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Abstract Introduction Cellular bone matrices (CBM) are allograft products that provide three components essential to new bone formation: an osteoconductive scaffold, extracellular growth factors for cell proliferation and differentiation, and viable cells with osteogenic potential. This is an emerging technology being applied to augment spinal fusion procedures as an alternative to autografts. Methods We aim to compare the ability of six commercially‐available human CBMs (Trinity ELITE®, ViviGen®, Cellentra®, Osteocel® Pro, Bio4® and Map3®) to form a stable spinal fusion using an athymic rat model of posterolateral fusion. Iliac crest bone from syngeneic rats was used as a control to approximate the human gold standard. The allografts were implanted at L4‐5 according to vendor specifications in male athymic rats, with 15 rats in each group. MicroCT scans were performed at 48 hours and 6 weeks post‐implantation. The rats were euthanized 6 weeks after surgery and the lumbar spines were harvested for X‐ray, manual palpation and histology analysis by blinded reviewers. Results By manual palpation, five of 15 rats of the syngeneic bone group were fused at 6 weeks. While Trinity ELITE had eight of 15 and Cellentra 11 of 15 rats with stable fusion, only 2 of 15 of ViviGen‐implanted spines were fused and zero of 15 of the Osteocel Pro, Bio4 and Map3 produced stable fusion. MicroCT analysis indicated that total bone volume increased from day 0 to week 6 for all groups except syngeneic bone group. Trinity ELITE (65%) and Cellentra (73%) had significantly greater bone volume increases over all other implants, which was consistent with the histological analysis. Conclusion Trinity ELITE and Cellentra were significantly better than other implants at forming new bone and achieving spinal fusion in this rat model at week 6. These results suggest that there may be large differences in the ability of different CBMs to elicit a successful fusion in the posterolateral spine.

Coronavirus disease 2019 (COVID‐19) has become a pandemic disease globally. Although COVID-19 directly invades lungs, it also involves the nervous system. Therefore, patients with nervous system involvement as the presenting symptoms in the early stage of infection may easily be misdiagnosed and their treatment delayed. They become silent contagious sources or ‘virus spreaders’. In order to help neurologists to better understand the occurrence, development and prognosis, we have developed this consensus of prevention and management of COVID‐19. It can also assist other healthcare providers to be familiar with and recognise COVID-19 in their evaluation of patients in the clinic and hospital environment.

Background The COVID-19 pandemic has already stressed the healthcare system in the world. Many hospitals have been overwhelmed by the large number of patients with COVID-19. Due to the shortage of equipment and personnel and the highly contagious nature of COVID-19, many other healthcare services are on hold. However, at Beijing Tiantan Hospital, a rapid response system has been in place so that routine care is not interrupted. We, therefore, would like to share our hospital-wide prevention and management policy during this pandemic to help other healthcare systems to function in this crisis.Method Tiantan hospital is one of the leading neuroscience institutions in the world. With 1650 beds, its annual inpatient admission exceeds 30 000 patients. Its COVID-19 rapid response policy was reviewed for its functionality.Results There are nine key components of this policy: an incident management system; a comprehensive infection prevention and control, outpatient triage and flow system; a designated fever clinic; patient screening and administration; optimised surgical operations, enhanced nucleic acid testing; screening of returning employees; and a supervision and feedback system. In addition, a specific protocol was designed for treating patients with acute stroke.Conclusion A comprehensive policy is helpful to protect the employee from infection and to provide quality and uninterrupted care to all who need these, including patients with acute ischaemic stroke.

Coronavirus disease-2019 (COVID‐19) has become a global pandemic. COVID-19 runs its course in two phases, the initial incubation phase and later clinical symptomatic phase. Patients in the initial incubation phase often have insidious clinical symptoms, but they are still highly contagious. At the later clinical symptomatic phase, the immune system is fully activated and the disease may enter the severe infection stage in this phase. Although many patients are known for their respiratory symptoms, they had neurological symptoms in their first 1–2 days of clinical symptomatic phase, and ischaemic stroke occurred 2 weeks after the onset of the clinical symptomatic phase. The key is to prevent a patient from progressing to this severe infection from mild infection. We are sharing our experience on prevention and management of COVID-19.

Abstract Background Single acute infarction (SAI) usually had lower risk of stroke recurrence than multiple acute infarctions (MAIs) in minor stroke. To evaluate whether all SAI had lower risk of stroke recurrence than MAIs in minor stroke. Methods We derived data from the imaging subgroup of the Clopidogrel in High-risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial. Minor stroke were categorized into SAI and MAIs by infarction numbers in diffusion weighted imaging. SAI were classified as lacunar infarction and non-lacunar infarction. The outcome was stroke recurrence within one-year follow-up. We assessed the associations between infarction patterns and stroke recurrence using multivariable Cox regression models. Results Overall, 834 patients with minor stroke were included in this subgroup, 553 SAI (381 lacunar infarction, 172 non-lacunar infarction) and 281 MAIs. The rate of stroke recurrence was 7.6%, 15.1% and 15.3% in lacunar infarction of SAI, non-lacunar infarction of SAI and MAIs at one year, respectively. Compared with MAIs, lacunar infarction of SAI had lower risk of stroke recurrence (hazard ratio [HR] 0.41, 95% confidence interval [CI] 0.21–0.80, P = 0.009), but not in non-lacunar infarction of SAI (HR 1.01, 95% CI 0.60–1.69, P = 0.98). Conclusions Lacunar infarction of SAI have lower risk of stroke recurrence than MAIs, while non-lacunar infarction of SAI might have similar risk as MAIs. Except for the number of infarctions, size and location should also be considered to stratify risk of stroke recurrence in minor stroke. Trial registration http://www.clinicaltrials.gov Unique identifier: NCT00979589. Date of registration: September 2009.

The purpose of this article is to help Advanced Learning in Medicine Year 5 (ALM5) students focus on the high yield components when preparing for the University of Otago ALM5 common component exams (fifth year exams). These exams are known to be stressful as there is a wide breadth of knowledge that may be covered, leading to a feeling of not knowing where to start and not being able to evaluate your progress. Here, a systematic approach is described to minimise stress and make preparation for the exam more efficient by prioritising preparation that secures the most marks in the exams.

Vertical flow assays (VFAs) or flow-through assays have emerged as an alternate type of paper-based assay due to their faster detection time, larger sample volume capacity, and significantly higher multiplexing capabilities. They have been successfully employed to detect several different targets (polysaccharides, protein, and nucleic acids), although in a limited number of samples (serum, whole blood, plasma) compared to the more commonly known lateral flow assays (LFAs). The operation of a VFA relies mainly on gravity, coupled with capillary action or external force to help the sample flow through layers of stacked pads. With recent developments in this field, multiple layers of pads and signal readers have been optimized for more user-friendly operation, and VFAs have achieved a lower limit of detection for various analytes than the gold-standard methods. Thus, compared to the more widely used LFA, the VFA demonstrates certain advantages and is becoming an increasingly popular platform for obtaining qualitative and quantitative results in low-resource settings. Considering the wide application of gold nanoparticles (GNPs) in VFAs, we will mostly discuss (1) the design of GNP-based VFA along with its associated advantages/disadvantages, (2) fabrication and optimization of GNP-based VFAs for applications, and (3) the future outlook of flow-based assays for point-of-care testing (POCT) diagnostics.

Summary: Regulatory T cells (Tregs) are critical for maintaining immune homeostasis, but their presence in tumor tissues impairs anti-tumor immunity and portends poor prognoses in cancer patients. Here, we reveal a mechanism to selectively target and reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting their dependency on the histone H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) in tumors. Disruption of EZH2 activity in Tregs, either pharmacologically or genetically, drove the acquisition of pro-inflammatory functions in TI-Tregs, remodeling the tumor microenvironment and enhancing the recruitment and function of CD8+ and CD4+ effector T cells that eliminate tumors. Moreover, abolishing EZH2 function in Tregs was mechanistically distinct from, more potent than, and less toxic than a generalized Treg depletion approach. This study reveals a strategy to target Tregs in cancer that mitigates autoimmunity by reprogramming their function in tumors to enhance anti-cancer immunity. : EZH2 plays an intrinsic role in neoplastic cells as an oncogene, prompting the development of EZH2 inhibitors for cancer therapy. Wang et al. show that disrupting EZH2 function also has immunomodulatory activities and, when blocked in Tregs, promotes potent cancer immunity.

Abstract Neuroinflammation is primarily characterized by overexpression of proinflammatory mediators produced by glial activation or immune cell infiltration. Several kinases have been shown to be critical mediators in neuroinflammation. One of the largest groups of kinases is protein kinases, which have been the second most studied group of drug targets after G-protein-coupled receptors. Thus far, most of the approved kinase inhibitor drugs are adenosine triphosphate-competitive inhibitors with various off-target liabilities because of cross-reactivities; however, marine-derived compounds provide opportunities for discovering allosteric kinase inhibitors. This review summarizes the potential of marine-derived protein kinase inhibitors in the field of neuroinflammatory diseases, such as Parkinson disease, Alzheimer disease, multiple sclerosis, and pain. The previous studies from 1990 to 2017 in this review have shown that marine-derived protein kinase inhibitors have great potential to elicit anti-neuroinflammatory or neuroprotective responses in in vitro and in vivo models of neuroinflammatory diseases. This suggests that further exploration and investigation of these marine-derived protein kinase inhibitors on neuroinflammatory diseases are warranted. Therefore, this review may inspire further discovery of new protein kinase inhibitors from a marine origin and additional neuroscience studies focusing on these valuable marine-derived protein kinase inhibitors.

The recovery of physiologically bioactive ingredients from agricultural wastes as an abundant and low-cost source for the production of high value-added mutraceuticlas has been recognized and supported for the commercial interests and sustainable managements. In the extraction of geniposide for the development of natural food colorants from the dried fruits of Gardenia jasminoides Rubiaceae, the gardenia fruit waste (GFW) still remaining 0.86% (w/w) of crocins has always been discarded without any further treatments Until now, there was no simple and effective protocol for high-purity trans-crocein (TC) preparation without the coexistence of non-biologically active cis-crocein from GFW. We proposed an effective process to obtain the compound as follows. Crocins were extracted firstly by 50% of ethanol in the highest yield of 8.61 mg/g (w/w) from GFW. After the HPD-100 column fractionation in the collecting of crocins, the conversion ratio of 75% of crocins to crocetins can be obtained from the commercial available enzyme- Celluclast® 1.5 L. The crocins hydrolyzed products, were then separated through the HPD-100 resin adsorption and finally purified with the centrifugal partition chromatography (CPC) in single-step to obtain TC in a purity of 96.76 ± 0.17%. Conclusively, the effective enzyme transformation and purification co-operated with CPC technologies on crocins resulted in a high purity product of TC may be highly application in the commercial production.

The viral infection process is a battle between host defense response and pathogen antagonizing action. Several studies have established a tight link between the viral RNA silencing suppressor (RSS) and the repression of salicylic acid (SA)-mediated defense responses, nonetheless host factors directly linking an RSS and the SA pathway remains unidentified. From yeast two-hybrid analysis, we identified an interaction between the potyviral RSS helper-component proteinase (HCPro) and SA–binding protein SABP3. Co-localization and bimolecular fluorescence complementation analyses validated the direct in vivo interaction between Turnip mosaic virus (TuMV) HCPro and the Arabidopsis homologue of SABP3, AtCA1. Additionally, transient expression of TuMV HCPro demonstrated its ability to act as a negative regulator of AtCA1. When the plants of the AtCA1 knockout mutant line were inoculated with TuMV, our results indicated that AtCA1 is essential to restrict viral spreading and accumulation, induce SA accumulation, and trigger the SA pathway. Unexpectedly, the AtCA1 overexpression line also displayed a similar phenotype, suggesting that the constitutive expression of AtCA1 antagonizes the SA pathway. Taken together, our results depict AtCA1 as an essential regulator of SA defense responses. Moreover, the interaction of potyviral HCPro with this regulator compromises the SA pathway to weaken host defense responses and facilitate viral infection.

Different types of cells, such as endothelial cells, tumor-associated fibroblasts, pericytes, and immune cells, release extracellular vesicles (EVs) in the tumor microenvironment. The components of EVs include proteins, DNA, RNA, and microRNA. One of the most important functions of EVs is the transfer of aforementioned bioactive molecules, which in cancer cells may affect tumor growth, progression, angiogenesis, and metastatic spread. Furthermore, EVs affect the presentation of antigens to immune cells via the transfer of nucleic acids, peptides, and proteins to recipient cells. Recent studies have also explored the potential application of EVs in cancer treatment. This review summarizes the mechanisms by which EVs regulate melanoma development, progression, and their potentials to be applied in therapy. We initially describe vesicle components; discuss their effects on proliferation, anti-melanoma immunity, and drug resistance; and finally focus on the effects of EV-derived microRNAs on melanoma pathobiology. This work aims to facilitate our understanding of the influence of EVs on melanoma biology and initiate ideas for the development of novel therapeutic strategies.

The optimization of fermentation medium is important for synthetic biological secondary metabolite productions. The effect of rotation speed, inoculum amount, and medium supplements on the cell growth and Lycogen⢠secretion of photobacterium Rhodobacter sphaeroides WL-APD911 was evaluated. The results reveal that a higher rotational speed exhibit a higher cell density, and the increasing in the amount of inoculum amount show a slight augment on the growth of R. sphaeroides WL-APD911.In the case of nitrogen sources adding, Lycogen⢠production was achieved with a 0.5 mM l-lysine supplementation. Moreover, the attention of Tween 80 presented a tremendous increase in the secondary metabolite. Response surface methodology (RSM) exhibited the optimization of medium supplements for Lycogen⢠invention is accomplished at molasses concentration of 10 g/L, yeast extract concentration of 40 g/L, 0.3% Tween 80 and NaCl concentration of 5 g/L, respectively. Further, the batch fermentation is carried out in both 5 L and 20 L fermentors to study the scale-up process factors to be adopted. At a 20 L fermentor, Lycogen⢠yields under the optimal culture condition are over 2 times than in the shake flask. The present results provide the Lycogen⢠optimal culture mediums, scale-up procedures and efficient extractions from R. sphaeroides WL-APD911. Keywords: Rhodobacter sphaeroides WL-APD911, Lycogenâ¢, Response surface methodology (RSM), Ferementation

Abstract Background Caenorhabditis elegans is a powerful model organism for probing many biological processes including host-pathogen interactions with bacteria and fungi. The recent identification of nematode viruses that naturally infect C. elegans and Caenorhabditis briggsae provides a unique opportunity to define host-virus interactions in these model hosts. Results We analyzed the transcriptional response of pathogen infected C. elegans and C. briggsae by RNA-seq. We identified a total of 320 differentially expressed genes (DEGs) in C. elegans following Orsay virus infection. The DEGs of known function were enriched for ubiquitin ligase related genes; however, the majority of the genes were of unknown function. Interestingly, many DEGs that responded to Orsay virus infection were similar to those induced by Nematocida parisii infection, which is a natural microsporidia pathogen of C. elegans that like Orsay virus infects intestinal cells. Furthermore, comparison of the Orsay virus DEGs in C. elegans to Santeuil virus DEGs in C. briggsae identified 58 C. elegans genes whose orthologs were likewise differentially expressed in C. briggsae, thereby defining an evolutionarily conserved response to viral infection. Conclusions The two different species C. elegans and C. briggsae, which diverged ~18 million years ago, share a common set of transcriptionally responsive genes to viral infection. Furthermore, a subset of these genes were also differentially expressed following infection by a eukaryotic pathogen, N. parisii, suggesting that these genes may constitute a broader pan-microbial response to infection.

This study assessed the use of astaxanthin as an anticancer agent for increasing inhibition to melanoma cells (A375 and A2058). Wound healing and invasion assays presented that astaxanthin treatment reduced melanoma cell migration in a dose-dependent manner. The effects on melanoma cell migration were conferred via suppressed expressions of matrix metalloproteinases 1, 2 and 9. Dichlorofluorescein diacetate assay further showed that astaxanthin treatment reduced production of cellular reactive oxygen species. Cellular proliferation assay revealed potent dose-dependent inhibiting effects on melanoma cells. One-dimensional flow cytometric analysis demonstrated that astaxanthin induced cell cycle arrest in G1 phase. Mechanisms of apoptosis were verified by double fluorescence staining with annexin V-fluorescein isothiocyanate and propidium iodide. The antitumor effects of astaxanthin significantly decreased tumor size in a xenograft model. In summary, the experimental results showed that astaxanthin has potent in vivo and in vitro inhibiting effects on melanoma tumor growth for developing as chemotherapeutic agents.

[This corrects the article DOI: 10.1371/journal.pone.0197744.].

Comprehensive knowledge of the host factors required for picornavirus infection would facilitate antiviral development. Here we demonstrate roles for three human genes, TNK2, WASL, and NCK1, in infection by multiple picornaviruses. CRISPR deletion of TNK2, WASL, or NCK1 reduced encephalomyocarditis virus (EMCV), coxsackievirus B3 (CVB3), poliovirus and enterovirus D68 infection, and chemical inhibitors of TNK2 and WASL decreased EMCV infection. Reduced EMCV lethality was observed in mice lacking TNK2. TNK2, WASL, and NCK1 were important in early stages of the viral lifecycle, and genetic epistasis analysis demonstrated that the three genes function in a common pathway. Mechanistically, reduced internalization of EMCV was observed in TNK2 deficient cells demonstrating that TNK2 functions in EMCV entry. Domain analysis of WASL demonstrated that its actin nucleation activity was necessary to facilitate viral infection. Together, these data support a model wherein TNK2, WASL, and NCK1 comprise a pathway important for multiple picornaviruses.

Background: Pre-morbid chronic hyperglycemia is associated with the poor outcome of ischemic stroke, but the association between chronic hyperglycemia, and the long-term outcome of acute intracerebral hemorrhage is still poor understood.Methods: Data on patients with acute intracerebral hemorrhage in the ACROSS-China registry (Abnormal Glucose Regulation in Patients With Acute Stroke Across China) were reviewed. Elevated hemoglobin A1c (HbA1c) level on admission was indicative of chronic hyperglycemia. According to the clinical categories of HbA1c, patients were divided into three groups. Multivariable logistic regression or Cox method was performed to analyze the association of HbA1c and the prognosis of patients with acute intracerebral hemorrhage (poor functional outcome [modified Rankin scale score 3–6] and mortality) at 1 year.Results: A total of 416 patients were included in this study. Fifty-two (12.5%) patients died and 130 (31.8%) had poor functional outcome at 1-year follow-up. The higher levels of HbA1c (≥6.5%) was associated with a poor functional outcome (OR 2.35, 95% CI, 1.28–4.29) and increased mortality (OR 2.63, 95% CI 1.34–5.15), compared with the lowest category. When further stratified by diabetic or non-diabetic medical history, higher HbA1c (≥6.5%) still increased the risk of poor functional outcome (OR 3.42, 95% CI 1.39–8.44) and mortality (OR 4.48, 95% CI 1.64–12.24) in patients with non-diabetic medical history. However, higher HbA1c didn't have the association with the increased risk of poor functional outcome (OR 1.06, 95% CI 0.37–3.03) and mortality (OR 1.20, 95% CI 0.39–3.72) in patients with diabetic medical history.Conclusions: Higher HbA1c was associated with a higher risk of death and poor functional outcome 1 year after intracerebral hemorrhage, especially in patients without a diabetic history.

Human astroviruses (HAstV) are understudied positive-strand RNA viruses that cause gastroenteritis mostly in children and the elderly. Three clades of astroviruses, classic, MLB-type and VA-type have been reported in humans. One limitation towards a better understanding of these viruses has been the lack of a physiologically relevant cell culture model that supports growth of all clades of HAstV. Herein, we demonstrate infection of HAstV strains belonging to all three clades in epithelium-only human intestinal enteroids (HIE) isolated from biopsy-derived intestinal crypts. A detailed investigation of infection of VA1, a member of the non-canonical HAstV-VA/HMO clade, showed robust replication in HIE derived from different patients and from different intestinal regions independent of the cellular differentiation status. Flow cytometry and immunofluorescence analysis revealed that VA1 infects several cell types, including intestinal progenitor cells and mature enterocytes, in HIE cultures. RNA profiling of VA1-infected HIE uncovered that the host response to infection is dominated by interferon (IFN)-mediated innate immune responses. A comparison of the antiviral host response in non-transformed HIE and transformed human colon carcinoma Caco-2 cells highlighted significant differences between these cells, including an increased magnitude of the response in HIE. Additional studies confirmed the sensitivity of VA1 to exogenous IFNs, and indicated that the endogenous IFN response of HIE to curtail the growth of strains from all three clades. Genotypic variation in the permissiveness of different HIE lines to HAstV could be overcome by pharmacologic inhibition of JAK/STAT signaling. Collectively, our data identify HIE as a universal infection model for HAstV and an improved model of the intestinal epithelium to investigate enteric virus-host interactions.

ABSTRACT Recent advances in unbiased pathogen discovery have implicated astroviruses as pathogens of the central nervous system (CNS) of mammals, including humans. However, the capacity of astroviruses to be cultured in CNS-derived cells in vitro has not been reported to date. Both astrovirus VA1/HMO-C (VA1; mamastrovirus 9) and classic human astrovirus 4 (HAstV4; mamastrovirus 1) have been previously detected from cases of human encephalitis. We tested the ability of primary human neurons, primary human astrocytes, and other immortalized human nervous system cell lines (SK-N-SH, U87 MG, and SW-1088) to support infection and replication of these two astrovirus genotypes. Primary astrocytes and SK-N-SH cells supported the full viral life cycle of VA1 with a >100-fold increase in viral RNA levels during a multistep growth curve, detection of viral capsid, and a >100-fold increase in viral titer. Primary astrocytes were permissive with respect to HAstV4 infection and replication but did not yield infectious virus, suggesting abortive infection. Similarly, abortive infection of VA1 was observed in SW-1088 and U87 MG cells. Elevated expression of the chemokine CXCL10 was detected in VA1-infected primary astrocytes and SK-N-SH cells, suggesting that VA1 infection can induce a proinflammatory host response. These findings establish an in vitro cell culture model that is essential for investigation of the basic biology of astroviruses and their neuropathogenic potential. IMPORTANCE Encephalitis remains a diagnostic conundrum in humans as over 50% of cases are managed without the identification of an etiology. Astroviruses have been detected from the central nervous system of mammals in association with disease, suggesting that this family of RNA viruses could be responsible for cases of some neurological diseases that are currently without an ascribed etiology. However, there are significant barriers to understanding astrovirus infection as the capacity of these viruses to replicate in nervous system cells in vitro has not been determined. We describe primary and immortalized cultured cells of the nervous system that support infection by astroviruses. These results further corroborate the role of astroviruses in causing neurological diseases and will serve as an essential model to interrogate the neuropathogenesis of astrovirus infection.

The generation and evolution of ocean waves by wind is one of the most complex phenomena in geophysics, and is of great practical significance. Predictive capabilities of respective wave models, however, are impaired by lack of field in situ observations, particularly in extreme Metocean conditions. The paper outlines and highlights important gaps in understanding the Metocean processes and suggests a major observational program in the Southern Ocean. This large, but poorly investigated part of the World Ocean is home to extreme weather around the year. The observational network would include distributed system of buoys (drifting and stationary) and autonomous surface vehicles (ASV), intended for measurements of waves and air-sea fluxes in the Southern Ocean. It would help to resolve the issues of limiting fetches, extreme Extra-Tropical cyclones, swell propagation and attenuation, wave-current interactions, and address the topics of wave-induced dispersal of floating objects, wave-ice interactions in the Marginal Ice Zone, Metocean climatology and its connection with the global climate.

Bourbon virus (BRBV) is an emerging tick-borne RNA virus in the orthomyxoviridae family that was discovered in 2014. Although fatal human cases of BRBV have been described, little is known about its pathogenesis, and no antiviral therapies or vaccines exist. We obtained serum from a fatal case in 2017 and successfully recovered the second human infectious isolate of BRBV. Next-generation sequencing of the St. Louis isolate of BRBV (BRBV-STL) showed >99% nucleotide identity to the original reference isolate. Using BRBV-STL, we developed a small animal model to study BRBV-STL tropism in vivo and evaluated the prophylactic and therapeutic efficacy of the experimental antiviral drug favipiravir against BRBV-induced disease. Infection of Ifnar1-/- mice lacking the type I interferon receptor, but not congenic wild-type animals, resulted in uniformly fatal disease 6 to 10 days after infection. RNA in situ hybridization and viral yield assays demonstrated a broad tropism of BRBV-STL with highest levels detected in liver and spleen. In vitro replication and polymerase activity of BRBV-STL were inhibited by favipiravir. Moreover, administration of favipiravir as a prophylaxis or as post-exposure therapy three days after infection prevented BRBV-STL-induced mortality in immunocompromised Ifnar1-/- mice. These results suggest that favipiravir may be a candidate treatment for humans who become infected with BRBV.

Multidisciplinary team (MDT) diagnosis of interstitial lung disease (ILD) has been proposed as a gold standard, but there are no formal recommendations for MDT process or composition and limited knowledge regarding prevalence in routine practice. We performed a systematic evaluation of ILD diagnostic practice across a range of healthcare settings around the world. Electronic questionnaires were distributed across all global regions via society and collaborators networks. Responses from 457 unique centres across 64 countries were included in the analysis. Of the 350 (76.6%) centres holding formal meetings, the majority held face-to-face MDT meetings (80%), for a minimum of 30 min (93%), and discussed diagnosis (96.9%) and patient management (94.9%) at the meetings. Compared with non-academic and academic non-ILD centres, ILD academic centres reported a higher ILD caseload, held more formal MDT meetings, and were more likely to include histopathology and rheumatology specialists in their diagnostic team. Of the centres holding MDT meetings, 5.5% routinely discussed all new cases at such meetings. An MDT approach to ILD diagnosis is consistently interpreted and widely implemented across a range of routine care settings around the world. This observation will inform future ILD diagnostic agreement studies and diagnostic pathway recommendations.

The persistence of food insecurity leads millions of Americans to seek assistance from hunger relief programs including charitable organizations such as food banks. A greater understanding of the relationships between diet and disease has led to discussions on the role of the food banking industry to source more nutritious foods. However, an empirical process for how nutritional quality can be applied in a food bank setting has not been well defined. The aim of this study is to use the Nutrient-Rich Food Index (NRFI) to establish a set of cut-point values that score and categorize the nutrient density of foods, while developing an application with visual appeal and function. NRFI scores were calculated using nutrition information available for 8,751 foods recorded in the U.S. Department of Agriculture (USDA) Standard Reference Database. Tertile cut points (>26; 5.5-26.0;