Optical Coherence Tomography Angiography Findings after Acute Intraocular Pressure Elevation in Patients with Diabetes Mellitus versus Healthy Subjects

Purpose: To assess the changes in optic nerve head and macular microvascular networks after acute intraocular pressure (IOP) rise in healthy eyes versus the eyes of diabetic patients. Methods: In this prospective, interventional, comparative study, 24 eyes of 24 adults including 12 eyes of healthy nondiabetic subjects and 12 eyes with mild or moderate non-proliferative diabetic retinopathy (NPDR) were enrolled. IOP elevation was induced by a suction cup attached to the conjunctiva. IOP and optical coherence tomography angiographic (OCTA) images of the optic disc and macula were obtained before and immediately after the IOP rise. Results: Baseline and post-suction IOPs were not significantly different between the two groups (all Ps > 0.05). The mean IOP elevation was 13.93 ± 3.41 mmHg among all eyes and was statistically significant as compared to the baseline in both groups (both Ps < 0.05). After IOP elevation, healthy eyes demonstrated a reduction in the vessel density in the whole image deep and superficial capillary plexuses and parafoveal deep capillary plexus (DCP) (all Ps < 0.05). In diabetic retinopathy, foveal vessel density at DCP decreased significantly following IOP rise (Ps = 0.003). In both groups, inside the disc, vessel density decreased significantly after IOP rise (both Ps < 0.05), however, no significant change was observed in peripapillary vessel density (both Ps > 0.05). Conclusion: Acute rise of IOP may induce different levels of microvascular changes in healthy and diabetic eyes. Optic disc microvasculature originating from the posterior ciliary artery may be more susceptible to IOP elevation than that of retinal microvasculature

Equivalent porous media (EPM) simulation of groundwater hydraulics and contaminant transport in Karst aquifers

Karst aquifers have a high degree of heterogeneity and anisotropy in their geologic and hydrogeologic properties which makes predicting their behavior difficult. This paper evaluates the application of the Equivalent Porous Media (EPM) approach to simulate groundwater hydraulics and contaminant transport in karst aquifers using an example from the North Coast limestone aquifer system in Puerto Rico. The goal is to evaluate if the EPM approach, which approximates the karst features with a conceptualized, equivalent continuous medium, is feasible for an actual project, based on available data and the study scale and purpose. Existing National Oceanic Atmospheric Administration (NOAA) data and previous hydrogeological U. S. Geological Survey (USGS) studies were used to define the model input parameters. Hydraulic conductivity and specific yield were estimated using measured groundwater heads over the study area and further calibrated against continuous water level data of three USGS observation wells. The water-table fluctuation results indicate that the model can practically reflect the steady-state groundwater hydraulics (normalized RMSE of 12.4%) and long-term variability (normalized RMSE of 3.0%) at regional and intermediate scales and can be applied to predict future water table behavior under different hydrogeological conditions. The application of the EPM approach to simulate transport is limited because it does not directly consider possible irregular conduit flow pathways. However, the results fromthe present study suggest that the EPM approach is capable to reproduce the spreading of a TCE plume at intermediate scales with sufficient accuracy (normalized RMSE of 8.45%) for groundwater resources management and the planning of contamination mitigation strategies

Régulation des domaines nucléaires par le réseau associé aux microtubules dans les muscles striés squelettiques

Skeletal muscle is composed of thousands of giant cells, known as myofibers. To develop myofibers, progenitor mononuclear cells, called myoblasts, fuse together and share their cytoplasm and nucleus with the forming syncytia. Within each myofiber, hundreds of nuclei, also termed myonuclei, are regularly positioned at the periphery, with exception of specialized zones such as neuromuscular junctions (NMJs) where several myonuclei are clustered. This precise myonuclei organization gives rise to myonuclear domains, which are theoretical territories transcriptionally supported by each myonucleus to guarantee a spatial and coordinated transcriptomic activity all along myofibers. Myonuclear domains are challenged in different types of myopathies where mispositioned myonuclei can be observed along and within myofibers. Yet, how myonuclear domains are regulated at the periphery of myofibers and how their disruption may contribute to the development of myopathies remain poorly understood. Microtubules (MTs) are highly dynamic structures which go through cycles of polymerization and depolymerization under the influence of their microtubules-associated proteins (MAPs) or post-translational modifications (PTMs). During the early steps of myofibers development, MTs actively participate in myonuclear domains formation by serving as railways for motor molecules which disperse myonuclei along the growing myofiber. Later on, it is the assembly of muscular sarcomeres which will push the dispersed myonuclei to the periphery of myofibers. How myonuclei are held at the periphery of myofibers is not clear, however, the presence of dense MTs cage around the peripheral myonuclei suggests that MTs and their associated proteins network may contribute to myonuclei positioning also in mature myofibers. In this study, we challenged MTs dynamics by altering its MAPs network or its PTMs proportion during myogenesis. By using various in vitro and in vivo knock-down and knock-out models, we show that MTs dynamics is reduced during myogenesis toward a more stable network in mature myofibers. We also report that increasing MTs dynamics can directly disrupt myonuclear domains at the periphery of myofibers, either by increasing myonuclei dynamics or by increasing myonuclei content per myofiber. In both cases, we propose mechanisms explaining how each form of disrupted myonuclear domains results in reduced muscle functionality.Le muscle squelettique est composé de milliers de cellules géantes, appelées les myofibres. Pour développer les myofibres, des cellules progénitrices mononucléées, appelées myoblastes, fusionnent et partagent leur cytoplasme et leur noyau avec les syncytiums en formation. Au sein de chaque myofibre, des centaines de noyaux sont régulièrement positionnés à la périphérie, à l'exception de zones spécialisées telles que les jonctions neuromusculaires (NMJs, pour neuromuscular junctions) où plusieurs noyaux sont regroupés. Cette organisation précise des noyaux donne naissance à des domaines nucléaires, qui sont des territoires théoriques supportés transcriptionnellement par chaque noyau pour garantir une activité transcriptomique coordonnée tout au long des myofibres. Les domaines nucléaires sont dérégulés dans différents types de myopathies où on observe des noyaux mal positionnés au long ou à l'intérieur des myofibres. Cependant, comment les domaines nucléaires sont régulés à la périphérie des myofibres et comment leur perturbation peut contribuer au développement de myopathies reste peu compris. Les microtubules (MT) sont des structures dynamiques qui passent par des cycles de polymérisation et de dépolymérisation sous l'influence de protéines associées (MAPs, pour microtubules associated proteins) ou des modifications post-traductionnelles (PTMs, pour post translational modifications). Au cours des premières étapes du développement des myofibres, les MT participent activement à la formation des domaines nucléaires en servant comme un guide pour les molécules motrices qui dispersent les noyaux le long de la myofibre en croissance. Plus tard, c'est l'assemblage des sarcomères musculaires qui vont pousser les noyaux dispersés à la périphérie des myofibres. Comment les noyaux sont maintenus à la périphérie des myofibres n'est pas clair, cependant, la présence d'une cage dense de MT autour des noyaux périphériques suggère que les MT et leur réseau de protéines associées peuvent contribuer au positionnement des noyaux également dans les myofibres matures. Dans cette étude, nous avons défié la dynamique des MT en modifiant son réseau des MAPs ou sa proportion des PTMs au cours de la myogenèse. En utilisant divers modèles in vitro et in vivo de sous expression ou knock-out, nous montrons que la dynamique des MT est réduite au cours de la myogenèse vers un réseau plus stable dans les myofibres matures. Nous rapportons également que l'augmentation de la dynamique des MT peut perturber directement les domaines nucléaires à la périphérie des myofibres, soit en augmentant la dynamique des noyaux soit en augmentant le nombre des noyaux par myofibre. Dans les deux cas, nous proposons des mécanismes expliquant comment chaque forme de perturbation des domaines nucléaires peut entraîner une réduction de la fonctionnalité musculaire

Regulation of myonuclear domains by microtubules network in skeletal muscle

Le muscle squelettique est composé de milliers de cellules géantes, appelées les myofibres. Pour développer les myofibres, des cellules progénitrices mononucléées, appelées myoblastes, fusionnent et partagent leur cytoplasme et leur noyau avec les syncytiums en formation. Au sein de chaque myofibre, des centaines de noyaux sont régulièrement positionnés à la périphérie, à l'exception de zones spécialisées telles que les jonctions neuromusculaires (NMJs, pour neuromuscular junctions) où plusieurs noyaux sont regroupés. Cette organisation précise des noyaux donne naissance à des domaines nucléaires, qui sont des territoires théoriques supportés transcriptionnellement par chaque noyau pour garantir une activité transcriptomique coordonnée tout au long des myofibres. Les domaines nucléaires sont dérégulés dans différents types de myopathies où on observe des noyaux mal positionnés au long ou à l'intérieur des myofibres. Cependant, comment les domaines nucléaires sont régulés à la périphérie des myofibres et comment leur perturbation peut contribuer au développement de myopathies reste peu compris. Les microtubules (MT) sont des structures dynamiques qui passent par des cycles de polymérisation et de dépolymérisation sous l'influence de protéines associées (MAPs, pour microtubules associated proteins) ou des modifications post-traductionnelles (PTMs, pour post translational modifications). Au cours des premières étapes du développement des myofibres, les MT participent activement à la formation des domaines nucléaires en servant comme un guide pour les molécules motrices qui dispersent les noyaux le long de la myofibre en croissance. Plus tard, c'est l'assemblage des sarcomères musculaires qui vont pousser les noyaux dispersés à la périphérie des myofibres. Comment les noyaux sont maintenus à la périphérie des myofibres n'est pas clair, cependant, la présence d'une cage dense de MT autour des noyaux périphériques suggère que les MT et leur réseau de protéines associées peuvent contribuer au positionnement des noyaux également dans les myofibres matures. Dans cette étude, nous avons défié la dynamique des MT en modifiant son réseau des MAPs ou sa proportion des PTMs au cours de la myogenèse. En utilisant divers modèles in vitro et in vivo de sous expression ou knock-out, nous montrons que la dynamique des MT est réduite au cours de la myogenèse vers un réseau plus stable dans les myofibres matures. Nous rapportons également que l'augmentation de la dynamique des MT peut perturber directement les domaines nucléaires à la périphérie des myofibres, soit en augmentant la dynamique des noyaux soit en augmentant le nombre des noyaux par myofibre. Dans les deux cas, nous proposons des mécanismes expliquant comment chaque forme de perturbation des domaines nucléaires peut entraîner une réduction de la fonctionnalité musculaire.Skeletal muscle is composed of thousands of giant cells, known as myofibers. To develop myofibers, progenitor mononuclear cells, called myoblasts, fuse together and share their cytoplasm and nucleus with the forming syncytia. Within each myofiber, hundreds of nuclei, also termed myonuclei, are regularly positioned at the periphery, with exception of specialized zones such as neuromuscular junctions (NMJs) where several myonuclei are clustered. This precise myonuclei organization gives rise to myonuclear domains, which are theoretical territories transcriptionally supported by each myonucleus to guarantee a spatial and coordinated transcriptomic activity all along myofibers. Myonuclear domains are challenged in different types of myopathies where mispositioned myonuclei can be observed along and within myofibers. Yet, how myonuclear domains are regulated at the periphery of myofibers and how their disruption may contribute to the development of myopathies remain poorly understood. Microtubules (MTs) are highly dynamic structures which go through cycles of polymerization and depolymerization under the influence of their microtubules-associated proteins (MAPs) or post-translational modifications (PTMs). During the early steps of myofibers development, MTs actively participate in myonuclear domains formation by serving as railways for motor molecules which disperse myonuclei along the growing myofiber. Later on, it is the assembly of muscular sarcomeres which will push the dispersed myonuclei to the periphery of myofibers. How myonuclei are held at the periphery of myofibers is not clear, however, the presence of dense MTs cage around the peripheral myonuclei suggests that MTs and their associated proteins network may contribute to myonuclei positioning also in mature myofibers. In this study, we challenged MTs dynamics by altering its MAPs network or its PTMs proportion during myogenesis. By using various in vitro and in vivo knock-down and knock-out models, we show that MTs dynamics is reduced during myogenesis toward a more stable network in mature myofibers. We also report that increasing MTs dynamics can directly disrupt myonuclear domains at the periphery of myofibers, either by increasing myonuclei dynamics or by increasing myonuclei content per myofiber. In both cases, we propose mechanisms explaining how each form of disrupted myonuclear domains results in reduced muscle functionality

Régulation des domaines nucléaires par le réseau associé aux microtubules dans les muscles striés squelettiques

Skeletal muscle is composed of thousands of giant cells, known as myofibers. To develop myofibers, progenitor mononuclear cells, called myoblasts, fuse together and share their cytoplasm and nucleus with the forming syncytia. Within each myofiber, hundreds of nuclei, also termed myonuclei, are regularly positioned at the periphery, with exception of specialized zones such as neuromuscular junctions (NMJs) where several myonuclei are clustered. This precise myonuclei organization gives rise to myonuclear domains, which are theoretical territories transcriptionally supported by each myonucleus to guarantee a spatial and coordinated transcriptomic activity all along myofibers. Myonuclear domains are challenged in different types of myopathies where mispositioned myonuclei can be observed along and within myofibers. Yet, how myonuclear domains are regulated at the periphery of myofibers and how their disruption may contribute to the development of myopathies remain poorly understood. Microtubules (MTs) are highly dynamic structures which go through cycles of polymerization and depolymerization under the influence of their microtubules-associated proteins (MAPs) or post-translational modifications (PTMs). During the early steps of myofibers development, MTs actively participate in myonuclear domains formation by serving as railways for motor molecules which disperse myonuclei along the growing myofiber. Later on, it is the assembly of muscular sarcomeres which will push the dispersed myonuclei to the periphery of myofibers. How myonuclei are held at the periphery of myofibers is not clear, however, the presence of dense MTs cage around the peripheral myonuclei suggests that MTs and their associated proteins network may contribute to myonuclei positioning also in mature myofibers. In this study, we challenged MTs dynamics by altering its MAPs network or its PTMs proportion during myogenesis. By using various in vitro and in vivo knock-down and knock-out models, we show that MTs dynamics is reduced during myogenesis toward a more stable network in mature myofibers. We also report that increasing MTs dynamics can directly disrupt myonuclear domains at the periphery of myofibers, either by increasing myonuclei dynamics or by increasing myonuclei content per myofiber. In both cases, we propose mechanisms explaining how each form of disrupted myonuclear domains results in reduced muscle functionality.Le muscle squelettique est composé de milliers de cellules géantes, appelées les myofibres. Pour développer les myofibres, des cellules progénitrices mononucléées, appelées myoblastes, fusionnent et partagent leur cytoplasme et leur noyau avec les syncytiums en formation. Au sein de chaque myofibre, des centaines de noyaux sont régulièrement positionnés à la périphérie, à l'exception de zones spécialisées telles que les jonctions neuromusculaires (NMJs, pour neuromuscular junctions) où plusieurs noyaux sont regroupés. Cette organisation précise des noyaux donne naissance à des domaines nucléaires, qui sont des territoires théoriques supportés transcriptionnellement par chaque noyau pour garantir une activité transcriptomique coordonnée tout au long des myofibres. Les domaines nucléaires sont dérégulés dans différents types de myopathies où on observe des noyaux mal positionnés au long ou à l'intérieur des myofibres. Cependant, comment les domaines nucléaires sont régulés à la périphérie des myofibres et comment leur perturbation peut contribuer au développement de myopathies reste peu compris. Les microtubules (MT) sont des structures dynamiques qui passent par des cycles de polymérisation et de dépolymérisation sous l'influence de protéines associées (MAPs, pour microtubules associated proteins) ou des modifications post-traductionnelles (PTMs, pour post translational modifications). Au cours des premières étapes du développement des myofibres, les MT participent activement à la formation des domaines nucléaires en servant comme un guide pour les molécules motrices qui dispersent les noyaux le long de la myofibre en croissance. Plus tard, c'est l'assemblage des sarcomères musculaires qui vont pousser les noyaux dispersés à la périphérie des myofibres. Comment les noyaux sont maintenus à la périphérie des myofibres n'est pas clair, cependant, la présence d'une cage dense de MT autour des noyaux périphériques suggère que les MT et leur réseau de protéines associées peuvent contribuer au positionnement des noyaux également dans les myofibres matures. Dans cette étude, nous avons défié la dynamique des MT en modifiant son réseau des MAPs ou sa proportion des PTMs au cours de la myogenèse. En utilisant divers modèles in vitro et in vivo de sous expression ou knock-out, nous montrons que la dynamique des MT est réduite au cours de la myogenèse vers un réseau plus stable dans les myofibres matures. Nous rapportons également que l'augmentation de la dynamique des MT peut perturber directement les domaines nucléaires à la périphérie des myofibres, soit en augmentant la dynamique des noyaux soit en augmentant le nombre des noyaux par myofibre. Dans les deux cas, nous proposons des mécanismes expliquant comment chaque forme de perturbation des domaines nucléaires peut entraîner une réduction de la fonctionnalité musculaire

Improved Regional Groundwater Flow Modeling Using Drainage Features: a Case Study of the Central Northern Karst Aquifer System of Puerto Rico (usa)

In northern Puerto Rico (USA), subsurface conduit networks with unknown characteristics, and surface features such as springs, rivers, lagoons and wetlands, drain the coastal karst aquifers. In this study, drain lines connecting sinkholes and springs are used to improve the developed regional model by simulating the drainage effects of conduit networks. Implemented in an equivalent porous media (EPM) approach, the model with drains is able to roughly reproduce the spring discharge hydrographs in response to rainfall. Hydraulic conductivities are found to be scale dependent and significantly increase with higher test radius, indicating scale dependency of the EPM approach. Similar to other karst regions in the world, hydraulic gradients are steeper where the transmissivity is lower approaching the coastline. This study enhances current understanding of the complex flow patterns in karst aquifers and suggests that using a drainage feature improves modeling results where available data on conduit characteristics are minimal

High-grade B-cell Lymphoma with MYC and BCL2 Rearrangement Arising from Follicular Lymphoma: Presentation as a Large Peripancreatic Mass

Follicular lymphoma, the second most common non-Hodgkin lymphoma (NHL), primarily affects adults and shows an indolent clinical course. Rare cases of follicular lymphoma transform to a high-grade B-cell lymphoma with MYC and BCL2 rearrangements or “double-hit lymphoma”. Transformation to a “double-hit lymphoma” portends a worse prognosis and requires aggressive treatment. We report a comprehensive clinical, pathologic and radiographic review of a patient with previously undiagnosed low-grade follicular lymphoma that transformed into a “double-hit lymphoma”. The patient presented with a large heterogeneous mass 16 x 19 cm involving pancreatic head and neck and a mildly enlarged inguinal lymph node. Positron emission tomography (PET) study demonstrated Fluorodeoxyglucose (18F) (FDG)-avid peripancreatic mass. Tissue biopsy demonstrated a high-grade B-cell lymphoma with rearrangements t(14;18) and MYC, leading to the diagnosis of high-grade B-cell lymphoma with MYC and BCL2 rearrangements. Excisional biopsy of an inguinal lymph node demonstrated low-grade follicular lymphoma. Clonality studies demonstrated the same immunoglobulin clone V7-4 in inguinal lymph node and peripancreatic mass. Therefore, diagnosis of a high-grade B-cell lymphoma with MYC and BCL2 rearrangements that transformed from a low-grade follicular lymphoma was rendered. It is ultimately important to establish a tissue-based diagnosis at the different sites that are involved with lymphoma. Patient proceeded with the aggressive treatment with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (EPOCH-R) treatment

Improved regional groundwater flow modeling using drainage features: a case study of the central northern karst aquifer system of Puerto

In northern Puerto Rico (USA), subsurface conduit networks with unknown characteristics, and surface features such as springs, rivers, lagoons and wetlands, drain the coastal karst aquifers. In this study, drain lines connecting sinkholes and springs are used to improve the developed regional model by simulating the drainage effects of conduit networks. Implemented in an equivalent porous media (EPM) approach, the model with drains is able to roughly reproduce the spring discharge hydrographs in response to rainfall. Hydraulic conductivities are found to be scale dependent and significantly increase with higher test radius, indicating scale dependency of the EPM approach. Similar to other karst regions in the world, hydraulic gradients are steeper where the transmissivity is lower approaching the coastline. This study enhances current understanding of the complex flow patterns in karst aquifers and suggests that using a drainage feature improves modeling results where available data on conduit characteristics are minimal

High-grade B-cell Lymphoma with MYC and BCL2 Rearrangement Arising from Follicular Lymphoma: Presentation as a Large Peripancreatic Mass.

Follicular lymphoma, the second most common non-Hodgkin lymphoma (NHL), primarily affects adults and shows an indolent clinical course. Rare cases of follicular lymphoma transform to a high-grade B-cell lymphoma with MYC and BCL2 rearrangements or "double-hit lymphoma". Transformation to a "double-hit lymphoma" portends a worse prognosis and requires aggressive treatment. We report a comprehensive clinical, pathologic and radiographic review of a patient with previously undiagnosed low-grade follicular lymphoma that transformed into a "double-hit lymphoma". The patient presented with a large heterogeneous mass 16 x 19 cm involving pancreatic head and neck and a mildly enlarged inguinal lymph node. Positron emission tomography (PET) study demonstrated Fluorodeoxyglucose (18F) (FDG)-avid peripancreatic mass. Tissue biopsy demonstrated a high-grade B-cell lymphoma with rearrangements t(14;18) and MYC, leading to the diagnosis of high-grade B-cell lymphoma with MYC and BCL2 rearrangements. Excisional biopsy of an inguinal lymph node demonstrated low-grade follicular lymphoma. Clonality studies demonstrated the same immunoglobulin clone V7-4 in inguinal lymph node and peripancreatic mass. Therefore, diagnosis of a high-grade B-cell lymphoma with MYC and BCL2 rearrangements that transformed from a low-grade follicular lymphoma was rendered. It is ultimately important to establish a tissue-based diagnosis at the different sites that are involved with lymphoma. Patient proceeded with the aggressive treatment with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (EPOCH-R) treatment