title: Design Research Education and Global Concerns,

text: Abstract If the ecosystems that we are part of and rely on are to flourish, we must urgently transform how we live, and how we imagine living. Design education has a critical role to play in this transformation, as design is a materially engaged, world-building activity. Design is complicit in the problems we are facing, and informs and shapes how people live. In this article, I seed ideas about design research education for global challenges. I speak to the merits of post-disciplinary and hybrid strategies, and look to science for clues about how to respond to twenty-first-century challenges through design. I posit sustainability brokering as a new pathway for design, and anticipating alternative futures as a critical step in developing transformative innovation. I then propose participatory research through design as a foundational methodology; describe four pillars of practice to scaffold sophisticated research at undergraduate and master’s level; and lay out a work plan for building research capacity in a doctoral school. Through this process, I articulate core skills that design researchers will likely require if they are to contribute to global challenges constructively. My aim is to seed fruitful regenerative discussion with these propositions.


title: Amino Terminal Region of Dengue Virus NS4A Cytosolic Domain Binds to Highly Curved Liposomes

text: Dengue virus (DENV) is an important human pathogen causing millions of disease cases and thousands of deaths worldwide. Non-structural protein 4A (NS4A) is a vital component of the viral replication complex (RC) and plays a major role in the formation of host cell membrane-derived structures that provide a scaffold for replication. The N-terminal cytoplasmic region of NS4A(1–48) is known to preferentially interact with highly curved membranes. Here, we provide experimental evidence for the stable binding of NS4A(1–48) to small liposomes using a liposome floatation assay and identify the lipid binding sequence by NMR spectroscopy. Mutations L6E;M10E were previously shown to inhibit DENV replication and to interfere with the binding of NS4A(1–48) to small liposomes. Our results provide new details on the interaction of the N-terminal region of NS4A with membranes and will prompt studies of the functional relevance of the curvature sensitive membrane anchor at the N-terminus of NS4A.


title: Expression, crystallization and preliminary crystallographic study of mouse hepatitis virus (MHV) nucleocapsid protein C-terminal domain

text: Mouse hepatitis virus (MHV) belongs to the group II coronaviruses. The virus produces nine genes encoding 11 proteins that could be recognized as structural proteins and nonstructural proteins and are crucial for viral RNA synthesis. The nucleocapsid (N) protein, one of the structural proteins, interacts with the 30.4 kb virus genomic RNA to form the helical nucleocapsid and associates with the membrane glycoprotein via its C-terminus to stabilize virion assembly. Here, the expression and crystallization of the MHV nucleocapsid protein C-terminal domain are reported. The crystals diffracted to 2.20 Å resolution and belonged to space group P422, with unit-cell parameters a = 66.6, c = 50.8 Å. Assuming the presence of two molecules in the asymmetric unit, the solvent content is 43.0% (V (M) = 2.16 Å(3) Da(−1)).


title: The three lives of viral fusion peptides

text: Fusion peptides comprise conserved hydrophobic domains absolutely required for the fusogenic activity of glycoproteins from divergent virus families. After 30 years of intensive research efforts, the structures and functions underlying their high degree of sequence conservation are not fully elucidated. The long-hydrophobic viral fusion peptide (VFP) sequences are structurally constrained to access three successive states after biogenesis. Firstly, the VFP sequence must fulfill the set of native interactions required for (meta) stable folding within the globular ectodomains of glycoprotein complexes. Secondly, at the onset of the fusion process, they get transferred into the target cell membrane and adopt specific conformations therein. According to commonly accepted mechanistic models, membrane-bound states of the VFP might promote the lipid bilayer remodeling required for virus-cell membrane merger. Finally, at least in some instances, several VFPs co-assemble with transmembrane anchors into membrane integral helical bundles, following a locking movement hypothetically coupled to fusion-pore expansion. Here we review different aspects of the three major states of the VFPs, including the functional assistance by other membrane-transferring glycoprotein regions, and discuss briefly their potential as targets for clinical intervention.


title: The Immunopathology of Sepsis: Pathogen Recognition, Systemic Inflammation, the Compensatory Anti‐Inflammatory Response, and Regulatory T Cells

text: Sepsis, the systemic inflammatory response to infection, represents the major cause of death in critically ill veterinary patients. Whereas important advances in our understanding of the pathophysiology of this syndrome have been made, much remains to be elucidated. There is general agreement on the key interaction between pathogen‐associated molecular patterns and cells of the innate immune system, and the amplification of the host response generated by pro‐inflammatory cytokines. More recently, the concept of immunoparalysis in sepsis has also been advanced, together with an increasing recognition of the interplay between regulatory T cells and the innate immune response. However, the heterogeneous nature of this syndrome and the difficulty of modeling it in vitro or in vivo has both frustrated the advancement of new therapies and emphasized the continuing importance of patient‐based clinical research in this area of human and veterinary medicine.


Isolation of infectious bronchitis virus from a flock of racing pigeons


title: How to manage lymphoid malignancies during novel 2019 coronavirus (CoVid-19) outbreak: a Brazilian task force recommendation

text: Abstract The novel Coronavirus (CoVid-19) outbreak is now consider a world pandemic, affecting more than 300,000 people worldwide. Cancer patients are in risk for severe disease, including a higher risk of intensive care unit (ICU) admission, need for invasive ventilation or death. Management of patients with lymphoid malignancies can be challenging during the outbreak, due to need of multiple hospital visits and admissions, immunosuppression and need for chemotherapy, radiotherapy and stem cell transplantation. In this article, we will focus on the practical management of patients with lymphoid malignancies during the COVID-19 pandemic, focusing on minimizing the risk for patients.


title: Molecular detection and characterisation of feline morbillivirus in domestic cats in Malaysia

text: Abstract Feline morbillivirus (FeMV), a novel virus from the family of Paramyxoviridae, was first identified in stray cat populations. The objectives of the current study were to (i) determine the molecular prevalence of FeMV in Malaysia; (ii) identify risk factors associated with FeMV infection; and (iii) characterise any FeMV isolates by phylogenetic analyses. Molecular analysis utilising nested RT-PCR assay targeting the L gene of FeMV performed on either urine, blood and/or kidney samples collected from 208 cats in this study revealed 82 (39.4%) positive cats. FeMV-positive samples were obtained from 63/124 (50.8%) urine and 20/25 (80.0%) kidneys while all blood samples were negative for FeMV. In addition, from the 35 cats that had more than one type of samples collected (blood and urine; blood and kidney; blood, urine and kidney), only one cat had FeMV RNA in the urine and kidney samples. Risk factors such as gender, presence of kidney-associated symptoms and cat source were also investigated. Male cats had a higher risk (p = 0.031) of FeMV infection than females. In addition, no significant association (p = 0.083) was observed between the presence of kidney-associated symptoms with FeMV status. From the 82 positive samples, FeMV RNA was detected from 48/82 (58.5%) pet cats and 34/126 (27.0%) shelter cats (p < 0.0001). Partial L and N gene sequencing of the RT-PCR-positive samples showed 85–99% identity to the published FeMV sequences and it was significantly different from all other morbilliviruses. A phylogenetic analysis of the identified Malaysian FeMVs was performed with isolates from Japan, Thailand and China. Molecular characterisation revealed high relatedness of the Malaysian isolates with other Asian FeMVs, indicating that the virus had been circulating only within the region. Therefore, this study confirmed the existence of FeMV among domestic cats in Malaysia. The findings suggest further characterisation of the local isolates, including the whole genome sequencing and that studies at determining the direct consequences of FeMV infection in domestic cats are needed.


title: Effectiveness of Antibiotic Use Management in Tianjin (2011–2013): A Quasi-Experimental Study

text: BACKGROUND: In this study we investigated changes in the status of antibiotic use in Tianjin since the implementation of the Antibiotic Stewardship Program (ASP) (2011–2013), as well as existing problems, strategies, and outcomes to promote rational clinical antibiotic use. MATERIAL/METHODS: A quasi-experimental study was performed to investigate situations of antibiotic use in secondary and tertiary general hospitals in Tianjin from April 2011 to 2013. Five major indicators were analyzed: percentage of antibiotic use in inpatient cases (%), antibacterial use density (AUD), proportion of prophylactic antibiotic application for type I surgical incision, compliance rate of medication administration 0.5–2.0 h before such procedures, and antibiotic prophylaxis for ≤24 h in patients receiving these surgeries. RESULTS: There was a decrease in the percentage of antibiotic use across general hospitals (60.38% to 46.88%), in AUD (51.60% to 35.37%), and in the proportion of prophylactic antibiotic applications for type I incisions (86.67% to 25.08%). For patients undergoing these procedures, there was an increased compliance rate of medication administration of 0.5–2.0 h prior to surgery (86.38% to 100%), and of antibiotic prophylactic use for ≤24 h (40.30% to 96.37%). CONCLUSIONS: Implementation of the ASP campaign has reduced irrational antibiotic use, promoted rational antibiotic use, and delayed antibiotic resistance.


RNA conversion of COVID‐19 in respiratory and alimentary specimens during asymptomatic convalescence


title: Interaction of the Amino-Terminal Domain of the ISAV Fusion Protein with a Cognate Cell Receptor

text: The infectious salmon anemia virus (ISAV), etiological agent of the disease by the same name, causes major losses to the salmon industry. Classified as a member of the Orthomyxoviridae family, ISAV is characterized by the presence of two surface glycoproteins termed hemagglutinin esterase (HE) and fusion protein (F), both of them directly involved in the initial interaction of the virus with the target cell. HE mediates receptor binding and destruction, while F promotes the fusion process of the viral and cell membranes. The carboxy-terminal end of F (F(2)) possesses canonical structural characteristics of a type I fusion protein, while no functional properties have been proposed for the amino-terminal (F(1)) region. In this report, based on in silico modeling, we propose a tertiary structure for the F(1) region, which resembles a sialic acid binding domain. Furthermore, using recombinant forms of both HE and F proteins and an in vitro model system, we demonstrate the interaction of F with a cell receptor, the hydrolysis of this receptor by the HE esterase, and a crucial role for F(1) in the fusion mechanism. Our interpretation is that binding of F to its cell receptor is fundamental for membrane fusion and that the esterase in HE modulates this interaction.


title: Inhibition of betanodavirus infection by inhibitors of endosomal acidification

text: Betanodaviruses, members of the family Nodaviridae, have small positive-stranded bipartite RNA genomes and are the causal agent of viral nervous necrosis (VNN) in many species of marine farmed fish. In the aquaculture industry, outbreaks of betanodavirus infection and spread in larval and juvenile fish result in devastating damage and heavy economic loss. Although an urgent need exists to develop drugs that inhibit betanodavirus infection, there have been no reports about anti-betanodavirus drugs. Recently, it was reported that betanodaviruses were detected in the endosomes of infected cells, suggesting that betanodaviruses enter fish cells by endocytosis. This finding prompted us to examine whether blocking this endosomal pathway could provide a target for antiviral drug development. In this study, we examined the inhibitory effect of several lysosomotropic agents against betanodavirus infection in fish E-11 cells. The presence of 1 mM NH(4)Cl or 1 µM chloroquine in the medium inhibited the entry of betanodaviruses into cells and inhibited viral infection. The lysosomotropic agents bafilomycin A1 and monensin also inhibited virus-induced cytopathology and virus production. Our data demonstrate that inhibitors of endosomal acidification are candidates as antiviral agents against betanodavirus.


title: Dietary habits in adults during quarantine in the context of COVID-19 pandemic

text: • Quarantine leads to stress condition that can change in dietary habits. • Better dietary habits are critical to enhance the body’s immune system against COVID-19.


title: Chapter One Discrimination Between Self and Non-Self-Nucleic Acids by the Innate Immune System

text: Abstract During viral and bacterial infections, the innate immune system recognizes various types of pathogen-associated molecular patterns (PAMPs), such as nucleic acids, via a series of membrane-bound or cytosolic pattern-recognition receptors. These include Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), AIM2-like receptors (ALRs), and cytosolic DNA sensors. The binding of PAMPs to these receptors triggers the production of type I interferon (IFN) and inflammatory cytokines. Type I IFN induces the expression of interferon stimulated genes (ISGs), which protect surrounding cells from infection. Some ISGs are nucleic acids-binding proteins that bind viral nucleic acids and suppress their replication. As nucleic acids are essential components that store and transmit genetic information in every species, infectious pathogens have developed systems to escape from the host nucleic acid recognition system. Host cells also have their own nucleic acids that are frequently released to the extracellular milieu or the cytoplasm during cell death or stress responses, which, if able to bind pattern-recognition receptors, would induce autoimmunity and inflammation. Therefore, host cells have acquired mechanisms to protect themselves from contact with their own nucleic acids. In this review, we describe recent research progress into the nucleic acid recognition mechanism and the molecular bases of discrimination between self and non-self-nucleic acids.


title: Organisation de la réanimation en situation de pandémie de grippe aviaire

text: Résumé La survenue probable d’une pandémie grippale liée au virus H5N1 va entraîner un afflux massif de patients à l’hôpital, notamment en réanimation. Ce texte, rédigé par des experts des 7 sociétés savantes les plus impliquées, rappelle les principes généraux de l’organisation des hôpitaux en situation pandémique. Les points particuliers concernant la réanimation concernent le risque majeur de débordement et la nécessité imposée pas les autorités de tutelle d’un doublement de la capacité d’accueil. La réanimation pédiatrique semble particulièrement exposée, les jeunes enfants, particulièrement les petits nourrissons, devant être les plus affectés par les formes graves de grippe aviaire, dans le contexte actuel de pénurie relative de lits de réanimation pédiatrique. Il est donc proposé que les enfants de plus de 20kg soient admis en réanimation adulte. Il est souhaitable que les unités de réanimation néonatales restent à basse densité virale. Les services de réanimation mixtes (néonatale et pédiatrique) pourraient n’accueillir que les enfants. La baisse de la capacité d’admission en réanimation néonatale devrait amener à s’interroger sur une limitation des admissions de grands prématurés en situation de crise. Le doublement des capacités d’admission en réanimation pédiatrique pourrait se faire grâce à l’utilisation des unités de soins continus, des salles de réveil et le renforcement par du personnel, médical et non médical, libéré par les déprogrammations d’activités. Ces personnels seraient encadrés par les personnels habituels des unités. Des actions de formations spécifiques sont à mettre en œuvre pour les personnels destinés à renforcer les unités de réanimation. Summary The influenza pandemic will create a major increase in demand for hospital admissions, particularly for critical care services. The recommendations detailed herein have been elaborated by experts from medical societies potentially involved in this situation and focus on general hospital organization. Intensive care units will initially face high demand for admission; the Healthcare Authorities must therefore study how ICU capacity can be expanded. Pediatric intensive care units will be particularly affected by this situation of relative bed shortage, since young children, particularly infants, are expected to be affected by severe clinical forms of avian flu. Therefore, the weight threshold for admission to the adult ICU was lowered to 20kg. Neonatal intensive care units (NICU) should remain, if possible, low viral density areas. Mixed (neonatal and pediatric) intensive care units could be dedicated to infants and children only. NICU admission of extreme premature babies should be limited in this difficult situation. Pediatric intensive care units (PICU) admission capacity could be doubled by using intermediate care and postoperative care units. The staff could be increased by doctors and nurses involved in canceled programmed activities. Healthcare workers transferred to PICU should be given special training.


¿Está España preparada para apoyo psicológico durante la crisis COVID-19?


title: Chapter Four Cephalotaxus Alkaloids

text: Abstract Cephalotaxus alkaloids represent a family of plant secondary metabolites known for 60 years. Significant activity against leukemia in mice was demonstrated for extracts of Cephalotaxus. Cephalotaxine (CET) (1), the major alkaloid of this series was isolated from Cephalotaxus drupacea species by Paudler in 1963. The subsequent discovery of promising antitumor activity among new Cephalotaxus derivatives reported by Chinese, Japanese, and American teams triggered extensive structure elucidation and biological studies in this family. The structural feature of this cephalotaxane family relies mainly on its tetracyclic alkaloid backbone, which comprises an azaspiranic 1-azaspiro[4.4]nonane unit (rings C and D) and a benzazepine ring system (rings A and B), which is linked by its C3 alcohol function to a chiral oxygenated side chain by a carboxylic function alpha to a tetrasubstituted carbon center. The botanical distribution of these alkaloids is limited to the Cephalotaxus genus (Cephalotaxaceae). The scope of biological activities of the Cephalotaxus alkaloids is mainly centered on the antileukemic activity of homoharringtonine (HHT) (2), which in particular demonstrated marked benefits in the treatment of orphan myeloid leukemia and was approved as soon as 2009 by European Medicine Agency and by US Food and Drug Administration in 2012. Its exact mechanism of action was partly elucidated and it was early recognized that HHT (2) inhibited protein synthesis at the level of the ribosome machinery. Interestingly, after a latency period of two decades, the topic of Cephalotaxus alkaloids reemerged as a prolific source of new natural structures. To date, more than 70 compounds have been identified and characterized. Synthetic studies also regained attention during the past two decades, and numerous methodologies were developed to access the first semisynthetic HHT (2) of high purity suitable for clinical studies, and then high grade enantiomerically pure CET (1), HHT (2), and analogs.


title: Mild COVID-19 Symptoms in an Infliximab-Treated Ulcerative Colitis Patient: Can Ongoing Anti-TNF Therapy Protect against the Viral Hyperinflammatory Response and Avoid Aggravated Outcomes?

text: The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, represents a potentially major challenge to patients with immune-mediated inflammatory diseases who are treated with immunomodulatory therapies. We report the case of an 18-year-old ulcerative colitis patient in sustained clinical remission who 4 days after application of her ongoing therapy with the anti-TNF antibody infliximab developed mild respiratory and abdominal symptoms. The patient was subsequently diagnosed with COVID-19 but did not need hospitalization. The clinical symptoms completely resolved within 1 week after onset and there was no change in ulcerative colitis activity. The recently applied anti-TNF therapy did not lead to exacerbation of the infectious symptoms. Current recommendations strongly favor continuation of effective maintenance anti-TNF therapy in inflammatory bowel disease patients, as there is no evidence for aggravated COVID-19 upon infection. It is unclear whether anti-TNF treatment might even have assisted in preventing worsening of COVID-19 and improving outcome. Further data in the group of immune-mediated inflammatory disease patients under anti-TNF therapy are urgently needed.


docid: rmmmhrjy

title: Air Quality Variation in Wuhan, Daegu, and Tokyo during the Explosive Outbreak of COVID-19 and Its Health Effects

text: This study was designed to assess the variation of the air quality actually measured from the air pollution monitoring stations (AQMS) in three cities (Wuhan, Daegu, and Tokyo), in Asian countries experiencing the explosive outbreak of COVID-19, in a short period of time. In addition, we made a new attempt to calculate the reduced Dose(PM)(2.5) (μg) at the bronchiolar (Br.) and alveolar-interstitial (AI) regions of the 10-year-old children after the city lockdown/self-reflection of each city. A comparison of the average PM(2.5) of a month before and after the lockdown (Wuhan) and self-reflection (Daegu and Tokyo) clearly shows that the PM(2.5) concentration was decreased by 29.9, 20.9, and 3.6% in Wuhan, Daegu and Tokyo, respectively. Wuhan, Daegu and Tokyo also recorded 53.2, 19.0, and 10.4% falls of NO(2) concentration, respectively. Wuhan, which had the largest decrease of PM(2.5) concentration due to COVID-19, also marked the largest reduced Dose(PM)(2.5 10-year-old children) (μg) (3660 μg at Br. and 6222 μg at AI), followed by Daegu (445 μg at Br. and 1287 μg at AI), and Tokyo (18 μg at Br. and 52 μg at AI), over two months after the city lockdown/self-reflection. Our results suggest that the city lockdown/self-reflection had the effect of lowering the concentration of PM(2.5), resulting in an extension of the period it took to the acute allergic airway inflammation (AAI) for the 10-year-old children.


Severe exacerbation of immune thrombocytopenia and COVID-19: the favorable response to corticosteroid-based therapy—a case report


title: Deformations of Ti-6Al-4 V additive-manufacturing-induced isotropic and anisotropic columnar structures: In situ measurements and underlying mechanisms

text: The deformations of isotropic and anisotropic Ti-6Al-4 V columnar structures fabricated by additive manufacturing were extensively examined. The distinct texture and microstructure distributions were characterised. In situ X-ray diffraction measurements show different lattice activities resulting from the different microstructure distributions. Spatially resolved mapping revealed manufacturing-induced crystallite-orientation distributions that determine the deformation mechanisms. We propose a self-consistent model to correlate the multi-scale characteristics, from the anisotropic-texture-distribution microstructure to the bulk mechanical properties. We determined that basal and pyramidal slip activities were activated by tension deformation. The underlying additive-manufacturing-induced crystal plasticity plays a major role. We find that the texture development of the columnar structures and the distribution of crystallite orientation achieved by different processing conditions during additive manufacturing have important effects on the mechanical properties. The dominant deformation mode for the anisotropic Ti-6Al-4 V columnar structure is basal slip, and that for the isotropic Ti-6Al-4 V columnar structure is pyramidal slip. The difference may be important for determining the fatigue behaviour.


title: Effectiveness of rapid multiplex polymerase chain reaction for early diagnosis and treatment of pertussis

text: Abstract Background Pertussis, is an infectious respiratory disease caused by Bordetella pertussis. The incidence of pertussis has been increasing in South Korea to due to waning vaccine-induced immunity. Culture has a low sensitivity and a long turnaround time (TAT). Recently, a rapid multi-polymerase chain reaction (mPCR) test with a TAT of about 1 hour was developed for the detection of respiratory pathogens (17 viruses and three bacteria), including Bordetella pertussis. This study aimed to investigate the effectiveness of mPCR for early diagnosis and treatment of pertussis. Methods We performed a retrospective study of patients with pertussis diagnosed from May 2017 to June 2019 at a university hospital in South Korea. Nasopharyngeal swab specimens were tested using mPCR. Data were extracted from medical records. Results A total of 27 patients with a median age of 48.9 years (range: 3.3–82.2 years) were diagnosed with pertussis, of whom 9 (33.3%) were male. Eleven (40.7%) had fever, 12 (44.4%) had dyspnea, three (11.1%) had paroxysmal cough, and nine (33.3%) had inspiratory whooping. The median interval from symptom onset to diagnosis was 9.0 days (range: 1–31 days). Twenty-four patients (81.5%) were diagnosed within 2 weeks from symptom onset. All but one patient was prescribed macrolide antibiotics. Twenty-two patients (81.5%) required hospitalization, including three (11.1%) who required intensive care unit care for ventilation. Conclusion Testing patients with respiratory symptoms using mPCR can improve early diagnosis of pertussis, ensure proper treatment, and may help with outbreak control.


title: Thoracic ultrasound and SARS-COVID-19: a pictorial essay

text: Thoracic ultrasound seems to adapt to the screening for lung involvement of patients with suspected or ascertained SARS-COVID-19 infection due to its characteristics of easy applicability. It can be also a relevant method in monitoring patients. B lines are early finding of COVID-19, even in mild-symptomatic subjects; in the most serious cases such as pre-ARDS or ARDS, the B lines end up filling the ultrasound image almost completely, until it merges, so as to create a single hyperechoic image named as “white lung”, with distortion and irregularity of the pleural line. In advanced stage, lung consolidations are present, representing pulmonary pathological areas that are no longer normally ventilated.


title: A recombinant Fab neutralizes dengue virus in vitro

text: Abstract A recombinant Fab that recognizes a neutralizing epitope located in the (296–400) region of protein E of dengue virus was obtained from cloned hybridoma cells secreting the mouse monoclonal antibody (mAb) 4E11. The Fd and light chain antibody genes were amplified by polymerase chain reaction, cloned into the phagemid vector pMad, expressed in bacteria to produce Fab fragments and sequenced. The mAb 4E11, in particular its light chain complementary-determining regions, shared homologies with two other anti-viral mAbs. The affinity of the parental mAb and the cloned Fab to the MalE-E(296–400) fusion protein were shown to be of the same magnitude, i.e. nanomolar. Fab 4E11 neutralization capacity was found between 8 and 4-times or less lower than that of mAb 4E11, depending on serotypes, thus the Fab could have a smaller antiviral activity than the mAb in vitro.


title: Ultraviolet radiation for flavonoid augmentation in Isatis tinctoria L. hairy root cultures mediated by oxidative stress and biosynthetic gene expression

text: Abstract Search of cost-effective strategies that can enhance the accumulation of phytochemicals of pharmaceutical interest in plant in vitro cultures is an essential task. For the first time, Isatis tinctoria L. hairy root cultures were exposed to ultraviolet radiation (ultraviolet-A, ultraviolet-B, and ultraviolet-C) in an attempt to promote the production of pharmacologically active flavonoids. Results showed that the maximum flavonoid accumulation (7259.12 ± 198.19 μg/g DW) in I. tinctoria hairy root cultures treated by 108 kJ/m2 dose of UV-B radiation increased 16.51-fold as compared with that in control (439.68 ± 8.27 μg/g DW). Additionally, antioxidant activity enhancement and cell wall reinforcement were found in the treated I. tinctoria hairy root cultures, indicating the positive-feedback responses to oxidative stress mediated by ultraviolet-B radiation. Moreover, the expression of chalcone synthase gene was tremendously up-regulated (up to 405.84-fold) in I. tinctoria hairy root cultures following ultraviolet-B radiation, which suggested chalcone synthase gene might play a crucial role in flavonoid augmentation. Overall, the present work provides a feasible approach for the enhanced production of biologically active flavonoids in I. tinctoria hairy root cultures via the simple supplementation of ultraviolet-B radiation, which is useful for the biotechnological production of these high-added value compounds to fulfil the ever-increasing demand in pharmaceutical fields.


title: Antioxidant effect of angiotensin (1-7) in the protection of pancreatic β cell function

text: It is well known that the local renin-angiotensin system (RAS) is activated in the diabetic state, which results in an increase in the level of oxidative stress injury to pancreatic β cells. The angiotensin-converting enzyme 2 (ACE2)/angiotensin (1-7) [Ang (1-7)]/Mas axis is a negative regulator of the classical renin-angiotensin system. In order to investigate the antioxidant effect of Ang (1-7) on pancreatic β cells, INS-1 cells were cultured and oxidative stress was induced by treatment with H(2)O(2). Glucose-stimulated insulin secretion (GSIS), the generation of reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and glucose-stimulated calcium (GSCa) responses in β cells were determined following treatment with Ang (1-7). It was observed that H(2)O(2) significantly impaired the insulin secreting function, increased the production of ROS, and also decreased the levels of GSCa and MMP. Pre-treatment with Ang (1-7) alleviated these effects and treatment with A779 [antagonist of Ang (1-7)] prevented the effects of Ang (1-7). Based on these findings, it was concluded that Ang (1-7) can protect pancreatic β cells from oxidative injury and such protection can be blocked by its antagonist A779.


title: Rampant C→U Hypermutation in the Genomes of SARS-CoV-2 and Other Coronaviruses: Causes and Consequences for Their Short- and Long-Term Evolutionary Trajectories

text: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has motivated an intensive analysis of its molecular epidemiology following its worldwide spread. To understand the early evolutionary events following its emergence, a data set of 985 complete SARS-CoV-2 sequences was assembled. Variants showed a mean of 5.5 to 9.5 nucleotide differences from each other, consistent with a midrange coronavirus substitution rate of 3 × 10(−4) substitutions/site/year. Almost one-half of sequence changes were C→U transitions, with an 8-fold base frequency normalized directional asymmetry between C→U and U→C substitutions. Elevated ratios were observed in other recently emerged coronaviruses (SARS-CoV, Middle East respiratory syndrome [MERS]-CoV), and decreasing ratios were observed in other human coronaviruses (HCoV-NL63, -OC43, -229E, and -HKU1) proportionate to their increasing divergence. C→U transitions underpinned almost one-half of the amino acid differences between SARS-CoV-2 variants and occurred preferentially in both 5′ U/A and 3′ U/A flanking sequence contexts comparable to favored motifs of human APOBEC3 proteins. Marked base asymmetries observed in nonpandemic human coronaviruses (U ≫ A > G ≫ C) and low G+C contents may represent long-term effects of prolonged C→U hypermutation in their hosts. The evidence that much of sequence change in SARS-CoV-2 and other coronaviruses may be driven by a host APOBEC-like editing process has profound implications for understanding their short- and long-term evolution. Repeated cycles of mutation and reversion in favored mutational hot spots and the widespread occurrence of amino acid changes with no adaptive value for the virus represent a quite different paradigm of virus sequence change from neutral and Darwinian evolutionary frameworks and are not incorporated by standard models used in molecular epidemiology investigations. IMPORTANCE The wealth of accurately curated sequence data for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its long genome, and its low substitution rate provides a relatively blank canvas with which to investigate effects of mutational and editing processes imposed by the host cell. The finding that a large proportion of sequence change in SARS-CoV-2 in the initial months of the pandemic comprised C→U mutations in a host APOBEC-like context provides evidence for a potent host-driven antiviral editing mechanism against coronaviruses more often associated with antiretroviral defense. In evolutionary terms, the contribution of biased, convergent, and context-dependent mutations to sequence change in SARS-CoV-2 is substantial, and these processes are not incorporated by standard models used in molecular epidemiology investigations.


The case for routine screening for SARS-CoV-2 before surgery


title: SARS-CoV-2 and DPP4 inhibition: is it time to pray for Janus Bifrons?

text: Abstract Diabetes could be a risk factor for severity and mortality in patients with coronavirus disease 2019 Covid-19. It has been hypothesized that DPP4 inhibition, a therapy currently available for type 2 diabetes, might represent a target for decreasing the risk of the acute respiratory complications of the COVID-19 infection but 1) lack of demonstration of SARS-CoV2 binding to DPP4 2) possible protective role of sDPP4 in Middle East respiratory Syndrome (MERS-CoV 3) demonstrated inhibition and downregulation of DPP4 by HIV1 and MERS-CoV and 4) not exclusive role of the receptor binding in tropism of the Coronavirus family, support that DPP4 inhibition at present doesn’t represent a plausible approach to mitigate Covid-19.


title: Porcine aminopeptidase N mediated polarized infection by porcine epidemic diarrhea virus in target cells

text: Abstract Infection of polarized intestinal epithelial cells by porcine epidemic diarrhea virus (PEDV) was characterized. Indirect immunofluorescence assay, real-time PCR, and transmission electron microscopy confirmed PEDV can be successfully propagated in immortalized swine small intestine epithelial cells (IECs). Infection involved porcine aminpeptidase N (pAPN), a reported cellular receptor for PEDV, transient expression of pAPN and siRNA targeted pAPN increased and decreased the infectivity of PEDV in IECs, respectively. Subsequently, polarized entry into and release from both Vero E6 and IECs was analyzed. PEDV entry into polarized cells and pAPN grown on membrane inserts occurs via apical membrane. The progeny virus released into the medium was also quantified which demonstrated that PEDV is preferentially released from the apical membrane. Collectively, our data demonstrate that pAPN, the cellular receptor for PEDV, mediates polarized PEDV infection. These results imply the possibility that PEDV infection may proceed by lateral spread of virus in intestinal epithelial cells.


title: Aptamers Chemistry: Chemical Modifications and Conjugation Strategies

text: Soon after they were first described in 1990, aptamers were largely recognized as a new class of biological ligands that can rival antibodies in various analytical, diagnostic, and therapeutic applications. Aptamers are short single-stranded RNA or DNA oligonucleotides capable of folding into complex 3D structures, enabling them to bind to a large variety of targets ranging from small ions to an entire organism. Their high binding specificity and affinity make them comparable to antibodies, but they are superior regarding a longer shelf life, simple production and chemical modification, in addition to low toxicity and immunogenicity. In the past three decades, aptamers have been used in a plethora of therapeutics and drug delivery systems that involve innovative delivery mechanisms and carrying various types of drug cargos. However, the successful translation of aptamer research from bench to bedside has been challenged by several limitations that slow down the realization of promising aptamer applications as therapeutics at the clinical level. The main limitations include the susceptibility to degradation by nucleases, fast renal clearance, low thermal stability, and the limited functional group diversity. The solution to overcome such limitations lies in the chemistry of aptamers. The current review will focus on the recent arts of aptamer chemistry that have been evolved to refine the pharmacological properties of aptamers. Moreover, this review will analyze the advantages and disadvantages of such chemical modifications and how they impact the pharmacological properties of aptamers. Finally, this review will summarize the conjugation strategies of aptamers to nanocarriers for developing targeted drug delivery systems.


Acute myocarditis with ventricular non compaction in a COVID-19 patient


title: Integrated urban hydrometeorological, climate and environmental services: Concept, methodology and key messages

text: Abstract Integrated Urban hydrometeorological, climate and environmental Services (IUS) is a WMO initiative to aid development of science-based services to support safe, healthy, resilient and climate friendly cities. Guidance for Integrated Urban Hydrometeorological, Climate and Environmental Services (Volume I) has been developed with the intent to provide an overview of the concept, methods and good practices for producing and providing these services to respond to the hazards across a range of time scales (weather to climate). This involves combining (dense) heterogeneous observation networks, high-resolution forecasts, multi-hazard early warning systems and climate services to assist cities in setting and implementing mitigation and adaptation strategies for the management and building of resilient and sustainable cities. IUS include research, evaluation and delivery with a wide participation from city governments, national hydrometeorological services, international organizations, universities, research institutions and private sector stakeholders. An overview of the IUS concept with key messages, examples of good practice and recommendations are provided. The research community will play an important role to: identify critical research challenges; provide impact forecasts and warnings; develop and deliver IUS internationally, and; support national and local communities in the implementation of IUS thereby contributing to the United Nations' Sustainable Development Goals at all scales.


title: Fight or Flight: The Ethics of Emergency Physician Disaster Response

text: Most disaster plans depend on using emergency physicians, nurses, emergency department support staff, and out-of-hospital personnel to maintain the health care system’s front line during crises that involve personal risk to themselves or their families. Planners automatically assume that emergency health care workers will respond. However, we need to ask: Should they, and will they, work rather than flee? The answer involves basic moral and personal issues. This article identifies and examines the factors that influence health care workers’ decisions in these situations. After reviewing physicians’ response to past disasters and epidemics, we evaluate how much danger they actually faced. Next, we examine guidelines from medical professional organizations about physicians’ duty to provide care despite personal risks, although we acknowledge that individuals will interpret and apply professional expectations and norms according to their own situation and values. The article goes on to articulate moral arguments for a duty to treat during disasters and social crises, as well as moral reasons that may limit or override such a duty. How fear influences behavior is examined, as are the institutional and social measures that can be taken to control fear and to encourage health professionals to provide treatment in crisis situations. Finally, the article emphasizes the importance of effective risk communication in enabling health care professionals and the public to make informed and defensible decisions during disasters. We conclude that the decision to stay or leave will ultimately depend on individuals’ risk assessment and their value systems. Preparations for the next pandemic or disaster should include policies that encourage emergency physicians, who are inevitably among those at highest risk, to “stay and fight.”


title: Recent Advances in the Study of Human Antibody Responses to Influenza Virus Using Optimized Human Hybridoma Approaches

text: Influenza viruses exhibit a fascinating level of antigenic heterogeneity that facilitates re-infection in the human population. The human antibody repertoire also manifests endless capability for variation in the genes that specify the portion of antibody molecules interacting with epitopes. A recent explosion of techniques for isolating human monoclonal antibodies to viruses has led to isolation of new antibodies that allow glimpses into the molecular basis for recognition and escape that underlies the constant antigenic drift in influenza surface proteins. These studies also reveal evidence for lifelong persistence of immunity to some influenza viruses.


title: Coping with diabetes during the COVID – 19 lockdown in India: Results of an online pilot survey

text: AIM: The management of diabetes has become a challenge due to the COVID 19 lockdown. An online-based pilot survey was conducted to study how people with diabetes were coping with their Diabetes during the COVID - 19 lockdown. METHOD: The questions were designed in an online survey, Survey Monkey, to conduct this cross-sectional study. The link was generated and sent to 100 registered patients of the MV Hospital for Diabetes Royapuram who had not contacted the hospital after the lockdown announcement. The survey was done between April 1 and April 15, 2020.Oral consent was obtained through telephone before the link was sent by Whatsapp to them.The questionnaire consisted of questions on home blood glucose monitoring, regularity in doing their physical activity and dietary compliance and anxiety about the viral infection. RESULTS: 92% of the participants had Type 2 diabetes. Only 28% of the participants were checking their blood glucose levels regularly. 80% of the participants mentioned that they were following regular exercise and diet control during the lockdown period. 40% of the participants were anxious about the Covid infection. CONCLUSION: SMBG needs to be practiced on regular basis, especially among the patients with diabetes on insulin therapy. Most of the people surveyed were coping well with their Diabetes. Patients have reported that they were able to maintain proper dietary compliance and be more physically active at home during this lockdown. These findings need to be ascertained in larger sample of patients.


title: The interaction of animal cytoplasmic RNA viruses with the nucleus to facilitate replication

text: Abstract A number of positive and negative strand RNA viruses whose primary site of replication is the cytoplasm use the nucleus and/or nuclear components in order to facilitate their replicative processes and alter host cell function. The nucleus itself is divided into a number of different sub-domains including structures such as the nucleolus. Many of the nuclear proteins that localise to these domains are involved in RNA processing, and because of their limited coding capacity, it may be necessary for RNA viruses to sequester such cellular factors in order to facilitate the replication, transcription and translation of their genomes. Amongst the best-studied examples of this are the picornaviruses, whose infection results in the redistribution of nuclear proteins to the cytoplasm and their interaction with the internal ribosome entry site (IRES) to facilitate translation of the picornavirus polyprotein. Examples can be found of other positive and also negative strand RNA virus proteins that localise to the nucleus and sub-domains (especially the nucleolus) during virus infection, and several localisation motifs have been defined. Apart from sequestering nuclear proteins for a role in replication, such viruses may also target the nucleus to disrupt nuclear functions and to inhibit antiviral responses.


title: Comparison of nasopharyngeal and oropharyngeal swabs for SARS-CoV-2 detection in 353 patients received tests with both specimens simultaneously

text: Abstract Background Since the outbreak of coronavirus disease (COVID-19) in Wuhan in December 2019, by March 10, 2020, a total of 80,932 confirmed cases have been reported in China. Two consecutively negative RT-PCR test results in respiratory tract specimens is required for the evaluation of discharge from hospital, and oropharyngeal swabs were the most common sample. However, false negative results occurred in the late stage of hospitalization, and avoiding false negative result is critical essential. Methods We reviewed the medical record of 353 patients who received tests with both specimens simultaneously, and compared the performance between nasopharyngeal and oropharyngeal swabs. Results Of the 353 patients (outpatients, 192; inpatients, 161) studied, the median age was 54 years, and 177 (50.1%) were women. Higher positive rate (positive tests/total tests) was observed in nasopharyngeal swabs than oropharyngeal swabs, especially in inpatients. Nasopharyngeal swabs from inpatients showed higher positive rate than outpatients. Nasopharyngeal swabs from male showed higher positive rate than female, especially in outpatients. Detection with both specimens slightly increased the positive rate than nasopharyngeal swab only. Moreover, the consistency between from nasopharyngeal and oropharyngeal swabs were poor (Kappa=0.308). Conclusion In conclusion, our study suggests that nasopharyngeal swabs may be more suitable than oropharyngeal swab at this stage of COVID-19 outbreak.


title: Viral gastroenteritis in children in Colorado 2006–2009

text: Acute gastroenteritis accounts for a significant burden of medically attended illness in children under the age of five. For this study, four multiplex reverse transcription PCR assays were used to determine the incidence of adenovirus, astrovirus, coronavirus, norovirus GI and GII, rotavirus, and sapovirus in stool samples submitted for viral electron microscopy (EM) to the Children's Hospital Colorado. Of 1105 stool samples available, viral RNA/DNA was detected in 247 (26.2%) of 941 pediatric samples (median age = 2.97 years, 54% male) with 28 (3.0%) positive for more than one virus. Adenovirus, astrovirus, norovirus GI, norovirus GII, rotavirus, and sapovirus were detected in 95 (10.0%), 33 (3.5%), 8 (0.9%), 90 (9.6%), 49 (5.2%), and 2 (0.2%) of the pediatric samples, respectively. No coronaviruses were identified. Sequencing of norovirus positive samples indicated an outbreak of norovirus strain GII.4 in 2006 with evidence of numerous circulating strains. Multiple samples from the same immunocompromised patients demonstrated symptomatic shedding of norovirus for up to 32 weeks and astrovirus for 12 weeks. RT‐PCR detected 99 of 111 (89%) adenovirus‐positive samples versus 12 (11%) by EM, and 186 of 192 (97%) sapovirus/astrovirus/norovirus‐positive samples versus 21 (11%) by EM. Noroviruses and adenoviruses are common causes of gastroenteritis in children. Immunocompromised patients can be infected with multiple viruses and shed viruses in their stools for prolonged periods. This data support the superiority of RT‐PCR compared to EM for diagnosis of viral gastroenteritis. J. Med. Virol. 87:931–939, 2015. © 2015 Wiley Periodicals, Inc.


title: Unanswered questions about the Middle East respiratory syndrome coronavirus (MERS-CoV)

text: BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) represents a current threat to the Arabian Peninsula, and potential pandemic disease. As of June 3, 2014, MERS CoV has reportedly infected 688 people and killed 282. We briefly summarize the state of the outbreak, and highlight unanswered questions and various explanations for the observed epidemiology. FINDINGS: The continuing but infrequent cases of MERS-CoV reported over the past two years have been puzzling and difficult to explain. The epidemiology of MERS-CoV, with many sporadic cases and a few hospital outbreaks, yet no sustained epidemic, suggests a low reproductive number. Furthermore, a clear source of infection to humans remains unknown. Also puzzling is the fact that MERS-CoV has been present in Saudi Arabia over several mass gatherings, including the 2012 and 2013 Hajj and Umrah pilgrimages, which predispose to epidemics, without an epidemic arising. CONCLUSIONS: The observed epidemiology of MERS-CoV is quite distinct and does not clearly fit either a sporadic or epidemic pattern. Possible explanations of the unusual features of the epidemiology of MERS-CoV include sporadic ongoing infections from a non-human source; human to human transmission with a large proportion of undetected cases; or a combination of both. The virus has been identified in camels; however the mode of transmission of the virus to humans remains unknown, and many cases have no history of animal contact. In order to gain a better understanding of the epidemiology of MERS CoV, further investigation is warranted.


title: SARS coronavirus nucleocapsid immunodominant T-cell epitope cluster is common to both exogenous recombinant and endogenous DNA-encoded immunogens

text: Abstract Correspondence between the T-cell epitope responses of vaccine immunogens and those of pathogen antigens is critical to vaccine efficacy. In the present study, we analyzed the spectrum of immune responses of mice to three different forms of the SARS coronavirus nucleocapsid (N): (1) exogenous recombinant protein (N-GST) with Freund's adjuvant; (2) DNA encoding unmodified N as an endogenous cytoplasmic protein (pN); and (3) DNA encoding N as a LAMP-1 chimera targeted to the lysosomal MHC II compartment (p-LAMP-N). Lysosomal trafficking of the LAMP/N chimera in transfected cells was documented by both confocal and immunoelectron microscopy. The responses of the immunized mice differed markedly. The strongest T-cell IFN-γ and CTL responses were to the LAMP-N chimera followed by the pN immunogen. In contrast, N-GST elicited strong T cell IL-4 but minimal IFN-γ responses and a much greater antibody response. Despite these differences, however, the immunodominant T-cell ELISpot responses to each of the three immunogens were elicited by the same N peptides, with the greatest responses being generated by a cluster of five overlapping peptides, N76–114, each of which contained nonameric H2d binding domains with high binding scores for both class I and, except for N76–93, class II alleles. These results demonstrate that processing and presentation of N, whether exogenously or endogenously derived, resulted in common immunodominant epitopes, supporting the usefulness of modified antigen delivery and trafficking forms and, in particular, LAMP chimeras as vaccine candidates. Nevertheless, the profiles of T-cell responses were distinctly different. The pronounced Th-2 and humoral response to N protein plus adjuvant are in contrast to the balanced IFN-γ and IL-4 responses and strong memory CTL responses to the LAMP-N chimera.


title: Replication of murine coronaviruses in somatic cell hybrids between murine fibroblasts and rat Schwannoma cells

text: Abstract The replication of the murine coronaviruses MHV3 and JHM has been studied in somatic cell hybrids formed between murine fibroblast L2 cells which support lytic infections with both these agents, and rat RN2 Schwannoma cells which support the replication of JHM in a temperature-sensitive, persistent manner but are restrictive to the replication of MHV3. The results described in this report indicate that the totally permissive state is dominant over the persistent or restricted state since the hybrid cells permit the replication of both these viral agents in a lytic manner.


title: Capacity building in health care professions within the Gulf cooperation council countries: paving the way forward

text: BACKGROUND: There is a worldwide shortage of health care workers. This problem is particularly severe in the Gulf Cooperation Council (GCC) countries because of shortages in certain medical disciplines, due to a lack of nationally-trained professionals and a less developed educational system compared to other high income countries. Consequently, GCC countries are heavily dependent on an expatriate health care workforce; a problem exacerbated by high turnover. We discuss challenges and potential strategies for improving and strengthening capacity building efforts in health care professions in the GCC. MAIN TEXT: In the GCC, there are 139 schools providing professional health education in medicine, dentistry, pharmacy, nursing, midwifery, and other specialties. Health education school density reported for the GCC countries ranges between 2.2 and 2.8 schools per one million inhabitants, except in Oman where it is 4.0 per one million inhabitants. The GCC countries rely heavily on expatriate health professionals. The number of physicians and nurses in the GCC countries are 2.1 and 4.5 per 1000 respectively, compared to 2.8 and 7.9 among member countries of the Organisation for Economic Cooperation and Development (OECD). Interestingly, the number of dentists and pharmacists is higher in the GCC countries compared to OECD countries. A nationally trained health care workforce is essential for the GCC countries. Physiotherapy and occupational therapy are two identified areas where growth and development are recommended. Custom-tailored continuing medical education and continuing professional development (CPD) programs can augment the skills of health practitioners, and allow for the expansion of their scope of practice when warranted. CONCLUSION: Capacity building can play an essential role in addressing the major health challenges and improving the overall quality of health care in the region. Efforts aimed at increasing the number of locally-trained graduates and developing and implementing need-based CPD programs are vital for capacity building and lifelong learning in health care professions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12909-019-1513-2) contains supplementary material, which is available to authorized users.


title: Impact of enhanced infection control procedures on clinical outcome following resuscitation attempts

text: Summary The impact of infection control measures (ICMs) on emergency resuscitation during an outbreak is unclear. The purpose of this retrospective observational study was to investigate the outcomes of emergency resuscitation after implementation of ICMs. Data were collected for the period 1 January to 4 July in 2003 from a 1732-bed tertiary care hospital in central Taiwan. Non-trauma patients who required emergency resuscitation were classified into two groups: before (period 1), and after (period 2), the date on which strict ICMs were implemented. The analysis variables included demographic data of patients, place of resuscitation, number of participating resuscitators, response time and duration of resuscitation, fever, pneumonia status and results of resuscitation. The response time was unchanged but the number of patient resuscitations without an emergency intubation, rapid sequence intubation or a ‘do not resuscitate’ order increased from 88 (24.4%), 23 (6.4%) and 16 (4.4%) in period 1 to 103 (33.0%), 32 (10.3%) and 29 (9.3%) in period 2, respectively. The failure rate of resuscitation was significantly higher in period 2 (odds ratio: 1.59, 95% confidence interval: 1.17–2.16). The number of emergency resuscitations in patients with fever or pneumonia was not significantly different between these two periods. In conclusion, strict ICM implementation appeared to play a role in the increased failure rate in emergency resuscitation. Normal provision of healthcare to patients and adequate protection of healthcare workers during emergency resuscitation will be of paramount importance during the next outbreak of a highly contagious disease.


title: Identification of synthetic vaccine candidates against SARS CoV infection

text: Abstract Three peptides, D1 (amino acid residues 175–201), D2 (a.a. 434–467), and TM (a.a. 1128–1159), corresponding to the spike protein (S) of severe acute respiratory syndrome corona virus (SARS CoV) were synthesized and their immunological functions were investigated in three different animals models (mice, guinea pigs, and rabbits). The peptides mixture formulated either with Freund’s adjuvant or synthetic adjuvant Montanide ISA-51/oligodeoxy nucleotide CpG (ISA/CpG) could elicit antisera in immunized animals which were capable of inhibiting SARS/HIV pseudovirus entry into HepG2 cells. The neutralizing epitopes were identified using peptides to block the neutralizing effect of guinea pig antisera. The major neutralizing epitope was located on the D2 peptide, and the amino acid residue was fine mapped to 434–453. In BALB/c mice T-cell proliferation assay revealed that only D2 peptide contained T-cell epitope, the sequence of which corresponded to amino acid residue 434–448. The ISA/CpG formulation generated anti-D2 IgG titer comparable to those obtained from Freund’s adjuvant formulation, but generated fewer antibodies against D1 or TM peptides. The highly immunogenic D2 peptide contains both neutralizing and Th cell epitopes. These results suggest that synthetic peptide D2 would be useful as a component of SARS vaccine candidates.


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title: Detection of human coronaviruses in children with acute gastroenteritis

text: Abstract Background Human coronaviruses (HCoVs) are known respiratory pathogens. Moreover, coronavirus-like particles have been seen by electron microscope in stools, and SARS-HCoV has been isolated from intestinal tissue and detected in stool samples. Objectives To find out if HCoVs can be found in stools of children with acute gastroenteritis and to assess the significance of HCoVs in the etiology of acute gastroenteritis in children. Study design 878 stool specimens from children with acute gastroenteritis and 112 from control children were tested by RT-PCR to detect HCoV groups 1B, 2A and SARS. HCoVs were typed by sequencing all PCR positive samples. Results Twenty-two (2.5%) of the 878 stool specimens of children with acute gastroenteritis were positive for HCoVs. The following HCoV types were detected: OC43 (10 cases, 45.5%), HKU1 (6 cases, 27.3%), 229E (2 cases, 9.1%) and NL63 (4 cases, 18.2%). In 4 of the cases a HCoV was the only detected virus; in the remaining cases rotavirus or norovirus was found in the same sample. In control groups there were two HCoV positive samples of 112 tested. Conclusions This study shows that all known non-SARS HCoVs can be found in stools of children with acute gastroenteritis. On the basis of this study, the significance of coronaviruses as gastrointestinal pathogens in children appears minor, since most of the coronavirus findings were co-infections with known gastroenteritis viruses.


title: Real-time reverse transcriptase polymerase chain reaction assays for Middle East Respiratory Syndrome

text: Abstract Here we designed and tested two highly specific quantitative TaqMan®-MGB-based reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) assays for Middle East Respiratory Syndrome (MERS). The primers and probes for these assays were evaluated and found to have a limit of detection (LOD) of 0.005 plaque-forming units/PCR (pfu/PCR).


title: Evolution of Viral Proteins Originated De Novo by Overprinting

text: New protein-coding genes can originate either through modification of existing genes or de novo. Recently, the importance of de novo origination has been recognized in eukaryotes, although eukaryotic genes originated de novo are relatively rare and difficult to identify. In contrast, viruses contain many de novo genes, namely those in which an existing gene has been “overprinted” by a new open reading frame, a process that generates a new protein-coding gene overlapping the ancestral gene. We analyzed the evolution of 12 experimentally validated viral genes that originated de novo and estimated their relative ages. We found that young de novo genes have a different codon usage from the rest of the genome. They evolve rapidly and are under positive or weak purifying selection. Thus, young de novo genes might have strain-specific functions, or no function, and would be difficult to detect using current genome annotation methods that rely on the sequence signature of purifying selection. In contrast to young de novo genes, older de novo genes have a codon usage that is similar to the rest of the genome. They evolve slowly and are under stronger purifying selection. Some of the oldest de novo genes evolve under stronger selection pressure than the ancestral gene they overlap, suggesting an evolutionary tug of war between the ancestral and the de novo gene.


Hydroxychloroquine hitting the headlines—retinal considerations


title: Recent advances in Cordyceps sinensis polysaccharides: Mycelial fermentation, isolation, structure, and bioactivities: A review

text: Abstract Cordyceps (Ophiocordyceps sinensis) sinensis, the Chinese caterpillar fungus, is a unique and precious medicinal fungus in traditional Chinese medicine which has been used as a prestigious tonic and therapeutic herb in China for centuries. Polysaccharides are bioactive constituents of C. sinensis, exhibiting several activities such as immunomodulation, antitumour, antioxidant and hypoglycaemic. As natural C. sinensis fruiting body-caterpillar complexes are very rare and expensive, the polysaccharides documented over the last 15–20years from this fungal species were mostly extracted from cultivated fungal mycelia (intracellular polysaccharides) or from mycelial fermentation broth (exopolysaccharides). Extraction and purification of the polysaccharides is a tedious process involving numerous steps of liquid and solid phase separations. Nevertheless, a large number of polysaccharide structures have been purified and elucidated. However, relationships between the structures and activities of these polysaccharides are not well established. This review provides a comprehensive summary of the most recent developments in various aspects (i.e., production, extraction, structure, and bioactivity) of the intracellular and exopolysaccharides from mycelial fermentation of C. sinensis fungi. The contents and data will serve as useful references for further investigation, production and application of these polysaccharides in functional foods and therapeutic agents.


title: Preparing IR for COVID-19: The Singapore Experience

text: This paper describes country-wide special measures undertaken for interventional radiology (IR) staff during the current coronavirus disease 2019 (COVID-19) pandemic. Although each IR service around the world faces unique challenges, the principles outlined in this paper will be useful when designing or strengthening individual practices and integrating them within wider hospital and national measures. Moving beyond the current outbreak, these measures will be useful for any future infectious diseases which are likely to arise.


title: Jatrophane and rearranged jatrophane-type diterpenes: biogenesis, structure, isolation, biological activity and SARs (1984–2019)

text: Diterpene compounds specially macrocyclic ones comprising jatrophane, lathyrane, terracinolide, ingenane, pepluane, paraliane, and segetane skeletons occurring in plants of the Euphorbiaceae family are of considerable interest in the context of natural product drug discovery programs. They possess diverse complex skeletons and a broad spectrum of therapeutically relevant biological activities including anti-inflammatory, anti-chikungunya virus, anti-HIV, cytotoxic, and multidrug resistance-reversing activities as well as curative effects on thrombotic diseases. Among macrocyclic diterpenes of Euphorbia, the discovery of jatrophane and modified jatrophane diterpenes with a wide range of structurally unique polyoxygenated polycyclic derivatives and as a new class of powerful inhibitors of P-glycoprotein has opened new frontiers for research studies on this genus. In this review, an attempt has been made to give in-depth coverage of the articles on the naturally occurring jatrophanes and rearranged jatrophane-type diterpenes isolated from species belonging to the Euphorbiaceae family published from 1984 to March 2019, with emphasis on the biogenesis, isolation methods, structure, biological activity, and structure–activity relationship. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11101-020-09667-8) contains supplementary material, which is available to authorized users.


title: Immune response to a murine coronavirus: Identification of a homing receptor-negative CD4+ T cell subset that responds to viral glycoproteins

text: Abstract The lymphocyte proliferative response to mouse hepatitis virus, strain JHM (MHV-JHM), a well-described cause of chronic and acute neurological infections, has been studied using vaccinia virus recombinants expressing individual MHV proteins. The surface (S) and transmembrane (M) glycoproteins were the most active proteins in causing proliferation of lymphocytes isolated from immunized adult mice, whereas lymphocytes from persistently infected mice proliferated only in response to the S protein. The cells from immunized mice which proliferated most actively in response to MHV were positive for the CD4 antigen and secreted interferon-γ. In addition, the most responsive subset of cells did not express gpg0MEL-14, the lymph node-specific homing receptor. The results identify a subpopulation of CD4+ T cells that may be an important component of the cell-mediated immune response to this virus. The data also suggest that response to the M protein is important in preventing disease progression in C57BL/6 mice since cells which recognize this protein are absent from persistently infected mice.


title: Effects of feeding pregnant beef cows selenium-enriched alfalfa hay on passive transfer of ovalbumin in their newborn calves

text: Abstract Intestinal absorption of immunoglobulins is critical for health and survival of newborn calves because there is no transfer of immunoglobulins in utero. The objective of this study was to determine if feeding beef cows Se-enriched alfalfa hay during the last trimester of gestation improves passive transfer of ovalbumin (OVA), a surrogate protein marker for IgG absorption. Control cows (n = 15) were fed non-Se-fortified alfalfa hay (5.3 mg Se/head daily) plus a mineral supplement containing inorganic Se (3 mg Se/head daily). Med-Se (n = 15) and High-Se cows (n = 15) were fed Se-biofortified alfalfa hay (27.6 and 57.5 mg Se/head daily, respectively); both groups received mineral supplement without added Se. Calves were randomly assigned to receive orally administered OVA at 12, 24, or 36 h of age. Calves that received their oral dose of OVA at 12 h of age had higher serum OVA concentrations across the first 48 h of life if born to High-Se cows compared to calves born to Control cows (P = 0.05), with intermediate values for calves born to Med-Se cows. Our results, using OVA as a model for passive transfer, suggest that if calves do not receive adequate colostrum to reach maximum pinocytosis, then supranutritional Se supplementation in beef cattle may improve passive transfer in their calves, if calves receive colostrum within the first 12 h of age.


Time‐Critical Goals of Care in the Emergency Department during COVID‐19: A Three‐Stage Protocol


title: Identification of a linear epitope on the capsid protein of classical swine fever virus

text: Abstract The capsid (C) protein of Classical swine fever virus (CSFV) is proposed to play an essential role in the replication and translation of the viral RNA. In this study, a monoclonal antibody (mAb) directed against the C protein was generated with the recombinant C protein expressed in Escherichia coli as immunogen. IFA and IPMA analysis showed that the native C protein of CSFV virions was reactive to the mAb. By truncating the C protein, we identified a linear epitope recognized by the mAb, corresponding to amino acids 61TQDGLYHNKN70 of the CSFV C protein, which is well conserved among pestiviruses. Laser confocal analysis showed that the C protein mainly locates in the cellular nucleoplasm and nucleolus of PK-15 cells. The results have implications for further study of CSFV replication.


title: Hyperglycemia, hydroxychloroquine, and the COVID‐19 pandemic

text: Coronavirus disease‐2019 (COVID‐19) infection and its severity can be explained by the concentration of glycosylated severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) viral particles in the lung epithelium, the concentration of glycosylated angiotensin‐converting enzyme receptor 2 (ACE2) in the lung epithelium, and the degree and control of the pulmonary immune response to the SARS‐CoV‐2 spike protein at approximately day 8 to 10 after symptom onset, which may be related to both. Binding of ACE2 by SARS‐CoV‐2 in COVID‐19 also suggests that prolonged uncontrolled hyperglycemia, and not just a history of diabetes mellitus, may be important in the pathogenesis of the disease. It is tempting to consider that the same mechanism acts in COVID‐19 as in SARS, where an overactive macrophage M1 inflammatory response, as neutralizing antibodies to the SARS‐CoV‐2 spike protein form at day 7 to 10, results in acute respiratory distress syndrome (ARDS) in susceptible patients. It also allows consideration of agents, such as hydroxychloroquine, which may interfere with this overly brisk macrophage inflammatory response and perhaps influence the course of the disease, in particular, those that blunt but do not completely abrogate the M1 to M2 balance in macrophage polarization, as well as viral load, which in SARS appears to be temporally related to the onset of ARDS.


Microbial molecular markers and epidemiological surveillance in the era of high throughput sequencing: an update from the IMMEM-10 conference


title: Risk of COVID-19 among frontline healthcare workers and the general community: a prospective cohort study

text: BACKGROUND: Data for frontline healthcare workers (HCWs) and risk of SARS-CoV-2 infection are limited and whether personal protective equipment (PPE) mitigates this risk is unknown. We evaluated risk for COVID-19 among frontline HCWs compared to the general community and the influence of PPE. METHODS: We performed a prospective cohort study of the general community, including frontline HCWs, who reported information through the COVID Symptom Study smartphone application beginning on March 24 (United Kingdom, U.K.) and March 29 (United States, U.S.) through April 23, 2020. We used Cox proportional hazards modeling to estimate multivariate-adjusted hazard ratios (aHRs) of a positive COVID-19 test. FINDINGS: Among 2,035,395 community individuals and 99,795 frontline HCWs, we documented 5,545 incident reports of a positive COVID-19 test over 34,435,272 person-days. Compared with the general community, frontline HCWs had an aHR of 11·6 (95% CI: 10·9 to 12·3) for reporting a positive test. The corresponding aHR was 3·40 (95% CI: 3·37 to 3·43) using an inverse probability weighted Cox model adjusting for the likelihood of receiving a test. A symptom-based classifier of predicted COVID-19 yielded similar risk estimates. Compared with HCWs reporting adequate PPE, the aHRs for reporting a positive test were 1·46 (95% CI: 1·21 to 1·76) for those reporting PPE reuse and 1·31 (95% CI: 1·10 to 1·56) for reporting inadequate PPE. Compared with HCWs reporting adequate PPE who did not care for COVID-19 patients, HCWs caring for patients with documented COVID-19 had aHRs for a positive test of 4·83 (95% CI: 3·99 to 5·85) if they had adequate PPE, 5·06 (95% CI: 3·90 to 6·57) for reused PPE, and 5·91 (95% CI: 4·53 to 7·71) for inadequate PPE. INTERPRETATION: Frontline HCWs had a significantly increased risk of COVID-19 infection, highest among HCWs who reused PPE or had inadequate access to PPE. However, adequate supplies of PPE did not completely mitigate high-risk exposures. FUNDING: Zoe Global Ltd., Wellcome Trust, EPSRC, NIHR, UK Research and Innovation, Alzheimer’s Society, NIH, NIOSH, Massachusetts Consortium on Pathogen Readiness


Letter to the Editor: From Katrina to COVID-19: Still Re-building New Orleans, One Nurse At A Time


title: Patients who challenge

text: Individuals have different values. They seek to express their individuality even when receiving medical care. It is a part of modern medical practice and respect for patient autonomy to show respect for different values. We give an account of what it means to respect different values and challenging patients in medical practice. Challenging choices are often choices which are perceived by many to be either irrational or against a person's interests, such as engaging in harmful or excessively risky activities. When the medical profession is involved in such choices, the basic medical principle of acting in a person's best interests is challenged. Often doctors refuse to respect controversial choices on paternalistic grounds. We should all respect and facilitate the controversial choices of competent individuals, subject to resource limitations, our own and others well-being and autonomy, and the public interest. But more importantly, sometimes such choices make for a better, more autonomous life. Sometimes, such choices reflect considerations of global well-being or altruism, or idiosyncratic attitudes to risk. Sometimes, they reflect unusual values. However, in some other cases, controversial choices are irrational and are not expressions of our autonomy. Doctors should assist patients to make rational if individual choices. The patient also bears the responsibility for bringing his beliefs to the attention of the clinician.


Mental health services in Italy during the Covid‐19 Pandemic


title: Is there really such a thing as “one health”? Thinking about a more than human world from the perspective of cultural anthropology

text: Today's era of globalization is characterized by intensified interspecies encounters, growing ecological concerns and the (re-)emergence of infectious diseases, manifesting themselves in the interplay of medical and biological, but also social, cultural and political processes. One health approaches – which combine multidisciplinary efforts to stimulate collaborations between different health professionals such as veterinarians, medical practitioners, biologists, and public health professionals – can be understood as a response to this complex interconnectedness. Integrating a social science perspective might prove beneficial to this endeavor. This essay locates the one health discussion on disease ecologies in a more than human world within recent developments in cultural and medical anthropology that focus on the entanglements between health and a multitude of animals, plants or microbes, as they are characteristic of a globalized modernity. The paper aims to examine the social dimensions of human–animal-disease-interactions, claiming that disease is a biocultural phenomenon and that social factors generally play a crucial role in the emergence, spread and management of (infectious) disease. Consequently, it will be argued that there is a need to rethink our objects of inquiry and any given assumptions of human health, the human body or the constitution of “the global” as such. Incorporating the social sciences into one health approaches can help address topics such as consumption patterns, human–animal behavior or environmental conflicts in a novel way and on a grander scale than ever before. Yet, a greater sensitivity to context may entail some skepticism about the idea of one health – not in spite of the complex entanglements between humans, environments, animals and pathogens, but precisely because of them.


title: Clinical Hepatozoon canis infection in a dog in Turkey

text: A five‐year‐old female dog was presented with a four‐week history of inappetence, weight loss, and skin and gait abnormalities. Physical examination revealed weakness, depression, incoordination of the posterior limbs, emaciation, skin and hair coat alterations, peripheral lymphadenopathy, pale mucous membranes and fever. Laboratory analysis of samples revealed abnormalities which included anaemia, neutrophilic leucocytosis, thrombocytopenia, low serum glucose and albumin concentrations, and increased serum alkaline phosphatase activity. The diagnosis was confirmed microscopically, by demonstrating the presence of Hepatozoon canis gametocytes within neutrophils in Giemsa‐stained peripheral blood smears. Treatment consisting of toltrazuril and a trimethoprim‐sulfamethoxazole combination was effective in relieving the clinical signs and clearing the blood of H canis gametocytes. To the authors’knowledge, this is the first detailed clinical description of H canis infection in a dog in Turkey.


title: Are infection control measures helpful in reducing paediatric ward infections?

text: As the majority of children on paediatric wards, especially in winter, have infections all paediatricians will be involved in infection control and prevention (ICP) without realising it. ICP measures include decisions on isolation of patients, which can be difficult with small numbers of cubicles. Children, who are highly infectious, have potential severe infections and those who are more at risk of developing severe infections (e.g. immunocompromised) should be isolated. Handwashing/decontamination is the central and most essential part of ICP measures. It should be actively encouraged and regularly monitored to ensure adherence. The ward layout will influence how we manage ICP. This includes placement and number of alcohol dispensers, sinks, bathrooms, equipment storage and the number of cubicles. It is also worth reviewing ward cleaning policies to assess whether these can be streamlined, potentially freeing up beds/cubicles earlier and leading to cost improvement without putting patients and staff at risk. We encourage all our staff to be fully vaccinated (including seasonal influenza vaccines and MMR). Paediatricians need to be closely involved in antibiotic stewardship and act as role models for all aspects of infection control, particularly proper handwashing.


title: Disaster and emergency management systems in urban areas

text: This article focuses on the factors shaping and constituting governance in urban/metropolitan emergency management. The main focus of the article is the multi-faceted inter-organizational relationships producing shared goals that are practiced at the local level, and specifically within the context of county-level metropolitan emergency management. The article presents a conceptual understanding of the governance concept, a brief summary of related research in the context of emergency management, and an example of the Orlando Metropolitan Area in the State of Florida for practical purposes.


title: Why are ethnic minorities worse affected?

text: Inequalities mean a disproportionate number of covid-19 patients are from minority ethnic backgrounds, reports Layal Liverpool


title: RNA delivery by extracellular vesicles in mammalian cells and its applications

text: The term ‘extracellular vesicles’ refers to a heterogeneous population of vesicular bodies of cellular origin that derive either from the endosomal compartment (exosomes) or as a result of shedding from the plasma membrane (microvesicles, oncosomes and apoptotic bodies). Extracellular vesicles carry a variety of cargo, including RNAs, proteins, lipids and DNA, which can be taken up by other cells, both in the direct vicinity of the source cell and at distant sites in the body via biofluids, and elicit a variety of phenotypic responses. Owing to their unique biology and roles in cell–cell communication, extracellular vesicles have attracted strong interest, which is further enhanced by their potential clinical utility. Because extracellular vesicles derive their cargo from the contents of the cells that produce them, they are attractive sources of biomarkers for a variety of diseases. Furthermore, studies demonstrating phenotypic effects of specific extracellular vesicle-associated cargo on target cells have stoked interest in extracellular vesicles as therapeutic vehicles. There is particularly strong evidence that the RNA cargo of extracellular vesicles can alter recipient cell gene expression and function. During the past decade, extracellular vesicles and their RNA cargo have become better defined, but many aspects of extracellular vesicle biology remain to be elucidated. These include selective cargo loading resulting in substantial differences between the composition of extracellular vesicles and source cells; heterogeneity in extracellular vesicle size and composition; and undefined mechanisms for the uptake of extracellular vesicles into recipient cells and the fates of their cargo. Further progress in unravelling the basic mechanisms of extracellular vesicle biogenesis, transport, and cargo delivery and function is needed for successful clinical implementation. This Review focuses on the current state of knowledge pertaining to packaging, transport and function of RNAs in extracellular vesicles and outlines the progress made thus far towards their clinical applications.


COVID 19 Fear, Stress, Anxiety, and Substance Use Among Russian and Belarusian University Students


title: Inhibition of SARS Pseudovirus Cell Entry by Lactoferrin Binding to Heparan Sulfate Proteoglycans

text: It has been reported that lactoferrin (LF) participates in the host immune response against Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) invasion by enhancing NK cell activity and stimulating neutrophil aggregation and adhesion. We further investigated the role of LF in the entry of SARS pseudovirus into HEK293E/ACE2-Myc cells. Our results reveal that LF inhibits SARS pseudovirus infection in a dose-dependent manner. Further analysis suggested that LF was able to block the binding of spike protein to host cells at 4°C, indicating that LF exerted its inhibitory function at the viral attachment stage. However, LF did not disrupt the interaction of spike protein with angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV. Previous studies have shown that LF colocalizes with the widely distributed cell-surface heparan sulfate proteoglycans (HSPGs). Our experiments have also confirmed this conclusion. Treatment of the cells with heparinase or exogenous heparin prevented binding of spike protein to host cells and inhibited SARS pseudovirus infection, demonstrating that HSPGs provide the binding sites for SARS-CoV invasion at the early attachment phase. Taken together, our results suggest that, in addition to ACE2, HSPGs are essential cell-surface molecules involved in SARS-CoV cell entry. LF may play a protective role in host defense against SARS-CoV infection through binding to HSPGs and blocking the preliminary interaction between SARS-CoV and host cells. Our findings may provide further understanding of SARS-CoV pathogenesis and aid in treatment of this deadly disease.


title: Implications for lipids during replication of enveloped viruses

text: Abstract Enveloped viruses, which include many medically important viruses such as human immunodeficiency virus, influenza virus and hepatitis C virus, are intracellular parasites that acquire lipid envelopes from their host cells. Success of replication is intimately linked to their ability to hijack host cell mechanisms, particularly those related to membrane dynamics and lipid metabolism. Despite recent progress, our knowledge of lipid mediated virus–host interactions remains highly incomplete. In addition, diverse experimental systems are used to study different stages of virus replication thus complicating comparisons. This review aims to present a unifying view of the widely diverse strategies used by enveloped viruses at distinct stages of their replication cycles.


Peer-Based Education Regarding the COVID-19 Pandemic


title: Forecasting US recessions: The role of economic uncertainty()

text: This letter highlights the role of macroeconomic and financial uncertainty in predicting US recessions. In-sample forecasts using probit models indicate that the two variables are the best predictors of recessions at short horizons. Macroeconomic uncertainty has the highest predictive power up to 7 months ahead and becomes the second best predictor—after the yield curve slope—at longer horizons. Using data up to end-2018, out-of-sample forecasts show that uncertainty has significantly contributed to lower the probability of a recession in 2019, which indeed did not occur.


A Previously Unrecognized Unr Stem-Loop Structure in the Coronavirus 5’ Untranslated Region Plays a Functional role in Replication


title: Structure of a SARS coronavirus-derived peptide bound to the human major histocompatibility complex class I molecule HLA-B*1501

text: The human leukocyte antigen (HLA) class I system comprises a highly polymorphic set of molecules that specifically bind and present peptides to cytotoxic T cells. HLA-B*1501 is a prototypical member of the HLA-B62 supertype and only two peptide–HLA-B*1501 structures have been determined. Here, the crystal structure of HLA-B*1501 in complex with a SARS coronavirus-derived nonapeptide (VQQESSFVM) has been determined at high resolution (1.87 Å). The peptide is deeply anchored in the B and F pockets, but with the Glu4 residue pointing away from the floor in the peptide-binding groove, making it available for interactions with a potential T-cell receptor.


title: A Descriptive Study of Coronavirus Disease 2019–Related Experiences and Perspectives of a National Sample of College Students in Spring 2020

text: PURPOSE: This is one of the first surveys of a USA-wide sample of full-time college students about their coronavirus disease 2019 (COVID-19)–related experiences in spring 2020. METHODS: We surveyed 725 full-time college students aged 18–22 years recruited via Instagram promotions on April 25–30, 2020. We inquired about their COVID-19–related experiences and perspectives, documented opportunities for transmission, and assessed COVID-19's perceived impacts to date. RESULTS: Thirty-five percent of participants experienced any COVID-19–related symptoms from February to April 2020, but less than 5% of them got tested, and only 46% stayed home exclusively while experiencing symptoms. Almost all (95%) had sheltered in place/stayed primarily at home by late April 2020; 53% started sheltering in place before any state had an official stay-at-home order, and more than one-third started sheltering before any metropolitan area had an order. Participants were more stressed about COVID-19's health implications for their family and for American society than for themselves. Participants were open to continuing the restrictions in place in late April 2020 for an extended period of time to reduce pandemic spread. CONCLUSIONS: There is substantial opportunity for improved public health responses to COVID-19 among college students, including for testing and contact tracing. In addition, because most participants restricted their behaviors before official stay-at-home orders went into effect, they may continue to restrict movement after stay-at-home orders are lifted, including when colleges reopen for in-person activities, if they decide it is not yet prudent to circulate freely. The public health, economic, and educational implications of COVID-19 are continuing to unfold; future studies must continue to monitor college student experiences and perspectives.


title: Pathogenesis and outcome of extrahepatic biliary obstruction in cats

text: Extrahepatic biliary obstruction (EHBO) was confirmed at surgery or necropsy in 22 cats. Biliary or pancreatic adenocarcinoma was diagnosed by histopathology in six cats and one cat had an undiagnosed mass in the common bile duct. The remaining 15 cats had at least one of a complex of inflammatory diseases including pancreatitis, cholangiohepatitis, cholelithiasis and cholecystitis. The most common clinical signs were jaundice, anorexia, lethargy, weight loss and vomiting. Hyperbilirubinaemia was present in all cases. Distension of the common bile duct and gall bladder was the most commonly observed finding on abdominal ultrasound. Nineteen cats underwent exploratory laparotomy for biliary decompression and diversion. Mortality in cats with underlying neoplasia was 100 per cent and, in those with non‐neoplastic lesions, was 40 per cent. Long‐term complications, in those that survived, included recurrence of cholangiohepatitis, chronic weight loss and recurrence of obstruction. Based on these findings, the prognosis for EHBO in cats must be considered guarded.


title: Asymptotic estimates of SARS-CoV-2 infection counts and their sensitivity to stochastic perturbation

text: Despite the importance of having robust estimates of the time-asymptotic total number of infections, early estimates of COVID-19 show enormous fluctuations. Using COVID-19 data from different countries, we show that predictions are extremely sensitive to the reporting protocol and crucially depend on the last available data point before the maximum number of daily infections is reached. We propose a physical explanation for this sensitivity, using a susceptible–exposed–infected–recovered model, where the parameters are stochastically perturbed to simulate the difficulty in detecting patients, different confinement measures taken by different countries, as well as changes in the virus characteristics. Our results suggest that there are physical and statistical reasons to assign low confidence to statistical and dynamical fits, despite their apparently good statistical scores. These considerations are general and can be applied to other epidemics.


title: Filoviruses: Interactions with the host cell

text: The highly pathogenic filoviruses, Marburg and Ebola virus, are difficult to handle and knowledge of the interactions between filoviruses and their host cells remained enigmatic for many years. Two developments were crucial for the presented advances in our understanding of the cell biology of filoviruses, which is still fragmentary. On the one hand, the number of high containment laboratories increased where handling of the highly pathogenic filoviruses is possible. On the other hand, molecular biological tools have been developed that allow investigation of certain aspects of filoviral replication under normal laboratory conditions which considerably accelerated research on filoviruses. This review describes advances in understanding the interactions between host cells and filoviruses during viral attachment, entry, transcription, assembly and budding.


title: Detection of bovine viral diarrhea virus genotype 1 in aerosol by a real time RT-PCR assay

text: BACKGROUND: As a pestivirus of the Flaviviridae family, bovine viral diarrhea virus (BVDV), has imposed a large burden on animal husbandry worldwide, and such virus can be transmitted mainly through direct contact with other infected animals and probably via aerosols. In the present study, we aimed to develop a real-time RT-PCR method for detection of BVDV-1 in aerosol samples. METHODS: A pair of primers specific for highly conserved regions of the BVDV-1 5′-UTR was designed. The standard curve and sensitivity of the developed assay were assessed based on 10-fold serial dilutions of RNA molecular standard. The specificity of the assay was evaluated with other pestiviruses and infectious bovine viruses. The clinical performance was examined by testing 169 aerosol samples. RESULTS: The results showed that a good linear relationship existed between the standard curve and the concentration of template. The lowest detection limit was 5.2 RNA molecules per reaction. This assay was specific for detection of BVDV-1, and no amplification was found for other pestiviruses such as classical swine fever virus (CSFV), border disease virus (BDV), and common infectious bovine viruses, including BVDV-2, infectious bovine rhinotracheitis virus (IBRV), bovine parainfluenza virus type 3 (BPIV-3), bovine respiratory syncytial virus (BRSV), bovine ephemeral fever virus (BEFV) and bovine coronavirus (BcoV). The assay was highly reproducible with low variation coefficient values (CVs) for intra-assay and inter-assay. A total of 169 aerosol samples collected from six dairy herds were tested using this method. The results showed that the positive detection rate of BVDV-1 was 17.2% (29/169), which was significantly higher compared with the conventional RT-PCR. Additionally, the positive samples (n = 29) detected by real-time RT-PCR were verified by BVDV RPA-LFD, and a concordance rate of 100% was obtained between them. CONCLUSIONS: Taken together, we developed a real-time RT-PCR assay for quantitative analysis of BVDV-1 in aerosol samples, and our finding provided valuable insights into the risk on aerosol transmission of BVDV-1.


title: Nasoseptal Flap Necrosis After Endoscopic Skull Base Surgery in the Setting of SARS-CoV-2/COVID-19

text: ABSTRACT Background A novel viral strain known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a worldwide pandemic known as Coronavirus 2019 (COVID-19). Early reports from China highlighted the risks associated with performing endoscopic endonasal skull base surgery in patients with SARS-CoV-2. We present a rare complication of nasoseptal flap (NSF) necrosis associated with COVID-19, further emphasizing the challenges of performing these procedures in this era. Case Description A 78-year-old male underwent an extended endoscopic endonasal transplanum resection of a pituitary macroadenoma for decompression of the optic chiasm. The resulting skull base defect was repaired using a pedicled nasoseptal flap (NSF). The patient developed meningitis and a cerebrospinal fluid (CSF) leak on post-operative day thirteen requiring revision repair of the defect. Twelve days later, he developed persistent fevers and rhinorrhea. The patient was re-explored endoscopically, and the NSF was noted to be necrotic and devitalized with evident CSF leakage. At that time, the patient tested positive for Sars-CoV-2. Post-operatively, he developed acute respiratory distress syndrome complicated by hypoxic respiratory failure and death. Conclusion To our knowledge, this is the first reported case of NSF necrosis in a patient with COVID-19. We postulate that the thrombotic complications of COVID-19 may have contributed to vascular pedicle thrombosis and NSF necrosis. Although the pathophysiology of SARS-CoV-2 and its effect on the nasal tissues is still being elucidated, this case highlights some challenges of performing endoscopic skull base surgery in the era of COVID-19.


title: CRISPR-Cas Targeting of Host Genes as an Antiviral Strategy

text: Currently, a new gene editing tool—the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) associated (Cas) system—is becoming a promising approach for genetic manipulation at the genomic level. This simple method, originating from the adaptive immune defense system in prokaryotes, has been developed and applied to antiviral research in humans. Based on the characteristics of virus-host interactions and the basic rules of nucleic acid cleavage or gene activation of the CRISPR-Cas system, it can be used to target both the virus genome and host factors to clear viral reservoirs and prohibit virus infection or replication. Here, we summarize recent progress of the CRISPR-Cas technology in editing host genes as an antiviral strategy.


Virtually-supported home peanut introduction during COVID-19 for at-risk infants


title: Too little too late: Waiting for TB to come

text: Abstract There is a new paradigm that preventing tuberculosis (TB) and addressing the reservoir of latent TB infection in combination with curing all TB cases is essential to accelerate the decline of TB rates and ending TB by 2050. However, complacency and incremental change eludes radical policy transformation needed to meet global targets. This essay explores current attitudes, policy disparities between high and lower burden settings, and what changes are needed to remove the obstacles to progress.


title: Food Markets with Live Birds as Source of Avian Influenza

text: A patient may have been infected with highly pathogenic avian influenza virus H5N1 in Guangzhou, People's Republic of China, at a food market that had live birds. Virus genes were detected in 1 of 79 wire cages for birds at 9 markets. One of 110 persons in the poultry business at markets had neutralizing antibody against H5N1.