title: Serum interleukin-6 as a prognostic marker in neonatal calf diarrhea

text: Abstract Neonatal calf diarrhea is still one of the most important diseases in calf rearing, and severe diarrhea has a marked effect on animal welfare. Furthermore, significant economic losses can result from this disease due to high mortality rates, high medical costs, and low weight gain. To avoid a fatal outcome of the disease, it is crucial that vulnerable calves are identified as early as possible. Interleukin-6 is described as an early and reliable prognostic marker in several diseases. In this study, 20 scouring calves were tested by ELISA for their IL-6 serum concentrations. Samples were collected twice, at the beginning of diarrhea and 7 to 10d later. Regarding the clinical outcome after 7 to 10d, calves were classified as recovered or nonrecovered. A receiver operating characteristic analysis was conducted to determine the prognostic value of IL-6 for the progress of clinical symptoms. At the beginning of diarrhea, the IL-6 concentration was significantly higher in nonrecovering calves compared with those that recover 7 to 10d after the onset of diarrhea. Interleukin-6 proved to be a useful additional parameter in the clinical examination. High initial IL-6 values can support the decision for closer monitoring and an adapted therapeutic strategy for the respective calves. This may help to prevent unnecessary animal suffering and reduce economic losses.


title: Detection of bovine enteric coronavirus in clinical specimens by hybridization with cDNA probes

text: Abstract Molecular hybridization, previously optimized for purified bovine coronavirus (BCV), was adapted for detection of virus in clinical specimens. For this purpose, the accuracy of the existing tests had to be improved and suitable means for removal of extraneous molecules had to be established. Six radioactive probes were used to obtain adequate detection signals. These probes, containing the complete N and E1 gene sequences and other sequences, hybridized to about 1 4 of the total length of the viral RNA. Genomic RNA could be detected after direct spotting of samples, but prior Freo-nextraction or centrifugation of specimens on a cushion of sucrose improved considerably the positive identification of virus containing samples. RNA detection in positive clinical specimens was significantly better by hybridization than immunological detection of BCV by ELISA, although differences were slight after two passages of the virus on HRT-18 cell monolayers. Consequently, the reliability of positive and negative test results in hybridization tests on Freon extracted specimens was better than in ELISA. However, results after extraction with other organic solvents were inferior. The accuracy of ELISA was surpassed by hybridization assays. Background signals, due to vector homology were found to be negligible in all the samples analyzed.


title: Continuum Models of Membrane Fusion: Evolution of the Theory

text: Starting from fertilization, through tissue growth, hormone secretion, synaptic transmission, and sometimes morbid events of carcinogenesis and viral infections, membrane fusion regulates the whole life of high organisms. Despite that, a lot of fusion processes still lack well-established models and even a list of main actors. A merger of membranes requires their topological rearrangements controlled by elastic properties of a lipid bilayer. That is why continuum models based on theories of membrane elasticity are actively applied for the construction of physical models of membrane fusion. Started from the view on the membrane as a structureless film with postulated geometry of fusion intermediates, they developed along with experimental and computational techniques to a powerful tool for prediction of the whole process with molecular accuracy. In the present review, focusing on fusion processes occurring in eukaryotic cells, we scrutinize the history of these models, their evolution and complication, as well as open questions and remaining theoretical problems. We show that modern approaches in this field allow continuum models of membrane fusion to stand shoulder to shoulder with molecular dynamics simulations, and provide the deepest understanding of this process in multiple biological systems.


title: Transition metal-free cross-coupling of furan ring with haloacetylenes

text: Abstract On the example of menthofuran, a naturally abundant compound, it has been shown for the first time that the furan ring can be readily cross-coupled with acylhaloacetylenes in the solid Al2O3 powder at room temperature to afford the corresponding 2-ethynyl derivatives in up to 88% yield. The reaction represents a ring closing/ring opening process that includes reversible formation of the intermediate cycloadducts further producing acetylene derivatives with elimination of HHal.


title: Expression profile of immune response genes in patients with Severe Acute Respiratory Syndrome

text: BACKGROUND: Severe acute respiratory syndrome (SARS) emerged in later February 2003, as a new epidemic form of life-threatening infection caused by a novel coronavirus. However, the immune-pathogenesis of SARS is poorly understood. To understand the host response to this pathogen, we investigated the gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from SARS patients, and compared with healthy controls. RESULTS: The number of differentially expressed genes was found to be 186 under stringent filtering criteria of microarray data analysis. Several genes were highly up-regulated in patients with SARS, such as, the genes coding for Lactoferrin, S100A9 and Lipocalin 2. The real-time PCR method verified the results of the gene array analysis and showed that those genes that were up-regulated as determined by microarray analysis were also found to be comparatively up-regulated by real-time PCR analysis. CONCLUSIONS: This differential gene expression profiling of PBMCs from patients with SARS strongly suggests that the response of SARS affected patients seems to be mainly an innate inflammatory response, rather than a specific immune response against a viral infection, as we observed a complete lack of cytokine genes usually triggered during a viral infection. Our study shows for the first time how the immune system responds to the SARS infection, and opens new possibilities for designing new diagnostics and treatments for this new life-threatening disease.


title: The Structural Characterization and Antigenicity of the S Protein of SARS-CoV

text: The corona-like spikes or peplomers on the surface of the virion under electronic microscope are the most striking features of coronaviruses. The S (spike) protein is the largest structural protein, with 1,255 amino acids, in the viral genome. Its structure can be divided into three regions: a long N-terminal region in the exterior, a characteristic transmembrane (TM) region, and a short C-terminus in the interior of a virion. We detected fifteen substitutions of nucleotides by comparisons with the seventeen published SARS-CoV genome sequences, eight (53.3%) of which are non-synonymous mutations leading to amino acid alternations with predicted physiochemical changes. The possible antigenic determinants of the S protein are predicted, and the result is confirmed by ELISA (enzyme-linked immunosorbent assay) with synthesized peptides. Another profound finding is that three disulfide bonds are defined at the C-terminus with the N-terminus of the E (envelope) protein, based on the typical sequence and positions, thus establishing the structural connection with these two important structural proteins, if confirmed. Phylogenetic analysis reveals several conserved regions that might be potent drug targets.


title: La, PTB, and PAB proteins bind to the 3′ untranslated region of Norwalk virus genomic RNA

text: Abstract Noroviruses are human enteric caliciviruses for which no cell culture is available. Consequently, the mechanisms and factors involved in their replication have been difficult to study. In an attempt to analyze the cis- and trans-acting factors that could have a role in NV replication, the 3′-untranslated region of the genome was studied. Use of Zuker’s mfold-2 software predicted that NV 3′UTR contains a stem-loop structure of 47 nts. Proteins from HeLa cell extracts, such as La and PTB, form stable complexes with this region. The addition of a poly(A) tail (24 nts) to the 3′UTR permits the specific binding of the poly(A) binding protein (PABP) present in HeLa cell extracts, as well as the recombinant PABP. Since La, PTB, and PABP are important trans-acting factors required for viral translation and replication, these RNA–protein interactions may play a role in NV replication or translation.


title: Ancient oncogenesis, infection and human evolution

text: The recent discovery that malignant neoplastic lesions date back nearly 2 million years ago not only highlights the antiquity of cancer in the human lineage, but also provides remarkable insight into ancestral hominin disease pathology. Using these Early Pleistocene examples as a point of departure, we emphasize the prominent role of viral and bacterial pathogens in oncogenesis and evaluate the impact of pathogens on human evolutionary processes in Africa. In the Shakespearean vernacular “what's past is prologue,” we highlight the significance of novel information derived from ancient pathogenic DNA. In particular, and given the temporal depth of human occupation in sub‐Saharan Africa, it is emphasized that the region is ideally positioned to play a strategic role in the discovery of ancient pathogenic drivers of not only human mortality, but also human evolution. Ancient African pathogen genome data can provide novel revelations concerning human‐pathogen coevolutionary processes, and such knowledge is essential for forecasting the ways in which emerging zoonotic and increasingly transmissible diseases might influence human demography and longevity in the future.


title: Building porosity for better urban ventilation in high-density cities – A computational parametric study

text: Abstract Shape-edged buildings impose large frictional drag on the flow in the urban boundary layer. In the sub-tropics, especially during hot and humid summers, compact building blocks create stagnant air that worsens outdoor urban thermal comfort. The current study adapts the κ–ω SST turbulence model to simulate air flow in urban areas. The accuracy of the κ–ω SST turbulence model in detecting air flow around a rectangular block is validated by comparing it with the data from the wind tunnel experiment. In the computational parametric study, wind speed classification is derived based on Physiological Equivalent Temperature (PET) to evaluate the effect of wind speed on outdoor thermal comfort. Numerical analysis compares the effects of different building morphology modifications on pedestrian-level natural ventilation. Critical design issues are also identified. From both the accuracy and practical points of view, the current study allows city planners and architects to improve building porosity efficiently for better pedestrian-level urban ventilation, without losing land use efficacy.


title: Anti-microbial immunity is impaired in COPD patients with frequent exacerbations

text: Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) sub-group requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD. We measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virus-associated exacerbations. Ex vivo immune responses to rhinovirus infection in differentiated bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated. Patients were stratified as frequent exacerbators (≥2 exacerbations in the preceding year) or infrequent exacerbators (<2 exacerbations in the preceding year) with comparisons made between these groups. Frequent exacerbators had reduced sputum cell mRNA expression of the anti-viral immune mediators type I and III interferons and reduced interferon-stimulated gene (ISG) expression when clinically stable and during virus-associated exacerbation. RV-induction of interferon and ISGs ex vivo was also impaired in differentiated BECs from frequent exacerbators. Frequent exacerbators also had reduced sputum levels of the anti-microbial peptide mannose-binding lectin (MBL)-2 with an associated increase in sputum bacterial loads at 2 weeks following virus-associated exacerbation onset. MBL-2 levels correlated negatively with bacterial loads during exacerbation. These data implicate deficient airway innate immunity in the increased propensity to exacerbations observed in some patients with COPD. Therapeutic approaches to boost innate antimicrobial immunity in the lung could be a viable strategy for prevention/treatment of frequent exacerbations.


title: The Pathogenesis of Rift Valley Fever

text: Rift Valley fever (RVF) is an emerging zoonotic disease distributed in sub-Saharan African countries and the Arabian Peninsula. The disease is caused by the Rift Valley fever virus (RVFV) of the family Bunyaviridae and the genus Phlebovirus. The virus is transmitted by mosquitoes, and virus replication in domestic ruminant results in high rates of mortality and abortion. RVFV infection in humans usually causes a self-limiting, acute and febrile illness; however, a small number of cases progress to neurological disorders, partial or complete blindness, hemorrhagic fever, or thrombosis. This review describes the pathology of RVF in human patients and several animal models, and summarizes the role of viral virulence factors and host factors that affect RVFV pathogenesis.


title: Meaning of Health-related Quality of Life among Children and Adolescents in an Asian Country: A Focus Group Approach

text: Aims: We aimed to evaluate the extent to which HRQoL instruments developed based on the Western notion of health is applicable to Asian children and adolescents by assessing their conceptualization of QoL. A secondary objective is to evaluate the necessity of developing age- or gender-specific HRQoL instruments. Methods: We explored the meaning of general and health-related QoL through focus group discussions in Singapore, a multi-ethnic Asian society. Two investigators independently analysed the data. They extracted major and sub-themes related to both general and health-related QoL. The agreement between the analyses was compared and disagreement was resolved through discussion. Results: Thirty-two subjects (children: 50.0%, female: 50.0%) participated. There were few disagreements. Meanings of general and health-related QoL could be grouped under three broad themes: (1) physical, (2) psychological and (3) social health, consistent with the current definition of HRQoL. We found that Singaporean and Western children/adolescents share a remarkably similar notion of general and health-related QoL. Compared to adolescents, children were more likely to report positive emotions, be less mindful of others’ opinions and had less varied social activities. Conclusion: The results suggest that currently available instruments are potentially useful for Singaporean children/adolescents. We also found that age-specific HRQoL instruments are necessary.


title: Diagnostics and Discovery in Viral Hemorrhagic Fevers

text: The rate of discovery of new microbes and of new associations of microbes with health and disease is accelerating. Many factors contribute to this phenomenon including those that favor the true emergence of new pathogens as well as new technologies and paradigms that enable their detection and characterization. This chapter reviews recent progress in the field of pathogen surveillance and discovery with a focus on viral hemorrhagic fevers.


title: Rapid Deployment of a Drive-Through Prenatal Care Model in Response to the Coronavirus Disease 2019 (COVID-19) Pandemic

text: Coronavirus disease 2019 (COVID-19) has been declared a public health emergency for the entire United States. Providing access to prenatal health care while limiting exposure of both obstetric health care professionals and patients to COVID-19 is challenging. Although reductions in the frequency of prenatal visits and implementation of telehealth interventions provide some options, there still remains a need for patient–health care professional visits. A drive-through prenatal care model was developed in which pregnant women would remain in their automobiles while being assessed by the health care professional, thus reducing potential patient, health care professional, and staff exposure to COVID-19. Drive-through prenatal visits would include key elements that some institutions cannot perform by telehealth encounters, such as blood pressure measurements for evaluation for hypertensive disorders of pregnancy, fetal heart rate assessment, and selected ultrasound-based measurements or observations, as well as face-to-face patient–health care professional interaction, thereby reducing patient anxiety resulting from the reduction in the number of planned clinic visits with an obstetric health care professional as well as fear of virus exposure in the clinic setting. We describe the rapid development of a drive-through prenatal care model that is projected to reduce the number of in-person clinic visits by 33% per patient compared with the traditional prenatal care paradigm, using equipment and supplies that most obstetric clinics in the United States can access.


title: Potential Indirect Effects of the COVID-19 Pandemic on Use of Emergency Departments for Acute Life-Threatening Conditions — United States, January–May 2020

text: On March 13, 2020, the United States declared a national emergency in response to the coronavirus disease 2019 (COVID-19) pandemic. Subsequently, states enacted stay-at-home orders to slow the spread of SARS-CoV-2, the virus that causes COVID-19, and reduce the burden on the U.S. health care system. CDC* and the Centers for Medicare & Medicaid Services (CMS)† recommended that health care systems prioritize urgent visits and delay elective care to mitigate the spread of COVID-19 in health care settings. By May 2020, national syndromic surveillance data found that emergency department (ED) visits had declined 42% during the early months of the pandemic (1). This report describes trends in ED visits for three acute life-threatening health conditions (myocardial infarction [MI, also known as heart attack], stroke, and hyperglycemic crisis), immediately before and after declaration of the COVID-19 pandemic as a national emergency. These conditions represent acute events that always necessitate immediate emergency care, even during a public health emergency such as the COVID-19 pandemic. In the 10 weeks following the emergency declaration (March 15-May 23, 2020), ED visits declined 23% for MI, 20% for stroke, and 10% for hyperglycemic crisis, compared with the preceding 10-week period (January 5-March 14, 2020). EDs play a critical role in diagnosing and treating life-threatening conditions that might result in serious disability or death. Persons experiencing signs or symptoms of serious illness, such as severe chest pain, sudden or partial loss of motor function, altered mental state, signs of extreme hyperglycemia, or other life-threatening issues, should seek immediate emergency care, regardless of the pandemic. Clear, frequent, highly visible communication from public health and health care professionals is needed to reinforce the importance of timely care for medical emergencies and to assure the public that EDs are implementing infection prevention and control guidelines that help ensure the safety of their patients and health care personnel.


title: Antiviral IFN-γ responses of monocytes at birth predict respiratory tract illness in the first year of life

text: Background Viral respiratory tract infections are the leading cause of acute illness during infancy and are closely linked to chronic inflammatory airway diseases later in life. However, the determinants of susceptibility to acute respiratory tract infections still need to be defined. Objective We investigated whether the individual variation in antiviral response at birth determines the risk for acute respiratory tract illness in the first year of life. Methods We studied 82 children who were enrolled in a birth cohort study of inner-city children with at least 1 parent with allergy or asthma. We cultured cord blood monocytes and assessed IFNG and CCL5 mRNA production at 24 hours after inoculation with respiratory syncytial virus. We also monitored the frequency of acute respiratory tract illness at 3-month intervals and analyzed nasal lavage samples for respiratory tract viruses at the time of illness during the first year. Results Respiratory tract infection was reported for 88% of subjects, and respiratory tract viruses were recovered in 74% of symptomatic children. We observed a wide range of antiviral responses in cord blood monocytes across the population. Furthermore, a decrease in production of IFNG (but not CCL5) mRNA in response to respiratory syncytial virus infection of monocytes was associated with a significant increase in the frequency of upper respiratory tract infections (r = −0.42, P < .001) and the prevalence of ear and sinus infections, pneumonias, and respiratory-related hospitalizations. Conclusion Individual variations in the innate immune response to respiratory tract viruses are detectable even at birth, and these differences predict the susceptibility to acute respiratory tract illness during the first year of life.


Community Outreach Panel Explores and Addresses Higher Rates of COVID-19–Related Deaths in the African American Population


title: Type 5 phosphodiesterase (PDE5) and the vascular tree: from embryogenesis to aging and disease

text: Vascular tree development depends on the timely differentiation of endothelial and vascular smooth muscle cells. These latter are key players in the formation of the vascular scaffold that offers resistance to the blood flow. This review aims at providing an overview on the role of PDE5, the cGMP-specific phosphodiesterase that historically attracted much attention for its involvement in male impotence, in the regulation of vascular smooth muscle cell function. The overall goal is to underscore the importance of PDE5 expression and activity in this cell type in the context of the organs where its function has been extensively studied.


title: Relationship between the GOLD combined COPD assessment staging system and bacterial isolation

text: BACKGROUND: Acute exacerbations, which are a significant cause of mortality and morbidity, adversely affect chronic obstructive pulmonary disease (COPD) prognosis by accelerating loss of lung function. It is important to know the microorganisms that commonly cause exacerbations in the patient groups classified according to clinical and functional characteristics for fast and accurate treatment of acute exacerbations. OBJECTIVES: The last Global Initiative for Chronic Obstructive Lung Disease (GOLD) publication recommended a new staging system containing obstruction degree, frequency of exacerbations, and quality of life questionnaires. This study is designed to analyze the relationship between the bacteria isolated in acute exacerbations and new GOLD stages. METHODS: Potentially pathogenic bacteria (PPB) isolation with culture and polymerase chain reaction methods were obtained from 114 acute exacerbation COPD patients, classified into A, B, C, and D groups by analyzing the forced expiratory volume in 1 second (FEV(1)) value, COPD Assessment Test (CAT) score, and exacerbation frequency according to the new GOLD staging system. RESULTS: There was a significant correlation between exacerbation frequency and PPB isolation (P=0.002). There was no relationship between GOLD stage, FEV(1), and CAT score with PPB isolation. The isolated bacteria diversity and mixed infection frequency were higher in the GOLD stage D group. Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii were isolated only from D group patients. CONCLUSION: Bacterial infection may cause an acute exacerbation equally in each stage for COPD. The difference in bacterial etiology is more related to exacerbation frequency than FEV(1) and CAT scores for an acute exacerbation. Determining exacerbation frequency is significant for treatment success in empirical antibiotic selection.


title: Social Distancing and Transmission-reducing Practices during the 2019 Coronavirus Disease and 2015 Middle East Respiratory Syndrome Coronavirus Outbreaks in Korea

text: BACKGROUND: The absence of effective antiviral medications and vaccines increased the focus on non-pharmaceutical preventive behaviors for mitigating against the coronavirus disease 2019 (COVID-19) pandemic. To examine the current status of non-pharmaceutical preventive behaviors practiced during the COVID-19 outbreak and factors affecting behavioral activities, we compared to the 2015 Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in Korea. METHODS: This was a serial cross-sectional population-based study in Korea with four surveys conducted on June 2 and 25, 2015 (MERS-CoV surveys), and February 4, and April 2, 2020 (COVID-19 surveys). Of 25,711 participants selected using random digit dialing numbers, 4,011 participants (aged ≥ 18 years) were successfully interviewed, for the 2020 COVID-19 (n = 2,002) and 2015 MERS-CoV (n = 2,009) epidemics were included. Participants were selected post-stratiﬁcation by sex, age, and province. The total number of weighted cases in this survey equaled the total number of unweighted cases at the national level. We measured the levels of preventive behaviors (social distancing [avoiding physical contact with others]), and practicing transmission-reducing behaviors such as wearing face mask and handwashing. RESULTS: Between the surveys, respondents who reported practicing social distancing increased from 41.9%–58.2% (MERS-CoV) to 83.4%–92.3% (COVID-19). The response rate for the four surveys ranged between 13.7% and 17.7%. Practicing transmission-reducing behaviors (wearing face masks and handwashing) at least once during COVID-19 (78.8%, 80.2%) also increased compared to that during MERS-CoV (15.5%, 60.3%). The higher affective risk perception groups were more likely to practice transmission-reducing measures (adjusted odds ratio, 3.24–4.81; 95 confidence interval, 1.76–6.96) during both COVID-19 and MERS-CoV. CONCLUSION: The study findings suggest markedly increased proportions of non-pharmaceutical behavioral practices evenly across all subgroups during the two different novel virus outbreaks in Korea. Strategic interventions are needed to attempt based on preventive behavior works.


title: What about COVID-19 and arachidonic acid pathway?

text: BACKGROUND AND OBJECTIVE: COVID-19 is a highly contagious viral disease. In this study, we tried to define and discuss all the findings on the potential association between arachidonic acid (AA) pathway and COVID-19 pathophysiology. METHODS: A literature search across PubMed, Scopus, Embase, and Cochrane database was conducted. A total of 25 studies were identified. RESULTS: The data elucidated that COX-2 and prostaglandins (PGs), particularly PGE(2), have pro-inflammatory action in COVID-19 pathophysiology. Arachidonic acid can act as endogenous antiviral compound. A deficiency in AA can make humans more susceptible to COVID-19. Targeting these pro-inflammatory mediators may help in decreasing the mortality and morbidity rate in COVID-19 patients. CONCLUSIONS: PGE(2) levels and other PGs levels should be measured in patients with COVID-19. Lowering the PGE(2) levels through inhibition of human microsomal prostaglandin E synthase-1 (mPGES-1) can enhance the host immune response against COVID-19. In addition, the hybrid compounds, such as COX-2 inhibitors/TP antagonists, can be an innovative treatment to control the overall balance between AA mediators in patients with COVID-19.


title: Exploration of strategies to reduce aerosol-spread during chest compressions: A simulation and cadaver model

text: Abstract Objective To evaluate the effect of strategies to reduce the spread of simulated aerosol during chest compressions on manikin and cadaver experimental models. Methods To evaluate aerosol-spread we nebulized ultraviolet sensitive detergents into the artificial airway of a resuscitation dummy and performed CPR. The spread of the visualized aerosol was documented by a camera. In a further approach we applied nebulized detergents into the airways of human cadavers and detected the simulated spread on the same way. Among others we did recordings with undergoing compression-only-CPR, with a surgical mask or an oxygen mask on the patients face and with an inserted supraglottic airway device with and without a connected airway filter. Results Most aerosol-spread at the direction of the provider was visualized during compression-only-CPR. The use of a surgical mask and of an oxygen mask on the patient's face deflected the spread. Inserting a supraglottic airway device connected to an airway filter lead to a remarkable reduction of aerosol-spread. Conclusion The early insertion of a supraglottic airway device connected to an airway filter before starting chest compression may be beneficial for staff protection during CPR.


title: The Advantages and Limitations of International Classification of Diseases, Injuries and Causes of Death from Aspect of Existing Health Care System of Bosnia and Herzegovina

text: CONFLICT OF INTEREST: NONE DECLARED INTRODUCTION: The International classification of diseases (ICD) is the most important classification in medicine. It is used by all medical professionals. CONCEPT: The basic concept of ICD is founded on the standardization of the nomenclature for the names of diseases and their basic systematization in the hierarchically structured category. ADVANTAGES AND DISADVANTAGES: The health care provider institutions such as hospitals are subjects that should facilitate implementation of medical applications that follows the patient medical condition and facts connected with him. The definitive diagnosis that can be coded using ICD can be achieved after several visits of patient and rarely during the first visit. CONCLUSION: The ICD classification is one of the oldest and most important classifications in medicine. In the scope of ICD are all fields of medicine. It is used in statistical purpose and as a coding system in medical databases.


title: Paediatric Virology and its interaction between basic science and clinical practice (Review)

text: The 3rd Workshop on Paediatric Virology, which took place on October 7th, 2017 in Athens, Greece, highlighted the role of breast feeding in the prevention of viral infections during the first years of life. Moreover, it focused on the long-term outcomes of respiratory syncytial virus and rhinovirus infections in prematurely born infants and emphasised the necessity for the development of relevant preventative strategies. Other topics that were covered included the vaccination policy in relation to the migration crisis, mother-to-child transmission of hepatitis B and C viruses, vaccination against human papilloma viruses in boys and advances on intranasal live-attenuated vaccination against influenza. Emphasis was also given to the role of probiotics in the management of viral infections in childhood, the potential association between viral infections and the pathogenesis of asthma, fetal and neonatal brain imaging and the paediatric intensive care of children with central nervous system viral infections. Moreover, an interesting overview of the viral causes of perinatal mortality in ancient Greece was given, where recent archaeological findings from the Athenian Agora’s bone well were presented. Finally, different continuing medical educational options in Paediatric Virology were analysed and evaluated. The present review provides an update of the key topics discussed during the workshop.


title: Tracking Social Media Discourse About the COVID-19 Pandemic: Development of a Public Coronavirus Twitter Data Set

text: BACKGROUND: At the time of this writing, the coronavirus disease (COVID-19) pandemic outbreak has already put tremendous strain on many countries' citizens, resources, and economies around the world. Social distancing measures, travel bans, self-quarantines, and business closures are changing the very fabric of societies worldwide. With people forced out of public spaces, much of the conversation about these phenomena now occurs online on social media platforms like Twitter. OBJECTIVE: In this paper, we describe a multilingual COVID-19 Twitter data set that we are making available to the research community via our COVID-19-TweetIDs GitHub repository. METHODS: We started this ongoing data collection on January 28, 2020, leveraging Twitter’s streaming application programming interface (API) and Tweepy to follow certain keywords and accounts that were trending at the time data collection began. We used Twitter’s search API to query for past tweets, resulting in the earliest tweets in our collection dating back to January 21, 2020. RESULTS: Since the inception of our collection, we have actively maintained and updated our GitHub repository on a weekly basis. We have published over 123 million tweets, with over 60% of the tweets in English. This paper also presents basic statistics that show that Twitter activity responds and reacts to COVID-19-related events. CONCLUSIONS: It is our hope that our contribution will enable the study of online conversation dynamics in the context of a planetary-scale epidemic outbreak of unprecedented proportions and implications. This data set could also help track COVID-19-related misinformation and unverified rumors or enable the understanding of fear and panic—and undoubtedly more.


title: Is wearing a face mask a good idea?

text: Official advice on masks for the general public is mixed, and there are concerns about taking vital supplies away from healthcare workers, reports Jessica Hamzelou


title: The 8ab protein of SARS-CoV is a luminal ER membrane-associated protein and induces the activation of ATF6

text: Abstract The 8ab protein of SARS-CoV is a group-specific accessory protein, which is lost when the virus was transmitted from animals to humans due to a 29-nucleotide deletion in the ORF8ab region. Here we found that 8ab protein is associated with ER membrane at luminal surface. 8ab protein was found to up-regulate the synthesis of endogenous ER-resident chaperons involved in protein folding through the activation of the transcription factor ATF6, while it showed no effect on the CHOP induction and XBP1 splicing associated with the unfolded protein response (UPR). When ectopically expressed in mammalian cells, 8ab induced the proteolysis of ATF6 and the translocation of its cleaved DNA-binding and transcription-activation domains from the ER to the nucleus. Finally, we showed that 8ab binds to the luminal domain of ATF6. These findings suggest that 8ab could modulate the UPR by activating ATF6 to facilitate protein folding and processing. Thus, the loss of 8ab in SARS-CoV through viral evolution in animals may play a role in its pathogenicity.


Sars and Other Coronaviruses in Humans and Animals


title: Analysis of genetic variability of respiratory syncytial virus groups A and B in Kuwait

text: Respiratory syncytial virus (RSV) is the most frequently identified viral agent in infants, children, and elderly people with acute respiratory tract infections (ARTIs). This study is the only one of its kind in Kuwait, and its purpose was to investigate the genetic variability of the G protein gene in RSV strains prevalent in Kuwait. Respiratory samples were collected from patients with ARTIs in various hospitals in Kuwait and subjected to reverse transcription PCR (RT-PCR) amplifying a fragment of the G gene of RSV. A total of 305 samples were collected between January and mid-December 2016, and 77 (25.2%) were positive for RSV. Group A viruses were predominant over group B viruses; the RSV-A group was detected in 52 (67.5%) of the positive samples, while the RSV-B group was detected in 25 (32.5%) of the positive samples. Phylogenetic analysis showed that all RSV-A strains grouped into eight clusters of identical sequences of untyped strains. Twelve RSV-B strains, on the other hand, belonged to the RSV-B/BA10 genotype, while the rest were untyped. These data suggest that new and untyped strains of RSV-A group likely predominated in Kuwait and that the BA10 genotype of the RSV-B group became the dominant genotype in the 2016 season.


title: Characterization of retrovirus-based reporter viruses pseudotyped with the precursor membrane and envelope glycoproteins of four serotypes of dengue viruses

text: Abstract In this study, we successfully established retrovirus-based reporter viruses pseudotyped with the precursor membrane and envelope (PrM/E) proteins of each of the four serotypes of dengue viruses, which caused the most important arboviral diseases in this century. Co-sedimentation of the dengue E protein and HIV-1 core proteins by sucrose gradient analysis of the pseudotype reporter virus of dengue virus type 2, D2(HIVluc), and detection of HIV-1 core proteins by immunoprecipitation with anti-E monoclonal antibody suggested that dengue viral proteins were incorporated into the pseudotype viral particles. The infectivity in target cells, as assessed by the luciferase activity, can be inhibited by the lysosomotropic agents, suggesting a pH-dependent mechanism of entry. Amino acid substitutions of the leucine at position 107, a critical residue at the fusion loop of E protein, with lysine resulted in severe impairment in infectivity, suggesting that entry of the pseudotype reporter virus is mediated through the fusogenic properties of E protein. With more and more dengue viral sequences available from different outbreaks worldwide, this sensitive and convenient tool has the potential to facilitate molecular characterization of the PrM/E proteins of dengue field isolates.


title: Exploring the purine core of 3′-C-ethynyladenosine (EAdo) in search of novel nucleoside therapeutics

text: A series of new nucleoside analogues based on a C-3 branched ethynyl sugar derivative as present in 3′-C-ethynylcytidine (ECyd) and -adenosine (EAdo), combined with modified purine bases was synthetized and evaluated against a broad array of viruses and tumour cell lines. The pronounced cytostatic activity of EAdo was confirmed. EAdo and its 2,6-diaminopurine analogue showed inhibitory activity against vaccinia virus (EC(50): 0.31 and 51 μM, respectively). Derivative 10 on the other hand was found active against varicella zoster virus (EC(50): 4.68 μM).


title: Daylight-driven rechargeable antibacterial and antiviral nanofibrous membranes for bioprotective applications

text: Emerging infectious diseases (EIDs) are a significant burden on global economies and public health. Most present personal protective equipment used to prevent EID transmission and infections is typically devoid of antimicrobial activity. We report on green bioprotective nanofibrous membranes (RNMs) with rechargeable antibacterial and antiviral activities that can effectively produce biocidal reactive oxygen species (ROS) solely driven by the daylight. The premise of the design is that the photoactive RNMs can store the biocidal activity under light irradiation and readily release ROS under dim light or dark conditions, making the biocidal function “always online.” The resulting RNMs exhibit integrated properties of fast ROS production, ease of activity storing, long-term durability, robust breathability, interception of fine particles (>99%), and high bactericidal (>99.9999%) and virucidal (>99.999%) efficacy, which enabled to serve as a scalable biocidal layer for protective equipment by providing contact killing against pathogens either in aerosol or in liquid forms. The successful synthesis of these fascinating materials may provide new insights into the development of protection materials in a sustainable, self-recharging, and structurally adaptive form.


title: Clinical Characteristics of COVID‐19 After Gynecologic Oncology Surgery in Three Women: A Retrospective Review of Medical Records

text: From a large medical center in Wuhan, the epicenter of the 2019 novel coronavirus disease (COVID‐19), we report clinical features and prognosis for three women diagnosed with COVID‐19 after gynecologic oncology surgery and hospitalized in January 2020. The incidence of COVID‐19 was 0.77% (3 of 389) of total hospitalizations and 1.59% (3 of 189) of patients undergoing surgeries in the ward. The infection of severe acute respiratory syndrome coronavirus 2 may be related to the older age, comorbidities, malignant tumor, and surgery in gynecologic hospitalizations. By February 20, 2020, only two of the three patients had met the clinical discharge criteria. Given the long and uncertain incubation period of COVID‐19, screening for the virus infection should be carried out for all patients, both preoperatively and postoperatively. Postponement of scheduled gynecologic surgery for patients in the epidemic area should be considered.


Responding to COVID-19: Perspectives from the Chinese Society of Gastroenterology


title: Completion of the Porcine Epidemic Diarrhoea Coronavirus (PEDV) Genome Sequence

text: The sequence of the replicase gene of porcine epidemic diarrhoea virus (PEDV) has been determined. This completes the sequence of the entire genome of strain CV777, which was found to be 28,033 nucleotides (nt) in length (excluding the poly A-tail). A cloning strategy, which involves primers based on conserved regions in the predicted ORF1 products from other coronaviruses whose genome sequence has been determined, was used to amplify the equivalent, but as yet unknown, sequence of PEDV. Primary sequences derived from these products were used to design additional primers resulting in the amplification and sequencing of the entire ORF1 of PEDV. Analysis of the nucleotide sequences revealed a small open reading frame (ORF) located near the 5′ end (no 99–137), and two large, slightly overlapping ORFs, ORF1a (nt 297–12650) and ORF1b (nt 12605–20641). The ORF1a and ORF1b sequences overlapped at a potential ribosomal frame shift site. The amino acid sequence analysis suggested the presence of several functional motifs within the putative ORF1 protein. By analogy to other coronavirus replicase gene products, three protease and one growth factor-like motif were seen in ORF1a, and one polymerase domain, one metal ion-binding domain, and one helicase motif could be assigned within ORF1b. Comparative amino acid sequence alignments revealed that PEDV is most closely related to human coronavirus (HCoV)-229E and transmissible gastroenteritis virus (TGEV) and less related to murine hepatitis virus (MHV) and infectious bronchitis virus (IBV). These results thus confirm and extend the findings from sequence analysis of the structural genes of PEDV.


Solidarität und Verantwortung in der Corona-Krise : Ad-hoc-Empfehlung Berlin, 27.3.2020


title: Telemedicine and the 2019 Coronavirus (SARS‐CoV‐2)

text: In 2020 during the CoronaVirus Disease19 (COVID19) pandemic caused by da SARS‐CoV‐2, the weakness of e‐health (electronic health) (i.e. the lack of direct contact between physician and patient) may prove to be a strength, given the high contagiousness and relative lethality of the virus. In Italy the lack of preparation for supporting the patient load (shortage of personal protection devices, shortage of Intensive Care Unit (ICU) beds in comparison to other European Countries, and the poor early diagnostic and therapeutic activity) has led us to suggest a project that uses an online platform between General Practitioners and patients, in order to reduce moving infected individuals and to perform the diagnosis and treatment early on.


title: A discrete epidemic model for SARS transmission and control in China

text: Abstract Severe acute respiratory syndrome (SARS) is a rapidly spreading infectious disease which was transmitted in late 2002 and early 2003 to more than 28 countries through the medium of international travel. The evolution and spread of SARS has resulted in an international effort coordinated by the World Health Organization (WHO). We have formulated a discrete mathematical model to investigate the transmission of SARS and determined the basic reproductive number for this model to use as a threshold to determine the asymptotic behavior of the model. The dependence of the basic reproductive number on epidemic parameters has been studied. The parameters of the model have been estimated on the basis of statistical data and numerical simulations have been carried out to describe the transmission process for SARS in China. The simulation results matches the statistical data well and indicate that early quarantine and a high quarantine rate are crucial to the control of SARS.


title: Practical considerations for the diagnosis and treatment of fibrotic interstitial lung disease during the COVID-19 pandemic

text: Abstract The 2019 coronavirus disease (COVID-19) pandemic caused by the SARS-CoV-2 virus has affected virtually all aspects of patient care. Healthcare systems around the world are trying to simultaneously treat patients with COVID-19 infection, prepare for its long-term impacts, and manage patients with other acute and chronic diseases. There are multiple ways that the COVID-19 pandemic will directly affect patients with fibrotic interstitial lung disease (ILD), particularly given their common risk factors for poor outcomes. Major issues for patients with ILD will include restricted access to key components of the diagnostic process, new uncertainties in the use of common ILD pharmacotherapies, limited ability to monitor both disease severity and the presence of medication adverse effects, and significantly curtailed research activities. The purpose of this review is to summarize how COVID-19 has impacted key components of the diagnosis and management of fibrotic ILD as well as to provide strategies to mitigate these challenges. We further review major obstacles for researchers and identify priority areas for future ILD research related to COVID-19. Our goals are to provide practical considerations to support the care of patients with ILD during the COVID-19 pandemic and to provide a road map for clinicians caring for these patients during future infectious disease outbreaks.


title: Immunoinformatics-guided designing of epitope-based subunit vaccine against the SARS Coronavirus-2 (SARS-CoV-2)

text: SARS Coronavirus-2 (SARS-CoV-2) pandemic has become a global issue which has raised the concern of scientific community to design and discover a counter-measure against this deadly virus which has caused deaths of numerous infected people upon infection and spreading. To date, no effective vaccine is available which can combat the infection caused by this virus. This study was conducted to design possible epitope-based subunit vaccines against the SARS-CoV-2 virus using the approaches of reverse vaccinology and immunoinformatics. Upon continual computational experimentation three possible vaccine constructs were designed and one vaccine construct was selected as the best vaccine based on molecular docking study which is supposed to effectively act against SARS-CoV-2. Thereafter, molecular dynamics simulation and in silico codon adaptation experiments were carried out in order to check biological stability and find effective mass production strategy of the selected vaccine. This study should contribute to uphold the present efforts of the researches to secure a definitive treatment for this lethal disease.


title: Increasing the X-ray Diffraction Power of Protein Crystals by Dehydration: The Case of Bovine Serum Albumin and a Survey of Literature Data

text: Serum albumin is one of the most widely studied proteins. It is the most abundant protein in plasma with a typical concentration of 5 g/100 mL and the principal transporter of fatty acids in plasma. While the crystal structures of human serum albumin (HSA) free and in complex with fatty acids, hemin, and local anesthetics have been characterized, no crystallographic models are available on bovine serum albumin (BSA), presumably because of the poor diffraction power of existing hexagonal BSA crystals. Here, the crystallization and diffraction data of a new BSA crystal form, obtained by the hanging drop method using MPEG 5K as precipitating agent, are presented. The crystals belong to space group C2, with unit-cell parameters a = 216.45 Å, b = 44.72 Å, c = 140.18 Å, β = 114.5°. Dehydration was found to increase the diffraction limit of BSA crystals from ~8 Å to 3.2 Å, probably by improving the packing of protein molecules in the crystal lattice. These results, together with a survey of more than 60 successful cases of protein crystal dehydration, confirm that it can be a useful procedure to be used in initial screening as a method of improving the diffraction limits of existing crystals.


title: Infection and Coinfection of Human Rhinovirus C in Stem Cell Transplant Recipients

text: In 54 adult stem cell transplant recipients, the presence and persistence of human rhinoviruses (including the novel lineage C) were evaluated by molecular detection and phylogenetic analysis, independently from respiratory symptoms. In the same group of patients, the presence of other coinfecting respiratory pathogens, including the novel enterovirus 109, was also evaluated.


title: Synthesis and in vitro antiviral evaluation of 4-substituted 3,4-dihydropyrimidinones

text: Abstract A series of 4-substituted 3,4-dihydropyrimidine-2-ones (DHPM) was synthesized, characterized by IR, 1H NMR, 13C NMR and HRMS spectra. The compounds were evaluated in vitro for their antiviral activity against a broad range of DNA and RNA viruses, along with assessment for potential cytotoxicity in diverse mammalian cell lines. Compound 4m, which possesses a long lipophilic side chain, was found to be a potent and selective inhibitor of Punta Toro virus, a member of the Bunyaviridae. For Rift Valley fever virus, which is another Bunyavirus, the activity of 4m was negligible. DHPMs with a C-4 aryl moiety bearing halogen substitution (4b, 4c and 4d) were found to be cytotoxic in MT4 cells.


title: Evolution of pathogens in a man‐made world

text: Human activities have resulted in substantial, large‐scale environmental modifications, especially in the past century. Ecologists and evolutionary biologists are increasingly coming to realize that parasites and pathogens, like free‐living organisms, evolve as the consequence of these anthropogenic changes. Although this area now commands the attention of a variety of researchers, a broad predictive framework is lacking, mainly because the links between human activities, the environment and parasite evolution are complex. From empirical and theoretical examples chosen in the literature, we give an overview of the ways in which humans can directly or indirectly influence the evolution of different traits in parasites (e.g. specificity, virulence, polymorphism). We discuss the role of direct and indirect factors as diverse as habitat fragmentation, pollution, biodiversity loss, climate change, introduction of species, use of vaccines and antibiotics, ageing of the population, etc. We also present challenging questions for further research. Understanding the links between anthropogenic changes and parasite evolution needs to become a cornerstone of public health planning, economic development and conservation biology.


Is the SARS-CoV-2 virus present intraperitoneally in patients with COVID infection undergoing emergency operations?


title: COVID‐19 pneumonia in kidney transplant recipients: Focus on immunosuppression management

text: BACKGROUND: The coronavirus disease of 2019, also known as COVID‐19, has been declared a global pandemic. Significant controversies exist regarding treatment modalities for this novel disease, especially in immunocompromised patients. Experience with management of COVID‐19 in kidney transplant recipients is scarce; effects of this virus on immunosuppressed individuals are not well understood. METHODS: We identified 30 renal transplant recipients with confirmed COVID‐19 pneumonia who were admitted to inpatient between March 2020 and April 2020. All patients received a 5‐day course of hydroxychloroquine and azithromycin; half of the patients received methylprednisolone. During hospitalization, calcineurin inhibitors and antimetabolites were held; prednisone was continued. RESULTS: Clinical presentation of flu‐like symptoms was similar to those in the general population. Hyponatremia, lymphopenia, acute kidney injury, and elevated inflammatory markers were common. Over the course of follow‐up, 23 have been discharged home with a functioning allograft and in stable condition; 4 experienced acute kidney injury requiring renal replacement therapy; 7 patients were intubated, and 6 expired. The mortality rate in our cohort was 20%. CONCLUSION: Our findings described the characteristics and outcomes of this highly fatal illness in a multi‐ethnic kidney transplant cohort, with insights on immunosuppression management that could further our understanding of this unique disease in immunocompromised populations.


title: Acute cor pulmonale from saddle pulmonary embolism in a patient with previous Covid-19 – should we prolong prophylactic anticoagulation?

text: Abstract Severe corona virus disease 19 (Covid-19) is known to be associated with exaggerated risk of thromboembolism. However, the risk associated with mild and moderate illness from Covid-19 is unknown, and there is no current recommendation for prophylaxis against thromboembolism in patients after hospital treatment unless there are established thrombophilic risk factors. We report the case of a 52-year old woman, who presented with massive saddle pulmonary embolism after one week of initial hospital discharge, successfully thrombolysed that raises the question of consideration of extended prophylactic anticoagulation even in low risk Covid-19 cases.


title: Legal rights during pandemics: Federalism, rights and public health laws – a view from Australia

text: Summary Pandemic influenza will cause significant social and economic disruption. Legal frameworks can play an important role in clarifying the rights and duties of individuals, communities and governments for times of crisis. In addressing legal frameworks, there is a need for jurisdictional clarity between different levels of government in responding to public health emergencies. Public health laws are also informed by our understandings of rights and responsibilities for individuals and communities, and the balancing of public health and public freedoms. Consideration of these issues is an essential part of planning for pandemic influenza.


title: Structure(s), function(s), and inhibition of the RNA-dependent RNA polymerase of noroviruses

text: Abstract Noroviruses belong to the Caliciviridae family of single-stranded positive-sense RNA viruses. The genus Norovirus includes seven genogroups (designated GI-GVII), of which GI, GII and GIV infect humans. Human noroviruses are responsible for widespread outbreaks of acute gastroenteritis and represent one of the most common causes of foodborne illness. No vaccine or antiviral treatment options are available for norovirus infection. The RNA-dependent RNA polymerase (RdRp) of noroviruses is a key enzyme responsible for transcription and replication of the viral genome. Here, we review the progress made in understanding the structures and functions of norovirus RdRp and its use as a target for small molecule inhibitors. Crystal structures of the RdRp at different stages of substrate interaction have been determined, which shed light on its multi-step catalytic cycle. The in vitro assays and in vivo animal models that have been developed to identify and characterize inhibitors of norovirus RdRp are also summarized, followed by an update on the current antiviral research targeting different regions of norovirus RdRp. In the future, structure-based drug design and rational optimization of known nucleoside and non-nucleoside inhibitors of norovirus RdRp may pave the way towards the next generation of direct-acting antivirals.


title: Infections with A(H1N1)2009 Influenza Virus in Poland During the Last Pandemic: Experience of the National Influenza Center

text: This study presents epidemiological and clinical data on non-sentinel patients considered by physicians as suspected to be infected with pandemic A(H1N1)2009 virus, from whom clinical specimens were sent for testing to the National Influenza Center, NIPH-NIH in Warsaw, Poland. Between April 28, 2009 and August 10, 2010, 988 (15.7%) out of the 6,311 specimens were tested by the National Influenza Center, including 798 from non-sentinel sources and 190 from sentinel influenza surveillance network. The non-sentinel specimens were tested by conventional RT-PCR to detect influenza A and in the case of positive specimens – one-step real-time RT-PCR to detect the pandemic virus A(H1N1)2009. In 145 (18.2%) cases, infections with the pandemic virus were confirmed, with the highest number in patients aged 15–25. In 45% of the confirmed cases, a history of travel to other countries was registered. The most common symptoms were fever ≥38°C (72.7%), cough (50%), sore throat, and myalgia (26.1%). In 40.7% of the swabbed patients, clinical and epidemiological criteria for the novel influenza A(H1N1)2009, set by the European Commission, were met. There were, however, specimens from persons without any reasonable indication for testing for the pandemic virus, specimens collected incorrectly, and documentation without basic information. These weaknesses resulted in unnecessary costs and overload of health care units. An improvement should be achieved in the area of communication between different pandemic players in the future. More attention is also needed to ensure that requirements and recommendations are known and used.


title: Development of a Positive-readout Mouse Model of siRNA Pharmacodynamics

text: Development of RNAi-based therapeutics has the potential to revolutionize treatment options for a range of human diseases. However, as with gene therapy, a major barrier to progress is the lack of methods to achieve and measure efficient delivery for systemic administration. We have developed a positive-readout pharmacodynamic transgenic reporter mouse model allowing noninvasive real-time assessment of siRNA activity. The model combines a luciferase reporter gene under the control of regulatory elements from the lac operon of Escherichia coli. Introduction of siRNA targeting lac repressor results in increased luciferase expression in cells where siRNA is biologically active. Five founder luciferase-expressing and three founder Lac-expressing lines were generated and characterized. Mating of ubiquitously expressing luciferase and lac lines generated progeny in which luciferase expression was significantly reduced compared with the parental line. Administration of isopropyl β-D-1-thiogalactopyranoside either in drinking water or given intraperitoneally increased luciferase expression in eight of the mice examined, which fell rapidly when withdrawn. Intraperitoneal administration of siRNA targeting lac in combination with Lipofectamine 2000 resulted in increased luciferase expression in the liver while control nontargeting siRNA had no effect. We believe a sensitive positive readout pharmacodynamics reporter model will be of use to the research community in RNAi-based vector development.


title: Development of remdesivir repositioning as a nucleotide analog against COVID-19 RNA dependent RNA polymerase

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative representative of a severe respiratory illness resulted in widespread human infections and deaths in nearly all of the countries since late 2019. There is no therapeutic FDA-approved drug against SARS-CoV-2 infection, although a combination of anti-viral drugs is directly being practiced in some countries. A broad-spectrum of antiviral agents are being currently evaluated in clinical trials, and in this review, we specifically focus on the application of Remdesivir (RVD) as a potential anti-viral compound against Middle East respiratory syndrome (MERS) -CoV, SARS-CoV and SARS-CoV-2. First, we overview the general information about SARS-CoV-2, followed by application of RDV as a nucleotide analogue which can potentially inhibits RNA-dependent RNA polymerase of COVs. Afterwards, we discussed the kinetics of SARS- or MERS-CoV proliferation in animal models which is significantly different compared to that in humans. Finally, some ongoing challenges and future perspective on the application of RDV either alone or in combination with other anti-viral agents against CoVs infection were surveyed to determine the efficiency of RDV in preclinical trials. As a result, this paper provides crucial evidence of the potency of RDV to prevent SARS-CoV-2 infections. Communicated by Ramaswamy H. Sarma


title: Bilateral acute cardioembolic limb ischemia after Covid-19 pneumonia in a lung transplant recipient: a case report

text: ABSTRACT Very few cases of lung transplant patients affected by Covid-19 have been reported to date. A 31-year-old patient with bilateral lung transplantation for cystic fibrosis in 2012 was admitted for severe acute lower limb pain. He had a confirmed exposure to Covid-19, and a 3-week history of upper respiratory tract infection. Whole body computed tomography (CT) angiography revealed an occlusion of the two common femoral arteries. CT angiography detected an intracardiac thrombus in the left ventricle. Chest CT angiography showed ground-glass opacities consistent with a Covid-19. A bilateral femoral surgical embolectomy using Fogarty probe was successfully performed. Specific RT-PCR for SARS-CoV-2 performed on an extracted thrombus was negative but IgM antibodies specific to Covid-19 were detected. Cardiac MRI demonstrated a sub-endocardial and almost transmural late gadolinium enhancement in the mid and distal inferolateral and inferior wall segments, consistent with a non-recent myocardial infarction and an apical centimetric thrombus adjacent to the lesion. Thrombophilia laboratory tests found the presence of a positive lupus anticoagulant.Treatment with low-molecular weight heparin and aspirin was prescribed. On day 13, patient was discharged from hospital. This case underlines the need to be vigilant with respect to the thrombotic complications of Covid-19 and raises the issue of thrombosis prevention in Covid-19 patients.


title: Emerging infectious diseases and pandemic potential: status quo and reducing risk of global spread

text: Summary Emerging infectious diseases are an important public health threat and infections with pandemic potential are a major global risk. Although much has been learned from previous events the evidence for mitigating actions is not definitive and pandemic preparedness remains a political and scientific challenge. A need exists to develop trust and effective meaningful collaboration between countries to help with rapid detection of potential pandemic infections and initiate public health actions. This collaboration should be within the framework of the International Health Regulations. Collaboration between countries should be encouraged in a way that acknowledges the benefits that derive from sharing biological material and establishing equitable collaborative research partnerships. The focus of pandemic preparedness should include upstream prevention through better collaboration between human and animal health sciences to enhance capacity to identify potential pathogens before they become serious human threats, and to prevent their emergence where possible. The one-health approach provides a means to develop this and could potentially enhance alignment of global health and trade priorities.


title: 3B11-N, a monoclonal antibody against MERS-CoV, reduces lung pathology in rhesus monkeys following intratracheal inoculation of MERS-CoV Jordan-n3/2012

text: Abstract Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was identified in 2012 as the causative agent of a severe, lethal respiratory disease occurring across several countries in the Middle East. To date there have been over 1600 laboratory confirmed cases of MERS-CoV in 26 countries with a case fatality rate of 36%. Given the endemic region, it is possible that MERS-CoV could spread during the annual Hajj pilgrimage, necessitating countermeasure development. In this report, we describe the clinical and radiographic changes of rhesus monkeys following infection with 5×106 PFU MERS-CoV Jordan-n3/2012. Two groups of NHPs were treated with either a human anti-MERS monoclonal antibody 3B11-N or E410-N, an anti-HIV antibody. MERS-CoV Jordan-n3/2012 infection resulted in quantifiable changes by computed tomography, but limited other clinical signs of disease. 3B11-N treated subjects developed significantly reduced lung pathology when compared to infected, untreated subjects, indicating that this antibody may be a suitable MERS-CoV treatment.


title: Phacomatoses in the pediatric age group

text: The most common phacomatoses in children that need surgical attention are neurofibromatosis 1 and 2, tuberous sclerosis complex, Sturge-Weber disease, Von Hippel-Lindau disease, and neurocutaneous melanocytosis. All are rare and, as genetically determined disorders, all complex multisystem diseases with multiple manifestations outside the CNS. Diagnostics, management recommendations, and surgical care are age-specific and require individualization. The lifelong multidimensional disease burden demands a multidisciplinary and well-coordinated management approach. The consequence of these boundary conditions is that management of children with a phacomatosis is everything else but simple, straight forward, and intuitive. This Special Annual Issue is designed to serve as an up-to-date encyclopedic reference for all aspects of management of phacomatoses in the pediatric age group.


Emergency department registered nurses’ disaster medicine competencies. An exploratory study utilizing a modified Delphi technique


title: A Chemographic Audit of anti‐Coronavirus Structure‐Activity Information from Public Databases (ChEMBL)

text: Discovery of drugs against newly emerged pathogenic agents like the SARS‐CoV‐2 coronavirus (CoV) must be based on previous research against related species. Scientists need to get acquainted with and develop a global oversight over so‐far tested molecules. Chemography (herein used Generative Topographic Mapping, in particular) places structures on a human‐readable 2D map (obtained by dimensionality reduction of the chemical space of molecular descriptors) and is thus well suited for such an audit. The goal is to map medicinal chemistry efforts so far targeted against CoVs. This includes comparing libraries tested against various virus species/genera, predicting their polypharmacological profiles and highlighting often encountered chemotypes. Maps are challenged to provide predictive activity landscapes against viral proteins. Definition of “anti‐CoV” map zones led to selection of therein residing 380 potential anti‐CoV agents, out of a vast pool of 800 M organic compounds.


title: Future risk of dengue fever to workforce and industry through global supply chain

text: The primary vector of the dengue fever virus, the Aedes aegypti mosquito, is distributed across the tropical and sub-tropical latitudes; however, the area at risk of infection has been expanding steadily. This study aimed to identify the industries most vulnerable to the effects of dengue fever by 2030. The assessment was done by considering the international supply chain, with aspects such as the labor intensity, and the relevant geographical and socioeconomic aspects being taken into account. In addition, multi-regional input-output tables were employed to analyze the ripple effects of productivity losses resulting from workers contracting the disease. The results indicate that more than 10% of the workers involved in the supply chain of all the major industries in the United States (USA), China, Japan, and Germany could be considered at risk of contracting dengue fever by 2030. Moreover, the risk was even higher in India and Brazil, namely, more than 70%. The effect of widespread dengue fever infection could influence industrial activities severely, not only in the regions most at risk (India and Brazil) but also in the other regions (USA, Japan, and Germany). Labor-intensive industries, such as agriculture, fisheries, and the distribution sector are particularly at risk and will have to consider appropriate contingency measures. It is recommended that the downstream side of the supply chain, the industries in the USA, Japan, and Germany, supports the introduction of worker’s health management system against the infectious disease into their business partners. This study employed limited data and only estimated the possible effects of the disease by 2030. Further comprehensive analysis is required with more data modeled for the future to verify and enhance the reliability of the present results.


title: COVID‐19 under the SARS Cloud: Mental Health Nursing during the Pandemic in Hong Kong

text: This editorial presents a commentary on COVID-19 and mental health in Hong Kong. We outline the current measures being used to contain the outbreak and how the experience of the SARS epidemic may have influenced the response in Hong Kong. We also discuss the potential mental health ill-effects of the pandemic and its impact on mental health nursing locally.


title: Identification of an Unclassified Paramyxovirus in Coleura afra: A Potential Case of Host Specificity

text: Bats are known to harbor multiple paramyxoviruses. Despite the creation of two new genera, Aquaparamyxovirus and Ferlavirus, to accommodate this increasing diversity, several recently isolated or characterized viruses remain unclassified beyond the subfamily level. In the present study, among 985 bats belonging to 6 species sampled in the Belinga caves of Gabon, RNA of an unclassified paramyxovirus (Belinga bat virus, BelPV) was discovered in 14 African sheath-tailed bats (Coleura afra), one of which exhibited several hemorrhagic lesions at necropsy, and viral sequence was obtained in two animals. Phylogenetically, BelPV is related to J virus and Beilong virus (BeiPV), two other unclassified paramyxoviruses isolated from rodents. In the diseased BelPV-infected C. afra individual, high viral load was detected in the heart, and the lesions were consistent with those reported in wild rodents and mice experimentally infected by J virus. BelPV was not detected in other tested bat species sharing the same roosting sites and living in very close proximity with C. afra in the two caves sampled, suggesting that this virus may be host-specific for C. afra. The mode of transmission of this paramyxovirus in bat populations remains to be discovered.


title: Metagenomic Approach to Characterizing Disease Epidemiology in a Disease-Endemic Environment in Northern Thailand

text: In this study, we used a metagenomic approach to analyze bacterial communities from diverse populations (humans, animals, and vectors) to investigate the role of these microorganisms as causative agents of disease in human and animal populations. Wild rodents and ectoparasites were collected from 2014 to 2018 in Nan province, Thailand where scrub typhus is highly endemic. Samples from undifferentiated febrile illness (UFI) patients were obtained from a local hospital. A total of 200 UFI patient samples were obtained and 309 rodents and 420 pools of ectoparasites were collected from rodents (n = 285) and domestic animals (n = 135). The bacterial 16S rRNA gene was amplified and sequenced with the Illumina. Real-time PCR and Sanger sequencing were used to confirm the next-generation sequencing (NGS) results and to characterize pathogen species. Several pathogens were detected by NGS in all populations studied and the most common pathogens identified included Bartonella spp., Rickettsia spp., Leptospira spp., and Orientia tsutsugamushi. Interestingly, Anaplasma spp. was detected in patient, rodent and tick populations, although they were not previously known to cause human disease from this region. Candidatus Neoehrlichia, Neorickettsia spp., Borrelia spp., and Ehrlichia spp. were detected in rodents and their associated ectoparasites. The same O. tsutsugamushi genotypes were shared among UFI patients, rodents, and chiggers in a single district indicating that the chiggers found on rodents were also likely responsible for transmitting to people. Serological testing using immunofluorescence assays in UFI samples showed high prevalence (IgM/IgG) of Rickettsia and Orientia pathogens, most notably among samples collected during September–November. Additionally, a higher number of seropositive samples belonged to patients in the working age population (20–60 years old). The results presented in this study demonstrate that the increased risk of human infection or exposure to chiggers and their associated pathogen (O. tsutsugamushi) resulted in part from two important factors; working age group and seasons for rice cultivation and harvesting. Evidence of pathogen exposure was shown to occur as there was seropositivity (IgG) in UFI patients for bartonellosis as well as for anaplasmosis. Using a metagenomic approach, this study demonstrated the circulation and transmission of several pathogens in the environment, some of which are known causative agents of illness in human populations.


title: TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes

text: Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA are frequently observed in COVID-19 patients. However, it is unclear whether SARS-CoV-2 replicates in the human intestine and contributes to possible fecal-oral transmission. Here, we report productive infection of SARS-CoV-2 in ACE2(+) mature enterocytes in human small intestinal enteroids. Expression of two mucosa-specific serine proteases, TMPRSS2 and TMPRSS4, facilitated SARS-CoV-2 spike fusogenic activity and promoted virus entry into host cells. We also demonstrate that viruses released into the intestinal lumen were inactivated by simulated human colonic fluid, and infectious virus was not recovered from the stool specimens of COVID-19 patients. Our results highlight the intestine as a potential site of SARS-CoV-2 replication, which may contribute to local and systemic illness and overall disease progression.


How to Deal With Post-viral Cutaneous Eruptions in the Era of Coronavirus Infection


title: Network pharmacology to dissect the mechanisms of Yinlai Decoction for pneumonia

text: BACKGROUND: Pneumonia is a common respiratory disorder, which brings an enormous financial burden to the medical system. However, the current treatment options for pneumonia are limited because of drug resistance and side effects. Our previous study preliminarily confirmed that Yinlai Decoction (YD), a common prescription for pneumonia in clinical practice, can regulate the expression of inflammatory factors, but the mechanisms are unknown yet. METHODS: In our work, a method named network pharmacology was applied, which investigated the underlying mechanisms of herbs based on a variety of databases. We obtained bioactive ingredients of YD on TCMSP database and collected potential targets of these ingredients by target fishing. Then the pneumonia-related targets database was built by TTD, Drugbank, HPO, OMIM, and CTD. Based on the matching targets between YD and pneumonia, the PPI network was built by STRING to analyze the interactions among these targets and then input into Cytoscape for further topological analysis. DAVID and KEGG were utilized for GO and pathway enrichment analysis. Then rat model based on LPS stimulated pneumonia was used to verify the possible mechanism of YD in treating pneumonia. RESULTS: Sixty-eight active ingredients, 103 potential targets and 8 related pathways, which likely exert a number of effects, were identified. Three networks were constructed using Cytoscape, which were herb-component-network, YD-pneumonia target network, and herb-component-YD target-pneumonia network. YD was verified to treat LPS-induced pneumonia by regulating the inflammatory factor IL-6, which was a predicted target. CONCLUSION: Network analysis indicated that YD could alleviate the symptoms and signs of pneumonia through regulating host immune inflammatory response, angiogenesis and vascular permeability, the barrier function of the airway epithelial cells, hormone releasing and cell growth, proliferation, and apoptosis.


title: SOFFCO-MM guidelines for the resumption of bariatric and metabolic surgery during and after the Covid-19 pandemic

text: ABSTRACT Bariatric/metabolic surgery was paused during the Covid-19 pandemic. The impact of social confinement and the interruption of this surgery on the population with obesity has been underestimated, with weight gain and worsened comorbidities. Some candidates for this surgery are exposed to a high risk of mortality linked to the pandemic. Obesity and diabetes are two major risk factors for severe forms of Covid-19. The only currently effective treatment for obesity is metabolic surgery, which confers prompt, lasting benefits. It is thus necessary to resume such surgery.To ensure that this resumption is both gradual and well-founded, we have devised a priority ranking plan. The flow charts we propose will help centres to identify priority patients according to a benefit/risk assessment. Diabetes holds a central place in the decision tree. Resumption patterns will vary from one centre to another according to human, physical and medical resources, and will need adjustment as the epidemic unfolds.Specific informed consent will be required. Screening of patients with obesity should be considered, based on available knowledge. If Covid-19 is suspected, surgery must be postponed. Emphasis must be placed on infection control measures to protect patients and healthcare professionals. Confinement is strongly advocated for patients for the first month post-operatively. Patient follow-up should preferably be by teleconsultation.


title: Delayed allogeneic skin graft rejection in CD26-deficient mice

text: Organ transplantation is an effective therapeutic tool for treating many terminal diseases. However, one of the biggest challenges of transplantation is determining how to achieve the long-term survival of the allogeneic or xenogeneic transplant by, for example, preventing transplant rejection. In the current study, CD26 gene-knockout mice were used to investigate the potential role of CD26/dipeptidyl peptidase-4 (DPPIV) in allogeneic skin graft rejection by tail-skin transplantation. Compared with wild-type (CD26(+/+)) counterparts, CD26(–/–) mice showed reduced necrosis of grafts and delayed graft rejection after skin transplantation. Concentrations of serum IgG, including its subclasses IgG1 and IgG2a, were significantly reduced in CD26(–/–) mice during graft rejection. Moreover, after allogeneic skin transplantation, the secretion levels of the cytokines IFN-γ, IL-2, IL-6, IL-4, and IL-13 were significantly reduced, whereas the level of the cytokine IL-10 was increased in the serum of CD26(–/–) mice compared with that in the serum of CD26(+/+) mice. Additionally, the concentration of IL-17 in serum and the percentage of cells secreting IL-17 in mouse peripheral blood lymphocytes (MPBLs) were both significantly lower, while the percentage of regulatory T cells (Tregs) was significantly higher in MPBLs of CD26(–/–) mice than in those of CD26(+/+) mice. Furthermore, a lower percentage of CD8(+) T cells in MPBLs and fewer infiltrated macrophages and T cells in graft tissues of CD26(–/–) mice were detected during graft rejection. These results indicate that CD26 is involved in allogeneic skin graft rejection and provides another hint that CD26 deficiency leads to less rejection due to lower activation and proliferation of host immune cells.


title: Advances that facilitate the study of large RNA structure and dynamics by nuclear magnetic resonance spectroscopy

text: The characterization of functional yet nonprotein coding (nc) RNAs has expanded the role of RNA in the cell from a passive player in the central dogma of molecular biology to an active regulator of gene expression. The misregulation of ncRNA function has been linked with a variety of diseases and disorders ranging from cancers to neurodegeneration. However, a detailed molecular understanding of how ncRNAs function has been limited; due, in part, to the difficulties associated with obtaining high‐resolution structures of large RNAs. Tertiary structure determination of RNA as a whole is hampered by various technical challenges, all of which are exacerbated as the size of the RNA increases. Namely, RNAs tend to be highly flexible and dynamic molecules, which are difficult to crystallize. Biomolecular nuclear magnetic resonance (NMR) spectroscopy offers a viable alternative to determining the structure of large RNA molecules that do not readily crystallize, but is itself hindered by some technical limitations. Recently, a series of advancements have allowed the biomolecular NMR field to overcome, at least in part, some of these limitations. These advances include improvements in sample preparation strategies as well as methodological improvements. Together, these innovations pave the way for the study of ever larger RNA molecules that have important biological function. RNA Structure and Dynamics > RNA Structure, Dynamics, and Chemistry. Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs. RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems.


title: Bacterial ribonuclease binase exerts an intra-cellular anti-viral mode of action targeting viral RNAs in influenza a virus-infected MDCK-II cells

text: BACKGROUND: Influenza is a severe contagious disease especially in children, elderly and immunocompromised patients. Beside vaccination, the discovery of new anti-viral agents represents an important strategy to encounter seasonal and pandemic influenza A virus (IAV) strains. The bacterial extra-cellular ribonuclease binase is a well-studied RNase from Bacillus pumilus. Treatment with binase was shown to improve survival of laboratory animals infected with different RNA viruses. Although binase reduced IAV titer in vitro and in vivo, the mode of action (MOA) of binase against IAV at the molecular level has yet not been studied in depth and remains elusive. METHODS: To analyze whether binase impairs virus replication by direct interaction with the viral particle we applied a hemagglutination inhibition assay and monitored the integrity of the viral RNA within the virus particle by RT-PCR. Furthermore, we used Western blot and confocal microscopy analysis to study whether binase can internalize into MDCK-II cells. By primer extension we examined the effect of binase on the integrity of viral RNAs within the cells and using a mini-genome system we explored the effect of binase on the viral expression. RESULTS: We show that (i) binase does not to attack IAV particle-protected viral RNA, (ii) internalized binase could be detected within the cytosol of MDCK-II cells and that (iii) binase impairs IAV replication by specifically degrading viral RNA species within the infected MDCK-II cells without obvious effect on cellular mRNAs. CONCLUSION: Our data provide novel evidence suggesting that binase is a potential anti-viral agent with specific intra-cellular MOA. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-017-0915-1) contains supplementary material, which is available to authorized users.


title: Involvement of the nucleolus in replication of human viruses

text: Viruses are intracellular pathogens that have to usurp some of the cellular machineries to provide an optimal environment for their own replication. An increasing number of reports reveal that many viruses induce modifications of nuclear substructures including nucleoli, whether they replicate or not in the nucleus of infected cells. Indeed, during infection of cells with various types of human viruses, nucleoli undergo important morphological modifications. A large number of viral components traffic to and from the nucleolus where they interact with different cellular and/or viral factors, numerous host nucleolar proteins are redistributed in other cell compartments or are modified and some cellular proteins are delocalised in the nucleolus of infected cells. Well‐documented studies have established that several of these nucleolar modifications play a role in some steps of the viral cycle, and also in fundamental cellular pathways. The nucleolus itself is the place where several essential steps of the viral cycle take place. In other cases, viruses divert host nucleolar proteins from their known functions in order to exert new unexpected role(s). Copyright © 2009 John Wiley & Sons, Ltd.


New sensations in molecular diagnostics—NucliSENS easyMAG extraction platform and NucliSENs EasyQ assays


title: Early detection of dynamic harmful cascades in large-scale networks

text: Abstract Quickly detecting harmful cascades in networks can allow us to analyze the causes and prevent further spreading of destructive influence. Since it is often impossible to observe the state of all nodes in a network, a common method is to detect harmful cascades from sparsely placed sensors. However, the harmful cascades are usually dynamic (e.g., the cascade initiators and diffusion trajectories can change over the time), which can severely destroy the robustness of selected sensors. Meanwhile the large scale of current networks greatly increases the time complexity of sensor selection. Motivated by the observation, in this paper we investigate the scalable sensor selection problem for early detection of dynamic harmful cascades in networks. Specifically, we first put forward a dynamic susceptible-infected model to describe harmful cascades, and formally define a detection time minimization (DTM) problem which focuses on effective sensors placement for early detection of dynamic cascades. We prove that it is #P-hard to calculate the objective function exactly and propose two Monte-Carlo methods to estimate it efficiently. We prove the NP-hardness of DTM problem and design a corresponding greedy algorithm. Based on that, we propose an efficient upper bound based greedy (UBG) algorithm with the theoretical performance guarantee reserved. To further meet different types of large-scale networks, we propose two accelerations of UBG: Quickest-Path-UBG for sparse networks and Local-Reduction-UBG for dense networks to improve the time complexity. The experimental results on synthetic and real-world social networks demonstrate the practicality of our approaches.


title: Quasispecies of bovine enteric and respiratory coronaviruses based on complete genome sequences and genetic changes after tissue culture adaptation

text: Abstract The genetic diversity of 2 pairs (AH65 and AH187) of wild type bovine coronaviruses (BCoV) sequenced directly from nasal (respiratory) and rectal (enteric) swabs of two feedlot calves with respiratory and enteric symptoms [Hasoksuz, M., Sreevatsan, S., Cho, K.O., Hoet, A.E., Saif, L.J., 2002b. Molecular analysis of the S1 subunit of the spike glycoprotein of respiratory and enteric bovine coronavirus isolates. Virus Res. 84 (1–2), 101–109.]. was analyzed. Sequence analysis of the complete genomes revealed differences at 123 and 149 nucleotides (nt) throughout the entire genome between the respiratory and enteric strains for samples AH65 and AH187, respectively, indicating the presence of intra-host BCoV quasispecies. In addition, significant numbers of sequence ambiguities were found in the genomes of some BCoV-R and BCoV-E strains, suggesting intra-isolate quasispecies. The tissue culture (TC) passaged counterparts of AH65 respiratory BCoV (AH65-R-TC) and enteric BCoV (AH65-E-TC) were also sequenced after 14 and 15 passages and 1 plaque purification in human rectal tumor cells (HRT-18), respectively. Compared to the parental wild type strains, tissue culture passage generated 104 nt changes in the AH65-E-TC isolate but only 8 nt changes in the AH65-R-TC isolate. Particularly noteworthy, the majority of nucleotide changes in the AH65-E-TC isolate occurred at the identical positions as the mutations occurring in the AH65-R strain from the same animal. These data suggest that BCoV evolves through quasispecies development, and that enteric BCoV isolates are more prone to genetic changes and may mutate to resemble respiratory BCoV strains after tissue culture passage.


title: Relationship of SARS-CoV to other pathogenic RNA viruses explored by tetranucleotide usage profiling

text: BACKGROUND: The exact origin of the cause of the Severe Acute Respiratory Syndrome (SARS) is still an open question. The genomic sequence relationship of SARS-CoV with 30 different single-stranded RNA (ssRNA) viruses of various families was studied using two non-standard approaches. Both approaches began with the vectorial profiling of the tetra-nucleotide usage pattern V for each virus. In approach one, a distance measure of a vector V, based on correlation coefficient was devised to construct a relationship tree by the neighbor-joining algorithm. In approach two, a multivariate factor analysis was performed to derive the embedded tetra-nucleotide usage patterns. These patterns were subsequently used to classify the selected viruses. RESULTS: Both approaches yielded relationship outcomes that are consistent with the known virus classification. They also indicated that the genome of RNA viruses from the same family conform to a specific pattern of word usage. Based on the correlation of the overall tetra-nucleotide usage patterns, the Transmissible Gastroenteritis Virus (TGV) and the Feline CoronaVirus (FCoV) are closest to SARS-CoV. Surprisingly also, the RNA viruses that do not go through a DNA stage displayed a remarkable discrimination against the CpG and UpA di-nucleotide (z = -77.31, -52.48 respectively) and selection for UpG and CpA (z = 65.79,49.99 respectively). Potential factors influencing these biases are discussed. CONCLUSION: The study of genomic word usage is a powerful method to classify RNA viruses. The congruence of the relationship outcomes with the known classification indicates that there exist phylogenetic signals in the tetra-nucleotide usage patterns, that is most prominent in the replicase open reading frames.


title: Advanced “lab-on-a-chip” to detect viruses – Current challenges and future perspectives

text: Massive viral outbreaks draw attention to viruses that have not been thoroughly studied or understood. In recent decades, microfluidic chips, known as “lab-on-a-chip”, appears as a promising tool for the detection of viruses. Here, we review the development of microfluidic chips that could be used in response to viral detection, specifically for viruses involved in more recent outbreaks. The advantages as well as the disadvantages of microfluidic systems are discussed and analyzed. We also propose ideas for future development of these microfluidic chips and we expect this advanced technology to be used in the future for viral outbreaks.


title: Cytosolic DNA sensing through cGAS and STING is inactivated by gene mutations in pangolins

text: The release of DNA into the cytoplasm upon damage to the nucleus or during viral infection triggers an interferon-mediated defense response, inflammation and cell death. In human cells cytoplasmic DNA is sensed by cyclic GMP-AMP Synthase (cGAS) and Absent In Melanoma 2 (AIM2). Here, we report the identification of a “natural knockout” model of cGAS. Comparative genomics of phylogenetically diverse mammalian species showed that cGAS and its interaction partner Stimulator of Interferon Genes (STING) have been inactivated by mutations in the Malayan pangolin whereas other mammals retained intact copies of these genes. The coding sequences of CGAS and STING1 are also disrupted by premature stop codons and frame-shift mutations in Chinese and tree pangolins, suggesting that expression of these genes was lost in a common ancestor of all pangolins that lived more than 20 million years ago. AIM2 is retained in a functional form in pangolins whereas it is inactivated by mutations in carnivorans, the phylogenetic sister group of pangolins. The deficiency of cGAS and STING points to the existence of alternative mechanisms of controlling cytoplasmic DNA-associated cell damage and viral infections in pangolins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10495-020-01614-4) contains supplementary material, which is available to authorized users.


Cancer and COVID‐19: Patients’ and Psychologists’ Reflections regarding Psycho‐oncology Service Changes


title: Therapeutic effect of post-exposure treatment with antiserum on severe fever with thrombocytopenia syndrome (SFTS) in a mouse model of SFTS virus infection

text: Abstract Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral disease that is endemic in China, Korea and Japan. No effective vaccine or specific treatment for SFTS is currently available. Here, we used a mouse model to examine the effects of ribavirin, site-1 protease inhibitor PF-429242, steroids, and combination of minocycline and ciprofloxacin (MC) on SFTS infection. The antiserum from a patient who recovered from SFTS was also examined for its effect on mice. Administration of antiserum completely protected mice against lethal infection with SFTSV. It could also protect mice from showing clinical signs of the disease due to non-lethal infection. MC-treatment resulted in prolonged survival times during lethal infection. Although other agents had no significant protective effects, they did not provide detrimental effects that could lead to progression of the disease in mice. Our results suggest that antiserum treatment may be clinically useful for post-exposure prophylaxis against SFTSV infection.


title: Emergence and Evolution of Novel Reassortant Influenza A Viruses in Canines in Southern China

text: The capacity of influenza A viruses (IAVs) to host jump from animal reservoir species to humans presents an ongoing pandemic threat. Birds and swine are considered major reservoirs of viral genetic diversity, whereas equines and canines have historically been restricted to one or two stable IAV lineages with no transmission to humans. Here, by sequencing the complete genomes of 16 IAVs obtained from canines in southern China (Guangxi Zhuang Autonomous Region [Guangxi]) in 2013 to 2015, we demonstrate that the evolution of canine influenza viruses (CIVs) in Asian dogs is increasingly complex, presenting a potential threat to humans. First, two reassortant H1N1 virus genotypes were introduced independently from swine into canines in Guangxi, including one genotype associated with a zoonotic infection. The genomes contain segments from three lineages that circulate in swine in China: North American triple reassortant H3N2, Eurasian avian-like H1N1, and pandemic H1N1. Furthermore, the swine-origin H1N1 viruses have transmitted onward in canines and reassorted with the CIV-H3N2 viruses that circulate endemically in Asian dogs, producing three novel reassortant CIV genotypes (H1N1r, H1N2r, and H3N2r [r stands for reassortant]). CIVs from this study were collected primarily from pet dogs presenting with respiratory symptoms at veterinary clinics, but dogs in Guangxi are also raised for meat, and street dogs roam freely, creating a more complex ecosystem for CIV transmission. Further surveillance is greatly needed to understand the full genetic diversity of CIV in southern China, the nature of viral emergence and persistence in the region’s diverse canine populations, and the zoonotic risk as the viruses continue to evolve.


title: Inhibition of severe acute respiratory syndrome coronavirus replication in a lethal SARS-CoV BALB/c mouse model by stinging nettle lectin, Urtica dioica agglutinin

text: Urtica dioica agglutinin (UDA) is a small plant monomeric lectin, 8.7 kDa in size, with an N-acetylglucosamine specificity that inhibits viruses from Nidovirales in vitro. In the current study, we first examined the efficacy of UDA on the replication of different SARS-CoV strains in Vero 76 cells. UDA inhibited virus replication in a dose-dependent manner and reduced virus yields of the Urbani strain by 90% at 1.1 ± 0.4 µg/ml in Vero 76 cells. Then, UDA was tested for efficacy in a lethal SARS-CoV-infected BALB/c mouse model. BALB/c mice were infected with two LD(50) (575 PFU) of virus for 4 hours before the mice were treated intraperitoneally with UDA at 20, 10, 5 or 0 mg/kg/day for 4 days. Treatment with UDA at 5 mg/kg significantly protected the mice against a lethal infection with mouse-adapted SARS-CoV (p<0.001), but did not significantly reduce virus lung titers. All virus-infected mice receiving UDA treatments were also significantly protected against weight loss (p<0.001). UDA also effectively reduced lung pathology scores. At day 6 after virus exposure, all groups of mice receiving UDA had much lower lung weights than did the placebo-treated mice. Thus, our data suggest that UDA treatment of SARS infection in mice leads to a substantial therapeutic effect that protects mice against death and weight loss. Furthermore, the mode of action of UDA in vitro was further investigated using live SARS-CoV Urbani strain virus and retroviral particles pseudotyped with SARS-CoV spike (S). UDA specifically inhibited the replication of live SARS-CoV or SARS-CoV pseudotyped virus when added just before, but not after, adsorption. These data suggested that UDA likely inhibits SARS-CoV infection by targeting early stages of the replication cycle, namely, adsorption or penetration. In addition, we demonstrated that UDA neutralizes the virus infectivity, presumably by binding to the SARS-CoV spike (S) glycoprotein. Finally, the target molecule for inhibition of virus replication was partially characterized. When UDA was exposed to N-acetylglucosamine and then UDA was added to cells just prior to adsorption, UDA did not inhibit the virus infection. These data support the conclusion that UDA might bind to N-acetylglucosamine-like residues present on the glycosylated envelope glycoproteins, thereby preventing virus attachment to cells.