title: Simultaneous detection of hemagglutinin and neuraminidase genes of novel influenza A (H7N9) by duplex real-time reverse transcription polymerase chain reaction

text: Abstract A novel reassortant influenza A (H7N9) virus emerged recently in China. In this study, a duplex real-time reverse transcription polymerase chain reaction (rRT-PCR) assay was developed for the simultaneous detection of hemagglutinin (HA) and neuraminidase (NA) genes of H7N9 influenza viruses. The sensitivity of the assay was determined to be 10 RNA copies per reaction for both HA and NA genes. No cross-reactivity was observed with other influenza virus subtypes or respiratory tract viruses. One hundred and forty-six clinical and environmental specimens were tested and compared with reference methods and were found to be consistent. The assay is suitable for large-scale screening due to short turnaround times and high specificity, sensitivity, and reproducibility.


title: Early Growth Response gene 1 (Egr-1) regulates HSV-1 ICP4 and ICP22 gene expression

text: The molecular mechanisms mediating herpes simplex virus type 1 (HSV-1) gene silencing during latent infection are not clear. Five copies of early growth response gene 1 (Egr-1) binding elements were identified in the intron of HSV-1 ICP22 (infected cell protein No. 22) gene, leading to the hypothesis that Egr-1 binds to the viral genome and regulates the viral gene expression. Transient co-transfection assays indicated that Egr-1 negatively regulated the transcription of both full-length and intron-removed ICP22 promoters. The same assays also revealed that Egr-1 repressed ICP4 (infected cell protein No. 4) promoter activity in a dose-dependent manner but showed less inhibition when the intron was removed. Histone deacetylation was not involved in this regulation since histone deacetylase inhibitor trichostatin A did not exhibit any effect on Egr-1-mediated repression. Chromatin immunoprecipitation assays showed that Egr-1 reduced the binding of Sp1 to the promoters and that the co-repressor Nab2 (NGFI-A/EGR1-binding protein) was recruited to the proximity of ICP4 in the presence of Egr-1. These results suggested that the multifunctional transcription factor Egr-1 can repress HSV-1 immediate-early gene expression through the recruitment of co-repressor Nab2 and reduction of Sp1 occupancy, and thus may play a critical role in HSV-1 gene silencing during latency.


title: Common infection control practices in the emergency department: A literature review

text: BACKGROUND: Health care-associated infections (HAIs) are a major health concern, despite being largely avoidable. The emergency department (ED) is an essential component of the health care system and subject to workflow challenges, which may hinder ED personnel adherence to guideline-based infection prevention practices. METHODS: The purpose of this review was to examine published literature regarding adherence rates among ED personnel to selected infection control practices, including hand hygiene (HH) and aseptic technique during the placement of central venous catheters and urinary catheters. We also reviewed studies reporting rates of ED equipment contamination. PubMed was searched for studies that included adherence rates among ED personnel to HH during routine patient care, aseptic technique during the placement of central venous catheters and urinary catheters, and rates of equipment contamination. RESULTS: In total, 853 studies was screened, and 589 abstracts were reviewed. The full texts of 36 papers were examined, and 23 articles were identified as meeting inclusion criteria. Eight studies used various scales to measure HH compliance, which ranged from 7.7% to 89.7%. Seven articles examined central venous catheters inserted in the ED or by emergency medicine residents. Detail of aseptic technique practices during urinary catheterization was lacking. Four papers described equipment contamination in the ED. CONCLUSION: Standardized methods and definitions of compliance monitoring are needed to compare results across settings.


title: Emerging pathogens: the epidemiology and evolution of species jumps

text: Novel pathogens continue to emerge in human, domestic animal, wildlife and plant populations, yet the population dynamics of this kind of biological invasion remain poorly understood. Here, we consider the epidemiological and evolutionary processes underlying the initial introduction and subsequent spread of a pathogen in a new host population, with special reference to pathogens that originate by jumping from one host species to another. We conclude that, although pathogen emergence is inherently unpredictable, emerging pathogens tend to share some common traits, and that directly transmitted RNA viruses might be the pathogens that are most likely to jump between host species.


Telemedicine and Telehepatology During the COVID‐19 Pandemic


Psychiatry residency during the COVID-19 pandemic: navigating uncharted waters


Reply to Letter to Editor “Consequences of a COVID-19 Pandemic on Ophthalmologists”


Solidarity and transparency against the COVID‐19 pandemic


title: Toward the identification of viral cap-methyltransferase inhibitors by fluorescence screening assay

text: Abstract Two highly pathogenic human coronaviruses associated with severe respiratory syndromes emerged since the beginning of the century. The severe acute respiratory syndrome SARS-coronavirus (CoV) spread first in southern China in 2003 with about 8000 infected cases in few months. Then in 2012, the Middle East respiratory syndrome (MERS-CoV) emerged from the Arabian Peninsula giving a still on-going epidemic associated to a high fatality rate. CoVs are thus considered a major health threat. This is especially true as no vaccine nor specific therapeutic are available against either SARS- or MERS-CoV. Therefore, new drugs need to be identified in order to develop antiviral treatments limiting CoV replication. In this study, we focus on the nsp14 protein, which plays a key role in virus replication as it methylates the RNA cap structure at the N7 position of the guanine. We developed a high-throughput N7-MTase assay based on Homogenous Time Resolved Fluorescence (HTRF®) and screened chemical libraries (2000 compounds) on the SARS-CoV nsp14. 20 compounds inhibiting the SARS-CoV nsp14 were further evaluated by IC50 determination and their specificity was assessed toward flavivirus- and human cap N7-MTases. Our results reveal three classes of compounds: 1) molecules inhibiting several MTases as well as the dengue virus polymerase activity unspecifically, 2) pan MTases inhibitors targeting both viral and cellular MTases, and 3) inhibitors targeting one viral MTase more specifically showing however activity against the human cap N7-MTase. These compounds provide a first basis towards the development of more specific inhibitors of viral methyltransferases.


title: Lung Infection—A Public Health Priority

text: The pervasive burden of lung infections receives proportionately little attention from the biomedical and public health communities, argues Mizgerd.


title: Characterization of a protein tyrosine phosphatase as a host factor promoting baculovirus replication in silkworm, Bombyx mori

text: Abstract The relevance of protein tyrosine phosphatase (PTP) to host–pathogen interaction is highlighted in mammalian studies, whereas less is known in insects. Here we presented the categorization of the PTP complement of silkworm and characterized their homologous relationship with human and fruit fly PTPs. Among the 36 PTP genes, ptp-h, which was proposed to be the origin of baculovirus ptp belongs to atypical VH1-like dual-specific PTP subset and encodes a catalytic active protein. The maximum expression level of Bmptp-h was at 5th instar and in fat body. Bombyx mori nucleopolyhedrovirus (BmNPV) infection potently induced its expression in silkworm larvae and in BmE cells. Knock-down of Bmptp-h by RNA interference significantly inhibited viral replication, and over-expression enhanced viral replication as determined by viral DNA abundance and BmNPV-GFP positive cells. These results suggest that BmPTP-h might be one of the host factors that is beneficial to baculovirus infection by promoting viral replication.


title: Biophysical characterization of Vpu from HIV‐1 suggests a channel‐pore dualism

text: Vpu from HIV‐1 is an 81 amino acid type I integral membrane protein which consists of a cytoplasmic and a transmembrane (TM) domain. The TM domain is known to alter membrane permeability for ions and substrates when inserted into artificial membranes. Peptides corresponding to the TM domain of Vpu (Vpu(1‐32)) and mutant peptides (Vpu(1‐32)‐W23L, Vpu(1‐32)‐R31V, Vpu(1‐32)‐S24L) have been synthesized and reconstituted into artificial lipid bilayers. All peptides show channel activity with a main conductance level of around 20 pS. Vpu(1‐32)‐W23L has a considerable flickering pattern in the recordings and longer open times than Vpu(1‐32). Whilst recordings for Vpu(1‐32)‐R31V are almost indistinguishable from those of the WT peptide, recordings for Vpu(1‐32)‐S24L do not exhibit any noticeable channel activity. Recordings of WT peptide and Vpu(1‐32)‐W23L indicate Michaelis–Menten behavior when the salt concentration is increased. Both peptide channels follow the Eisenman series I, indicative for a weak ion channel with almost pore like characteristics. Proteins 2008. © 2007 Wiley‐Liss, Inc.


title: Environmental Cleaning and Disinfection

text: The guidelines in this article provide veterinarians, veterinary technicians, and veterinary health care workers with an overview of evidence-based recommendations for the best practices associated with environmental cleaning and disinfection of a veterinary clinic that deals with small animals. Hospital-associated infections and the control and prevention programs necessary to alleviate them are addressed from an environmental perspective. Measures of hospital cleaning and disinfection include understanding mechanisms and types of contamination in veterinary settings, recognizing areas of potential concern, addressing appropriate decontamination techniques and selection of disinfectants, the management of potentially contaminated equipment, laundry, and waste management, and environmental surveillance strategies.


title: Outcomes of Early Administration of Cidofovir in Non-Immunocompromised Patients with Severe Adenovirus Pneumonia

text: The benefits of treatment with antiviral therapy for severe adenovirus (AdV) pneumonia are not well established. We described the clinical characteristics and treatment outcomes of early cidofovir treatment of severe AdV pneumonia in non-immunocompromised patients. We retrospectively reviewed the medical records of all patients diagnosed with severe AdV pneumonia between 2012 and 2014. A total of seven non-immunocompromised patients with severe AdV pneumonia were identified, and all isolates typed (n = 6) were human AdV-B55. All patients had progressive respiratory failure with lobar consolidation with or without patchy ground glass opacity. Three patients required vasopressors and mechanical ventilation. All patients had abnormal laboratory findings including: leukopenia, thrombocytopenia, or elevated liver enzymes. After admission, all patients received antiviral therapy with cidofovir, and the median time from admission to cidofovir administration was 48 h and median the time from onset of symptoms to cidofovir administration was 7.1 days. After cidofovir administration, complete symptomatic improvement occurred after a median of 12 days and radiographic resolution occurred after a median of 21 days. Consequently, all patients completely improved without complications. Our data suggest that early administration of cidofovir in the course of treatment for respiratory failure as a result of AdV pneumonia in non-immunocompromised patients could be a treatment strategy worth considering, especially in cases of HAdV-55 infection.


title: Microevolution of Outbreak-Associated Middle East Respiratory Syndrome Coronavirus, South Korea, 2015

text: During the 2015 Middle East respiratory syndrome coronavirus outbreak in South Korea, we sequenced full viral genomes of strains isolated from 4 patients early and late during infection. Patients represented at least 4 generations of transmission. We found no evidence of changes in the evolutionary rate and no reason to suspect adaptive changes in viral proteins.


title: Grass carp reovirus VP56 represses interferon production by degrading phosphorylated IRF7

text: Abstract Grass carp reovirus (GCRV) is an efficient pathogen causing high mortality in grass carp, meanwhile, fish interferon (IFN) is a powerful cytokine enabling host cells to establish an antiviral state; therefore, the strategies used by GCRV to escape the cellular IFN response need to be investigated. Here, we report that GCRV VP56 inhibits host IFN production by degrading the transcription factor IFN regulatory factor 7 (IRF7). First, overexpression of VP56 inhibited the IFN production induced by the polyinosinic-polycytidylic acid (poly I:C) and mitochondrial antiviral signaling protein (MAVS), while the capacity of IRF7 on IFN induction was unaffected. Second, VP56 interacted with RLRs but did not affect the stabilization of the proteins in the normal state, while the phosphorylated IRF7 activated by TBK1 was degraded by VP56 through K48-linked ubiquitination. Finally, overexpression of VP56 remarkably reduced the host cellular ifn transcription and facilitated viral proliferation. Taken together, our results demonstrate that GCRV VP56 suppresses the host IFN response by targeting phosphorylated IRF7 for ubiquitination and degradation.


title: Novel agents targeting leukemia cells and immune microenvironment for prevention and treatment of relapse of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation

text: Relapse remains the worst life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML), whose prognosis has been historically dismal. Given the rapid development of genomics and immunotherapies, the interference strategies for AML recurrence have been changing these years. More and more novel targeting agents that have received the U.S. Food and Drug Administration (FDA) approval for de novo AML treatment have been administrated in the salvage or maintenance therapy of post-HSCT relapse. Targeted strategies that regulate the immune microenvironment of and optimize the graft versus leukemia (GVL) effect of immune cells are gradually improved. Such agents not only have been proven to achieve clinical benefits from a single drug, but if combined with classic therapies, can significantly improve the poor prognosis of AML patients who relapse after allo-HSCT. This review will focus on currently available and promising upcoming agents and also discuss the challenges and limitations of targeted therapies in the allogeneic hematopoietic stem cell transplantation community.


African Federation for Emergency Medicine resources for managing COVID-19 in low resourced settings


title: Identification of new anti-nCoV drug chemical compounds from Indian spices exploiting SARS-CoV-2 main protease as target

text: The 2019-novel coronavirus (nCoV) has caused a global health crisis by causing coronavirus disease-19 (COVID-19) pandemic in the human population. The unavailability of specific vaccines and anti-viral drug for nCoV, science demands sincere efforts in the field of drug design and discovery for COVID-19. The novel coronavirus main protease (SARS-CoV-2 Mpro) play a crucial role during the disease propagation, and hence SARS-CoV-2 Mpro represents as a drug target for the drug discovery. Herein, we have applied bioinformatics approach for screening of chemical compounds from Indian spices as potent inhibitors of SARS-CoV-2 main protease (PDBID: 6Y84). The structure files of Indian spices chemical compounds were taken from PubChem database or Zinc database and screened by molecular docking, by using AutoDock-4.2, MGLTools-1.5.6, Raccoon virtual screening tools. Top 04 hits based on their highest binding affinity were analyzed. Carnosol exhibited highest binding affinity -8.2 Kcal/mol and strong and stable interactions with the amino acid residues present on the active site of SARS-CoV-2 Mpro. Arjunglucoside-I (-7.88 Kcal/mol) and Rosmanol (-7.99 Kcal/mol) also showed a strong and stable binding affinity with favourable ADME properties. These compounds on MD simulations for 50 ns shows strong hydrogen-bonding interactions with the protein active site and remains stable inside the active site. Our virtual screening results suggest that these small chemical molecules can be used as potential inhibitors against SARS-CoV-2 Mpro and may have an anti-viral effect on nCoV. However, further validation and investigation of these inhibitors against SARS-CoV-2 main protease are needed to claim their candidacy for clinical trials. Communicated by Ramaswamy H. Sarma


The Middle East respiratory syndrome puzzle: A familiar virus, a familiar disease, but some assembly still required


title: Comparative sequence analysis of the distal one-third of the genomes of a systemic and an enteric ferret coronavirus

text: Abstract Ferret systemic coronavirus (FRSCV) infection is associated with an emerging, highly fatal disease of ferrets. Enhanced macrophage tropism and the resulting induction of pyogranulomatous lesions are shared with feline infectious peritonitis virus (FIPV) infection in cats, but are not features of ferret enteric coronavirus (FRECV) infection. Comparative sequence analysis of the distal one-third of the genomes of one FRSCV and one FRECV strain showed that these two ferret coronaviruses share >96% nucleotide sequence identities in the membrane (M), nucleocapsid (N) and non-structural protein genes (partial polymerase, open reading frames [ORFs] 3 and 7b). The envelope (E) protein gene showed a moderate nucleotide sequence similarity of 91.6%. In contrast, nucleotide and amino acid sequence similarities observed with the spike (S) protein were only 79.5 and 79.6%, respectively. Twenty-one amino acid differences within a 195–199-amino acid C-terminal portion of the S protein were conserved between 3 strains each of FRSCV and FRECV. Both systemic and enteric strains were found to carry a single ORF 3 gene with truncated proteins observed in two out of three FRSCV strains examined. The two enteric strains analyzed each contained an intact ORF 3 gene. Phylogenetically, FRSCV is more closely related to FRECV than to other group 1 coronaviruses.


title: Pandemic influenza: What infection control professionals should know

text: During the last century, 3 influenza A pandemics have occurred, and pandemic influenza will inevitably occur in the future. Although the timing and severity of the next pandemic cannot be predicted, the probability that a pandemic will occur has increased based on the current outbreaks of A(H5N1) in Asia, Europe, and Africa. Because of these widespread outbreaks, the World Health Organization declared a phase 3 pandemic alert in the fall of 2005. Early detection is essential to prevent the spread of avian influenza. Planning now can be achieved by integrating interventions to ensure a prompt and effective response to a pandemic. This article provides an overview of the current status of A(H5N1) influenza worldwide and recommendations for the prevention and control of avian influenza should it emerge in humans in the United States.


title: PEOPLE EXPERIENCING HOMELESSNESS: THEIR POTENTIAL EXPOSURE TO COVID-19

text: Abstract Background : Insufficient housing quality is associated with stress and mental health impacts. Crowding, pollution, noise, inadequate lighting, lack of access to green spaces, and other environmental factors associated with slums can exacerbate mental health disorders, including depression, anxiety, violence, and other forms of social dysfunction. Method : The studies were identified using large-sized newspapers with international circulation. Results : Experts say that people who sleep in shelters or on the streets already have lower life expectancy, suffer from addiction, and have underlying health conditions that put them at greater risk should they develop the virus. There are just so many competing and unmet needs, which makes it much harder for homeless to contend with all of this. If exposed, people experiencing homelessness might be more susceptible to illness or death due to the prevalence of underlying physical and mental medical conditions and a lack of reliable and affordable health care. Nevertheless, without an urgent solution, people experiencing homelessness will remain in limbo. Conclusions : Many people living on the streets already have a diminished health condition, higher rates of chronic illnesses or compromised immune systems, all of which are risk factors for developing a more serious manifestation of the coronavirus infection. Those suffering from mental illness may have difficulty in recognizing and responding to the threat of infection. Homeless people have less access to health care providers who could otherwise order diagnostic testing and, if confirmed, isolate them from others in coordination with local health departments.


title: IL-13 is associated with reduced illness and replication in primary respiratory syncytial virus infection in the mouse

text: The role of IL-13 in respiratory syncytial virus (RSV) immunopathogenesis is incompletely described. To assess the effect of IL-13 on primary RSV infection, transgenic mice which either overexpress IL-13 in the lung (IL-13 OE) or nontransgenic littermates (IL-13 NT) were challenged intranasally with RSV. IL-13 OE mice had significantly decreased peak viral titers four days after infection compared to non-transgenic littermates. In addition, the IL-13 OE mice had significantly lower RSV-induced weight loss and reduced lung IFN-γ protein expression compared with IL-13 NT mice. In contrast, primary RSV challenge of IL-13 deficient mice resulted in a small, but statistically significant increase in viral titers on day four after infection, no difference in RSV-induced weight loss compared to wild type mice, and augmented IFN-γ production on day 6 after infection. In STAT1-deficient (STAT1 KO) mice, where primary RSV challenge produced high levels of IL-13 production in the lungs, treatment with an IL-13 neutralizing protein resulted in greater peak viral titers both four and six days after RSV and greater RSV-induced weight loss compared to mice treated with a control protein. These results suggest that IL-13 modulates illness from RSV-infection.


title: Chapter 497 Arterivirus nsp2 Cysteine Proteinase

text: The third edition of the Handbook of Proteolytic Enzymes aims to be a comprehensive reference work for the enzymes that cleave proteins and peptides, and contains over 800 chapters. Each chapter is organized into sections describing the name and history, activity and specificity, structural chemistry, preparation, biological aspects, and distinguishing features for a specific peptidase. The subject of Chapter 500 is Arterivirus nsp2 Cysteine Proteinase. Keywords: Arterivirus, nidovirus, deubiquitinating enzyme, ovarian tumor domain, de-ubiquitinating enzyme (DUB), innate immunity control, non-structural protein, multidomain proteinase, multifunctional proteinase, papain-like fold, polyprotein processing, RNA virus.


title: Financing entrepreneurship in times of crisis: Exploring the impact of COVID-19 on the market for entrepreneurial finance in the United Kingdom

text: This commentary explores the manner in which the current COVID-19 crisis is affecting key sources of entrepreneurial finance in the United Kingdom. We posit that the unique relational nature of entrepreneurial finance may make it highly susceptible to such a shock owing to the need for face-to-face interaction between investors and entrepreneurs. The article explores this conjecture by scrutinising a real-time data source of equity investments. Our findings suggest that the volume of new equity transactions in the United Kingdom has declined markedly since the outbreak of the COVID-19 pandemic. It appears that seed finance is the main type of entrepreneurial finance most acutely affected by the crisis, which typically goes to the most nascent entrepreneurial start-ups facing the greatest obstacles obtaining finance. Policy makers can utilise these real-time data sources to help inform their strategic policy interventions to assist the firms most affected by crisis events.


Research Communications of the 26(th) ECVIM‐CA CONGRESS


title: Early Epidemiological Assessment of the Virulence of Emerging Infectious Diseases: A Case Study of an Influenza Pandemic

text: BACKGROUND: The case fatality ratio (CFR), the ratio of deaths from an infectious disease to the number of cases, provides an assessment of virulence. Calculation of the ratio of the cumulative number of deaths to cases during the course of an epidemic tends to result in a biased CFR. The present study develops a simple method to obtain an unbiased estimate of confirmed CFR (cCFR), using only the confirmed cases as the denominator, at an early stage of epidemic, even when there have been only a few deaths. METHODOLOGY/PRINCIPAL FINDINGS: Our method adjusts the biased cCFR by a factor of underestimation which is informed by the time from symptom onset to death. We first examine the approach by analyzing an outbreak of severe acute respiratory syndrome in Hong Kong (2003) with known unbiased cCFR estimate, and then investigate published epidemiological datasets of novel swine-origin influenza A (H1N1) virus infection in the USA and Canada (2009). Because observation of a few deaths alone does not permit estimating the distribution of the time from onset to death, the uncertainty is addressed by means of sensitivity analysis. The maximum likelihood estimate of the unbiased cCFR for influenza may lie in the range of 0.16–4.48% within the assumed parameter space for a factor of underestimation. The estimates for influenza suggest that the virulence is comparable to the early estimate in Mexico. Even when there have been no deaths, our model permits estimating a conservative upper bound of the cCFR. CONCLUSIONS: Although one has to keep in mind that the cCFR for an entire population is vulnerable to its variations among sub-populations and underdiagnosis, our method is useful for assessing virulence at the early stage of an epidemic and for informing policy makers and the public.


title: Possible involvement of infection with human coronavirus 229E, but not NL63, in Kawasaki disease

text: Although human coronavirus (HCoV)‐NL63 was once considered a possible causative agent of Kawasaki disease based on RT‐PCR analyses, subsequent studies could not confirm the result. In this study, this possibility was explored using serological tests. To evaluate the role of HCoV infection in patients with Kawasaki disease, immunofluorescence assays and virus neutralizing tests were performed. Paired serum samples were obtained from patients with Kawasaki disease who had not been treated with γ‐globulin. HCoV‐NL63 and two antigenically different isolates of HCoV‐229E (ATCC‐VR740 and a new isolate, Sendai‐H) were examined as controls. Immunofluorescence assays detected no difference in HCoV‐NL63 antibody positivity between the patients with Kawasaki disease and controls, whereas the rate of HCoV‐229E antibody positivity was higher in the patients with Kawasaki disease than that in controls. The neutralizing tests revealed no difference in seropositivity between the acute and recovery phases of patients with Kawasaki disease for the two HCoV‐229Es. However, the Kawasaki disease specimens obtained from patients in recovery phase displayed significantly higher positivity for Sendai‐H, but not for ATCC‐VR740, as compared to the controls. The serological test supported no involvement of HCoV‐NL63 but suggested the possible involvement of HCoV‐229E in the development of Kawasaki disease. J. Med. Virol. 86:2146–2153, 2014. © 2014 Wiley Periodicals, Inc.


title: MHV S peplomer protein expressed by a recombinant vaccinia virus vector exhibits IgG Fc-receptor activity

text: Abstract We have previously shown that cells infected with mouse hepatitis virus (MHV) bind rabbit, mouse, and rat IgG by the Fc portion of the IgG molecule. This Fc-binding activity appeared to be mediated by the MHV S protein. S protein could also be precipitated from MHV-infected cells by a monoclonal antibody directed against the murine Fc γ receptor (FcγR). To prove definitively that the S protein mediates Fc-binding activity, we have expressed the MHV S protein utilizing recombinant vaccinia viruses. The anti-FcγR monoclonal antibody, 2.4G2, precipitated recombinant S protein in cells of murine, human, and rabbit origin. Since the anti-Fc receptor monoclonal antibody does not react with human and rabbit Fc receptors these results demonstrate that the epitope recognized by this antibody is carried on the MHV S protein and is not murine in origin. Examination of various MHV isolates and escape mutants failed to identify the precise sequences in S responsible for the molecular mimicry of the murine FcγR. These data are consistent with the hypothesis that a previously identified region of similarity between the S protein and the FcγR mediates this activity. The Fc binding activity of S was expressed on the cell surface, since MHV-JHM-infected cells, but not uninfected cells, formed rosettes with anti-sheep red blood cell (SRBC) antibody-coated SRBC. The anti-FcγR monoclonal antibody neutralized MHV-JHM and inhibited syncytium formation induced by the MHV S protein.


title: Definitive Care for the Critically Ill During a Disaster: A Framework for Optimizing Critical Care Surge Capacity From a Task Force for Mass Critical Care Summit Meeting, January 26–27, 2007, Chicago, IL

text: Background Plausible disasters may yield hundreds or thousands of critically ill victims. However, most countries, including those with widely available critical care services, lack sufficient specialized staff, medical equipment, and ICU space to provide timely, usual critical care for a large influx of additional patients. Shifting critical care disaster preparedness efforts to augment limited, essential critical care (emergency mass critical care [EMCC]), rather than to marginally increase unrestricted, individual-focused critical care may provide many additional people with access to life-sustaining interventions. In 2007, in response to the increasing concern over a severe influenza pandemic, the Task Force on Mass Critical Care (hereafter called the Task Force) convened to suggest the essential critical care therapeutics and interventions for EMCC. Task Force suggestions EMCC should include the following: (1) mechanical ventilation, (2) IV fluid resuscitation, (3) vasopressor administration, (4) medication administration for specific disease states (eg, antimicrobials and antidotes), (5) sedation and analgesia, and (6) select practices to reduce adverse consequences of critical illness and critical care delivery. Also, all hospitals with ICUs should prepare to deliver EMCC for a daily critical care census at three times their usual ICU capacity for up to 10 days. Discussion By using the Task Force suggestions for EMCC, communities may better prepare to deliver augmented critical care in response to disasters. In light of current mass critical care data limitations, the Task Force suggestions were developed to guide preparedness but are not intended as strict policy mandates. Additional research is required to evaluate EMCC and revise the strategy as warranted.


title: Reductions in traffic-related black carbon and ultrafine particle number concentrations in an urban neighborhood during the COVID-19 pandemic

text: Abstract We investigated changes in traffic-related air pollutant concentrations in an urban area during the COVID-19 pandemic. The study area was in a mixed commercial-residential neighborhood in Somerville (MA, USA), where traffic is the dominant source of air pollution. Measurements were conducted between March 27 and May 14, 2020, coinciding with a dramatic reduction in traffic (71% drop in car and 46% drop in truck traffic) due to business shutdowns and a statewide stay-at-home advisory. Indicators of fresh vehicular emissions (ultrafine particle number concentration [PNC] and black carbon [BC]) were measured with a mobile monitoring platform on an interstate highway and major and minor roadways. Depending on road class, median PNC and BC contributions from traffic were 60–68% and 22–46% lower, respectively, during the lockdown compared to pre-pandemic conditions. A higher BC:PNC concentration ratio was observed during the lockdown period perhaps indicative of the higher fraction of diesel vehicles in the fleet during the lockdown. Overall, the scale of reductions in ultrafine particle and BC concentrations was commensurate with the reductions in traffic. This natural experiment allowed us to quantify the direct impacts of reductions in traffic emissions on neighborhood-scale air quality, which are not captured by the regional regulatory-monitoring network. Results underscore the importance of measurements of appropriate proxies for traffic emissions at relevant spatial scales. Our results are also useful for exposure analysts, and city, and regional planners evaluating traffic-related air pollution impact mitigation strategies.


title: High prevalence of Trypanosoma vegrandis in bats from Western Australia

text: Abstract The present study describes the first report of Trypanosoma vegrandis in bats using morphology and sequence analysis of the 18S rRNA gene. The PCR prevalence of T. vegrandis in bats was 81.8% (18/22). The high prevalence of T. vegrandis in the present study suggests that bats may play an important role in the epidemiology of T. vegrandis in Australia. T. vegrandis appears to be geographically dispersed, has a wide distribution in Australia and low levels of host specificity.


title: Airborne infectious disease and the suppression of pulmonary bioaerosols

text: The current understanding of airborne pathogen spread in relation to the new methods of suppressing exhaled bioaerosols using safe surface-active materials, such as isotonic saline, is reviewed here. We discuss the physics of bioaerosol generation in the lungs, what is currently known about the relationship between expired bioaerosols and airborne infectious disease and current methods of airborne infectious disease containment. We conclude by reviewing recent experiments that suggest the delivery of isotonic saline can significantly diminish exhaled aerosol – generated from airway lining fluid in the course of natural breathing. We also discuss these implications in relation to airborne infectious disease control.


title: Outbreak of cryptosporidiosis due to Cryptosporidium parvum subtype IIdA19G1 in neonatal calves on a dairy farm in China

text: Abstract Neonatal diarrhea is one of the most important syndromes in dairy cattle. Among enteropathogens, Cryptosporidium spp. are primary causes of diarrhea, but outbreaks due to cryptosporidiosis are rarely reported in cattle. From January to April in 2016, severe diarrhea was observed in over 400 neonatal dairy calves on a large dairy farm in Jiangsu Province of East China. Approximately 360 calves died due to watery diarrhea despite antibiotic therapy. In this study, 18 fecal specimens were collected from seriously ill calves on this farm during the diarrhea outbreak, and analysed for common enteropathogens by enzymatic immunoassay (EIA). In a post-outbreak investigation, 418 and 1372 specimens collected from animals of various age groups were further analysed for rotavirus and Cryptosporidium spp. by EIA and PCR, respectively, to assess their roles in the occurrence of diarrhea on the farm. Cryptosporidium spp. were genotyped using established techniques. Initial EIA tests showed that 15/18 seriously ill calves during the outbreak were positive for Cryptosporidium parvum, while 8/18 were positive for rotavirus. The overall infection rate of Cryptosporidium in pre-weaned calves on the farm was 22.7%, with odds of the Cryptosporidium infection during the outbreak 4.4–23.5 times higher than after the outbreak. Four Cryptosporidium spp. were identified after the outbreak including C. parvum (n = 79), Cryptosporidium ryanae (n = 48), Cryptosporidium bovis (n = 31), and Cryptosporidium andersoni (n = 3), with co-infections of multiple species being detected in 34 animals. Infection with C. parvum (73/79) was found in the majority of calves aged ≤3 weeks, consistent with the age of ill calves during the outbreak. All C. parvum isolates were identified as subtype IIdA19G1. In the post-outbreak investigation, C. parvum infection was associated with the occurrence of watery diarrhea in pre-weaned calves, C. ryanae infection was associated with moderate diarrhea in both pre- and post-weaned calves, while no association was identified between rotavirus infection and the occurrence of diarrhea. Results of logistic regression analysis further suggested that C. bovis infection might also be a risk factor for moderate diarrhea in calves. Thus, we believe this is the first report of a major outbreak of severe diarrhea caused by C. parvum IIdA19G1 in dairy calves. More attention should be directed toward preventing the dissemination of this virulent subtype in China.


title: Pathogen elimination and prevention within a regulated, Designated Pathogen Free, closed pig herd for long‐term breeding and production of xenotransplantation materials

text: BACKGROUND: We established a Source Animal (barrier) Facility (SAF) for generating designated pathogen‐free (DPF) pigs to serve as donors of viable organs, tissues, or cells for xenotransplantation into clinical patients. This facility was populated with caesarian derived, colostrum deprived (CDCD) piglets, from sows of conventional‐specific (or specified) pathogen‐free (SPF) health status in six cohorts over a 10‐month period. In all cases, CDCD piglets fulfilled DPF status including negativity for porcine circovirus (PCV), a particularly environmentally robust and difficult to inactivate virus which at the time of SAF population was epidemic in the US commercial swine production industry. Two outbreaks of PCV infection were subsequently detected during sentinel testing. The first occurred several weeks after PCV‐negative animals were moved under quarantine from the nursery into an animal holding room. The apparent origin of PCV was newly installed stainless steel penning, which was not sufficiently degreased thereby protecting viral particles from disinfection. The second outbreak was apparently transmitted via employee activities in the Caesarian‐section suite adjacent to the barrier facility. In both cases, PCV was contained in the animal holding room where it was diagnosed making a complete facility depopulation‐repopulation unnecessary. METHOD: Infectious PCV was eliminated during both outbreaks by the following: euthanizing infected animals, disposing of all removable items from the affected animal holding room, extensive cleaning with detergents and degreasing agents, sterilization of equipment and rooms with chlorine dioxide, vaporized hydrogen peroxide, and potassium peroxymonosulfate, and for the second outbreak also glutaraldehyde/quaternary ammonium. Impact on other barrier animals throughout the process was monitored by frequent PCV diagnostic testing. RESULT: After close monitoring for 6 months indicating PCV absence from all rooms and animals, herd animals were removed from quarantine status. CONCLUSION: Ten years after PCV clearance following the second outbreak, due to strict adherence to biosecurity protocols and based on ongoing sentinel diagnostic monitoring (currently monthly), the herd remains DPF including PCV negative.


title: Feline Vaccination Guidelines

text: The 1998 Report of the American Association of Feline Practitioners and Academy of Feline Medicine Advisory Panel on Feline Vaccines was developed to help veterinary practitioners formulate vaccination protocols for cats. The current panel report updates information, addresses questions, and speaks to concerns raised by the 1998 report. In addition it reviews vaccine licensing, labeling, and liability issues and suggests ways to successfully incorporate vaccination protocol changes into a private practice setting.


title: Clinical characteristics and prognosis in cancer patients with COVID-19: A single center's retrospective study

text: • We describe the demographics, clinical characteristics, and prognosis of cancer patients with COVID-19 infection. • Cancer patients had a high infection rate of SARS-CoV-2 and were easy to become severe or critical cases. • Among cancer patients with COVID-19, the numbers of neutrophil, NLR(ratio of neutrophil to lymphocyte, IL-6, LDH and PCT in the severe/critical group were significantly higher than those in the mild group.


title: Humoral immunity to human metapneumovirus infection in adults()

text: Human metapneumovirus (hMPV) is a significant cause of respiratory illness in children and adults. Presently, there are no human data regarding the role of antibody for protection against hMPV illness. Therefore, we measured serum and nasal antibody titers against hMPV by EIA and neutralization assay at baseline in hMPV infected adults compared with subjects who remained uninfected. Antibody titers were also compared in patients with mild and severe illness. Mean serum binding and neutralizing antibody titers of hMPV infected subjects were significantly lower compared to uninfected subjects. Seventy-one percent of subjects with titers ≤10.5 (log 2) were infected compared to 36% with titers >10.5, p = 0.003. There was no difference in the mean acute antibody titers for patients with mild compared to severe illness. Serum antibody may play a role in protection from hMPV infection supporting the development of an hMPV vaccine that stimulates humoral immunity.


title: Respiratory Viral Infections after Hematopoietic Stem Cell Transplantation in Children

text: This study was performed to characterize respiratory viral infections in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Study samples included 402 respiratory specimens obtained from 358 clinical episodes that occurred in the 116 children of the 175 consecutive HSCT cohort at Seoul National University Children's Hospital, Korea from 2007 to 2010. Multiplex reverse-transcription polymerase chain reactions were performed for rhinovirus, respiratory syncytial virus (RSV), parainfluenza viruses (PIVs), adenovirus, human coronavirus (hCoV), influenza viruses and human metapneumovirus. Viruses were identified in 89 clinical episodes that occurred in 58 patients. Among the 89 clinical episodes, frequently detected viruses were rhinovirus in 25 (28.1%), RSV in 23 (25.8%), PIV-3 in 16 (18.0%), adenovirus in 12 (13.5%), and hCoV in 10 (11.2%). Lower respiratory tract infections were diagnosed in 34 (38.2%). Neutropenia was present in 24 (27.0%) episodes and lymphopenia was in 31 (34.8%) episodes. Sixty-three percent of the clinical episodes were hospital-acquired. Three patients died of respiratory failure caused by respiratory viral infections. Respiratory viral infections in pediatric patients who have undergone HSCT are common and are frequently acquired during hospitalization. Continuous monitoring is required to determine the role of respiratory viruses in immunocompromised children and the importance of preventive strategies.


title: Epitope Addition and Ablation via Manipulation of a Dengue Virus Serotype 1 Infectious Clone

text: Despite the clinical relevance, dengue virus (DENV) research has been hampered by the absence of robust reverse genetic systems to manipulate the viral serotypes for propagation and generation of mutant viruses. In this article, we describe application of an infectious clone system for DENV serotype 1 (DENV1). Similar to previous clones in both flaviviruses and coronaviruses, the approach constructs a panel of contiguous cDNAs that span the DENV genome and can be systematically and directionally assembled to produce viable, full-length viruses. Comparison of the virus derived from the infectious clone with the original viral isolate reveals identical sequence, comparable endpoint titers, and similar focus staining. Both focus-forming assays and percent infection by flow cytometry revealed overlapping replication levels in two different cell types. Moreover, serotype-specific monoclonal antibodies (MAbs) bound similarly to infectious clone and the natural isolate. Using the clone, we were able to insert a DENV4 type-specific epitope recognized by primate MAb 5H2 into envelope (E) protein domain I (EDI) of DENV1 and recover a viable chimeric recombinant virus. The recombinant DENV1 virus was recognized and neutralized by the DENV4 type-specific 5H2 MAb. The introduction of the 5H2 epitope ablated two epitopes on DENV1 EDI recognized by human MAbs (1F4 and 14C10) that strongly neutralize DENV1. Together, the work demonstrates the utility of the infectious clone and provides a resource to rapidly manipulate the DENV1 serotype for generation of recombinant and mutant viruses. IMPORTANCE Dengue viruses (DENVs) are significant mosquito-transmitted pathogens that cause widespread infection and can lead to severe infection and complications. Here we further characterize a novel and robust DENV serotype 1 (DENV1) infectious clone system that can be used to support basic and applied research. We demonstrate how the system can be used to probe the antigenic relationships between strains by creating viable recombinant viruses that display or lack major antibody epitopes. The DENV1 clone system and recombinant viruses can be used to analyze existing vaccine immune responses and inform second-generation bivalent vaccine designs.


COVID‐19 and dermatologic surgery: hazards of surgical plume


ASTHO at 75: Celebrating the Past and Preparing for the Future


title: A multicenter surveillance of antimicrobial resistance in Serratia marcescens in Taiwan

text: Background Serratia marcescens is an important nosocomial pathogen and the characteristic property of resistance conferred by extended-spectrum beta-lactamase or a novel AmpC cephalosporinase was not unusual in Taiwan. This study investigated the trends in antimicrobial resistance in S. marcescens from a nationwide surveillance in Taiwan. Materials and methods S. marcescens isolates were collected biennially between 2002 and 2010 from medical centers and regional hospitals throughout Taiwan, as part of the Taiwan Surveillance of Antimicrobial Resistance program. Minimal inhibitory concentrations were determined by the Clinical and Laboratory Standards Institute reference broth microdilution method. Results A total of 403 nonduplicate S. marcescens isolates were collected, mostly from respiratory samples (157, 39.0%), followed by the urinary tract samples (90, 22.3%). Overall, 99.3% isolates were susceptible to imipenem, 93.8% to ceftazidime, 89.2% to minocycline, 87.8% to amikacin, 86.8% to cefepime, 82.9% to aztreonam, 73.2% to ceftriaxone, 72.7% to levofloxacin, 63.8% to ciprofloxacin, 60.8% to trimethoprim/sulfamethoxazole (TMP/SMX), and 59.6% to gentamicin. A significantly increased susceptibility rate after 2004 was observed for the following antibiotics: amikacin (73.8% vs. 97.1%), gentamicin (40.0% vs. 72.4%), ciprofloxacin (53.8% vs. 70.4%), ceftriaxone (53.8% vs. 86.0%), cefepime (74.4% vs. 95.1%), aztreonam (72.5% vs. 89.7%), and TMP/SMX (41.3% vs. 73.7%). Conclusion In this 8-year study, the susceptibility of S. marcescens to ceftazidime and imipenem remained consistently high in Taiwan. S. marcescens isolates demonstrated relatively higher resistance to ciprofloxacin and levofloxacin, and therefore continued surveillance of antimicrobial resistance, especially for fluoroquinolone, is warranted.


title: COVID-19 complicated by Acute Pulmonary Embolism and Right-Sided Heart Failure

text: Abstract A patient with Coronavirus Disease-2019 (COVID-19) developed sudden shortness of breath and hypoxia. She was diagnosed with a massive pulmonary embolism (PE) complicated by right sided heart failure, which was successfully managed conservatively. This marks the first report of COVID-19 induced PE in association with acute heart failure.


title: Bayesian Monitoring of Emerging Infectious Diseases

text: We define data analyses to monitor a change in R, the average number of secondary cases caused by a typical infected individual. The input dataset consists of incident cases partitioned into outbreaks, each initiated from a single index case. We split the input dataset into two successive subsets, to evaluate two successive R values, according to the Bayesian paradigm. We used the Bayes factor between the model with two different R values and that with a single R value to justify that the change in R is statistically significant. We validated our approach using simulated data, generated using known R. In particular, we found that claiming two distinct R values may depend significantly on the number of outbreaks. We then reanalyzed data previously studied by Jansen et al. [Jansen et al. Science 301 (5634), 804], concerning the effective reproduction number for measles in the UK, during 1995–2002. Our analyses showed that the 1995–2002 dataset should be divided into two separate subsets for the periods 1995–1998 and 1999–2002. In contrast, Jansen et al. take this splitting point as input of their analysis. Our estimated effective reproduction numbers R are in good agreement with those found by Jansen et al. In conclusion, our methodology for detecting temporal changes in R using outbreak-size data worked satisfactorily with both simulated and real-world data. The methodology may be used for updating R in real time, as surveillance outbreak data become available.


title: Tracking the Origin and Deciphering the Phylogenetic Relationship of Porcine Epidemic Diarrhea Virus in Ecuador

text: In 2010, new Chinese strains of porcine epidemic diarrhea virus (PEDV), clinically more severe than the classical strains, emerged. These strains were spread to United States in 2013 through an intercontinental transmission from China with further spreading across the world, evidencing the emergent nature of these strains. In the present study, an analysis of PEDV field sequences from Ecuador was conducted by comparing all the PEDV S gene sequences available in the GenBank database. Phylogenetic comparisons and Bayesian phylogeographic inference based on complete S gene sequences were also conducted to track the origin and putative route of PEDV. The sequence from the PED-outbreak in Ecuador was grouped into the clade II of PEDV genogroup 2a together with other sequences of isolates from Mexico, Canada, and United States. The phylogeographic study revealed the emergence of the Chinese PEDV strains, followed by spreading to US in 2013, from US to Korea, and later the introduction of PEDV to Canada, Mexico, and Ecuador directly from the US. The sources of imports of live swine in Ecuador in 2014 were mainly from Chile and US. Thus, this movement of pigs is suggested as the main way for introducing PEDV to Ecuador.


title: How Risk Perceptions, Not Evidence, Have Driven Harmful Policies on COVID-19

text: COVID-19 hits all of the cognitive triggers for how the lay public misjudges risk. Robust findings from the field of risk perception have identified unique characteristics of a risk that allow for greater attribution of frequency and probability than is likely to be aligned with the base-rate statistics of the risk. COVID-19 embodies these features. It is unfamiliar, invisible, dreaded, potentially endemic, involuntary, disproportionately impacts vulnerable populations such as the elderly and has the potential for widespread catastrophe. When risks with such characteristics emerge, it is imperative for there to be trust between those in governance and communication and the lay public in order to quell public fears. This is not the environment in which COVID-19 has emerged, potentially resulting in even greater perceptions of risk.


title: Viral infections of aquatic animals with special reference to Asian aquaculture

text: Abstract Worldwide, the number of communicable diseases of animals raised in aquaculture continue to increase. Viral infections of cultivated shellfish, crustacea, and finfish have been frequently recognized in the past few years. In the Asian regions, penaeid shrimp and several teleost fish underwent epizootics associated with heavy losses in aquaculture. Baculoviruses are particularly harmful to shrimp and prawns. Herpes-, irido-, reo-, or rhabdovirus-like agents can cause outbreaks in fish farms. Viral diseases are important limiting factors in the expansion of aquaculture. However, studies on viral infections of aquatic animals have been focused primarily on economically important farmed fish. Therfore, certain viral diseases of teleost fish are relatively well understood. In contrast, our knowledge of viral infections of farmed aquatic invertebrates is still very spare. Although a great number of viruses have been detected in farmed molluscs and crustaceans, the pathogenicity and epizootiology of most of the agents is not known.


title: The Effects of Social Support on Sleep Quality of Medical Staff Treating Patients with Coronavirus Disease 2019 (COVID-19) in January and February 2020 in China

text: BACKGROUND: Coronavirus disease 2019 (COVID-19), formerly known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 2019 novel coronavirus (2019-nCoV), was first identified in December 2019 in Wuhan City, China. Structural equation modeling (SEM) is a multivariate analysis method to determine the structural relationship between measured variables. This observational study aimed to use SEM to determine the effects of social support on sleep quality and function of medical staff who treated patients with COVID-19 in January and February 2020 in Wuhan, China. MATERIAL/METHODS: A one-month cross-sectional observational study included 180 medical staff who treated patients with COVID-19 infection. Levels of anxiety, self-efficacy, stress, sleep quality, and social support were measured using the and the Self-Rating Anxiety Scale (SAS), the General Self-Efficacy Scale (GSES), the Stanford Acute Stress Reaction (SASR) questionnaire, the Pittsburgh Sleep Quality Index (PSQI), and the Social Support Rate Scale (SSRS), respectively. Pearson’s correlation analysis and SEM identified the interactions between these factors. RESULTS: Levels of social support for medical staff were significantly associated with self-efficacy and sleep quality and negatively associated with the degree of anxiety and stress. Levels of anxiety were significantly associated with the levels of stress, which negatively impacted self-efficacy and sleep quality. Anxiety, stress, and self-efficacy were mediating variables associated with social support and sleep quality. CONCLUSIONS: SEM showed that medical staff in China who were treating patients with COVID-19 infection during January and February 2020 had levels of anxiety, stress, and self-efficacy that were dependent on sleep quality and social support.


title: Why G3139 works poorly in cancer trials but might work well against HIV

text: Summary The antisense drug G3139 (oblimersen sodium, Genta, Inc.) is a phosphorothioate oligodeoxynucleotide (ODN) containing unmethylated CpG units, which is targeted to suppress Bcl-2. To date, its effectiveness in cancer clinical trials has been minimal. Some suggestions are provided for that disappointment and recent citations are provided that support the idea that G3139 may be effective at clearing viral infections, specifically HIV. At the time G3139 was conceived as an anti-cancer drug candidate, it was viewed optimistically because Bcl-2 was widely believed to be the most important protein blocking p53-dependent apoptosis caused by internal stress. Since that time, we have learnt that Bcl-2 is not the only protein that inhibits apoptosis and that p53 itself is frequently malfunctioning in tumors. Thus, the anti-cancer utility of suppressing Bcl-2 in cancer cells is limited. Moreover, Bcl-2 has a role in halting the cell cycle (though p27), which may slow down tumor growth; and Bcl-2 even has pro-apoptotic roles in the execution of apoptosis initiated by external death signals (via Fas/CD95 and caspase 3). Overall, in the clinical setting, G3139 usually has statistically significant but medically unimportant benefit. These results have greatly diminished the enthusiasm for the drug especially when the side effects are considered. Specifically, the unmethylated CpG ODN (and/or the phosphorothioate group) activates the immune system, but this potentially important anti-cancer effect is lost when the immune cells undergo premature apoptosis apparently because their Bcl-2 levels have been lowered by the antisense effect of G3139. While this effect on immune cells is usually undesirable, it is exactly what would be useful for activating immune cells, initiating provirus transcription in retrovirus-infected cells, and facilitating selective apoptosis of these infected cells. In general, G3139 might have benefit in clearing chronic infections by intracellular parasites including viruses (HIV, SIV, HTLV, HBV, coronavirus, etc.). Indeed, G3139 has been shown to cause apoptosis in EBV-infected cells leading to clearance of the virus.


title: A mathematical design of vector vaccine against autoimmune disease

text: Abstract Viruses have been implicated in the initiation, progression, and exacerbation of several human autoimmune diseases. Evidence also exists that viruses can protect against autoimmune disease. Several proposed mechanisms explain the viral effects. One mechanism is “molecular mimicry” which represents a shared immunologic epitope with a microbe and the host. We consider, using a simple mathematical model, whether and how a viral infection with molecular mimicry can be beneficial or detrimental for autoimmune disease. Furthermore, we consider the possibility of development of a vector therapeutic vaccine that can relieve autoimmune disease symptoms. Our findings demonstrate that vaccine therapy success necessitates (i) appropriate immune response function, (ii) appropriate affinities with self and non-self antigen, and (iii) a replicative vector vaccine. Moreover, the model shows that the viral infection can cause autoimmune relapses.


title: Chapter 9 The Detection of Waterborne Viruses

text: Publisher Summary Viruses in water are usually present in concentrations too low for detection by direct analysis. Virological investigation of water samples is always a multi-stage process involving concentration of viruses present followed by an appropriate detection procedure. There are several approaches to detection of viruses. Part or all of the concentrate may be inoculated into cell cultures to detect infectious cytopathogenic virus, and if this is done in a quantitative fashion the virus can be enumerated, the count being reported as plaque-forming units, the tissue culture infectious dose, or most probable number units. The virus may be isolated and identified from the cell cultures. Viruses that multiply without producing an identifiable cytopathic effect in culture may sometimes be detected by immunoperoxidase or immunofluorescence staining. The concentrate may also be analyzed by molecular biological procedures (usually polymerase chain reaction (PCR) or real-time-PCR). The problem then is that such techniques do not usually detect the infectious virus, and novel approaches have been made recently to meet this challenge.


title: 19 Antimicrobial Coatings Based on Linseed Oil/TiO2 Nanocomposites

text: Abstract Linseed oil is a cheap, biodegradable, and nontoxic vegetable oil with antimicrobial properties, which has recently attained a lot of interest for the manufacturing of coatings, surfactants, soaps cosmetic products, lubricants, and so forth. Titanium dioxide (TiO2) is an important semiconductor material frequently employed in foods, cosmetics, paints, coatings, food packaging materials, optical devices, and particularly, antimicrobials due to its strong photocatalytic disinfection ability. This chapter describes the preparation and characterization of acrylated epoxidized linseed oil nanocomposite coatings reinforced with TiO2 nanoparticles. The effect of TiO2 loading on the morphology, barrier, thermal, mechanical, tribological, and antibacterial performance of the coatings is summarized. The coatings exhibit antimicrobial activity against gram-negative Escherichia coli and gram-positive Staphylococcus aureus bacteria even in the absence of UV light, and the bactericidal effect increases with the TiO2 loading. These nanocomposite coatings could be used to prevent microbial proliferation in public places with high risk of infections such as hospitals.


title: Initial data from an experiment to implement a safe procedure to perform PA erect chest radiographs for COVID-19 patients with a mobile radiographic system in a “clean” zone of the hospital ward

text: Abstract Introduction With the current Covid-19 pandemic, general wards have been converted into cohort wards for Covid-19 patients who are stable and ambulant. A 2-radiographer mobile radiography team is required to perform bedside Chest X-rays (CXR) for these patients. Hospital guidelines require both radiographers to be in full Personal Protective Equipment (PPE) throughout the image acquisition process and the mobile radiographic unit needs to be disinfected twice after each case. This affects the efficiency of the procedure and an increase usage of limited PPE resources. This study aims to explore the feasibility of performing mobile chest radiography with the mobile radiographic unit in a “clean” zone of the hospital ward. Methods An anthropomorphic body phantom was used during the test. With the mobile radiographic unit placed in a “clean” zone, the phantom and the mobile radiographic unit was segregated by the room door with a clear glass panel. The test was carried out with the room door open and closed. Integrated radiation level and patient dose were measured. A consultant radiologist was invited to review and score all the images acquired using a Barco Medical Grade workstation. The Absolute Visual Grading Analysis (VGA) scoring system was used to score these images. Results A VGA score of 4 was given to all the 40 test images, suggesting that there is no significant differences in the image quality of the images acquired using the 2 different methods. Radiation exposure received by the patient at the highest kV setting through the glass is comparable to the regular CXR on patient without glass panel at 90kV, suggesting that there is no significant increase in patient dose. Conclusion The result suggests that acquiring CXR with the X-ray beam attenuating through a glass panel is a safe and feasible way of performing CXR for COVID-19 patients in the newly converted COVID wards. This will allow the mobile radiographic unit as well as one radiographer to be completely segregated from the patient. Implications for practice This new method of acquiring CXR in an isolation facility set up requires a 2-Radiographer mobile radiography team, and is applicable only for patients who are generally well and not presented with any mobility issues. It is also important to note that a clear glass panel must be present in the barriers set up for segregation between the “clean” zone and patient zone in order to use this new method of acquiring CXR.


title: The N-terminal octapeptide acts as a dimerization inhibitor of SARS coronavirus 3C-like proteinase

text: Abstract The 3C-like proteinase of severe acute respiratory syndrome (SARS) coronavirus has been proposed to be a key target for structural-based drug design against SARS. Accurate determination of the dimer dissociation constant and the role of the N-finger (residues 1–7) will provide more insights into the enzyme catalytic mechanism of SARS 3CL proteinase. The dimer dissociation constant of the wild-type protein was determined to be 14.0μM by analytical ultracentrifugation method. The N-finger fragment of the enzyme plays an important role in enzyme dimerization as shown in the crystal structure. Key residues in the N-finger have been studied by site-directed mutagenesis, enzyme assay, and analytical ultracentrifugation. A single mutation of M6A was found to be critical to maintain the dimer structure of the enzyme. The N-terminal octapeptide N8 and its mutants were also synthesized and tested for their potency as dimerization inhibitors. Peptide cleavage assay confirms that peptide N8 is a dimerization inhibitor with a K i of 2.20mM. The comparison of the inhibitory activities of N8 and its mutants indicates that the hydrophobic interaction of Met-6 and the electrostatic interaction of Arg-4 contribute most for inhibitor binding. This study describes the first example of inhibitors targeting the dimeric interface of SARS 3CL proteinase, providing a novel strategy for drug design against SARS and other coronaviruses.


title: Advantages of mRNA display selections over other selection techniques for investigation of protein–protein interactions

text: mRNA display is a genotype–phenotype conjugation method that allows for amplification-based, iterative rounds of in vitro selection to be applied to peptides and proteins. mRNA display can be used to display both long natural protein and short synthetic peptide libraries with unusually high diversities for the investigation of protein–protein interactions. Here, we summarize the advantages of mRNA display by comparing it with other widely used peptide or protein-selection techniques, and discuss various applications of this technique in studying protein–protein interactions.


title: A bioassay-based protocol for chemical neutralization of human faecal wastes treated by physico-chemical disinfection processes: A case study on benzalkonium chloride

text: Abstract In situ physico-chemical disinfection of high risk faecal waste is both effective and widely used as a sanitation management strategy for infection prevention and control. Systematic tests where the performance of alternative physico-chemical disinfection methods is systematically compared and optimized must be based on reliable protocols. These protocol are currently not adequately addressing the neutralization related issues: the neutralization of the tested disinfectant after specified conditions of concentration and contact time (CT) is necessary to prevent continued disinfection after the intended contact time; moreover such neutralization is often necessary in practice and on a large scale to prevent adverse health and ecological impacts from remaining disinfectant after the target CT is achieved. Few studies adequately assess the extent of neutralization of the chemical disinfectant and are intended to optimize on-site disinfection practices for waste matrices posing high microbial risks. Hence, there is a need for effective and reproducible neutralization protocols in chemical disinfection trials and practice. Furthermore, for most of chemical disinfectants used in healthcare settings there is no practical methodology to reliably and conveniently measure the residual disinfectant concentration after its neutralization and also determine the optimum concentration of the neutralizer. Because some neutralizing compounds can themselves be toxic to the test microorganisms, it is necessary to optimize neutralization procedures in disinfection experiments for the development of infection control practices using accepted positive control microbes. In the presented work, a stepwise bioassay-based protocol using representative faecal indicator microbes is described for optimizing chemical disinfection and subsequent disinfectant neutralization of any infectious faecal waste matrix. The example described is for the quaternary ammonium compound benzalkonium chloride and its recommended chemical neutralizer in a high strength human faecal waste matrix.


title: Viral membrane fusion

text: Infection by viruses having lipid-bilayer envelopes proceeds through fusion of the viral membrane with a membrane of the target cell. Viral ‘fusion proteins’ facilitate this process. They vary greatly in structure, but all seem to have a common mechanism of action, in which a ligand-triggered, large-scale conformational change in the fusion protein is coupled to apposition and merger of the two bilayers. We describe three examples—the influenza virus hemagglutinin, the flavivirus E protein and the vesicular stomatitis virus G protein—in some detail, to illustrate the ways in which different structures have evolved to implement this common mechanism. Fusion inhibitors can be effective antiviral agents.


title: Feasibility of a Pilot Program for COVID‐19 Convalescent Plasma Collection in Wuhan, China

text: BACKGROUND: A novel coronavirus has caused an international outbreak. Currently, there are no specific therapeutic agents for coronavirus infections. Convalescent plasma (CP) therapy is a potentially effective treatment option. METHODS: Patients who had recovered from COVID‐19 and had been discharged from the hospital for more than two weeks were recruited. COVID‐19 convalescent plasma (CCP)‐specific donor screening and selection were performed based the following criteria: 1) aged 18‐55 years; 2) eligible for blood donation; 3) diagnosed with COVID‐19; 4) had two consecutive negative COVID‐19 nasopharyngeal swab tests based on PCR (at least 24 h apart) prior to hospital discharge; 5) had been discharged from the hospital for more than 2 weeks; and 6) had no COVID‐19 symptoms prior to convalescent plasma donation. In addition, preference was given to CCP donors who had a fever lasting more than 3 days or a body temperature exceeding 38.5 Celsius, and 4 weeks after the onset of symptoms. CCP collection was performed using routine plasma collection procedures via plasmapheresis. In addition to routine donor testing, the CCP donors’ plasma was also tested for SARS‐CoV‐2 nucleic acid and S‐RBD‐specific IgG antibody. RESULTS: Of the 81 potential CCP donors, 64 (79%) plasma products were collected. There were 18 female donors and 46 male donors. There were 34 first‐time blood donors and 30 repeat donors. The average time between CCP collection and initial symptom onset was 49.1 days, and the average time between CCP collection and hospital discharge was 38.7 days. The average volume of CCP collected was 327.7 ml. All Alanine transaminase ( ALT ) testing results met blood donation requirements. HIV Ag/Ab, anti‐HCV, anti‐syphilis and HBsAg were all negative; NAT for HIV, HBV, and HCV were also negative. In addition, all of the CCP donors’ plasma units were negative for SARS‐CoV‐2 RNA. Of the total 64 CCP donors tested, only one had an S‐RBD‐specific IgG titer of 1:160, all others had a titer of ≥1:320. CONCLUSION: Based on a feasibility study of a pilot CCP program in Wuhan China, we demonstrated the success and feasibility of CCP collection. In addition, all of the CCP units collected had a titer of ≥ 1:160 for S‐RBD‐specific IgG antibody, which met the CCP quality control requirements based on the Chinese national guidelines for CCP. This article is protected by copyright. All rights reserved.


title: Development of human neutralizing monoclonal antibodies for prevention and therapy of MERS-CoV infections

text: The recent Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak poses a serious threat to public health. Here, we summarize recent advances in identifying human neutralizing monoclonal antibodies (mAbs) against MERS-CoV, describe their mechanisms of action, and analyze their potential for treatment of MERS-CoV infections.


title: Highly Distinguished Amino Acid Sequences of 2019-nCoV (Wuhan Coronavirus)

text: Using a method for pathogen screening in DNA synthesis orders, we have identified a number of amino acid sequences that distinguish 2019-nCoV (Wuhan Coronavirus) from all other known viruses in Coronaviridae. We find three main regions of unique sequence: two in the 1ab polyprotein QHO60603.1, one in surface glycoprotein QHO60594.1.


title: Pharmaceutical and biomedical applications of surface engineered carbon nanotubes

text: Surface engineered carbon nanotubes (CNTs) are attracting recent attention of scientists owing to their vivid biomedical and pharmaceutical applications. The focus of this review is to highlight the important role of surface engineered CNTs in the highly challenging but rewarding area of nanotechnology. The major strength of this review lies in highlighting the exciting applications of CNTs to boost the research efforts, which unfortunately are otherwise scattered in the literature making the reading non-coherent and non-homogeneous.


title: Spatio-temporal fluctuations in the global airport hierarchies

text: Abstract The global air transportation network is responsible for moving millions of domestic and international passengers each year. Not surprisingly, relationships between airports vary widely, due to a myriad of geographic, economic, political and historical determinants. Further, given the dynamic nature of the many influences acting on the air transportation system, inter-airport relationships and the structure of the global air network as a whole are also constantly changing. The purpose of this paper is to explore such spatio-temporal variations in the structure of the global airport hierarchies. Here, we show how the concept of nodal regions can be applied to measure the extent of these variations. To facilitate this analysis, a database of nearly 900 airline carrier schedules and 4650 worldwide origins and destinations, representing a nearly complete record of commercial air travel over a six-year period, is examined. Given this dataset, nodal regions are derived for all airports represented. In general, results suggest that regions associated with individual airports are often relatively dynamic at the yearly as well as quarterly level. Los Angeles International Airport (LAX) is utilized as a local case-study to provide a detailed examination of these dynamics.


title: Detection and molecular characterisation of bovine corona and toroviruses from Croatian cattle

text: BACKGROUND: Bovine coronavirus (BCoV) together with bovine torovirus (BToV), both members of the Coronaviridae family, order Nidovirales are the most common viral enteric pathogens. Although studied separately, their joint occurrence and the molecular diversity in cattle in Croatia have not been investigated. METHODS: A survey is carried out on 101 fecal samples from diarrheic young and adult cattle during the 3-year period from i) one large dairy herd, ii) four small herds and iii) three nasal and paired fecal samples from calves with symptoms of respiratory disease. Samples were submitted to RT-PCR and sequencing for BCoV Nucleocapsid gene, BCoV Spike gene and BToV Spike gene. RESULTS: BCoV was detected in 78.8 % of fecal samples from symptomatic cattle and three nasal and paired fecal samples from calves with respiratory symptoms. BToV was detected in 43.2 % of fecal samples from symptomatic cattle and a fecal sample from calves with respiratory symptoms. Molecular characterisation of those viruses revealed some nucleotide and aminoacid differences in relation to reference strains. CONCLUSIONS: BToV should be regarded as a relevant pathogen for cattle that plays a synergistic role in mixed enteric infections.


title: Differential removal of human pathogenic viruses from sewage by conventional and ozone treatments

text: Abstract Sewage contains a mixed ecosystem of diverse sets of microorganisms, including human pathogenic viruses. Little is known about how conventional as well as advanced treatments of sewage, such as ozonation, reduce the environmental spread of viruses. Analyses for viruses were therefore conducted for three weeks in influent, after conventional treatment, after additional ozonation, and after passing an open dam system at a full-scale treatment plant in Knivsta, Sweden. Viruses were concentrated by adsorption to a positively charged filter, from which they were eluted and pelleted by ultracentrifugation, with a recovery of about 10%. Ion Torrent sequencing was used to analyze influent, leading to the identification of at least 327 viral species, most of which belonged to 25 families with some having unclear classification. Real-time PCR was used to test for 21 human-related viruses in inlet, conventionally treated, and ozone-treated sewage and outlet waters. The viruses identified in influent and further analyzed were adenovirus, norovirus, sapovirus, parechovirus, hepatitis E virus, astrovirus, pecovirus, picobirnavirus, parvovirus, and gokushovirus. Conventional treatment reduced viral concentrations by one to four log10, with the exception of adenovirus and parvovirus, for which the removal was less efficient. Ozone treatment led to a further reduction by one to two log10, but less for adenovirus. This study showed that the amount of all viruses was reduced by conventional sewage treatment. Further ozonation reduced the amounts of several viruses to undetectable levels, indicating that this is a promising technique for reducing the transmission of many pathogenic human viruses.


COVID 19: Management of Decompensated Cirrhosis and Liver Transplant Recipients


title: Expression of Interferon-γ by a Coronavirus Defective-Interfering RNA Vector and Its Effect on Viral Replication, Spread, and Pathogenicity

text: Abstract A defective-interfering (DI) RNA of the murine coronavirus mouse hepatitis virus (MHV) was developed as a vector for expressing interferon-γ (IFN-γ). The murine IFN-γ gene was cloned into the DI vector under the control of an MHV transcriptional promoter and transfected into MHV-infected cells. IFN-γ was secreted into culture medium as early as 6 hr posttransfection and reached a peak level (up to 180 U/ml) at 12 hr posttransfection. The DI-expressed IFN-γ (DE-IFN-γ) exhibited an antiviral activity comparable to that of recombinant IFN-γ and was blocked by a neutralizing monoclonal antibody against IFN-γ. Treatment of macrophages with DE-IFN-γ selectively induced the expression of the cellular inducible nitric oxide synthase and the IFN-γ-inducing factor (IGIF) but did not affect the amounts of the MHV receptor mRNA. Antiviral activity was detected only when cells were pretreated with IFN-γ for 24 hr prior to infection; no inhibition of virus replication was detected when cells were treated with IFN-γ during or after infection. Furthermore, addition of IFN-γ together with MHV did not prevent infection, but appeared to prevent subsequent viral spread. MHV variants with different degrees of neurovirulence in mice had correspondingly different levels of sensitivities to IFN-γ treatmentin vitro,with the most virulent strain being most resistant to IFN-γ treatment. Infection of susceptible mice with DE-IFN-γ-containing virus caused significantly milder disease, accompanied by more pronounced mononuclear cell infiltrates into the CNS and less virus replication, than that caused by virus containing a control DI vector. This study thus demonstrates the feasibility and usefulness of this MHV DI vector for expressing cytokines and may provide a model for studying the role of cytokines in MHV pathogenesis.


title: Cooperative enzymatic control of N-acyl amino acids by PM20D1 and FAAH

text: The N-acyl amino acids are a family of bioactive lipids with pleiotropic physiologic functions, including in energy homeostasis. Their endogenous levels are regulated by an extracellular mammalian N-acyl amino acid synthase/hydrolase called PM20D1 (peptidase M20 domain containing 1). Using an activity-guided biochemical approach, we report the molecular identification of fatty acid amide hydrolase (FAAH) as a second intracellular N-acyl amino acid synthase/hydrolase. In vitro, FAAH exhibits a more restricted substrate scope compared to PM20D1. In mice, genetic ablation or selective pharmacological inhibition of FAAH bidirectionally dysregulates intracellular, but not circulating, N-acyl amino acids. Dual blockade of both PM20D1 and FAAH reveals a dramatic and non-additive biochemical engagement of these two enzymatic pathways. These data establish FAAH as a second intracellular pathway for N-acyl amino acid metabolism and underscore enzymatic division of labor as an enabling strategy for the regulation of a structurally diverse bioactive lipid family.


title: The macro domain protein family: Structure, functions, and their potential therapeutic implications

text: Abstract Macro domains are ancient, highly evolutionarily conserved domains that are widely distributed throughout all kingdoms of life. The ‘macro fold’ is roughly 25kDa in size and is composed of a mixed α–β fold with similarity to the P loop-containing nucleotide triphosphate hydrolases. They function as binding modules for metabolites of NAD+, including poly(ADP-ribose) (PAR), which is synthesized by PAR polymerases (PARPs). Although there is a high degree of sequence similarity within this family, particularly for residues that might be involved in catalysis or substrates binding, it is likely that the sequence variation that does exist among macro domains is responsible for the specificity of function of individual proteins. Recent findings have indicated that macro domain proteins are functionally promiscuous and are implicated in the regulation of diverse biological functions, such as DNA repair, chromatin remodeling and transcriptional regulation. Significant advances in the field of macro domain have occurred in the past few years, including biological insights and the discovery of novel signaling pathways. To provide a framework for understanding these recent findings, this review will provide a comprehensive overview of the known and proposed biochemical, cellular and physiological roles of the macro domain family. Recent data that indicate a critical role of macro domain regulation for the proper progression of cellular differentiation programs will be discussed. In addition, the effect of dysregulated expression of macro domain proteins will be considered in the processes of tumorigenesis and bacterial pathogenesis. Finally, a series of observations will be highlighted that should be addressed in future efforts to develop macro domains as effective therapeutic targets.


title: Detección automática de bacterias y hongos en sangre

text: La sepsis es una de las principales causas de mortalidad y morbilidad en los hospitales. La detección temprana de los patógenos mediante técnicas basadas en ácidos nucleicos puede facilitar el diagnóstico rápido de la bacteriemia y/o fungemia, la rápida adecuación del tratamiento antibiótico, reducir el uso de antibióticos innecesarios y disminuir la mortalidad. Se describen 2 técnicas disponibles comercialmente que ayudan, en un tiempo reducido, a identificar distintas bacterias y hongos productores de sepsis: LightCycler® SeptiFast Test Mgrade (Roche Diagnostic SL) y GenoType Blood Culture (Hain Lifescience). De estas 2 técnicas, mostramos los resultados de un estudio inicial propio con el LightCycler® SeptiFast Test Mgrade. El estudio se realizó con 50 muestras correspondientes a 28 pacientes (1-3 muestras por paciente) con síndrome séptico ingresados en la unidad de cuidados intensivos, comparando la nueva técnica con el hemocultivo convencional. La concordancia entre los resultados del hemocultivo y el SeptiFast fue buena, 79% en el primer ensayo, y 89% en el segundo, después de corregir defectos técnicos. Inicialmente se observó inhibición importante de los controles internos para los bacilos gramnegativos, por la presencia de heparina en la sangre empleada y un exceso de ácido desoxirribonucleico (ADN) debido al número de leucocitos. Con la finalidad de disminuir las inhibiciones, en otro estudio posterior se trabajó con 24 muestras a la mitad de volumen original, llevando el ácido nucleico extraído a dilución 1:4. Con estas modificaciones, se apreciaron reducciones importantes de las inhibiciones. En comparación con el hemocultivo, el SeptiFast diferencia mejor las contaminaciones por estafilococos coagulasa-negativa y especies de estreptococos. Sepsis is one of the main causes of mortality and morbidity in hospitals. Early detection of pathogens using nucleic acid-based techniques speeds diagnosis of bacteremia and/or fungemia, aids the rapid application of appropriate antibiotics, reduces the use of unnecessary antibiotics, and lowers mortality. Two commercially available techniques that help to identify different sepsisproducing bacteria and fungi in a shorter time period are: LightCycler® SeptiFast Test Mgrade (Roche Diagnostic SL) and GenoType Blood Culture (Hain Lifescience). We present the results of an initial in-house study using the LightCycler® SeptiFast Test Mgrade. The study was carried out in 50 samples from 28 patients (1-3 samples per patient) with septic syndrome admitted to the intensive care unit by comparing the new technique with conventional blood culture. The concordance between the results of blood culture and SeptiFast was good, 79%, in the first trial and 89% in the second, after correcting for technical defects. We initially observed substantial inhibition of internal controls in Gram-negative bacilli, due to the presence of heparin in the blood used, and excess DNA because of the high number of leucocytes. To minimize these inhibitions, the second study used 24 samples at half the original volume (extracted DNA at 1/4 concentration). With these modifications, inhibitions were substantially reduced. SeptiFast is more effective than blood culture in discriminating between contamination by coagulase-negative staphylococci and species of streptococci.


title: Nursing in the COVID‐19 pandemic and beyond: protecting, saving, supporting and honouring nurses

text: As the world tackles the largest public health event in more than a century, the COVID‐19 pandemic, the true value of nursing is being seen by politicians and the public. But while nurses are being praised for the vital work they do, many are being put into high‐risk situations, and some have died, because of a shortage of appropriate, high‐quality personal protective equipment. The International Council of Nurses has called for governments to make the provision of such equipment their number one priority to prevent further loss of life among the nurses caring for the world’s most vulnerable patients.


CORONAVIRUS DISEASE (COVID)-19: WORLD HEALTH ORGANIZATION DEFINITIONS AND CODING TO SUPPORT THE ALLERGY COMMUNITY AND HEALTH PROFESSIONALS


title: Emerging novel coronavirus (2019-nCoV)—current scenario, evolutionary perspective based on genome analysis and recent developments

text: Coronaviruses are the well-known cause of severe respiratory, enteric and systemic infections in a wide range of hosts including man, mammals, fish, and avian. The scientific interest on coronaviruses increased after the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) outbreaks in 2002-2003 followed by Middle East Respiratory Syndrome CoV (MERS-CoV). This decade’s first CoV, named 2019-nCoV, emerged from Wuhan, China, and declared as ‘Public Health Emergency of International Concern’ on January 30(th), 2020 by the World Health Organization (WHO). As on February 4, 2020, 425 deaths reported in China only and one death outside China (Philippines). In a short span of time, the virus spread has been noted in 24 countries. The zoonotic transmission (animal-to-human) is suspected as the route of disease origin. The genetic analyses predict bats as the most probable source of 2019-nCoV though further investigations needed to confirm the origin of the novel virus. The ongoing nCoV outbreak highlights the hidden wild animal reservoir of the deadly viruses and possible threat of spillover zoonoses as well. The successful virus isolation attempts have made doors open for developing better diagnostics and effective vaccines helping in combating the spread of the virus to newer areas.


title: Chapter 4 Ensuring Quality, Safety and Efficacy

text: Publisher Summary Medicines might largely be avoided if enough evidence of quality, safety, and efficacy are not provided by the manufacturer prior to their introduction. A concurrent problem is the fact that the standards prescribed by the law—which calls for quality, efficacy, and safety—are not as exact as they appear on paper. If the quality standards are set too low, the medicine may be ineffective or dangerous, whereas if too much is demanded, the work of making the medicine and checking the quality of every batch may be so laborious as to render it unaffordable. In various parts of the world, there is a considerable market of spurious and counterfeit products, many of which are of extremely poor quality. A product should clearly have the type of pharmacological effect and the potency that it claims, explicitly or by obvious implication, to possess; a product sold as an antibiotic or a corticosteroid must possess these properties to a clinically significant degree.


Delayed presentation of breast necrotising fasciitis due to COVID‐19 anxiety


title: Photopolarimetrical properties of coronavirus model particles: Spike proteins number influence

text: Abstract Coronavirus virions have spherical shape surrounded by spike proteins. The coronavirus spike proteins are very effective molecular mechanisms, which provide the coronavirus entrance to the host cell. The number of these spikes is different; it dramatically depends on external conditions and determines the degree of danger of the virus. A larger number of spike proteins makes the virus infectivity stronger. This paper describes a mathematical model of the shape of coronavirus virions. Based on this model, the characteristics of light scattered by the coronavirus virions were calculated. It was found two main features of coronavirus model particles in the spectral region near 200 nm: a minimum of intensity and a sharp leap of the linear polarization degree. The effect of the spike protein number on the intensity and polarization properties of the scattered light was studied. It was determined that when the number of spike proteins decreases, both the intensity minimum and the position of the linear polarization leap shift to shorter wavelengths. This allows us to better evaluate the shape of the coronavirus virion, and, therefore, the infectious danger of the virus. It was shown that the shorter the wavelength of scattered light, the more reliably one can distinguish viruses from non-viruses. The developed model and the light scattering simulations based on it can be applied not only to coronaviruses, but also to other objects of a similar structure, for example, pollen.


Neurologic Involvement in COVID-19: Radiologists’ Perspective


title: Asthma in the elderly: Current understanding and future research needs—a report of a National Institute on Aging (NIA) workshop

text: Asthma in the elderly is underdiagnosed and undertreated, and there is a paucity of knowledge on the subject. The National Institute on Aging convened this workshop to identify what is known and what gaps in knowledge remain and suggest research directions needed to improve the understanding and care of asthma in the elderly. Asthma presenting at an advanced age often has similar clinical and physiologic consequences as seen with younger patients, but comorbid illnesses and the psychosocial effects of aging might affect the diagnosis, clinical presentation, and care of asthma in this population. At least 2 phenotypes exist among elderly patients with asthma; those with longstanding asthma have more severe airflow limitation and less complete reversibility than those with late-onset asthma. Many challenges exist in the recognition and treatment of asthma in the elderly. Furthermore, the pathophysiologic mechanisms of asthma in the elderly are likely to be different from those seen in young asthmatic patients, and these differences might influence the clinical course and outcomes of asthma in this population.


title: Survival of rhinoviruses on human fingers

text: Abstract Rhinovirus is the main cause of the common cold, which remains the most frequent infection worldwide among humans. Knowledge and understanding of the rhinovirus transmission route is important to reduce morbidity as only preventive measures are effective. In this study, we investigated the potential of rhinovirus to survive on fingers. Rhinovirus-B14 was deposited on fingers for 30, 60, 90 and 120 min. Survival was defined as the ability of the virus to grow after 7 days, confirmed by immunofluorescence. Rhinovirus survival was not dependent on incubation time on fingers. Droplet disruption had no influence on survival. Survival was frequent with high rhinovirus concentrations, but rare with low-concentration droplets, which corresponded to the usual rhinovirus concentrations in mucus observed in children and adults, respectively. Our study confirms that rhinovirus infectiousness is related to the viral concentration in droplets and suggests that children represent the main transmission source, which occurs only rarely via adults. It confirms also that rhinovirus hand-related transmission is possible and supports hand hygiene as a key prevention measure.


title: Preliminary study to identify severe from moderate cases of COVID-19 using combined hematology parameters

text: Background: The third fatal coronavirus is the novel coronavirus (SARS-CoV-2) that causes novel coronavirus pneumonia (COVID-19) which first broke out in December 2019 Patients will develop rapidly if there is no any intervention, so the risk identification of severe patients is critical The aim of this study was to investigate the characteristics and rules of hematology changes in patients with COVID-19, and to explore the possibility differentiating moderate and severe patients using conventional hematology parameters or combined parameters Methods: The clinical data of 45 moderate and severe type patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Jingzhou Central Hospital from January 23 to February 13, 2020 were collected The epidemiological indexes, clinical symptoms, and laboratory test results of the patients were retrospectively analyzed Those parameters with significant differences between moderate and severe cases were analyzed, and the combination parameters with the best diagnostic performance were selected using the linear discriminant analysis (LDA) method Results: Of the 45 patients with the novel 2019 corona virus (COVID-19) (35 moderate and 10 severe cases), 23 were male and 22 were female, with ages ranging from 16 to 62 years The most common clinical symptoms were fever (89%) and dry cough (60%) As the disease progressed, white blood cell count (WBC), neutrophil count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), red blood cell distribution width-coefficient of variation (RDW-CV), and red cell volume distribution width-standard deviation (RDW-SD) parameters in the severe group were significantly higher than those in the moderate group (P<0 05);meanwhile, lymphocyte count (Lym#), eosinophil count (Eos#), high fluorescent cell percentage (HFC%), red blood cell count (RBC), hemoglobin (HGB), and hematocrit (HCT) parameters in the severe group were significantly lower than those in the moderate group (P<0 05) For NLR parameter, it's area under the curve (AUC), cutoff, sensitivity and specificity were 0 890, 13 39, 83 3% and 82 4% respectively;meanwhile, for PLR parameter, it's AUC, cutoff, sensitivity and specificity were 0 842, 267 03, 83 3% and 74 0% respectively The combined parameters of NLR and RDW-SD had the best diagnostic efficiency (AUC =0 938), and when the cutoff value was 1 046, the sensitivity and the specificity were 90 0% and 84 7% respectively, followed by the combined parameter NLR&RDW-CV (AUC =0 923) When the cut-off value was 0 62, the sensitivity and the specificity for distinguishing severe type from moderate cases of COVID-19 were 90 0% and 82 4% respectively Conclusions: The combined NLR and RDW-SD parameter is the best hematology index It may help clinicians to predict the severity of COVID-19 patients and can be used as a useful indicator to help prevent and control the epidemic


title: Human Hepatitis B Virus Core Protein Inhibits IFNα-Induced IFITM1 Expression by Interacting with BAF200

text: Human hepatitis B virus core protein (HBc) is a structural protein of the hepatitis B virus (HBV) and contributes to HBV regulation of host-cell transcription. However, the mechanisms of transcriptional regulation remain poorly characterized. To dissect the function of HBc, a yeast two-hybrid was performed to identify HBc-binding proteins, and the C-terminal of BRG1/hBRM-associated factors 200 (BAF200C) was identified. Then, the existence of HBc interactions with BAF200C and full-length BAF200 was confirmed via co-immunoprecipitation assays in 293T, HepG2 and HepG2-NTCP cells. Furthermore, we show that the binding between HBc and BAF200 was of vital importance to HBc mediated downregulation of interferon-induced transmembrane protein 1 (IFITM1) expression, and the mechanisms for the downregulation were disclosed as follows. Basal level of IFITM1 expression depends on BAF200, rather than the JAK–STAT1 pathway. The interaction of HBc with BAF200 disturbs the stability of the polybromo-associated BAF (PBAF) complex and results in the suppression of IFTM1 transcription. Finally, the antiviral effects of IFITM1 on cell proliferation and HBV replication were found to be partially restored when HBc was co-transfected with BAF200. Collectively, our findings indicate that HBc plays a role in HBV resistance against the antiviral activities of IFNα, providing details about HBV evasion of host innate immunity.