title: Microfluidic-RT-LAMP chip for the point-of-care detection of emerging and re-emerging enteric coronaviruses in swine

text: Porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome-coronavirus (SADS-CoV) are three emerging and re-emerging coronaviruses (CoVs). Symptoms caused by these three viruses are extremely similar, including acute diarrhea, vomiting and even death in piglets. To date, strict biosecurity is still the most effective disease prevention and control measures, and the early detection of pathogens is the most important link. Here, we developed a microfluidic-RT-LAMP chip detection system for the first time, which could detected PEDV, PDCoV and SADS-CoV simultaneously, and had advantages of rapid, simple, sensitive, high-throughput, and accurate at point-of-care settings. The lowest detection limits of the microfluidic-RT-LAMP chip method are 10(1) copies/μL, 10(2) copies/μL and 10(2) copies/μL for PEDV, PDCoV and SADS-CoV, respectively. The whole detection procedure can be finished rapidly in 40 min without any cross-reaction with other common swine viruses. A total of 173 clinical swine fecal samples characterized with diarrheal symptoms were used to evaluate the performance of the newly developed system, which presented good stabilities (C.V.s<5%) and specificities (100%), and possessed sensitivities of 92.24%, 92.19% and 91.23% for PEDV, PDCoV and SADS-CoV respectively. In summary, the established microfluidic-RT-LAMP chip detection system could satisfy the demanding in field diagnoses, which was suitable for promotion in remote areas due to its fast, portable and cost-effective characters.


Abstracts and Citations


A Turning Point, Securitization, and Policing in the Context of Covid-19: Building a New Social Contract Between State and Nation?


title: State of the art and challenges in sequence based T-cell epitope prediction

text: Sequence based T-cell epitope predictions have improved immensely in the last decade. From predictions of peptide binding to major histocompatibility complex molecules with moderate accuracy, limited allele coverage, and no good estimates of the other events in the antigen-processing pathway, the field has evolved significantly. Methods have now been developed that produce highly accurate binding predictions for many alleles and integrate both proteasomal cleavage and transport events. Moreover have so-called pan-specific methods been developed, which allow for prediction of peptide binding to MHC alleles characterized by limited or no peptide binding data. Most of the developed methods are publicly available, and have proven to be very useful as a shortcut in epitope discovery. Here, we will go through some of the history of sequence-based predictions of helper as well as cytotoxic T cell epitopes. We will focus on some of the most accurate methods and their basic background.


title: Characterization of the polyadenylation activity in a replicase complex from Bamboo mosaic virus-infected Nicotiana benthamiana plants

text: Abstract Bamboo mosaic virus (BaMV) has a positive-sense single-stranded RNA genome with a 5′ cap and a 3′ poly(A) tail. To characterize polyadenylation activity in the BaMV replicase complex, we performed the in vitro polyadenylation with various BaMV templates. We conducted a polyadenylation activity assay for BaMV RNA by using a partially purified BaMV replicase complex. The results showed that approximately 200 adenylates at the 3′ end of the RNA were generated on the endogenous RNA templates. Specific fractions derived from uninfected Nicotiana benthamiana plants enhanced the polyadenylation activity, implying that host factors are involved in polyadenylation. Furthermore, polyadenylation can be detected in newly synthesized plus-strand RNA in vitro when using the exogenous BaMV minus-strand minigenome. For polyadenylation on the exogenous plus-strand minigenome, the 3′ end requires at least 4A to reach 22% polyadenylation activity. The results indicate that the BaMV replicase complex recognizes the 3′ end of BaMV for polyadenylation.


title: Bacterial diversity of bat guano from Cabalyorisa Cave, Mabini, Pangasinan, Philippines: A first report on the metagenome of Philippine bat guano

text: Bats are highly diverse and ecologically valuable mammals. They serve as host to bacteria, viruses and fungi that are either beneficial or harmful to its colony as well as to other groups of cave organisms. The bacterial diversity of two bat guano samples, C1 and C2, from Cabalyorisa Cave, Mabini, Pangasinan, Philippines were investigated using 16S rRNA gene amplicon sequencing. V3-V4 hypervariable regions were amplified and then sequenced using Illumina MiSeq 250 PE system. Reads were processed using Mothur and QIIME pipelines and assigned 12,345 OTUs for C1 and 5,408 OTUs for C2. The most dominant OTUs in C1 belong to the Proteobacteria (61.7%), Actinobacteria (19.4%), Bacteroidetes (4.2%), Firmicutes (2.7%), Chloroflexi (2.5%), candidate phylum TM7 (2.3%) and Planctomycetes (1.9%) while Proteobacteria (61.7%) and Actinobacteria (34.9%) dominated C2. Large proportion of sequence reads mainly associated with unclassified bacteria indicated possible occurrence of novel bacteria in both samples. XRF spectrophotometric analyses of C1 and C2 guano revealed significant differences in the composition of both major and trace elements. C1 guano recorded high levels of Si, Fe, Mg, Al, Mn, Ti and Cu while C2 samples registered high concentrations of Ca, P, S, Zn and Cr. Community structure of the samples were compared with other published community profiling studies from Finland (SRR868695), Meghalaya, Northeast India (SRR1793374) and Maharashtra State, India (CGS). Core microbiome among samples were determined for comparison. Variations were observed among previously studied guano samples and the Cabalyorisa Cave samples were attributed to either bat sources or age of the guano. This is the first study on bacterial diversity of guano in the Philippines through high-throughput sequencing.


title: Repurposed immunomodulatory drugs for Covid-19 in pre-ICu patients - mulTi-Arm Therapeutic study in pre-ICu patients admitted with Covid-19 – Repurposed Drugs (TACTIC-R): A structured summary of a study protocol for a randomised controlled trial

text: OBJECTIVES: To determine if a specific immunomodulatory intervention reduces progression of COVID-19-related disease to organ failure or death, compared to standard of care (SoC). TRIAL DESIGN: Randomised, parallel 3-arm (1:1:1 ratio), open-label, Phase IV platform trial of immunomodulatory therapies in patients with late stage 1 or stage 2 COVID-19-related disease, with a diagnosis based either on a positive assay or high suspicion of COVID-19 infection by clinical and/or radiological assessment. PARTICIPANTS: Patients aged 18 and over, with a clinical picture strongly suggestive of COVID-19-related disease (with/without a positive COVID-19 test) AND a Risk count (as defined below) >3 OR ≥3 if risk count includes “Radiographic severity score >3”. A risk count is calculated by the following features on admission (1 point for each): radiographic severity score >3, male gender, non-white ethnicity, diabetes, hypertension, neutrophils >8.0 x10(9)/L, age >40 years and CRP >40 mg/L. Patients should be considered an appropriate subject for intervention with immunomodulatory therapies in the opinion of the investigator and be able to be maintained on venous thromboembolism prophylaxis during the inpatient dosing period, according to local guidelines. The complete inclusion and exclusion criteria as detailed in the additional file 1 should be fulfilled. Patients will be enrolled prior to the need for invasive mechanical ventilation, cardiac or renal support. Participants will be recruited across multiple centres including initially at Cambridge University Hospitals NHS Foundation Trust, King’s College Hospital NHS Foundation Trust, Guy’s and St Thomas’ NHS Foundation Trust, University Hospital of Wales, Gloucestershire Royal Hospitals NHS Foundation Trust and The Royal Wolverhampton NHS Trust. INTERVENTION AND COMPARATOR: Each active comparator arm will be compared against standard of care (SoC). The immunomodulatory drugs were selected from a panel of licenced candidates by a drug evaluation committee, which considered potential efficacy, potential toxicity, scalability and novelty of each strategy. The initial active arms comprise baricitinib and ravulizumab. Baricitinib will be given 4 mg orally (once daily (OD)) on days 1-14 or until day of discharge. The dose will be reduced to 2 mg OD for patients aged > 75 years and those with an estimated Cockcroft Gault creatinine clearance of 30-60 ml/min. Ravulizumab will be administered intravenously once according to the licensed weight-based dosing regimen (see Additional file 1). Each active arm will be compared with standard of care alone. No comparisons will be made between active arms in this platform trial. MAIN OUTCOMES: The primary outcome is the incidence (from baseline up to Day 14) of any one of the events (whichever comes first): death, invasive mechanical ventilation, extra corporeal membrane oxygenation, cardiovascular organ support (inotropes or balloon pump), or renal failure (estimated Cockcroft Gault creatinine clearance <15ml/min). RANDOMISATION: Eligible patients will be randomised using a central web-based randomisation service (Sealed Envelope) in a 1:1:1 ratio, stratified by site to one of the treatment arms or SoC. BLINDING (MASKING): This is an open-label trial. Data analysis will not be blinded. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): There is no fixed sample size for this study. Serial interim analyses will be triggered by an Independent Data Monitoring Committee (IDMC), including analysis after 125 patients are recruited to each arm, 375 in total assuming 3 arms. Additional interim analyses are projected after 229 patients per arm, and potentially then after 469 per arm, but additional analyses may be triggered by the IDMC. TRIAL STATUS: TACTIC-R Protocol version number 2.0 date May 20, 2020, recruitment began May 7, 2020 and the end trial will be the date 18 months after the last patient’s last visit. The recruitment end date cannot yet be accurately predicted. TRIAL REGISTRATION: Registered on EU Clinical Trials Register EudraCT Number: 2020-001354-22 Registered: 6 May 2020 It was registered on ClinicalTrials.gov (NCT04390464) and on ISRCTN (ISRCTN11188345) FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


title: A new approach to the prediction of transmembrane structures

text: About 20%–30% of genome products have been predicted as membrane proteins, which have significant biological functions. The prediction of the amount and position for the transmembrane protein helical segments (TMHs) is the hot spot in bioinformatics. In this paper, a new approach, maximum spectrum of continuous wavelet transform (MSCWT), is proposed to predict TMHs. The predictions for eight SARS-CoV membrane proteins indicate that MSCWT has the same capacity with software TMpred. Moreover, the test on a dataset of 131 structure-known proteins with 548 TMHs shows that the prediction accuracy of MSCWT for TMHs is 91.6% and that for membrane protein is 89.3%.


title: A Review of Multi-Threat Medical Countermeasures against Chemical Warfare and Terrorism

text: The Multi-Threat Medical Countermeasure (MTMC) hypothesis has been proposed with the aim of developing a single countermeasure drug with efficacy against different pathologies caused by multiple classes of chemical warfare agents. Although sites and mechanisms of action and the pathologies caused by different chemical insults vary, common biochemical signaling pathways, molecular mediators, and cellular processes provide targets for MTMC drugs. This article will review the MTMC hypothesis for blister and nerve agents and will expand the scope of the concept to include other chemicals as well as briefly consider biological agents. The article will also consider how common biochemical signaling pathways, molecular mediators, and cellular processes that contribute to clinical pathologies and syndromes may relate to the toxicity of threat agents. Discovery of MTMC provides the opportunity for the integration of diverse researchers and clinicians, and for the exploitation of cutting-edge technologies and drug discovery. The broad-spectrum nature of MTMC can augment military and civil defense to combat chemical warfare and chemical terrorism.


title: Empfehlungen zur Unterstützung von belasteten, schwerstkranken, sterbenden und trauernden Menschen in der Corona-Pandemie aus palliativmedizinischer Perspektive: Empfehlungen der Deutschen Gesellschaft für Palliativmedizin (DGP), der Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin (DIVI), des Bundesverbands Trauerbegleitung (BVT), der Arbeitsgemeinschaft für Psychoonkologie in der Deutschen Krebsgesellschaft, der Deutschen Vereinigung für Soziale Arbeit im Gesundheitswesen (DVSG) und der Deutschen Gesellschaft für Systemische Therapie, Beratung und Familientherapie (DGSF)

text: The corona pandemic has led to a number of restrictions and prohibitions, which in turn place large psychosocial or spiritual burdens on patients with COVID-19, their families and relatives and the treating personnel in the healthcare system. Patients with COVID-19 are not allowed to receive visitors and many hospitals and nursing homes have completely banned visitors. Many support services have been reduced or stopped completely. Necessary treatment interventions for other patients with critical and life-limiting diseases have been delayed or suspended in order to free resources for the expected COVID-19 patients; however, these people need to feel social connectedness with their relatives. Palliative care patients should be exempted from any ban on visitors. Families should be able to visit dying patients even on intensive care units or isolation wards, using adequate protective equipment. Alternative options, such as video telephone calls or via social media should be explored for patients in isolation. Families should also be enabled to say goodbye to the deceased with adequate protective equipment or should be offered alternative real or virtual options for remembrance and commemoration. Health care professionals coping with the exceptional stress should be continuously supported. This requires clear communication and leadership structures, communication training, psychosocial support, but most of all optimal framework conditions for the clinical work.


title: Further Defining the Human Virome using NGS: Identification of Redondoviridae

text: In this issue of Cell Host & Microbe, Abbas et al. (2019) uncover a previously undefined family of single-stranded DNA viruses, Redondoviridae, in human ororespiratory sites. The presence of Redondoviridae associates with critical illness such as respiratory failure and periodontitis, illustrating the power of metagenomics to define the human virome.


title: Croup

text: Summary Most children who present with acute onset of barky cough, stridor, and chest-wall indrawing have croup. A careful history and physical examination is the best method to confirm the diagnosis and to rule out potentially serious alternative disorders such as bacterial tracheitis and other rare causes of upper-airway obstruction. Epinephrine delivered via a nebuliser is effective for temporary relief of symptoms of airway obstruction. Corticosteroids are the mainstay of treatment, and benefit is seen in children with all levels of severity of croup, including mild cases.


title: Real-time, MinION-based, amplicon sequencing for lineage typing of infectious bronchitis virus from upper respiratory samples

text: Infectious bronchitis (IB) causes significant economic losses in the global poultry industry. Control of infectious bronchitis is hindered by the genetic diversity of the causative agent, infectious bronchitis virus (IBV), which has led to the emergence of several serotypes that lack complete serologic cross-protection. While serotyping by definition requires immunologic characterization, genotyping is an efficient means to identify IBVs detected in samples. Sanger sequencing of the S1 subunit of the spike gene is currently used to genotype IBV; however, the universal S1 PCR was created to work from cultured IBV and it is inefficient at detecting mixed isolates. This paper describes a MinION-based AmpSeq method that genetically typed IBV from clinical samples, including samples with multiple isolates. Total RNA was extracted from fifteen tracheal scrapings and choanal cleft swab samples, randomly reverse transcribed, and PCR amplified using modified S1-targeted primers. Amplicons were barcoded to allow for pooling of samples, processed per manufacturer’s instructions into a 1D MinION sequencing library, and sequenced on the MinION. The AmpSeq method detected IBV in 13 of 14 IBV-positive samples. AmpSeq accurately detected and genotyped both IBV lineages in three of five samples containing two IBV lineages. Additionally, one sample contained three IBV lineages, and AmpSeq accurately detected two of the three. Strain identification, including detection of different strains from the same lineage, was also possible with this AmpSeq method. The results demonstrate the feasibility of using MinION-based AmpSeq for rapid and accurate identification and lineage typing of IBV from oral swab samples.


title: A systematic review to identify areas of enhancements of pandemic simulation models for operational use at provincial and local levels

text: BACKGROUND: In recent years, computer simulation models have supported development of pandemic influenza preparedness policies. However, U.S. policymakers have raised several concerns about the practical use of these models. In this review paper, we examine the extent to which the current literature already addresses these concerns and identify means of enhancing the current models for higher operational use. METHODS: We surveyed PubMed and other sources for published research literature on simulation models for influenza pandemic preparedness. We identified 23 models published between 1990 and 2010 that consider single-region (e.g., country, province, city) outbreaks and multi-pronged mitigation strategies. We developed a plan for examination of the literature based on the concerns raised by the policymakers. RESULTS: While examining the concerns about the adequacy and validity of data, we found that though the epidemiological data supporting the models appears to be adequate, it should be validated through as many updates as possible during an outbreak. Demographical data must improve its interfaces for access, retrieval, and translation into model parameters. Regarding the concern about credibility and validity of modeling assumptions, we found that the models often simplify reality to reduce computational burden. Such simplifications may be permissible if they do not interfere with the performance assessment of the mitigation strategies. We also agreed with the concern that social behavior is inadequately represented in pandemic influenza models. Our review showed that the models consider only a few social-behavioral aspects including contact rates, withdrawal from work or school due to symptoms appearance or to care for sick relatives, and compliance to social distancing, vaccination, and antiviral prophylaxis. The concern about the degree of accessibility of the models is palpable, since we found three models that are currently accessible by the public while other models are seeking public accessibility. Policymakers would prefer models scalable to any population size that can be downloadable and operable in personal computers. But scaling models to larger populations would often require computational needs that cannot be handled with personal computers and laptops. As a limitation, we state that some existing models could not be included in our review due to their limited available documentation discussing the choice of relevant parameter values. CONCLUSIONS: To adequately address the concerns of the policymakers, we need continuing model enhancements in critical areas including: updating of epidemiological data during a pandemic, smooth handling of large demographical databases, incorporation of a broader spectrum of social-behavioral aspects, updating information for contact patterns, adaptation of recent methodologies for collecting human mobility data, and improvement of computational efficiency and accessibility.


title: Applications of PCR (Real-Time and MassTag) and Enzyme-Linked Immunosorbent Assay in Diagnosis of Respiratory Infections and Diarrheal Illness Among Deployed U.S. Military Personnel During Exercise Balikatan 2009, Philippines

text: Laboratory-based surveillance for diarrheal and respiratory illness was conducted at the 2009 Republic of the Philippines–United States Balikatan exercise to determine the presence of specific pathogens endemic in the locations where the military exercises were conducted. Ten stool and 6 respiratory specimens were obtained from individuals meeting case definitions for diarrhea or respiratory illness. Stool specimens were frozen in dry ice and remotely tested using enzyme-linked immunosorbent assay for Rotavirus, Astrovirus, Adenovirus, Entamoeba histolytica, Giardia, and Cryptosporidium and polymerase chain reaction for enterotoxigenic Escherichia coli, Campylobacter, Shigella, Vibrio, Salmonella, and Norovirus. Eight (4 for Campylobacter jejuni, 2 for Campylobacter coli, 1 for Norovirus genogroup II, and 1 for both Campylobacter coli and enterotoxigenic Escherichia coli) of 10 samples were positive for at least 1 enteric pathogen. MassTag polymerase chain reaction for influenza A and B, respiratory syncytial virus groups A and B, human coronavirus-229E and human coronavirus-OC43, human metapneumovirus, enterovirus, human parainfluenza viruses 2,3, and 4a, human adenovirus, Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae, Legionella pneumonia, and Mycoplasma pneumonia was done on respiratory specimens. Out of 6 samples, 3 tested positive for H. influenzae; 1 tested positive for both H. influenzae and human parainfluenza virus 3; and 2 tested negative. Laboratory-based surveillance can be useful in determining etiologies of diarrheal and respiratory illness of deployed military personnel.


COVID-19 Outbreak Provides a Unique Platform to Study Behavioral Changes in Iran


title: Laparoscopy in the coronavirus disease 2019 (COVID-19) era

text: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in China at the end of 2019 has become a pandemic infection that has now involved 200 countries with 465,915 confirmed cases and 21,031 confirmed deaths. Unfortunately, many data have shown that the high number of undocumented infections could have a major role in the rapid diffusion of the disease. In most of the nations involved, non-urgent, non-cancer procedures have been stopped to reallocate medical and paramedical staff to face the emergency. Moreover, concerns have been raised that minimally invasive surgery could be a procedure that carries the risk of virus diffusion in the operating theater during surgery. This paper reports clinical recommendations and scientific studies to assist clinicians in this field.


Herd immunity – estimating the level required to halt the COVID-19 epidemics in affected countries


title: Crystal structure of Middle East respiratory syndrome coronavirus helicase

text: Middle East respiratory syndrome coronavirus (MERS-CoV) remains a threat to public health worldwide; however, effective vaccine or drug against CoVs remains unavailable. CoV helicase is one of the three evolutionary most conserved proteins in nidoviruses, thus making it an important target for drug development. We report here the first structure of full-length coronavirus helicase, MERS-CoV nsp13. MERS-CoV helicase has multiple domains, including an N-terminal Cys/His rich domain (CH) with three zinc atoms, a beta-barrel domain and a C-terminal SF1 helicase core with two RecA-like subdomains. Our structural analyses show that while the domain organization of nsp13 is conserved throughout nidoviruses, the individual domains of nsp13 are closely related to the equivalent eukaryotic domains of Upf1 helicases. The most distinctive feature differentiating CoV helicases from eukaryotic Upf1 helicases is the interaction between CH domain and helicase core.


Author reply to Letters to the Editor “CT chest findings in coronavirus disease (COVID-19)”


Eosinopenia as an early diagnostic marker of COVID-19 at the time of the epidemic


title: Human Eye Infections

text: The eye contains a variety of cell and tissue types. Conjunctivitis due to respiratory RNA viruses represents by far the most common viral eye disorder. However, any ocular tissue can sustain infection by human viruses, including those viruses with predilection for neural sites. As elsewhere in the body, ocular pathologic changes induced by viruses tend to follow stereotypical patterns. Classical viral mechanisms of infection, including latency, reactivation, and carcinogenesis, can all be demonstrated in the eye. The eye's tissues also demonstrate a wide variety of immune responses, including those of mucosa-associated lymphoid tissue and immune privilege. The ocular complications of AIDS, including viral retinitis and ocular surface squamous carcinoma, remain significant causes of morbidity throughout the world.


title: Chapter 47 Infections in Pregnancy

text: Publisher Summary Despite advances in peripartum care, maternal morbidity and mortality associated with infections in pregnancy are increasing even in developed countries. Recently published data from the Center for Disease Control's Pregnancy Mortality Surveillance System indicates that although maternal mortality from hemorrhage, embolism, and anesthesia has declined in the United States, the proportion of maternal deaths due to infections has increased. During 1991–7 infection accounted for 13.2% of pregnancy-related deaths overall and 36.3% of abortion-related deaths. The greatest infection risk is found in blacks, older women, women without prenatal care, and women with multiple pregnancy. In the United States pregnancy rates are stable or increasing in these groups. Infection is also a major cause of morbidity and mortality for the fetus and newborn. Many perinatal infections are associated with intra-uterine growth retardation and low birthweight, or cause fetal and neonatal brain injury. Infections, particularly bacterial vaginosis and chorioamnionitis, can result in preterm delivery of live-born infants (delivery before 37 weeks gestation), or stillbirth. A multitude of immunologic, endocrinologic, metabolic, physiologic, and anatomic changes influence the likelihood and course of many infections during pregnancy. Some of these changes are intrinsic, and occur in all normal pregnancies, while others occur to varying degrees in normal and abnormal pregnancies.


title: Rapid In‐Vitro Inactivation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) Using Povidone‐Iodine Oral Antiseptic Rinse

text: PURPOSE: To investigate the optimal contact time and concentration for viricidal activity of oral preparation of povidone‐iodine (PVP‐I) against SARS‐CoV‐2 (‘corona virus’) to mitigate the risk and transmission of the virus in the dental practice. MATERIALS AND METHODS: The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) USA‐WA1/2020 strain, virus stock was tested against oral antiseptic solutions consisting of aqueous povidone‐iodine (PVP‐I) as the sole active ingredient. The PVP‐I was tested at diluted concentrations of 0.5%, 1%, and 1.5%. Test media without any virus was added to 2 tubes of the compounds to serve as toxicity and neutralization controls. Ethanol (70%) was tested in parallel as a positive control, and water only as a negative control. The test solutions and virus were incubated at room temperature (22 ± 2 °C) for time periods of 15 and 30 seconds. The solution was then neutralized by a 1/10 dilution in minimum essential medium (MEM) 2% fetal bovine serum (FBS), 50 µg/mL gentamicin. Surviving virus from each sample was quantified by standard end‐point dilution assay and the log reduction value (LRV) of each compound compared to the negative (water) control was calculated. RESULTS: PVP‐I oral antiseptics at all tested concentrations of 0.5%, 1%, and 1.5%, completely inactivated SARS‐CoV‐2 within 15 seconds of contact. The 70% ethanol control group was unable to completely inactivate SARS‐CoV‐2 after 15 seconds of contact, but was able to inactivate the virus at 30 seconds of contact. CONCLUSIONS: PVP‐I oral antiseptic preparations rapidly inactivated SARS‐CoV‐2 virus in vitro. The viricidal activity was present at the lowest concentration of 0.5 % PVP‐I and at the lowest contact time of 15 seconds. This important finding can justify the use of preprocedural oral rinsing with PVP‐I (for patients and health care providers) may be useful as an adjunct to personal protective equipment, for dental and surgical specialties during the COVID‐19 pandemic.


title: In Vitro Antiviral Activity of some Novel Isatin Derivatives against HCV and SARS-CoV Viruses

text: 4-[(1,2-dihydro-2-oxo-3H-indol-3-ylidene)amino]-N(4,6-dimethyl-2-pyrimidiny)benzene sulphonamide and its derivatives were evaluated for antiviral activity against Pathogenic viruses such as Hepatitis C Virus and SARS-CoV in Vero and Huh 5-2 cells, respectively. The 5-fluoro derivative inhibited the HCV RNA synthesis at 6 μg/ml, without toxicity at a concentration up to 42 μg/ml in Huh 5-2 cells. Among the compounds tested SPIII-5F exhibits the 45% maximum protection against replication of SARS-CoV in Vero cells.


The Importance of Diagnostic Testing during a Viral Pandemic: Early Lessons from Novel Coronavirus Disease (COVID-19).


title: Guide to Immunopharmacology: a database to boost immunology education, research and therapy

text: In the era of big data, the establishment of a free database, containing all the immune drug targets and associated cell types, is of great value. To this aim, the Guide to Immunopharmacology has been created in a joint effort between the International Union of Basic and Clinical Pharmacology (IUPHAR) and the International Union of Immunological Societies (IUIS). Here we highlight the structure and content of the database, which includes up‐to‐date quantitative information on the fundamental science underlying each immune target. A set of practical examples and tools for data mining are summarized to support immune research into drug discovery and therapeutics.


title: Therapeutic Use of Mesenchymal Stem Cell-Derived Exosomes: From Basic Science to Clinics

text: Mesenchymal stem cells (MSC) are, due to their immunosuppressive and regenerative properties, used as new therapeutic agents in cell-based therapy of inflammatory and degenerative diseases. A large number of experimental and clinical studies revealed that most of MSC-mediated beneficial effects were attributed to the effects of MSC-sourced exosomes (MSC-Exos). MSC-Exos are nano-sized extracellular vesicles that contain MSC-derived bioactive molecules (messenger RNA (mRNA), microRNAs (miRNAs)), enzymes, cytokines, chemokines, and growth factors) that modulate phenotype, function and homing of immune cells, and regulate survival and proliferation of parenchymal cells. In this review article, we emphasized current knowledge about molecular and cellular mechanisms that were responsible for MSC-Exos-based beneficial effects in experimental models and clinical trials. Additionally, we elaborated on the challenges of conventional MSC-Exos administration and proposed the use of new bioengineering and cellular modification techniques which could enhance therapeutic effects of MSC-Exos in alleviation of inflammatory and degenerative diseases.


title: Adipose Stem Cells (ASCs) and Stromal Vascular Fraction (SVF) as a Potential Therapy in Combating (COVID-19)-Disease

text: A recent and interesting study reported improved respiratory activity after intravenous administration of mesenchymal stem cells (MSCs) into patients affected by coronavirus disease 2019 (COVID-19). These outcomes displayed that intravenous infiltration of MSCs is a safe and efficacy treatment for COVID-19 pneumonia, a severe acute respiratory illness caused by the coronavirus 2 (SARS-CoV-2). Only 7 patients were treated, but with extraordinary results, opening a new strategy in COVID-19 therapy. Currently, no specific therapies against SARS-CoV-2 are available. The MSCs therapy outcomes reported, are striking, as these cells inhibit the over-activation of the immune system, promoting endogenous repair, by improving the lung microenvironment after the SARS-CoV-2 infection. The MSCs could represent an effective, autologous and safe therapy, and therefore, sharing these published results, here is reported the potential use possibilities in COVID-19 of the most common MSCs represented by Adipose Stem Cells (ASCs).


title: A cohort study of the effect of winter dysentery on herd-level milk production

text: ABSTRACT Winter dysentery (WD) is a contagious disease caused by bovine coronavirus. It is characterized by acute onset of diarrhea, fever, depression, and reduced milk yield in adult cattle. Although production loss is a well-known consequence of WD, large-scale studies estimating the effect on milk production are lacking. The objective of this study was to estimate the effect of farmer-reported WD on herd-level milk production and milk composition. A cohort study was performed based on reports of herd outbreaks of winter dysentery during a regional epidemic in Norway during the winter of 2011–2012. Reports were made by farmers, and diagnosis was based on a herd outbreak of acute diarrhea in adults. Milk shipment data were retrieved from the dairy company, and information on herd size and milking system were retrieved from the Norwegian Dairy Herd Recording System. We compared milk production in herds with reported outbreaks of WD (n = 224) with all herds in the same area without a reported outbreak (n = 2,093) during the same period. The outcome variable in the analysis was milk volume per cow per day, and the main predictor was whether the herd had a reported outbreak of WD or not. We assessed the effect of WD on milk production by fitting a linear mixed model, adjusting for milk production in the herd before the outbreak. Similarly, we assessed the effect of WD on milk composition using linear regression, adjusting for the levels of milk components before the outbreak. This study estimated a total loss of 51 L/cow during the study period, from 7 d before to 19 d after a reported outbreak. The lowest estimated production was 2 d after the outbreak was reported, when the average milk yield was 19.4 L/cow per day, compared with 23.0 L/cow per day 7 days before notification (i.e., a difference of 3.6 L/cow, or 15%). The effect gradually declined with time. The estimated effect on milk composition was modest, but an increase of 11% in free fatty acids and a small increase in fat/protein ratio indicated that WD might put cows into negative energy balance. Descriptive analysis indicated that herd milk yield was still reduced 4 mo after an outbreak. This cohort study showed that WD causes considerable decreases in milk production, and it alters milk composition. These findings highlight the important negative consequences of WD, and should motivate actions to prevent between-herd spread of bovine coronavirus.


title: Detection of Group 1 Coronaviruses in Bats Using Universal Coronavirus Reverse Transcription Polymerase Chain Reactions

text: The zoonotic transmission of SARS coronavirus from animals to humans revealed the potential impact of coronaviruses on mankind. This incident also triggered several surveillance programs to hunt for novel coronaviruses in human and wildlife populations. Using classical RT-PCR assays that target a highly conserved sequence among coronaviruses, we identified the first coronaviruses in bats. These assays and the cloning and sequencing of the PCR products are described in this chapter. Using the same approach in our subsequent studies, we further detected several novel coronaviruses in bats. These findings highlighted the fact that bats are important reservoirs for coronaviruses.


Acute arterial thrombosis in a breast cancer survivor with coronavirus disease 2019 (COVID-19)


title: Pandemic influenza: implications for occupational medicine

text: This article reviews the biological and occupational medicine literature related to H5N1 pandemic influenza and its impact on infection control, cost and business continuity in settings outside the health care community. The literature on H5N1 biology is reviewed including the treatment and infection control mechanisms as they pertain to occupational medicine. Planning activity for the potential arrival of pandemic avian influenza is growing rapidly. Much has been published on the molecular biology of H5N1 but there remains a paucity of literature on the occupational medicine impacts to organizations. This review summarizes some of the basic science surrounding H5N1 influenza and raises some key concerns in pandemic planning for the occupational medicine professional. Workplaces other than health care settings will be impacted greatly by an H5N1 pandemic and the occupational physician will play an essential role in corporate preparation, response, and business continuity strategies.


title: Delicate structural coordination of the Severe Acute Respiratory Syndrome coronavirus Nsp13 upon ATP hydrolysis

text: To date, an effective therapeutic treatment that confers strong attenuation toward coronaviruses (CoVs) remains elusive. Of all the potential drug targets, the helicase of CoVs is considered to be one of the most important. Here, we first present the structure of the full-length Nsp13 helicase of SARS-CoV (SARS-Nsp13) and investigate the structural coordination of its five domains and how these contribute to its translocation and unwinding activity. A translocation model is proposed for the Upf1-like helicase members according to three different structural conditions in solution characterized through H/D exchange assay, including substrate state (SARS-Nsp13-dsDNA bound with AMPPNP), transition state (bound with ADP-AlF(4)(−)) and product state (bound with ADP). We observed that the β19–β20 loop on the 1A domain is involved in unwinding process directly. Furthermore, we have shown that the RNA dependent RNA polymerase (RdRp), SARS-Nsp12, can enhance the helicase activity of SARS-Nsp13 through interacting with it directly. The interacting regions were identified and can be considered common across CoVs, which provides new insights into the Replication and Transcription Complex (RTC) of CoVs.


title: Discontinuous transcription or RNA processing of vaccinia virus late messengers results in a 5′ poly(A) leader

text: Abstract We have demonstrated by primer elongation and cap analysis that mature vaccinia virus late transcripts are discontinuously synthesized. We have shown that RNA transcripts from a translocated 11K and from the authentic 11K and 4b late promoters are extended by approximately 35 nucleotides beyond the “start site” determined by S1 mapping using vaccinia genomic DNA as a probe. Sequencing of the RNA and of the first strand cDNA reveal that a homopolymeric poly(A) sequence is linked to the 5′ terminus of the RNA transcripts. S1 mapping of RNA transcripts with a DNA probe containing an A-stretch, replacing promoter sequences upstream of position −1, confirms the existence of a poly(A) leader of approximately 35 A-residues.


Covid‐19 infection in psoriasis patients treated with cyclosporin


title: Gene optimization leads to robust expression of human respiratory syncytial virus nucleoprotein and phosphoprotein in human cells and induction of humoral immunity in mice

text: Abstract Human respiratory syncytial virus (HRSV) is the major pathogen leading to respiratory disease in infants and neonates worldwide. An effective vaccine has not yet been developed against this virus, despite considerable efforts in basic and clinical research. HRSV replication is independent of the nuclear RNA processing constraints, since the virus genes are adapted to the cytoplasmic transcription, a process performed by the viral RNA-dependent RNA polymerase. This study shows that meaningful nuclear RNA polymerase II dependent expression of the HRSV nucleoprotein (N) and phosphoprotein (P) proteins can only be achieved with the optimization of their genes, and that the intracellular localization of N and P proteins changes when they are expressed out of the virus replication context. Immunization tests performed in mice resulted in the induction of humoral immunity using the optimized genes. This result was not observed for the non-optimized genes. In conclusion, optimization is a valuable tool for improving expression of HRSV genes in DNA vaccines.


The Importance of Fit-Testing in Decontamination of N95 Respirators: A Cautionary Note


title: Overview of the perceived risk of transboundary pig diseases in South Africa

text: Pig production is one of the most important animal agricultural activities in South Africa, and plays a definite role in providing food security for certain population groups in the country. As with all animal production systems, it is subject to the risk of outbreak of transboundary diseases. In the present overview, evaluations of the perceived risk of selected transboundary animal diseases of pigs, as collated from the willing participants from the provincial veterinary services of South Africa, are presented. A scenario tree revealed that infected but undetected pigs were the greatest perceived threat. The provincial veterinary services, according to participants in the study, face certain difficulties, including the reporting of disease and the flow of disease information amongst farmers. Perceived strengths in surveillance and disease monitoring include the swiftness of sample despatch to the national testing laboratory, as well as the ease of flow of information between the provincial and national agricultural authorities. The four factors were identified that were perceived to most influence animal health-service delivery: transport, access, livestock policy and resources. African swine fever was perceived to be the most important pig disease in South Africa. Because the decentralisation of veterinary services in South Africa was identified as a potential weakness, it is recommended that national and provincial veterinary services need to work together and interdependently to achieve centrally controlled surveillance systems. Regionally-coordinated surveillance activities for certain transboundary diseases were identified as needing priority for the southern African region. It is proposed that an emergency preparedness document be made available and regularly revised according to the potential risks identified on a continuous basis for South Africa.


title: Rabies trend in China (1990–2007) and post-exposure prophylaxis in the Guangdong province

text: BACKGROUND: Rabies is a major public-health problem in developing countries such as China. Although the recent re-emergence of human rabies in China was noted in several epidemiological studies, little attention was paid to the reasons behind this phenomenon paralleling the findings of the previous reports. The purpose of this study is thus first to characterize the current trends of human rabies in China from 1990 to 2007, and then to define better recommendations for improving the post-exposure prophylaxis (PEP) schedules delivered to rabies patients. METHODS: The most updated epidemiological data for 22527 human rabies cases from January 1990 to July 2007, retrieved from the surveillance database of reportable diseases managed by the Ministry of Health of China, were analysed. To investigate the efficiency for the post-exposure treatment of rabies, the details of 244 rabies patients, including their anti-rabies treatment of injuries or related incidents, were ascertained in Guangdong provincial jurisdiction. The risk factors to which the patients were predisposed or the regimens given to 80 patients who received any type of PEP were analysed to identify the reasons for the PEP failures. RESULTS: The results from analysis of the large number of human rabies cases showed that rabies in China was largely under control during the period 1990–1996. However, there has been a large jump in the number of reported rabies cases since 2001 up to a new peak (with an incidence rate of 0.20 per 100000 people) that was reached in 2004, and where the level has remained until present. Then, we analysed the PEP in 244 rabies cases collected in the Guangdong province in 2003 and 2004, and found that 67.2% of the patients did not seek medical services or did not receive any PEP. Further analysis of PEP for the 80 rabies patients who received any type of PEP indicated that almost all of the patients did not receive proper or timely treatment on the wounds or post-exposure vaccination or rabies immunoglobulins. CONCLUSION: While the issue of under-reporting of rabies in previous years may well be a factor in the apparent upwards trend of human rabies in recent years, the analysis of PEP in the Guangdong province provides evidence that suggests that the failure to receive PEP was a major factor in the number of human cases in China. Thus, the data underline the need for greatly improved availability and timely application of high-quality anti-rabies biologicals, both vaccines and immunoglobulins, in the treatment of human bite victims. Controlling dog rabies through pet vaccination schemes may also play a huge role in reducing the rate of human exposure. Education of the public, health care staff and veterinarians will also help to change the current situation.


title: A Histopathological Study of Bovine Ganglia

text: Summary One hundred and sixty-eight ganglia from 54 cattle aged 10 days to 10 years were examined microscopically. Samples from six autonomic ganglia and one sensory ganglion were represented. Thirteen animals were clinically normal and 41 were submitted for post-mortem examination. Neuronal vacuolation, spheroid formation, lipofuscin accumulation and central chromatolysis were observed sporadically and were of varying magnitude. Neuronal vacuolation and spheroid formation were not age-related changes, while lipofuscin accumulation was more common in older animals and central chromatolysis was more common in younger cattle. Non-suppurative inflammation and neuronophagia were also common findings (23 out of 54 animals, 42.6%) in autonomic ganglia that did not contain herpesvirus DNA as determined by polymerase chain reaction. Renaut bodies, features of peripheral nerves, were most commonly noted in the vagus. None of the histopathological findings were related to any particular disease in which loss of autonomic nervous system function might be expected. Furthermore, all changes were as common in clinically normal animals as in animals with disease.


title: Load reduction in live PRRS vaccines using oil and polymer adjuvants

text: Abstract PRRSV live vaccines are widely used in pig farming practice and are usually not adjuvanted. For safety issues, it would be useful to reduce the antigenic load of such vaccines while preserving their efficacy. In this study we show that the addition of polymer or oil adjuvants in a PRRS live vaccine enhanced the protection to challenge of vaccinated animals compared to a non-adjuvanted commercial reference. Moreover, for both types of adjuvants, despite lower antibody titers, the protection to challenge given by the adjuvanted vaccine containing only 50% of the antigen load was equivalent to the protection given by the non-adjuvanted vaccine. These results demonstrate that the addition of relevant adjuvants can enhance the efficacy of the protection conferred to animals by live vaccines.


title: Pneumocystis jirovecii pneumonia as an initial manifestation of hyper-IgM syndrome in an infant: A case report

text: RATIONALE: Pneumocystis jirovecii causes severe pneumonia in immunocompromised hosts. Human immunodeficiency virus infection, malignancy, solid organ or hematopoietic cell transplantation, and primary immune deficiency compose the risk factors for Pneumocystis pneumonia (PCP) in children, and PCP can be an initial clinical manifestation of primary immune deficiency. PATIENT CONCERNS: A 5-month-old infant presented with cyanosis and tachypnea. He had no previous medical or birth history suggesting primary immune deficiency. He was diagnosed with interstitial pneumonia on admission. DIAGNOSES: He was diagnosed with PCP, and further evaluations revealed underlying X-linked hyper-IgM syndrome. INTERVENTIONS: He was treated with trimethoprim/sulfamethoxazole for PCP, and eventually received allogeneic hematopoietic cell transplantation for hyper-IgM syndrome. OUTCOMES: Twenty months have passed after transplantation without severe complications. LESSONS: PCP should be considered in infants presenting with severe interstitial pneumonia even in the absence of evidence of immune deficiency. Primary immune deficiency should also be suspected in infants diagnosed with PCP.


title: Inhibitory effects of Lactobacillus casei upon the adhesion of enterotoxigenic Escherichia coli K99 to the intestinal mucosa in gnotobiotic lambs

text: Abstract Observations were carried out of the interactions between Lactobacillus casei 294/89 and enterotoxigenic Escherichia coli CCM 612 (O101:K99) in vivo. In gnotobiotic lambs, inoculation with enterotoxigenic E. coli (ETEC) resulted in diarrhea with a typical clinical picture and patho-anatomical findings. E. coli adhered to the mucosa of the digestive tract at counts amounting to 105 per cm2. In these lambs, disturbances of intestinal biochemical processes became evident; proteolytic enzyme activity was significantly reduced. Preventive administration of Lactobacillus casei inhibited the negative effects of ETEC in gnotobiotic lambs, minimized the clinical signs to those of a very moderate diarrhea in the first 12 h after inoculation and significantly reduced the patho-anatomical findings. Enterotoxigenic E. coli counts decreased by 99.1 and 76% on days 2 and 4 after inoculation respectively, and amounted to 103 per cm2. The inhibitory effects of L. casei against E. coli were most obvious in the jejunum and ileum. The numbers of adhering E. coli increased from the duodenum with the length of the gut. ETEC counts in the digestive tract of lambs that had been preventively treated with L. casei amounted to 107 ml−1. It can be assumed that, in addition to competitive exclusion, the inhibitory effect of L. casei upon ETEC adherence was also mediated by a Lactobacillus-produced substance that inhibited E. coli adhesion to the gut mucosa.


A Call to Arms, Not to Disarm: The Importance of Psychiatric Care in the Acute Medical Setting During the COVID 19 Pandemic


De-isolation of COVID- positive haemodialysis patients in the outpatient setting: a single centre experience


title: Breastfeeding during the COVID-19 pandemic: suggestions on behalf of Woman Study Group of AMD

text: Abstract SARS-Cov2 infection has recently spread to Italy with important consequences on pregnancy management, mother and child health and mother-child contact. Breastfeeding improves the health of mother and child and reduces risk of neonatal infection with other pathogens that are likely to cause serious illness. To date no evidence confirmed COVID-19 vertical transmission from infected pregnant mother to their fetus. However it is well known that an infected mother can transmit the COVID-19 virus through respiratory droplets during breastfeeding or intimate contact. Thus, the mothers with known or suspected COVID-19 should adhere to standard and contact precautions during breastfeeding. Woman Study Group of AMD, after reviewing current knowledge about COVID-19 vertical transmission and the compatibility of breastfeeding in COVID-19 mother, the available recommendations from Health Care Organizations and main experts opinions, issued the following suggestions on breastfeeding during the COVID-19 pandemic, addressed both to mothers with and without diabetes It should be considered that following suggestions may change in the future when more evidence is acquired regarding SARS-Cov2 infection.


title: Bioinformatics and Molecular Analysis of the Evolutionary Relationship between Bovine Rhinitis A Viruses and Foot-And-Mouth Disease Virus

text: Bovine rhinitis viruses (BRVs) cause mild respiratory disease of cattle. In this study, a near full-length genome sequence of a virus named RS3X (formerly classified as bovine rhinovirus type 1), isolated from infected cattle from the UK in the 1960s, was obtained and analyzed. Compared to other closely related Aphthoviruses, major differences were detected in the leader protease (L(pro)), P1, 2B, and 3A proteins. Phylogenetic analysis revealed that RS3X was a member of the species bovine rhinitis A virus (BRAV). Using different codon-based and branch-site selection models for Aphthoviruses, including BRAV RS3X and foot-and-mouth disease virus, we observed no clear evidence for genomic regions undergoing positive selection. However, within each of the BRV species, multiple sites under positive selection were detected. The results also suggest that the probability (determined by Recombination Detection Program) for recombination events between BRVs and other Aphthoviruses, including foot-and-mouth disease virus was not significant. In contrast, within BRVs, the probability of recombination increases. The data reported here provide genetic information to assist in the identification of diagnostic signatures and research tools for BRAV.


title: Letter to the Editor in relation to Bistrian BR. Parenteral fish oil emulsions in critically ill COVID‐19 emulsions [published online ahead of print, 2020 May 8]. JPEN J Parenter Enteral Nutr. 2020;10.1002/jpen.1871

text: In this letter we discuss the proposition of Bristian BR (2020) to use the intravenous administration of fish oil emulsions in critically ill COVID‐19. We consider that immune modulatory properties of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, rapidly provided in high amounts by fish oil emulsion, may be important to change the course of COVID‐19's death pathway. Prescriptions should be based on body weight (e.g. 0.2 g pure FOLE/kg body weight/day) and also should consider combining the parenteral administration of fish oil emulsion to low oral aspirin intake, in order to trigger resolvin synthesis from EPA and DHA. This article is protected by copyright. All rights reserved


title: Progress in the development of virus-like particle vaccines against respiratory viruses

text: Introduction: Influenza virus, human respiratory syncytial virus (RSV), and human metapneumovirus (HMPV) are important human respiratory pathogens. Recombinant virus-like particle (VLP) vaccines are suggested to be potential promising platforms to protect against these respiratory viruses. This review updates important progress in the development of VLP vaccines against respiratory viruses. Areas Covered: This review summarizes progress in developing VLP and nanoparticle-based vaccines against influenza virus, RSV, and HMPV. The PubMed was mainly used to search for important research articles published since 2010 although earlier key articles were also referenced. The research area covered includes VLP and nanoparticle platform vaccines against seasonal, pandemic, and avian influenza viruses as well as RSV and HMPV respiratory viruses. The production methods, immunogenic properties, and vaccine efficacy of respiratory VLP vaccines in preclinical animal models and clinical studies were reviewed in this article. Expert opinion: Previous and current preclinical and clinical studies suggest that recombinant VLP and nanoparticle vaccines are expected to be developed as promising alternative platforms against respiratory viruses in future. Therefore, continued research efforts are warranted.


title: Porcine epidemic diarrhea virus through p53-dependent pathway causes cell cycle arrest in the G0/G1 phase

text: Abstract Porcine epidemic diarrhea virus (PEDV), an enteropathogenic Alphacoronavirus, has caused enormous economic losses in the swine industry. p53 protein exists in a wide variety of animal cells, which is involved in cell cycle regulation, apoptosis, cell differentiation and other biological functions. In this study, we investigated the effects of PEDV infection on the cell cycle of Vero cells and p53 activation. The results demonstrated that PEDV infection induces cell cycle arrest at G0/G1 phase in Vero cells, while UV-inactivated PEDV does not cause cell cycle arrest. PEDV infection up-regulates the levels of p21, cdc2, cdk2, cdk4, Cyclin A protein and down-regulates Cyclin E protein. Further research results showed that inhibition of p53 signaling pathway can reverse the cell cycle arrest in G0/G1 phase induced by PEDV infection and cancel out the up-regulation of p21 and corresponding Cyclin/cdk mentioned above. In addition, PEDV infection of the cells synchronized in various stages of cell cycle showed that viral subgenomic RNA and virus titer were higher in the cells released from G0/G1 phase synchronized cells than that in the cells released from the G1/S phase and G2/M phase synchronized or asynchronous cells after 18 h p.i.. This is the first report to demonstrate that the p53-dependent pathway plays an important role in PEDV induced cell cycle arrest and beneficially contributes to viral infection.


title: Perceptions of emergency nurses during the human swine influenza outbreak: A qualitative study

text: Abstract Introduction The primary aim of this study was to explore the perception of Hong Kong emergency nurses regarding their work during the human swine influenza pandemic outbreak. Methods In this exploratory, qualitative study, 10 emergency nurses from a regional hospital in Hong Kong were recruited using purposive sampling. Semi-structured, face-to-face individual interviews were conducted. Qualitative content analysis was utilized to analyze the transcripts. Results The three following categories emerged from the interview data: concerns about health, comments on the administration, and attitudes of professionalism. Nurses viewed the human swine influenza as a threat to their personal and families’ health. However, nurses perceived that the severity of the disease was exaggerated by the public. Improvements in planning the circulation of information, allocation of manpower, and utilization of personal protective equipment were indicated. The emergency nurses demonstrated a sense of commitment and professional morale in promoting a high quality of nursing care. Discussion Various factors affecting the perceptions of emergency nurses toward their professional duties during the influenza pandemic were identified. By understanding these perceptions, appropriate planning, policies, and guidelines can be formulated to meet the healthcare needs of patients during future pandemic outbreaks.


title: Morphological and biological properties of a new coronavirus associated with diarrhea in infant mice

text: Biological and morphological properties of a virus, isolated from the intestine of infant mice with clinical signs of diarrhea and designated as diarrhea virus of infant mice (DVIM), were examined. The first infective virus was detected on the cells 4 hours post infection, followed by rapid release of the virus into the culture fluids. Virus-induced syncytia in BALB/c-3T3 cell cultures caused hemadsorption at 4° C and viral antigens were shown to be located in the cytoplasm of the syncytia by immunofluorescent techniques. By scanning electron-microscopy, budding virus-like particles were detected on the surface of virus-induced syncytia. Morphologically the virus was shown to be enveloped and approximately 100 nm in diameter. Two types of projections were demonstrated, one type of projection was club-shaped, 20 nm in length and the other type was small, granular, 5 nm in length. The latter type of projection might be the basal part of the clubshaped type and related to the hemagglutinating activity.


title: Aminopeptidase N (CD13) functionally interacts with FcγRs in human monocytes

text: Aminopeptidase N (E.C. 3.4.11.2) is a membrane‐bound metalloproteinase expressed in many tissues. Although its cytoplasmic portion has only eight amino acids, cross‐linking of CD13 by monoclonal antibodies (mAb) has been shown to trigger intracellular signaling. A functional association between CD13 and receptors for immunoglobulin G (FcγRs) has been proposed. In this work, we evaluated possible functional interactions between CD13 and FcγRs in human peripheral blood monocytes and in U‐937 promonocytic cells. Our results show that during FcγR‐mediated phagocytosis, CD13 redistributes to the phagocytic cup and is internalized into the phagosomes. Moreover, modified erythrocytes that interact with the monocytic cell membrane through FcγRI and CD13 are ingested simultaneously, more efficiently than those that interact through the FcγRI only. Also, co‐cross‐linking of CD13 with FcγRI by specific mAbs increases the level and duration of Syk phosphorylation induced by FcγRI cross‐linking. Finally, FcγRI and CD13 colocalize in zones of cellular polarization and coredistribute after aggregation of either of them. These results demonstrate that CD13 and FcγRI can functionally interact on the monocytic cell membrane and suggest that CD13 may act as a signal regulator of FcγR function.


title: Moyens de prévention du risque d’exposition au SARS-Cov-2: Enquête auprès des pharmaciens d’une ville de l’Est Algérien

text: Résumé Contexte. — La pandémie Covid-19 est en progression dans le monde faisant à ce jour plus de 7,5 millions de personnes contaminées et plus de 400000 morts. Le taux de mortalité en Algérie est le plus haut en Afrique, la wilaya de Sétif, enregistrant actuellement une augmentation du nombre de malades, remonte à la 3ème place à l'échelle nationale. Objectif. — Évaluer es mesures de sécurité et de protection mises en œuvre dans les pharmacies en vue de limiter la propagation du virus parmi le personnel et les clients. Méthode. — Cette enquête a concerné 63 pharmacies de la ville de Sétif (Nord Est d’Algérie), sous confinement partiel. Les informations ont été recueillies à l’aide d’un questionnaire auprès des pharmaciens ou par constatation directe. Résultats. — La proportion de femmes touchées par le congé exceptionnel est de 24,8%, et celle des hommes de 6,8%. Une barrière maintenant une distance de sécurité entre pharmaciens et clients est présente dans 95,2% des pharmacies. Cette distance est respectée dans 38,1% des cas entre les pharmaciens, et dans 76,8% des cas entre les clients. Dans 50,8% des cas, le masque est porté par la majorité des employés, mais plus rarement par les clients. Des réunions en présentiel sont tenues dans près de la moitié des cas. Les moyens nécessaires pour une bonne hygiène des mains sont disponibles pour tout le personnel ; les clients n’ont accès que rarement (6,3%) à la solution hydroalcoolique. Dans la majorité des cas la désinfection se déroule fréquemment. Disscussion. — Plusieurs mesures à but de limiter la propagation du virus ont été mises en œuvre dans les pharmacies. Néanmoins, le port de masques de protection devrait être généralisé pour le personnel et les clients, de même que l’affichage des consignes de sécurité et la mise à la disposition des clients de solution hydroalcoolique. Summary Context. — The Covid-19 pandemic is on the rise worldwide, causing more than 7.5 million people infected and more than 400,000 dead to date. The mortality rate in Algeria is the highest in Africa, the wilaya of Sétif, currently registering an increase in the number of patients, goes back to 3rd place nationwide. Method. — This investigation involved 63 pharmacies in the city of Sétif (northeast of Algeria), under partial confinement. The information was collected using a questionnaire from pharmacists or by direct observation. Results. — The proportion of women that were on exceptional leave is 24.8%, and that of men 6.8%. A barrier maintaining a safe distance between pharmacists and customers is present in 95.2% of pharmacies. This distance is respected in 38.1% of cases between pharmacists, and in 76.8% of cases between clients. In 50.8% of cases, the mask is worn by the majority of employees, but more rarely by customers. Physical meetings are held in almost half of the cases. The means necessary for good hand hygiene are available to all staff; customers rarely (6.3%) have access to the alcohol-based solution. In most cases disinfection takes place frequently. Discussion. — Several measures to limit the spread of the virus have been implemented in pharmacies. However, the wearing of protective masks should be generalized for staff and customers, as well as the posting of safety instructions and the availability of hydroalcoholic solutions to customers.


title: Active learning strategies with COMBINE analysis: new tricks for an old dog

text: The COMBINE method was designed to study congeneric series of compounds including structural information of ligand–protein complexes. Although very successful, the method has not received the same level of attention than other alternatives to study Quantitative Structure Active Relationships (QSAR) mainly because lack of ways to measure the uncertainty of the predictions and the need for large datasets. Active learning, a semi-supervised learning approach that makes use of uncertainty to enhance models’ performance while reducing the size of the training sets, has been used in this work to address both problems. We propose two estimators of uncertainty: the pool of regressors and the distance to the training set. The performance of the methods has been evaluated by testing the resulting active learning workflows in 3 diverse datasets: HIV-1 protease inhibitors, Taxol-derivatives and BRD4 inhibitors. The proposed strategies were successful in 80% of the cases for the taxol-derivatives and BRD4 inhibitors, while outperformed random selection in the case of the HIV-1 protease inhibitors time-split. Our results suggest that AL-COMBINE might be an effective way of producing consistently superior QSAR models with a limited number of samples. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10822-018-0181-3) contains supplementary material, which is available to authorized users.


title: Coronavirus disease 2019 (COVID-19) and cardiovascular complications

text: Abstract The coronavirus disease 2019 (COVID-19) has become a global pandemic. It has been spread to more than 100 countries and more than 1 million patients have been confirmed. Although coronavirus causes severe respiratory infections in human, accumulating data have demonstrated cardiac complications and poor outcome in patients with coronavirus disease 2019. A large percent of patients have underlying cardiovascular disease and they are at a high risk of developing cardiac complications. We review the basics of the virus, the clinical manifestation, and the possible mechanisms of cardiac complications in patients with coronavirus disease 2019. Before the effective vaccine or medicine is available, supportive therapy and identifying patients who are at high risk of cardiac complications are important.


title: Fever and Rash: A Changing Landscape in the 21st Century

text: Although “fever and rash” is a common complaint in the pediatric emergency department, most causes are benign. Of the more severe causes, several have been greatly reduced by vaccination programs. In addition, new vaccines such as those for invasive meningococcal disease hold promise for an even brighter future. Although meningococcemia remains an important concern when evaluating a child with fever and a rash, the resurgence of measles, the emergence of invasive group A streptococcal disease and antibiotic-resistant Staphylococcus aureus, as well as the fear of agents of bioterrorism (anthrax, smallpox) have changed the landscape of fever and rash in the 21st century. The purpose of this article is not to offer a comprehensive differential of febrile exanthema, but rather to highlight some new concerns related to the evaluation of fever and rash in today's emergency department.


title: Pharmacologic Treatment of Transplant Recipients Infected With SARS-CoV-2: Considerations Regarding Therapeutic Drug Monitoring and Drug–Drug Interactions

text: COVID-19 is a novel infectious disease caused by the severe acute respiratory distress (SARS)-coronavirus-2 (SARS-CoV-2). Several therapeutic options are currently emerging but none with universal consensus or proven efficacy. Solid organ transplant recipients are perceived to be at increased risk of severe COVID-19 because of their immunosuppressed conditions due to chronic use of immunosuppressive drugs (ISDs). It is therefore likely that solid organ transplant recipients will be treated with these experimental antivirals. METHODS: This article is not intended to provide a systematic literature review on investigational treatments tested against COVID-19; rather, the authors aim to provide recommendations for therapeutic drug monitoring of ISDs in transplant recipients infected with SARS-CoV-2 based on a review of existing data in the literature. RESULTS: Management of drug–drug interactions between investigational anti-SARS-CoV-2 drugs and immunosuppressants is a complex task for the clinician. Adequate immunosuppression is necessary to prevent graft rejection while, if critically ill, the patient may benefit from pharmacotherapeutic interventions directed at limiting SARS-CoV-2 viral replication. Maintaining ISD concentrations within the desired therapeutic range requires a highly individualized approach that is complicated by the pandemic context and lack of hindsight. CONCLUSIONS: With this article, the authors inform the clinician about the potential interactions of experimental COVID-19 treatments with ISDs used in transplantation. Recommendations regarding therapeutic drug monitoring and dose adjustments in the context of COVID-19 are provided.


The Ups and Downs of COVID-19 Epidemics for Orthopedic Community


title: The Human Bocaviruses: A Review and Discussion of Their Role in Infection

text: Respiratory tract infections are a leading cause of morbidity and mortality worldwide. The human bocavirus (HBoV) is a newly recognized human parvovirus first reported in 2005. Since its discovery, this virus has been associated with upper and lower respiratory tract disease and gastroenteritis worldwide. This article is a comprehensive review of what is known about HBoV. It includes an evaluation of diagnostic modalities, symptoms occurring in affected patients, and a discussion as to whether HBoV is responsible for identified clinical manifestations. The article reviews the incidence and effect of coinfection and updates on related members (HBoV-2 and HBoV-3) recently reported. Understanding of respiratory viruses such as HBoV remains vitally important to the health of adult and pediatric patients.


title: International Research Networks in Viral Structural Proteomics: again, lessons from SARS

text: Emerging and re-emerging pathogens and bioterror threats require an organized and coherent response from the worldwide research community to maximize available resources and competencies with the primary goals to understand the pathogen and enable intervention. In 2001, the Structural Proteomics In Europe project prototyped the pan-viral structural genomic approach, and the SARS outbreak in 2003 accelerated the concept of structural characterization of all proteins from a viral proteome and the interaction with their host partners. Following that approach, in 2004 the center for Functional and Structural Proteomics for SARS-CoV related proteins was initiated as part of the US NIH NIAID proteomics resource centers. Across worldwide efforts in Asia, Europe and America, the international research teams working on SARS-CoV have now determined experimental structural information for 45% of the SARS-CoV proteins and 53% of all its soluble proteins. This data is fully available to the scientific community and is providing an unprecedented level of insight to this class of RNA viruses. The efforts and results by the international scientific community to the SARS outbreak are serving as an example and roadmap of a rapid response using modern research methods.


title: Physicochemical properties of SARS‐CoV‐2 for drug targeting, virus inactivation and attenuation, vaccine formulation and quality control

text: The material properties of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and its proteins are discussed. We review the viral structure, size, rigidity, lipophilicity, isoelectric point, buoyant density and centrifugation conditions, stability against pH, temperature, UV light, gamma radiation, and susceptibility to various chemical agents including solvents and detergents. Possible inactivation, downstream, and formulation conditions are given including suitable buffers and some first ideas for quality‐control methods. This information supports vaccine development and discussion with competent authorities during vaccine approval and is certainly related to drug‐targeting strategies and hygienics. Several instructive tables are given, including the pI and grand average of hydropathicity (GRAVY) of SARS‐CoV‐1 and ‐2 proteins in comparison. SARS‐CoV‐1 and SARS‐CoV‐2 are similar in many regards, so information can often be derived. Both are unusually stable, but sensitive at their lipophilic membranes. However, since seemingly small differences can have strong effects, for example, on immunologically relevant epitope settings, unevaluated knowledge transfer from SARS‐CoV‐1 to SARS‐CoV‐2 cannot be advised. Published knowledge regarding downstream processes, formulations and quality assuring methods is, as yet, limited. However, standard approaches employed for other viruses and vaccines seem to be feasible including virus inactivation, centrifugation conditions, and the use of adjuvants.


Sharing malarias


title: Metagenomics in Virology

text: Abstract Metagenomics, i.e., the sequencing and analysis of genomic information extracted directly from clinical or environmental samples, has become a fundamental tool to explore the viral world. Against the background of an extensive viral diversity revealed by metagenomics across many environments, new sequence assembly approaches that reconstruct complete genome sequences from metagenomes have recently revealed surprisingly cosmopolitan viruses in specific ecological niches. Metagenomics is also applied to clinical samples as a non-targeted diagnostic and surveillance tool. By enabling the study of these uncultivated viruses, metagenomics provides invaluable insights into the virus-host interactions, epidemiology, ecology, and evolution of viruses across all ecosystems.


Addressing Hearing loss to Improve Communication during COVID‐19 Pandemic


title: Evaluation of the Inhibitory Activities of COVID‐19 of Melaleuca cajuputi Oil Using Docking Simulation

text: GC‐MS was applied to identify 24 main substances in Melaleuca cajuputi essential oil (TA) extracted from fresh cajeput leaves through steam distilling. The inhibitory capability of active compounds in the TA from Thua Thien Hue, Vietnam over the Angiotensin‐Converting Enzyme 2 (ACE2) protein in human body ‐ the host receptor for SARS‐CoV‐2 and the main protease (PDB6LU7) of the SARS‐CoV‐2 using docking simulation has been studied herein. The results indicate that the ACE2 and PDB6LU7 proteins were strongly inhibited by 10 out of 24 compounds accounting for 70.9% in the TA. The most powerful anticoronavirus activity is expressed in the order: Terpineol (TA2) ≈ Guaiol (TA5) ≈ Linalool (TA19) > Cineol (TA1) > β‐Selinenol (TA3) > α‐Eudesmol (TA4) > γ‐Eudesmol (TA7). Interestingly, the synergistic interactions of these 10 substances of the TA exhibit excellent inhibition into the ACE2 and PDB6LU7 proteins. The docking results orient that the natural Melaleuca cajuputi essential oil is considered as a valuable resource for preventing SARS‐CoV‐2 invasion into human body.


title: Evolution of infectious bronchitis virus in China over the past two decades

text: Avian infectious bronchitis is a highly contagious disease caused by infectious bronchitis virus (IBV) that affects poultry production worldwide. The absence of vaccine cross-protection and the frequent emergence of new variant strains complicate control of IBV. Here we designed a study to measure the evolution dynamics of IBV strains in China. One hundered and seven complete sequences and 1022 S1-region sequences of Chinese IBVs isolated between 1994 and 2014 were analysed by using MEGA 5.0 software and the Bayesian analysis sampling trees (BEAST) method, and selection pressure on different proteins was assessed. The phylogenetic dissimilarity of different gene trees in the data set indicated possible recombination. Fourteen isolates were identified as recombinants, possibly generated from vaccines of the Massachusetts serotype in recombination with circulating viruses. The earliest IBV in China was found to have existed in the early 1900s, and continues to evolve at a rate of approximately 10(−) (5) substitutions per site per year. We found that purifying selection was the main evolutionary pressure in the protein-coding regions, while the S1 gene bears the greatest positive selection pressure. The proportion of QX-like genotype strains increased over time. These results indicate that the genotypes of Chinese IBVs have undergone a remarkable transition during the past 20 years.


title: The pandemic of COVID-19 and its implications for the purity and authenticity of alcohol-based hand sanitizers: The health risks associated with falsified sanitizers and recommendations for regulatory and public health bodies

text: Abstract With the beginning of the pandemic of COVID-19 throughout the world, the demand and consumption of hand sanitizers has increased, which had led to a sharp crunch in these products at all levels. This shortage has led to an increase in the prevalence of falsified alcohol-based hand sanitizers, including the illegal addition of methanol to hand sanitizers and the production of hand sanitizers with an alcohol concentration of less than 60%. These findings indicate that regulatory and public health bodies should take an active role in ensuring the safety and quality of antimicrobial products such as alcohol-based hand sanitizers at every stage of the products’ lifecycle, including distribution, manufacture and import.


Mystery virus slow to yield its identity as patient numbers rise


title: Opposite Roles of RNase and Kinase Activities of Inositol-Requiring Enzyme 1 (IRE1) on HSV-1 Replication

text: In response to the endoplasmic reticulum (ER) stress induced by herpes simplex virus type 1 (HSV-1) infection, host cells activate the unfolded protein response (UPR) to reduce the protein-folding burden in the ER. The regulation of UPR upon HSV-1 infection is complex, and the downstream effectors can be detrimental to viral replication. Therefore, HSV-1 copes with the UPR to create a beneficial environment for its replication. UPR has three branches, including protein kinase RNA (PKR)-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activated transcription factor 6 (ATF6). IRE1α is the most conserved branch of UPR which has both RNase and kinase activities. Previous studies have shown that IRE1α RNase activity was inactivated during HSV-1 infection. However, the effect of the two activities of IRE1α on HSV-1 replication remains unknown. Results in this study showed that IRE1α expression was up-regulated during HSV-1 infection. We found that in HEC-1-A cells, increasing RNase activity, or inhibiting kinase activity of IRE1α led to viral suppression, indicating that the kinase activity of IRE1α was beneficial, while the RNase activity was detrimental to viral replication. Further evidence showed that the kinase activity of IRE1α leads to the activation of the JNK (c-Jun N-terminal kinases) pathway, which enhances viral replication. Taken together, our evidence suggests that IRE1α is involved in HSV-1 replication, and its RNase and kinase activities play differential roles during viral infection.


title: Correlation between Pneumonia Severity and Pulmonary Complications in Middle East Respiratory Syndrome

text: This nationwide, prospective cohort study evaluated pulmonary function and radiological sequelae according to infection severity in 73 survivors from the 2015 Middle East respiratory syndrome (MERS) outbreak in Korea. Patients with severe pneumonia in MERS-coronavirus infection had more impaired pulmonary function than those with no or mild pneumonia at the 1-year follow-up, which was compatible with the radiological sequelae. Severe pneumonia significantly impairs pulmonary function and makes long radiological sequelae in MERS.


title: Anatomy and Disorders of the Oral Cavity of Rat-like and Squirrel-like Rodents

text: The order Rodentia comprises more than 2000 species divided into 3 groups based on anatomic and functional differences of the masseter muscle. Myomorph and sciuromorph species have elodont incisors and anelodont cheek teeth, unlike hystrichomorph species which have full anelodont dentition. Diseases of incisors and cheek teeth of rat-like and squirrel-like rodents result in a wide variety of symptoms and clinical signs. Appropriate diagnostic testing and imaging techniques are required to obtain a definitive diagnosis, formulate a prognosis, and develop a treatment plan. A thorough review of elodontoma, odontoma, and pseudo-odontoma is provided, including treatment of pseudo-odontomas in prairie dogs.


title: UBXN1 interacts with the S1 protein of transmissible gastroenteritis coronavirus and plays a role in viral replication

text: Transmissible gastroenteritis coronavirus (TGEV) is an enteropathogenic coronavirus that causes diarrhea in pigs and is associated with high morbidity and mortality in sucking piglets. S1 is one of two protein domains in the spike (S) glycoprotein and is responsible for enteric tropism, sialic acid recognition, and host receptor binding. Although there has been extensive research on the S1 protein of TGEV, little is known about the intracellular role of TGEV-S1. In the present study, we used yeast two-hybrid screening of a cDNA library from porcine intestinal cells to identify proteins that interact with TGEV-S1. Among 120 positive clones from the library, 12 intracellular proteins were identified after sequencing and a BLAST search. These intracellular proteins are involved in protein synthesis and degradation, biological signal transduction, and negative control of signaling pathways. Using a glutathione-S-transferase (GST) pulldown assay and Co-IP, we found that UBXN1 interacts with the S1 protein. Here, we observed that TGEV infection led to increased UBXN1 expression levels during the late phase of infection in IPEC-J2 cells. Inhibition of UBXN1 in IPEC-J2 cells via siRNA interference significantly decreased the viral titer and downregulated the expression of S1. UBXN1 overexpression significantly increased the viral copy number. Additionally, we provided data suggesting that UBXN1 negatively regulates IFN-β expression after TGEV infection. Finally, our research indicated that UBXN1 plays a vital role in the process of TGEV infection, making it a candidate target for the development of a novel antiviral method.


title: Creation of a vascular surgical Hub responding to the COVID-19 emergency: the italian USL Toscana Centro model

text: Spreading of the COVID-19 pandemic in Italy forced health facilities to drastically change their organization to face the overwhelming number of infected patients needing hospitalization. The USL (Unità Sanitaria Locale) Toscana Centro adopted a protocol of reorganization of the Vascular Surgery Unit during the first difficult weeks of the epidemic, consisting in the creation of a Vascular Hub for urgent cases with a profound reorganization of activities, wards, surgical operators, operating blocks and ICU beds. The aim of this paper is to share the protocol with all the vascular community, hoping to help other institutions to face the emergency during the hard weeks coming.


title: AGE IS ASSOCIATED WITH INCREASED EXPRESSION OF PATTERN RECOGNITION RECEPTOR GENES AND ACE2, THE RECEPTOR FOR SARS-COV-2: IMPLICATIONS FOR THE EPIDEMIOLOGY OF COVID-19 DISEASE

text: Older aged adults and those with pre-existing conditions are at highest risk for severe COVID-19 associated outcomes. Using a large dataset of genome-wide RNA-seq profiles derived from human dermal fibroblasts (GSE113957) we investigated whether age affects the expression of pattern recognition receptor (PRR) genes and ACE2, the receptor for SARS-CoV-2. Older age was associated with increased expression of PRR genes, ACE2 and four genes that encode proteins that have been shown to interact with SAR2-CoV-2 proteins. Assessment of PRR expression might provide a strategy for stratifying the risk of severe COVID-19 disease at both the individual and population levels.


title: Core protein-mediated 5′–3′ annealing of the West Nile virus genomic RNA in vitro

text: Abstract Genome cyclization through conserved RNA sequences located in the 5′ and 3′ terminal regions of flavivirus genomic RNA is essential for virus replication. Although the role of various cis-acting RNA elements in panhandle formation is well characterized, almost nothing is known about the potential contribution of protein cofactors to viral RNA cyclization. Proteins with nucleic acid chaperone activities are encoded by many viruses (e.g., retroviruses, coronaviruses) to facilitate RNA structural rearrangements and RNA–RNA interactions during the viral replicative cycle. Since the core protein of flaviviruses is also endowed with potent RNA chaperone activities, we decided to examine the effect of West Nile virus (WNV) core on 5′–3′ genomic RNA annealing in vitro. Core protein binding resulted in a dramatic, dose-dependent increase in 5′–3′ complex formation. Mutations introduced in either the UAR (upstream AUG region) or CS (conserved sequence) elements of the viral RNA diminished core protein-dependent annealing, while compensatory mutations restored the 5′–3′ RNA interaction. The activity responsible for stimulating RNA annealing was mapped to the C-terminal RNA-binding region of WNV core protein. These results indicate that core protein – besides its function in viral particle formation – might be involved in the regulation of flavivirus genomic RNA cyclization, and thus virus replication.


title: SARS-CoV-2: minireview and review of first case in Foshan, China

text: The first case of #COVID19 in Foshan provides a reference for the treatment of severe #SARSCoV2 pneumonia https://bit.ly/3eD81qj


title: Potential benefits and limitations of various strategies to mitigate the impact of an influenza pandemic

text: Abstract The recent avian influenza outbreaks underscore the importance of improving our preparedness for an impending influenza pandemic. Various strategies, including pharmaceutical interventions (such as vaccines and antivirals) and nonpharmaceutical interventions (such as quarantine, isolation, and social distancing) may be implemented to mitigate the impact of a pandemic. It is necessary to understand the potential benefits and limitations of each strategy to determine the most appropriate strategies to be implemented. In this article, each strategy is reviewed to define its potential benefits and limitations during a pandemic. Vaccines are probably the most effective measure to reduce morbidity and mortality. However, vaccines are not likely to be available at an early stage of a pandemic. The supply of vaccines is most likely to be insufficient due to limited worldwide production capacity. Antivirals, particularly neuraminidase inhibitors, are expected to be effective against a pandemic influenza strain and are the only available pharmaceutical intervention until enough vaccines are produced. Shortage of supply and high cost is still a major limiting factor in amassing large stockpiles of neuraminidase inhibitors. The possible emergence of resistant strains should also be considered. Nonpharmaceutical interventions can be effective in preventing the spread of the virus under certain conditions. The effectiveness of nonpharmaceutical interventions depends on how influenza viruses are transmitted. There are still significant gaps in the scientific evidence of the way in which influenza viruses are transmitted. Further studies should be conducted to define the basic transmission patterns of influenza viruses.


title: Detection of Respiratory Viruses in Deceased Persons, Spain, 2017

text: During the 2016–17 influenza season in Spain, we tested specimens from 57 elderly deceased persons for respiratory viruses. Influenza viruses were detected in 18% of the specimens and any respiratory virus in 47%. Only 7% of participants had received a diagnosis of infection with the detected virus before death.


title: Long-term shedding of Canine alphaherpesvirus 1 in naturally infected newborn pups

text: Abstract The long-term shedding of Canine alphaherpesvirus 1 (CaHV-1) by neonatal pups with natural infection is reported. The pups belonged to a litter of 11 pointers of a breeding kennel in southern Italy, 9 of which developed a fatal form of systemic infection, as resulted by the detection of CaHV-1 in internal organs (kidney, liver, lung and brain) of one of this dogs and in the vaginal swab of their mother. The two remaining animals displayed a milder form of disease, with one pup showing ocular involvement, and underwent a progressive recovery. These pups were monitored from 11 to 36 days of age, showing a long-term shedding of the virus through the nasal and ocular secretions and the faeces. CaHV-1 shedding, as assessed by means of a specific and sensitive real-time PCR assay, occurred mainly through the nasal secretions, although the pup displaying ocular disease shed the virus at high titres and for a long period even in the ocular secretions.


title: Community perspectives on the benefits and risks of technologically enhanced communicable disease surveillance systems: a report on four community juries

text: BACKGROUND: Outbreaks of infectious disease cause serious and costly health and social problems. Two new technologies – pathogen whole genome sequencing (WGS) and Big Data analytics – promise to improve our capacity to detect and control outbreaks earlier, saving lives and resources. However, routinely using these technologies to capture more detailed and specific personal information could be perceived as intrusive and a threat to privacy. METHOD: making pathogen WGS and linked administrative data available for public health research; using this information in concert with data linkage and machine learning to enhance communicable disease surveillance systems. Fifty participants of diverse backgrounds, mixed genders and ages were recruited by random-digit-dialling and topic-blinded social-media advertising. Each jury was presented with balanced factual evidence supporting different expert perspectives on the potential benefits and costs of technologically enhanced public health research and communicable disease surveillance and given the opportunity to question experts. RESULTS: Almost all jurors supported data linkage and WGS on routinely collected patient isolates for the purposes of public health research, provided standard de-identification practices were applied. However, allowing this information to be operationalised as a syndromic surveillance system was highly contentious with three juries voting in favour, and one against by narrow margins. For those in favour, support depended on several conditions related to system oversight and security being met. Those against were concerned about loss of privacy and did not trust Australian governments to run secure and effective systems. CONCLUSIONS: Participants across all four events strongly supported the introduction of data linkage and pathogenomics to public health research under current research governance structures. Combining pathogen WGS with event-based data surveillance systems, however, is likely to be controversial because of a lack of public trust, even when the potential public health benefits are clear. Any suggestion of private sector involvement or commercialisation of WGS or surveillance data was unanimously rejected.


title: COVID-19: the First Documented Coronavirus Pandemic in History

text: Abstract The novel human coronavirus disease COVID-19 has become the fifth documented pandemic since the 1918 flu pandemic. COVID-19 was first reported in Wuhan, China, and subsequently spread worldwide. The coronavirus was officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses based on phylogenetic analysis. SARS-CoV-2 is believed to be a spillover of an animal coronavirus and later adapted the ability of human-to-human transmission. Because the virus is highly contagious, it rapidly spreads and continuously evolves in the human population. In this review article, we discuss the basic properties, potential origin, and evolution of the novel human coronavirus. These factors may be critical for studies of pathogenicity, antiviral designs, and vaccine development against the virus.


title: Three-dimensional printing in the fight against novel virus COVID-19: Technology helping society during an infectious disease pandemic

text: Indeed, the scientific milestones set by the ever-emerging three-dimensional printing (3DP) technologies are tremendous. Till now, the innovative 3DP technologies have benefitted the aerospace, automobile, textile, pharmaceutical, and biomedical sectors by developing pre-requisite designed and customized performance standards of the end-user products. As the scientific world, at this moment, is expediting efforts to fight against the highly damaging novel coronavirus (COVID-19) pandemic, the 3DP technologies are facilitating creative solutions in terms of personal protective equipment (PPE), medical equipment (such as ventilators and other respiratory devices), and other health and welfare tools to aid the personal hygiene as well as safe environment for humans by restricting the communication of risks. Various sources (including journal articles, news articles, white papers of the government and other non-profit organizations, commercial enterprises, as well as academic institutions have been reviewed for the collection of the information relevant to COVID-19 and 3DP. This communication presents the recent applications of the 3DP technologies aiding in developing innovative products designed to save the lives of millions of people around the world. Moreover, the potential of 3DP technologies in developing test swabs and controlled medicines has been highlighted. The literature reviewed in the present study indicated that the fused filament fabrication (FFF) is one of the most preferred technologies and contribute about 62% in the overall production of the protective gears developed through overall class of 3DP.


title: Rabbit Hemorrhagic Disease Virus Non-structural Protein 6 Induces Apoptosis in Rabbit Kidney Cells

text: Rabbit hemorrhagic disease (RHD) is a highly contagious disease caused by rabbit hemorrhagic disease virus (RHDV). Previous research has shown that RHDV induces apoptosis in numerous cell types, although the molecular mechanisms underlying the apoptosis induced by RHDV are not well understood. One possible factor is non-structural protein 6 (NSP6), a 3C-like protease that plays an important role in processing viral polyprotein precursors into mature non-structural proteins. To fully establish a role for NSP6, the present study examined the effects of ectopic expression of the protein in rabbit (RK13) and human (HeLa and HepG2) cells. We found that NSP6 suppressed cell viability and promoted apoptosis in all three cell types in a dose-dependent manner. We also identified increased caspase-3, -8, and -9 activities in RK13 cell, and an increased Bax to Bcl2 mRNA ratio. Mechanistically, the ability of NSP6 to induce apoptosis was impaired by mutation of the catalytic His27 residue. Our study has shown that RHDV NSP6 can induce apoptosis in host cells and is likely an important contributor to RHDV-induced apoptosis and pathogenesis.


title: Epstein-barr virus induced cellular changes in nasal mucosa

text: A 21-year-old man presented with nasal obstruction of the right nasal fossa of 1 year duration. Nasal endoscopy revealed in the right inferior turbinate head a rounded neoplasm about 1 cm in diameter. Cytologic study of a nasal scraping specimen disclosed numerous clusters containing columnar cells with cytomegaly, prominent multinucleation, markedly sparse shortened cilia; the cytoplasm contained an acidophil area and a small round area that stained poorly; cells with a large intracytoplasmic vacuole that was acidophil and PAS+. Serology tests using the nested polymer chain reaction (PCR) technique on serum, nasal and pharyngeal smears revealed an Epstein-Barr virus (EBV) infection that was confirmed at electron microscopy. The clinical and cytological features resolved 19 months after the initial evaluation. CONCLUSION: The authors advise carrying out clinical (endoscopy, serology, etc.) evaluation of all endonasal neoplasms and to routinely perform cytological study on nasal scraping specimens. When samples test positive for EBV, nasal and nasopharyngeal endoscopy should be performed regularly to detect possible evidence for nasopharyngeal carcinoma (NPC).