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Inherited retinal degenerations (IRDs) are characterized by the progressive loss of photoreceptors and represent one of the most prevalent causes of blindness among working-age populations. Cyclic nucleotide dysregulation is a common pathological feature linked to numerous forms of IRD, yet the precise mechanisms through which this contributes to photoreceptor death remain elusive. Here we demonstrate that cAMP induced upregulation of the dependence receptor neogenin in the retina. Neogenin levels were also elevated in both human and murine degenerating photoreceptors. We found that overexpressing neogenin in mouse photoreceptors was sufficient to induce cell death, whereas silencing neogenin in degenerating murine photoreceptors promoted survival, thus identifying a pro-death signal in IRDs. A possible treatment strategy is modeled whereby peptide neutralization of neogenin in Rd1, Rd10, and Rho P23H-knockin mice promotes rod and cone survival and rescues visual function as measured by light-evoked retinal ganglion cell recordings, scotopic/photopic electroretinogram recordings, and visual acuity tests. These results expose neogenin as a critical link between cAMP and photoreceptor death, and identify a druggable target for the treatment of retinal degeneration.BACKGROUNDHBV-related acute-on-chronic liver failure (HBV-ACLF) is hallmarked by high short-term mortality rates, calling for accurate prognostic biomarkers for initial risk stratification.METHODSThree tandem mass tag-labeled (TMT-labeled) quantitative proteomic studies were performed on 10 patients with HBV-related acute hepatic decompensation and on 20 patients with HBV-ACLF. Candidate biomarkers were preliminarily verified in a cross-sectional cohort (n = 144) and further confirmed in 2 prospective cohorts (n = 207 and n = 148).RESULTSPlasminogen, a potential prognostic biomarker for HBV-ACLF, was identified by TMT quantitative proteomics and preliminarily verified in the cross-sectional cohort. Further validation with a prospective cohort (n = 207) showed that plasminogen levels at admission were significantly lower (P less then 0.001) in HBV-ACLF nonsurvivors than in survivors. The cumulative survival duration of patients with high plasminogen levels was significantly longer (P less then 0.001) than prognostic biomarker for HBV-ACLF, and sequential plasminogen measurements could profile the clinical course of HBV-ACLF. P5 is a high-performance prognostic score for HBV-ACLF.FUNDINGThe National Key Research and Development Program (2017YFC1200204); the National Natural Science Foundation of China (81400589, 81600497); the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (81121002); the Chinese High-Tech Research and Development Programs (2012AA020204); the National S&T Major Project (2012ZX10002004); and the Zhejiang Provincial Medicine and Health Science and Technology Project (2016147735).Cystic fibrosis (CF) is a multisystem disorder, but progressive inflammatory lung disease causes the greatest burden of morbidity and death. Recent translational and mechanistic studies of samples from patients, and observations in animal models, indicate that platelets may drive lung injury and contribute to dysregulated host defense in CF lung disease. In this issue of the JCI, Ortiz-Muñoz and Yu et al. explored the role that the cystic fibrosis transmembrane conductance regulator (CFTR) plays in platelet-related inflammation. The authors used mouse and human model systems to show that CFTR dysfunction in platelets increased calcium entry though the transient receptor potential cation channel 6 (TRPC6), causing hyperactivation and consequent experimental lung inflammation. The study persuasively suggests that platelets are critical thromboinflammatory effector cells in CF lung disease. In the context of platelet-related organ injury seen in a variety of other diseases and syndromes, platelets may also contribute to nonpulmonary manifestations and comorbidities of CF.To distinguish between chemical bonding and physical binding is usually simple. They differ, in the normal case, in both interaction strength (binding energy) and interaction length (structure). However, chemical bonding can be weak (e.g. in some metallic bonding) and physical binding can be strong (e.g. due to permanent electrostatic moments, hydrogen binding, etc) making differentiation non-trivial. But since these are shared-electron or unshared-electron interactions, respectively, it is in principle possible to distinguish the type of interaction by analyzing the electron density around the interaction point(s)/interface. After all, the former should be a contact while the latter should be a tunnelling barrier. Here, we investigate within the framework of density functional theory (DFT) typical molecules and crystals to show the behaviour of the electron localization function (ELF) in different shared-electron interactions, such as chemical (covalent) and metallic bonding and compare to unshared-electron interactions typical for physical binding, such as ionic, hydrogen and Keesom, dispersion (van der Waals) binding and attempt to categorise them only by the ELF and the electron population in the interaction region. It is found that ELF method is not only useful for the characterization of covalent bonds but a lot of information can be extracted also for weaker types of binding. Furthermore, from the charge integration over the interaction region(s) can reveal the strength of the bonding/binding ranging from the triple bonds to weak dispersion. Creative Commons Attribution license.There are many proteins or protein complexes which have multiple DNA binding domains. check details This allows them to bind to multiple points on a DNA molecule (or chromatin fibre) at the same time. There are also many proteins which have been found to be able to compact DNA in vitro, and many others have been observed in foci or puncta when fluorescently labelled and imaged in vivo. In this work we study, using coarse-grained Langevin dynamics simulations, the compaction of polymers by simple model proteins and a phenomenon known as the "bridging-induced attraction". The latter is a mechanism observed in previous simulations [Brackley et al., Proc. Natl. Acad. Sci. USA 110 (2013)], where proteins modelled as spheres form clusters via their multivalent interactions with a polymer, even in the absence of any explicit protein-protein attractive interactions. Here we extend this concept to consider more detailed model proteins, represented as simple "patchy particles" interacting with a semi-flexible bead-and-spring polymer. We find that both the compacting ability and the effect of the bridging-induced attraction depend on the valence of the model proteins. These effects also depend on the shape of the protein, which determines its ability to form bridges. Creative Commons Attribution license.BACKGROUND eConsulta is a teleconsultation service involving general practitioners (GPs) and patients. It is part of the information system belonging to Catalonia's primary care service. It has been in operation since the end of 2015 in conjunction with face-to-face consultations with Primary Care Teams as one of the services offered in the patient's Personal Health Folder. OBJECTIVE This study aimed to assess the ability of using eConsulta to reduce the number of face-to-face visits to Primary Care Teams. METHODS Using 13 categories proposed by the researchers, 18 GPs from the Central Catalonia Health Region retrospectively classified 2268 cases managed with eConsulta and indicated whether, in their opinion, the teleconsultations reduced the number of face-to-face visits. RESULTS There was broad consensus among the GPs that eConsulta has the potential to resolve patient queries for every type of consultation. eConsulta avoided the need for a face-to-face visit in 87.9% of cases. In addition, the GPs reportedSeguí, Josep Vidal-Alaball, Marta Sagarra Castro, Anna García-Altés, Francesc García Cuyàs. Originally published in the Journal of Medical Internet Research (http//www.jmir.org), 16.03.2020.BACKGROUND Patient monitoring is central to perioperative and intensive care patient safety. Current state-of-the-art monitors display vital signs as numbers and waveforms. Visual Patient technology creates an easy-to-interpret virtual patient avatar model that displays vital sign information as it would look in a real-life patient (eg, avatar changes skin color from healthy to cyanotic depending on oxygen saturation). In previous studies, anesthesia providers using Visual Patient perceived more vital signs during short glances than with conventional monitoring. OBJECTIVE We aimed to study the deeper mechanisms underlying information perception in conventional and avatar-based monitoring. METHODS In this prospective, multicenter study with a within-subject design, we showed 32 anesthesia providers four 3- and 10-second monitoring scenarios alternatingly as either routine conventional or avatar-based in random sequence. All participants observed the same scenarios with both technologies and reported the vital ff), and body temperature (heatwaves or ice crystals). This study adds a new and higher level of empirical evidence about why avatar-based monitoring improves vital sign perception compared with conventional monitoring. ©David Werner Werner Tscholl, Julian Rössler, Lucas Handschin, Burkhardt Seifert, Donat R Spahn, Christoph B Nöthiger. Originally published in the Journal of Medical Internet Research (http//www.jmir.org), 16.03.2020.BACKGROUND Empirical research has linked psychological distress with fatigue. However, few studies have analyzed the factors (eg, stimuli from bedtime media use) that affect the relationship between psychological distress and fatigue. OBJECTIVE The aim of this study was to examine whether visual stimuli from bedtime media use mediate the relationship between psychological distress and fatigue among college students. METHODS The sample included 394 participants (92 males, 302 females) with a mean age of 19.98 years (SD 1.43 years), all of whom were Chinese college students at an occupational university in Sichuan Province, China. Data were collected using a paper-based questionnaire that addressed psychological distress, stimuli from bedtime media use, and fatigue. Mediation analysis was conducted using the PROCESS macro version 2.16.2 for SPSS 22, which provided the 95% CIs. RESULTS Both psychological distress (r=.43, P less then .001) and visual stimuli from bedtime media use (r=.16, P less then .001) were positively related to fatigue. The association between auditory stimuli from bedtime media use and fatigue was not significant (r=.09, P=.08). The relationship between psychological distress and fatigue was partially mediated by visual stimuli from bedtime media use (beta=.01, SE 0.01, 95% CI 0.0023-0.0253). CONCLUSIONS The findings imply that psychological distress has an indirect effect on fatigue via visual stimuli from bedtime media use. In contrast, auditory stimuli from bedtime media use did not have the same effect. We suggest that college students should reduce bedtime media use, and this could be achieved as part of an overall strategy to improve health. Mobile health apps could be an option to improving young students' health in daily life. ©Yuan Guan, Wenjie Duan. Originally published in JMIR Mental Health (http//mental.jmir.org), 16.03.2020.
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