title: Dynamic efficiency assessment of the Chinese hotel industry

text: Abstract The paper introduces for the first time a totally dynamic two-stage approach to analyzing the hotel industry's technical efficiency at the sub-national level. The first stage uses data envelopment window analysis (DEWA) to assess regional hotel sectors' technical efficiency over time. Unlike previous studies, the second stage uses a dynamic Tobit model to investigate the impact of macro contextual factors on the hotel sector efficiency. The study chooses the Chinese hotel industry during the period 2001–2006 as its application setting. The findings of the investigation indicate that the Chinese hotel industry is approaching an efficient operation in general, recovering from a major dip in 2003 resulting from the Severe Acute Respiratory Syndrome (SARS) outbreak. In addition, the study introduces a novel two-dimensional efficiency-based matrix to assess the competitive advantage of different regions of the Chinese hotel sector. The paper presents strategic market implications for hoteliers, government decision-makers, and destination management organizations. The proposed methods are applicable for situations in which an exogenous event of a destabilizing impact (e.g., SARS) does occur.


title: Potential drug‐drug interactions associated with drugs currently proposed for COVID‐19 treatment in patients receiving other treatments

text: Patients with COVID‐19 are sometimes already being treated for one or more other chronic conditions, especially if they are elderly. Introducing a treatment against COVID‐19, either on an outpatient basis or during hospitalization for more severe cases, raises the question of potential drug‐drug interactions. Here, we analyzed the potential or proven risk of the co‐administration of drugs used for the most common chronic diseases and those currently offered as treatment or undergoing therapeutic trials for COVID‐19. Practical recommendations are offered, where possible.


title: Principles of Diagnosis of Infectious Diseases

text: Abstract Infectious diseases are diagnosed by detection of a bacterium, virus, fungus, protozoan, or helminth in a patient with a compatible clinical illness. The methods of detection include cultivation of bacteria and fungi on growth medium, isolation of viruses in cell culture, and identification of the agent biochemically, antigenically, or genetically. Infectious diseases can also be identified by detection of a specific immune response, usually antibodies, that develop during the course of illness. Visualization of an agent in infected tissue can provide a diagnosis based on specific morphological characteristics or identify the category of organism, for example, gram-positive or gram-negative bacterium or virus (e.g., eosinophilic cytoplasmic inclusion bodies in neurons in rabies virus infection). Methods that detect and allow visualization of antigens (immunohistochemistry) or nucleic acid sequences (in situ hybridization) provide more specific diagnoses. Detection of specific nucleic acid sequences amplified by polymerase chain reaction is a powerful molecular diagnostic tool. Since the elucidation of the etiology of the first infectious disease, anthrax, more than 135 years ago, Koch's postulates have been applied and modified as novel technologies and agents have emerged. During the last 45 years, more than 70 previously unknown agents of infections have been identified in emerging infectious diseases, a phenomenon that is likely to continue.


title: Epidemiology and predictors of survival of MERS-CoV infections in Riyadh region, 2014–2015

text: Abstract Background MERS-CoV emerged as a zoonotic disease in Saudi Arabia with 1437 cases as of July 2016. This study aimed at describing the epidemiology of MERS-CoV infection, clinical aspects of the disease and the determinants of survival. Methods The medical records of Prince Mohamed Bin Abdulaziz Hospital were reviewed between April 2014 and December 2015 to identify admission and discharge with MERS-CoV. Patient’s characteristics, epidemiologic and clinical data and laboratory results were extracted and described. Logistic regression analyses were used to model the determinants of the survival of these patients. Significance of the results were judged at the 5% level. Results 249 confirmed cases were admitted mostly in August (20.48%) and September (14.86%) of the year 2015. A third (39.36%) reported contact with an index case, developed the disease after 6.2days and continued to shed the virus for 13.17days on average. The case fatality rate was 20.08%. Independent predictors of being discharged alive among confirmed cases were younger age (ORA =0.953), breathing ambient air (ORA =8.981), not being transferred to the ICU (ORA =24.240) and not receiving renal replacement therapy (ORA =8.342). These variables explain 63.9% of the variability of patients’ status at discharge. Conclusion MERS-CoV spread from human-to-human as community acquired and nosocomial infection. The study identified high risk patients in need for special medical attention in order to improve patients’ outcome.


title: The ‘precautionary principle’ as a guide for future drug development

text: During the last decade, the ‘precautionary principle’ health has gained importance. It is an approach to manage uncertain risks and to prevent any damage to the environment or human. A key element is to take action, even if some cause and effect relationships are not fully established scientifically. Although there are also critics of this principle, it is meanwhile, also increasingly implemented in medicine. An important subject is medicinal products of human or animal origin. Manifold official precaution‐guided regulations have been stated to improve their safety, particularly to avoid any infection by viruses and pathogens causing transmissible spongiform encephalopathies. In addition to numerous regulations and decisions, it is generally recommended to substitute animal and human‐derived products with adequate alternatives wherever possible. This is a great challenge for research and drug development. One option is recombinant proteins, which however, are not generally free of any risk of contamination. Therefore, the best strategy might be the development of synthetic, specifically acting drugs. The most widely used medicinal product of animal origin at present is heparin. Although there has been no indication of any viral contamination, many other reasons suggest its substitution by alternative antithrombotics. These actually promoted the research on new anticoagulants. With the approval of fondaparinux, the first synthetic, selective factor Xa, a first alternative to the porcine‐derived heparin has become available. In addition, other synthetic antithrombotics are currently in clinical development. In principle, it is thus possible that the prophylaxis and therapy of thromboembolic diseases will become completely independent of animal‐derived drugs, which would be in line with the precautionary principle.


title: Exploiting Existing Molecular Scaffolds for Long-Term COVID Treatment

text: [Image: see text] Discovery and development of COVID-19 prophylactics and treatments remains a global imperative. This perspective provides an overview of important molecular pathways involved in the viral life cycle of SARS-CoV-2, the infectious agent of COVID-19. We highlight past and recent findings in essential coronavirus proteins, including RNA polymerase machinery, proteases, and fusion proteins, that offer opportunities for the design of novel inhibitors of SARS-CoV-2 infection. By discussing the current inventory of viral inhibitors, we identify molecular scaffolds that may be improved by medicinal chemistry efforts for effective therapeutics to treat current and future coronavirus-caused diseases.


Nexus of COVID-19 and diabetes pandemics: global public health lessons


title: Factors influencing disaster nursing core competencies of emergency nurses

text: Abstract Background Emergency nurses are expected to provide required nursing services by using their professional expertise to reduce the risk posed by disasters. Thus, emergency nurses' disaster nursing core competencies are essential for coping with disasters. The purpose of the study reported here was to identify factors influencing the disaster nursing core competencies of emergency nurses. Methods A survey was conducted among 231 emergency nurses working in 12 hospitals in South Korea. Data were collected on disaster-related experience, attitude, knowledge, and disaster nursing core competencies by means of a questionnaire. Results In multiple regression analysis, disaster-related experience exerted the strongest influence on disaster nursing core competencies, followed by disaster-related knowledge. The explanatory power of these factors was 25.6%, which was statistically significant (F =12.189, p <0.001). Conclusions These findings indicate that the disaster nursing core competencies of emergency nurses could be improved through education and training programs that enhance their disaster preparedness. The nursing profession needs to participate actively in the development of disaster nursing education and training programs.


title: Natural RNA Dependent RNA Polymerase Inhibitors: Molecular Docking Studies of Some Biologically Active Alkaloids of Argemone mexicana

text: COVID-19 has become disastrous for world and spread all over. Researchers all around the globe are working to discover a drug to cure from COVID-19. RNA dependent RNA polymerase plays a key role in SARS-CoV-2 replication and thus it could be a potential target for SARS-CoV-2. This study revealed that Protopine, Allocryptopine and (±) 6- Acetonyldihydrochelerythrine could be potential RdRp inhibitors of SARS-CoV-2.


title: Infections in Confined Spaces: Cruise Ships, Military Barracks, and College Dormitories

text: The presence of a vast cohort of individuals in semi-confined settings such as cruise ships, military barracks, and college dormitories is often accompanied by an increase in the risk of particular infections. These are often gastrointestinal infections on cruise ships and respiratory pathogens that are easily transmitted in the barrack and dormitory setting. The control of these infections involves attention to good personal hygiene, safe food and water handling, and use of vaccines to prevent vaccine-preventable diseases.


title: Antiviral, Antibacterial, Antifungal, and Cytotoxic Silver(I) BioMOF Assembled from 1,3,5-Triaza-7-Phoshaadamantane and Pyromellitic Acid

text: The present study reports the synthesis, characterization, and crystal structure of a novel bioactive metal-organic framework, [Ag(4)(µ-PTA)(2)(µ(3)-PTA)(2)(µ(4)-pma)(H(2)O)(2)](n)·6nH(2)O (bioMOF 1), which was assembled from silver(I) oxide, 1,3,5-triaza-7-phosphaadamantane (PTA), and pyromellitic acid (H(4)pma). This product was isolated as a stable microcrystalline solid and characterized by standard methods, including elemental analysis, (1)H and (31)P{(1)H} NMR and FTIR spectroscopy, and single crystal X-ray diffraction. The crystal structure of 1 disclosed a very complex ribbon-pillared 3D metal-organic framework driven by three different types of bridging ligands (µ-PTA, µ(3)-PTA, and µ(4)-pma(4−)). Various bioactivity characteristics of bioMOF 1 were investigated, revealing that this compound acts as a potent antimicrobial against pathogenic strains of standard Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria, as well as a yeast (Candida albicans). Further, 1 showed significant antiviral activity against human adenovirus 36 (HAdV-36). Finally, bioMOF 1 revealed high cytotoxicity toward an abnormal epithelioid cervix carcinoma (HeLa) cell line with low toxicity toward a normal human dermal fibroblast (NHDF) cell line. This study not only broadens the family of PTA-based coordination polymers but also highlights their promising multifaceted bioactivity.


Nursing Homes and Long Term Care After COVID-19: A New ERA?


NeoCORE Conference Abstracts


title: The glycoprotein of vesicular stomatitis virus promotes release of virus-like particles from tetherin-positive cells

text: Vesicular stomatitis virus (VSV) release from infected cells is inhibited by the interferon (IFN)-inducible antiviral host cell factor tetherin (BST-2, CD317). However, several viruses encode tetherin antagonists and it is at present unknown whether residual VSV spread in tetherin-positive cells is also promoted by a virus-encoded tetherin antagonist. Here, we show that the viral glycoprotein (VSV-G) antagonizes tetherin in transfected cells, although with reduced efficiency as compared to the HIV-1 Vpu protein. Tetherin antagonism did not involve alteration of tetherin expression and was partially dependent on a GXXXG motif in the transmembrane domain of VSV-G. However, mutation of the GXXXG motif did not modulate tetherin sensitivity of infectious VSV. These results identify VSV-G as a tetherin antagonist in transfected cells but fail to provide evidence for a contribution of tetherin antagonism to viral spread.


title: Chikungunya Virus Vaccines: Viral Vector–Based Approaches

text: In 2013, a major chikungunya virus (CHIKV) epidemic reached the Americas. In the past 2 years, >1.7 million people have been infected. In light of the current epidemic, with millions of people in North and South America at risk, efforts to rapidly develop effective vaccines have increased. Here, we focus on CHIKV vaccines that use viral-vector technologies. This group of vaccine candidates shares an ability to potently induce humoral and cellular immune responses by use of highly attenuated and safe vaccine backbones. So far, well-described vectors such as modified vaccinia virus Ankara, complex adenovirus, vesicular stomatitis virus, alphavirus-based chimeras, and measles vaccine Schwarz strain (MV/Schw) have been described as potential vaccines. We summarize here the recent data on these experimental vaccines, with a focus on the preclinical and clinical activities on the MV/Schw-based candidate, which is the first CHIKV-vectored vaccine that has completed a clinical trial.


title: Visceral target organs in systemic St. Louis encephalitis virus infection of hamsters

text: Abstract Ultrastructural aspects of St. Louis encephalitis virus infection of the major extraneutral organs and tissues of suckling hamsters were examined. In the pancreas, both the exocrine and endocrine portions were equally affected by the virus. A feature apparently unique to flaviviruses was the accumulation of virus particles in all types of secretory granules in this organ. Virus particles were seen within myocardial fibers and within the smooth muscle cells and endothelial cells of small blood vessels of the heart. In the intestines, the lamina propria was the most severely infected, with virus particles accumulated in all cell types.


title: Management of Idiopathic CNS inflammatory diseases during the COVID-19 pandemic: Perspectives and strategies for continuity of care from a South East Asian Center with limited resources.

text: The Covid-19 pandemic poses a grave health management challenge globally of unprecedented nature. Management of idiopathic Central Nervous system inflammatory disorders (iCNSID) such as Multiple sclerosis, Neuromyelitis optica and its spectrum disorders and related conditions during this pandemic needs to be addressed with affirmative and sustainable strategies in order to prevent disease related risks, medication related complications and possible COVID-19 disease associated effects. Global international iCNSIDs agencies and recent publications are attempting to address this but such guidance is not available in South East Asia. Here we outline prospectively qualitatively and quantitatively novel strategies at a tertiary center in Malaysia catering for neuroimmunological disorders despite modest resources during this pandemic. In this retrospective study with longitudinal follow-up, we describe stratification of patients for face to face versus virtual visits in the absence of formal teleneurology, stratification of patients for treatment according to disease activity, rescheduling, deferring initiation or extending treatment intervals of certain disease modifying therapies(DMT's) or immunosuppressants(IS), especially those producing lymphocyte depletion in MS and the continuation of IS in patients with NMO/NMOSD. Furthermore, we highlight the use off-label treatments such as Intravenous immunoglobulins/rituximab,bridging interferons/Teriflunomide temporarily replacing more potent DMT choices,supply challenges of IS/DMT'sand tailoring blood watches and neuroimaging surveillance based on the current health needs to stave off the pandemic and prevent at risk patients with iCNSID/health care workers from possibly being exposed to the COVID-19.


title: Overview of Protein Expression by Mammalian Cells

text: This unit reviews the stages involved in protein production in mammalian cells using a stable‐expression approach. Choice of cell type is discussed, as is transfection of the host cells, methods for selection and amplification of transformants, and growth of cells at appropriate scale for protein production. Since post‐transcriptional modification and intracellular protein transportation are important features of recombinant‐protein production in mammalian cells, some description of these mechanisms is included.


title: Reduced incidence of pneumonia in influenza-vaccinated solid organ transplant recipients with influenza disease

text: Whether influenza vaccination influences the severity of illness in cases of clinical failure in solid organ transplant (SOT) recipients receiving influenza vaccine has not been extensively studied. Our goal was to evaluate the frequency of influenza vaccination among SOT recipients with influenza disease and its impact on the illness severity during the 2010–2011 season. Adult SOT recipients with confirmed influenza infection were included from December 2010 to April 2011. Follow-up data were recorded and antibody titres were determined using a microneutralization assay. Sixty-four SOT recipients were included in the study, ten (15.6%) with severe disease, requiring admission to intensive care units, of whom four (6.3%) died. In all, 34 (53.1%) received the 2010–2011 seasonal influenza vaccine and 32 (50.0%) received the 2009-H1N1 pandemic vaccine, and none had detectable antibodies against influenza at the time of diagnosis of influenza infection. Twenty-three (67.6%) of the patients that received the vaccine required hospital admission and presented less dyspnoea (10, 29.4% versus 14 (50.0%), p 0.09) and pneumonia (8, 23.8% versus 15, 50.0%, p 0.03, relative risk 0.3, 95% CI 0.1-0.9) than unvaccinated patients, with relative risk reductions of 60% and 70%, respectively. Although influenza vaccination confers protection on SOT recipients against developing influenza pneumonia, the rate of clinical failure is still high. New strategies to improve influenza immunization are needed for this group of patients.


title: Newly identified viral genomes in pangolins with fatal disease

text: Epizootic pathogens pose a major threat to many wildlife species, particularly in the context of rapidly changing environments. Pangolins (order Pholidota) are highly threatened mammals, in large part due to the trade in illegal wildlife. During July to August 2018 four sick wild pangolins (three Manis javanica and one Manis pentadactyla) exhibiting a variety of clinical symptoms were rescued by the Jinhua Wildlife Protection Station in Zhejiang province, China. Although three of these animals died, fortunately one recovered after 2 weeks of symptomatic treatment. Using meta-transcriptomics combined with reverse transcription polymerase chain reaction (RT-PCR), we identified two novel RNA viruses in two of the dead pangolins. Genomic analysis revealed that these viruses were most closely related to pestiviruses and coltiviruses, although still highly genetically distinct, with more than 48 and 25 per cent sequence divergence at the amino acid level, respectively. We named these Dongyang pangolin virus (DYPV) and Lishui pangolin virus (LSPV) based on the sampling site and hosts. Although coltiviruses (LSPV) are known to be transmitted by ticks, we found no evidence of LSPV in ticks sampled close to where the pangolins were collected. In addition, although DYPV was present in nymph ticks (Amblyomma javanense) collected from a diseased pangolin, they were not found in the local tick population. Epidemiological investigation revealed that both novel viruses might have been imported following the illegal international trade of pangolins. Hence, these data indicate that illegal wildlife trafficking not only threatens the status of pangolin populations, but may also spread epizootic pathogens.


title: Meeting report: 27th International conference on antiviral research, in Raleigh, NC, USA

text: Abstract The 27th International Conference on Antiviral Research (ICAR) was held in Raleigh, North Carolina, USA from May 12 to 16, 2014. This article summarizes the principal invited lectures. John Drach (Elion Award) described the early days of antiviral drugs and their novel modes of action. Piet Herdewijn (Holý Award) used evolutionary pressure to select DNA polymerases that accept nucleoside analogs. Replacing thymine by 5-chlorouracil led to the generation of a new form of Escherichia coli. Adrian Ray (Prusoff Award) demonstrated how prodrugs can markedly improve both the efficacy and safety of potential drugs. The keynote addresses, by David Margolis and Myron Cohen, tackled two emerging areas of HIV research, to find an HIV “cure” and to prevent HIV transmission, respectively. These topics were discussed further in other presentations – a cure seems to be a distant prospect but there are exciting developments for reducing HIV transmission. TDF-containing vaginal rings and GSK-744, as a long-lasting injection, offer great hope. There were three mini-symposia. Although therapy with TDF/FTC gives excellent control of HBV replication, there are only a few patients who achieve a functional cure. Myrcludex, an entry inhibitor, is active against both HBV and HDV. The recent progress with HBV replication in cell cultures has transformed the search for new antiviral compounds. The HBV capsid protein has been recognized as key player in HBV DNA synthesis. Unexpectedly, compounds which enhance capsid formation, markedly reduce HBV DNA synthesis. The development of BCX4430, which is active against Marburg and Ebola viruses, is of great current interest.


title: Hematopoietic cell transplantation with cryopreserved grafts for severe aplastic anemia

text: ABSTRACT The COVID-19 pandemic and the ensuing barriers to the collection and transport of donor cells, it is often necessary to collect and cryopreserve grafts before initiation of transplant conditioning. The effect on transplant outcomes in non-malignant disease is unknown. This analysis examined the effect of cryopreservation of related and unrelated donor grafts for transplantation for severe aplastic anemia in the US during 2013-2019. Included are 52 recipients of cryopreserved grafts who were matched for age, donor type, and graft type to 194 recipients who received non-cryopreserved grafts. Marginal Cox regression models were built to study the effect of cryopreservation and other risk factors associated with outcomes. We recorded higher 1-year rates of graft failure (HR 2.26, 95% CI 1.17 – 4.35, p=0.01) and of 1-year overall mortality (HR 3.13, 95% CI 1.60 – 6.11, p=0.0008) after transplantation of cryopreserved compared to non-cryopreserved grafts with adjustment for sex, performance score, comorbidity, cytomegalovirus serostatus, and ABO blood group match). Acute and chronic GVHD did not differ between groups. Adjusted probabilities of 1-year survival were 73% (95% 60 – 84) and 91% (95% CI 86 – 94) with cryopreserved and non-cryopreserved grafts, respectively. These data support the use of non-cryopreserved grafts, when possible, for severe aplastic anemia.


title: Public Health Network Structure and Collaboration Effectiveness during the 2015 MERS Outbreak in South Korea: An Institutional Collective Action Framework

text: Following the 2015 Middle East Respiratory Syndrome (MERS) outbreak in South Korea, this research aims to examine the structural effect of public health network explaining collaboration effectiveness, which is defined as joint efforts to improve quality of service provision, cost savings, and coordination. We tested the bonding and bridging effects on collaboration effectiveness during the MERS outbreak response by utilizing an institutional collective action framework. The analysis results of 114 organizations responding during the crisis show a significant association between the bonding effect and the effectiveness of collaboration, as well as a positive association between risk communication in disseminating public health information and the effectiveness of collaboration.


title: The European Virus Archive: A new resource for virology research

text: Abstract The European Virus Archive (EVA) was conceived as a direct response to the need for a coordinated and readily accessible collection of viruses that could be made available to academia, public health organisations and industry, initially within Europe, but ultimately throughout the world. Although scientists worldwide have accumulated virus collections since the early twentieth century, the quality of the collections and the viruses collected may vary according to the personal interests and agenda of the scientists. Moreover, when laboratories are re-organised or closed, collections are no longer maintained and gradually cease to exist. The tragedy of 9/11 and other disruptive activities have also meant that some previously available biological reagents are no longer openly exchanged between countries. In 2008, funding under the FP7–EU infrastructure programme enabled the initiation of the EVA. Within three years, it has developed from a consortium of nine European laboratories to encompass associated partners in Africa, Russia, China, Turkey, Germany and Italy. There is every reason to believe that EVA will continue to expand and ultimately exist as a globally networked, quality-controlled non-profit archive for the benefit of science. Organizations or individuals who would like to be considered as contributors are invited to contact the EVA coordinator, Jean–Louis Romette, at jean-louis.romette@univmed.fr.


title: Cyclophilin A: a key player for human disease

text: Cyclophilin A (CyPA) is a ubiquitously distributed protein belonging to the immunophilin family. CyPA has peptidyl prolyl cis-trans isomerase (PPIase) activity, which regulates protein folding and trafficking. Although CyPA was initially believed to function primarily as an intracellular protein, recent studies have revealed that it can be secreted by cells in response to inflammatory stimuli. Current research in animal models and humans has provided compelling evidences supporting the critical function of CyPA in several human diseases. This review discusses recently available data about CyPA in cardiovascular diseases, viral infections, neurodegeneration, cancer, rheumatoid arthritis, sepsis, asthma, periodontitis and aging. It is believed that further elucidations of the role of CyPA will provide a better understanding of the molecular mechanisms underlying these diseases and will help develop novel pharmacological therapies.


title: Tularaemia: A challenging zoonosis

text: Abstract In recent years, several emerging zoonotic vector-borne infections with potential impact on human health have been identified in Europe, including tularaemia, caused by Francisella tularensis. This remarkable pathogen, one of the most virulent microorganisms currently known, has been detected in increasingly new settings and in a wide range of wild species, including lagomorphs, rodents, carnivores, fish and invertebrate arthropods. Also, a renewed concern has arisen with regard to F. tularensis: its potential use by bioterrorists. Based on the information published concerning the latest outbreaks, the aim of this paper is to review the main features of the agent, its biology, immunology and epidemiology. Moreover, special focus will be given to zoonotic aspects of the disease, as tularaemia outbreaks in human populations have been frequently associated with disease in animals.


title: Biophysical characterisation of the nucleocapsid protein from a highly pathogenic porcine reproductive and respiratory syndrome virus strain

text: Abstract The arterivirus nucleocapsid (N) protein is a multifunctional protein that binds viral RNA for encapsidation and has potential roles in host cell processes. This study characterised the N protein from a highly virulent North American strain of porcine reproductive and respiratory syndrome virus (PRRSV). The association with viral RNA was mapped to defined motifs on the N protein. The results indicated that disulphide bridge formation played a key role in RNA binding, offering an explanation why infectious virus cannot be rescued if cysteine residues are mutated, and that multiple sites may promote RNA binding.


title: Comparative and functional genomics of closteroviruses

text: Abstract The largest extant RNA genomes are found in two diverse families of positive-strand RNA viruses, the animal Coronaviridae and the plant Closteroviridae. Comparative analysis of the viruses from the latter family reveals three levels of gene conservation. The most conserved gene module defines RNA replication and is shared with plant and animal viruses in the alphavirus-like superfamily. A module of five genes that function in particle assembly and transport is a hallmark of the family Closteroviridae and was likely present in the ancestor of all three closterovirus genera. This module includes a homologue of Hsp70 molecular chaperones and three diverged copies of the capsid protein gene. The remaining genes show dramatic variation in their numbers, functions, and origins among closteroviruses within and between the genera. Proteins encoded by these genes include suppressors of RNA silencing, RNAse III, papain-like proteases, the AlkB domain implicated in RNA repair, Zn-ribbon-containing protein, and a variety of proteins with no detectable homologues in the current databases. The evolutionary processes that have shaped the complex and fluid genomes of the large RNA viruses might be similar to those that have been involved in evolution of genomic complexity in other divisions of life.


title: Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis) with atypical encephalitis and painful testitis: a case report

text: BACKGROUND: Kikuchi-Fujimoto disease is a self-limited clinicopathologic entity that is increasingly recognized worldwide. Kikuchi-Fujimoto disease is characterized by cervical lymphadenopathy occurring in young adults. Neurologic involvement is rare, and testitis directly caused by Kikuchi-Fujimoto disease has not yet been reported. CASE PRESENTATION: A 19-year-old man was brought to our clinic with complaints of fever, headache, fatigue, and left lower quadrant pain that had persisted for 3 weeks. On physical examination, painful cervical lymphadenopathies were observed. Meningitis was suspected based on a cerebrospinal fluid examination, and left-sided orchitis was diagnosed based on findings from magnetic resonance imaging and ultrasonography. However, neither antibiotics nor antiviral drugs were effective in treating the patient’s symptoms. On the 20(th) day of hospitalization, the patient experienced a loss of consciousness, and brain T2-weighted magnetic resonance imaging showed asymmetrical, high-signal intensities in both basal nuclei and the left temporal lobe. Encephalitis was suspected, and the patient was treated with intravenous prednisolone pulse therapy (1 g/day) for 3 days and intravenous immunoglobulin therapy for 5 days. A left cervical lymph node biopsy showed apoptotic necrosis in paracortical and cortical areas with an abundance of macrophages and large lymphoid cells, which had irregular nuclei suggestive of Kikuchi-Fujimoto disease; the pathological findings from a brain biopsy were the same as those of the cervical lymph node biopsy. The encephalitis and cervical lymphadenopathies followed a benign course, as did the testitis. CONCLUSIONS: This is the first report of Kikuchi-Fujimoto disease involving painful testitis and pathologically proven asymmetrical brain regions. Kikuchi-Fujimoto disease should be included in the differential diagnosis when a patient presents with encephalitis, testitis, and fever of unknown origin.


title: Newcastle disease virus RNA-induced IL-1β expression via the NLRP3/caspase-1 inflammasome

text: Newcastle disease virus (NDV) infection causes severe inflammation and is a highly contagious disease in poultry. Virulent NDV strains (GM) induce large quantities of interleukin-1β (IL-1β), which is the central mediator of the inflammatory reaction. Excessive expression of IL-1β exacerbates inflammatory damage. Therefore, exploring the mechanisms underlying NDV-induced IL-1β expression can aid in further understanding the pathogenesis of Newcastle disease. Here, we showed that anti-IL-1β neutralizing antibody treatment decreased body temperature and mortality following infection with virulent NDV. We further explored the primary molecules involved in NDV-induced IL-1β expression from the perspective of both the host and virus. This study showed that overexpression of NLRP3 resulted in increased IL-1β expression, whereas inhibition of NLRP3 or caspase-1 caused a significant reduction in IL-1β expression, indicating that the NLRP3/caspase-1 axis is involved in NDV-induced IL-1β expression. Moreover, ultraviolet-inactivated GM (chicken/Guangdong/GM/2014) NDV failed to induce the expression of IL-1β. We then collected virus from GM-infected cell culture supernatant using ultracentrifugation, extracted the viral RNA, and stimulated the cells further with GM RNA. The results revealed that RNA alone was capable of inducing IL-1β expression. Moreover, NLRP3/caspase-1 was involved in GM RNA-induced IL-1β expression. Thus, our study elucidated the critical role of IL-1β in the pathogenesis of Newcastle disease while also demonstrating that inhibition of IL-1β via anti-IL-1β neutralizing antibodies decreased the damage associated with NDV infection; furthermore, GM RNA induced IL-1β expression via NLRP3/caspase-1.


title: The role of rhinovirus infections in young children with cystic fibrosis

text: Rhinovirus (RV) is an important virus in children with chronic respiratory conditions such as asthma; however, little is known about its role in CF. Our aim was to examine the prevalence and clinical impact of different RV species in young children with CF. We collected clinical data and nasal swabs on patients at home and in the hospital setting. Parents filled out symptom diaries and collected nasal swabs when their children were symptomatic and asymptomatic. A novel RV typing PCR assay was used to determine the RV species present. We collected 55 nasal swab samples from ten preschool CF patients over a six month period. The quality of parent collected samples at home was sufficient for PCR analysis. RV was the most common virus detected in young children with CF. There was no difference in the frequency of RV species between symptomatic and asymptomatic subjects. However, parental home-sampling is an acceptable and feasible approach to monitoring young children with CF.


title: Porcine deltacoronavirus nucleocapsid protein antagonizes IFN-β production by impairing dsRNA and PACT binding to RIG-I

text: Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus that causes watery diarrhea, vomiting and mortality in newborn piglets. Previous studies have suggested that PDCoV infection antagonizes RIG-I-like receptor (RLR)-mediated IFN-β production to evade host innate immune defense, and PDCoV-encoded nonstructural protein nsp5 and accessory protein NS6 are associated with this process. However, whether the structural protein(s) of PDCoV also antagonize IFN-β production remains unclear. In this study, we found that PDCoV nucleocapsid (N) protein, the most abundant viral structural protein, suppressed Sendai virus (SEV)-induced IFN-β production and transcription factor IRF3 activation, but did not block IFN-β production induced by overexpressing RIG-I/MDA5. Furthermore, study revealed that PDCoV N protein interacted with RIG-I and MDA5 in an in vitro overexpression system and evident interactions between N protein and RIG-I could be detected in the context of PDCoV infection, which interfered with the binding of dsRNA and protein activator of protein kinase R (PACT) to RIG-I. Together, our results demonstrate that PDCoV N protein is an IFN antagonist and utilizes diverse strategies to attenuate RIG-I recognition and activation.


title: Emerging vector-borne diseases in dromedaries in Tunisia: West Nile, bluetongue, epizootic haemorrhagic disease and Rift Valley fever

text: A total of 118 sera were collected during 2016 from two groups of dromedaries from Kebili and Medenine governorates in the south of Tunisia. The aim of this study was to provide the first serological investigation of four emerging vector-borne diseases in two groups of dromedaries in Tunisia. Sera were tested by ELISA and serum neutralisation test to identify West Nile virus (WNV), bluetongue virus (BTV), epizootic haemorrhagic disease virus (EHDV) and Rift Valley fever virus (RVFV). In the first group, the seroprevalence for BTV was 4.6%, while in the second group, it was 25.8% for WNV and 9.7% for BTV. Only serotype 1 was detected for BTV in the two groups. No evidence for circulation of RVF and EHD viruses was revealed. Results indicated that dromedaries can be infected with BTV and WNV, suggesting that this species might play a significant role in the epizootiology of these viral diseases in Tunisia and neighbouring countries.


title: Variation in the Glycoprotein and VP35 Genes of Marburg Virus Strains

text: Abstract Marburg virus, the prototype of the familyFiloviridae,differs genetically, serologically, and morphologically from Ebola viruses. To better define the genetic variation within the species, VP35 and glycoprotein (GP) genes of representative human isolates from four known episodes of Marburg virus hemorrhagic fever were analyzed. The percentage nucleotide differences in the GP gene coding regions of Marburg viruses (0.1–21%) was nearly equal to the percentage amino acid changes (0–23%), while the percentage nucleotide differences in VP35 coding regions (0.3–20.9%) were higher than the percentage amino acid changes (0.9–6.1%), indicating a greater number of nonsynonymous changes occurring in the GP gene. The higher variation in the GP gene and the corresponding protein, especially those changes in the variable middle region of the GP, suggests that the variability may be the result of responses to natural host pressures. Analysis of the GP gene open reading frame shows a nonrandom distribution of nonsynonymous mutations that may indicate positive Darwinian selection is operating within the variable region. A heptad repeat region and an adjoining predicted fusion peptide are found in the C-terminal third of Marburg virus GPs, as has been previously shown for Ebola virus, and are similar to those found in transmembrane glycoproteins of retroviruses, paramyxoviruses, coronaviruses, and influenza viruses. Comparative analyses showed that there are two lineages within the Marburg virus species of filoviruses. The most recent isolate from Kenya (1987) represents a separate genetic lineage within the Marburg virus species (21–23% amino acid difference). However, this lineage likely does not represent a separate Marburg subtype, as the extent of divergence is less than that separating Ebola virus subtypes.


title: Of mice and men: COVID‐19 challenges translational neuroscience

text: "Mouse Is Not Man and Blood Is Not Brain" is a frequent response when neurologists are confronted with findings from translational medicine.


title: Coronavirus IBV-induced membrane fusion occurs at near-neutral pH

text: The lysosomotropic agent NH(4)Cl caused a reduction of 80–95% in the number of chick kidney (CK) cells and Vero cells infected by infectious bronchitis virus (IBV) strain Beaudette, as determined by immunofluorescence at the end of the first replication cycle. Inhibition only occurred when NH(4)Cl was present during the first 2 h after infection. Syncytium formation was studied during replication of IBV-Beaudette in Vero cells. Some cell-cell fusion occurred at pH 7.0 and pH 6.5 but it was optimal at pH 6.7. IBV strain UK/123/82 did not replicate in Vero cells and was studied in CK cells in which it grew well but without forming syncytia. In contrast to IBV-Beaudette, NH(4)Cl had virtually no effect on the replication of UK/123/82. The results show that the IBV spike glycoprotein induces membrane fusion at near neutral pH although some IBV strains may require a mildly acidic environment for the efficient uncoating of the virion RNA.


Telehealth in Response to the COVID‐19 Pandemic in Rural Veteran and Military Beneficiaries


title: The prevalence of viral infections in children with cystic fibrosis in a tertiary care center in Saudi Arabia

text: Abstract Introduction Studies have shown that pulmonary exacerbations in cystic fibrosis (CF) patients are associated with respiratory viruses. The most common agent causing viral infections in patients with CF before the age of 3 years is respiratory syncytial virus. Objectives To obtain the prevalence of the different types of viral infection in CF patients and to identify its relation with the type of bacterial infection, (CFTR) mutations and pulmonary function test (PFT). Methodology A retrospective charts review of 387 patients with CF of all age groups who were screened for the detection of viruses during respiratory exacerbation from the period of January 1, 1984 to June 1, 2016. Results A total of 159 CF patients had pulmonary exacerbation and had viral PCR obtained. Fifty-eight patients (36%) had positive viral PCR. Males were more commonly infected in 30/58 patients (52%) compared to females in 28 patients (48%). Forty-five of 58 patients (78%) were alive and 13 patients (22%) died. Rhinovirus was the most frequently reported viral PCR in 33/74 sample (45%). Out of 74 viral PCR, 41 (55.4%) were during the colder seasons (October–February) and 33 (44.5%) during the warmer seasons (March–September). During viral infection and viral recurrence, there was an increase in bacterial colonization specifically of H. influenza and staphylococcus aureus. The most common CFTR mutation for the CF viral infection is: 3120+1G>A in Intron 16 in 11/57 patients (19%). The Eastern Province had the highest viral infection of 24 out of 57 patients (42%). Follow-up PFT post viral infection showed no significant difference in the type and the severity of PFT compared to the initial PFT during the viral illness. Conclusion Viral infections contributed to the increase in morbidity and mortality of CF patients in our population, and rhinovirus was the most common causative agent. Viral infections and viral recurrence increased the prevalence of bacterial infection of specific pathogens such as H. influenza and S. aureus. Physicians should be aware to prevent progressive lung damage in CF patients by treating the concomitant viral and bacterial infections. Viral infection may be associated with some common CFTR mutations.


title: Receptor-Activated Binding of Viral Fusion Proteins to Target Membranes

text: Publisher Summary This chapter describes three assays to monitor receptor-induced association of the envelope glycoprotein (EnvA) of avian sarcoma/leukosis virus (ASLV) with target bilayers: (1) the original assay for monitoring binding of the EnvA ectodomain (EnvA-PI) to target membranes (liposomes), (2) a modified and miniaturized EnvA-PI-liposome binding assay, and (3) an assay to measure binding of intact sarcoma/leukosis virus subtype A (ASLV-A) virus particles to target membranes. These assays are also useful for studying other receptor-activated viral fusion proteins. When one viral glycoprotein and one “simple” host cell receptor are involved, it should be possible to develop assays directly analogous to those described above for studying Tva-induced binding of the EnvA ectodomain (EnvA-PI) to target membranes. A general prerequisite for a fusion protein/target membrane binding assay is a soluble and correctly oligomeric form of the viral fusion protein ectodomain. The simplest host cell receptors that would be amenable to this type of analysis are type I or type II integral membrane proteins. The soluble versions of the ectodomains of these receptors, produced by genetic engineering or proteolytic release, could then be used to trigger the cognate fusion protein. The methodology could, similarly, be applicable to multimembrane-spanning host cell receptors when the functional part of the receptor is tethered at only one end or where an ectodomain loop preserves enough structure to function as a soluble analog, perhaps by generating a cyclic peptide analog of the loop. The same “receptor reagents” could be employed for intact virus particle/target membrane binding assays.


title: Evaluation of botanical powders and extracts from Nigerian plants as protectants of maize grains against maize weevil, Sitophilus zeamais (Motschulsky) [oleoptera: Curculionidae]

text: Toxicities of leaf powders and extracts of Acanthus montanus, Acanthospermum hispidum, Alchornea laxiflora and Argyreia nervosa against maize weevil (Sitophilus zeamais) were evaluated. Powders were tested at dose 3.0g/20g while extracts were tested at concentration 3%/20g of maize grains. Mortality, oviposition, and adult emergence rates as well as weight loss, seeds damage and weevil perforation index (WPI) were evaluated. Phytochemical constituents of the experimental plants were also carried out. The results showed that Acanthus montanus powder was the most potent with 65% adult mortality after 24 h of treatment. This is followed by Argyreia nervosa powder that evoked 52.5% weevil mortality. The least toxic to S. zeamais was Acanthospermum hispidum powder with 32.5% adult mortality. Extracts were more toxic than the powders of the tested plants. Acanthus montanus extract was the most toxic since it promoted 80% adult mortality after 24 h of treatment. Acanthus montanus, Alchornea laxiflora and Argyreia nervosa leaf powders and extracts completely prevented oviposition by adult insect, adult emergence, weight loss and seeds damaged. The phytochemicals present in Acanthus montanus were alkaloids (3.67 mg/g), saponin (3.33 mg/g), tannin (3.00 mg/g) and flavonoid (2.67 mg/g) contents. Acanthospermum hispidum had the least alkaloid (2.67 mg/g), saponin (1.67 mg/g), tannin (1.33 mg/g) and flavonoid (1.00 mg/g) contents. Acanthus montanus, Argyreia nervosa, Alchornea laxiflora and Acanthospermum hispidum were efficacious against S. zeamais instead of synthetic chemical insecticides that have environmental health hazards and they can be used in integrated pest management by farmers and foods merchants.


title: One-Tube Nested RT-PCR Enabled by Using a Plastic Film and its Application for the Rapid Detection of SARS-Virus

text: A general strategy based on the use of a plastic film that allows reverse transcription and nested-PCR in a single closed-tube has been developed. The reaction mixture for the second PCR amplification is quarantined in the cap of the reaction tube during the first round amplification by a piece of plastic film, and later introduced into the PCR amplicons from the first round reaction by centrifugation without opening the reaction tube. The main advantages of our method are its high sensitivity, specificity, simplicity, cost effectiveness, low risk of contamination and the ease in establishment of conditions for nested-PCR. The method has been successfully applied to the detection of the genomic RNA from SARS-CoV, the detection limit of this method is comparable to that of the conventional two-tube nested PCR system. This method could be easily adapted to the detection of other targets.


title: Prevalence and clinical characteristics of human respiratory syncytial virus in Chinese adults with acute respiratory tract infection

text: Respiratory syncytial virus (RSV) is a leading cause of respiratory tract illnesses worldwide. Although the prevalence and clinical manifestations of the two subtypes, RSV‐A and RSV‐B, have been studied in some detail in infants and young children, they have not been determined in adults. To evaluate the prevalence of the RSV subtypes and disease severity between RSV‐A and RSV‐B infections in adults, nasal and throat swabs that were collected from patients ≥15 years old who sought medical care for acute respiratory infections at the Fever Clinic of the Peking Union Medical College Hospital in Beijing, China between May 2005 and April 2010. The samples were tested for RSV infection using PCR and sequencing analysis. RSV was detected in 95 (1%) of the adult patients, of whom 53 (55.8%) were positive for RSV‐A and 42 (44.2%) for RSV‐B. The incidence of RSV infections increased with age (χ(2) = 37.17, P = 1.66E−07). Demographic data and clinical manifestations of RSV‐A were similar to those of RSV‐B. Although RSV‐A and RSV‐B co‐circulated during the 2005–2006 and 2008–2009 seasons, RSV‐A was predominant in the 2006–2008 seasons, whereas RSV‐B was predominant in the 2009–2010 season. Upper respiratory tract infections were diagnosed in most RSV‐infected patients (n = 80, 84.2%), and three patients suffered from pulmonary infection. This is the first study to provide data on the prevalence and clinical manifestations of RSV subgroups among Chinese adults with fever and acute illness, over five successive epidemic seasons. J. Med. Virol. 85:348–353, 2013. © 2012 Wiley Periodicals, Inc.


title: Discovery of Keap1−Nrf2 small−molecule inhibitors from phytochemicals based on molecular docking

text: Abstract Various phytochemicals have been reported to protect against oxidative stress. However, the mechanism underlying has not been systematically evaluated, which limited their application in disease treatment. Nuclear factor erythroid 2−related factor 2 (Nrf2), a central transcription factor in oxidative stress response related to numerous diseases, is activated after dissociating from the cytoskeleton−anchored Kelch−like ECH−associated protein 1 (Keap1). The Keap1–Nrf2 protein–protein interaction has become an important drug target. This study was designed to clarify whether antioxidantive phytochemicals inhibit the Keap1–Nrf2 protein–protein interaction and activate the Nrf2-ARE signaling pathway efficiently. Molecular docking and 3D−QSAR were applied to evaluate the interaction effects between 178 antioxidant phytochemicals and the Nrf2 binding site in Keap1. The Nrf2 activation effect was tested on a H2O2−induced oxidative−injured cell model. Results showed that the 178 phytochemicals could be divided into high−, medium−, and low−total−score groups depending on their binding affinity with Keap1, and the high−total−score group consisted of 24 compounds with abundant oxygen or glycosides. Meanwhile, these compounds could bind with key amino acids in the structure of the Keap1−Nrf2 interface. Compounds from high−total−score group show effective activation effects on Nrf2. In conclusion, phytochemicals showed high binding affinity with Keap1 are promising new Nrf2 activators.


Questions concerning the New Haven Coronavirus


title: Development of a real-time RT-PCR for the detection of Swine-lineage Influenza A (H1N1) virus infections

text: Abstract Background A novel influenza A virus, subtype H1N1 of swine-lineage (H1N1 swl) has transmitted rapidly to many regions of the world with evidence of sustained transmission within some countries. Rapid detection and differentiation from seasonal influenza is essential to instigate appropriate patient and public health management and for disease surveillance. Objectives To develop a rapid and sensitive real-time reverse transcriptase polymerase chain reaction (rtRT-PCR) for confirmation of H1N1 swl. Study design A one-step rtRT-PCR approach was employed to target the matrix gene of the novel influenza A/H1N1 swl and validated against a panel of seasonal influenza A (H1N1 and H3N2), swine influenza A/H1N1 and avian influenza A/H5N1 viruses. The assay following validation was then used prospectively to detect H1N1 swl positive specimens from the recent outbreaks in the UK and the Republic of Ireland. Results The one-step H1N1 swl matrix rtRT-PCR successfully detected H1N1 swl clinical specimens and did not cross-react with seasonal influenza A, subtypes H1N1 and H3N2 viruses and swine influenza A (H1N1). The H1N1 swl matrix assay did cross react with H5N1. The H1N1 swl matrix assay was then compared to two other assays using a dilution series and a panel of untyped influenza A positive clinical samples. These experiments found the assay to have a comparable sensitivity to the established universal influenza A rtRT-PCR and was more sensitive than the H1N1 swl specific assay that targeted the H1 region. Conclusions The results demonstrate that the rtRT-PCR is sensitive and should be used alongside existing universal influenza A assays to rapidly detect the novel H1N1 swl virus.


title: Resident Response During Pandemic: This Is Our Time

text: This commentary discusses the value of residents during the coronavirus disease 2019 pandemic. The author also evaluates the role of program leadership and administration during this health crisis.


title: The Past, Present, and Future of Simulation-based Education for Pediatric Emergency Medicine

text: Abstract The pediatric emergency medicine (PEM) environment is well suited for simulation-based activities, be they educational interventions for PEM learners, evaluations of the interface between health providers and the environment that they work in, or research investigations using simulation as a tool to answer specific clinical questions. As such, PEM has been among the leaders in the integration of this modality for clinical training. Traditionally, simulation has been used extensively for the dissemination of clinical training in the areas of clinical knowledge and its application, and the clinical, technical, and teamwork skills involved in PEM care. Increasingly, simulation is being used in novel applications, including breaking bad news, disclosure of error, family-centered care, quality and patient safety education, and system-level integration. The future will look to further identify, measure, and inform the integration of simulation with new and innovative adjuncts in the clinical environment, as well as to determine the optimal timing and use of simulation-based education to enhance the quality of care delivered to patients by the interprofessional and multidisciplinary team.


title: Endocrine surgery during and after the Covid-19 epidemic: Expert guidelines in France

text: Abstract The Covid-19 pandemic commands a major reorganization of the entire French healthcare system. In France, general rules have been issued nationally and implemented by each healthcare center, both public and private, throughout France. Guidelines drafted by an expert group led by the French-speaking Association of Endocrine Surgery (AFCE) propose specific surgical management principles for thyroid, parathyroid, endocrine pancreas and adrenal surgery during and after the Covid-19 epidemic.


title: What we know about 2019-nCoV in Iran in the early stage?

text: On 10 January 2020, a new coronavirus causing a pneumonia outbreak spread rapidly in all of the World. On 19 February 2020, the first official announcement of death from 2019-Nov was made in Iran. As of 7 March 2020, there were 101,927 confirmed cases of Covid-19 infection, including 3486 deaths, reported in the World. In the eastern and Mediterranean region Iran with 4747 confirmed cases of Covid-19 infection and 124 deaths, is in the critical stage. Therefore, there is a matter of urgency combating this new virus and stopping the epidemic. Here, we focus on symptoms and the development of fast diagnosis methods, as well as potential management to prevent or treat the Covid-19 infection.


title: Yeast expression and characterization of SARS-CoV N protein

text: Abstract The severe acute respiratory syndrome human coronavirus (SARS-CoV) nucleocapsid protein (N protein) is its most antigenic structural protein. The N protein gene has been cloned into a yeast expression vector pPIC9, transformed into Pichia pastoris strain GS115 and induced for expression by methanol. SDS-PAGE and Western blot showed that the N protein was expressed at a level of 3mg/ml of culture medium. Characterization by mass spectrometry, circular dichroism and fluorescence luminescence assays showed that the expressed N protein displayed a β-sheet secondary structure in solution and it is stable in the pH range between 5.0 and 8.0. The P. pastoris-expressed N protein is believed to more closely resemble native SARS N protein than the bacterially expressed N protein.


title: Spike protein homology between the SARS-associated virus and murine hepatitis virus implies existence of a putative receptor-binding region

text: Coronavirus has been determined to be the cause of the recent outbreak of severe acute respiratory syndrome (SARS). Human coronavirus 229E had been studied well and its receptor-binding domain was restricted to aa417–547 of S protein. However, this region has no homology with the newly separated SARS-associated virus (Hong Kong isolate CUHK-W1). Then we analyzed the phylogenesis of S1 subunit of the coronavirus spike protein (SARS-associated virus, Hong Kong isolate CUHK-W1). Interestingly, the highest homology between murine hepatitis virus (MHV) and SARS-associated coronavirus was found. And the important sites (aa62–65 and aa214–216) on the spike protein of MHV with receptor-binding capacity were highly conservative in comparison with the newly separated SARS-associated virus (the corresponding sites are aa51–54 and aal95–197). These results from bioinformatics analysis might help us to study the receptor-binding sites of SARS-associated virus and the mechanism of the virus entry into the target cell, and design antiviral drugs and potent vaccines.


title: Cell-Based Strategies to Reconstitute Lung Function in Infants with Severe Bronchopulmonary Dysplasia

text: Recent advances in our understanding of stem/progenitor cells and their potential to repair damaged organs offer the possibility of cell-based treatments for neonatal lung injury. This review summarizes basic concepts of stem/progenitor cell biology and discusses the recent advances and challenges of cell-based therapies for lung diseases, with a particular focus on bronchopulmonary dysplasia (BPD), a form of chronic lung disease that primarily affects very preterm infants. Despite advances in perinatal care, BPD still remains the most common complication of extreme prematurity, and there is no specific treatment.


title: Vascular Epiphytic Medicinal Plants as Sources of Therapeutic Agents: Their Ethnopharmacological Uses, Chemical Composition, and Biological Activities

text: This is an extensive review on epiphytic plants that have been used traditionally as medicines. It provides information on 185 epiphytes and their traditional medicinal uses, regions where Indigenous people use the plants, parts of the plants used as medicines and their preparation, and their reported phytochemical properties and pharmacological properties aligned with their traditional uses. These epiphytic medicinal plants are able to produce a range of secondary metabolites, including alkaloids, and a total of 842 phytochemicals have been identified to date. As many as 71 epiphytic medicinal plants were studied for their biological activities, showing promising pharmacological activities, including as anti-inflammatory, antimicrobial, and anticancer agents. There are several species that were not investigated for their activities and are worthy of exploration. These epipythes have the potential to furnish drug lead compounds, especially for treating cancers, and thus warrant indepth investigations.


title: Phylogenetic history demonstrates two different lineages of dengue type 1 virus in Colombia

text: BACKGROUND: Dengue Fever is one of the most important viral re-emergent diseases affecting about 50 million people around the world especially in tropical and sub-tropical countries. In Colombia, the virus was first detected in the earliest 70's when the disease became a major public health concern. Since then, all four serotypes of the virus have been reported. Although most of the huge outbreaks reported in this country have involved dengue virus serotype 1 (DENV-1), there are not studies about its origin, genetic diversity and distribution. RESULTS: We used 224 bp corresponding to the carboxyl terminus of envelope (E) gene from 74 Colombian isolates in order to reconstruct phylogenetic relationships and to estimate time divergences. Analyzed DENV-1 Colombian isolates belonged to the formerly defined genotype V. Only one virus isolate was clasified in the genotype I, likely representing a sole introduction that did not spread. The oldest strains were closely related to those detected for the first time in America in 1977 from the Caribbean and were detected for two years until their disappearance about six years later. Around 1987, a split up generated 2 lineages that have been evolving separately, although not major aminoacid changes in the analyzed region were found. CONCLUSION: DENV-1 has been circulating since 1978 in Colombia. Yet, the phylogenetic relationships between strains isolated along the covered period of time suggests that viral strains detected in some years, although belonging to the same genotype V, have different recent origins corresponding to multiple re-introduction events of viral strains that were circulating in neighbor countries. Viral strains used in the present study did not form a monophyletic group, which is evidence of a polyphyletic origin. We report the rapid spread patterns and high evolution rate of the different DENV-1 lineages.


title: Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020

text: On 5 February 2020, in Yokohama, Japan, a cruise ship hosting 3,711 people underwent a 2-week quarantine after a former passenger was found with COVID-19 post-disembarking. As at 20 February, 634 persons on board tested positive for the causative virus. We conducted statistical modelling to derive the delay-adjusted asymptomatic proportion of infections, along with the infections’ timeline. The estimated asymptomatic proportion was 17.9% (95% credible interval (CrI): 15.5–20.2%). Most infections occurred before the quarantine start.


title: Viruses exacerbating chronic pulmonary disease: the role of immune modulation

text: Chronic pulmonary diseases are a major cause of morbidity and mortality and their impact is expected to increase in the future. Respiratory viruses are the most common cause of acute respiratory infections and it is increasingly recognized that respiratory viruses are a major cause of acute exacerbations of chronic pulmonary diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis. There is now increasing evidence that the host response to virus infection is dysregulated in these diseases and a better understanding of the mechanisms of abnormal immune responses has the potential to lead to the development of new therapies for virus-induced exacerbations. The aim of this article is to review the current knowledge regarding the role of viruses and immune modulation in chronic pulmonary diseases and discuss avenues for future research and therapeutic implications.


title: Complement inhibition in biomaterial- and biosurface-induced thromboinflammation

text: Abstract Therapeutic medicine today includes a vast number of procedures involving the use of biomaterials, transplantation of therapeutic cells or cell clusters, as well as of solid organs. These treatment modalities are obviously of great benefit to the patient, but also present a great challenge to the innate immune system, since they involve direct exposure of non-biological materials, cells of non-hematological origin as well as endothelial cells, damaged by ischemia-perfusion in solid organs to proteins and cells in the blood. The result of such an exposure may be an inappropriate activation of the complement and contact/kallikrein systems, which produce mediators capable of triggering the platelets and PMNs and monocytes, which can ultimately result in thrombotic and inflammatory (i.e., a thrombo-inflammatory) response to the treatment modality. In this concept review, we give an overview of the mechanisms of recognition within the innate immunity system, with the aim to identify suitable points for intervention. Finally, we discuss emerging and promising techniques for surface modification of biomaterials and cells with specific inhibitors in order to diminish thromboinflammation and improve clinical outcome.


Better the drug you know: Commentary on “Daughton 2020, Natural experiment concept to accelerate the re-purposing of existing therapeutics for Covid-19”


Commentary on two reports on animal models of COVID‐19


title: A Plasmid-Based Reverse Genetics System for Animal Double-Stranded RNA Viruses

text: Mammalian orthoreoviruses (reoviruses) are highly tractable experimental models for studies of double-stranded (ds) RNA virus replication and pathogenesis. Reoviruses infect respiratory and intestinal epithelium and disseminate systemically in newborn animals. Until now, a strategy to rescue infectious virus from cloned cDNA has not been available for any member of the Reoviridae family of dsRNA viruses. We report the generation of viable reovirus following plasmid transfection of murine L929 (L) cells using a strategy free of helper virus and independent of selection. We used the reovirus reverse genetics system to introduce mutations into viral capsid proteins σ1 and σ3 and to rescue a virus that expresses a green fluorescent protein (GFP) transgene, thus demonstrating the tractability of this technology. The plasmid-based reverse genetics approach described here can be exploited for studies of reovirus replication and pathogenesis and used to develop reovirus as a vaccine vector.


title: Clinical characteristics and outcomes of influenza and other influenza-like illnesses in Mexico City

text: BACKGROUND: Influenza-like illnesses (ILI) are estimated to cause millions of deaths annually. Despite this disease burden, the etiologic causes of ILI are poorly described for many geographical regions. METHODS: Beginning in April 2010, we conducted an observational cohort study at five hospitals in Mexico City, enrolling subjects who met the criteria for ILI. Evaluations were conducted at enrollment and on day 28, with the collection of clinical data and a nasopharyngeal swab (or nasal aspirate in children). Swabs were tested by multiplex PCR for 15 viral pathogens and real-time PCR for influenza. RESULTS: During the first year, 1065 subjects were enrolled in this study, 55% of whom were hospitalized; 24% of all subjects were children. One or more pathogens were detected by PCR in 64% of subjects, most commonly rhinovirus (25% of all isolates) and influenza (24% of isolates). Six percent of subjects died, and of those, 54% had no pathogen identified. Rhinovirus was the most common pathogen among those who died, although it did not have the highest case fatality rate. CONCLUSIONS: Multiple respiratory viruses beyond influenza are associated with significant morbidity and mortality among adults and children in Mexico City. Detection of these agents could be useful for the adjustment of antibiotic treatment in severe cases.


Synthesis of Liver Associations Recommendations for Hepatology and Liver Transplant Care During the COVID‐19 Pandemic


title: Bridging protein local structures and protein functions

text: One of the major goals of molecular and evolutionary biology is to understand the functions of proteins by extracting functional information from protein sequences, structures and interactions. In this review, we summarize the repertoire of methods currently being applied and report recent progress in the field of in silico annotation of protein function based on the accumulation of vast amounts of sequence and structure data. In particular, we emphasize the newly developed structure-based methods, which are able to identify locally structural motifs and reveal their relationship with protein functions. These methods include computational tools to identify the structural motifs and reveal the strong relationship between these pre-computed local structures and protein functions. We also discuss remaining problems and possible directions for this exciting and challenging area.


title: Comparison of culturable antibiotic-resistant bacteria in polluted and non-polluted air in Beijing, China

text: Abstract Background Air pollution has been a serious health issue in Beijing for years. Airborne antibiotic-resistant bacteria could be a potential health crisis as reserve of antibiotic resistance transmission in environment. The composition and antibiotic resistance pattern of culturable bacterial community and how these are affected by air pollution remain unclear. Objectives This study aimed to compare the compositions and antibiotic resistance patterns of culturable bacteria in polluted and non-polluted weather conditions in Beijing. Methods Air samples were collected indoors and outdoors during polluted and non-polluted weather using six-stage Andersen Samplers. For each isolated bacterium, the 16S ribosomal RNA gene was amplified, sequenced, and blasted against the National Center for Biotechnology Information database Antibiotic resistance was conducted by antimicrobial susceptibility testing. Results Bacterial concentration in polluted weather was significantly higher than in non-polluted weather, both indoors and outdoors (P < 0.05). Gram-positive bacteria (GPB) were dominant in both weathers but gram-negative bacteria (GNB) were more abundant in polluted weather than non-polluted weather both indoors and outdoors. Multidrug-resistant (MDR) bacteria occupied 23.7% of all bacterial isolates, 22.4% of isolates from polluted weather and 27.8% of isolates from non-polluted weather. Penicillins were resisted by 72.4% and 83.3% of isolates from polluted and non-polluted weather, respectively. Conclusions The bacterial concentration was significantly higher in polluted weather, compared to non-polluted weather. Polluted weather is correlated with changes in the bacterial composition in the air, with a greater abundance of GNB. Penicillins was resisted by over 70% of bacterial isolates. The abundance of MDR bacteria suggested potential risks for human health.


title: Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission

text: BACKGROUND: Human infection with a novel coronavirus named Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia and the Middle East in September, 2012, with 44 laboratory-confirmed cases as of May 23, 2013. We report detailed clinical and virological data for two related cases of MERS-CoV disease, after nosocomial transmission of the virus from one patient to another in a French hospital. METHODS: Patient 1 visited Dubai in April, 2013; patient 2 lives in France and did not travel abroad. Both patients had underlying immunosuppressive disorders. We tested specimens from the upper (nasopharyngeal swabs) or the lower (bronchoalveolar lavage, sputum) respiratory tract and whole blood, plasma, and serum specimens for MERS-CoV by real-time RT-PCR targeting the upE and Orf1A genes of MERS-CoV. FINDINGS: Initial clinical presentation included fever, chills, and myalgia in both patients, and for patient 1, diarrhoea. Respiratory symptoms rapidly became predominant with acute respiratory failure leading to mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Both patients developed acute renal failure. MERS-CoV was detected in lower respiratory tract specimens with high viral load (eg, cycle threshold [Ct] values of 22·9 for upE and 24 for Orf1a for a bronchoalveolar lavage sample from patient 1; Ct values of 22·5 for upE and 23·9 for Orf1a for an induced sputum sample from patient 2), whereas nasopharyngeal specimens were weakly positive or inconclusive. The two patients shared the same room for 3 days. The incubation period was estimated at 9–12 days for the second case. No secondary transmission was documented in hospital staff despite the absence of specific protective measures before the diagnosis of MERS-CoV was suspected. Patient 1 died on May 28, due to refractory multiple organ failure. INTERPRETATION: Patients with respiratory symptoms returning from the Middle East or exposed to a confirmed case should be isolated and investigated for MERS-CoV with lower respiratory tract sample analysis and an assumed incubation period of 12 days. Immunosuppression should also be taken into account as a risk factor. FUNDING: French Institute for Public Health Surveillance, ANR grant Labex Integrative Biology of Emerging Infectious Diseases, and the European Community's Seventh Framework Programme projects EMPERIE and PREDEMICS.


title: The transmission and diagnosis of 2019 novel coronavirus infection disease (COVID‐19): A Chinese perspective

text: 2019 novel coronavirus (SARS‐CoV‐2), which originated in Wuhan, China, has attracted the world's attention over the last month. The Chinese government has taken emergency measures to control the outbreak and has undertaken initial steps in the diagnosis and treatment of 2019 novel coronavirus infection disease (COVID‐19). However, SARS‐CoV‐2 possesses powerful pathogenicity as well as transmissibility and still holds many mysteries that are yet to be solved, such as whether the virus can be transmitted by asymptomatic patients or by mothers to their infants. Our research presents selected available cases of COVID‐19 in China to better understand the transmission and diagnosis regarding this infectious disease.


title: Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (n=4532)

text: Background Cell entry of SARS-CoV-2 depends on binding of the viral spike (S) proteins to ACE2 and on S protein priming by TMPRSS2. Inhibition of TMPRSS2 may work to block or decrease the severity of SARS-CoV-2 infections. Intriguingly, TMPRSS2 is an androgen-regulated gene that is upregulated in prostate cancer where it supports tumor progression and is involved in a frequent genetic translocation with the ERG gene. First- or second-generation androgen-deprivation therapies (ADTs) decrease the levels of TMPRSS2. Here we put forward the hypothesis that ADTs may protect patients affected by prostate cancer from SARS-CoV-2 infections. Materials and methods We extracted data regarding 9280 patients (4532 males) with laboratory-confirmed SARS-CoV-2 infection from 68 hospitals in Veneto, one of the Italian regions that was most affected by the COVID-19 pandemic. The parameters used for each COVID-19 positive patient were gender, hospitalization, admission to intensive care unit (ICU), death, tumor diagnosis, prostate cancer diagnosis, and androgen-deprivation therapy (ADT). Results There were 9280 SARS-CoV-2 positive patients in the Veneto on April 1, 2020. Overall, males developed more severe complications, were more frequently hospitalized, and had a worse clinical outcome than females. Considering only the Veneto male population (2.4 Million men), 0.2% and 0.3% of non-cancer and cancer patients, respectively, tested positive for SARS-CoV-2. Comparing the total number of SARS-CoV-2 positive cases, prostate cancer patients receiving ADT had a significantly lower risk of SARS-CoV-2 infection compared to patients who did not receive ADT (OR 4.05; 95% CI 1.55-10.59). A greater difference was found comparing prostate cancer patients receiving ADT to patients with any other type of cancer (OR 5.17; 95% CI 2.02-13.40). Conclusion Our data suggest that cancer patients have an increased risk of SARS-CoV-2 infections than non-cancer patients. However, prostate cancer patients receiving ADT appear to be partially protected from SARS-CoV-2 infections.


title: Certainties and Uncertainties Facing Emerging Respiratory Infectious Diseases: Lessons from SARS

text: Every emerging infectious disease is a challenge to the whole of mankind. There are uncertainties regarding whether there will be a pandemic, if it will be caused by the highly pathogenic H5N1 influenza virus, when or where it will occur, how imminent or how severe it will be. No one can accurately predict if and when a given virus will become a pandemic virus. Pandemic prevention strategies must be based on preparing for the unexpected and being capable of reacting accordingly. There is growing evidence that infection control measures were helpful in containment of severe acute respiratory syndrome (SARS) as well as avian influenza. Compliance of standard infection control measures, intensive promotion of hand and respiratory hygiene, vigilance and triage of patients with febrile illness, and specific infection control measures are key components to contain a highly contagious disease in hospital and to protect healthcare workers, patients and visitors. The importance of standard precautions for any patient and cleaning and disinfection for the healthcare environment cannot be overemphasized. SARS illustrated dramatically the potential of air travel and globalization for the dissemination of an emerging infectious disease. To prevent the potential serious consequences of pandemic influenza, timely implementation of pharmaceutical and non-pharmaceutical interventions locally within the outbreak area is the key to minimizing global spread. Herein, we relate our perspective on useful lessons derived from a review of the SARS epidemic that may be useful to physicians, especially when looking ahead to the next epidemic.


Trends in influenza and pneumococcal vaccine coverage in Thai patients with type 2 diabetes mellitus 2010-2018: Experience from a tertiary diabetes center in Bangkok BACKGROUND: Routine vaccination is an important part of preventive services in treating patients with type 2 diabetes (T2DM). There are no available data in temporal trends of vaccination coverage rates in both influenza and pneumococcal vaccines among Thai patients with T2DM. AIM: This study aimed to elucidate influenza and pneumococcal vaccination trends and to identify factors that affect vaccination rates in those patients. METHOD: A retrospective study of randomly medical records stratified by 13 diabetologists was conducted in patients with T2DM from 2010-2018 at Theptarin Hospital, a private multi-disciplinary diabetes center in Bangkok. Adherence to influenza and pneumococcal vaccinations according to current guidance on adult immunization in Thailand had been studied. The rate of both vaccinations from each diabetologist had also been recorded. RESULTS: A total of 2,114 medical records (female 51.7%, mean age 65.2±12.8 years, BMI 26.5±4.6 kg/m(2), A1C 7.1±1.3%, median duration of diabetes 13 years) were retrospectively reviewed covering a 9-year period. We audited 3,554 selected outpatient visits for influenza and pneumococcal vaccinations rates as key performance index in each year. The overall vaccination rate was 39.6% for influenza, 17.4% for the pneumococcal vaccine, and only 13.7%, for both vaccines. The trends of influenza vaccination rates increased from 32.9% in 2010 to 52.2% in 2018 but the trends of pneumococcal vaccination rates were relatively stable at less than 20%. The rate of both vaccinations varied considerably from 0-44% among our diabetologists. Age ≥ 65 years, duration of DM ≥ 15 years, the presence of chronic respiratory disease, and moderate to severe Charlson Comorbidity Index (CCI) score were positively associated with both received vaccinations. CONCLUSIONS: The completeness and timeliness of influenza and pneumococcal vaccinations were unsatisfactory in Thai patients with T2DM. More efforts are needed to increase both influenza and pneumococcal vaccination rates.


Telemedicine against CoVID-19 crisis


title: Epidemics-in-waiting

text: Could the next SARS-like virus reach epidemic proportions? Quantifying the likely threat of emerging diseases isn't easy, but evolution is a crucial factor that may tip the balance in favour of such human parasites.


Impact of COVID-19 on ophthalmic specialist training in the United Kingdom—the trainees’ perspective


A modified phantom (dummy mount) for stallion semen collection


title: trans-Golgi retention of a plasma membrane protein: mutations in the cytoplasmic domain of the asialoglycoprotein receptor subunit H1 result in trans-Golgi retention

text: Unlike the wild-type asialoglycoprotein receptor subunit H1 which is transported to the cell surface, endocytosed and recycled, a mutant lacking residues 4-33 of the 40-amino acid cytoplasmic domain was found to be retained intracellularly upon expression in different cell lines. The mutant protein accumulated in the trans-Golgi, as judged from the acquisition of trans-Golgi-specific modifications of the protein and from the immunofluorescence staining pattern. It was localized to juxtanuclear, tubular structures that were also stained by antibodies against galactosyltransferase and gamma-adaptin. The results of further mutagenesis in the cytoplasmic domain indicated that the size rather than the specific sequence of the cytoplasmic domain determines whether H1 is retained in the trans-Golgi or transported to the cell surface. Truncation to less than 17 residues resulted in retention, and extension of a truncated tail by an unrelated sequence restored surface transport. The transmembrane segment of H1 was not sufficient for retention of a reporter molecule and it could be replaced by an artificial apolar sequence without affecting Golgi localization. The cytoplasmic domain thus appears to inhibit interaction(s) of the exoplasmic portion of H1 with trans-Golgi component(s) for example by steric hindrance or by changing the positioning of the protein in the membrane. This mechanism may also be functional in other proteins.


title: Chapter 1 Introduction

text: Abstract This chapter tells why it is important to study soil–plant–water relations. Water is the most important substance necessary for food production. People depend upon plants for food, so the challenge of feeding a growing population is discussed. The human population growth curve, a logarithmic one, is presented. Rules of logarithms are then given. A calculation is done to show that the human population is limited by the productivity of the land. The calculation shows that it requires two square yards (16,700cm2) to feed one person. The sigmoid plant growth curve is presented followed by a mathematical analysis of Blackman's compound interest law for plant growth. Finally, data from corn and soybean are analyzed to show that their growth rate is exponential. A biography of Napier, the inventor of logarithms, is given in the appendix.


title: Fatal disease associated with Swine Hepatitis E virus and Porcine circovirus 2 co-infection in four weaned pigs in China

text: BACKGROUND: In recent decades, Porcine circovirus 2 (PCV2) infection has been recognized as the causative agent of postweaning multisystemic wasting syndrome, and has become a threat to the swine industry. Hepatitis E virus (HEV) is another high prevalent pathogen in swine in many regions of the world. PCV2 and HEV are both highly prevalent in pig farms in China. CASE PRESENTATION: In this study, we characterized the HEV and PCV2 co-infection in 2–3 month-old piglets, based on pathogen identification and the pathological changes observed, in Hebei Province, China. The pathological changes were severe, and general hyperemia, hemorrhage, inflammatory cell infiltration, and necrosis were evident in the tissues of dead swine. PCR was used to identify the pathogen and we tested for eight viruses (HEV, Porcine reproductive and respiratory syndrome virus, PCV2, Classical swine fever virus, Porcine epidemic diarrhea virus, Transmissible gastroenteritis coronavirus, Porcine parvovirus and Pseudorabies virus) that are prevalent in Chinese pig farms. The livers, kidneys, spleens, and other organs of the necropsied swine were positive for HEV and/or PCV2. Immunohistochemical staining showed HEV- and PCV2-antigen-positive signals in the livers, kidneys, lungs, lymph nodes, and intestine. CONCLUSION: HEV and PCV2 co-infection in piglets was detected in four out of seven dead pigs from two pig farms in Hebei, China, producing severe pathological changes. The natural co-infection of HEV and PCV2 in pigs in China has rarely been reported. We speculate that co-infection with PCV2 and HEV may bring some negative effect on pig production and recommend that more attention should be paid to this phenomenon.


title: Epidemic Investigation

text: Abstract One of the key roles of public health is to manage outbreaks that endanger the health of the population. The nature of an outbreak can be due to a wide range of causes, and a variety of approaches to detection of epidemics are possible, but the main points are very similar for all outbreaks and are described in this article. The first challenge is to notice an increase in cases, and this is followed by a confirmation that there is indeed an outbreak. Based on descriptive epidemiology, a case definition and a hypothesis are developed, which are preferably confirmed by at least an epidemiologic study. Other aspects of investigation described in this article are the organization of the outbreak investigation, public health action, and the importance of communication.


title: Live Bird Exposure among the General Public, Guangzhou, China, May 2013

text: BACKGROUND: A novel avian-origin influenza A(H7N9) caused a major outbreak in Mainland China in early 2013. Exposure to live poultry was believed to be the major route of infection. There are limited data on how the general public changes their practices regarding live poultry exposure in response to the early outbreak of this novel influenza and the frequency of population exposure to live poultry in different areas of China. METHODOLOGY: This study investigated population exposures to live birds from various sources during the outbreak of H7N9 in Guangzhou city, China in 2013 and compared them with those observed during the 2006 influenza A(H5N1) outbreak. Adults were telephone-interviewed using two-stage sampling, stratified by three residential areas of Guangzhou: urban areas and two semi-rural areas in one of which (Zengcheng) A(H7N9) virus was detected in a chicken from wet markets. Logistic regression models were built to describe practices protecting against avian influenza, weighted by age and gender, and then compare these practices across residential areas in 2013 with those from a comparable 2006 survey. PRINCIPAL FINDINGS: Of 1196 respondents, 45% visited wet markets at least daily and 22.0% reported buying live birds from wet markets at least weekly in April-May, 2013, after the H7N9 epidemic was officially declared in late March 2013. Of those buying live birds, 32.3% reported touching birds when buying and 13.7% would slaughter the poultry at home. Although only 10.1% of the respondents reported raising backyard birds, 92.1% of those who did so had physical contact with the birds they raised. Zengcheng respondents were less likely to report buying live birds from wet markets, but more likely to buy from other sources when compared to urban respondents. Compared with the 2006 survey, the prevalence of buying live birds from wet markets, touching when buying and slaughtering birds at home had substantially declined in the 2013 survey. CONCLUSION/SIGNIFICANCE: Although population exposures to live poultry were substantially fewer in 2013 compared to 2006, wet markets and backyard poultry remained the two major sources of live bird exposures for the public in Guangzhou in 2013. Zengcheng residents seemed to have reduced buying live birds from wet markets but not from other sources in response to the detection of H7N9 virus in wet markets.


title: Severe Respiratory Illness Outbreak Associated with Human Coronavirus NL63 in a Long-Term Care Facility

text: We describe an outbreak of severe respiratory illness associated with human coronavirus NL63 in a long-term care facility in Louisiana in November 2017. Six of 20 case-patients were hospitalized with pneumonia, and 3 of 20 died. Clinicians should consider human coronavirus NL63 for patients in similar settings with respiratory disease.


Response to: low dose radiation therapy for COVID-19 pneumonia a double-edged sword


title: A Novel Paramyxovirus?

text: In public databases, we identified sequences reported as human genes expressed in kidney mesangial cells. The similarity of these genes to paramyxovirus matrix, fusion, and phosphoprotein genes suggests that they are derived from a novel paramyxovirus. These genes are sufficiently unique to suggest the existence of a novel paramyxovirus genus.


title: Oligonucleotide-Based Antiviral Strategies

text: In the age of extensive global traffic systems, the close neighborhood of man and livestock in some regions of the world, as well as inadequate prevention measures and medical care in poorer countries, greatly facilitates the emergence and dissemination of new virus strains. The appearance of avian influenza viruses that can infect humans, the spread of the severe acute respiratory syndrome (SARS) virus, and the unprecedented raging of human immunodeficiency virus (HIV) illustrate the threat of a global virus pandemic. In addition, viruses like hepatitis B and C claim more than one million lives every year for want of efficient therapy. Thus, new approaches to prevent virus propagation are urgently needed. Antisense strategies are considered a very attractive means of inhibiting viral replication, as oligonucleotides can be designed to interact with any viral RNA, provided its sequence is known. The ensuing targeted destruction of viral RNA should interfere with viral replication without entailing negative effects on ongoing cellular processes. In this review, we will give some examples of the employment of antisense oligonucleotides, ribozymes, and RNA interference strategies for antiviral purposes. Currently, in spite of encouraging results in preclinical studies, only a few antisense oligonucleotides and ribozymes have turned out to be efficient antiviral compounds in clinical trials. The advent of RNA interference now seems to be refueling hopes for decisive progress in the field of therapeutic employment of antisense strategies.


title: Rapid diagnostic tests for infectious diseases in the emergency department

text: Abstract Background Rapid diagnostic tests (RDTs) for infectious diseases, with a turn-around time <2 hours, are promising tools that could improve patient care, antimicrobial stewardship and infection prevention in the emergency department (ED) setting. Numerous RDTs have been developed but not necessarily for the ED environment. Their successful implementation in the ED relies on their performance and impact on patient management. Objectives The aim of this narrative review is to provide an overview of currently available RDTs for infectious diseases in the ED. Sources PubMed was searched through August 2019 for available studies on RDTs for infectious diseases. Inclusion criteria included: commercial tests approved by the FDA or CE-IVD with data on clinical samples, ability to run on fully-automated systems and result delivery within 2 hours. Content A non-exhaustive list of representative commercially available FDA or CE approved assays was categorized by clinical syndrome: pharyngitis and upper respiratory tract infection, lower respiratory tract infection, gastrointestinal infection, meningitis and encephalitis, fever in the returning traveler and sexually-transmitted infection including HIV. The performance of tests was described based on clinical validation studies. Further, their impact on clinical outcomes and anti-infective use was discussed with a focus on ED-based studies. Implications Clinicians should be familiar with the distinctive features of each RDT and individual performance characteristics for each target. Their integration into ED workflow should be pre-planned considering local constraints of given settings. Additional clinical studies are needed to further evaluate their clinical and cost effectiveness.


title: Prediction of the COVID-19 spread in African countries and implications for prevention and controls: A case study in South Africa, Egypt, Algeria, Nigeria, Senegal and Kenya

text: Abstract COVID-19 (Corona Virus Disease 2019) is globally spreading and the international cooperation is urgently required in joint prevention and control of the epidemic. Using the Maximum-Hasting (MH) parameter estimation method and the modified Susceptible Exposed Infectious Recovered (SEIR) model, the spread of the epidemic under three intervention scenarios (suppression, mitigation, mildness) is simulated and predicted in South Africa, Egypt, and Algeria, where the epidemic situations are severe. The studies are also conducted in Nigeria, Senegal and Kenya, where the epidemic situations are growing rapidly and the socio-economic are relatively under-developed, resulting in more difficulties in preventing the epidemic. Results indicated that the epidemic can be basically controlled in late April with strict control of scenario one, manifested by the circumstance in the South Africa and Senegal. Under moderate control of scenario two, the number of infected people will increase by 1.43–1.55 times of that in scenario one, the date of the epidemic being controlled will be delayed by about 10 days, and Algeria, Nigeria, and Kenya are in accordance with this situation. In the third scenario of weak control, the epidemic will be controlled by late May, the total number of infected cases will double that in scenario two, and Egypt is in line with this prediction. In the end, a series of epidemic controlling methods are proposed, including patient quarantine, close contact tracing, population movement control, government intervention, city and county epidemic risk level classification, and medical cooperation and the Chinese assistance.


title: No antibody response in acral cutaneous manifestations associated with COVID‐19 ?

text: Skins symptoms during COVID‐19 have been recently described but their relation to SARS‐CoV‐2 is unclear while results for real‐time reverse transcriptase polymerase chain reaction (rRT‐PCR) testing were variable. Recalcati et al. reported 14 cases of patients with skin symptoms consistent with previous described COVID‐19 lesions but all the patients were tested negative. They asked for a serology to validate the hypothesis that these lesions are related to COVID‐19.


title: Dying patients with COVID-19: What should Hospital Palliative Care Teams (HPCTs) be prepared for?

text: OBJECTIVE: The COVID-19 pandemic is a care crisis of unknown duration which has seemingly not yet reached its peak in many countries. A significant number of elderly and frail people and those with underlying serious illness will continue to develop severe forms of the COVID-19 infection. Most of them are not eligible for intensive care treatment but can still expect palliative care — in many cases provided by a Hospital Palliative Care Team (HPCT). Several teams have already gained experience in caring for these patients and their families, others are preparing for it. METHOD: We report on a COVID-19 patient with pre-existing acute myeloid leukemia who was looked after by a HPCT until death. We discuss the challenges and difficulties while caring for COVID-19-positive palliative patients in a non-ICU setting. RESULTS: Hospitalization of the patient in an isolation ward caused an enormous burden for the dying patient and his family. Symptom control was particularly difficult because of rapid deteriorating dyspnea and the scarce presence of medical staff in the patient's room. SIGNIFICANCE OF RESULTS: COVID-19 patients who are not eligible for ICU treatment may have a particularly high need for palliative care. Since beds in specialist palliative care units are limited, the HPCT should be prepared to care for these patients. They may offer support in decision-making, optimize symptom control, and provide psychosocial care for patients and their families. Visiting restrictions aimed to protect the general public must be weighted against the patient's and family's suffering.


title: Respiratory Viruses and Torque Teno Virus in Adults with Acute Respiratory Infections

text: OBJECTIVE: To define the molecular epidemiology of respiratory viral infections in adult patients. METHODS: Nasal and throat swabs were collected from all adult patients with influenza-like illness (ILI), acute respiratory infection (ARI), or severe ARI (SARI) admitted to a tertiary hospital in Surakarta, Indonesia, between March 2010 and April 2011 and analyzed for 19 respiratory viruses and for torque teno virus (TTV) and human gyrovirus (HGyV). RESULTS: Respiratory viruses were detected in 61.3% of the subjects, most of whom had ARI (90.8%, OR = 11.39), were hospitalized (96.9%, OR = 22.31), had asthma exacerbation (90.9%, OR = 8.67), and/or had pneumonia (80%, OR = 4.0). Human rhinovirus (HRV) A43 predominated. Influenza A H3N2, human metapneumovirus (HMPV) subtypes A1 and A2, the influenza B virus, human adenovirus B, and human coronavirus OC43 were also detected. All respiratory viruses were detected in the transition month between the rainy and dry seasons. No mixed respiratory virus infection was found. Coinfections of the influenza A H3N2 virus with TTV, HMPV with TTV, HRV with TTV, and human parainfluenza virus-3 with TTV were found in 4.7, 2.8, 19.8, and 0.9% of the samples, respectively. CONCLUSIONS: This study highlights the need to perform routine detection of respiratory viruses in adults hospitalized with ARI, asthma exacerbation, and/or pneumonia.


Heartbreaking applause: an unexpected consequence of the COVID-19 crisis