135 research outputs found

    Telehealth During COVID-19: A Look at Healthcare Providers’ Experiences

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    Healthcare providers were placed under considerable strain during the COVID-19 pandemic. To exacerbate matters more, a sudden shift to telehealth became necessary to provide safe provider-patient visits. The increased strain created by the sudden need to implement a telehealth protocol is believed to have decreased workplace satisfaction. This study aims to investigate how the rapid shift to telehealth during the COVID-19 pandemic affected healthcare providers’ workplace satisfaction, how virtual visits created challenges and opportunities for provider-patient communication, and how the use of telemedicine during the COVID-19 pandemic affected healthcare providers’ capacity to engage in patient-centered communication. For this study, 15 primary healthcare providers were interviewed. Learning a new system and protocols in order to conduct virtual visits, as well as new obstacles that providers never encountered before, created a challenge for providers all over. A year after the World Health Organization declared COVID-19 a global pandemic, telehealth has demonstrated the benefits of permanently incorporating it as a tool for providers to utilize in the future of medicine

    Multi-layered spatial transcriptomics identify secretory factors promoting human hematopoietic stem cell development

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    Hematopoietic stem cells (HSCs) first emerge in the embryonic aorta-gonad-mesonephros (AGM) region. Studies of model organisms defined intersecting signaling pathways that converge to promote HSC emergence predominantly in the ventral domain of the dorsal aorta. Much less is known about mechanisms driving HSC development in humans. Here, to identify secreted signals underlying human HSC development, we combined spatial transcriptomics analysis of dorsoventral polarized signaling in the aorta with gene expression profiling of sorted cell populations and single cells. Our analysis revealed a subset of aortic endothelial cells with a downregulated arterial signature and a predicted lineage relationship with the emerging HSC/progenitor population. Analysis of the ventrally polarized molecular landscape identified endothelin 1 as an important secreted regulator of human HSC development. The obtained gene expression datasets will inform future studies on mechanisms of HSC development in vivo and on generation of clinically relevant HSCs in vitro

    Application of hydrides in hydrogen storage and compression: Achievements, outlook and perspectives

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    Metal hydrides are known as a potential efficient, low-risk option for high-density hydrogen storage since the late 1970s. In this paper, the present status and the future perspectives of the use of metal hydrides for hydrogen storage are discussed. Since the early 1990s, interstitial metal hydrides are known as base materials for Ni – metal hydride rechargeable batteries. For hydrogen storage, metal hydride systems have been developed in the 2010s [1] for use in emergency or backup power units, i. e. for stationary applications. With the development and completion of the first submarines of the U212 A series by HDW (now Thyssen Krupp Marine Systems) in 2003 and its export class U214 in 2004, the use of metal hydrides for hydrogen storage in mobile applications has been established, with new application fields coming into focus. In the last decades, a huge number of new intermetallic and partially covalent hydrogen absorbing compounds has been identified and partly more, partly less extensively characterized. In addition, based on the thermodynamic properties of metal hydrides, this class of materials gives the opportunity to develop a new hydrogen compression technology. They allow the direct conversion from thermal energy into the compression of hydrogen gas without the need of any moving parts. Such compressors have been developed and are nowadays commercially available for pressures up to 200 bar. Metal hydride based compressors for higher pressures are under development. Moreover, storage systems consisting of the combination of metal hydrides and high-pressure vessels have been proposed as a realistic solution for on-board hydrogen storage on fuel cell vehicles. In the frame of the “Hydrogen Storage Systems for Mobile and Stationary Applications” Group in the International Energy Agency (IEA) Hydrogen Task 32 “Hydrogen-based energy storage”, different compounds have been and will be scaled-up in the near future and tested in the range of 500 g to several hundred kg for use in hydrogen storage applications.Fil: Bellosta von Colbe, Jose. Helmholtz-Zentrum Geesthacht; AlemaniaFil: Ares Fernández, José Ramón. Universidad Autónoma de Madrid; EspañaFil: Jussara, Barale. Università di Torino; ItaliaFil: Baricco, Marcello. Università di Torino; ItaliaFil: Buckley, Craig E.. Curtin University; AustraliaFil: Capurso, Giovanni. Helmholtz Zentrum Geesthacht; AlemaniaFil: Gallandat, Noris. GRZ Technologies Ltd; SuizaFil: Grant, David M.. Science and Technology Facilities Council of Nottingham. Rutherford Appleton Laboratory; Reino Unido. University of Nottingham; Estados UnidosFil: Guzik, Matylda N.. University of Oslo; NoruegaFil: Jacob, Isaac. Ben Gurion University of the Negev; IsraelFil: Jensen, Emil H.. University of Oslo; NoruegaFil: Jensen, Torben. University Aarhus; DinamarcaFil: Jepsen, Julian. Helmholtz Zentrum Geesthacht; AlemaniaFil: Klassen, Thomas. Helmholtz Zentrum Geesthacht; AlemaniaFil: Lototskyy, Mykhaylol V.. University of Cape Town; SudáfricaFil: Manickam, Kandavel. University of Nottingham; Estados Unidos. Science and Technology Facilities Council of Nottingham. Rutherford Appleton Laboratory; Reino UnidoFil: Montone, Amelia. Casaccia Research Centre; ItaliaFil: Puszkiel, Julián Atilio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Helmholtz Zentrum Geesthacht; AlemaniaFil: Sartori, Sabrina. University of Oslo; NoruegaFil: Sheppard, Drew A.. Curtin University; AustraliaFil: Stuart, Alastair. University of Nottingham; Estados Unidos. Science and Technology Facilities Council of Nottingham. Rutherford Appleton Laboratory; Reino UnidoFil: Walker, Gavin. University of Nottingham; Estados Unidos. Science and Technology Facilities Council of Nottingham. Rutherford Appleton Laboratory; Reino UnidoFil: Webb, Colin J.. Griffith University; AustraliaFil: Yang, Heena. Empa Materials Science & Technology; Suiza. École Polytechnique Fédérale de Lausanne; SuizaFil: Yartys, Volodymyr. Institute for Energy Technology; NoruegaFil: Züttel, Andreas. Empa Materials Science & Technology; Suiza. École Polytechnique Fédérale de Lausanne; SuizaFil: Dornheim, Martin. Helmholtz Zentrum Geesthacht; Alemani

    Globally, functional traits are weak predictors of juvenile tree growth, and we do not know why

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    1. Plant functional traits, in particular specific leaf area (SLA), wood density and seed mass, are often good predictors of individual tree growth rates within communities. Individuals and species with high SLA, low wood density and small seeds tend to have faster growth rates. 2. If community-level relationships between traits and growth have general predictive value, then similar relationships should also be observed in analyses that integrate across taxa, biogeographic regions and environments. Such global consistency would imply that traits could serve as valuable proxies for the complex suite of factors that determine growth rate, and, therefore, could underpin a new generation of robust dynamic vegetation models. Alternatively, growth rates may depend more strongly on the local environment or growth–trait relationships may vary along environmental gradients. 3. We tested these alternative hypotheses using data on 27 352 juvenile trees, representing 278 species from 27 sites on all forested continents, and extensive functional trait data, 38% of which were obtained at the same sites at which growth was assessed. Data on potential evapotranspiration (PET), which summarizes the joint ecological effects of temperature and precipitation, were obtained from a global data base. 4. We estimated size-standardized relative height growth rates (SGR) for all species, then related them to functional traits and PET using mixed-effect models for the fastest growing species and for all species together. 5. Both the mean and 95th percentile SGR were more strongly associated with functional traits than with PET. PET was unrelated to SGR at the global scale. SGR increased with increasing SLA and decreased with increasing wood density and seed mass, but these traits explained only 3.1% of the variation in SGR. SGR–trait relationships were consistently weak across families and biogeographic zones, and over a range of tree statures. Thus, the most widely studied functional traits in plant ecology were poor predictors of tree growth over large scales. 6. Synthesis. We conclude that these functional traits alone may be unsuitable for predicting growth of trees over broad scales. Determining the functional traits that predict vital rates under specific environmental conditions may generate more insight than a monolithic global relationship can offer

    Phospho-dependent Regulation of SAMHD1 Oligomerisation Couples Catalysis and Restriction.

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    SAMHD1 restricts HIV-1 infection of myeloid-lineage and resting CD4+ T-cells. Most likely this occurs through deoxynucleoside triphosphate triphosphohydrolase activity that reduces cellular dNTP to a level where reverse transcriptase cannot function, although alternative mechanisms have been proposed recently. Here, we present combined structural and virological data demonstrating that in addition to allosteric activation and triphosphohydrolase activity, restriction correlates with the capacity of SAMHD1 to form "long-lived" enzymatically competent tetramers. Tetramer disruption invariably abolishes restriction but has varied effects on in vitro triphosphohydrolase activity. SAMHD1 phosphorylation also ablates restriction and tetramer formation but without affecting triphosphohydrolase steady-state kinetics. However phospho-SAMHD1 is unable to catalyse dNTP turnover under conditions of nucleotide depletion. Based on our findings we propose a model for phosphorylation-dependent regulation of SAMHD1 activity where dephosphorylation switches housekeeping SAMHD1 found in cycling cells to a high-activity stable tetrameric form that depletes and maintains low levels of dNTPs in differentiated cells

    De Novo Unbalanced Translocations in Prader-Willi and Angelman Syndrome Might Be the Reciprocal Product of inv dup(15)s

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    The 15q11-q13 region is characterized by high instability, caused by the presence of several paralogous segmental duplications. Although most mechanisms dealing with cryptic deletions and amplifications have been at least partly characterized, little is known about the rare translocations involving this region. We characterized at the molecular level five unbalanced translocations, including a jumping one, having most of 15q transposed to the end of another chromosome, whereas the der(15)(pter->q11-q13) was missing. Imbalances were associated either with Prader-Willi or Angelman syndrome. Array-CGH demonstrated the absence of any copy number changes in the recipient chromosome in three cases, while one carried a cryptic terminal deletion and another a large terminal deletion, already diagnosed by classical cytogenetics. We cloned the breakpoint junctions in two cases, whereas cloning was impaired by complex regional genomic architecture and mosaicism in the others. Our results strongly indicate that some of our translocations originated through a prezygotic/postzygotic two-hit mechanism starting with the formation of an acentric 15qter->q1::q1->qter representing the reciprocal product of the inv dup(15) supernumerary marker chromosome. An embryo with such an acentric chromosome plus a normal chromosome 15 inherited from the other parent could survive only if partial trisomy 15 rescue would occur through elimination of part of the acentric chromosome, stabilization of the remaining portion with telomere capture, and formation of a derivative chromosome. All these events likely do not happen concurrently in a single cell but are rather the result of successive stabilization attempts occurring in different cells of which only the fittest will finally survive. Accordingly, jumping translocations might represent successful rescue attempts in different cells rather than transfer of the same 15q portion to different chromosomes. We also hypothesize that neocentromerization of the original acentric chromosome during early embryogenesis may be required to avoid its loss before cell survival is finally assured

    Discovery of a Novel, Isothiazolonaphthoquinone-Based Small Molecule Activator of FOXO Nuclear-Cytoplasmic Shuttling

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    FOXO factors are tumour suppressor proteins commonly inactivated in human tumours by posttranslational modifications. Furthermore, genetic variation within the FOXO3a gene is consistently associated with human longevity. Therefore, the pharmacological activation of FOXO proteins is considered as an attractive therapeutic approach to treat cancer and age-related diseases. In order to identify agents capable of activating FOXOs, we tested a collection of small chemical compounds using image-based high content screening technology. Here, we report the discovery of LOM612 (compound 1a), a newly synthesized isothiazolonaphthoquinone as a potent FOXO relocator. Compound 1a induces nuclear translocation of a FOXO3a reporter protein as well as endogenous FOXO3a and FOXO1 in U2OS cells in a dose-dependent manner. This activity does not affect the subcellular localization of other cellular proteins including NFkB or inhibit CRM1-mediated nuclear export. Furthermore, compound 1a shows a potent antiproliferative effect in human cancer cell lines
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