title: Protection afforded by respirators when performing endotracheal intubation using a direct laryngoscope, GlideScope®, and i-gel® device: A randomized trial

text: Emergency physicians are at risk of infection during invasive procedures, and wearing a respirator can reduce this risk. The aim of this study was to determine whether the protection afforded by a respirator during intubation is affected by the type of airway device used. In this randomized crossover study, 26 emergency physicians underwent quantitative fit tests for a N95 respirator (cup-type or fold-type) before and during intubation with a direct laryngoscope, GlideScope®, or i-gel® airway device. The primary outcome was the fit factor value of the respirator and the secondary outcome was the level of acceptable protection provided (percentage of fit factor scores above 100). Compared with the GlideScope and i-gel device, the fit factor values and level of acceptable protection provided were lower when physicians wore the cup-type respirator while intubating using the direct laryngoscope (200 fit factor [152–200] and 200 fit factor [121.25–200] versus 166 fit factor [70–200], 100% and 100% versus 75%, respectively; all P < 0.001). There were no significant differences in the fit factor value or level of acceptable protection provided when the physicians wore the fold-type respirator while intubating using any of the three airway devices (all P > 0.05). The type of airway device used for endotracheal intubation may influence the protective performance of some types of respirators. Emergency physicians should consider the effects of airway device types on fit factor of N95 respirators, when they perform intubation at risk of infection.


title: Case Study 1 Ocean Park In the Face of Competition from Hong Kong Disneyland

text: In April 2006, Ocean Park, Hong Kong’s only home-grown theme park, launched a syndicated loan to raise HK$4.1 billion for a master plan to revamp the Park. The master plan represented the Park’s strategic response to the arrival of Hong Kong Disneyland, which had opened the previous year. Ocean Park had expected attendance to drop significantly with Disney’s opening, but attendance at the Park had remained strong. Nonetheless, the competition posed by Disney was not to be underestimated. How would the commercial banks assess Ocean Park’s strategic plan? Would they buy the Park’s strategy in light of the competition posed by Disney?


title: Rapid Detection Strategies for the Global Threat of Zika Virus: Current State, New Hypotheses, and Limitations

text: The current scenario regarding the widespread Zika virus (ZIKV) has resulted in numerous diagnostic studies, specifically in South America and in locations where there is frequent entry of travelers returning from ZIKV-affected areas, including pregnant women with or without clinical symptoms of ZIKV infection. The World Health Organization, WHO, announced that millions of cases of ZIKV are likely to occur in the USA in the near future. This situation has created an alarming public health emergency of international concern requiring the detection of this life-threatening viral candidate due to increased cases of newborn microcephaly associated with ZIKV infection. Hence, this review reports possible methods and strategies for the fast and reliable detection of ZIKV with particular emphasis on current updates, knowledge, and new hypotheses that might be helpful for medical professionals in poor and developing countries that urgently need to address this problem. In particular, we emphasize liposome-based biosensors. Although these biosensors are currently among the less popular tools for human disease detection, they have become useful tools for the screening and detection of pathogenic bacteria, fungi, and viruses because of their versatile advantageous features compared to other sensing devices. This review summarizes the currently available methods employed for the rapid detection of ZIKV and suggests an innovative approach involving the application of a liposome-based hypothesis for the development of new strategies for ZIKV detection and their use as effective biomedicinal tools.


title: Prevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels in Abu Dhabi Emirate, United Arab Emirates

text: High seroprevalence of Middle East respiratory syndrome corona virus (MERS-CoV) in dromedary camels has been previously reported in United Arab Emirates (UAE). However, the molecular detection of the virus has never been reported before in UAE. Of the 7,803 nasal swabs tested in the epidemiological survey, MERS-CoV nucleic acid was detected by real-time PCR in a total of 126 (1.6 %) camels. Positive camels were detected at the borders with Saudi Arabia and Oman and in camels’ slaughter houses. MERS-CoV partial sequences obtained from UAE camels were clustering with human- and camel-derived MERS-CoV sequences in the same geographic area. Results provide further evidence of MERS-CoV zoonosis.


title: Porcine epidemic diarrhea virus ORF3 gene prolongs S-phase, facilitates formation of vesicles and promotes the proliferation of attenuated PEDV

text: Porcine epidemic diarrhea virus (PEDV) is a porcine enteropathogenic coronavirus that has received increasing attention since the emergence of a PEDV variant worldwide. Previous studies have shown that PEDV ORF3 encodes an ion channel protein. However, its influence on cell cycle and subcellular structure still require more research. In this study, we developed a Vero cell line that stably expresses PEDV ORF3 gene. Subcellular localization and influences of PEDV ORF3 on host cells were investigated. We further verified whether or not this gene enhances virus production. The results showed that PEDV ORF3 protein localizes in the cytoplasm and affects cell cycle progression by prolonging the S phase. In addition, the ORF3-expressing Vero cells had more vesicles than the host Vero cells. Furthermore, the attenuated PEDV rather than virulent PEDV could grow better in ORF3-expressing Vero cells. The expression level of the PEDV nucleocapsid protein also increased. These results provided information on the function of PEDV ORF3 and were helpful in understanding the mechanisms of PEDV replication. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11262-015-1257-y) contains supplementary material, which is available to authorized users.


title: Telemedicine and support groups could be used to improve adherence to treatment and health‐related quality of life in patients affected by inflammatory skin conditions during the COVID‐19 pandemic

text: We have read with great interest the article by Deepak et al. which reported the measures applied during the COVID-19 emergency in order to answer to the request of consultations. Particularly they described the growing importance that telemedicine is having during this emergency, focusing on the use of mobile technology (particularly the use of WhatsApp) as a method to communicate via text messages, voice messages, photos and videos, which is rapidly expanding within the field of telemedicine.


title: COVID-19 and the craniomaxillofacial surgical community.

text: The global outbreak of the novel coronavirus, SARS-CoV-2, or COVID-19, has dramatically transformed all aspects of our daily lives The continually evolving understanding of the disease process and uncertainty regarding the availability of vital resources have created an unprecedented challenge, matched in magnitude by concerns for the well-being of our patients, families, colleagues, and communities Our global craniomaxillofacial (CMF) community has met this challenge head on, whether providing care for acute injuries or aggressive pathology, performing modified duties in support of our frontline medical colleagues, assisting in the development of triage and care plans, supporting public health responses, or assisting friends and neighbors in this austere climate Public health measures for containing the spread of disease (social distancing) and to optimize the allocation of limited resources, such as personal protective equipment, have now been widely adopted and there is hope that they will be effective Similarly, principles for the safe practice of craniomaxillofacial surgery during this crisis cannot be overemphasized The AO CMF International Task Force has developed guidelines to support surgeons caring for patients during the COVID-19 pandemic 1 These recommendations trace their evolution to expert opinions and guidelines set forth by a number of national and international societies, as well as the limited, but increasing, available data in the peer-reviewed medical literature The complete report from the Task Force is available online, and we strongly encourage you to review this document, if you have not already had an opportunity to do so 1


title: Cross‐sectional survey and surveillance for influenza viruses and MERS‐CoV among Egyptian pilgrims returning from Hajj during 2012‐2015

text: BACKGROUND: Approximately 80 000 Egyptians participate in Hajj pilgrimage annually. The purpose of this study was to estimate influenza virus and MERS‐CoV prevalence among Egyptian pilgrims returning from Hajj. STUDY: A cross‐sectional survey among 3 364 returning Egyptian pilgrims from 2012 to 2015 was conducted. Nasopharyngeal (NP) and oropharyngeal (OP) swabs were collected from all participants. Sputum specimens were collected from participants with respiratory symptoms and productive cough at the time of their interview. Specimens were tested for influenza viruses, and a convenience sample of NP/OP specimens was tested for MERS‐CoV. Thirty percent of participants met the case definition for influenza‐like illness (ILI), 14% tested positive for influenza viruses, and none tested positive for MERS‐CoV. Self‐reported influenza vaccination was 20%. CONCLUSIONS: High prevalence of reported ILI during pilgrimage and confirmed influenza virus on return from pilgrimage suggest a continued need for influenza prevention strategies for Egyptian Hajj pilgrims. An evaluation of the Ministry of Health and Population's current risk communication campaigns to increase influenza vaccine use among pilgrims may help identify strategies to improve vaccine coverage.


title: Chapter 96 Critical Care Viral Infections

text: Abstract Viral infections are a common cause of critical illness, particularly of the respiratory, gastrointestinal, and central nervous systems. Most are managed by supportive care alone. Early identification is critical to proper care to facilitate antimicrobial de-escalation. A small subset of viruses has directed treatment, and critical care providers should be knowledgeable about the diagnosis and treatment of influenza, herpes simplex meningoencephalitis, and viral hepatitis. Antivirals can reduce the morbidity and mortality associated with each of these illnesses.


Personal Protection Prior to Preoperative Assessment—Little more an anaesthesiologist can do to prevent SARS-CoV-2 transmission and COVID-19 infection


title: Chapter 186 Angiotensin II Peptides

text: ABSTRACT Much evidence supports the notion that angiotensin II (Ang II), the central product of the renin–angiotensin system (RAS), may play a central role not only in the etiology of hypertension but also in the pathophysiology of cardiovascular diseases in humans. Ang II, via the Ang II type 1 receptor, directly causes cellular phenotypic changes and cell growth, regulates the gene expression of various bioactive substances, and activates multiple intracellular signaling cascades in cardiac myocytes and fibroblasts, as well as vascular endothelial and smooth muscle cells. Recently, new factors have been discovered, such as angiotensin-converting enzyme 2, angiotensin-(1-7), and its receptor Mas. This section summarizes the current knowledge about the broad RAS in the pathophysiology of cardiac hypertrophy and remodeling, heart failure, vascular thickening, and atherosclerosis.


COVID-19 PNEUMONIA IN A DUAL HEART-KIDNEY RECIPIENT


title: Immunization strategy based on the critical node in percolation transition

text: Abstract The problem of finding a better immunization strategy for controlling the spreading of the epidemic with limited resources has attracted much attention since its great theoretical significance and wide application. In this letter, we propose a novel and successful targeted immunization strategy based on percolation transition. Our strategy repeatedly looks for the critical nodes for immunizing. The critical node, which leads to the emergence of the giant connected component as the degree threshold increases, is determined when the maximal second-largest connected component disappears. To test the effectiveness of the proposed method, we conduct the experiments on several artificial networks and real-world networks. The results show that the proposed method outperforms the degree centrality strategy, the betweenness centrality strategy and the adaptive degree centrality strategy with 18% to 50% fewer immunized nodes for same amount of immunization.


title: Experimental investigation of far‐field human cough airflows from healthy and influenza‐infected subjects

text: Seasonal influenza epidemics have been responsible for causing increased economic expenditures and many deaths worldwide. Evidence exists to support the claim that the virus can be spread through the air, but the relative significance of airborne transmission has not been well defined. Particle image velocimetry (PIV) and hot‐wire anemometry (HWA) measurements were conducted at 1 m away from the mouth of human subjects to develop a model for cough flow behavior at greater distances from the mouth than were studied previously. Biological aerosol sampling was conducted to assess the risk of exposure to airborne viruses. Throughout the investigation, 77 experiments were conducted from 58 different subjects. From these subjects, 21 presented with influenza‐like illness. Of these, 12 subjects had laboratory‐confirmed respiratory infections. A model was developed for the cough centerline velocity magnitude time history. The experimental results were also used to validate computational fluid dynamics (CFD) models. The peak velocity observed at the cough jet center, averaged across all trials, was 1.2 m/s, and an average jet spread angle of θ = 24° was measured, similar to that of a steady free jet. No differences were observed in the velocity or turbulence characteristics between coughs from sick, convalescent, or healthy participants.


title: Why “good enough” isn’t good enough: scientific data, not supply chain deficiencies should be driving CDC recommendations.

text: Abstract: Obstetricians and clinicians previously requested clarification from the Centers for Disease Control and Prevention (CDC) on the need for full personal protective equipment including N95 respirators during the second stage of labor. The CDC responded with new guidance excluding the second stage of labor from its list of aerosol generating procedures (AGPs), based on research from which experience on labor and delivery units was notably absent. Additional literature that explores other modes of aerosol generation, such as coughing, vomiting, passing flatus and loud vocalization, all of which are prevalent during the labor course, was notably omitted. It is clear that the CDC based their guidance not from the application of scientific principles but pragmatism due to the lack of equipment, and our colleagues were urged to follow suit. If we replace recommendations based on scientific principles with recommendations based on supply chain deficiencies, we become complacent with that which is “good enough under the circumstances.” This is a dangerous precedent on which to base our Professional Society guidelines. We should continue to address these inadequate responses even as CDC guidelines evolve and the pandemic winds down. We will certainly face similar conflict again, whether during a fall resurgence of the current pandemic or future infectious disease outbreak.


title: Designing of CD8(+) and CD8(+)-overlapped CD4(+) epitope vaccine by targeting late and early proteins of human papillomavirus

text: BACKGROUND AND AIM: Human papillomavirus (HPV) is an oncogenic agent that causes over 90% of cases of cervical cancer in the world. Currently available prophylactic vaccines are type specific and have less therapeutic efficiency. Therefore, we aimed to predict the potential species-specific and therapeutic epitopes from the protein sequences of HPV45 by using different immunoinformatics tools. METHODS: Initially, we determined the antigenic potential of late (L1 and L2) and early (E1, E2, E4, E5, E6, and E7) proteins. Then, major histocompatibility complex class I-restricted CD8(+) T-cell epitopes were selected based on their immunogenicity. In addition, epitope conservancy, population coverage (PC), and target receptor-binding affinity of the immunogenic epitopes were determined. Moreover, we predicted the possible CD8(+), nested interferon gamma (IFN-γ)-producing CD4(+), and linear B-cell epitopes. Further, antigenicity, allergenicity, immunogenicity, and system biology-based virtual pathway associated with cervical cancer were predicted to confirm the therapeutic efficiency of overlapped epitopes. RESULTS: Twenty-seven immunogenic epitopes were found to exhibit cross-protection (≥55%) against the 15 high-risk HPV strains (16, 18, 31, 33, 35, 39, 51, 52, 56, 58, 59, 68, 69, 73, and 82). The highest PC was observed in Europe (96.30%), North America (93.98%), West Indies (90.34%), North Africa (90.14%), and East Asia (89.47%). Binding affinities of 79 docked complexes observed as global energy ranged from −10.80 to −86.71 kcal/mol. In addition, CD8(+) epitope-overlapped segments in CD4(+) and B-cell epitopes demonstrated that immunogenicity and IFN-γ-producing efficiency ranged from 0.0483 to 0.5941 and 0.046 to 18, respectively. Further, time core simulation revealed the overlapped epitopes involved in pRb, p53, COX-2, NF-X1, and HPV45 infection signaling pathways. CONCLUSION: Even though the results of this study need to be confirmed by further experimental peptide sensitization studies, the findings on immunogenic and IFN-γ-producing CD8(+) and overlapped epitopes provide new insights into HPV vaccine development.


title: Innate Immune Responses and Viral-Induced Neurologic Disease

text: Multiple sclerosis (MS) is a disease of the central nervous system (CNS) characterized by chronic neuroinflammation, axonal damage, and demyelination. Cellular components of the adaptive immune response are viewed as important in initiating formation of demyelinating lesions in MS patients. This notion is supported by preclinical animal models, genome-wide association studies (GWAS), as well as approved disease modifying therapies (DMTs) that suppress clinical relapse and are designed to impede infiltration of activated lymphocytes into the CNS. Nonetheless, emerging evidence demonstrates that the innate immune response e.g., neutrophils can amplify white matter damage through a variety of different mechanisms. Indeed, using a model of coronavirus-induced neurologic disease, we have demonstrated that sustained neutrophil infiltration into the CNS of infected animals correlates with increased demyelination. This brief review highlights recent evidence arguing that targeting the innate immune response may offer new therapeutic avenues for treatment of demyelinating disease including MS.


title: A warm welcome to our new editors

text: In this Editorial, the Editor‐in‐Chief Professor Miguel A. De la Rosa introduces the new members of the Editorial Board and discusses the effects of COVID‐19 on the journal. [Image: see text]


title: A new prokaryotic expression vector for the expression of antimicrobial peptide abaecin using SUMO fusion tag

text: BACKGROUND: Despite the growing demand for antimicrobial peptides (AMPs) for clinical use as an alternative approach against antibiotic-resistant bacteria, the manufacture of AMPs relies on expensive, small-scale chemical methods. The small ubiquitin-related modifier (SUMO) tag is industrially practical for increasing the yield of recombinant proteins by increasing solubility and preventing degradation in expression systems. RESULTS: A new vector system, pKSEC1, was designed to produce AMPs, which can work in prokaryotic systems such as Escherichia coli and plant chloroplasts. 6xHis was tagged to SUMO for purification of SUMO-fused AMPs. Abaecin, a 34-aa-long antimicrobial peptide from honeybees, was expressed in a fusion form to 6xHis-SUMO in a new vector system to evaluate the prokaryotic expression platform of the antimicrobial peptides. The fusion sequences were codon-optimized in three different combinations and expressed in E. coli. The combination of the native SUMO sequence with codon-optimized abaecin showed the highest expression level among the three combinations, and most of the expressed fusion proteins were detected in soluble fractions. Cleavage of the SUMO tag by sumoase produced a 29-aa-long abaecin derivative with a C-terminal deletion. However, this abaecin derivative still retained the binding sequence for its target protein, DnaK. Antibacterial activity of the 29-aa long abaecin was tested against Bacillus subtilis alone or in combination with cecropin B. The combined treatment of the abaecin derivative and cecropin B showed bacteriolytic activity 2 to 3 times greater than that of abaecin alone. CONCLUSIONS: Using a SUMO-tag with an appropriate codon-optimization strategy could be an approach for the production of antimicrobial peptides in E.coli without affecting the viability of the host cell. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12896-019-0506-x) contains supplementary material, which is available to authorized users.


title: Coronavirus Pandemic as Black Swan Event

text: Nowadays coronavirus is the hottest break news around the world. This paper aims to study why coronavirus became so meaningful for worldwide life. On one side many countries closed their boarders to prevent coronavirus spreading. On another side some people said that coronavirus is no scared than simple influence. Where is true? The health effects and mortality of coronavirus and influenza were compared. Situation Reports of World Health Organization have been analyzed and signs of Black Swan event considered. Total confirmed cases, total, deaths, and Rate of coronavirus distribution was calculated based on Situation Reports of the World Health Organization. To conclude this paper Coronavirus Pandemic recognized as Black Swan event according to considered figures and facts from recent references.


title: The morphology of virus particles. Classification of viruses

text: This chapter focuses on the studies on morphology of virus particles and their classification. The composition of a conventional virus can be described as follows. Centrally, the particle contains nucleic acid of varying quantity. This nucleic acid is either RNA or DNA but never both kinds simultaneously. Only certain non-enveloped virions can be crystallized. The availability of viral crystals has facilitated three-dimensional analyses by aid of X-ray diffraction. Through earlier studies, it has been possible to shed light upon the interaction between virus nucleic acid and capsid protein. A single-stranded nucleic acid can direct the synthesis of a protein that has a size corresponding to about 1/7 of its molecular weight. Nature generally utilizes symmetrical building principles in the construction of more comprehensive three-dimensional structures. The name of Coronavirus has been given to designate the pattern of the club-like peplomers that radiate from the envelope.


title: Antibody-Dependent Cellular Phagocytosis of HIV-1-Infected Cells Is Efficiently Triggered by IgA Targeting HIV-1 Envelope Subunit gp41

text: Antibodies mediate a broad array of non-neutralizing Fc-mediated functions against HIV-1 including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Accordingly, ADCC and ADCP induced by anti-HIV envelope gp120 IgG have been correlated to the limited success of the HIV-1 phase III vaccine trial RV144. It remains elusive whether ADCP can also be triggered by IgA, the isotype predominant at mucosal surfaces through which HIV-1 is mainly transmitted. Yet, we have previously shown that the HIV envelope subunit gp41-specific broadly neutralizing antibody 2F5 under the IgA isotype (2F5-IgA) triggers ADCC and cooperates with 2F5-IgG to increase HIV-1-infected cell lysis. Here, we now demonstrate that 2F5-IgA, more efficiently than 2F5-IgG, induces ADCP not only of gp41-coated beads but also of primary HIV-1-infected cells in a FcαRI-dependent manner. Both primary monocytes and neutrophils can act as effector cells of 2F5-IgA-mediated ADCP, although with different kinetics with faster neutrophil phagocytosis. However, unlike for ADCC, 2F5-IgA and 2F5-IgG do not cooperate to increase ADCP. Altogether, our results reveal that gp41-specific IgA mediate the efficient phagocytosis of HIV-1-infected cells. Inducing such ADCC and ADCP-prone IgA response by vaccination in addition to anti-HIV envelope IgG, might increase the protection against HIV acquisition at mucosal level.


title: Converting monoclonal antibody-based immunotherapies from passive to active: bringing immune complexes into play

text: Monoclonal antibodies (mAbs), which currently constitute the main class of biotherapeutics, are now recognized as major medical tools that are increasingly being considered to fight severe viral infections. Indeed, the number of antiviral mAbs developed in recent years has grown exponentially. Although their direct effects on viral blunting have been studied in detail, their potential immunomodulatory actions have been overlooked until recently. The ability of antiviral mAbs to modulate antiviral immune responses in infected organisms has recently been revealed. More specifically, upon recognition of their cognate antigens, mAbs form immune complexes (ICs) that can be recognized by the Fc receptors expressed on different immune cells of infected individuals. This binding may be followed by the modulation of the host immune responses. Harnessing this immunomodulatory property may facilitate improvements in the therapeutic potential of antiviral mAbs. This review focuses on the role of ICs formed with different viral determinants and mAbs in the induction of antiviral immune responses in the context of both passive immunotherapies and vaccination strategies. Potential deleterious effects of ICs on the host immune response are also discussed.


title: Comparing the protective performances of 3 types of N95 filtering facepiece respirators during chest compressions: A randomized simulation study

text: OBJECTIVE: Healthcare providers in emergency departments should wear respirators for infection protection. However, the wearer's vigorous movements during cardiopulmonary resuscitation may affect the protective performance of the respirator. Herein, we aimed to assess the effects of chest compressions (CCs) on the protective performance of respirators. METHODS: This crossover study evaluated 30 healthcare providers from 1 emergency department who performed CC with real-time feedback. The first, second, and third groups started with a cup-type, fold-type, and valve-type respirator, respectively, after which the respirators were randomized for each group. The fit factors were measured using a quantitative fit testing device before and during the CC in each experiment. The protection rate was defined as the proportion of respirators achieving a fit factor ≥100. RESULTS: The fold-type respirator had a significantly greater protection rate at baseline (100.0% ± 0.0%) compared to the cup-type (73.6% ± 39.6%, P = .003) and valve-type respirators (87.5% ± 30.3%, P = .012). During the CC, the fit factor values significantly decreased for the cup-type (44.9% ± 42.8%, P < .001) and valve-type respirators (59.5% ± 41.7%, P = .002), but not for the fold-type respirator (93.2% ± 21.7%, P = .095). CONCLUSIONS: The protective performances of respirators may be influenced by CC. Healthcare providers should identify the respirator that provides the best fit for their intended tasks.


title: Mechanisms involved in the development of thrombocytopenia in patients with COVID-19

text: Corona Virus Disease 2019 (COVID-19) is caused by the novel coronavirus SARS-CoV-2. Emerging genetic and clinical evidence suggests similarities between COVID-19 patients and those with severe acute respiratory syndrome and Middle East respiratory syndrome. Hematological changes such as lymphopenia and thrombocytopenia are not rare in COVID-19 patients, and a smaller population of these patients had leukopenia. Thrombocytopenia was detected in 5–41.7% of the patients with COVID-19. Analyzing the dynamic decrease in platelet counts may be useful in the prognosis of patients with COVID-19. However, the mechanisms underlying the development of thrombocytopenia remain to be elucidated. This review summarizes the hematological changes in patients infected with SARS-CoV-2 and possible underlying mechanisms of thrombocytopenia development.


Recovering from COVID-19: the key issues


Failure to detect MERS‐CoV RNA in urine of naturally infected dromedary camels


title: Construction of a recombinant rhinovirus accommodating fluorescent marker expression

text: BACKGROUND: Rhinovirus (RV) causes the common cold and asthma exacerbations. The RV genome is a 7.3 kb single‐strand positive‐sense RNA. OBJECTIVE: Using minor group RV1A as a backbone, we sought to design and generate a recombinant RV1A accommodating fluorescent marker expression, thereby allowing tracking of viral infection. METHOD: Recombinant RV1A infectious cDNA clones harboring the coding sequence of green fluorescent protein (GFP), Renilla luciferase, or iLOV (for light, oxygen, or voltage sensing) were engineered and constructed. RV‐infected cells were determined by flow cytometry, immunohistochemistry, and immunofluorescence microscopy. RESULTS: RV1A‐GFP showed a cytopathic effect in HeLa cells but failed to express GFP or Renilla luciferase due to deletion. The smaller fluorescent protein construct, RV1A‐iLOV, was stably expressed in infected cells. RV1A‐iLOV expression was used to examine the antiviral effect of bafilomycin in HeLa cells. Compared to parental virus, RV1A‐iLOV infection of BALB/c mice yielded a similar viral load and level of cytokine mRNA expression. However, imaging of fixed lung tissue failed to reveal a fluorescent signal, likely due to the oxidation and bleaching of iLOV‐bound flavin mononucleotide. We therefore employed an anti‐iLOV antibody for immunohistochemical and immunofluorescence imaging. The iLOV signal was identified in airway epithelial cells and CD45+ CD11b+ lung macrophages. CONCLUSIONS: These results suggest that RV1A‐iLOV is a useful molecular tool for studying RV pathogenesis. The construction strategy for RV1A‐iLOV could be applied to other RV serotypes. However, the detection of iLOV‐expressing RV in fixed tissue required the use of an anti‐iLOV antibody, limiting the value of this construct.


title: Human quarantine: Toward reducing infectious pressure on chimpanzees at the Taï Chimpanzee Project, Côte d'Ivoire

text: Due to their genetic relatedness, great apes are highly susceptible to common human respiratory pathogens. Although most respiratory pathogens, such as human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV), rarely cause severe disease in healthy human adults, they are associated with considerable morbidity and mortality in wild great apes habituated to humans for research or tourism. To prevent pathogen transmission, most great ape projects have established a set of hygiene measures ranging from keeping a specific distance, to the use of surgical masks and establishment of quarantines. This study investigates the incidence of respiratory symptoms and human respiratory viruses in humans at a human‐great ape interface, the Taï Chimpanzee Project (TCP) in Côte d'Ivoire, and consequently, the effectiveness of a 5‐day quarantine designed to reduce the risk of potential exposure to human respiratory pathogens. To assess the impact of quarantine as a preventative measure, we monitored the quarantine process and tested 262 throat swabs for respiratory viruses, collected during quarantine over a period of 1 year. Although only 1 subject tested positive for a respiratory virus (HRSV), 17 subjects developed symptoms of infection while in quarantine and were subsequently kept from approaching the chimpanzees, preventing potential exposure in 18 cases. Our results suggest that quarantine—in combination with monitoring for symptoms—is effective in reducing the risk of potential pathogen exposure. This research contributes to our understanding of how endangered great apes can be protected from human‐borne infectious disease.


title: A comparison study between GeXP-based multiplex-PCR and serology assay for Mycoplasma pneumoniae detection in children with community acquired pneumonia

text: BACKGROUND: Diagnosis of community-acquired pneumonia (CAP) caused by Mycoplasma pneumoniae (Mp) in children has been hampered by difficulty in obtaining convalescent serum and time constraints. In this study, the two diagnostic assays that targeted respectively on Mp-antibody and Mp-DNA were retrospectively investigated. METHODS: A total of 3146 children were clinically diagnosed to have CAP and were confirmed by chest X-ray during March 2015 to February 2016 in Children’s hospital of Hebei Province (China). Both of the sera and sputum samples were collected in 24 h after their admission. The Mp-antibody was examined by the passive particle agglutination assay and a fourfold or greater increase of antibody titers of paired sera or≧1:160 titer of single serum was set as the serology positive. Mp-DNA in the sputum samples was tested by a multiplex-PCR method named GeXP assay (multiplex PCR combined with automated capillary electrophoresis). In order to eliminate the false positive results caused by the asymptomatic carriage after infected by M. pneumoniae, the inconsistent samples were tested by the real-time isothermal transcription-mediated RNA amplification assay (SAT). RESULTS: The inter-rated agreement test was performed in 3146 CAP patients, with a highest kappa value in the school-age children as 0.783. There were 6.29% (198/3146) cases showed inconsistent results determined by GeXP and serology assay. All of the 19 GeXP(+)/Serology (−) samples and a randomly chosen 27 from 179 GeXP(−)/Serology (+) samples were tested by SAT assay, and a 97.8% diagnosis agreement was observed between SAT and GeXP assay, but not with the serology assay. In addition, patients who were detected only by serology or only by multiplex-PCR were significantly younger than those with both methods positive (3.0 and 1.5 years vs. 5.0 years, p < 0.01). The Viral-Mp coinfection accounted for 37.0% (97/262), which was more common in winter and spring (p < 0.05) and in the infantile group (p < 0.01), compared to the pure Mp positive ones. CONCLUSION: In some children CAP cases, the Mp laboratory diagnosis was inconsistent between serology and multiplex-PCR assay. Verified by the SAT assay, the GeXP showed a more sensitive and reliable performance compared with the serology assay. Furthermore, employing the multiplex-PCR could provide more information on the associated pathogens for clinical assessment of CAP. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-017-2614-3) contains supplementary material, which is available to authorized users.


title: Could sudden sensorineural hearing loss be the sole manifestation of COVID-19? An investigation into SARS-COV-2 in the etiology of sudden sensorineural hearing loss

text: Abstract Objective The aim of this study is to investigate the presence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in patients presenting with only sudden sensorineural hearing loss (SSNHL) during the pandemic. Methods The study included 5 male patients who presented with the sole complaint of unilateral SSNHL to the otolaryngology outpatient clinic between April 3 and April 12, 2020. The patients were referred to the infectious diseases clinic to be evaluated for SARS-CoV-2 by using real time polymerase chain reaction (RT-PCR) testing. Results RT-PCR testing for SARS-CoV-2 were positive in one of the patient and negative in rest four patients. We also noted positive response to Coronavirus Disease-19 (COVID-19) specific treatment in SARS-CoV-2 positive SSNHL patient. Conclusion It should be kept in mind that non-specific symptoms such as SSNHL could be the only sign to recognize a COVID-19 case. Awareness of such a non-specific presentation of COVID-19 patients is crucial during this pandemic period for the prevention of infectious spread through isolation and early initiation of COVID-19 targeted treatment.


title: The Diagnosis of Viral Respiratory Disease in Older Adults

text: Viral respiratory disease in older adults has been increasingly recognized as a significant cause of hospitalizations and death. Unfortunately, the recognition and diagnosis of infection due to many viral respiratory pathogens in older adults can be elusive due to atypical clinical presentations and the insensitivity of current laboratory diagnostic tests in this population. For influenza diagnosis, rapid antigen tests followed by viral culture if negative, can be useful in older adults as long as clinicians are mindful of test limitations. Although specific, rapid antigen tests are insensitive in this population. Erroneous negative results may lead to delays in timely administration of antiviral treatment and institution of appropriate isolation precautions. The increasing availability of new rapid and sensitive molecular diagnostics such as polymerase chain reaction testing, should provide more accurate and timely diagnoses of viral respiratory infections in older adults in the near future.


title: Health risks at the Hajj

text: Summary Annually, millions of Muslims embark on a religious pilgrimage called the “Hajj” to Mecca in Saudi Arabia. The mass migration during the Hajj is unparalleled in scale, and pilgrims face numerous health hazards. The extreme congestion of people and vehicles during this time amplifies health risks, such as those from infectious diseases, that vary each year. Since the Hajj is dictated by the lunar calendar, which is shorter than the Gregorian calendar, it presents public-health policy planners with a moving target, demanding constant preparedness. We review the communicable and non-communicable hazards that pilgrims face. With the rise in global travel, preventing disease transmission has become paramount to avoid the spread of infectious diseases, including SARS (severe acute respiratory syndrome), avian influenza, and haemorrhagic fever. We examine the response of clinicians, the Saudi Ministry of Health, and Hajj authorities to these unique problems, and list health recommendations for prospective pilgrims.


title: On the responsible use of digital data to tackle the COVID-19 pandemic

text: Large-scale collection of data could help curb the COVID-19 pandemic, but it should not neglect privacy and public trust. Best practices should be identified to maintain responsible data-collection and data-processing standards at a global scale.


title: Molecular Characterization of Major Structural Protein Genes of Avian Coronavirus Infectious Bronchitis Virus Isolates in Southern China

text: To gain comprehensive genetic information of circulating avian coronavirus infectious bronchitis virus (IBV) isolates in China, analysis of the phylogenetic tree, entropy of the amino acid sequences, and the positive selection as well as computational recombinations of S1, M and N genes of 23 IBV isolates was conducted in the present study. The phylogenetic trees based on the S1, M and N genes exhibited considerably different topology and the CK/CH/LSC/99I-type isolates were the predominant IBVs based on the phylogenetic analysis of S1 gene. Results of entropy of amino acid sequences revealed that the S1 gene had the largest variation; the M gene had less variation than the N gene. Positive selections were detected in not only S1 but also M and N gene proteins. In addition, five S1 gene recombinants between vaccine strain 4/91 and CK/CH/LSC/99I-type field isolate were confirmed. In conclusion, multiple IBV genotypes co-circulated; genetic diversity and positive selections existed in S1, M and N genes; 4/91 vaccine recombinants emerged in China. Our results show that field IBVs in China are continuing to evolve and vaccine strains may have an important role in the appearance of new IBV strains via recombination. In addition, the present study indicates that IBV evolution is driven by both generations of genetic diversity and selection.


title: Case fatality rate analysis of Italian COVID‐19 outbreak

text: The Italian outbreak of COVID‐19 cases is a public health emergency and there is a worldwide tremendous interest in the evaluation of the Italian epidemic evolution. Indeed, from February 2020, Italy is facing an explosion of COVID‐19 cases. In particular, the Italian observed case fatality rate (CFR) is much higher than the other countries. Recently, it has been hypothesized that the extensive number of intergenerational contacts—typical of Italian culture—could contribute to explain the high number of deaths observed in Italy. However, through an analysis performed for all the Italian regions, here it is shown that the deaths are localized in specific regions and that the CFRs of different Italian regions are overlapping with the rates of European countries. Moreover, through correlation analyses between CFRs and different social habits, it is shown that no positive correlation is observed between social behaviors and CFRs. In conclusion, this analysis clearly rejects the possibility that social habits and intergenerational contacts can contribute to explaining such a profound effect on the number of deaths observed in Italy during the COVID‐19 outbreak and more effort should be addressed to evaluate the real amount of positive cases.


title: Behavioral predictors of subsequent respiratory illness signs in dogs admitted to an animal shelter

text: Individual variability is evident in behavior and physiology of animals. Determining whether behavior at intake may predict subsequent illness in the animal shelter may influence the management of dogs housed at animal shelters and reduce overall disease. While normally associated with mild disease and low mortality rates, respiratory disease nevertheless poses significant challenges to the management of dogs in the stressful environment of animal shelters due to its highly infectious nature. Therefore, the aim of the study was to explore whether behavior at intake can predict subsequent occurrence and progression of upper respiratory disease in dogs at animal shelters. In a correlational study, 84 dogs were assessed throughout their stay at a city animal shelter. The dogs were subjected to a behavioral assessment, 1 min in-kennel behavioral observations across two observation periods, and the collection of urinary cortisol:creatinine (C:C) ratio. The occurrence and progression of upper respiratory disease was monitored through repeated clinical exams (rectal temperature and the occurrence of nasal and ocular discharge, and presence of coughing and sneezing). A basic PLS Path regression model revealed that time in the shelter (estimate = .53, p < .001), and sociability (estimate = .24, p < .001) and curiosity scores (estimate = .09, p = .026) were associated with increased illness. Activity and anxiety scores, however, were not associated with illness. Urinary C:C, taken on the first full day, did not predict subsequent illness when accounting for time. Limitations included attrition of dogs, a small percentage receiving vaccinations, and continuous and non-systematic rotation of dogs in the kennels. Understanding if behavior can predict subsequent illness may improve shelter management practices, and in turn, result in improved live-release outcomes.


title: Remyelination-Promoting Human IgMs: Developing a Therapeutic Reagent for Demyelinating Disease

text: Promoting remyelination following injury to the central nervous system (CNS) promises to be an effective neuroprotective strategy to limit the loss of surviving axons and prevent disability. Studies confirm that multiple sclerosis (MS) and spinal cord injury lesions contain myelinating cells and their progenitors. Recruiting these endogenous cells to remyelinate may be of therapeutic value. This review addresses the use of antibodies reactive to CNS antigens to promote remyelination. Antibody-induced remyelination in a virus-mediated model of chronic spinal cord injury was initially observed in response to treatment with CNS reactive antisera. Monoclonal mouse and human IgMs, which bind to the surface of oligodendrocytes and myelin, were later identified that were functionally equivalent to antisera. A recombinant form of a human remyelination-promoting IgM (rHIgM22) targets areas of CNS injury and promotes maximal remyelination within 5 weeks after a single low dose (25 μg/kg). The IgM isoform of this reparative antibody is required for in vivo function. We hypothesize that the IgM clusters membrane domains and associated signaling molecules on the surface of target cells. Current therapies for MS are designed to modulate inflammation. In contrast, remyelination promoting IgMs are the first potential therapeutic molecules designed to induce tissue repair by acting within the CNS at sites of damage on the cells responsible for myelin synthesis.


title: FDG PET/CT in Diagnosing COVID-19 Infection in a Cancer Patient With Exposure History But Minimal Symptoms

text: A 56-year-old woman with high-grade neuroendocrine small cell carcinoma had known contact history of COVID-19 about 16 days prior to the restaging PET/CT. The patient was instructed to self-quarantine for 14 days, and no COVID-19 test was performed. Upon arrival, the patient had low-grade fever of 37.1°C, but did not meet infection control criteria for COVID-19 testing, and it was approved to proceed with PET/CT. The FDG PET/CT images revealed new multifocal hypermetabolic bilateral pulmonary ground-glass opacities that are suggestive of COVID-19 pneumonia. Meanwhile, the patient’s symptoms worsened, and a blood test later confirmed COVID-19 infection.


title: Rapid and simple colorimetric detection of multiple influenza viruses infecting humans using a reverse transcriptional loop-mediated isothermal amplification (RT-LAMP) diagnostic platform

text: BACKGROUND: In addition to seasonal influenza viruses recently circulating in humans, avian influenza viruses (AIVs) of H5N1, H5N6 and H7N9 subtypes have also emerged and demonstrated human infection abilities with high mortality rates. Although influenza viral infections are usually diagnosed using viral isolation and serological/molecular analyses, the cost, accessibility, and availability of these methods may limit their utility in various settings. The objective of this study was to develop and optimized a multiplex detection system for most influenza viruses currently infecting humans. METHODS: We developed and optimized a multiplex detection system for most influenza viruses currently infecting humans including two type B (both Victoria lineages and Yamagata lineages), H1N1, H3N2, H5N1, H5N6, and H7N9 using Reverse Transcriptional Loop-mediated Isothermal Amplification (RT-LAMP) technology coupled with a one-pot colorimetric visualization system to facilitate direct determination of results without additional steps. We also evaluated this multiplex RT-LAMP for clinical use using a total of 135 clinical and spiked samples (91 influenza viruses and 44 other human infectious viruses). RESULTS: We achieved rapid detection of seasonal influenza viruses (H1N1, H3N2, and Type B) and avian influenza viruses (H5N1, H5N6, H5N8 and H7N9) within an hour. The assay could detect influenza viruses with high sensitivity (i.e., from 100 to 0.1 viral genome copies), comparable to conventional RT-PCR-based approaches which would typically take several hours and require expensive equipment. This assay was capable of specifically detecting each influenza virus (Type B, H1N1, H3N2, H5N1, H5N6, H5N8 and H7N9) without cross-reactivity with other subtypes of AIVs or other human infectious viruses. Furthermore, 91 clinical and spiked samples confirmed by qRT-PCR were also detected by this multiplex RT-LAMP with 98.9% agreement. It was more sensitive than one-step RT-PCR approach (92.3%). CONCLUSIONS: Results of this study suggest that our multiplex RT-LAMP assay may provide a rapid, sensitive, cost-effective, and reliable diagnostic method for identifying recent influenza viruses infecting humans, especially in locations without access to large platforms or sophisticated equipment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-4277-8) contains supplementary material, which is available to authorized users.


title: Factors Associated with Resilience Among Medical Staff in Radiology Departments During The Outbreak of 2019 Novel Coronavirus Disease (COVID-19): A Cross-Sectional Study

text: BACKGROUND: A growing body of evidence suggests that in the face of life adversity, threats, or other major stressful events, resilience is more conducive to individual adaptation and growth. MATERIAL/METHODS: The Connor-Davidson Resilience Scale and the Chinese Perceived Stress Scale were used to evaluate the resilience and perceived stress of 600 medical staff members from the radiology departments in 32 public hospitals in Sichuan Province, China, respectively. Multiple linear regression was used to analyze factors related to resilience. RESULTS: The total resilience score was 65.76±17.26, wherein the toughness dimension score was 33.61±9.52, the strength dimension score was 21.25±5.50, and the optimism dimension score was 10.91±3.15. There was a significant negative correlation between perceived stress and resilience (r=−0.635, P<0.001). According to multivariate analysis, the total perceived stress score (β=−1.318, P<0.001), gender (β=−4.738, P<0.001), knowledge of COVID-19 (β=2.884, P=0.043), knowledge of COVID-19 protective measures (β=3.260, P=0.042), and availability of adequate protective materials (β=−1.268, P=0.039) were independent influencing factors for resilience. CONCLUSIONS: The resilience level of the medical staff in the radiology departments during the outbreak of COVID-19 was generally low, particularly regarding toughness. More attention should be paid to resilience influence factors such as high perceived stress, female gender, lack of understanding of COVID-19 and protective measures, and lack of protective materials, and targeted interventions should be undertaken to improve the resilience level of the medical staff in the radiology departments during the outbreak of COVID-19.


title: Management of primary cutaneous lymphoma patients during COVID‐19 pandemic: EORTC CLTF guidelines Maarten Vermeer

text: During severe inflammatory coronavirus infectious disease (CoVID‐19) pandemic and based on evidence on COVID‐19 epidemiology, patients with primary cutaneous lymphomas (PCLs) have risk for developing complicated COVID‐19 infections in consideration of their older age (majority above 60) and their potential underlying predisposing conditions (e.g. hypertension, diabetes).(1,2,3) Moreover, PCL patients with aggressive biologic behavior should be carefully monitored according to guidelines for patients with neoplastic disease.


title: Detection of Pneumococcal DNA in Blood by Polymerase Chain Reaction for Diagnosing Pneumococcal Pneumonia in Young Children From Low- and Middle-Income Countries

text: BACKGROUND. We investigated the performance of polymerase chain reaction (PCR) on blood in the diagnosis of pneumococcal pneumonia among children from 7 low- and middle-income countries. METHODS. We tested blood by PCR for the pneumococcal autolysin gene in children aged 1–59 months in the Pneumonia Etiology Research for Child Health (PERCH) study. Children had World Health Organization–defined severe or very severe pneumonia or were age-frequency–matched community controls. Additionally, we tested blood from general pediatric admissions in Kilifi, Kenya, a PERCH site. The proportion PCR-positive was compared among cases with microbiologically confirmed pneumococcal pneumonia (MCPP), cases without a confirmed bacterial infection (nonconfirmed), cases confirmed for nonpneumococcal bacteria, and controls. RESULTS. In PERCH, 7.3% (n = 291/3995) of cases and 5.5% (n = 273/4987) of controls were blood pneumococcal PCR-positive (P < .001), compared with 64.3% (n = 36/56) of MCPP cases and 6.3% (n = 243/3832) of nonconfirmed cases (P < .001). Blood pneumococcal PCR positivity was higher in children from the 5 African countries (5.5%–11.5% among cases and 5.3%–10.2% among controls) than from the 2 Asian countries (1.3% and 1.0% among cases and 0.8% and 0.8% among controls). Among Kilifi general pediatric admissions, 3.9% (n = 274/6968) were PCR-positive, including 61.7% (n = 37/60) of those with positive blood cultures for pneumococcus. DISCUSSION. The utility of pneumococcal PCR on blood for diagnosing childhood pneumococcal pneumonia in the 7 low- and middle-income countries studied is limited by poor specificity and by poor sensitivity among MCPP cases.


Optimizing Clinical Staffing in Times of a Pandemic Crisis Such as Coronavirus Disease 2019


title: In-Vivo Toxicity Studies and In-Vitro Inactivation of SARS-CoV-2 by Povidone-iodine In-situ Gel Forming Formulations

text: To curb the spread of SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, we characterize the virucidal activity of long-acting Povidone Iodine (PVP-I) compositions developed using an in-situ gel forming technology. The PVP-I gel forming nasal spray (IVIEW-1503) and PVP-I gel forming ophthalmic eye drop (IVIEW-1201) rapidly inactivated SARS-CoV-2, inhibiting the viral infection of VERO76 cells. No toxicity was observed for the PVP-I formulations. Significant inactivation was noted with preincubation of the virus with these PVP-I formulations at the lowest concentrations tested. It has been demonstrated that both PVP-I formulations can inactivate SARS-CoV-2 virus efficiently in both a dose-dependent and a time-dependent manner. These results suggest IVIEW-1503 and IVIEW-1201 could be potential agents to reduce or prevent the transmission of the virus through the nasal cavity and the eye, respectively. Further studies are needed to clinically evaluate these formulations in early-stage COVID-19 patients.


title: Discovering human history from stomach bacteria

text: Recent analyses of human pathogens have revealed that their evolutionary histories are congruent with the hypothesized pattern of ancient and modern human population migrations. Phylogenetic trees of strains of the bacterium Helicobacter pylori and the polyoma JC virus taken from geographically diverse groups of human beings correlate closely with relationships of the populations in which they are found.


title: Characterization of Human Coronaviruses on Well-Differentiated Human Airway Epithelial Cell Cultures

text: The human airway serves as the entry point of human respiratory viruses, including human coronaviruses. In this chapter we outline the methods by which we establish fully differentiated airway epithelium and its use for human coronavirus propagation. Additionally, we outline methods for immunofluorescence staining of these cultures for virus detection, characterization of cell tropism, and how to perform antiviral assays and quantify viral replication.


title: Ayurvedic Treatment of COVID-19/ SARS-CoV-2: a case report

text: This is the first known case of a Coronavirus disease (COVID-19) positive patient treated entirely with Ayurveda. So far in Modern Western Medicine (MWM), no cure has been found which is specific to COVID-19. The only literature relevant to the treatment of Coronavirus disease has surfaced from Traditional Chinese Medicine (TCM). TCM which was extensively used to control the epidemic in China, also consists of herbal medicines similar to Ayurveda. In this case, the patient, who was familiar with the use of Ayurvedic medicines, fully aware that no proven cure exists in MWM, decided to entirely rely on the limited Ayurvedic medicines that he had in his possession at the time of falling ill. Despite the patient presenting with symptoms, namely high fever, severe body pain and severe cough, along with many of the other associated symptoms of COVID-19, the progress of the disease could be arrested within a short period by being exclusively on Ayurvedic medicines. This illustrates that there is a wide scope to explore the variety of pertinent medicines present in Ayurvedic pharmacopoeia which can be used more rationally to suit every stage of the disease. Being the first-of -its-kind it is a valuable contribution to scientific literature from the world of Ayurveda. This should encourage the healthcare policy makers to quickly use Ayurveda to bring COVID-19 pandemic under control in India, as they seemed to have demonstrated it in China with TCM.


Assessment of ST-Segment Elevation Myocardial Infarction Volume Trends During The COVID-19 Pandemic


Current pharmacy practices in low- and middle-income countries; recommendations in response to the COVID-19 pandemic


title: Challenges in the analysis of viral metagenomes

text: Genome sequencing technologies continue to develop with remarkable pace, yet analytical approaches for reconstructing and classifying viral genomes from mixed samples remain limited in their performance and usability. Existing solutions generally target expert users and often have unclear scope, making it challenging to critically evaluate their performance. There is a growing need for intuitive analytical tooling for researchers lacking specialist computing expertise and that is applicable in diverse experimental circumstances. Notable technical challenges have impeded progress; for example, fragments of viral genomes are typically orders of magnitude less abundant than those of host, bacteria, and/or other organisms in clinical and environmental metagenomes; observed viral genomes often deviate considerably from reference genomes demanding use of exhaustive alignment approaches; high intrapopulation viral diversity can lead to ambiguous sequence reconstruction; and finally, the relatively few documented viral reference genomes compared to the estimated number of distinct viral taxa renders classification problematic. Various software tools have been developed to accommodate the unique challenges and use cases associated with characterizing viral sequences; however, the quality of these tools varies, and their use often necessitates computing expertise or access to powerful computers, thus limiting their usefulness to many researchers. In this review, we consider the general and application-specific challenges posed by viral sequencing and analysis, outline the landscape of available tools and methodologies, and propose ways of overcoming the current barriers to effective analysis.


title: Challenges in RNA virus bioinformatics

text: Motivation: Computer-assisted studies of structure, function and evolution of viruses remains a neglected area of research. The attention of bioinformaticians to this interesting and challenging field is far from commensurate with its medical and biotechnological importance. It is telling that out of >200 talks held at ISMB 2013, the largest international bioinformatics conference, only one presentation explicitly dealt with viruses. In contrast to many broad, established and well-organized bioinformatics communities (e.g. structural genomics, ontologies, next-generation sequencing, expression analysis), research groups focusing on viruses can probably be counted on the fingers of two hands. Results: The purpose of this review is to increase awareness among bioinformatics researchers about the pressing needs and unsolved problems of computational virology. We focus primarily on RNA viruses that pose problems to many standard bioinformatics analyses owing to their compact genome organization, fast mutation rate and low evolutionary conservation. We provide an overview of tools and algorithms for handling viral sequencing data, detecting functionally important RNA structures, classifying viral proteins into families and investigating the origin and evolution of viruses. Contact: manja@uni-jena.de Supplementary information: Supplementary data are available at Bioinformatics online. The references for this article can be found in the Supplementary Material.


title: Chapter 19 Species Inquirendae in the Carnivora

text: Abstract There are at least 483 reports of carnivore apicomplexans in the literature citing 17 genera or generic categoriesthat have not been described sufficiently or there was so little information provided by the author(s), that their validity, and sometimes even their identity is in question. These include: 2 “Apicomplexa protozoa,” 1 Besnoitia sp., 34 Coccidia-like or Coccidia spp., 135 Cryptosporidium spp., 2 Cyclospora spp., 26 Cystoisospora spp., 36 Eimeria spp., 3 Hammondia-like forms; 7 Hammondia–Neospora-like forms; 7 Hammondia–Toxoplasma-like forms; 14 Hepatozoon spp., 1 Hoareosporidium sp., 72 Isospora spp., 1 Klossia sp., 1 “oocysts,” 135 Sarcocystis spp., and 3 Toxoplasma-like forms. All are considered species inquirendae. In addition, two names, Isospora novocati of Pellérdy, 1974b and Isospora mustelae of Galli-Valerio, 1932, are considered nomen nuda, by definition. There is no record that 37/72 (51%) Caniformia genera, and all their 60 species, and 37/54 (68.5%) Feliformia genera, and all their 49 species, have any of these abbreviated identifications attached to them because most, if not all, likely were never surveyed for intestinal coccidian parasites. And, in the 52 genera that have been surveyed, the vast majority of their 177 species have not yet been looked at for coccidia.


title: Cutaneous manifestations in patients with COVID‐19: A preliminary review of an emerging issue

text: BACKGROUND: The infection caused by the recently identified SARS‐CoV‐2, called COronaVIrus Disease‐19 (COVID‐19), has rapidly spread throughout the world. With the exponential increase of patients worldwide, the clinical spectrum of COVID‐19 is being better defined and new symptoms are emerging. Numerous reports are documenting the occurrence of different cutaneous manifestations in COVID‐19 patients. OBJECTIVES: To provide a brief overview of the COVID‐19‐associated cutaneous lesions. METHODS: Literature search was performed in the PubMed, Scopus and Web of Science databases up to 30 April 2020. This narrative review summarizes the available data regarding clinical and histological features of COVID‐19‐associated skin manifestations. RESULTS: Literature reports showed a great heterogeneity in COVID‐19‐associated cutaneous manifestations, as well as in their latency periods and associated extracutaneous symptoms. Pathogenic mechanisms are unknown, although the role of hyperactive immune response, complement activation and microvascular injury has been hypothesized. Based on our experience and the literature data, we subdivided the reported cutaneous lesions into six main clinical patterns: i) urticarial rash, ii) confluent erythematous/maculo‐papular/morbilliform rash, iii) papulovesicular exanthem, iv) chilblain‐like acral pattern, v) livedo reticularis/racemosa‐like pattern, vi) purpuric “vasculitic” pattern. These six patterns can be merged into two main settings: the first one – inflammatory/exanthematous – including the first three groups cited above and the second one including the vasculopathic/vasculitic lesions of the last three aforementioned groups. CONCLUSIONS: The possible presence of cutaneous findings leading to suspect COVID‐19 puts dermatologists in a relevant position. Further studies are needed to delineate the diagnostic and prognostic value of such cutaneous manifestations.


Mental health in the Covid-19 pandemic


title: A DNA miniarray system for simultaneous visual detection of porcine circovirus type 1 (PCV1) and 2 (PCV2) in pigs

text: A miniarray system was developed for the simultaneous detection of porcine circovirus type 1 (PCV1) and type 2 (PCV2) in pigs. The system consists of a polymerase chain reaction (PCR) step to amplify target viral DNA, followed by detection of the amplified DNA using a membrane-anchored probe array and an avidin-alkaline phosphatase (Av-AP) indicator system. The lower limit of detection of PCV using the miniarray was 10(1.9) tissue culture infectious dose 50 (TCID(50))/ml and 10(2.08)TCID(50)/ml for PCV1 and PCV2, respectively, and 100 viral copies/μl for both PCV1 and PCV2. We validated the miniarray system using 141 lymph node specimens from pigs with suspected postweaning multisystemic wasting syndrome or porcine dermatitis and nephropathy syndrome. Of the 141 samples evaluated, 55 were identified as positive for PCV by the miniarray. Relative to in situ hybridization, the sensitivity and specificity of the miniarray was 100% and 98.9%, respectively. In contrast to other microarray systems, the miniarray does not require a DNA chip reader, since the results can be determined by visual inspection of colorized spots on a nylon membrane. This system represents an effective alternative method for the differential detection of PCV1 and PCV2 in pigs, as well as the maintenance of PCV-free cell lines and pre-screening of commercial vaccines for possible contamination.


title: Valuation Effect of Capital Account Liberalization: Evidence from the Chinese Stock Market

text: This paper examines the valuation effect of capital account liberalization. Using an event study approach and the policy announcement for RMB Qualified Foreign Institutional Investors (short for RQFII) as the event date, we find that overall, the stock market responded positively to the capital account liberalization announcement. In addition, we provide some heterogeneity that firms with more stringent financing constraints earn higher returns than their counterparts. Finally, existing local institutions play an important role in determining announcement returns.


title: Virus PCR Assay Panels: An Alternative to the Mouse Antibody Production Test

text: Antibody production tests have traditionally been used to test biological materials for viral contamination. Now molecular biology techniques have emerged as an alternative. The authors compare MAP testing with PCR-based detection methods, focusing on differences in animal use, laboratory requirements, sample size, and limits of detection.


title: The use of endogenous and exogenous reference RNAs for qualitative and quantitative detection of PRRSV in porcine semen

text: Abstract Semen is known to be a route of porcine reproductive and respiratory syndrome virus (PRRSV) transmission. A method was developed for qualitative and quantitative detection of the seminal cell-associated PRRSV RNA in relation to endogenous and exogenous reference RNAs. As endogenous control for one-step real-time reverse transcription (RT)-PCR UBE2D2 mRNA was selected. Particularly for the analysis of persistent infections associated with low copy numbers of PRRSV RNA, UBE2D2 mRNA is an ideal control due to its low expression in seminal cells and its detection in all samples analysed (n =36). However, the amount of UBE2D2 mRNA in porcine semen varied (up to 106-fold), thus its use is limited to qualitative detection of PRRSV RNA. For quantitation, a synthetic, non-metazoan RNA was added to the RNA isolation reaction at an exact copy number. The photosynthesis gene ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL) from Arabidopsis thaliana was used as an exogenous spike. Unexpectedly, PRRSV RNA was detected in a herd of specific pathogen-free (SPF) boars which were tested ELISA-negative for anti-PRRSV antibodies. Therefore, RT-PCR for seminal cell-associated PRRSV is a powerful tool for managing the SPF status during quarantine programs and for routine outbreak investigations.


Artemisia and COVID-19


title: Informations

text: COVID-19 et nutrition sur le site de la SFN La SFN a relayé sur son site plusieurs informations concernant le COVID-19, les pathologies chroniques et les risques nutritionnels La SFN a contribué activement à l’établissement des recommandations à visée des personnels de santé et des patients souffrant d’obésité Ainsi, la SFN s’est associée à l’AFERO et à la FFN pour élaborer le document de la HAS « Réponses rapides dans le cadre du COVID-19 —– pathologies chroniques et risques nutritionnels en ambulatoire » La SFN s’est aussi associée à l’AFERO, aux CSOs et aux Associations Nationales de Patients pour élaborer des conseils à destination des personnes en situation d’obésité pendant le confinement Le « Replay du Webinaire » coorganisé par la SFN et l’AFERO sur COVID-19 et obésité animé par Eric Bertin et Karine Clément est aussi relayé


title: Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus

text: Summary The outbreak of SARS warrants the search for antiviral compounds to treat the disease. At present, no specific treatment has been identified for SARS-associated coronavirus infection. We assessed the antiviral potential of ribavirin, 6-azauridine, pyrazofurin, mycophenolic acid, and glycyrrhizin against two clinical isolates of coronavirus (FFM-1 and FFM-2) from patients with SARS admitted to the clinical centre of Frankfurt University, Germany. Of all the compounds, glycyrrhizin was the most active in inhibiting replication of the SARS-associated virus. Our findings suggest that glycyrrhizin should be assessed for treatment of SARS.


title: Stratégie pour la pratique de la chirurgie digestive et oncologique en situation d’épidémie de COVID-19

text: Résumé La pandémie due au COVID-19 modifie l’organisation des soins et change la réalisation de la chirurgie digestive. Les priorités sanitaires et les circuits de soins sont modifiés. La chirurgie d’urgence reste prioritaire. Les interventions pour chirurgie fonctionnelles sont à reporter. La chirurgie par laparoscopie doit suivre des règles strictes pour ne pas exposer les professionnels à un surrisque. Le questionnement principal concerne la chirurgie oncologique, opérer ou reporter ? Il existe probablement un sur risque opératoire induit par la pandémie qui doit être mis en balance avec le retard de prise en charge chirurgical. Pour chaque type de cancer, colon, pancréas, œsogastrique, hépatocarcinome, la morbi-mortalité est rappelée et mise en parallèle avec le risque oncologique lié au retard à la chirurgie et/ou au temps de doublement de la tumeur. Cette comparaison permet de proposer des stratégies, ainsi pour les cancers coliques (T1-2, N0), il est souhaitable de retarder la chirurgie. Pour les lésions coliques avancées, il semble prudent de recommander une chimiothérapie néo adjuvante et d’attendre. Pour les cancers du rectum T3-4 et/ou N+, une radio-chimiothérapie est indiquée, une radiothérapie courte devra être discutée (suivie d’une période d’attente) afin de réduire le temps d’exposition à l’hôpital et d’éviter les infections. La majorité des chirurgies complexes à forte morbi-mortalité, œsogastrique, hépatique ou pancréatique doivent sans doute le plus souvent être reportée. Summary The COVID-19 pandemic is changing the organization of healthcare and has a direct impact on digestive surgery. Healthcare priorities and circuits are being modified. Emergency surgery is still a priority. Functional surgery is to be deferred. Laparoscopic surgery must follow strict rules so as not to expose healthcare professionals (HCPs) to added risk. The question looms large in cancer surgery – go ahead or defer? There is probably an added risk due to the pandemic that must be balanced against the risk incurred by deferring surgery. For each type of cancer – colon, pancreas, oesogastric, hepatocellular carcinoma – morbidity and mortality rates are stated and compared with the oncological risk incurred by deferring surgery and/or the tumour doubling time. Strategies can be proposed based on this comparison. For colonic cancers T1-2, N0, it is advisable to defer surgery. For advanced colonic lesions, it seems judicious to undertake neoadjuvant chemotherapy and then wait. For rectal cancers T3–4 and /or N+, chemoradiotherapy is indicated, short radiotherapy must be discussed (followed by a waiting period) to reduce time of exposure in the hospital and to prevent infections. Most complex surgery with high morbidity and mortality – oesogastric, hepatic or pancreatic – is most often best deferred.


title: Molecular epidemiology of KI and WU polyomaviruses in infants with acute respiratory disease and in adult hematopoietic stem cell transplant recipients

text: Polyomaviruses KI (KIPyV) and WU (WUPyV) were described recently in children with acute respiratory disease. The pathogenic potential of these human viruses has not been determined completely, but a correlation between immunosuppression and virus reactivation has been suggested. In the present study, the association between KI/WUPyV infection and immunosuppression was investigated using sequential nasopharyngeal aspirates from asymptomatic adult hematopoietic stem cell transplant recipients. In parallel, an investigation on the WU/KIPyV prevalence in children with acute respiratory disease was also carried out. Two of the 126 samples obtained from the 31 hematopoietic transplant recipients were positive for KIPyV (1 sample, 0.79%) and WUPyV (1 sample, 0.79%). Both samples were obtained 15 days after allogeneic transplantation and virus persistence was not observed in subsequent samples. In symptomatic children, 7 of the 486 nasopharyngeal aspirates were positive for WUPyV (1.4%) and 1 for KIPyV (0.2%). Single polyomavirus infection was detected in four patients, whereas the remaining patients were co‐infected with respiratory syncityal virus (three patients) or adenovirus (one patient). The results suggest that WU/KIPyVs have a limited circulation in Italy and a low pathogenic potential in young children. Brief and asymptomatic infection can occur in hematopoietic transplant recipients. J. Med. Virol. 82:153–156, 2010. © 2009 Wiley‐Liss, Inc.


Acute generalized exanthematous pustulosis after COVID‐19 treatment with hydroxychloroquine


title: Liver impairment associated with disease progression in COVID‐19 patients

text: We read with great interest the study by YF Zhang et al ([1]). The authors found that abnormalities of liver function tests are common in COVID‐19 patients, but the clinically significant liver dysfunction in COVID‐19 was not a prominent feature of this illness and also may not have serious clinical consequences. This study is important and interesting; however, we still have some concerns about it.


title: Uterine adenocarcinoma with feline leukemia virus infection

text: Feline endometrial adenocarcinomas are uncommon malignant neoplasms that have been poorly characterized to date. In this study, we describe a uterine adenocarcinoma in a Persian cat with feline leukemia virus infection. At the time of presentation, the cat, a female Persian chinchilla, was 2 years old. The cat underwent surgical ovariohystectomy. A cross-section of the uterine wall revealed a thickened uterine horn. The cat tested positive for feline leukemia virus as detected by polymerase chain reaction. Histopathological examination revealed uterine adenocarcinoma that had metastasized to the omentum, resulting in thickening and the formation of inflammatory lesions. Based on the histopathological findings, this case was diagnosed as a uterine adenocarcinoma with abdominal metastasis. To the best of our knowledge, this is the first report of a uterine adenocarcinoma with feline leukemia virus infection.


title: Smell dysfunction: a biomarker for COVID‐19

text: BACKGROUND: SARS‐CoV‐2, the virus that causes COVID‐19 disease, is responsible for the largest pandemic since the 1918 H1N1 influenza outbreak. The symptoms presently recognized by the World Health Organization are cough, fever, tiredness, and difficulty breathing. Patient‐reported smell and taste loss has been associated with COVID‐19 infection, yet no empirical olfactory testing on a cohort of COVID‐19 patients has been performed. METHODS: The University of Pennsylvania Smell Identification Test (UPSIT), a well‐validated 40‐odorant test, was administered to 60 confirmed COVID‐19 inpatients and 60 age‐ and sex‐matched controls to assess the magnitude and frequency of their olfactory dysfunction. A mixed effects analysis of variance determined whether meaningful differences in test scores existed between the two groups and if the test scores were differentially influenced by sex. RESULTS: Fifty‐nine (98%) of the 60 patients exhibited some smell dysfunction [mean (95% CI) UPSIT score: 20.98 (19.47,22.48); controls: 34.10 (33.31,34.88); p<0.0001]. Thirty‐five of the 60 patients (58%) were either anosmic (15/60; 25%) or severely microsmic (20/60; 33%); 16 exhibited moderate microsmia (16/60; 27%), 8 mild microsmia (8/60; 13%), and one normosmia (1/60; 2%). Deficits were evident for all 40 UPSIT odorants. No meaningful relationships between the test scores and sex, disease severity, or comorbidities were found. CONCLUSIONS: Quantitative smell testing demonstrates that decreased smell function, but not always anosmia, is a major marker for SARS‐CoV‐2 infection and suggests the possibility that smell testing may help, in some cases, to identify COVID‐19 patients in need of early treatment or quarantine. This article is protected by copyright. All rights reserved


title: Genetic immunization with Hantavirus vaccine combining expression of G2 glycoprotein and fused interleukin-2

text: In this research, we developed a novel chimeric HTNV-IL-2-G2 DNA vaccine plasmid by genetically linking IL-2 gene to the G2 segment DNA and tested whether it could be a candidate vaccine. Chimeric gene was first expressed in eukaryotic expression system pcDNA3.1 (+). The HTNV-IL-2-G2 expressed a 72 kDa fusion protein in COS-7 cells. Meanwhile, the fusion protein kept the activity of its parental proteins. Furthermore, BALB/c mice were vaccinated by the chimeric gene. ELISA, cell microculture neutralization test in vitro were used to detect the humoral immune response in immunized BALB/c mice. Lymphocyte proliferation assay was used to detect the cellular immune response.- The results showed that the chimeric gene could simultaneously evoke specific antibody against G2 glycoprotein and IL-2. And the immunized mice of every group elicited neutralizing antibodies with different titers. Lymphocyte proliferation assay results showed that the stimulation indexes of splenocytes of chimeric gene to G2 and IL-2 were significantly higher than that of other groups. Our results suggest that IL-2-based HTNV G2 DNA can induce both humoral and cellular immune response specific for HTNV G2 and can be a candidate DNA vaccine for HTNV infection.


title: A Brief History of Biocontainment

text: The concept of clinical biocontainment, otherwise known as high-level containment care (HLCC), had its birth among a confluence of near-simultaneous events in 1969. The U.S. Army’s Medical Research Institute of Infectious Diseases (USAMRIID) began construction of the first modern biocontainment unit that year, and opened the two-bed facility, often referred to as “the Slammer” in 1971. Over its 41-year existence, 21 persons exposed to highly hazardous infectious diseases were admitted to the Slammer, but none ever contracted the disease to which they had been exposed. Owing, in part, to this underutilization, some questioned the utility of HLCC units. This concern notwithstanding, Emory University and the University of Nebraska opened HLCC units in civilian academic medical centers in 2004 and 2005, respectively. These units, distinct from conventional infectious disease isolation wards found in most major medical centers, proved their worth during the West African Ebola Virus Disease (EVD) outbreak of 2014–2015. It is our opinion that such units, as well as the parallel high-level containment transport systems necessary to move patients to them, will continue to play an important role in the global response to emerging and highly hazardous contagious pathogens. Moreover, we feel that the lessons derived from their successful operation will lead to improvements in infection control procedures and practices throughout the healthcare system.


title: Characterization of rhinovirus C from a 4-year-old boy with acute onset dilated cardiomyopathy in Jakarta, Indonesia

text: INTRODUCTION: Myocarditis, inflammation of the heart muscle, can be caused by infections, autoimmune disease or exposure to toxins. The major cause of myocarditis in the paediatric population is viral infection, including coxsackievirus B3, adenovirus, herpesvirus, parvovirus, influenza A and B, and hepatitis. Here, we report the detection of rhinovirus C in a boy with a clinical presentation of myocarditis, suggesting a possible causative role of this virus in this case. CASE PRESENTATION: A previously well 4.5-year-old boy presented with increasing breathlessness for a week prior to admission. He also had upper respiratory tract infection a few days before the event. An echocardiogram revealed severe left ventricle (LV) systolic dysfunction with dilation of the LV. RNA was extracted from serum and two nasal swabs, and tested with conventional PCR at the family level for viruses including enterovirus, dengue, chikungunya, influenza, herpesvirus, paramyxovirus and coronavirus. Further characterization of the enterovirus group was carried out using PCR with primers targeting the VP4/VP2 gene, followed by sequencing. Molecular tests showed the presence of rhinovirus C genetic material in both serum and swab samples. Phylogenetic analysis of the VP4/VP2 region showed 96–97 % similarity with the closest strain isolated in Ulaanbaatar (Mongolia) and Japan in 2012. CONCLUSION: We report the possible association of rhinovirus C and myocarditis in a child presenting with acute onset of dilated cardiomyopathy.


title: Neurotropic virus tracing suggests a membranous‐coating‐mediated mechanism for transsynaptic communication

text: Swine hemagglutinating encephalomyelitis virus (HEV) has been shown to have a capability to propagate via neural circuits to the central nervous system after peripheral inoculation, resulting in acute deadly encephalomyelitis in natural host piglets as well as in experimental younger rodents. This study has systematically examined the assembly and dissemination of HEV 67N in the primary motor cortex of infected rats and provides additional evidence indicating that membranous‐coating‐mediated endo‐/exocytosis can be used by HEV for its transsynaptic transfer. In addition, our results suggested that this transsynaptic pathway could adapted for larger granular materials, such as viruses. These findings should help in understanding the mechanisms underlying coronavirus infections as well as the intercellular exchanges occurring at the synaptic junctions. J. Comp. Neurol. 521:203–212, 2013. © 2012 Wiley Periodicals, Inc.


Acute Otitis Media Is Not a Pure Bacterial Disease


title: Practical Guidance for Managing EMG Requests and Testing during the COVID‐19 Pandemic

text: The COVID‐19 pandemic has necessitated cancelation of elective or non‐urgent contact with the healthcare system, including non‐urgent nerve conduction studies and electromyography (electrodiagnostic [EDX] studies). The definitions of elective and non‐urgent are physician judgments, and often are not straightforward. Clinical care must be provided to help our patients in a timely manner, while keeping them, health care personnel and the community safe. Benefit/risk stratification is an important part of this process. We have stratified EDX studies into 3 categories: Urgent, Non‐urgent and Possibly Urgent, in an effort to help clinicians triage these referrals. For each category, we provide a rationale and some examples. However, each referral must be reviewed on a case‐by‐case basis, and the clinical situation will evolve over time, necessitating flexibility in managing EDX triaging. Engaging the referring clinician and, at times, the patient, may be useful in the triage process. This article is protected by copyright. All rights reserved.


title: Viral Hepatitis Other Than A, B, and C: Evaluation and Management

text: Viral hepatitis causes a wide spectrum of presentations from a benign form with minimal or no symptoms to acute liver failure or death. Hepatitis D coinfection and superinfection have distinct clinical courses with the latter more likely leading to chronic infection. Management of chronic HDV is individualized due to the paucity of treatment options and significant side effect profile of currently available treatments. Hepatitis E was once thought to be an infection limited to developing nations with high endemicity, but sporadic cases due to contaminated meats is becoming increasingly prevalent in immunocompromised hosts. Human herpes viruses are an important cause of disease also in the immunocompromised individual.


title: Fill the gap between traditional and new era: The medical educational reform in Taiwan

text: The 7-year medical education program in Taiwan has been established since 1949. More than 60 years later, many medical professionals have observed and voiced its deficiencies following the outbreak of severe acute respiratory syndrome. The deficiencies are three-fold: (1) specialties are excessively institutionalized, (2) students engage in passive learning and memorization, and (3) passing one written national examination serves as the means of granting permanent physician qualification. The situation has aroused concerns and discussions among medical professionals and educators for a new medical education program. Authorized by the Conference of Deans of Medical Schools in Taiwan, Prof. Chyi-Her Lin assembled a team for planning medical curricular reform. Subsequently, Prof. Shan-Chwen Chang organized a task force team which has been monitoring the new 6-year program since 2013. The aims of medical reform by Prof. Lin are (1) to eliminate the specialty training part, (2) to use innovative teaching methods to motivate students to learn proactively, and (3) to implement competency-based medical education. Now, the first class of physicians will enter the workplace in 2019, subject to various clinical challenges.


title: Treatment of pediatric sinusitis

text: The successful management of RS in children relies on careful diagnosis, recognition of causative factors, and judicious yet adequate antibiotic usage. Refractory cases will require surgical therapy, with adenoidectomy as the first-line intervention and ESS reserved for those cases refractory to adenoidectomy. This overall approach will improve quality of life and prevent complications in children with RS.


title: The ongoing crises in China illustrate that the assessment of epidemics in isolation is no longer sufficient

text: The interplay of simultaneous COVID-19, African swine fever, and avian influenza emergencies on global health and industries is constantly evolving and difficult to predict, and therefore warrants further scrutiny. The need for a health network of global scope for the rapid and open exchange of information needs to be strengthened in order to address ongoing and future epidemics under competing resources.


title: Mouse Models of Viral Infection

text: Viral respiratory tract infections are common in both children and adults. Mouse models of viral infection enable the characterization of host immune factors that protect against or promote virus infection; thus, mouse models are essential for interrogation of potential therapeutic targets. Moreover, they serve as critical models for the development of novel vaccine strategies. In this chapter, we describe methods for establishing mouse models of respiratory syncytial virus (RSV) and H1N1 influenza A virus infection. Protocols are provided for viral culture and expansion, plaque-forming assays for viral quantification, and infection of mice. Alternate modifications to the models are also described, and their potential impact is discussed.


title: Quantifying Pathogen Surveillance Using Temporal Genomic Data

text: With the advent of deep sequencing, genomic surveillance has become a popular method for detection of infectious disease, supplementing information gathered by classic clinical or serological techniques to identify host-determinant markers and trace the origin of transmission. However, two main factors complicate genomic surveillance. First, pathogens exhibiting high genetic diversity demand higher levels of scrutiny to obtain an accurate representation of the entire population. Second, current systems of detection are nonuniform, with significant gaps in certain geographic locations and animal reservoirs. Despite past unforeseen pandemics like the 2009 swine-origin H1N1 influenza virus, there is no standardized way of evaluating surveillance. A more complete surveillance system should capture a greater proportion of pathogen diversity. Here we present a novel quantitative method of assessing the completeness of genomic surveillance that incorporates the time of sequence collection, as well as the pathogen’s evolutionary rate. We propose the q2 coefficient, which measures the proportion of sequenced isolates whose closest neighbor in the past is within a genetic distance equivalent to 2 years of evolution, roughly the median time of changing strain selection for influenza A vaccines. Easily interpretable and significantly faster than other methods, the q2 coefficient requires no full phylogenetic characterization or use of arbitrary clade definitions. Application of the q2 coefficient to influenza A virus confirmed poor sampling of swine and avian populations and identified regions with deficient surveillance. We demonstrate that the q2 coefficient can not only be applied to other pathogens, including dengue and West Nile viruses, but also used to describe surveillance dynamics, particularly the effects of different public health policies.


title: Clinical and molecular investigation of a canine distemper outbreak and vector-borne infections in a group of rescue dogs imported from Hungary to Switzerland

text: BACKGROUND: Canine distemper virus (CDV) is a major pathogen of dogs and wild carnivores worldwide. In Switzerland, distemper in domestic dogs is rarely reported. In recent years, the import of dogs from Eastern Europe to Switzerland has steadily increased. In the present study, we describe a distemper outbreak in 15 rescue dogs that were imported from Hungary to Switzerland by an animal welfare organisation. The data on vaccination and medical history were recorded (14 dogs), and the samples were collected to investigate CDV and vector-borne infections (13 dogs) and canine parvovirus infection (12 dogs). The dogs were monitored for six months. RESULTS: One dog was euthanised directly after import. Thirteen dogs showed clinical signs after arrival, i.e., diarrhoea (57 %), coughing (43 %) and nasal and/or ocular discharge (21 %); radiographic findings that were compatible with bronchopneumonia were present in four dogs. CDV infection was diagnosed in 11 dogs (85 %); 10 dogs (91 %) tested PCR-positive in conjunctival swabs. Vector-borne infections (Babesia spp., Leishmania infantum, Dirofilaria immitis) were found in 4 dogs (31 %). Three dogs were hospitalized, and six dogs received ambulatory therapy for up to two months until recovery. None of the dogs developed neurological disease. CDV shedding was detected for a period of up to four months. Because dogs were put under strict quarantine until CDV shedding ceased, CDV did not spread to any other dogs. The CDV isolates showed 99 % sequence identity in the HA gene among each other and belonged to the Arctic-like lineage of CDV. CONCLUSIONS: The present study highlights the imminent risks of spreading contagious viral and vector-borne infections through the non-selective import of sick dogs and dogs with incomplete vaccination from Eastern Europe. CDV shedding was detected for several months after the cessation of clinical signs, which emphasised the roles of asymptomatic carriers in CDV epidemiology. A long-term follow-up using sensitive PCR and strict quarantine measures is of upmost importance in preventing the spread of infection. Dog owners and animal welfare organisations should be educated regarding the importance of complete vaccinations and the impact of dog imports on the spread of viral and vector-borne pathogens.


title: Intensive care of the cancer patient: recent achievements and remaining challenges

text: A few decades have passed since intensive care unit (ICU) beds have been available for critically ill patients with cancer. Although the initial reports showed dismal prognosis, recent data suggest that an increased number of patients with solid and hematological malignancies benefit from intensive care support, with dramatically decreased mortality rates. Advances in the management of the underlying malignancies and support of organ dysfunctions have led to survival gains in patients with life-threatening complications from the malignancy itself, as well as infectious and toxic adverse effects related to the oncological treatments. In this review, we will appraise the prognostic factors and discuss the overall perspective related to the management of critically ill patients with cancer. The prognostic significance of certain factors has changed over time. For example, neutropenia or autologous bone marrow transplantation (BMT) have less adverse prognostic implications than two decades ago. Similarly, because hematologists and oncologists select patients for ICU admission based on the characteristics of the malignancy, the underlying malignancy rarely influences short-term survival after ICU admission. Since the recent data do not clearly support the benefit of ICU support to unselected critically ill allogeneic BMT recipients, more outcome research is needed in this subgroup. Because of the overall increased survival that has been reported in critically ill patients with cancer, we outline an easy-to-use and evidence-based ICU admission triage criteria that may help avoid depriving life support to patients with cancer who can benefit. Lastly, we propose a research agenda to address unanswered questions.


title: Potential of carbohydrate‐binding agents as therapeutics against enveloped viruses

text: Twenty‐seven years after the discovery of HIV as the cause of AIDS more than 25 drugs directed against four different viral targets (i.e. reverse transcriptase, protease, integrase, envelope gp41) and one cellular target (i.e. CCR5 co‐receptor) are available for treatment. However, the search for an efficient vaccine is still ongoing. One of the main problems is the presence of a continuously evolving dense carbohydrate shield, consisting of N‐linked glycans that surrounds the virion and protects it against efficient recognition and persistent neutralization by the immune system. However, several lectins from the innate immune system specifically bind to these glycans in an attempt to process the virus antigens to provoke an immune response. Across a wide variety of different species in nature lectins can be found that can interact with the glycosylated envelope of HIV‐1 and can block the infection of susceptible cells by the virus. In this review, we will give an overview of the lectins from non‐mammalian origin that are endowed with antiviral properties and discuss the complex interactions between lectins of the innate immune system and HIV‐1. Also, attention will be given to different carbohydrate‐related modalities that can be exploited for antiviral chemotherapy. © 2010 Wiley Periodicals, Inc. Med Res Rev


title: High altitude reduces infection rate of COVID-19 but not case-fatality rate

text: Coronavirus disease 19 (COVID-19) is a pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). It is suggested that life at high altitude may reduce COVID infections and case-fatality rates (cases/deaths). We study data from Peru COVID-19 pandemics, which first case was recorded on March 6th, 2020. By June 13, 2020 there were 6498 deaths, and 224,132 SARS-CoV-2 positives. Using data from 185 capitals of provinces with altitudes ranging from 3 to 4342 m, we confirm previous reports that infection with COVID-19 at high altitude is reduced. However, case-fatality rate is not dependent of altitude. We have also presented first evidence that female protection towards death by COVID-19 is reduced as altitude of residence increases.


title: Chapter 22 Animal Models with a Genetic Alteration of the ACE2/Ang-(1-7)/Mas Axis

text: Abstract The aim of this chapter is to describe the animal models generated by transgenic technology for the functional analysis of the protective axis of the renin–angiotensin system, consisting of angiotensin-converting enzyme 2 (ACE2), angiotensin (Ang)-(1-7), and Mas. Transgenic overexpression of the components of this axis in general led to an ameliorated cardiac and vascular damage in disease states and to an improved metabolic profile. Knockout models for ACE2 and Mas, however, show aggravated cardiovascular pathologies and a metabolic syndrome-like state. In particular, the local production of Ang-(1-7) in the vascular wall, in the heart, and in the brain was found to be of high physiological relevance by the use of transgenic animals overexpressing ACE2 or Ang-(1-7) in these tissues.