Cx43), which modulate neuronal fate in central nervous system disorders. In this study, we investigated retinal glial changes and neuronal loss following a novel NAION animal model using a 577 nm yellow laser. We induced unilateral photochemical thrombosis using rose bengal at the optic nerve head vasculature in adult C57BL/6 mice using a 577 nm laser and performed morphometric analysis of the retinal structure using serial in vivo optical coherence tomography (OCT) and histology for glial and neuronal markers. One day after experimental NAION, in acute phase, OCT imaging revealed peripapillary thickening of the retinal ganglion cell complex (GCC, baseline: 79.5 ±â€¯1.0 µm, n = 8; NAION: 93.0 ±â€¯2.5 µm, n = 8, P < 0.01) and total retina (baseline: 202.9 ±â€¯2.4 µm, n = 8; NAION: 228.1 ±â€¯6.8 µm, n = 8, P < 0.01). Twenty-one days after ischemia, at a chronic phase, there was significant GCC thinning (baseline 78.3 ±â€¯2.1 µm, n = 6; NAION: 72.2 ±â€¯1.9 µm, n = 5, P < 0.05), mimicking human disease. Examination of molecular changes in the retina one day after ischemia revealed that NAION induced a significant increase in retinal VEGF levels (control: 2319 ±â€¯195, n = 5; NAION: 4549 ±â€¯683 gray mean value, n = 5, P < 0.05), which highly correlated with retinal thickness (r = 0.89, P < 0.05). NAION also led to significant increase in mRNA level for Cx43 (Gj1a) at day 1 (control: 1.291 ±â€¯0.38; NAION: 3.360 ±â€¯0.58 puncta/mm2, n = 5, P < 0.05), but not of glial fibrillary acidic protein (Gfap) at the same time (control: 2,800 ±â€¯0.59; NAION: 4,690 ±â€¯0.90 puncta/mm2 n = 5, P = 0.19). Retinal ganglion cell loss at day 21 was confirmed by a 30% decrease in Brn3a+ cells (control: 2,844 ±â€¯235; NAION: 2,001 ±â€¯264 cells/mm2, n = 4, P < 0.05). We described a novel protocol of NAION induction by photochemical thrombosis using a 577 nm laser, leading to retinal edema and VEGF increase at day 1 and RGCs loss at day 21 after injury, consistent with the pathophysiology of human NAION. Early changes in glial cells intercommunication revealed by increased Cx43+ gap junctions are consistent with a retinal glial role in mediating cell-to-cell signaling after an ischemic insult. Our study demonstrates an early glial response in a novel NAION animal model and reveals glial intercommunication molecules such as Cx43 as a promising therapeutic target in acute NAION.

Hypoxia-induced inflammation: Profiling the first 24-hour posthypoxic plasma and central nervous system changes.

Central nervous system and visual dysfunction is an unfortunate consequence of systemic hypoxia in the setting of cardiopulmonary disease, including infection with SARS-CoV-2, high-altitude cerebral edema and retinopathy and other conditions. Hypoxia-induced inflammatory signaling may lead to retinal inflammation, gliosis and visual disturbances. We investigated the consequences of systemic hypoxia using serial retinal optical coherence tomography and by assessing the earliest changes within 24h after hypoxia by measuring a proteomics panel of 39 cytokines, chemokines and growth factors in the plasma and retina, as well as using retinal histology. We induced severe systemic hypoxia in adult C57BL/6 mice using a hypoxia chamber (10% O2) for 1 week and rapidly assessed measurements within 1h compared with 18h after hypoxia. Optical coherence tomography revealed retinal tissue edema at 18h after hypoxia. Hierarchical clustering of plasma and retinal immune molecules revealed obvious segregation of the 1h posthypoxia group away from that of controls. One hour after hypoxia, there were 10 significantly increased molecules in plasma and 4 in retina. Interleukin-1ß and vascular endothelial growth factor were increased in both tissues. Concomitantly, there was significantly increased aquaporin-4, decreased Kir4.1, and increased gliosis in retinal histology. In summary, the immediate posthypoxic period is characterized by molecular changes consistent with systemic and retinal inflammation and retinal glial changes important in water transport, leading to tissue edema. This posthypoxic inflammation rapidly improves within 24h, consistent with the typically mild and transient visual disturbance in hypoxia, such as in high-altitude retinopathy. Given hypoxia increases risk of vision loss, more studies in at-risk patients, such as plasma immune profiling and in vivo retinal imaging, are needed in order to identify novel diagnostic or prognostic biomarkers of visual impairment in systemic hypoxia.

Superparamagnetic iron oxide nanoparticles as a tool to track mouse neural stem cells in vivo.

Cell transplantation offers a promising approach in many neurological disorders. Neural stem (NS) cells are potential candidates for cell therapy. The ability to track the grafted cells in the host tissue will refine this therapy. Superparamagnetic iron oxide nanoparticles (SPION) have been suggested as a feasible method, but there is no consensus about its safety. Here we investigated the feasibility of label NS cells with SPION and track by MRI after transplantation into mouse striatum with SPION cells and its therapeutic effects by grafting the cells into mouse striatum. We demonstrated that SPION-labeled NS cells display normal patterns of cellular processes including proliferation, migration, differentiation and neurosphere formation. Transmission electron microscopy reveals SPION in the cytoplasm of the cells, which was confirmed by microanalysis. Neurons and astrocytes generated from SPION-labeled NS cells were able to carry nanoparticles after 7 days under differentiation. SPION-labeled NS cells transplanted into striatum of mice were detected by magnetic resonance imaging (MRI) and microscopy 51 days later. In agreement with others reports, we demonstrated that NS cells are able to incorporate SPION in vitro without altering the stemness, and can survive and be tracked by MRI after they have been grafted into mice striatum.

Proposal for a universal measurement system for school chairs and desks for children from 6 to 10 years old.

In a primary education classroom of any country, children of the same age have very different statures, reaching variations of 200 mm (Gonçalves, 2012). However, the school furniture provided is not suitable or adaptable to these differences. Designing school furniture able to respond to these variations is, therefore, a challenge for ergonomics and design in a global market. It is clearly not viable for industries to adapt productions for each country. When competitiveness and limitation of resources are essential for the viability of any product it becomes essential to find a universal system adapted to the requisites of any country. Taking as prescription measure the popliteal height obtained from the data of different countries, a universal measurement system for the school chair and desk set is proposed, combining the ellipse methodology used by Molenbroek et al. (2003) and the (mis)match equations mentioned by Castellucci et al. (2014b). From the results obtained, it can be concluded that only 5 sizes are needed to implement this new measurement system of evolutionary school furniture for the primary education classroom.

Prevalencia de las alteraciones biliopancreáticas asociadas a divertículo duodenal papilar / Yuxtapapillary duodenal diverticula relationship with biliopancreatic disorders

Aproximadamente 75 por ciento de los divertículos duodenales yuxtapapilares (DDY) se localizan a 2 cm o menos del ámpula de Vater y se asocian con una elevada incidencia de cálculos vesiculares del colédoco, y a cuadros de pancreatitis recurrente. En un estudio ambipectivo y descriptivo que se realizó en un periodo de 8 años encontramos que de 680 colangiopancreatografías endoscópicas (CPE), 33 pacientes (4.8 por ciento) tiene DDY, la variedad más común fue localizado al borde de la papila en 15 pacientes (45.4 por ciento). El diagnóstico clínico de referencia más frecuente fue ictericia en 19 casos (57.5 por ciento) y cuadros sugestivos de pancreatitis en 11 casos (33.3 por ciento). El hallazgo endoscópico fue la colédocolitiasis en 14 casos (52.5 por ciento) y dilatación del conducto pancreático en 7 (21.2 por ciento). La primera se trato por vía endoscópica satisfactoriamente en 10 casos (30.3 por ciento)