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  • Cannon Banke posted an update 3 days, 15 hours ago

    Viruses utilize cellular lipids and manipulate host lipid metabolism to ensure their replication and spread. Therefore, the identification of lipids and metabolic pathways that are suitable targets for antiviral development is crucial. Using a library of compounds targeting host lipid metabolic factors and testing them for their ability to block pseudorabies virus (PRV) and vesicular stomatitis virus (VSV) infection, we found that U18666A, a specific inhibitor of Niemann-Pick C1 (NPC1), is highly potent in suppressing the entry of diverse viruses including pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). NPC1 deficiency markedly attenuates viral growth by decreasing cholesterol abundance in the plasma membrane, thereby inhibiting the dynamics of clathrin-coated pits (CCPs), which are indispensable for clathrin-mediated endocytosis. Significantly, exogenous cholesterol can complement the dynamics of CCPs, leading to efficient viral entry and infectivity. Administration of U18666A improves the survival and pathology of PRV- and influenza A virus-infected mice. Thus, our studies demonstrate a unique mechanism by which NPC1 inhibition achieves broad antiviral activity, indicating a potential new therapeutic strategy against SARS-CoV-2, as well as other emerging viruses.The iron oxide nanoparticles (IONPs) that combine the nanozyme activity and magnetothermal properties have attracted significant interest for various biomedical applications. However, the effect of magnetic stimulation in fine-tuning the nanozyme activities remains unclear. Here, we have constructed a series of IONPs with different magneto-thermal conversion abilities, and systematically study the effect of magnetic field stimulation on the peroxidase (POD) activity of IONPs. The results show that POD activity is effectively amplified via an in situ alternating magnetic field (AMF) stimulation with no solution temperature rise, and the degree of activity enhancement is closely related to the magnetic heating ability of the IONPs, confirming the origin of activity enhancement arises from the local magnetothermal effect. As the first report to prove magnetothermal regulation on nanozyme activity and to shed lights on the underlying correlation between activity enhancement and the intrinsic specific absorption rate (SAR), this work is expected to provide important support for future design of new magnetoresponsive nanozymes in various practical applications.The relation between long-haul flights (LHF) and venous thromboembolic disease is well established. Nonetheless, the incidence of pulmonary embolisms after these flights is probably underestimated because of the difficulties in case ascertainment. Reunion Island appears to present the ideal geographic conditions for accurately assessing this incidence. We aimed to assess the incidence of pulmonary embolisms in people who had recently taken a LHF to Reunion Island. We conducted a retrospective multi-center descriptive study and included all cases of pulmonary embolisms diagnosed between January 1, 2015, and January 30, 2017 (according to the hospitals’ discharge summary database) in the island’s four public hospitals within 30 days after taking an LHF to Reunion. We took different delays of diagnosis to calculate the incidence. We have considered the time to diagnosis at 1 month as significant according to the time applied in the Geneva score for risk factors. The study included 45 patients landing on Reunion over a 2-year period. The total number of passengers arriving by LHF during this period was 1,223,001. The incidence of pulmonary embolism after an LHF was thus calculated at 36.8 per million travelers at 1 month. The incidence for PE diagnosed, after 15 days was 29.4 per million travelers, and after 7 days, it was 21.9 per million travelers. The male/female ratio was 0.67. The mean interval between the flight and symptom onset was 7 days. In our population, the incidence of pulmonary embolisms after LHFs in our study is clearly higher than that reported in the literature (36.8 vs 4.8). Our exhaustive data collection probably explains this difference. A case-control study appears necessary to analyze the risk factors for pulmonary embolism after a LHF.

    To describe the clinical features, risk factors and outcomes ofNeisseriakeratitis.

    This is a retrospective observational study wherein medical records of cases with microbiologically provenNeisseriakeratitis were reviewed. learn more Data pertaining to the underlying predisposing factors, clinical characteristics of the corneal ulcer, antibiotic susceptibility of theNeisseriaspecies isolate from the corneal scraping, the treatment given, and outcomes were collected and analyzed.

    Medical records of 60 patients (60 eyes) withNeisseriakeratitiswere reviewed.Among the causes of poor ocular surface as predisposing factor, vernal keratoconjunctivitis (n = 6 eyes), along with use of topical corticosteroids (n = 18 eyes) was the most common. The ulcer was characterized by a central infiltrate (31/60, 51.7%) involving up to the mid-stroma (43/60, 71.7%). Of theforty-four (73.3%) eyes with pureNeisseriakeratitis,31 eyes (72.1%) resolved with medical therapy alone while five eyes (11.6%) underwent therapeutic penetrating keratoplasty and in two(4.6%)eyes evisceration was performed. The other 5/44 (11.6%) patients were lost to follow-up. Resolution with medical therapy was found to be similar in cases with pure infection and mixed infection (p = 0.58).

    Neisseria keratitis most commonly causes a mild form of keratitis and is often associated with the poor ocular surface or prior steroid use. In most cases medical therapy is sufficient for complete resolution of the keratitis.

    Neisseria keratitis most commonly causes a mild form of keratitis and is often associated with the poor ocular surface or prior steroid use. In most cases medical therapy is sufficient for complete resolution of the keratitis.

    In this study, we aimed to determine the alterations in the retina and peripapillary vascular density in patients with vitamin B12 deficiency.

    The patients were divided into two groups regarding their vitamin B12 levels as the low vitamin B12 group (< 200 pg/ml) and the normal vitamin B12 group (≥ 200 pg/ml). The retinal nerve fiber layer thickness (RNFLT) and the central macular thickness (CMT) were measured through an SD-OCT analysis. The foveal avascular zone (FAZ), vessel density (VD) of the superficial capillary plexus (SCP), and deep capillary plexus (DCP) of the macula, and the VD of the radial peripapillary capillary plexus (RPCP) for the optic disk were determined by OCT-A.

    Thirty-three patients were in the low vitamin B12 group and 54 were in the normal group. The mean RNFLT measurements were significantly lower in the low vitamin B12 group (p = 0.001). The RPCP values in all quadrants were significantly lower in the patients with vitamin B12 deficiency (p = 0.001); moreover, there was a significant increase in the FAZ value with a decrease in both superficial (p = 0.

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