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Hepatitis E virus (HEV) is a major cause of acute viral hepatitis in humans. A convenient small mammalian model for basic research and antiviral testing is still greatly needed. Although a small rodent, the Mongolian gerbil, was reported to be susceptible to swine genotype-4 HEV infection, whether the previous results were reliable and consistent needs to be validated by using biologically pure HEV stocks or infectious RNA. In this study, we revisited this gerbil infection model for human HEV of genotype 1, 3, or 4 (G1, G3, or G4) by HEV reverse genetics. Gerbils inoculated intrahepatically with capped G3 HEV RNA transcripts or intraperitoneally with infectious G3 cloned HEV produced robust infection, as evidenced by presence of HEV in livers, spleens, and feces for up to 7 weeks post inoculation, seroconversion, and pathological liver lesions. Furthermore, the value of the gerbil model in antiviral testing and type I IFN in host defense was assessed. We demonstrated the effectiveness of peg-IFNα-2a and ribavd standards of experimental procedures. Fecal virus shedding, seroconversion, and pathological liver lesions could be detected in HEV-inoculated gerbils. We demonstrate the effectiveness and usefulness of this model in testing antiviral drugs, and in assessing the mechanism of host innate immune response upon HEV infection. This conventional rodent model will aid in future antiviral development and delineating mechanism of host immune response.

To assess how patients' dependent parameters may affect [68Ga]Ga-DOTANOC image quality and to propose a theoretical body mass index (BMI)-adjusted injected activity (IA) scheme, to improve imaging of high weight patients.

Among patients prospectively enrolled (June-2019 and May-2020) in an Institutional Ethical Committee-approved electronic archive, we included those affected by primary gastro-entero-pancreatic (GEP) or lung neuroendocrine tumour and referred by our Institutional clinicians (excluding even minimal radiopharmaceutical extravasation, movement artefacts, renal insufficiency). All PET/CT images were acquired following EANM guidelines and rated for visual quality (1 = non-diagnostic, 2 = poor, 3 = moderate, 4 = good). Collected data included patient's body mass, height, BMI, age, IA (injected activity), IA/Kg (IAkg), IA/BMI (IABMI), liver SUVmean, liver SUVmax standard deviation, liver-signal-to-noise (LSNR), normalised_LSNR (LSNR_norm) and contrast-to-noise ratio (CNR) for positive scans and n each patient.

BMI resulted the best predictor of image quality. The proposed theoretical BMI-adjusted IA scheme (4.17*BMI) should yield images of better quality (especially in high-BMI patients) maintaining practical scanning times (3 min/bed).

BMI resulted the best predictor of image quality. The proposed theoretical BMI-adjusted IA scheme (4.17*BMI) should yield images of better quality (especially in high-BMI patients) maintaining practical scanning times (3 min/bed).Flavescence dorée (FD) is a quarantine disease threatening European vineyards. Its management is based on mandatory insecticide treatments and the uprooting of infected plants identified during annual surveys. Field surveys are currently not optimized because the drivers affecting FD spread in vineyard landscapes remain poorly understood. We collated a georeferenced dataset of FD detection, collected from 34,581 vineyard plots over 5 years in the South West France wine region. Spatial models fitted with integrated nested Laplace approximation were used to identify local and landscape factors affecting FD detection and infection. Our analysis highlights the importance of sampling period on FD detection and of local practices and landscape context on FD infection. At field scale, altitude and cultivar choice were the main factors affecting FD infection. In particular, the odds ratio of FD infection in fields planted with the susceptible Cabernet Sauvignon, Cabernet Franc, or Muscadelle varieties were approximately twice those in fields planted with the less susceptible Merlot. Field infection was also affected by the field's immediate surroundings (within a circle with a radius of 150 to 200 m), corresponding to landscapes of 7 to 12 ha. In particular, the probability of FD infection increased with the proportions of forest and urban land and with the proportion of susceptible cultivars, demonstrating that the cultivar composition impacts FD epidemiology at landscape scale. The satisfactory predictive performance of the model for identifying districts with a prevalence of FD detection >10% of the fields suggests that it could be used to target areas in which future surveys would be most valuable.Insect-transmitted plant pathogens threaten crop production worldwide. Because a single feeding bout may be sufficient for a vector to transmit a pathogen that kills the plant, treatment thresholds for vectors of plant pathogens are low. For many vector species, overreliance on chemical controls has resulted in evolution of insecticide resistance. Analysis of complementary insecticide resistance and epidemiological models indicated that tactics for delaying resistance evolution conflict with tactics for limiting pathogen spread. Insecticide resistance models support maintaining untreated refuges that serve as a source of susceptible insects that reduce the likelihood of mating among rare resistant insects. In contrast, epidemiological models indicate that movement of vectors from untreated areas to insecticide-treated areas contributes to pathogen spread. Accordingly, epidemiological models support area-wide insecticide spray programs, although resistance models indicate that such an approach is likely to leation of such an approach will require innovations in vector control and sustained efforts in plant breeding.Purpose Data are presented from ophthalmology clinics in Spain participating in the VISIONARY study, examining the effectiveness, tolerability, and safety of the preservative-free tafluprost (0.0015%) and timolol (0.5%) fixed-dose combination (PF tafluprost/timolol FC) in the treatment of OAG and OHT. Methods An observational, multicenter prospective study examined treatment outcomes following a switch to PF tafluprost/timolol FC in adult OAG/OHT patients demonstrating insufficient response to beta-blocker or prostaglandin analog (PGA) monotherapy. Primary end point was mean change in intraocular pressure (IOP) from baseline at month 6. Changes in the severity of ocular signs and symptoms were also assessed. Results Overall, 92 patients (51.1% female) were included. Mean (standard deviation) age was 68.3 (12.1) years. Mean IOP was reduced from 21.9 mmHg at baseline to 16.7 mmHg at month 6 (22.3% decrease; P  less then  0.0001). Significant IOP reductions were observed at weeks 4 and 12 (P  less then  0.0001). Baseline PGA and beta-blocker users demonstrated mean month 6 IOP reductions of 5.5 mmHg (23.5%; P  less then  0.001) and 3.5 mmHg (14.6%; P = 0.029), respectively. Severity of conjunctival hyperemia, dry eye, irritation, itching, foreign body sensation, and eye pain was significantly reduced. Three treatment-related adverse events were reported, all were nonserious and mild/moderate in severity. NS 105 Conclusion In real-world clinical practice, PF tafluprost/timolol FC treatment provided significant IOP reductions over 6 months and was well tolerated among OAG/OHT patients showing poor response to PGA or beta-blocker monotherapy. IOP-lowering efficacy and improvements in ocular signs and symptoms were evident from week 4 and maintained over the 6-month study period. Trial Registration European Union electronic Register of Post-Authorisation Studies (EU PAS) register number EUPAS22204.Current frameworks of side-by-side phylogenetic trees comparison face two issues (1) accepting mainly binary trees as input and (2) assuming input trees having identical or highly overlapping taxa. However, cladistic comparative studies often lead with multiple nontotally resolved trees with nonidentical sets of taxa. We tackle these issues in this study, presenting the iPhyloC, an interactive web-based framework for comparing phylogenetic trees side by side. iPhyloC supports automatic identification of the common taxa in the input trees, comparison options between them, intuitive design, high usability, scalability to large trees, and cross-platform support. iPhyloC was tested using different trees and a supertree depicting the phylogenetic relationships within the insect order Diptera as examples.A major challenge to end the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is to develop a broadly protective vaccine that elicits long-term immunity. As the key immunogen, the viral surface spike (S) protein is frequently mutated, and conserved epitopes are shielded by glycans. Here, we revealed that S protein glycosylation has site-differential effects on viral infectivity. We found that S protein generated by lung epithelial cells has glycoforms associated with increased infectivity. Compared to the fully glycosylated S protein, immunization of S protein with N-glycans trimmed to the mono-GlcNAc-decorated state (SMG) elicited stronger immune responses and better protection for human angiotensin-converting enzyme 2 (hACE2) transgenic mice against variants of concern (VOCs). In addition, a broadly neutralizing monoclonal antibody was identified from SMG-immunized mice that could neutralize wild-type SARS-CoV-2 and VOCs with subpicomolar potency. Together, these results demonstrate that removal of glycan shields to better expose the conserved sequences has the potential to be an effective and simple approach for developing a broadly protective SARS-CoV-2 vaccine.Background Nebulizers are used to provide treatment to respiratory patients. Concerns over nosocomial infection risks from contaminated nebulizers raise the critical need to identify all microbial populations in nebulizers used by patients. However, conventional culture-dependent techniques are inadequate with the ability to identify specific microbial populations only. Therefore, the aims of this study were to acquire complete profiles of microbiomes in nebulizers used by in-patients with culture-independent high-throughput sequencing and identify sources of microbial contaminants for the development of effective practices to reduce microbial contamination in nebulizer devices. Methods This study was conducted at the University of Tennessee Medical Center in Knoxville, TN. Nebulizers were collected between May 2018 and October 2018 from inpatients admitted to the floors for pneumonia or chronic obstructive pulmonary disease exacerbations. Nebulizers were sampled for 16S rRNA gene-based amplicon sequencing toed differences in pathogenicity between closely related phylotypes. Microbiome profile-enabled community-wide culture-independent microbial source tracking suggested greater importance of environmental sources than human sources as contributors to nebulizer microbiomes, providing important insight for the development of effective strategies for the monitoring and control of nebulizer devices to mitigate infection risks in the hospital.

We aimed to evaluate the diagnostic accuracy (DA) of dual-source CT coronary angiography (DSCTCA) against invasive coronary angiography (ICA) in assessing stenotic cardiac allograft vasculopathy (CAV) in heart transplant (HTX) recipients.

Consecutive HTX recipients(

= 38) on annual surveillance, underwent DSCTCA prior to ICA on a 192-detector 384-slice DSCT scanner. Cases were classified as no CAV (no stenosis),

(any degree of stenosis) or

(>50% stenosis).

Mean age was 33.66 ± 11.45 years (MF = 2711, median time from HTX-23.5 months). Prevalence of

on DSCTCA and ICA was 44.7%(

= 17) and 39.5%(

= 15), respectively and that of

was 21.1%(

= 8) and 15.8%(

= 6), respectively. 557 (96.7%) segments were interpretable on DSCTCA. Mean radiation dose was 4.24 ± 2.15 mSv. At patient-level, the sensitivity, specificity, positive-predictive value, negative-predictive value (NPV), and DA of DSCTCA for detection of

and

were 100%, 91.3%, 88.2%, 100%, 94.73% and 100%, 94%, 75%, 100%, 95% respectively.

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