Systemic but not intraocular Epo Gene Transfer Protects the Retina from Light-and Genetic-Induced Degeneration

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Brain structural covariance networks in obsessive-compulsive disorder: a graph analysis from the ENIGMA Consortium.

Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T1-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P < 0.0001), lower modularity (P < 0.0001), and lower small-worldness (P = 0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions

Supporting alternative organizations? Exploring scholars’ involvement in the performativity of worker-recuperated enterprises

This article analyses the role of academics in the production and maintenance of alternative organizations within the capitalist system. Empirically, we focus on academics from the University of Buenos Aires who, through the extension programme Facultad Abierta, have supported worker-recuperated enterprises since their emergence in Argentina in the early 2000s. Conceptually, we build on prior studies on worker-recuperated enterprises as well as the ‘critical performativity’ concept that we define as scholars’ subversive interventions that can involve the production of new subjectivities, the constitution of new organizational models and/or the bridging of these models to current social movements. Our results uncover the multiple roles of academics in relation to these three facets and highlight the key interactions of these roles. In so doing, our analysis advances prior studies of worker-recuperated enterprises by clarifying how academics can support alternative organizations while offering a renewed conceptualization of critical performativity as a multifaceted process through which academics and workers interact

Association Between Anxiety, Depression, and Post-traumatic Stress Disorder and Outcomes After Ischemic Stroke

Background: Stroke patients are known to be at risk of developing anxiety, depression, and post-traumatic stress disorder (PTSD).Objective: To determine the overlap between anxiety, depression, and PTSD in patients after stroke and to determine the association between these disorders and quality of life, functional status, healthcare utilization, and return to work.Methods: A cross-sectional telephone survey was conducted to assess for depression, anxiety, PTSD, and health-related outcomes 6–12 months after first ischemic stroke in patients without prior psychiatric disease at a single stroke center.Results: Of 352 eligible subjects, 55 (16%) completed surveys. Seven subjects (13%) met criteria for probable anxiety, 6 (11%) for PTSD, and 11 for depression (20%). Of the 13 subjects (24%) who met criteria for any of these disorders, 6 (46%) met criteria for more than one, and 5 (39%) met criteria for all three. There were no significant differences in baseline characteristics, including stroke severity or neurologic symptoms, between those with or without any of these disorders. Those who had any of these disorders were less likely to be independent in their activities of daily living (ADLs) (54 vs. 95%, p < 0.001) and reported significantly worse quality of life (score of 0–100, median score of 50 vs. 80, p < 0.001) compared to those with none of these disorders.Conclusions: Anxiety, depression, and PTSD are common after stroke, have a high degree of co-occurrence, and are associated with worse outcomes, including quality of life and functional status

Thinking forward: Promising but unproven ideas for future intensive care

Progress toward determining the true worth of ongoing practices or value of recent innovations can be glacially slow when we insist on following the conventional stepwise scientific pathway. Moreover, a widely accepted but flawed conceptual paradigm often proves difficult to challenge, modify or reject. Yet, most experienced clinicians, educators and clinical scientists privately entertain untested ideas about how care could or should be improved, even if the supporting evidence base is currently thin or non-existent. This symposium encouraged experts to share such intriguing but unproven concepts, each based upon what the speaker considered a logical but unproven rationale. Such free interchange invited dialog that pointed toward new or neglected lines of research needed to improve care of the critically ill. In this summary of those presentations, a brief background outlines the rationale for each novel and deliberately provocative unconfirmed idea endorsed by the presenter

First Perihelion of EUI on the Solar Orbiter mission

Context. The Extreme Ultraviolet Imager (EUI), onboard Solar Orbiter consists of three telescopes: the two High Resolution Imagers in EUV (HRIEUV) and in Lyman-{\alpha} (HRILya), and the Full Sun Imager (FSI). Solar Orbiter/EUI started its Nominal Mission Phase on 2021 November 27. Aims. EUI images from the largest scales in the extended corona off limb, down to the smallest features at the base of the corona and chromosphere. EUI is therefore a key instrument for the connection science that is at the heart of the Solar Orbiter mission science goals. Methods. The highest resolution on the Sun is achieved when Solar Orbiter passes through the perihelion part of its orbit. On 2022 March 26, Solar Orbiter reached for the first time a distance to the Sun close to 0.3 au. No other coronal EUV imager has been this close to the Sun. Results. We review the EUI data sets obtained during the period 2022 March-April, when Solar Orbiter quickly moved from alignment with the Earth (2022 March 6), to perihelion (2022 March 26), to quadrature with the Earth (2022 March 29). We highlight the first observational results in these unique data sets and we report on the in-flight instrument performance. Conclusions. EUI has obtained the highest resolution images ever of the solar corona in the quiet Sun and polar coronal holes. Several active regions were imaged at unprecedented cadences and sequence durations. We identify in this paper a broad range of features that require deeper studies. Both FSI and HRIEUV operate at design specifications but HRILya suffered from performance issues near perihelion. We conclude emphasising the EUI open data policy and encouraging further detailed analysis of the events highlighted in this paper

The Necrotic Signal Induced by Mycophenolic Acid Overcomes Apoptosis-Resistance in Tumor Cells

The amount of inosine monophosphate dehydrogenase (IMPDH), a pivotal enzyme for the biosynthesis of the guanosine tri-phosphate (GTP), is frequently increased in tumor cells. The anti-viral agent ribavirin and the immunosuppressant mycophenolic acid (MPA) are potent inhibitors of IMPDH. We recently showed that IMPDH inhibition led to a necrotic signal requiring the activation of Cdc42.Herein, we strengthened the essential role played by this small GTPase in the necrotic signal by silencing Cdc42 and by the ectopic expression of a constitutive active mutant of Cdc42. Since resistance to apoptosis is an essential step for the tumorigenesis process, we next examined the effect of the MPA–mediated necrotic signal on different tumor cells demonstrating various mechanisms of resistance to apoptosis (Bcl2-, HSP70-, Lyn-, BCR-ABL–overexpressing cells). All tested cells remained sensitive to MPA–mediated necrotic signal. Furthermore, inhibition of IMPDH activity in Chronic Lymphocytic Leukemia cells was significantly more efficient at eliminating malignant cells than apoptotic inducers.These findings indicate that necrosis and apoptosis are split signals that share few if any common hub of signaling. In addition, the necrotic signaling pathway induced by depletion of the cellular amount of GTP/GDP would be of great interest to eliminate apoptotic-resistant tumor cells

SYMBIOmatics: Synergies in Medical Informatics and Bioinformatics – exploring current scientific literature for emerging topics

Background: The SYMBIOmatics Specific Support Action (SSA) is "an information gathering and dissemination activity" that seeks "to identify synergies between the bioinformatics and the medical informatics" domain to improve collaborative progress between both domains (ref. to http://www.symbiomatics.org). As part of the project experts in both research fields will be identified and approached through a survey. To provide input to the survey, the scientific literature was analysed to extract topics relevant to both medical informatics and bioinformatics. Results: This paper presents results ofa systematic analysis of the scientific literature from medical informatics research and bioinformatics research. In the analysis pairs of words (bigrams) from the leading bioinformatics and medical informatics journals have been used as indication of existing and emerging technologies and topics over the period 2000-2005 ("recent") and 1990-1990 ("past"). We identified emerging topics that were equally important to bioinformatics and medical informatics in recent years such as microarray experiments, ontologies, open source, text mining and support vector machines. Emerging topics that evolved only in bioinformatics were system biology, protein interaction networks and statistical methods for microarray analyses, whereas emerging topics in medical informatics were grid technology and tissue microarrays. Conclusion: We conclude that although both fields have their own specific domains of interest, they share common technological developments that tend to be initiated by new developments in biotechnology and computer science