title: Chapter 8 Single-Stranded RNA Viruses

text: In this chapter, we describe 73 zoonotic viruses that were isolated in Northern Eurasia and that belong to the different families of viruses with a single-stranded RNA (ssRNA) genome. The family includes viruses with a segmented negative-sense ssRNA genome (families Bunyaviridae and Orthomyxoviridae) and viruses with a positive-sense ssRNA genome (families Togaviridae and Flaviviridae). Among them are viruses associated with sporadic cases or outbreaks of human disease, such as hemorrhagic fever with renal syndrome (viruses of the genus Hantavirus), Crimean–Congo hemorrhagic fever (CCHFV, Nairovirus), California encephalitis (INKV, TAHV, and KHATV; Orthobunyavirus), sandfly fever (SFCV and SFNV, Phlebovirus), Tick-borne encephalitis (TBEV, Flavivirus), Omsk hemorrhagic fever (OHFV, Flavivirus), West Nile fever (WNV, Flavivirus), Sindbis fever (SINV, Alphavirus) Chikungunya fever (CHIKV, Alphavirus) and others. Other viruses described in the chapter can cause epizootics in wild or domestic animals: Geta virus (GETV, Alphavirus), Influenza A virus (Influenzavirus A), Bhanja virus (BHAV, Phlebovirus) and more. The chapter also discusses both ecological peculiarities that promote the circulation of these viruses in natural foci and factors influencing the occurrence of epidemic and epizootic outbreaks


COVID-19 reveals influence of physical activity on symptom severity in hereditary spastic paraplegia


title: Induction of autophagy enhances porcine reproductive and respiratory syndrome virus replication

text: Abstract Autophagy is an evolutionarily conserved lysosome-dependent degradation pathway that acts in the maintenance of cellular homeostasis and plays important functions in viral replication and pathogenesis. In this study, we investigated the role of autophagy in the replication of porcine reproductive and respiratory syndrome virus (PRRSV), an agent that has caused devastating losses in the international swine industry since the late 1980s. Using protein quantification and microscopy, we observed that PRRSV infection results in LC3-I/II conversion, an increased accumulation of punctate GFP-LC3-expressing cells, and a higher number of autophagosome-like double-membrane vesicles in the cytoplasm of host cells. Inhibition of autophagy using 3-methyladenine (3-MA) or small interfering RNAs targeting ATG7 and Beclin-1 led to a significant reduction in PRRSV titers and protein expression. Conversely, induction of autophagy by rapamycin resulted in increased viral replication. These results demonstrate that PRRSV infection induces autophagy which, in turn, enhances viral replication efficiency.


Editorial overview: Emerging viruses


title: Optimizing Viral Discovery in Bats

text: Viral discovery studies in bats have increased dramatically over the past decade, yet a rigorous synthesis of the published data is lacking. We extract and analyze data from 93 studies published between 2007–2013 to examine factors that increase success of viral discovery in bats, and specific trends and patterns of infection across host taxa and viral families. Over the study period, 248 novel viruses from 24 viral families have been described. Using generalized linear models, at a study level we show the number of host species and viral families tested best explained number of viruses detected. We demonstrate that prevalence varies significantly across viral family, specimen type, and host taxonomy, and calculate mean PCR prevalence by viral family and specimen type across all studies. Using a logistic model, we additionally identify factors most likely to increase viral detection at an individual level for the entire dataset and by viral families with sufficient sample sizes. Our analysis highlights major taxonomic gaps in recent bat viral discovery efforts and identifies ways to improve future viral pathogen detection through the design of more efficient and targeted sample collection and screening approaches.


title: ProOmpA is stabilized for membrane translocation by either purified E. coli trigger factor or canine signal recognition particle

text: Abstract We have isolated large amounts of E. coli outer-membrane protein A precursor (proOmpA). Purified proOmpA is active in membrane assembly, and this assembly is saturable with respect to the precursor protein. A proOmpA-Sepharose matrix allows affinity isolation of trigger factor, a soluble, 63,000 dalton monomeric protein that stabilizes proOmpA in assembly competent form. Comparison of trigger factor's amino-terminal sequence with those in a computer data bank and with those encoded by sec genes, as well as groEL and heat shock gene dnaK, suggests that trigger factor is encoded by a previously undescribed gene. Trigger factor and proOmpA form a 1:1 complex that can be isolated by gel filtration. Purified canine signal recognition particle (SRP) can also stabilize proOmpA for membrane insertion. This post-ribosomal activity of SRP suggests a unifying theme in protein translocation mechanisms.


Vaccinology in the twenty-first century


title: Telemedicine in the era of COVID-19: a neurosurgical perspective

text: Abstract Despite the substantial growth of telemedicine and the evidence of its advantages, utilization of telemedicine in neurosurgery has been limited. Barriers have included medicolegal issues surrounding provider reimbursement, interstate licensure, and malpractice liability as well as technological challenges. Recently, the COVID-19 pandemic has limited typical evaluation of patients with neurological issues and resulted in a surge in demand for virtual medical visits. Meanwhile, federal and state governments took action to facilitate the rapid implementation of telehealth programs, placing a temporary lift on medicolegal barriers that had previously limited its expansion. This created a unique opportunity for widespread telehealth use to meet the surge in demand for remote medical care. After initial hurdles and challenges, our experience with telemedicine in neurosurgery at Penn Medicine has been overall positive from both the provider and the patients’ perspective. One of the unique challenges we face is guiding patients to appropriately set up devices in a way that enables an effective neuro exam. However, we argue that an accurate and comprehensive neurologic exam can be conducted through a telemedicine platform, despite minor weaknesses inherent to absence of physical presence. Additionally, certain neurosurgical visits such as post-operative checks, vascular pathology, and brain tumors inherently lend themselves to easier evaluation through telehealth visits. In the era of COVID-19 and beyond, telemedicine remains a promising and effective approach to continue neurologic patient care.


title: Intranasal immunization with Mycobacterium tuberculosis Rv3615c induces sustained adaptive CD4(+) T‐cell and antibody responses in the respiratory tract

text: Sustained adaptive immunity to pathogens provides effective protection against infections, and effector cells located at the site of infection ensure rapid response to the challenge. Both are essential for the success of vaccine development. To explore new vaccination approach against Mycobacterium tuberculosis (M.tb) infection, we have shown that Rv3615c, identified as ESX‐1 substrate protein C of M.tb but not expressed in BCG, induced a dominant Th1‐type response of CD4(+) T cells from patients with tuberculosis pleurisy, which suggests a potential candidate for vaccine development. But subcutaneous immunization with Rv3615c induced modest T‐cell responses systemically, and showed suboptimal protection against virulent M.tb challenge at the site of infection. Here, we use a mouse model to demonstrate that intranasal immunization with Rv3615c induces sustained capability of adaptive CD4(+) T‐ and B‐cell responses in lung parenchyma and airway. Rv3615c contains a dominant epitope of mouse CD4(+) T cells, Rv3615c(41‐50), and elicits CD4(+) T‐cell response with an effector–memory phenotype and multi‐Th1‐type cytokine coexpressions. Since T cells resident at mucosal tissue are potent at control of infection at early stage, our data show that intranasal immunization with Rv3615c promotes a sustained regional immunity to M.tb, and suggests a potency in control of M.tb infection. Our study warranties a further investigation of Rv3615c as a candidate for development of effective vaccination against M.tb infection.


Sleep in University Students Prior to and During COVID-19 Stay-at-Home Orders


title: The index case of SARS-CoV-2 in Scotland

text: Summary Since its identification in December 2019, SARS-CoV-2 has infected 125,048 persons globally with cases identified in 118 countries across all continents. We report on the Scottish index case of SARS-CoV-2 infection, the virus causing COVID-19.


Suicide in the Time of COVID‐19: A Perfect Storm


title: Porcine IFITM1 is a host restriction factor that inhibits pseudorabies virus infection

text: Abstract Interferon-inducible transmembrane proteins (IFITMs) restrict infection by several viruses, such as influenza A virus, West Nile virus and dengue virus. It has not been determined whether porcine IFITMs (pIFITMs) inhibit infection by pseudorabies virus (PRV), an enveloped, double-stranded DNA virus, which is the etiological agent of Aujeszky’s disease in pigs. Here, we report that PRV infection elicited pIFITM1 expression in PK15 porcine kidney epithelial cells and 3D4/21 alveolar macrophages. pIFITM2 and pIFITM3 expression was only elevated in PK15 cells during PRV infection. Depletion of pIFITM1 using RNA interference, either in PK15 or in 3D4/21 cells, enhanced PRV infection while overexpression of pIFITM1 had the opposite effect. Knockdown of pIFITM2 and pIFITM3 did not influence PRV infection, suggesting that pIFITM2 and pIFITM3 are independent of PRV infection. PRV-induced pIFITM1 expression was dependent on the cGAS/STING/TBK1/IRF3 innate immune pathway and interferon-alpha receptor-1, suggesting that pIFITM1 is up-regulated by the type I interferon signaling pathway. The anti-PRV role of pIFITM1 was inhibited upon PRV entry. Our data demonstrate that pIFITM1 is a host restriction factor that inhibits PRV entry that may shed light on a strategy for prevention of PRV infection.


RNAi therapeutics: Can siRNAs conquer SARS?


title: Design and synthesis of novel chloramphenicol amine derivatives as potent aminopeptidase N (APN/CD13) inhibitors

text: Abstract Herein we report a series of novel chloramphenicol amine derivatives as aminopeptidase N (APN)/CD13 inhibitors. All compounds were synthesized starting from commercially available (1S,2S)-2-amino-1-(4-nitrophenyl) propane-1,3-diol. The preliminary biological screening showed that some compounds exhibited potent inhibitory activity against APN. It should be noted that one compound, 13b (IC50 =7.1μM), possess similar APN inhibitory activity compared with Bestatin (IC50 =3.0μM).


title: The sensitivity of respiratory tract specimens for the detection of SARS-CoV-2: A protocol for a living systematic review and meta-analysis

text: BACKGROUND: Highly sensitive, non-invasive, and easily accessible diagnostics for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are essential for the control of the Coronavirus Disease 2019 (COVID-19) pandemic. There is a clear need to establish a gold standard diagnostic for SARS-CoV-2 infection in humans using respiratory tract specimens. METHODS: Searches will be conducted in the bibliographic databases Medline, Embase, bioRxiv, medRxiv, F1000, ChemRxiv, PeerJ Preprints, Preprints.org, Beilstein Archive, and Research Square. Relevant government documents and grey literature will be sought on the FDA’s Emergency Use Authorizations website, the ECDC’s website, and the website of the Foundation for Innovative New Diagnostics. Finally, papers categorized as diagnosis papers by the EPPI Centre’s COVID-19 living systematic map will be added to our screening process; those papers are tagged with the diagnosis topic based on human review, rather than database searches, and thus this set of papers might include ones that have not been captured by our search strategy.


title: Cutting back on pro-protein convertases: the latest approaches to pharmacological inhibition

text: The secretory pathway in cells possesses an elaborate set of endoproteolytic enzymes that carry out a crucial step in protein precursor maturation. This step is proteolytic activation by cleavage at specific pairs of basic residues. These enzymes, named pro-protein convertases (PCs), are responsible for generating bioactive peptides and activating several enzymes and growth factors that are implicated in many important physiological events. PCs have roles in several pathologies including viral infections and cancers and, thus, are promising targets for therapeutic applications. Recent structural and homology-modeling studies demonstrate more similarity than expected at the catalytic site of the seven PCs, which makes the development of selective drugs to target individual PCs frustrating. Based on this information, we review the latest strategies to inhibit PCs, which might lead to the development of specific compounds.


title: Respiratory Viruses in Laryngeal Croup of Young Children

text: Objectives To determine the viral cause of laryngeal croup by use of highly sensitive methods, and including recently recognized viruses in the analysis. Study design One hundred forty-four consecutive children with hoarse voice and inspiratory stridor attending the emergency department were enrolled. Age- and season-matched children presenting with a wheezing illness served as control subjects (n = 76). Nasopharyngeal swabs were analyzed by polymerase chain reaction for rhinovirus and enterovirus, coronavirus, respiratory syncytial virus (RSV), parainfluenza virus (PIV), influenza A and B virus, human bocavirus, human metapneumovirus, adenovirus, and Mycoplasma pneumoniae. Results Virus infection was documented in 80% of patients with croup and 71% of control subjects. Children with croup had significantly more positive test results for PIV 1 and 2 (31% vs 4% and 6% vs 0%, respectively) and significantly fewer positive test results for RSV (15% vs 28%) than wheezing children. Rhinoviruses and enteroviruses were present equally in both groups (21% vs 25%). There was no significant difference in the frequency of influenza A virus or human bocavirus. Few subjects with adenovirus or M. pneumoniae were detected. Conclusion Acute laryngeal croup is most often associated with PIV, RSV, rhinovirus, and enterovirus. Rhinovirus and enterovirus appeared equally often in croup and in wheezing illness. During late fall, they were found in 39% and 40%, respectively, of the tested samples.


title: Health Inequalities

text: Health inequalities are embedded in a complex array of social, political, and economic inequalities. Responding to health inequalities will require systematic action targeting all the underlying (“upstream”) social determinants that powerfully affect health and well‐being. Systemic inequalities are a major reason for the rise of modern populism that has deeply divided polities and infected politics, perhaps nowhere more so than in the United States. Concerted action to mitigate shocking levels of inequality could be a powerful antidote to nationalist populism. A basic yet critical start to addressing health inequalities is to recognize them, which demands improving data collection and analysis. Certainly, global indicators show vast progress in reducing poverty and extending life. Yet aggregate health data mask a deeper reality: health gains have disproportionately benefited the well‐off, leaving the poor and middle‐class behind.


title: Coxsackievirus A21, Enterovirus 68, and Acute Respiratory Tract Infection, China

text: During August 2006–April 2010, in Beijing, China, 2 rare human enterovirus serotypes, coxsackievirus A21 and enterovirus 68, were detected most frequently in human enterovirus–positive adults with acute respiratory tract infections. Thus, during some years, these 2 viruses cause a substantial proportion of enterovirus-associated adult acute respiratory tract infections.


title: Advances in the diagnosis of respiratory tract infections: role of the Luminex xTAG respiratory viral panel

text: Clinical laboratories providing an etiological diagnosis of respiratory tract infections (RTI) have increasingly relied on nucleic acid amplification tests. Polymerase chain reaction‐based methods are becoming more standardized, and several have undergone the scrutiny of regulatory agencies mandated to assess the risks and benefits of implementing pathogen‐detection assays into diagnostic algorithms. Respiratory viruses lead to both upper and lower RTI and are implicated in exacerbations of chronic pulmonary conditions. Viruses from different taxonomic families present with overlapping clinical signs and symptoms, necessitating an accurate laboratory diagnosis. The clinical utility of diagnostic algorithms incorporating tests for respiratory viruses will depend on the breadth of pathogen coverage and the time to reliable and actionable results. This review covers strategies for detecting a panel of respiratory viruses employed over the last decade that have enabled an etiological diagnosis of RTI in a cost‐effective manner.


title: Modelling of Healthcare Associated Infections: A study on the dynamics of pathogen transmission by using an individual-based approach

text: Abstract Prevention and control of Healthcare Associated Infections (HAIs) has become a high priority for most healthcare organizations. Mathematical models can provide insights into the dynamics of nosocomial infections and help to evaluate the effect of infection control measures. The model presented in this paper adopts an individual-based and stochastic approach to investigate MRSA outbreaks in a hospital ward. A computer simulation was implemented to analyze the dynamics of the system associated with the spread of the infection and to carry out studies on space and personnel management. This study suggests that a strict spatial cohorting might be ineffective, if it is not combined with personnel cohorting.


title: The role of 9-O-acetylated glycan receptor moieties in the typhoid toxin binding and intoxication

text: Typhoid toxin is an A(2)B(5) toxin secreted from Salmonella Typhi-infected cells during human infection and is suggested to contribute to typhoid disease progression and the establishment of chronic infection. To deliver the enzymatic ‘A’ subunits of the toxin to the site of action in host cells, the receptor-binding ‘B’ subunit PltB binds to the trisaccharide glycan receptor moieties terminated in N-acetylneuraminic acid (Neu5Ac) that is α2–3 or α2–6 linked to the underlying disaccharide, galactose (Gal) and N-acetylglucosamine (GlcNAc). Neu5Ac is present in both unmodified and modified forms, with 9-O-acetylated Neu5Ac being the most common modification in humans. Here we show that host cells associated with typhoid toxin-mediated clinical signs express both unmodified and 9-O-acetylated glycan receptor moieties. We found that PltB binds to 9-O-acetylated α2–3 glycan receptor moieties with a markedly increased affinity, while the binding affinity to 9-O-acetylated α2–6 glycans is only slightly higher, as compared to the affinities of PltB to the unmodified counterparts, respectively. We also present X-ray co-crystal structures of PltB bound to related glycan moieties, which supports the different effects of 9-O-acetylated α2–3 and α2–6 glycan receptor moieties on the toxin binding. Lastly, we demonstrate that the cells exclusively expressing unmodified glycan receptor moieties are less susceptible to typhoid toxin than the cells expressing 9-O-acetylated counterparts, although typhoid toxin intoxicates both cells. These results reveal a fine-tuning mechanism of a bacterial toxin that exploits specific chemical modifications of its glycan receptor moieties for virulence and provide useful insights into the development of therapeutics against typhoid fever.


title: An Escherichia coli CS31A fibrillum chimera capable of inducing memory antibodies in outbred mice following booster immunization with the entero-pathogenic coronavirus transmissible gastroenteritis virus

text: Abstract CS31A fibrillae are thin, flexible, heteropolymeric proteinaceous appendages exposed as a capsule-like material around the cell surface of certain Escherichia coli strains. Two antigenic peptides of the S spike glycoprotein (TGEV-S) amino acids (aa) 363–371 and 521–531 of the transmissible gastroenteritis virus (TGEV) were tandemly introduced in the loop-structured, variable region aa 202–218 of the major ClpG subunit protein composing the bulk of CS31A. The resulting hybrid fibrillae with a 25 aa heterologous peptide were produced at the cell surface. Using a monoclonal antibody (Mab) specific for the TGEV epitopes, purified hybrid fibrillae were analysed in Western blotting under native conditions, which showed that the two viral epitopes were recognized immunologically as an integral part of the hybrid fibrillae, and therefore that they were antigenically active. The immunogenicity of the fusion construct was evaluated with live recombinant bacteria, purified hybrid ClpG monomers, and purified chimeric CS31A polymers. Whatever the form of hybrid used as antigen, intraperitoneally immunized outbred mice elicited serum anti-TGEV peptides antibodies (Abs) with significant titres and capable of recognizing native TGEV particles, indicating that the epitopes are exposed in an immunogenic conformation in all cases. However, virus neutralization titres were only obtained after immunization with either purified polymers or monomers. Furthermore, 4 months after an ultimate immunization with 20 μg of hybrid fibrillae mice developed a strong anamnestic Ab response against the two TGEV peptides following booster inoculation with virions. We conclude that CS31A fibrillae carrying a combination of TGEV epitopes as insert can induce an immunological memory in outbred animals infected with TGEV, and therefore that hybrid CS31A fibrillae may prove efficient as components of a subunit vaccine.


title: Predictions and measurements of the stack effect on indoor airborne virus transmission in a high-rise hospital building

text: Abstract As the viral diseases such as Severe Acute Respiratory Syndrome (SARS) and Influenza A (H1N1) occur in many countries recently, the epidemic of those influenza viruses causes many human casualties. Moreover, the second infection from infected patients particularly within general hospitals frequently takes places due to improperly hospitalized and/or quarantined patients. Accordingly, it becomes a great concern to accommodate safer ventilation system in general hospital wards against such airborne transmitted viruses. It is also a recent trend that many urban general hospitals are designed and constructed as high-rises. If a virus is transmitted through uncontrolled air movement within a hospital and then infected other patients or healthy visitors, it might be impossible to control the spread of the disease. Thus research has been preceded scrutinizing stack effect on the indoor airborne virus transmission in large hospitals by conducting both the field measurement and numerical analysis according to the outdoor temperature and the releasing vertical points of the tracer gas assumed as a viral contaminant. In the field measurement of a high-rise hospital, the indoor airflow was affected by the stack effect of vertical chute of the building. The numerical simulation was verified by comparing its prediction results and the field measurement data. In result, very high possibility has witnessed that the airborne contaminant emitted from the infected patients in the lower floors could be transported to the higher floors through the airflow driven by the stack effect.


title: A Novel Synonymous Mutation of SARS-CoV-2: Is This Possible to Affect Their Antigenicity and Immunogenicity?

text: The S glycoprotein of coronaviruses is important for viral entry and pathogenesis with most variable sequences. Therefore, we analyzed the S gene sequences of SARS-CoV-2 to better understand the antigenicity and immunogenicity of this virus in this study. In phylogenetic analysis, two subtypes (SARS-CoV-2a and -b) were confirmed within SARS-CoV-2 strains. These two subtypes were divided by a novel synonymous mutation of D614G. This may play a crucial role in the evolution of SARS-CoV-2 to evade the host immune system. The region containing this mutation point was confirmed as a B-cell epitope located in the S1 domain, and SARS-CoV-2b strains exhibited severe reduced antigenic indexes compared to SARS-CoV-2a in this area. This may allow these two subtypes to have different antigenicity. If the two subtypes have different serological characteristics, a vaccine for both subtypes will be more effective to prevent COVID-19. Thus, further study is urgently required to confirm the antigenicity of these two subtypes.


title: Drivers of airborne human-to-human pathogen transmission

text: Airborne pathogens — either transmitted via aerosol or droplets — include a wide variety of highly infectious and dangerous microbes such as variola virus, measles virus, influenza A viruses, Mycobacterium tuberculosis, Streptococcus pneumoniae, and Bordetella pertussis. Emerging zoonotic pathogens, for example, MERS coronavirus, avian influenza viruses, Coxiella, and Francisella, would have pandemic potential were they to acquire efficient human-to-human transmissibility. Here, we synthesize insights from microbiological, medical, social, and economic sciences to provide known mechanisms of aerosolized transmissibility and identify knowledge gaps that limit emergency preparedness plans. In particular, we propose a framework of drivers facilitating human-to-human transmission with the airspace between individuals as an intermediate stage. The model is expected to enhance identification and risk assessment of novel pathogens.


title: False positive antibody results against human T‐cell lymphotropic virus in patients with severe acute respiratory syndrome

text: Taiwan suffered from the outbreak of severe acute respiratory syndrome (SARS) in 2003. Our laboratory performed a series of virology and serology tests for SARS patients admitted to our hospital. Cross‐reactivity was found when testing for antibody against human T‐cell lymphotropic virus (HTLV) in one patient with SARS. Therefore, antibodies against HTLV were examined in paired‐sera from 26 SARS patients. ELISA and a neutralization test were used to measure anti‐SARS antibodies. Seroconversion for antibody against SARS‐CoV was observed in all patients. Surprisingly, with the use of ELISA for HTLV, sera for 13 patients were positive for HTLV (50%), and seroconversion for HTLV was also observed in 10 patients (38.5%). Western blot for HTLV on those 26 paired‐sera from 13 HTLV‐positive patients displayed 5 positive results for HTLV‐I, 7 positive results for HTLV‐II, 1 positive result for both HTLV‐I and II, 9 negative results for either HTLV‐I or HTLV‐II, and 4 “indeterminate” results. The findings that antibody to HTLV can be detected in blood samples collected from SARS patients provide important information for safe handling of blood products. Without such knowledge, blood products can be discarded mistakenly even though they contain anti‐SARS‐CoV antibodies that may be potentially valuable for SARS therapy. J. Med. Virol. 77:331–336, 2005. © 2005 Wiley‐Liss, inc.


title: Genomic characterization and pathogenicity of porcine deltacoronavirus strain CHN-HG-2017 from China

text: Porcine deltacoronavirus (PDCoV) was first detected in Hong Kong and has recently spread to many countries around the world. PDCoV causes acute diarrhea and vomiting in pigs, resulting in significant economic losses in the global pork industry. In this study, a Chinese PDCoV strain, designated CHN-HG-2017, was isolated from feces of a suckling piglet with severe watery diarrhea on a farm located in central China. Subsequently, the virus was identified by an indirect immunofluorescence assay and electron microscopy. A nucleotide sequence alignment showed that the whole genome of CHN-HG-2017 is 97.6%-99.1% identical to other PDCoV strains. Analysis of potential recombination sites showed that CHN-HG-2017 is a possible recombinant originating from the strains CH/SXD1/2015 and Vietnam/HaNoi6/2015. Furthermore, the pathogenicity of this recombinant PDCoV strain was investigated in 5-day-old piglets by oral inoculation. The challenged piglets developed typical symptoms, such as vomiting, anorexia, diarrhea and lethargy, from 1 to 7 days post-inoculation (DPI). Viral shedding was detected in rectal swabs until 14 DPI in the challenged piglets. Interestingly, high titers of virus-neutralizing antibodies in sera were detected at 21 DPI. Tissues of small intestines from CHN-HG-2017-infected piglets at 4 DPI displayed significant macroscopic and microscopic lesions with clear viral antigen expression. Our analysis of the full genome sequence of a recombinant PDCoV and its virulence in suckling piglets might provide new insights into the pathogenesis of PDCoV and facilitate further investigation of this newly emerged pathogen.


title: Correlation Between Abnormal Platelet Count and Respiratory Viral Infection in Patients From Cheonan, Korea

text: BACKGROUND: In this study, the effects of viral infections on platelet (PLT) count have been reported. This study examined the correlation between PLT count and respiratory virus (RV) infections. METHODS: Patients who visited Dankook University Hospital between December 2006 and February 2014 with symptoms of suspected RV infection were recruited. Multiplex reverse transcriptase polymerase chain reactions identified the causative virus(es). PLT counts were analyzed with respect to virus, age and sex of the patient, and length of hospital stay. RESULTS: Of the 8,147 patients, 62.8% were RV‐positive, and 18.6% of RV‐positive patients had abnormal PLT counts. There were no differences in the rates of abnormal PLT counts between single‐infection and virus co‐infection cases. In RV infection patients, the incidence of abnormal PLT count increased with age and varied depending on the RV infection type. Patients with abnormal PLT count stayed in hospital longer than those with normal PLT count. CONCLUSIONS: The incidence of thrombocytopenia was higher among the elderly; in younger patients, thrombocytosis was more prevalent than thrombocytopenia. Respiratory tract infections caused by different viruses resulted in varied PLT count changes. Further systematic research of PLT count changes related to viral infections is required.


title: Viral etiology and seasonality of influenza-like illness in Gabon, March 2010 to June 2011

text: BACKGROUND: Surveillance of influenza-like illness (ILI) in Central Africa began only recently, and few data are therefore available on the circulation of influenza virus and other respiratory viruses. In Gabon, a Central African country, we established a surveillance network in four major towns in order to analyze cases of ILI among patients who visited health centers between March 2010 and June 2011, and to determine the viral etiology. METHODS: Nasal swabs were sent for analysis to the Centre International de Recherches Médicales de Franceville, where they were screened for 17 respiratory viruses in a multiplex real-time reverse transcription polymerase chain reaction for all pathogens according the following pairs: adenovirus/parainfluenza virus 4, respiratory syncytial virus/human metapneumovirus, parainfluenza virus 1/parainfluenza virus 2, pandemic influenza virus A/seasonal influenza virus A (H1N1, H3N2)/seasonal influenza virus B, human coronaviruses 229E/OC43, human coronaviruses NL63/HKU1, rhinovirus/human parechovirus, and enterovirus/parainfluenza virus 3. RESULTS: We analyzed a total of 1041 specimens, of which 639 (61%) were positive for at least one virus. Three-quarters of the patients were children under five years old. We therefore focused on this age group, in which 68.1% of patients were positive for at least one virus. The most common viruses were adenoviruses (17.5%), followed by parainfluenza viruses (PIVs) 1–4 (16.8%), enteroviruses (EV) (14.7%), respiratory syncytial virus (RSV) (13.5%), and influenza virus (11.9%). The prevalence of some viruses was subject to geographic and seasonal variations. One-third of positive samples contained more than one virus. CONCLUSIONS: Like most studies in the world, the virus PIVs, EV, RSV, Influenza virus, HRV were predominant among children under five years old in Gabon. An exception is made for adenoviruses which have a high prevalence in our study. However adenoviruses can be detected in asymptomatic persons. These finding gave a better knowledge of the circulation and the seasonality of the viruses involved in ILI in Gabon.


title: Interventions to Mitigate Emergency Department and Hospital Crowding During an Infectious Respiratory Disease Outbreak: Results from an Expert Panel

text: Objective: To identify and prioritize potential Emergency Department (ED) and hospital-based interventions which could mitigate the impact of crowding during patient surge from a widespread infectious respiratory disease outbreak and determine potential data sources that may be useful for triggering decisions to implement these high priority interventions. Design: Expert panel utilizing Nominal Group Technique to identify and prioritize interventions, and in addition, determine appropriate “triggers” for implementation of the high priority interventions in the context of four different infectious respiratory disease scenarios that vary by patient volumes (high versus low) and illness severity (high versus low). Setting: One day in-person conference held November, 2011. Participants: Regional and national experts representing the fields of public health, disease surveillance, clinical medicine, ED operations, and hospital operations. Main Outcome Measure: Prioritized list of potential interventions to reduce ED and hospital crowding, respectively. In addition, we created a prioritized list of potential data sources which could be useful to trigger interventions. Results: High priority interventions to mitigate ED surge included standardizing admission and discharge criteria and instituting infection control measures. To mitigate hospital crowding, panelists prioritized mandatory vaccination and an algorithm for antiviral use. Data sources identified for triggering implementation of these interventions were most commonly ED and hospital utilization metrics. Conclusions: We developed a prioritized list of potentially useful interventions to mitigate ED and hospital crowding in various outbreak scenarios. The data sources identified to “trigger” the implementation of these high priority interventions consist mainly of sources available at the local, institutional level.


title: A virome sequencing approach to feline oral squamous cell carcinoma to evaluate viral causative factors

text: Abstract Feline oral squamous cell carcinoma (FOSCC) may be the best naturally-occurring model of human head and neck squamous cell carcinoma (HNSCC). HNSCC can be broadly divided into human papillomavirus (HPV)-negative cancers and HPV-positive cancers where HPV is the causative agent. Previous studies in FOSCC have used both species-specific and species-nonspecific PCR primers that may be insensitive to the detection of PVs and other viruses that may be divergent from known sequences. ViroCap is a targeted capture and next generation sequencing tool that was designed to identify all known vertebrate DNA and RNA viruses. In this study we used a metagenomic approach using ViroCap for DNA viruses in 20 FOSCC, 9 normal feline oral mucosal, and 8 suspected PV positive control samples. We tested the hypothesis that viruses would be enriched in FOSCC compared to normal oral mucosa. The virome of the FOSCC and normal feline oral mucosa consisted of feline foamy virus in 7/20 and 2/9 (35% and 22%), feline torque teno virus in 2/20 and 0/9 (10% and 0%), alphaherpesvirus in 2/10 and 0/9 (10% and 0%), FIV (0% and 22%), Epstein-Barr virus in 1/20 and 0/9 (5% and 0%) and feline papillomavirus in 1/20 and 0/9 samples (5% and 0% respectively). Felis catus papillomavirus-3 was found in 1 of 20 FOSCC samples. A virus was not associated consistently with FOSCC. If PVs have a role in FOSCC it is at most a supplementary or uncommon role. FOSCC appears most closely related to HPV-negative HNSCC. Future research on FOSCC should focus on identifying genetic and environmental causes.


title: Chapter 11 Solid and Suspension Microarrays for Microbial Diagnostics

text: Abstract Advancements in molecular technologies have provided new platforms that are being increasingly adopted for use in the clinical microbiology laboratory. Among these, microarray methods are particularly well suited for diagnostics as they allow multiplexing, or the ability to test for multiple targets simultaneously from the same specimen. Microarray technologies commonly used for the detection and identification of microbial targets include solid-state microarrays, electronic microarrays and bead suspension microarrays. Microarray methods have been applied to microbial detection, genotyping and antimicrobial resistance gene detection. Microarrays can offer a panel approach to diagnose specific patient presentations, such as respiratory or gastrointestinal infections, and can discriminate isolates by genotype for tracking epidemiology and outbreak investigations. And, as more information has become available on specific genes and pathways involved in antimicrobial resistance, we are beginning to be able to predict susceptibility patterns based on sequence detection for particular organisms. With further advances in automated microarray processing methods and genotype–phenotype prediction algorithms, these tests will become even more useful as an adjunct or replacement for conventional antimicrobial susceptibility testing, allowing for more rapid selection of targeted therapy for infectious diseases.


title: Vaccines for emerging infectious diseases: Lessons from MERS coronavirus and Zika virus

text: The past decade and a half has been characterized by numerous emerging infectious diseases. With each new threat, there has been a call for rapid vaccine development. Pathogens such as the Middle East Respiratory Syndrome coronavirus (MERS-CoV) and the Zika virus represent either new viral entities or viruses emergent in new geographic locales and characterized by novel complications. Both serve as paradigms for the global spread that can accompany new pathogens. In this paper, we review the epidemiology and pathogenesis of MERS-CoV and Zika virus with respect to vaccine development. The challenges in vaccine development and the approach to clinical trial design to test vaccine candidates for disease entities with a changing epidemiology are discussed.


title: Untersuchungen zur Virusätiologie der Nasopharynxkarzinome

text: Five carcinoma of the nasopharynx (four lymphoepithelial carcinoma of the Regaud type and one squamous cell carcinoma) were examined light and electron microscopically. In addition to the familiar histological and cytological features of these tumors, and because of an increased antibody titer against Epstein-Barr virus in all five patients, all those cytoplasmic and nuclear inclusions were examined which could be interpreted as indicative of a virus contact. The following structures were found: 1. Particles and microtubules which correspond in diameter, shape and location to Corona viruses. 2. Particles surrounded by a double membrane and resembling in form and diameter Onkorna viruses. 3. Tubulo-reticular, coil-shaped cytoplasmic inclusions interpreted as an unspecific reaction of the host cell to viral attack. 4. Spherical nuclear bodies, which are frequently observed in tumors and during viral infections. 5. Intranuclear particles which correspond in diameter, structure and distribution to viruses of the herpes type such as have been described in cell cultures of Burkitt lymphoma and nasopharyngeal carcinoma. The fifth group particularly was discussed in detail with regard to differentiation between those particles and other structures which could simulate a virus structure. Together with the appearance of increased ribosomes and of particular chromatin distribution within the tumor cell nuclei, the particles we discussed have been interpreted as morphological indications of a virus etiology of the examined tumors.


title: 3D-printed face protective shield in interventional radiology: evaluation of an immediate solution in the era of COVID-19 pandemic

text: Abstract Purpose: The purpose of this study was to report the clinical evaluation of a 3D-printed protective face shield designed to protect interventional radiologists from droplet transmission of the SARS-Cov-2. Materials and methods: A protective face shield consisting in a standard transparent polymerizing vinyl chloride (PVC) sheet was built using commercially available 3D printers. The 3D-printed face shield was evaluated in 31 interventional procedures in terms of ability to perform the assigned intervention as usual, quality of visual comfort and tolerance using a Likert scale (from 1, as very good to 5, as extremely poor). Results: The mean rating for ability to perform the assigned intervention as usual was 1.7 ± 0.8 (SD) (range: 1 - 4). The mean visual tolerance rating was 1.6 ± 0.7 (SD) (range: 1 - 4). The mean tolerability rating was 1.4 ± 0.7 (SD) (range: 1 - 3). Conclusion: The 3D-printed protective face shield is well accepted in various interventions. It may become an additional option for protection of interventional radiologists.


title: Current Disease and Epidemiologic Problems: What’s Hot?

text: Included among the many current world problems are viral diseases of considerable significance and threat. This talk could not possible cover them all but will discuss the emergence of Middle East respiratory syndrome in Saudi Arabia and nearby countries, ebolavirus hemorrhagic fever in West Africa, chikungunya in the Western Hemisphere, and the re-emergence of poliomyelitis.


title: Symmetrical polyneuropathy in Coronavirus Disease 2019 (COVID-19)

text: The outbreak of the novel coronavirus that began in late December 2019 was announced as a pandemic by the World Health Organization as the number of cases is increasing exponentially throughout the globe. We present a patient with confirmed SARS-CoV-2 pneumonia developing symmetric polyneuropathy. To our knowledge, extrapulmonary clinical presentations of 2019 novel coronavirus disease (COVID-19) have rarely been reported. This case highlights the possible association between SARS-CoV-2 infection and nervous system involvement.


title: Somatics of Early Buddhist Mindfulness and How to Face Anxiety

text: The body is a central object of the cultivation of mindfulness, in the way this has been described in relevant Pāli discourses and their parallels. At the background of such cultivation stands the absence of positing a mind-body duality and a lack of concern with a particular physical location of the mind in early Buddhist thought. Moreover, the various exercises that involve directing mindfulness to the body need to be considered in conjunction in order to arrive at a balanced understanding of their overarching purpose. Out of the different possible modalities of cultivating mindfulness in this way, the discourses present awareness directed to one’s own bodily postures as a practice already undertaken by the Buddha-to-be when he was still in quest of awakening. In this particular setting, such mindfulness of postures served as a way of facing fear. The potential of this exercise to provide a grounding in embodied mindfulness, being fully in the here and now, is of particular relevance to the challenges posed by the current pandemic.


title: A novel L-type lectin was required for the multiplication of WSSV in red swamp crayfish (Procambarus clakii)

text: Abstract L-type lectins are involved in glycoproteins secretory pathways and are associated with many immune responses. There is growing evidence that L-type lectins are also involved in viral replication. In this study, a novel L-type lectin (named as PcL-lectin) was identified from red swamp crayfish (Procambarus clakii). Gene sequencing and phylogenetic tree analysis results showed that the PcL-lectin was a kind of endoplasmic reticulum Golgi intermediate compartment-53 (ERGIC-53). The expression level of PcL-lectin was significantly down regulated in crayfish after challenged with white spot syndrome virus (WSSV). Recombinant PcL-lectin protein facilitated the replication of WSSV in crayfish. In addition, WSSV replication was decreased when endogenous PcL-lectin was knocked down by RNA interference in crayfish. Furthermore, PcL-lectin may interact with VP24, an envelope protein of WSSV. Our results suggest that PcL-lectin may be required for the multiplication of WSSV, and will pave a new way for the developing of strategies against WSSV infection.


title: Does high cardiorespiratory fitness confer some protection against pro‐inflammatory responses after infection by SARS‐CoV‐2?

text: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) originated in China in late 2019 and has since spread rapidly to every continent in the world. This pandemic continues to cause widespread personal suffering, along with severe pressure on medical and health care providers. The symtoms of SARS‐CoV‐2 and the subsequent prognosis is worsened in individuals who have pre‐exisiting comorbidities prior to infection by the virus. Individuals with obesity/overweight, insulin resistance and diabetes typically have chronic low‐grade inflammation characterized by increased levels of several pro‐inflammatory cytokines and the inflammasome: this state predisposes to greater risk for infection along with more adverse outcomes. Here we consider whether a high level of cardiorespiratory fitness induced by prior exercise training may confer some innate immune‐protection against Covid‐19 by attenuating the “cytokine storm syndrome” often experienced by “at risk” individuals.


title: A meta‐analysis suggesting that the relationship between biodiversity and risk of zoonotic pathogen transmission is idiosyncratic

text: Zoonotic pathogens are significant burdens on global public health. Because they are transmitted to humans from non‐human animals, the transmission dynamics of zoonoses are necessarily influenced by the ecology of their animal hosts and vectors. The ‘dilution effect’ proposes that increased species diversity reduces disease risk, suggesting that conservation and public health initiatives can work synergistically to improve human health and wildlife biodiversity. However, the meta‐analysis that we present here indicates a weak and highly heterogeneous relationship between host biodiversity and disease. Our results suggest that disease risk is more likely a local phenomenon that relies on the specific composition of reservoir hosts and vectors, and their ecology, rather than patterns of species biodiversity.


title: Etiology and characteristics of community-acquired pneumonia in an influenza epidemic period

text: Abstract Purpose The etiology of community-acquired pneumonia (CAP) in hospital patients is often ambiguous due to the limited pathogen detection. Lack of a microbiological diagnosis impairs precision treatment in CAP. Methods Specimens collected from the lower respiratory tract of 195 CAP patients, viruses were measured by the Single-plex real-time PCR assay and the conventional culture method was exploited for bacteria. Results Among the 195 patients, there were 46 (23.59%) pure bacterial infections, 20 (10.26%) yeast infections, 32 (16.41%) pure viral infections, 8 (4.10%) viral-yeast co-infections, and 17 (8.72%) viral-bacterial co-infections. The two most abundant bacteria were Acinetobacter baumannii and klebsiella pneumoniae, whereas the most common virus was influenza A. Conclusions Non-influenza respiratory microorganisms frequently co-circulated during the epidemic peaks of influenza, which easily being ignored in CAP therapy. In patients with bacterial and viral co-infections, identifying the etiologic agent is crucial for patient’s therapy.


title: The Swiss approach to the COVID‐19 outbreak

text: Angelico et al. described the impact of the novel coronavirus (COVID‐19) outbreak on organ transplantation in Italy (1), where only one center in Milan has limited transplant activity to most urgent cases. The rest of the country continued with the regular allocation policy (1). In Switzerland, which has more COVID‐19 cases per capita than Italy (2), we have opted for a stepwise approach.


title: ZCURVE_CoV: a new system to recognize protein coding genes in coronavirus genomes, and its applications in analyzing SARS-CoV genomes

text: Abstract A new system to recognize protein coding genes in the coronavirus genomes, specially suitable for the SARS-CoV genomes, has been proposed in this paper. Compared with some existing systems, the new program package has the merits of simplicity, high accuracy, reliability, and quickness. The system ZCURVE_CoV has been run for each of the 11 newly sequenced SARS-CoV genomes. Consequently, six genomes not annotated previously have been annotated, and some problems of previous annotations in the remaining five genomes have been pointed out and discussed. In addition to the polyprotein chain ORFs 1a and 1b and the four genes coding for the major structural proteins, spike (S), small envelop (E), membrane (M), and nuleocaspid (N), respectively, ZCURVE_CoV also predicts 5–6 putative proteins in length between 39 and 274 amino acids with unknown functions. Some single nucleotide mutations within these putative coding sequences have been detected and their biological implications are discussed. A web service is provided, by which a user can obtain the annotated result immediately by pasting the SARS-CoV genome sequences into the input window on the web site (http://tubic.tju.edu.cn/sars/). The software ZCURVE_CoV can also be downloaded freely from the web address mentioned above and run in computers under the platforms of Windows or Linux.


title: Decreased NHE3 activity and trafficking in TGEV-infected IPEC-J2 cells via the SGLT1-mediated P38 MAPK/AKt2 pathway

text: Abstract Transmissible gastroenteritis virus (TGEV) primarily replicates in intestinal epithelial cells and causes severe damage to host cells, resulting in diarrhea. Surface NHE3 serves as the key regulatory site controlling electroneutral Na+ absorption. In this study, our results showed that the surface NHE3 content was significantly reduced following TGEV infection, whereas the total level of protein expression was not significantly changed, and NHE3 activity gradually decreased with prolonged infection time. We then inhibited SGLT1 expression by lentiviral interference and drug inhibition, respectively. Inhibition studies showed that the level of phosphorylation of the downstream key proteins, MAPKAPK-2 and EZRIN, in the SGLT1-mediated p38MAPK/AKt2 signaling pathway was significantly increased. The surface NHE3 expression was also significantly increased, and NHE3 activity was also significantly enhanced. These results demonstrate that a TGEV infection can inhibit NHE3 translocation and attenuates sodium-hydrogen exchange activity via the SGLT1-mediated p38MAPK/AKt2 signaling pathway, affecting cellular electrolyte absorption leading to diarrhea.


title: Suggestions for the Care of Patients with Liver Disease During the Coronavirus 2019 Pandemic

text: This document, written by the French Association for the Study of the Liver (AFEF) board, aims to provide information to physicians involved in the care of patients with liver disease during the Coronavirus disease (COVID-19) epidemic. These are not based on a systematic review of the literature and a rigorous evaluation using the GRADE method. These are recommendations based on feedback from China available in the form of original articles or letters – for which the scientific evidence is often modest – and the rules put forward by American (1) and European (Boettler et al, 2020) hepatology societies, the French National Digestive Cancer Thesaurus (Di Fiore et al., 2020) and the Francophone Transplantation Society (4). These suggestions require adjustment according to the geographical particularities of the epidemic, available standard procedures and access to local resources. This document will be updated as regularly as possible according to the evolution of our knowledge and characteristics on the epidemic.


title: COVID-19 and emerging viral infections: The case for interferon lambda

text: With the first reports on coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the scientific community working in the field of type III IFNs (IFN-λ) realized that this class of IFNs could play an important role in this and other emerging viral infections. In this Viewpoint, we present our opinion on the benefits and potential limitations of using IFN-λ to prevent, limit, and treat these dangerous viral infections.


title: A sensitive retroviral pseudotype assay for influenza H5N1‐neutralizing antibodies

text: Background The World Health Organisation (WHO) recommended the development of simple, safe, sensitive and specific neutralization assays for avian influenza antibodies. We have used retroviral pseudotypes bearing influenza H5 hemagglutinin (HA) as safe, surrogate viruses for influenza neutralization assays which can be carried out at Biosafety Level 2. Results Using our assay, sera from patients who had recovered from infection with influenza H5N1, and sera from animals experimentally immunized or infected with H5 tested positive for the presence of neutralizing antibodies to H5N1. Pseudotype neutralizing antibody titers were compared with titers obtained by hemagglutinin inhibition (HI) assays and microneutralization (MN) assays using live virus, and showed a high degree of correlation, sensitivity and specificity. Conclusions The pseudotype neutralization assay is as sensitive as horse erythrocyte HI and MN for the detection of antibodies to H5N1. It is safer, and can be applied in a high‐throughput format for human and animal surveillance and for the evaluation of vaccines.


title: Pathology Consultation on Influenza Diagnostics

text: Objectives: To describe the strengths and limitations of the available influenza diagnostics, with a focus on rapid antigen detection assays and nucleic acid detection assays. Methods: A case-based presentation is used to illustrate the potential limitations of rapid antigen detection assays for influenza. Results: Influenza is a seasonal illness; estimates attribute influenza to approximately 200,000 hospitalizations and 41,000 deaths in the United States annually. Antigen detection assays for influenza are rapid and convenient, and thus are widely used in a variety of health care settings, even though the sensitivity of these assays may be suboptimal. The United States Food and Drug Administration has recently created new guidelines intended to improve the oversight and performance characteristics of influenza antigen detection assays. Molecular assays, although more costly and complex, are more sensitive and may be designed to simultaneously detect multiple respiratory pathogens within a single assay. Conclusions: Diagnostic assays for influenza can vary greatly with regards to analytical performance characteristics, complexity, turnaround time and cost. This can have important patient care and infection prevention implications.


Neuropathology of COVID‐19: where are the neuropathologists?


title: Immunohistochemical studies on meningoencephalitis in feline infectious peritonitis (FIP)

text: The present study describes the association between inflammatory cell types and feline infectious peritonitis virus (FIPV) antigen in the brain of 4 cats diagnosed as feline infectious peritonitis (FIP). Immunohistochemically, FIPV antigens were detected in the inflammatory foci of the leptomeninges, choroid plexus and ventricles in 3 of the 4 cats. In 3 cases, inflammatory foci mainly consisted of CD204- and Iba1-positive macrophages, and the FIPV antigens were found in the macrophages. In the other case which was negative for FIPV antigen, severe inflammation predominantly consisting of CD20-positive B lymphocytes was observed in the leptomeninges and subventricles, accompanied with diffuse proliferation of gemistocytic astrocytes. The difference in histopathology may reflect the inflammatory process or the strain variation of FIP virus.


title: Prevalence of human respiratory viruses in adults with acute respiratory tract infections in Beijing, 2005–2007

text: To determine the aetiological role and epidemiological profile of common respiratory viruses in adults with acute respiratory tract infections (ARTIs), a 2-year study was conducted in Beijing, China, from May 2005 to July 2007. Nose and throat swab samples from 5808 ARTI patients were analysed by PCR methods for common respiratory viruses, including influenza viruses (IFVs) A, B, and C, parainfluenza viruses (PIVs) 1–4, enteroviruses (EVs), human rhinoviruses (HRVs), respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human coronaviruses (HCoVs) OC43, 229E, NL63, and HKU1, and adenoviruses (ADVs). Viral pathogens were detected in 34.6% of patient samples, and 1.6% of the patients tested positive for more than one virus. IFVs (19.3%) were the dominant agents detected, followed by HRVs (6.5%), PIVs (4.3%), EVs (3.2%), and HCoVs (1.1%). ADVs, RSV and HMPV were also detected (<1%). The viral detection rates differed significantly between infections of the lower and upper respiratory tracts in the sample population: PIVs, the second most commonly detected viral agents in lower acute respiratory tract infections (LRTIs), were more prevalent than in upper acute respiratory tract infections, indicating that the pathogenic role of PIVs in LRTIs should be investigated. Currently, this study is the largest-scale investigation of respiratory virus infections in China with multiple agent detection, providing baseline data for further studies of respiratory virus infections in adults with ARTIs.


title: Mortality threats and technology effects on tourism

text: • Investigates people's responses to tourism during Covid-19 lockdown; • Uses an experimental approach in tourism; • Investigates preference for innovative touristic virtual tours in relation to threat and self-esteem; • Combines research in psychology (Terror Management Theory) with that in tourism; • Discusses practical and research implications and future research avenues for tourism research.


title: Porcine Epidemic Diarrhea Virus (PEDV) ORF3 Enhances Viral Proliferation by Inhibiting Apoptosis of Infected Cells

text: The genomes of coronaviruses carry accessory genes known to be associated with viral virulence. The single accessory gene of porcine epidemic diarrhea virus (PEDV), ORF3, is dispensable for virus replication in vitro, while viral mutants carrying ORF3 truncations exhibit an attenuated phenotype of which the underlying mechanism is unknown. Here, we studied the effect of ORF3 deletion on the proliferation of PEDV in Vero cells. To this end, four recombinant porcine epidemic diarrhea viruses (PEDVs) were rescued using targeted RNA recombination, three carrying the full-length ORF3 gene from different PEDV strains, and one from which the ORF3 gene had been deleted entirely. Our results showed that PEDVs with intact or naturally truncated ORF3 replicated to significantly higher titers than PEDV without an ORF3. Further characterization revealed that the extent of apoptosis induced by PEDV infection was significantly lower with the viruses carrying an intact or C-terminally truncated ORF3 than with the virus lacking ORF3, indicating that the ORF3 protein as well as its truncated form interfered with the apoptosis process. Collectively, we conclude that PEDV ORF3 protein promotes virus proliferation by inhibiting cell apoptosis caused by virus infection. Our findings provide important insight into the role of ORF3 protein in the pathogenicity of PEDV.


title: Coronavirus disease 2019 (COVID-19): A literature review

text: Abstract In early December 2019, an outbreak of coronavirus disease 2019 (COVID-19), caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred in Wuhan City, Hubei Province, China. On January 30, 2020 the World Health Organization declared the outbreak as a Public Health Emergency of International Concern. As of February 14, 2020, 49,053 laboratory-confirmed and 1,381 deaths have been reported globally. Perceived risk of acquiring disease has led many governments to institute a variety of control measures. We conducted a literature review of publicly available information to summarize knowledge about the pathogen and the current epidemic. In this literature review, the causative agent, pathogenesis and immune responses, epidemiology, diagnosis, treatment and management of the disease, control and preventions strategies are all reviewed.


title: Enfuvirtide−PEG conjugate: A potent HIV fusion inhibitor with improved pharmacokinetic properties

text: Enfuvirtide (ENF) is a clinically used peptide drug for the treatment of HIV infections, but its poor pharmacokinetic profile (T(1/2) = 1.5 h in rats) and low aqueous solubility make the therapy expensive and inconvenience. In this study, we present a simple and practical strategy to address these problems by conjugating ENF with polyethylene glycol (PEG). Site-specific attachment of a 2 kDa PEG at the N-terminus of ENF resulted in an ENF−PEG (EP) conjugate with high solubility (≥3 mg/mL) and long half-life in rats (T(1/2) = 16.1 h). This conjugate showed similar antiviral activity to ENF against various primary HIV-1 isolates (EC(50) = 6–91 nM). Mechanistic studies suggested the sources of the antiviral potency. The conjugate bound to a functional domain of the HIV gp41 protein in a helical conformation with high affinity (K(d) = 307 nM), thereby inhibiting the gp41-mediated fusion of viral and host-cell membranes. As PEG conjugation has advanced many bioactive proteins and peptides into clinical applications, the EP conjugate described here represents a potential new treatment for HIV infections that may address the unmet medical needs associated with the current ENF therapy.


Abstract 32. Borna virus encephalitis in rats: behavioral changes of aggression leading to apathy


title: Considerations for Bedside Urologic Procedures in Patients with Severe Acute Respiratory Syndrome Coronavirus-2

text: ABSTRACT Objective To provide guidance when performing bedside urologic procedures on SARS-CoV-2 positive patients and offer considerations to maximize the safety of the patients and providers, conserve supplies, and provide optimal management of urologic issues. Methods Urologic trainees and attending physicians at our institution, who are familiar with existing safety recommendations and guidelines regarding the care of infected patients, were queried regarding their experiences to determine an expert consensus on best practices for bedside procedures for SARS-CoV-2 positive patients. Results Our team developed the following general recommendations for urologic interventions on SARS-CoV-2 positive patients: maximize use of telehealth (even for inpatient consults), minimize in-room time, use personal protective equipment appropriately, enlist a colleague to assist, and acquire all supplies that may be needed and maintain them outside the room. Detailed recommendations were also developed for difficult urethral catheterization, bedside cystoscopy, incision and drainage of abscesses, and gross hematuria/clot irrigations. Conclusions As patients hospitalized with SARS-CoV-2 infection are predominantly men over 50 years old, there are significant urologic challenges common in this population that have emerged with this pandemic. While there is tremendous variation in how different regions have been affected, the demographics of SARS-CoV-2 mean that urologists will continue to have a unique role in helping to manage these patients. Here, we summarize recommendations for bedside urologic interventions specific to SARS-CoV-2 positive patients based on experiences from a large metropolitan hospital system. Regulations and requirements may differ on an institutional basis, so these guidelines are intended to augment specific local protocols.


title: Border Screening for SARS

text: With the rapid international spread of severe acute respiratory syndrome (SARS) from March through May 2003, Canada introduced various measures to screen airplane passengers at selected airports for symptoms and signs of SARS. The World Health Organization requested that all affected areas screen departing passengers for SARS symptoms. In spite of intensive screening, no SARS cases were detected. SARS has an extremely low prevalence, and the positive predictive value of screening is essentially zero. Canadian screening results raise questions about the effectiveness of available screening measures for SARS at international borders.


One Virus, Undivided … Equity, And The Corona Virus


title: Human coronaviruses: Viral and cellular factors involved in neuroinvasiveness and neuropathogenesis

text: Abstract Among the various respiratory viruses infecting human beings, coronaviruses are important pathogens, which usually infect the upper respiratory tract, where they are mainly associated with common colds. However, in more vulnerable populations, such as newborns, infants, the elderly and immune-compromised individuals, these opportunistic pathogens can also affect the lower respiratory tract, leading to pneumonia, exacerbations of asthma, and various types of respiratory distress syndrome. The respiratory involvement of human coronaviruses has been clearly established since the 1960s. Nevertheless, for almost three decades now, data reported in the scientific literature has also demonstrated that, like it was described for other human viruses, coronaviruses have neuroinvasive capacities since they can spread from the respiratory tract to the central nervous system (CNS). Once there, infection of CNS cells (neurotropism) could lead to human health problems, such as encephalitis and long-term neurological diseases. Neuroinvasive coronaviruses could damage the CNS as a result of misdirected host immune responses that could be associated with autoimmunity in susceptible individuals (virus-induced neuroimmunopathology) and/or viral replication, which directly induces damage to CNS cells (virus-induced neuropathology). Given all these properties, it has been suggested that these opportunistic human respiratory pathogens could be associated with the triggering or the exacerbation of neurologic diseases for which the etiology remains poorly understood. Herein, we present host and viral factors that participate in the regulation of the possible pathogenic processes associated with CNS infection by human coronaviruses and we try to decipher the intricate interplay between virus and host target cells in order to characterize their role in the virus life cycle as well as in the capacity of the cell to respond to viral invasion.


title: siRNAs targeting terminal sequences of the SARS-associated coronavirus membrane gene inhibit M protein expression through degradation of M mRNA

text: Abstract SARS-associated coronavirus (SCoV) M protein plays a key role in viral assembly and budding. Recent studies revealed that M protein could interact with N protein in the Golgi complex. In this study, we showed that SCoV M protein co-localized in the Golgi apparatus with a Golgi vector marker. To study M protein function, three candidate small interfering RNAs (siRNAs) corresponding to M gene sequences were designed, transcribed in vitro, and then tested for their ability to silence M protein expression. The plasmid, pEGFP-M, encoding SCoV M protein as a fusion protein with EGFP, was used for silencing and for reporter gene detection in HEK 293T cells transfected with siRNA constructs. The results showed that the mean green fluorescence intensity and M RNA transcripts were significantly reduced, and that the expression of M glycoprotein was strongly inhibited in those cells co-transfected with M-specific siRNAs. These findings demonstrated that the three M-specific siRNAs were able to specifically and effectively inhibit M glycoprotein expression in cultured cells by blocking the accumulation of mRNA, which provides an approach for studies on the functions of M protein and for the development of novel prophylactic or therapeutic agents for SCoV infection.


title: Molecular surveillance of traditional and emerging pathogens associated with canine infectious respiratory disease

text: Abstract A molecular survey for traditional and emerging pathogens associated with canine infectious respiratory disease (CIRD) was conducted in Italy between 2011 and 2013 on a total of 138 dogs, including 78 early acute clinically ill CIRD animals, 22 non-clinical but exposed to clinically ill CIRD dogs and 38 CIRD convalescent dogs. The results showed that canine parainfluenza virus (CPIV) was the most commonly detected CIRD pathogen, followed by canine respiratory coronavirus (CRCoV), Bordetella bronchiseptica, Mycoplasma cynos, Mycoplasma canis and canine pneumovirus (CnPnV). Some classical CIRD agents, such as canine adenoviruses, canine distemper virus and canid herpesvirus 1, were not detected at all, as were not other emerging respiratory viruses (canine influenza virus, canine hepacivirus) and bacteria (Streptococcus equi subsp. zooepidemicus). Most severe forms of respiratory disease were observed in the presence of CPIV, CRCoV and M. cynos alone or in combination with other pathogens, whereas single CnPnV or M. canis infections were detected in dogs with no or very mild respiratory signs. Interestingly, only the association of M. cynos (alone or in combination with either CRCoV or M. canis) with severe clinical forms was statistically significant. The study, while confirming CPIV as the main responsible for CIRD occurrence, highlights the increasing role of recently discovered viruses, such as CRCoV and CnPnV, for which effective vaccines are not available in the market.


title: The ADAM metalloproteinases

text: Abstract The ADAMs (a disintegrin and metalloproteinase) are a fascinating family of transmembrane and secreted proteins with important roles in regulating cell phenotype via their effects on cell adhesion, migration, proteolysis and signalling. Though all ADAMs contain metalloproteinase domains, in humans only 13 of the 21 genes in the family encode functional proteases, indicating that at least for the other eight members, protein–protein interactions are critical aspects of their biological functions. The functional ADAM metalloproteinases are involved in “ectodomain shedding” of diverse growth factors, cytokines, receptors and adhesion molecules. The archetypal activity is shown by ADAM-17 (tumour necrosis factor-α convertase, TACE), which is the principal protease involved in the activation of pro-TNF-α, but whose sheddase functions cover a broad range of cell surface molecules. In particular, ADAM-17 is required for generation of the active forms of Epidermal Growth Factor Receptor (EGFR) ligands, and its function is essential for the development of epithelial tissues. Several other ADAMs have important sheddase functions in particular tissue contexts. Another major family member, ADAM-10, is a principal player in signalling via the Notch and Eph/ephrin pathways. For a growing number of substrates, foremost among them being Notch, cleavage by ADAM sheddases is essential for their subsequent “regulated intramembrane proteolysis” (RIP), which generates cleaved intracellular domains that translocate to the nucleus and regulate gene transcription. Several ADAMs play roles in spermatogenesis and sperm function, potentially by effecting maturation of sperm and their adhesion and migration in the uterus. Other non-catalytic ADAMs function in the CNS via effects on guidance mechanisms. The ADAM family are thus fundamental to many control processes in development and homeostasis, and unsurprisingly they are also linked to pathological states when their functions are dysregulated, including cancer, cardiovascular disease, asthma, Alzheimer’s disease. This review will provide an overview of current knowledge of the human ADAMs, discussing their structure, function, regulation and disease involvement.


title: Improving care for older adults in the Emergency Department warrants greater investment in geriatric nursing—Stat!

text: Older adults use the Emergency Department (ED) more than any other age group besides infants. Despite high utilization, both the physical environment and care processes in the traditional ED are poorly suited to address the complex needs of older adults. As a result, older adults often experience poor outcomes in the ED. Geriatric nursing has been at the forefront of efforts to develop Geriatric Emergency Department Interventions (GEDI's) to try to address these deficits and improve care. As frontline providers with frequent patient contact, nursing brings critical viewpoints to these issues. This article provides some resources and other ideas for how frontline nurses can improve care for older adults in the ED. Ultimately, to have meaningful impacts on care of older adults in the ED, there is a dire need for greater financial investment specific to geriatric nursing education, training, and research in the ED.


title: Epidemiology and Potential Preventative Measures for Viral Infections in Children With Malignancy and Those Undergoing Hematopoietic Cell Transplantation

text: In pediatric patients with malignancy and those receiving hematopoietic stem cell transplants, bacterial and fungal infections have been the focus of fever and neutropenia episodes for decades. However, improved diagnostic capabilities have revealed viral pathogens as a significant cause of morbidity and mortality. Because of limited effective antiviral therapies, prevention of viral infections is paramount. Pre-exposure and post-exposure prophylaxis and antiviral suppressive therapeutic approaches are reviewed. Additionally, infection control practices specific to this patient population are discussed. A comprehensive approach utilizing each of these can be effective at reducing the negative impact of viral infections.


title: Efficacy of genogroup 1 based porcine epidemic diarrhea live vaccine against genogroup 2 field strain in Japan

text: BACKGROUND: Porcine epidemic diarrhea (PED) is a lethal infectious disease in suckling piglets with symptoms including watery diarrhea caused by PED virus (PEDV). Since the late 1990’s, live vaccines based on genogroup 1 virus have been used in Japan, and a significant amount of the vaccine has been used even after new genogroups invaded in 2013. In this study, we evaluated the effect of a conventional PED live vaccine on a newly prevalent genogroup 2 field strain in experimental and field situations. METHODS: Two pregnant sows were administered twice the live vaccine before farrowing. A pregnant sow was served as a negative control. All newborn piglets were challenged with the genogroup 2 virus, and clinical signs were monitored for 7 days post challenge. PEDV-specific immune responses in serum and milk of the sows were assayed by virus neutralization assay. The efficacy of PED live vaccine in vaccinated or non-vaccinated farms was evaluated by comparing the mortality rate of suckling piglets after the onset of PED. RESULTS: The challenged piglets exhibited watery diarrhea with or without vaccination. However, the clinical score of piglets born from vaccinated sows significantly improved after the 4th day of the challenge. The survival rate of piglets in the vaccinated group at the end of the experimental period was 80%, whereas in the control group was 0%. Neutralizing antibody titers in serum and milk of control sow was negative throughout the experimental period, whereas high titers were observed in the vaccinated sows. The vaccinated farms significantly reduced the mortality rate of suckling piglets after the onset of PED, compared to farms not vaccinated. CONCLUSIONS: The conventional PED live vaccine induced the lactogenic immunity to vaccinated sows and showed partial protection against the genogroup 2 virus both under the experimental and field conditions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-0940-8) contains supplementary material, which is available to authorized users.


Re: Silke Gillessen Sommer, Thomas Powles. Advice for Medical Oncology Care of Urological Cancer Patients During the COVID-19 Pandemic. Eur Urol. In press Is It Always Correct to Continue Androgen Receptor Signaling Inhibitors in the COVID-19 Era?


title: This Time Must Be Different: Disparities During the COVID-19 Pandemic

text: African Americans and Latinos are overrepresented among cases of and deaths from COVID-19 nationally and in many of the U.S. regions hardest hit by the pandemic. The editorialist discusses lessons that we should have learned from prior experiences and strategies to reduce observed disparities.


title: Considerations for a WHO European strategy on health-care-associated infection, surveillance, and control

text: Summary Health-care-associated infection (HAI) is a major issue of patient safety with a substantial impact on morbidity, mortality, and use of additional resources worldwide. In April 2004, the WHO Regional Office for Europe organised the first international consultation to address the issue of HAI in eastern and central Europe. The main objectives of the consultation were to identify the primary needs and obstacles for the prevention and control of HAI at country level, to design the essential components of an international strategy to effectively address the issue of HAI, and to identify specific priorities and recommendations for interventions by the WHO and other international institutions. An update on HAI activities and related networks throughout Europe, together with the outcome of the meeting, are presented, with special emphasis on future considerations for a European WHO strategy on HAI prevention.


title: Otolaryngology in the COVID-19 pandemic era: the impact on our clinical practice

text: PURPOSE: To give an overview of the current knowledge about COVID-19 pandemic and its impact on otolaryngology clinical practice. METHODS: Recent findings about SARS-CoV-2 virus and the COVID-19 infection it causes are reviewed. In addition to international databases and in the absence of hard scientific data, literature search included reports published online from scientific societies and other institutions. RESULTS: The role of anosmia as a COVID-19-related symptom is presented. Further, considerations about steroid administration in ENT-related conditions are also discussed. Due to the close work with mucosa surfaces of the upper aerodigestive tract, otolaryngologists and surrounding staff are considered high risk for coronavirus transmission. Hence, staff protection measures for ENT examinations, surgeries and other procedures during COVID-19 pandemic are recommended. CONCLUSION: Knowledge and evidence about the impact of COVID-19 infection on otolaryngology clinical practice are accumulating rapidly. Additionally to patient’s management, safety of health care professionals should be a main goal right now by following strict safety guidelines.


title: 5 Molecular Microbiology

text: Abstract Background Nucleic acid (NA) amplification techniques are now commonly used to diagnose and manage patients with infectious diseases. The growth in the number of Food and Drug Administration–approved test kits and analyte-specific reagents has facilitated the use of this technology in clinical laboratories. Technological advances in NA amplification techniques, automation, NA sequencing, and multiplex analysis have reinvigorated the field and created new opportunities for growth. Simple, sample-in, answer-out molecular test systems are now widely available that can be deployed in a variety of laboratory and clinical settings. Molecular microbiology remains the leading area in molecular pathology in terms of both the numbers of tests performed and clinical relevance. NA-based tests have reduced the dependency of the clinical microbiology laboratory on more traditional antigen detection and culture methods and created new opportunities for the laboratory to impact patient care. Content This chapter reviews NA testing as it applies to specific pathogens or infectious disease syndromes, with a focus on those diseases for which NA testing is now considered the standard of care and highlights the unique challenges and opportunities that these tests present for clinical laboratories.


title: Bayes' theorem, COVID19, and screening tests

text: The COVID19 crisis has provided a portal to revisit and understand qualities of screening tests and the importance of Bayes' theorem in understanding how to interpret results and implications of next actions.


title: Neurology and the clinical anatomist

text: Clinical examination allows the neurologist to test hypotheses generated by their interpretation of the patient's story. By eliciting abnormal clinical signs, the examining doctor works out a differential diagnosis for the part of the nervous system affected and, using information from the clinical history, a differential diagnosis of the pathology. Clinical examination also allows the clinician to observe and quantify function, hear more story and provide reassurance. The focus of the examination should be dictated by the hypothesis being tested, the patient's clinical state and the situation. Examination of the different parts of the nervous system remains very important in all clinical situations as the best available index of function of the nervous system as a whole.


Head and neck surgery is a high-risk procedure for COVID-19 transmission and there is a need for a preventive strategy to protect professionals


title: Potential use of Pichia pastoris strain SMD1168H expressing DNA topoisomerase I in the screening of potential anti-breast cancer agents

text: Cancer chemotherapy possesses high toxicity, particularly when a higher concentration of drugs is administered to patients. Therefore, searching for more effective compounds to reduce the toxicity of treatments, while still producing similar effects as current chemotherapy regimens, is required. Currently, the search for potential anticancer agents involves a random, inaccurate process with strategic deficits and a lack of specific targets. For this reason, the initial in vitro high-throughput steps in the screening process should be reviewed for rapid identification of the compounds that may serve as anticancer agents. The present study aimed to investigate the potential use of the Pichia pastoris strain SMD1168H expressing DNA topoisomerase I (SMD1168H-TOPOI) in a yeast-based assay for screening potential anticancer agents. The cell density that indicated the growth of the recombinant yeast without treatment was first measured by spectrophotometry. Subsequently, the effects of glutamate (agonist) and camptothecin (antagonist) on the recombinant yeast cell density were investigated using the same approach, and finally, the effect of camptothecin on various cell lines was determined and compared with its effect on recombinant yeast. The current study demonstrated that growth was enhanced in SMD1168H-TOPOI as compared with that in SMD1168H. Glutamate also enhanced the growth of the SMD1168H; however, the growth effect was not enhanced in SMD1168H-TOPOI treated with glutamate. By contrast, camptothecin caused only lower cell density and growth throughout the treatment of SMD1168H-TOPOI. The findings of the current study indicated that SMD1168H-TOPOI has similar characteristics to MDA-MB-231 cells; therefore, it can be used in a yeast-based assay to screen for more effective compounds that may inhibit the growth of highly metastatic breast cancer cells.


title: A pilot study of bioaerosol reduction using an air cleaning system during dental procedures

text: Background Bioaerosols are defined as airborne particles of liquid or volatile compounds that contain living organisms or have been released from living organisms. The creation of bioaerosols is a recognized consequence of certain types of dental treatment and represents a potential mechanism for the spread of infection. Objectives The aims of the present study were to assess the bioaerosols generated by certain dental procedures and to evaluate the efficiency of a commercially available Air Cleaning System (ACS) designed to reduce bioaerosol levels. Methods Bioaerosol sampling was undertaken in the absence of clinical activity (baseline) and also during treatment procedures (cavity preparation using an air rotor, history and oral examination, ultrasonic scaling and tooth extraction under local anaesthesia). For each treatment, bioaerosols were measured for two patient episodes (with and without ACS operation) and between five and nine bioaerosol samples were collected. For baseline measurements, 15 bioaerosol samples were obtained. For bioaerosol sampling, environmental air was drawn on to blood agar plates using a bioaerosol sampling pump placed in a standard position 20 cm from the dental chair. Plates were incubated aerobically at 37°C for 48 hours and resulting growth quantified as colony forming units (cfu/m(3)). Distinct colony types were identified using standard methods. Results were analysed statistically using SPSS 12 and Wilcoxon signed rank tests. Results The ACS resulted in a significant reduction (p = 0.001) in the mean bioaerosols (cfu/m(3)) of all three clinics compared with baseline measurements. The mean level of bioaerosols recorded during the procedures, with or without the ACS activated respectively, was 23.9 cfu/m(3) and 105.1 cfu/m(3) (p = 0.02) for cavity preparation, 23.9 cfu/m(3) and 62.2 cfu/m(3) (p = 0.04) for history and oral examination; 41.9 cfu/m(3) and 70.9 cfu/m(3) (p = 0.01) for ultrasonic scaling and 9.1 cfu/m(3) and 66.1 cfu/m(3) (p = 0.01) for extraction. The predominant microorganisms isolated were Staphylococcus species and Micrococcus species. Conclusion These findings indicate potentially hazardous bioaerosols created during dental procedures can be significantly reduced using an air cleaning system.


title: Meeting report: Global vaccine and immunization research forum, 2018

text: Abstract Every two years, the Global Vaccine and Immunization Research Forum takes stock of global research in vaccines and immunization. As in prior years, the 2018 meeting addressed vaccine discovery, development, decision-making, and deployment. This time, however, it also featured two overarching themes: “Innovating for Equity” and “End-to-End Integration.” Significant advances have been made in the last two years, but participants noted that some important goals of the Global Vaccine Action Plan are not being met and called urgently for innovation in improving access to vaccines. Two factors were highlighted as crucial to improving coverage: a focus on equity and sustainability throughout the immunization ecosystem, and an enabling political environment that prioritizes health and immunization.


title: Computational characterization and design of SARS coronavirus receptor recognition and antibody neutralization

text: Abstract The sequential determination of crystal structures of the SARS coronavirus spike receptor-binding domain (RBD) in complex with its cellular receptor or neutralizing antibody opened a door for the design and development of antiviral competitive inhibitors. Based on those complex structures, we conduct computational characterization and design of RBD-mediated receptor recognition and antibody neutralization. The comparisons between computational predictions and experimental evidences validate our structural bioinformatics protocols. And the calculations predict a number of single substitutions on RBD, receptor or antibody that could remarkably elevate the binding affinities of those complexes. It is reasonable to anticipate our structure-based computation-derived hypotheses could be informative to the future biochemical and immunological tests.


title: Preparing for the Unthinkable: Emergency Preparedness for the Hematopoietic Cell Transplant Program

text: Abstract Emergencies come at the most inopportune times. Some are totally unexpected, others come with short warnings. Although rare, an emergency comes with the potential to wreak disaster and pose serious risk to the services provided to hematopoietic cell transplant (HCT) patients. Yet, the consequences of an emergency can be mitigated by thinking the unthinkable and having a plan for emergency preparedness in place. Each HCT center should develop a plan containing steps of mitigation, preparedness, response and recovery. This report provides the framework for a HCT-specific emergency preparedness plan that can be used by individual centers to develop customized guidelines on preparing for, responding to, and recovering from an emergency.


title: Modelling management strategies for a disease including undetected sub-clinical infection: Bacterial kidney disease in Scottish salmon and trout farms

text: Disease is a major constraint on animal production and welfare in agriculture and aquaculture. Movement of animals between farms is one of the most significant routes of disease transmission and is particularly hard to control for pathogens with subclinical infection. Renibacterium salmoninarum causes bacterial kidney disease (BKD) in salmonid fish, but infection is often sub-clinical and may go undetected with major potential implications for disease control programmes. A Susceptible-Infected model of R. salmoninarum in Scottish aquaculture has been developed that subdivides the infected phase between known and undetected sub-clinically infected farms and diseased farms whose status is assumed to be known. Farms officially known to be infected are subject to movement controls restricting spread of infection. Model results are sensitive to prevalence of undetected infection, which is unknown. However, the modelling suggests that controls that reduce BKD prevalence include improve biosecurity on farms, including those not known to be infected, and improved detection of infection. Culling appears of little value for BKD control. BKD prevalence for rainbow trout farms is less sensitive to controls than it is for Atlantic salmon farms and so different management strategies may be required for the sectors.


title: One-Year Visiting Care Service Treatment with Korean Medicine for a Solitary Elderly Woman in a Public Health Setting: A Case Report

text: Abstracts In public health, the plight of the solitary elderly is associated with serious social and medical burden. In this vulnerable population, neuropsychiatric complications such as senile depression and dementia as well as chronic pain conditions often co-occur. In this case report, we present a case of an 81-year-old solitary woman who received one year of visiting care service with Korean medicine treatments in a public health setting. During the one year, her pain severity (measured using numeric rating scale) remained moderate after her initial decline and her depressive symptoms and cognitive function scales (Geriatric Depression Scale-Short Form Korean and the Korean version of the Mini-Mental State Examination for Dementia Screening) remained almost unchanged; however, another cognitive function scale (Korean version of the Montreal Cognitive Assessment) showed noticeable improvements. This case report suggests that providing visiting care services with Korean medicine may be a viable strategy for addressing the issues of the solitary elderly.


title: WU and KI polyomavirus infections in pediatric hematology/oncology patients with acute respiratory tract illness

text: Abstract Background WU and KI polyomaviruses (PyV) were discovered in 2007 in respiratory tract samples in adults and children. Other polyomaviruses (BKPyV and JCPyV) have been associated with illness in immunocompromised patients, and some studies suggest a higher prevalence of WUPyV and KIPyV in this population. Objective To determine whether a higher prevalence or viral load for WUPyV and KIPyV exists in immunocompromised children compared with immunocompetent children. Study design We measured the prevalence and viral load of WU and KI PyV by quantitative real-time PCR of viral DNA in respiratory tract specimens from pediatric hematology/oncology patients and immunocompetent controls with acute respiratory illnesses. Results The prevalence of WUPyV in the immunocompromised population was 5/161 (3%) versus 14/295 (5%) in the control population (P =0.5), and 9/161 (5.6%) versus 7/295 (2.3%) respectively for KIPyV (P =0.13). The mean viral load (in copies per cell or mL of sample) for KIPyV, was higher in the immunocompromised group compared to the control group (P =0.019), but was not statistically different for WUPyV. A higher prevalence was seen in the hematopoietic stem cell transplant recipients compared with other immunocompromised patients (6/26 versus 3/43, P =0.054). Viral persistence was demonstrated only in 1/25 (4%) of sequential samples for KIPyV, and no persistence was seen for WUPyV. Conclusions A higher prevalence of WUPyV or KIPyV in the immunocompromised population compared with the immunocompetent group was not demonstrated. Higher viral loads for KIPyV in the immunocompromised group may suggest an increased pathogenic potential in this population.


title: Pathobiology of secondary immune thrombocytopenia

text: Primary immune thrombocytopenic purpura (ITP) remains a diagnosis of exclusion both from nonimmune causes of thrombocytopenia and immune thrombocytopenia that develops in the context of other disorders (secondary immune thrombocytopenia). The pathobiology, natural history, and response to therapy of the diverse causes of secondary ITP differ from each other and from primary ITP, so accurate diagnosis is essential. Immune thrombocytopenia can be secondary to medications or to a concurrent disease, such as an autoimmune condition (eg, systemic lupus erythematosus [SLE], antiphospholipid antibody syndrome [APS], immune thyroid disease, or Evans syndrome), a lymphoproliferative disease (eg, chronic lymphocytic leukemia or large granular T-lymphocyte lymphocytic leukemia), or chronic infection, eg, with Helicobacter pylori, human immunodeficiency virus (HIV), or hepatitis C virus (HCV). Response to infection may generate antibodies that cross-react with platelet antigens (HIV, H pylori) or immune complexes that bind to platelet Fcγ receptors (HCV) and platelet production may be impaired by infection of megakaryocyte bone marrow-dependent progenitor cells (HCV and HIV), decreased production of thrombopoietin (TPO), and splenic sequestration of platelets secondary to portal hypertension (HCV). Sudden and severe onset of thrombocytopenia has been observed in children after vaccination for measles, mumps, and rubella or natural viral infections, including Epstein-Barr virus, cytomegalovirus, and varicella zoster virus. This thrombocytopenia may be caused by cross-reacting antibodies and closely mimics acute ITP of childhood. Proper diagnosis and treatment of the underlying disorder, where necessary, play an important role in patient management.


title: Evolution of the Chinese guarantee network under financial crisis and stimulus program

text: Our knowledge about the evolution of guarantee network in downturn period is limited due to the lack of comprehensive data of the whole credit system. Here we analyze the dynamic Chinese guarantee network constructed from a comprehensive bank loan dataset that accounts for nearly 80% total loans in China, during 01/2007-03/2012. The results show that, first, during the 2007-2008 global financial crisis, the guarantee network became smaller, less connected and more stable because of many bankruptcies; second, the stimulus program encouraged mutual guarantee behaviors, resulting in highly reciprocal and fragile network structure; third, the following monetary policy adjustment enhanced the resilience of the guarantee network by reducing mutual guarantees. Interestingly, our work reveals that the financial crisis made the network more resilient, and conversely, the government bailout degenerated network resilience. These counterintuitive findings can provide new insight into the resilience of real-world credit system under external shocks or rescues.


title: An arginine-to-proline mutation in a domain with undefined functions within the helicase protein (Nsp13) is lethal to the coronavirus infectious bronchitis virus in cultured cells

text: Abstract Genetic manipulation of the RNA genomes by reverse genetics is a powerful tool to study the molecular biology and pathogenesis of RNA viruses. During construction of an infectious clone from a Vero cell-adapted coronavirus infectious bronchitis virus (IBV), we found that a G–C point mutation at nucleotide position 15526, causing Arg-to-Pro mutation at amino acid position 132 of the helicase protein, is lethal to the infectivity of IBV on Vero cells. When the in vitro-synthesized full-length transcripts containing this mutation were introduced into Vero cells, no infectious virus was rescued. Upon correction of the mutation, infectious virus was recovered. Further characterization of the in vitro-synthesized full-length transcripts containing the G15526C mutation demonstrated that this mutation may block the transcription of subgenomic RNAs. Substitution mutation of the Arg132 residue to a positively charged amino acid Lys affected neither the infectivity of the in vitro-synthesized transcripts nor the growth properties of the rescued virus. However, mutation of the Arg132 residue to Leu, a conserved residue in other coronaviruses at the same position, reduced the recovery rate of the in vitro-synthesized transcripts. The recovered mutant virus showed much smaller-sized plaques. On the contrary, a G–C and a G–A point mutations at nucleotide positions 4330 and 9230, respectively, causing Glu–Gln and Gly–Glu mutations in or near the catalytic centers of the papain-like (Nsp3) and 3C-like (Nsp5) proteinases, did not show detectable detrimental effect on the rescue of infectious viruses and the infectivity of the rescued viruses.