Ophthalmic Disorders in Posterior Reversible Encephalopathy Syndrome Associated with Preeclampsia

Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological entity presented with different symptoms such as visual disturbances, headaches, seizures, severe hypertension and altered mental status. It has been recognized in a different pathological conditions, although preeclampsia/eclampsia is the most common cause of PRES. The pathogenesis of PRES is still not fully understood, but it seems that failure of cerebrovascular autoregulation causing vasogenic edema, cerebral vasoconstriction, and disruption of the blood brain barrier plays an important role. Cortical blindness, hypertensive retinopathy, serous retinal detachment (SRD), central retinal artery and vein occlusions, retinal or vitreous hemorrhages, anterior ischemic optic neuropathy (AION) and Purtscher’s retinopathy are ophthalmic disorders that may occur in PRES associated with preeclampsia. Among these, cortical blindness is the best documented complication of preeclampsia. Magnet resonance imaging (MRI) is a gold standard to establish the diagnosis of PRES because clinical findings are not sufficiently specific. Typically, there are bilateral cortical occipital lesions with hyperdensity on T2-weighted MRI. Blindness due to occipital lesions is reversible and the vision loss is usually regained within 4 h to 8 days

The Mediterranean deep-water kelp Laminaria rodriguezii is an endangered species in the Adriatic Sea

Acknowledgments Thanks are due to Klaus Lüning for a gametophyte culture of L. abyssalis, and to Britta Schaffelke for a herbarium specimen of L. rodriguezii from the western Mediterranean. We are grateful to the Total Foundation (Paris) for funding this study within the framework of the project “Brown algal ecology and biodiversity in the eastern Mediterranean Sea”, and to the MASTS pooling initiative (Marine Alliance for Science and Technology for Scotland, funded by the Scottish Funding Council and contributing institutions; grant reference HR09011), as well as Croatian Ministry of Science, Education and Sports for supporting project “Benthic communities in the Adriatic Sea (Project ID: 0001005)”. Open access via Springer Compact AgreementPeer reviewedPublisher PD

Spliceosome database: a tool for tracking components of the spliceosome.

The spliceosome is the extremely complex macromolecular machine responsible for pre-mRNA splicing. It assembles from five U-rich small nuclear RNAs (snRNAs) and over 200 proteins in a highly dynamic fashion. One important challenge to studying the spliceosome is simply keeping track of all these proteins, a situation further complicated by the variety of names and identifiers that exist in the literature for them. To facilitate studies of the spliceosome and its components, we created a database of spliceosome-associated proteins and snRNAs, which is available at http://spliceosomedb.ucsc.edu and can be queried through a simple browser interface. In the database, we cataloged the various names, orthologs and gene identifiers of spliceosome proteins to navigate the complex nomenclature of spliceosome proteins. We also provide links to gene and protein records for the spliceosome components in other databases. To navigate spliceosome assembly dynamics, we created tools to compare the association of spliceosome proteins with complexes that form at specific stages of spliceosome assembly based on a compendium of mass spectrometry experiments that identified proteins in purified splicing complexes. Together, the information in the database provides an easy reference for spliceosome components and will support future modeling of spliceosome structure and dynamics

StayHome: A FHIR-Native Mobile COVID-19 Symptom Tracker and Public Health Reporting Tool

As the COVID-19 pandemic continues to unfold and states experience the impacts of reopened economies, it is critical to efficiently manage new outbreaks through widespread testing and monitoring of both new and possible cases. Existing labor-intensive public health workflows may benefit from information collection directly from individuals through patient-reported outcomes (PROs) systems. Our objective was to develop a reusable, mobile-friendly application for collecting PROs and experiences to support COVID-19 symptom self-monitoring and data sharing with appropriate public health agencies, using Fast Healthcare Interoperability Resources (FHIR) for interoperability. We conducted a needs assessment and designed and developed StayHome, a mobile PRO administration tool. FHIR serves as the primary data model and driver of business logic. Keycloak, AWS, Docker, and other technologies were used for deployment. Several FHIR modules were used to create a novel “FHIR-native” application design. By leveraging FHIR to shape not only the interface strategy but also the information architecture of the application, StayHome enables the consistent standards-based representation of data and reduces the barrier to integration with public health information systems. FHIR supported rapid application development by providing a domain-appropriate data model and tooling. FHIR modules and implementation guides were referenced in design and implementation. However, there are gaps in the FHIR specification which must be recognized and addressed appropriately. StayHome is live and accessible to the public at https://stayhome.app. The code and resources required to build and deploy the application are available from https://github.com/uwcirg/stayhome-project

Dynamic of Serum TWEAK Levels in Critically Ill COVID-19 Male Patients

Although the number of cases and mortality of COVID-19 are seemingly declining, clinicians endeavor to establish indicators and predictors of such responses in order to optimize treatment regimens for future outbreaks of SARS-CoV-2 or similar viruses. Considering the importance of aberrant immune response in severe COVID-19, in the present study, we aimed to explore the dynamic of serum TNF-like weak inducer of apoptosis (TWEAK) levels in critically-ill COVID-19 patients and establish whether these levels may predict in-hospital mortality and if TWEAK is associated with impairment of testosterone levels observed in this population. The present single-center cohort study involved 66 men between the ages of 18 and 65 who were suffering from a severe type of COVID-19. Serum TWEAK was rising during the first week after admission to intensive care unit (ICU), whereas decline to baseline values was observed in the second week post-ICU admission (p = 0.032) but not in patients who died in hospital. Receiver-operator characteristics analysis demonstrated that serum TWEAK at admission to ICU is a significant predictor of in-hospital mortality (AUC = 0.689, p = 0.019). Finally, a negative correlation was found between serum TWEAK at admission and testosterone levels (r = −0.310, p = 0.036). In summary, serum TWEAK predicts in-hospital mortality in severe COVID-19. In addition, inflammatory pathways including TWEAK seem to be implicated in pathophysiology of reproductive hormone axis disturbance in severe form of COVID-19

OTX008, a selective small-molecule inhibitor of galectin-1, downregulates cancer cell proliferation, invasion and tumour angiogenesis

Background Galectin-1 (Gal1), a carbohydrate-binding protein is implicated in cancer cell proliferation, invasion and tumour angiogenesis. Several Gal1-targeting compounds have recently emerged. OTX008 is a calixarene derivative designed to bind the Gal1 amphipathic β-sheet conformation. Our study contributes to the current understanding of the role of Gal1 in cancer progression, providing mechanistic insights into the anti-tumoural activity of a novel small molecule Gal1-inhibitor. Methods We evaluated in vitro OTX008 effects in a panel of human cancer cell lines. For in vivo studies, an ovarian xenograft model was employed to analyse the antitumour activity. Finally, combination studies were performed to analyse potential synergistic effects of OTX008. Results In cultured cancer cells, OTX008 inhibited proliferation and invasion at micromolar concentrations. Antiproliferative effects correlated with Gal1 expression across a large panel of cell lines. Furthermore, cell lines expressing epithelial differentiation markers were more sensitive than mesenchymal cells to OTX008. In SQ20B and A2780-1A9 cells, OTX008 inhibited Gal1 expression and ERK1/2 and AKT-dependent survival pathways, and induced G2/M cell cycle arrest through CDK1. OTX008 enhanced the antiproliferative effects of Semaphorin-3A (Sema3A) in SQ20B cells and reversed invasion induced by exogenous Gal1. In vivo, OTX008 inhibited growth of A2780-1A9 xenografts. OTX008 treatment was associated with downregulation of Gal1 and Ki67 in treated tumours, as well as decreased microvessel density and VEGFR2 expression. Finally, combination studies showed OTX008 synergy with several cytotoxic and targeted therapies, principally when OTX008 was administered first. Conclusion This study provides insights into the role of Gal1 in cancer progression as well as OTX008 mechanism of action, and supports its further development as an anticancer agent.Fil: Astorgues Xerri, Lucile . Inserm; FranciaFil: Riveiro, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Tijeras Raballand, Annemila . Inserm; FranciaFil: Serova, Maria . Inserm; FranciaFil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Bieche, Ivan . Inserm; FranciaFil: Vidaud, Michel . Inserm; FranciaFil: de Gramont, Armand . Inserm; FranciaFil: Martinet, Mathieu. Inserm; FranciaFil: Cvitkovic, Esteban . Oncoethix SA; SuizaFil: Faivre, Sandrine. Inserm; FranciaFil: Raymond, Eric . Inserm; Franci

SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

This work was supported by grants of the German Research Foundation (DFG: KR 4073/11-1; SFBTRR219, 322900939; and CRU344, 428857858, and CRU5011 InteraKD 445703531), a grant of the European Research Council (ERC-StG 677448), the Federal Ministry of Research and Education (BMBF NUM-COVID19, Organo-Strat 01KX2021), the Dutch Kidney Foundation (DKF) TASK FORCE consortium (CP1805), the Else Kroener Fresenius Foundation (2017_A144), and the ERA-CVD MENDAGE consortium (BMBF 01KL1907) all to R.K.; DFG (CRU 344, Z to I.G.C and CRU344 P2 to R.K.S.); and the BMBF eMed Consortium Fibromap (to V.G.P, R.K., R.K.S., and I.G.C.). R.K.S received support from the KWF Kankerbestrijding (11031/2017–1, Bas Mulder Award) and a grant by the ERC (deFiber; ERC-StG 757339). J.J. is supported by the Netherlands Organisation for Scientific Research (NWO Veni grant no: 091 501 61 81 01 36) and the DKF (grant no. 19OK005). B.S. is supported by the DKF (grant: 14A3D104) and the NWO (VIDI grant: 016.156.363). R.P.V.R. and G.J.O. are supported by the NWO VICI (grant: 16.VICI.170.090). P.B. is supported by the BMBF (DEFEAT PANDEMIcs, 01KX2021), the Federal Ministry of Health (German Registry for COVID-19 Autopsies-DeRegCOVID, www.DeRegCOVID.ukaachen.de; ZMVI1-2520COR201), and the German Research Foundation (DFG; SFB/TRR219 Project-IDs 322900939 and 454024652). S.D. received DFG support (DJ100/1-1) as well as support from VGP and TBH (SFB1192). M.d.B,R.R., N.S., and A.A. are supported by an ERC Advanced Investigator grant (H2020-ERC-2017-ADV-788982-COLMIN) to N.S. A.A. is supported by the NWO (VI.Veni.192.094). We thank Saskia de Wildt, Jeanne Pertijs (Radboudumc, Department of Pharmacology), and Robert M. Verdijk (Erasmus Medical Center, Department of Pathology) for providing tissue controls (Erasmus MC Tissue Bank) and Christian Drosten (Charite´ Universitatsmedizin Berlin, Institute of € Virology) and Bart Haagmans (Erasmus Medical Center, Rotterdam) for providing the SARS-CoV-2 isolate. We thank Kioa L. Wijnsma (Department of Pediatric Nephrology, Radboud Institute for Molecular Life Sciences, Amalia Children’s Hospital, Radboud University Medical Center) for support with statistical analysis regarding the COVID-19 patient cohort.Peer reviewedPublisher PD