title: Puzzling haze events in China during the coronavirus (COVID‐19) shutdown

text: It is a puzzle as to why more severe haze formed during the New Year Holiday in 2020 (NYH‐20), when China was in an unprecedented state of shutdown to contain the coronavirus (COVID‐19) outbreak, than in 2019 (NYH‐19). We performed a comprehensive measurement and modeling analysis of the aerosol chemistry and physics at multiple sites in China (mainly in Shanghai) before, during, and after NYH‐19 and NYH‐20. Much higher secondary aerosol fraction in PM(2.5) were observed during NYH‐20 (73%) than during NYH‐19 (59%). During NYH‐20, PM(2.5) levels correlated significantly with the oxidation ratio of nitrogen (r (2) = 0.77, p < 0.01), and aged particles from northern China were found to impede atmospheric new particle formation and growth in Shanghai. A markedly enhanced efficiency of nitrate aerosol formation was observed along the transport pathways during NYH‐20, despite the overall low atmospheric NO(2) levels.


title: Flawed recommendations on surface hygiene within the existing Interim Influenza Pandemic National Infection Control Guidelines

text: Abstract The Interim Infection Control Guidelines for Pandemic Influenza in Healthcare and Community Settings, published by the Australian Commonwealth Government in 2006, have been reviewed and found to contain recommendations that, if they were made by a private organisation, would be potentially illegal under the Therapeutic Goods Act 1989, and also raise some concern in relation to occupational health and safety. The guidelines also fail to recommend the use of disinfecting products with specific claims relating to influenza virus that have been approved by the Therapeutic Goods Agency.


ISUOG Consensus Statement on rationalization of early‐pregnancy care and provision of ultrasonography in context of SARS‐CoV‐2


title: Mindful management of relationships during periods of crises: A model of trust, doubt and relational adjustments

text: Abstract This paper identifies practices of business-to-business relationship management that lead to building resilience during crisis. Business relationships play a significant role when firms face turbulence and disruption. Crises create resource limitations that businesses need to manage by the rapid formation of new relationships to access resources and build adequate capabilities. Mindfully managing such relationships requires a combination of trust, doubt and control mechanisms to enable exchange while safeguarding against relational vulnerabilities. Drawing on data from 33 firms operating within highly turbulent and uncertain environments, and crisis management literature, we apply the concept of mindfulness and introduce a model of mindful management of relationships as a process that combines the cognitive and behavioural capabilities of trusting, doubting, verifying, and adjusting relational exposure. This process enables a rapid acquisition of resources and building capabilities while enabling businesses dealing with issues before relational failure manifests. The mindful process supports ongoing and highly interactive relationships that adjust to changing circumstances fostering collaboration to deal with crises. Results encourage managers to rapidly develop relationships and trust new partners, whilst practicing suspicious thinking, enacting continuous interaction, empowering experienced boundary personnel, enabling frequent informal communication, and supporting the development of diverse social bonds.


title: A field study on indoor environment quality of Chinese inpatient buildings in a hot and humid region

text: Abstract In this research, objective physical measurements and subjective questionnaire surveys are used to investigate the indoor environment quality of Chinese inpatient buildings. The relative humidity in the inpatient buildings reaches 65%–75% during summer, resulting in the regular appearance of microbial growth on indoor surfaces. The average outdoor air change rate measured through the CO2 concentration decay method in the sampled inpatient rooms is 1.1 h−1, which is 45% below the standard threshold. The CO2 concentration in over 99% of the functional spaces is below the threshold of 1000 ppm. However, the dissatisfaction rate of the air freshness is higher than 25%, owing to the characteristics of healthcare activities. Insufficient fresh air volume and high supply air humidity ratio of the outdoor air system result in the inadequate dehumidification capacity and the over-humid environment in the inpatient buildings. From the perspective of indoor TVOC and PM2.5 concentration, a hospitable IAQ is achieved in the inpatient buildings. In the nurse unit, the illumination levels in public areas, such as patient corridors and nurse stations, are inadequate. The average noise levels (A) in the inpatient rooms and nurse stations are 50.7 and 61.6 dB, respectively, which exceeds the Chinese standard. According to the subjective survey, the dissatisfaction rates of overall IEQ in the summer for patients and visitors are 7.9% and 10.4%, respectively, while for staff it is 34.8%. Statistical analysis reveals that the satisfaction levels of the patient with the IEQ are higher than that of the visitor and staff.


title: SARS-CoV-2 in fruit bats, ferrets, pigs, and chickens: an experimental transmission study

text: BACKGROUND: In December, 2019, a novel zoonotic severe acute respiratory syndrome-related coronavirus emerged in China. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became pandemic within weeks and the number of human infections and severe cases is increasing. We aimed to investigate the susceptibilty of potential animal hosts and the risk of anthropozoonotic spill-over infections. METHODS: We intranasally inoculated nine fruit bats (Rousettus aegyptiacus), ferrets (Mustela putorius), pigs (Sus scrofa domesticus), and 17 chickens (Gallus gallus domesticus) with 10(5) TCID(50) of a SARS-CoV-2 isolate per animal. Direct contact animals (n=3) were included 24 h after inoculation to test viral transmission. Animals were monitored for clinical signs and for virus shedding by nucleic acid extraction from nasal washes and rectal swabs (ferrets), oral swabs and pooled faeces samples (fruit bats), nasal and rectal swabs (pigs), or oropharyngeal and cloacal swabs (chickens) on days 2, 4, 8, 12, 16, and 21 after infection by quantitative RT-PCR (RT-qPCR). On days 4, 8, and 12, two inoculated animals (or three in the case of chickens) of each species were euthanised, and all remaining animals, including the contacts, were euthanised at day 21. All animals were subjected to autopsy and various tissues were collected for virus detection by RT-qPCR, histopathology immunohistochemistry, and in situ hybridisation. Presence of SARS-CoV-2 reactive antibodies was tested by indirect immunofluorescence assay and virus neutralisation test in samples collected before inoculation and at autopsy. FINDINGS: Pigs and chickens were not susceptible to SARS-CoV-2. All swabs, organ samples, and contact animals were negative for viral RNA, and none of the pigs or chickens seroconverted. Seven (78%) of nine fruit bats had a transient infection, with virus detectable by RT-qPCR, immunohistochemistry, and in situ hybridisation in the nasal cavity, associated with rhinitis. Viral RNA was also identified in the trachea, lung, and lung-associated lymphatic tissue in two animals euthanised at day 4. One of three contact bats became infected. More efficient virus replication but no clinical signs were observed in ferrets, with transmission to all three direct contact animals. Mild rhinitis was associated with viral antigen detection in the respiratory and olfactory epithelium. Prominent viral RNA loads of 0–10(4) viral genome copies per mL were detected in the upper respiratory tract of fruit bats and ferrets, and both species developed SARS-CoV-2-reactive antibodies reaching neutralising titres of up to 1/1024 after 21 days. INTERPRETATION: Pigs and chickens could not be infected intranasally by SARS-CoV-2, whereas fruit bats showed characteristics of a reservoir host. Virus replication in ferrets resembled a subclinical human infection with efficient spread. Ferrets might serve as a useful model for further studies—eg, testing vaccines or antivirals. FUNDING: German Federal Ministry of Food and Agriculture.


title: Molecular profiling of the human nasal epithelium: A proteomics approach

text: Abstract A comprehensive proteomic profiling of nasal epithelium (NE) is described. This study relies on simple subcellular fractionation used to obtain soluble- and membrane-enriched fractions followed by 2-dimensional liquid chromatography (2D-LC) separation and tandem mass spectrometry (MS/MS). The cells were collected using a brushing technique applied on NE of clinically evaluated volunteers. Subsequently, the soluble- and the membrane-protein enriched fractions were prepared and analyzed in parallel using 2D-LC-MS/MS. In a set of 1482 identified proteins, 947 (63.9%) proteins were found to be associated to membrane fraction. Grand average hydropathy value index (GRAVY) analysis, the transmembrane protein mapping and annotations of primary location deposited in the Human Protein Reference Database (HPRD) confirmed an enrichment of hydrophobic proteins on this dataset. Ingenuity Pathway Analysis (IPA) of soluble fraction revealed an enrichment of molecular and cellular functions associated with cell death, protein folding and drug metabolism while in membrane fraction showed an enrichment of functions associated with molecular transport, protein trafficking and cell-to-cell signaling and interaction. The IPA showed similar enrichment of functions associated with cellular growth and proliferation in both soluble and membrane subproteomes. This finding was in agreement with protein content analysis using exponentially modified protein abundance index (emPAI). A comparison of our data with previously published studies focusing on respiratory tract epithelium revealed similarities related to identification of proteins associated with physical barrier function and immunological defence. In summary, we extended the NE molecular profile by identifying and characterizing proteins associated to pivotal functions of a respiratory epithelium, including the control of fluid volume and ionic composition at the airways' surface, physical barrier maintenance, detoxification and immunological defence. The extent of similarities supports the applicability of a less invasive analysis of NE to assess prognosis and treatment response of lung diseases such as asthma, cystic fibrosis and chronic obstructive pulmonary disease.


title: Structural Basis for the Identification of the N-Terminal Domain of Coronavirus Nucleocapsid Protein as an Antiviral Target

text: [Image: see text] Coronaviruses (CoVs) cause numerous diseases, including Middle East respiratory syndrome and severe acute respiratory syndrome, generating significant health-related and economic consequences. CoVs encode the nucleocapsid (N) protein, a major structural protein that plays multiple roles in the virus replication cycle and forms a ribonucleoprotein complex with the viral RNA through the N protein’s N-terminal domain (N-NTD). Using human CoV-OC43 (HCoV-OC43) as a model for CoV, we present the 3D structure of HCoV-OC43 N-NTD complexed with ribonucleoside 5′-monophosphates to identify a distinct ribonucleotide-binding pocket. By targeting this pocket, we identified and developed a new coronavirus N protein inhibitor, N-(6-oxo-5,6-dihydrophenanthridin-2-yl)(N,N-dimethylamino)acetamide hydrochloride (PJ34), using virtual screening; this inhibitor reduced the N protein’s RNA-binding affinity and hindered viral replication. We also determined the crystal structure of the N-NTD–PJ34 complex. On the basis of these findings, we propose guidelines for developing new N protein-based antiviral agents that target CoVs.


Prolonged Pyrexia and Hepatitis: Q fever


title: First report of Enterocytozoon bieneusi and Cryptosporidium spp. in peafowl (Pavo cristatus) in China

text: Enterocytozoon bieneusi and Cryptosporidium spp. are important pathogens causing diarrhea in humans and animals. However, few studies have been conducted on the infection of E. bieneusi and Cryptosporidium spp. in peafowl up to now. The purpose of the present study was to determine the prevalence and the involved genotypes of Cryptosporidium spp. and E. bieneusi in peafowl in Beijing and Jiangxi Province, China. In total, 258 peafowl fecal samples were collected. Overall, both Cryptosporidium spp. and E. bieneusi had the same prevalence, i.e. 6.59% (17/258). Higher infection rates of E. bieneusi and Cryptosporidium spp. were found in the adolescent peafowl. The prevalence of E. bieneusi in Beijing and Jiangxi Province was 5.23% and 8.57% respectively. For Cryptosporidium spp., the prevalence was 4.58% and 9.52% in Beijing and Jiangxi Province, respectively. Three zoonotic genotypes of E. bieneusi were confirmed, including two known genotypes, genotype Peru 6 and D, and one novel genotype, JXP1. Two avian specific species/genotypes of Cryptosporidium, Avian genotype Ⅲ and Goose genotype Ⅰ, were identified. To our knowledge, this is the first report of E. bieneusi and Cryptosporidium spp. occurrence in peafowl in China. The findings suggest that peafowl could be reservoirs of E. bieneusi and Cryptosporidium spp. which could be potentially transmitted to humans and other animals, and the present survey have implications for controlling E. bieneusi and Cryptosporidium spp. infection in peafowl.


title: Epidemiology of respiratory viruses in Saudi Arabia: toward a complete picture

text: Acute lower respiratory tract infection is a major health problem that affects more than 15% of the total population of Saudi Arabia each year. Epidemiological studies conducted over the last three decades have indicated that viruses are responsible for the majority of these infections. The epidemiology of respiratory viruses in Saudi Arabia is proposed to be affected mainly by the presence and mobility of large numbers of foreign workers and the gathering of millions of Muslims in Mecca during the Hajj and Umrah seasons. Knowledge concerning the epidemiology, circulation pattern, and evolutionary kinetics of respiratory viruses in Saudi Arabia are scant, with the available literature being inconsistent. This review summarizes the available data on the epidemiology and evolution of respiratory viruses. The demographic features associated with Middle East respiratory syndrome-related coronavirus infections are specifically analyzed for a better understanding of the epidemiology of this virus. The data support the view that continuous entry and exit of pilgrims and foreign workers with different ethnicities and socioeconomic backgrounds in Saudi Arabia is the most likely vehicle for global dissemination of respiratory viruses and for the emergence of new viruses (or virus variants) capable of greater dissemination.


title: Human Airway Epithelial Cell Culture to Identify New Respiratory Viruses: Coronavirus NL63 as a Model

text: Propagation of new human respiratory virus pathogens in established cell lines is hampered by a lack of predictability regarding cell line permissivity and by availability of suitable antibody reagents to detect infection in cell lines that do not exhibit significant cytopathic effect. Recently, molecular methods have been used to amplify and identify novel nucleic acid sequences directly from clinical samples, but these methods may be hampered by the quantity of virus present in respiratory secretions at different time points following the onset of infection. Human airway epithelial (HAE) cultures, which effectively mimic the human bronchial environment, allow for cultivation of a wide variety of human respiratory viral pathogens. The goal of the experiments described here was to determine if propagation and identification of a human respiratory virus may be achieved through inoculation of HAE cultures followed by whole transcriptome amplification (WTA) and sequence analysis. To establish proof-of-principle human coronavirus NL63 (HCoV-NL63) was evaluated, and the first visualization of HCoV-NL63 virus by transmission electron microscopy (TEM) is reported. Initial propagation of human respiratory secretions onto HAE cultures followed by TEM and WTA of culture supernatant may be a useful approach for visualization and detection of new human respiratory pathogens that have eluded identification by traditional approaches.


The role of SARS‐CoV‐2 antibodies in COVID‐19: Healing in most, harm at times


title: Screening and druggability analysis of some plant metabolites against SARS-CoV-2: An integrative computational approach

text: The sudden outbreak of novel coronavirus has caused a global concern due to its infection rate and mortality. Despite extensive research, there are still no specific drugs or vaccines to combat SARS-CoV-2 infection. Hence, this study was designed to evaluate some plant-based active compounds for drug candidacy against SARS-CoV-2 by using virtual screening methods and various computational analyses. A total of 27 plant metabolites were screened against SARS-CoV-2 main protease proteins (MPP), Nsp9 RNA binding protein, spike receptor binding domain, spike ecto-domain and HR2 domain using a molecular docking approach. Four metabolites, i.e., asiatic acid, avicularin, guajaverin, and withaferin showed maximum binding affinity with all key proteins in terms of lowest global binding energy. The crucial binding sites and drug surface hotspots were unravelled for each viral protein. The top candidates were further employed for ADME (absorption, distribution, metabolism, and excretion) analysis to investigate their drug profiles. Results suggest that none of the compounds render any undesirable consequences that could reduce their drug likeness properties. The analysis of toxicity pattern revealed no significant tumorigenic, mutagenic, irritating, or reproductive effects by the compounds. However, withaferin was comparatively toxic among the top four candidates with considerable cytotoxicity and immunotoxicity. Most of the target class by top drug candidates belonged to enzyme groups (e.g. oxidoreductases hydrolases, phosphatases). Moreover, results of drug similarity prediction revealed two approved structural analogs of Asiatic acid i.e. Hydrocortisone (DB00741) (previously used for SARS-CoV-1 and MERS) and Dinoprost-tromethamine (DB01160) from DrugBank. In addition, two other biologically active compounds, Mupirocin (DB00410) and Simvastatin (DB00641) could be an option for the treatment of viral infections. The study may pave the way to develop effective medications and preventive measure against SARS-CoV-2. Due to the encouraging results, we highly recommend further in vivo trials for the experimental validation of our findings.


title: Constant up-regulation of BiP/GRP78 expression prevents virus-induced apoptosis in BHK-21 cells with Japanese encephalitis virus persistent infection

text: BACKGROUND: Persistent infection of the Japanese Encephalitis Virus (JEV) has been reported in clinical cases, experimental animals, and various cell culture systems. We previously reported the establishment of spontaneous JEV persistent infection, assisted by defective interfering particle accumulation and/or attenuated helper viruses, in BHK-21 cells devoid of virus-induced apoptosis, cBS6-2 and cBS6-3. However, cell-specific factors may play important roles in controlling JEV replication and have never been assessed for this specific phenomenon. Recent evidence suggests that viruses have evolved various mechanisms to cope with endoplasmic reticulum stress signaling pathways for their efficient amplification and transmission, including the unfolded protein response (UPR). RESULTS: To identify the host cell factors that affect JEV persistence, we investigated the expression of essential UPR factors in cBS6-2 and cBS6-3 cells. Of the selected UPR factors tested, the most noticeable deviations from those of the normal BHK-21 cells with JEV acute infection were as follows: the suppression of C/EBP homologous binding protein (CHOP) and the constant up-regulation of immunoglobulin binding protein (BiP) expression in cBS6-2 and cBS6-3 cells. In JEV acute infection on normal BHK-21 cells, silencing CHOP expression through specific siRNA blocked cell death almost completely. Meanwhile, depletion of BiP by specific siRNA unlocked CHOP expression in cBS6-2 and cBS6-3 cells, resulting in massive cell death. Fulminant apoptotic cell death for both cell clones on tunicamycin treatment revealed that the JEV persistently infected cells still contained functional arms for cell fate decisions. CONCLUSIONS: BHK-21 cells with JEV persistent infection strive against virus-induced apoptosis through constant up-regulation of BiP expression, resulting in the complete depletion of CHOP even with apparent virus amplification in the cells. Accordingly, the attenuation of virus replication as well as the modifications to cell metabolism could be additional factors contributing to the development of JEV persistent infection in mammalian cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0269-5) contains supplementary material, which is available to authorized users.


title: Dataset to Support the Adoption of Social Media and Emerging Technologies for Students’ Continuous Engagement

text: The recent advancements in ICT have made it possible for teaching and learning to be conducted outside the four walls of a University. Furthermore, the recent COVID-19 pandemic that has crippled educational activities in all nations of the world has further revealed the urgent need for academic institutions to embrace and integrate alternative modes of teaching and learning via social media platforms and emerging technologies into existing teaching tools. This article contains data collected from 850 face to face University students during the COVID-19 pandemic lockdown. An online google form was used to elicit information from the students about their awareness and intention to use these alternative modes of teaching and learning. The questions were structured using the Unified Theory of Acceptance and Use of Technology (UTAUT) model. This data article includes the questionnaire used to retrieve the data, the responses obtained in spreadsheet format, the charts generated from the responses received, the Statistical Package of the Social Sciences (SPSS) file, the descriptive statistics, and reliability analysis computed for all the UTAUT variables. The dataset will enhance understanding of how face to face students use social media platforms and how these platforms could be used to engage the students outside their classroom activities. Also, the dataset exposes how familiar face to face University students are to these emerging teaching and learning technologies. The challenges that could inhibit the adoption of these technologies were also revealed.


title: The roles of PPARγ and its agonists in autoimmune diseases: A comprehensive review

text: Autoimmune diseases are common diseases of the immune system that are characterized by the loss of self-tolerance and the production of autoantibodies; the breakdown of immune tolerance and the prolonged inflammatory reaction are undisputedly core steps in the initiation and maintenance of autoimmunity. Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that belong to the nuclear hormone receptor family and act as ligand-activated transcription factors. There are three different isotypes of PPARs: PPARα, PPARγ, and PPARβ/δ. PPARγ is an established regulator of glucose homeostasis and lipid metabolism. Recent studies have demonstrated that PPARγ exhibits anti-inflammatory and anti-fibrotic effects in multiple disease models. PPARγ can also modulate the activation and polarization of macrophages, regulate the function of dendritic cells and mediate T cell survival, activation, and differentiation. In this review, we summarize the signaling pathways and biological functions of PPARγ and focus on how PPARγ and its agonists play protective roles in autoimmune diseases, including autoimmune thyroid diseases, multiple sclerosis, rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, primary Sjogren syndrome and primary biliary cirrhosis.


title: In silico approach toward the identification of unique peptides from viral protein infection: Application to COVID-19

text: We describe a method for rapid in silico selection of diagnostic peptides from newly described viral pathogens and applied this approach to SARS-CoV-2/COVID-19. This approach is multi-tiered, beginning with compiling the theoretical protein sequences from genomic derived data. In the case of SARS-CoV-2 we begin with 496 peptides that would be produced by proteolytic digestion of the viral proteins. To eliminate peptides that would cause cross-reactivity and false positives we remove peptides from consideration that have sequence homology or similar chemical characteristics using a progressively larger database of background peptides. Using this pipeline, we can remove 47 peptides from consideration as diagnostic due to the presence of peptides derived from the human proteome. To address the complexity of the human microbiome, we describe a method to create a database of all proteins of relevant abundance in the saliva microbiome. By utilizing a protein-based approach to the microbiome we can more accurately identify peptides that will be problematic in COVID-19 studies which removes 12 peptides from consideration. To identify diagnostic peptides, another 7 peptides are flagged for removal following comparison to the proteome backgrounds of viral and bacterial pathogens of similar clinical presentation. By aligning the protein sequences of SARS-CoV-2 field isolates deposited to date we can identify peptides for removal due to their presence in highly variable regions that may lead to false negatives as the pathogen evolves. We provide maps of these regions and highlight 3 peptides that should be avoided as potential diagnostic or vaccine targets. Finally, we leverage publicly deposited proteomics data from human cells infected with SARS-CoV-2, as well as a second study with the closely related MERS-CoV to identify the two proteins of highest abundance in human infections. The resulting final list contains the 24 peptides most unique and diagnostic of SARS-CoV-2 infections. These peptides represent the best targets for the development of antibodies are clinical diagnostics. To demonstrate one application of this we model peptide fragmentation using a deep learning tool to rapidly generate targeted LCMS assays and data processing method for detecting CoVID-19 infected patient samples. Graphical Abstract


In memoriam: Gita Ramjee


title: Upper airway gene expression differentiates COVID-19 from other acute respiratory illnesses and reveals suppression of innate immune responses by SARS-CoV-2

text: We studied the host transcriptional response to SARS-CoV-2 by performing metagenomic sequencing of upper airway samples in 238 patients with COVID-19, other viral or non-viral acute respiratory illnesses (ARIs). Compared to other viral ARIs, COVID-19 was characterized by a diminished innate immune response, with reduced expression of genes involved in toll-like receptor and interleukin signaling, chemokine binding, neutrophil degranulation and interactions with lymphoid cells. Patients with COVID-19 also exhibited significantly reduced proportions of neutrophils and macrophages, and increased proportions of goblet, dendritic and B-cells, compared to other viral ARIs. Using machine learning, we built 26-, 10- and 3-gene classifiers that differentiated COVID-19 from other acute respiratory illnesses with AUCs of 0.980, 0.950 and 0.871, respectively. Classifier performance was stable at low viral loads, suggesting utility in settings where direct detection of viral nucleic acid may be unsuccessful. Taken together, our results illuminate unique aspects of the host transcriptional response to SARS-CoV-2 in comparison to other respiratory viruses and demonstrate the feasibility of COVID-19 diagnostics based on patient gene expression.


Et COVID-19 nous frappa de plein fouet…


title: Strategies Using Bio-Layer Interferometry Biosensor Technology for Vaccine Research and Development

text: Bio-layer interferometry (BLI) real-time, label-free technology has greatly contributed to advances in vaccine research and development. BLI Octet platforms offer high-throughput, ease of use, reliability, and high precision analysis when compared with common labeling techniques. Many different strategies have been used to immobilize the pathogen or host molecules on BLI biosensors for real-time kinetics and affinity analysis, quantification, or high-throughput titer. These strategies can be used in multiple applications and shed light onto the structural and functional aspects molecules play during pathogen-host interactions. They also provide crucial information on how to achieve protection. This review summarizes some key BLI strategies used in human vaccine research and development.


title: Challenges and opportunities in pandemic influenza planning: lessons learned from recent infectious disease preparedness and response efforts

text: Abstract The impact of the next pandemic influenza is likely to be far greater, by orders of magnitude, than most bioterrorism (BT) scenarios. A written pandemic emergency plan and establishment of emergency management teams are critical to mounting a coordinated and effective response to what will be a catastrophic event. Members of these teams should include public health, medical, emergency response and public safety officials, organized at each local, state and federal level. The tragic events of September 11, 2001 and the subsequent anthrax attacks have substantially increased funding and support for bioterrorism planning in the United States. Thus, public health officials have an unprecedented opportunity to strengthen current systems' planning efforts by promoting dual use bioterrorism/pandemic influenza plans. Combining lessons learned from the 2001 terrorist incidents, recent preevent smallpox vaccine programs and the history of past influenza pandemics, more effective strategies can be developed. For example, enhanced influenza surveillance systems can provide data that will not only provide early identification of a novel influenza strain, but will provide more timely recognition of other outbreaks of infectious diseases, including public health threats that may initially present as an influenza-like illness (ILI). In recent years, we have witnessed emerging and reemerging infectious disease threats that have presented us with challenges similar to those posed by an influenza pandemic. Such events highlight the need for advance planning to ensure an optimal response to a health emergency that is certain to be unpredictable, complex, rapidly evolving and accompanied by considerable public alarm. While advance warning for a terrorist attack is unlikely, the warning already exists for a possible new influenza strain, as evidenced by the recent cases of H5N1 in Hong Kong and the rapid global spread of cases of Severe Acute Respiratory Syndrome.


title: Traitors of the immune system—Enhancing antibodies in HIV infection: Their possible implication in HIV vaccine development

text: Considering recent HIV vaccine failures, the authors believe that it would be most important to find new targets for vaccine-induced immunity, and to analyze the data from previous trials, using an innovative approach. In their review article, the authors briefly summarize the significance of the antibody-dependent enhancement of infection in different viral diseases and discuss role of these types of antibodies as the obstacles for vaccine development. Findings which indicate that complement-mediated antibody-dependent enhancement (C-ADE) is present also in HIV-infected patients, are summarized. Previous results of the authors, suggesting that C-ADE plays a very important role in the progression of HIV infection are described. Data reflecting that enhancing antibodies may develop even in vaccinated animals and human volunteers, and may be responsible for the paradoxical results obtained in some subgroups of vaccinees are discussed. Finally, based on their hypothesis, the authors offer some suggestions for the future development of vaccines.


title: Collateral damage of COVID‐19 pandemic: Delayed medical care

text: During the COVID‐19 pandemic, emergency room visits have drastically decreased for non‐COVID conditions such as appendicitis, heart attack, and stroke. Patients may be avoiding seeking medical attention for fear of catching the deadly condition or as an unintended consequence of stay‐at‐home orders. This delay in seeking care can lead to increased morbidity and mortality, which has not been figured in the assessment of the extent of damage caused by this pandemic. This case illustrates an example of “collateral damage” caused by the COVID‐19 pandemic. What would have been a standard ST‐elevation myocardial infarction treated with timely and successful stenting of a dominant right coronary artery occlusion, became a much more dangerous postinfarction ventricular septal defect; all because of a 2‐day delay in seeking medical attention by an unsuspecting patient.


title: Viral etiology of Parkinson's disease: Focus on influenza A virus

text: Abstract Some clinical reports and epidemiological data suggest that a virus may play a role in the etiology of Parkinson's disease (PD). Following intracerebral injection of a neurovirululent strain of influenza A virus into mice, the virus was found to be particularly localized in neurons of the substantia nigra and hippocampus. Although efforts to detect virus particles in the brains, or antibodies in the serum or CSF of patients with PD have been generally unsuccessful, recent immunohistochemical work has revealed the presence of complement proteins and the interferon-induced MxA in association with Lewy bodies and swollen neuronal processes. Although a viral etiology for PD is not now widely accepted, we proposed such an hypothesis. Neurovirulent influenza A virus is a candidate, but some other viruses or complex infection of these viruses may be responsible for the formation of Lewy bodies and the later death of nigral neurons.


title: The challenges of public health education with a particular reference to China

text: Summary A recent seminar on public health education at the Chinese University of Hong Kong posed some key questions for the future of public health, as well as how the next generation of public health specialists should be educated. This paper summarizes some of the discussions on the future of public health education in China within the context of China's healthcare reforms and trends in global public health education.


Transient cortical blindness in COVID-19 pneumonia; a PRES-like syndrome: A case report


Protecting patients and healthcare personnel from COVID-19: considerations for practice and outpatient care in cardiology


title: The genetic and cultural evolution of unsustainability

text: Anthropogenic changes are accelerating and threaten the future of life on earth. While the proximate mechanisms of these anthropogenic changes are well studied (e.g., climate change, biodiversity loss, population growth), the evolutionary causality of these anthropogenic changes have been largely ignored. Anthroecological theory (AET) proposes that the ultimate cause of anthropogenic environmental change is multi-level selection for niche construction and ecosystem engineering. Here, we integrate this theory with Lotka’s Maximum Power Principle and propose a model linking energy extraction from the environment with genetic, technological and cultural evolution to increase human ecosystem carrying capacity. Carrying capacity is partially determined by energetic factors such as the net energy a population can acquire from its environment and the efficiency of conversion from energy input to offspring output. These factors are under Darwinian genetic selection in all species, but in humans, they are also determined by technology and culture. If there is genetic or non-genetic heritable variation in the ability of an individual or social group to increase its carrying capacity, then we hypothesize that selection or cultural evolution will act to increase carrying capacity. Furthermore, if this evolution of carrying capacity occurs faster than the biotic components of the ecological system can respond via their own evolution, then we hypothesize that unsustainable ecological changes will result.


Occurrence of pulmonary embolism in a patient with mild clinical expression of COVID-19 infection


title: Demonstration of viral antigen and immunoglobulin (IgG and IgM) in brain tissue of pigs experimentally infected with haemagglutinating encephalomyelitis virus

text: Abstract Haemagglutinating encephalomyelitis virus (HEV) was inoculated either orally or intranasally into ten 3-day-old gnotobiotic piglets. All infected pigs showed inappetence and listlessness, but there were no clinical signs of nervous disorder. Severe encephalomyelitis, characterized by neuronophagia, focal gliosis and perivascular cuffing, was observed in the brain stem and cerebral cortex. Nasally infected pigs, in particular, developed lesions in the area of the stria olfactoria and tractus olfactorius. Coincident with the encephalitic changes, HEV antigen was observed first in the trigeminal ganglion cells and then in degenerating neurones. Immunoglobulin (IgG and IgM)-containing cells were also found in perivascular cuffs and glial foci. They appeared at first on PID 7 and after that increased in number. These findings suggest that these encephalitic lesions are a specific immune response to HEV following its multiplication in the central nervous system.


title: Open Development and Clinical Validation Of Multiple 3D-Printed Sample-Collection Swabs: Rapid Resolution of a Critical COVID-19 Testing Bottleneck

text: The SARS-CoV-2 pandemic has caused a severe international shortage of the nasopharyngeal swabs that are required for collection of optimal specimens, creating a critical bottleneck in the way of high-sensitivity virological testing for COVID-19. To address this crisis, we designed and executed an innovative, radically cooperative, rapid-response translational-research program that brought together healthcare workers, manufacturers, and scientists to emergently develop and clinically validate new swabs for immediate mass production by 3D printing. We performed a rigorous multi-step preclinical evaluation on 160 swab designs and 48 materials from 24 companies, laboratories, and individuals, and shared results and other feedback via a public data repository (http://github.com/rarnaout/Covidswab/). We validated four prototypes through an institutional review board (IRB)-approved clinical trial that involved 276 outpatient volunteers who presented to our hospital’s drive-through testing center with symptoms suspicious for COVID-19. Each participant was swabbed with a reference swab (the control) and a prototype, and SARS-CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR) results were compared. All prototypes displayed excellent concordance with the control (κ=0.85–0.89). Cycle-threshold (Ct) values were not significantly different between each prototype and the control, supporting the new swabs’ non-inferiority (Mann-Whitney U [MWU] p>0.05). Study staff preferred one of the prototypes over the others and the control swab overall. The total time elapsed between identification of the problem and validation of the first prototype was 22 days. Contact information for ordering can be found at http://printedswabs.org. Our experience holds lessons for the rapid development, validation, and deployment of new technology for this pandemic and beyond.


ISUOG Safety Committee Position Statement on use of personal protective equipment and hazard mitigation in relation to SARS‐CoV‐2 for practitioners undertaking obstetric and gynecological ultrasound


title: Incidental COVID-19 Pneumonia on (18)F-Fluorocholine PET/CT

text: We present the case of a patient who underwent (18)F-fluorocholine PET/CT for biochemical recurrence of prostate cancer in which bilateral pneumonia was diagnosed. In the current state of COVID-19 pandemic, a high prevalence of incidental pneumonia may be expected, even with previous clinical triage, explained by a nondefined number of patients who were asymptomatic or minimally symptomatic for infectious process. Therefore, nuclear medicine physicians should be prepared to recognize and diagnose incidental COVID-19 pneumonia manifestation on (18)F-fluorocholine PET/CT, due to the crucial epidemiological implications.


“A quick glance at selected topics in this issue” aims to highlight contents of the Journal and provide a quick review to the readers.


title: Artificial Intelligence and Echocardiography: A Primer for Cardiac Sonographers

text: Artificial intelligence (AI) is emerging as a key component in diagnostic medical imaging, including echocardiography. AI with deep learning has already been used with automated view labeling, measurements, and interpretation. As the development and use of AI in echocardiography increase, potential concerns may be raised by cardiac sonographers and the profession. This report, from a sonographer's perspective, focuses on defining AI, the basics of the technology, identifying some current applications of AI, and how the use of AI may improve patient care in the future.


title: COVID‐19 & Allogeneic Transplant: Activity and Preventive Measures for Best Outcomes in China

text: The COVID‐19 pandemic poses a great challenge to all aspects of medical activities, including haematopoietic stem cell transplantation (HSCT). To minimize the risk of infection in transplantation, we focused on preventive measures and strict screening in each section of transplantation, involving healthy donors, recipients, caregivers and medical workers. Due to the effective preventive work, our transplantation activity was not interrupted. In our centre, haploidentical donors are preferred over unrelated donors for reducing the uncertainty of COVID‐19 on the provision of stem cells, and graft compositions are advocated as fresh peripheral blood stem cells. We especially promoted telemedicine and avoided unnecessary clinic visits in the regular follow‐up after transplantation. Here, we describe the detailed preventive measures used during the outbreak of COVID‐19 in our centre to provide other countries with experience in transplantation.


title: mTOR inhibition and p53 activation, microRNAs: The possible therapy against pandemic COVID-19

text: mTOR is a serine-threonine kinase and participates in cell proliferation, cellular metabolism was found to be activated during Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection and replication. During viral replication mTOR, downstream target genes such as ribosomal protein S6 kinase beta 1 (S6K1) and Eukaryotic translational initiation factor 4E-binding protein1 (4-E-BP1) are activated result in ribosome biosynthesis and efficient protein synthesis. In plasmacytoid dendritic cells (pDCs), mTOR plays a key role in the association of adapter protein myeloid differentiation primary response gene 88 (MyD88), Toll-like receptor 9 (TLR9) and interferon regulatory factor (IRF-7) leading to the transcriptional activation of type-I interferon (IFN) genes. Viruses also inactivate the interferon α (IFN-α) pathway by impairing the IRF-7 mediated activation of IFN-α gene transcription. Thus, mammalian target of rapamycin (mTOR) inhibitors can help in suppressing the early stages of viral infection and replication. Interestingly, the key tumor-suppressor p53 protein will undergo degradation by virus-encoded E3 ubiquitin ligase Ring-finger and CHY zinc-finger domain-containing 1 (RCHY1) leading to an increased viral survival in host cells. Thus, the mTOR inhibitors and p53 activators or microRNAs that functions as p53 and can target 3′-UTR of mTOR and RPS6KB1 might effectively inhibit viral replication in the human respiratory tract and lung cells.


title: Canine Infectious Respiratory Disease

text: Canine infectious respiratory disease complex (CIRDC) refers to a syndrome of diseases that can be caused by several different bacterial and viral pathogens. These pathogens are often highly contagious, and coinfections are common. Clinical signs are frequently mild and self-limiting; however, some individual cases progress to severe disease. Clinical diagnosis of CIRDC is often based on history of exposure and physical examination findings; however, determining the etiologic agent requires application of specific diagnostic tests, and results can be difficult to interpret because of widespread subclinical infections.


title: A Modern Approach To Traditional Chinese Medicine

text: Abstract Traditional Chinese Medicine (TCM) is consisting of many practices that are common in East Asia. These practices have been around for more than 2000 years. Many of these methods are becoming increasingly popular in the Western world, where they are classified as alternative or complementary medicine. Most of these techniques are untested and some are even considered dangerous in the modern day world, however, they are sometimes able to help, where modern medicine can not. Therefore, it would be wrong to totally reject them. The SINOPOLL project is a joint R&D effort between Thor Medical Systems LLC and their Chinese partner Shenzhen Anke. Its goal is to combine the vast traditional knowledge in TCM with modern day medical system technology. This paper gives an overview of this research, as well, as proposes several possible solutions for common problems in this field.


title: Radiologist Reporting and Operational Management for Patients with Suspected COVID-19

text: Abstract Objective Evaluate adoption and outcomes of locally-designed reporting guidelines for patients with possible COVID-19. Methods We developed a departmental guideline for radiologists that specified reporting terminology and required communication for patients with imaging findings suggestive of COVID-19, based on patient test status and imaging indication. In this retrospective study, radiology reports completed 3/1/2020-5/3/2020 that mentioned COVID-19 were reviewed. Reports were divided into patients with known COVID-19, patients with “suspected” COVID-19 (having an order indication of respiratory or infectious signs or symptoms), and “unsuspected patients” (other order indications, e.g., trauma or non-chest pain). Primary outcome was percentage of COVID-19 reports using recommended terminology; secondary outcome was percentages of suspected and unsuspected patients diagnosed with COVID-19. Relationships between categorical variables were assessed with Fisher’s exact test. Results Among 77,400 total reports, 1,083 suggested COVID-19 based on imaging findings; 774 (71%) of COVID-19 reports used recommended terminology. Of 574 patients without known COVID-19 at time of interpretation, 345 (60%) were eventually diagnosed with COVID-19, including 61% (315/516) of suspected and 52% (30/58) of unsuspected patients. Nearly all (46/58) unsuspected patients were identified at CT. Discussion Radiologists rapidly adopted recommended reporting terminology for patients with suspected COVID-19. The majority of patients for whom radiologists raised concern for COVID-19 were subsequently diagnosed with the disease, including the majority of clinically unsuspected patients. Using unambiguous terminology and timely notification about previously unsuspected patients will become increasingly critical to facilitate COVID-19 testing and contact tracing as states begin to lift restrictions.


title: Schizophrenia: A Pathogenetic Autoimmune Disease Caused by Viruses and Pathogens and Dependent on Genes

text: Many genes have been implicated in schizophrenia as have viral prenatal or adult infections and toxoplasmosis or Lyme disease. Several autoantigens also target key pathology-related proteins. These factors are interrelated. Susceptibility genes encode for proteins homologous to those of the pathogens while the autoantigens are homologous to pathogens' proteins, suggesting that the risk-promoting effects of genes and risk factors are conditional upon each other, and dependent upon protein matching between pathogen and susceptibility gene products. Pathogens' proteins may act as dummy ligands, decoy receptors, or via interactome interference. Many such proteins are immunogenic suggesting that antibody mediated knockdown of multiple schizophrenia gene products could contribute to the disease, explaining the immune activation in the brain and lymphocytes in schizophrenia, and the preponderance of immune-related gene variants in the schizophrenia genome. Schizophrenia may thus be a “pathogenetic” autoimmune disorder, caused by pathogens, genes, and the immune system acting together, and perhaps preventable by pathogen elimination, or curable by the removal of culpable antibodies and antigens.


title: Infectious bronchitis corona virus establishes productive infection in avian macrophages interfering with selected antimicrobial functions

text: Infectious bronchitis virus (IBV) causes respiratory disease leading to loss of egg and meat production in chickens. Although it is known that macrophage numbers are elevated in the respiratory tract of IBV infected chickens, the role played by macrophages in IBV infection, particularly as a target cell for viral replication, is unknown. In this study, first, we investigated the ability of IBV to establish productive replication in macrophages in lungs and trachea in vivo and in macrophage cell cultures in vitro using two pathogenic IBV strains. Using a double immunofluorescent technique, we observed that both IBV Massachusetts-type 41 (M41) and Connecticut A5968 (Conn A5968) strains replicate in avian macrophages at a low level in vivo. This in vivo observation was substantiated by demonstrating IBV antigens in macrophages following in vitro IBV infection. Further, IBV productive infection in macrophages was confirmed by demonstrating corona viral particles in macrophages and IBV ribonucleic acid (RNA) in culture supernatants. Evaluation of the functions of macrophages following infection of macrophages with IBV M41 and Conn A5968 strains revealed that the production of antimicrobial molecule, nitric oxide (NO) is inhibited. It was also noted that replication of IBV M41 and Conn A5968 strains in macrophages does not interfere with the induction of type 1 IFN activity by macrophages. In conclusion, both M41 and Con A5968 IBV strains infect macrophages in vivo and in vitro resulting productive replications. During the replication of IBV in macrophages, their ability to produce NO can be affected without affecting the ability to induce type 1 IFN activity. Further studies are warranted to uncover the significance of macrophage infection of IBV in the pathogenesis of IBV infection in chickens.


title: Cluster of acute hemorrhagic appendicitis among high school students in Wuhan, China

text: Abstract Background Features of a cluster of acute appendicitis that occurred among a high school student population in China were investigated. Methods Epidemiologic data, medical records, and histologic slides of resected appendices were examined. Results During a period between April 10, 1997, and June 11, 1997, 11 cases occurred in a high school, with 10 cases among 290 students enrolled at the time. From the end of the initial cluster until June, 2000, 20 additional cases were encountered. Female cases (6.5%) are more frequent than male cases (1.9%). There was a clustering pattern. Many patients had a history of mutual contact before the onset of symptoms. Pathologically, the resected appendices exhibited diffuse or focal hemorrhages in the lamina propria or within hyperplastic lymphoid follicles, and infiltration by eosinophils and by lymphocytes. Appendical tissues were examined using immunohistochemistry, but no etiologic agent was identified. Conclusions This cluster of acute appendicitis represented a special kind of appendicitis, with features of an infectious disease in epidemiology.


title: Discovery, diversity and evolution of novel coronaviruses sampled from rodents in China

text: Abstract Although rodents are important reservoirs for RNA viruses, to date only one species of rodent coronavirus (CoV) has been identified. Herein, we describe a new CoV, denoted Lucheng Rn rat coronavirus (LRNV), and novel variants of two Betacoronavirus species termed Longquan Aa mouse coronavirus (LAMV) and Longquan Rl rat coronavirus (LRLV), that were identified in a survey of 1465 rodents sampled in China during 2011–2013. Phylogenetic analysis revealed that LAMV and LRLV fell into lineage A of the genus Betacoronavirus, which included CoVs discovered in humans and domestic and wild animals. In contrast, LRNV harbored by Rattus norvegicus formed a distinct lineage within the genus Alphacoronavirus in the 3CLpro, RdRp, and Hel gene trees, but formed a more divergent lineage in the N and S gene trees, indicative of a recombinant origin. Additional recombination events were identified in LRLV. Together, these data suggest that rodents may carry additional unrecognized CoVs.


title: Managing Clinical Risk and Measuring Participants’ Perceptions of the Clinical Research Process

text: Meticulous study design, exacting scientific review, scrupulous data management, rigorous human subjects protection, and effective recruitment strategies are essential components of all clinical research studies that must be in place prior to the conduct of the study. Equally important to the success of the study and to the well-being and protection of study participants is the assurance that safe clinical environments are provided for the care of research participants. This chapter describes approaches to managing clinical care and clinical research quality in clinical research, as well as the application of established health care-based clinical quality methods and tools to the complex processes of clinical research. Techniques for identifying clinical risks, tools for collecting data about the quality of clinical care processes, and strategies for measuring the participants' perceptions of the research process are discussed in detail.


title: Scaling up behavioral science interventions in online education

text: Online education is rapidly expanding in response to rising demand for higher and continuing education, but many online students struggle to achieve their educational goals. Several behavioral science interventions have shown promise in raising student persistence and completion rates in a handful of courses, but evidence of their effectiveness across diverse educational contexts is limited. In this study, we test a set of established interventions over 2.5 y, with one-quarter million students, from nearly every country, across 247 online courses offered by Harvard, the Massachusetts Institute of Technology, and Stanford. We hypothesized that the interventions would produce medium-to-large effects as in prior studies, but this is not supported by our results. Instead, using an iterative scientific process of cyclically preregistering new hypotheses in between waves of data collection, we identified individual, contextual, and temporal conditions under which the interventions benefit students. Self-regulation interventions raised student engagement in the first few weeks but not final completion rates. Value-relevance interventions raised completion rates in developing countries to close the global achievement gap, but only in courses with a global gap. We found minimal evidence that state-of-the-art machine learning methods can forecast the occurrence of a global gap or learn effective individualized intervention policies. Scaling behavioral science interventions across various online learning contexts can reduce their average effectiveness by an order-of-magnitude. However, iterative scientific investigations can uncover what works where for whom.


title: Ecology of zoonoses: natural and unnatural histories

text: Summary More than 60% of human infectious diseases are caused by pathogens shared with wild or domestic animals. Zoonotic disease organisms include those that are endemic in human populations or enzootic in animal populations with frequent cross-species transmission to people. Some of these diseases have only emerged recently. Together, these organisms are responsible for a substantial burden of disease, with endemic and enzootic zoonoses causing about a billion cases of illness in people and millions of deaths every year. Emerging zoonoses are a growing threat to global health and have caused hundreds of billions of US dollars of economic damage in the past 20 years. We aimed to review how zoonotic diseases result from natural pathogen ecology, and how other circumstances, such as animal production, extraction of natural resources, and antimicrobial application change the dynamics of disease exposure to human beings. In view of present anthropogenic trends, a more effective approach to zoonotic disease prevention and control will require a broad view of medicine that emphasises evidence-based decision making and integrates ecological and evolutionary principles of animal, human, and environmental factors. This broad view is essential for the successful development of policies and practices that reduce probability of future zoonotic emergence, targeted surveillance and strategic prevention, and engagement of partners outside the medical community to help improve health outcomes and reduce disease threats.


title: Combination Kinase Inhibitor Treatment Suppresses Rift Valley Fever Virus Replication

text: Viruses must parasitize host cell translational machinery in order to make proteins for viral progeny. In this study, we sought to use this signal transduction conduit against them by inhibiting multiple kinases that influence translation. Previous work indicated that several kinases involved in translation, including p70 S6K, p90RSK, ERK, and p38 MAPK, are phosphorylated following Rift Valley fever virus (RVFV) infection. Furthermore, inhibiting p70 S6K through treatment with the FDA approved drug rapamycin prevents RVFV pathogenesis in a mouse model of infection. We hypothesized that inhibiting either p70 S6K, p90RSK, or p90RSK’s upstream kinases, ERK and p38 MAPK, would decrease translation and subsequent viral replication. Treatment with the p70 S6K inhibitor PF-4708671 resulted in decreased phosphorylation of translational proteins and reduced RVFV titers. In contrast, treatment with the p90RSK inhibitor BI-D1870, p38MAPK inhibitor SB203580, or the ERK inhibitor PD0325901 alone had minimal influence on RVFV titers. The combination of PF-4708671 and BI-D1870 treatment resulted in robust inhibition of RVFV replication. Likewise, a synergistic inhibition of RVFV replication was observed with p38MAPK inhibitor SB203580 or the ERK inhibitor PD0325901 combined with rapamycin treatment. These findings serve as a proof of concept regarding combination kinase inhibitor treatment for RVFV infection.


title: Analysis of the mitigation strategies for COVID-19: from mathematical modelling perspective

text: In this article, a mathematical model for the transmission of COVID-19 disease is formulated and analysed. It is shown that the model exhibits a backward bifurcation at [Formula: see text] when recovered individuals do not develop a permanent immunity for the disease. In the absence of reinfection, it is proved that the model is without backward bifurcation and the disease free equilibrium is globally asymptotically stable for [Formula: see text]. By using available data, the model is validated and parameter values are estimated. The sensitivity of the value of [Formula: see text] to changes in any of the parameter values involved in its formula is analysed. Moreover, various mitigation strategies are investigated using the proposed model and it is observed that the asymptomatic infectious group of individuals may play the major role in the re-emergence of the disease in the future. Therefore, it is recommended that in the absence of vaccination, countries need to develop capacities to detect and isolate at least 30% of the asymptomatic infectious group of individuals while treating in isolation at least 50% of symptomatic patients to control the disease.


title: Update on SARS research and other possibly zoonotic coronaviruses

text: Abstract The global outbreak of severe acute respiratory syndrome (SARS) in 2003 led to an intense and effective global response that stopped the spread of the disease by July 2003. There was also an intensive and very productive research effort to identify the aetiological agent, characterise the clinical and epidemiological features of the disease, understand the pathogenesis of the disease and the molecular biology of the virus, and design antiviral drugs and vaccines to treat and prevent the disease. In parallel with the SARS research effort there have been continuous improvements in our ability to detect and characterise other novel viruses. The SARS outbreak illustrates the importance of such detection tools in the response to public health threats. Studies since the SARS outbreak suggest that many novel viruses exist in animals and some, but probably not many, will present a risk to humans.


title: Adiponectin Stimulates Exosome Release to Enhance Mesenchymal Stem-Cell-Driven Therapy of Heart Failure in Mice

text: Mesenchymal stem/stromal cells (MSCs) are cultured adult stem cells that originally reside in virtually all tissues, and the gain of MSCs by transplantation has become the leading form of cell therapy in various diseases. However, there is limited knowledge on the alteration of its efficacy by factors in recipients. Here, we report that the cardioprotective properties of intravenously injected MSCs in a mouse model of pressure-overload heart failure largely depend on circulating adiponectin, an adipocyte-secreted factor. The injected MSCs exert their function through exosomes, extracellular vesicles of endosome origin. Adiponectin stimulated exosome biogenesis and secretion through binding to T-cadherin, a unique glycosylphosphatidylinositol-anchored cadherin, on MSCs. A pharmacological or adenovirus-mediated genetic increase in plasma adiponectin enhanced the therapeutic efficacy of MSCs. Our findings provide novel insights into the importance of adiponectin in mesenchymal-progenitor-mediated organ protections.


title: Molecular diversity of coronaviruses in bats

text: Abstract The existence of coronaviruses in bats is unknown until the recent discovery of bat-SARS-CoV in Chinese horseshoe bats and a novel group 1 coronavirus in other bat species. Among 309 bats of 13 species captured from 20 different locations in rural areas of Hong Kong over a 16-month period, coronaviruses were amplified from anal swabs of 37 (12%) bats by RT-PCR. Phylogenetic analysis of RNA-dependent-RNA-polymerase (pol) and helicase genes revealed six novel coronaviruses from six different bat species, in addition to the two previously described coronaviruses. Among the six novel coronaviruses, four were group 1 coronaviruses (bat-CoV HKU2 from Chinese horseshoe bat, bat-CoV HKU6 from rickett's big-footed bat, bat-CoV HKU7 from greater bent-winged bat and bat-CoV HKU8 from lesser bent-winged bat) and two were group 2 coronaviruses (bat-CoV HKU4 from lesser bamboo bats and bat-CoV HKU5 from Japanese pipistrelles). An astonishing diversity of coronaviruses was observed in bats.


title: Innovative approach for improved rFVIII concentrate

text: The development of a new recombinant factor VIII was designed and implemented to answer a number of unmet needs of patients affected by hemophilia A. Turoctocog alfa is bioengineered in a specific Chinese hamster ovary clone to present translational and posttranslational characteristics (sulphation, glycosylation) biosimilar to natural circulating forms of FVIII, with the aim to devoid any minimal change which may impact immunogenicity and antigenicity of recombinant protein. Both producer cell line and media are maintained free of any animal or human plasma derivative. Downstream processes of purification are performed by five steps (immunoaffinity chromatography, ion‐exchange chromatography, virus inactivation by means of solvent‐detergent treatment and nanofiltration, and to end with gel filtration), to provide the best possible margin of safety from known and unknown infectious agents. Large clinical trials seem to confirm the expectations placed in Turoctocog alfa in terms of high quality and safety of recombinant FVIII toward the goal of overcoming actual and future challenges of hemophilia therapy.


title: The cytoplasmic tails of infectious bronchitis virus E and M proteins mediate their interaction

text: Abstract Virus-like particle (VLP) formation by the coronavirus E and M proteins suggests that interactions between these proteins play a critical role in coronavirus assembly. We studied interactions between the infectious bronchitis virus (IBV) E and M proteins using in vivo crosslinking and VLP assembly assays. We show that IBV E and M can be crosslinked to each other in IBV-infected and transfected cells, indicating that they interact. The cytoplasmic tails of both proteins are important for this interaction. We also examined the ability of the mutant and chimeric E and M proteins to form VLPs. IBV M proteins that are missing portions of their cytoplasmic tails or transmembrane regions were not able to support VLP formation, regardless of their ability to be crosslinked to IBV E. Interactions between the E and M proteins and the membrane bilayer are likely to play an important role in VLP formation and virus budding.


title: The Post-COVID-19 Functional Status (PCFS) Scale: a tool to measure functional status over time after COVID-19

text: We propose an ordinal tool to measure the full spectrum of functional outcomes following COVID-19. This “Post-COVID-19 Functional Status (PCFS) Scale” can be used for tracking functional status over time as well as for research purposes.


title: High‐resolution structure of HLA‐A*1101 in complex with SARS nucleocapsid peptide

text: The structure of the human MHC‐I molecule HLA‐A*1101 in complex with a nonameric peptide (KTFPPTEPK) has been determined by X‐ray crystallography to 1.45 Å resolution. The peptide is derived from the SARS‐CoV nucleocapsid protein positions 362–370 (SNP(362–370)). It is conserved in all known isolates of SARS‐CoV and has been verified by in vitro peptide‐binding studies to be a good to intermediate binder to HLA‐A*0301 and HLA‐A*1101, with IC(50) values of 70 and 186 nM, respectively [Sylvester‐Hvid et al. (2004), Tissue Antigens, 63, 395–400]. In terms of the residues lining the peptide‐binding groove, the HLA‐A*1101–SNP(362–370) complex is very similar to other known structures of HLA‐A*1101 and HLA‐A*6801. The SNP(362–370) peptide is held in place by 17 hydrogen bonds to the α‐chain residues and by nine water molecules which are also tightly bound in the peptide‐binding groove. Thr6 of the peptide (Thr6p) does not make efficient use of the middle (E) pocket. For vaccine development, there seems to be a potential for optimization targeted at this position. All residues except Thr2p and Lys9p are accessible for T‐cell recognition.


title: Impact of 2013 south Asian haze crisis: study of physical and psychological symptoms and perceived dangerousness of pollution level

text: BACKGROUND: The widespread forest fires in Indonesia in June 2013 led to widespread haze to neighbouring countries. This is the first study in the medical literature reporting the acute physical and psychological symptoms of the general population during a haze crisis. We evaluated the factors that are associated with psychological stress of haze exposure. METHODS: This study was conducted between June 21 to June 26, 2013. Participants were recruited by an online recruitment post and snowball sampling techniques. Participants were required to complete an online survey which was composed of demographics questionnaire, physical symptom checklist, perceived dangerous Pollutant Standard Index (PSI) value and views on the N-95 mask and the Impact of Event Scale-Revised (IES-R). RESULTS: A total of 298 participants returned the completed study questionnaire. The respondents reported a mean number of 4.03 physical symptoms (S.D. = 2.6). The five most common physical symptoms include mouth or throat discomfort (68.8%), nose discomfort (64.1%), eye discomfort (60.7%), headache (50.3%) and breathing difficulty (40.3%). The total IES-R score was 18.47 (S.D. = 11.69) which indicated that the study population experienced mild psychological stress but not to the extent of acute stress reaction syndrome. The perceived dangerous PSI level and number of physical symptoms were significantly associated with the mean intrusion score, mean hyper-arousal score, total mean IES-R score and total IES-R score (p < 0.05). CONCLUSIONS: Our findings suggest that a haze crisis is associated with acute physical symptoms and mild psychological stress. The number of physical symptoms and the perceived dangerous PSI values are important factors associated with psychological stress.


title: Vaccine development and therapeutic design for 2019‐nCoV/SARS‐CoV‐2: Challenges and chances

text: The ongoing outbreak of the recently emerged 2019 novel coronavirus (nCoV), which has seriously threatened global health security, is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) with high morbidity and mortality. Despite the burden of the disease worldwide, still, no licensed vaccine or any specific drug against 2019‐nCoV is available. Data from several countries show that few repurposed drugs using existing antiviral drugs have not (so far) been satisfactory and more recently were proven to be even highly toxic. These findings underline an urgent need for preventative and therapeutic interventions designed to target specific aspects of 2019‐nCoV. Again the major factor in this urgency is that the process of data acquisition by physical experiment is time‐consuming and expensive to obtain. Scientific simulations and more in‐depth data analysis permit to validate or refute drug repurposing opportunities predicted via target similarity profiling to speed up the development of a new more effective anti‐2019‐nCoV therapy especially where in vitro and/or in vivo data are not yet available. In addition, several research programs are being developed, aiming at the exploration of vaccines to prevent and treat the 2019‐nCoV. Computational‐based technology has given us the tools to explore and identify potentially effective drug and/or vaccine candidates which can effectively shorten the time and reduce the operating cost. The aim of the present review is to address the available information on molecular determinants in disease pathobiology modules and define the computational approaches employed in systematic drug repositioning and vaccine development settings for SARS‐CoV‐2.


title: The 2020 coronavirus lockdown and seismic monitoring of anthropic activities in Northern Italy

text: In March/April 2020 the Italian government drastically reduced vehicle traffic and interrupted all non-essential industrial activities over the entire national territory. Italy thus became the first country in the world, with the exception of Hubei, to enact lockdown measures as a consequence of the COVID-19 outbreak and the need to contain it. Italy is also a seismically active area, and as such is monitored by a dense permanent network of seismic stations. We analyse continuous seismic data from many stations in northern and central Italy, and quantify the impact of the lockdown on seismic ambient noise, as a function of time and location. We find that the lockdown reduces ambient noise significantly in the 1–10 Hz frequency range; because natural sources of seismic noise are not affected by the lockdown, the seismic signature of anthropic noise can be characterised with unprecedented clarity, by simply comparing the signal recorded before and after the lockdown. Our results correlate well with independent evaluations of the impact of the lockdown (e.g., cell phone displacements), and we submit that ambient-noise seismology is a useful tool to monitor containment measures such as the coronavirus lockdowns.


title: Influenza and other emerging respiratory viruses

text: Acute respiratory infections are one of the top five causes of mortality worldwide and contribute to >4 million deaths per year. Consequently, emerging respiratory viruses are a continuing threat to global health security and have the potential to affect our economies. Since the millennium, there have been around a dozen different outbreaks, several capturing international interest. The outbreak of severe acute respiratory syndrome coronavirus saw the beginning of an extensive global collaboration and has influenced many outbreak preparedness protocols now in place. Avian influenza is a particular threat, with cases of A(H5N1) and A(H7N9) reported most recently. Middle East respiratory syndrome coronavirus is causing continuing concerns with outbreaks in the Arabian Peninsula. Healthcare facilities worldwide play a crucial role in identifying threats and must be vigilant. Particularly important is identifying and managing emerging respiratory viruses when they are infrequently encountered. Surveillance, continuing research, vaccine and treatment developments are key to guiding the efforts and actions of healthcare workers, international health organizations, governments and other stakeholders. Each individual has a part to play in protecting our global health.


title: Characterization of DNA hybridization kinetics in a microfluidic flow channel

text: Abstract In this investigation we report on the influence of volumetric flow rate, flow velocity, complementary DNA concentration, height of a microfluidic flow channel and time on DNA hybridization kinetics. A syringe pump was used to drive Cy3-labeled target DNA through a polydimethylsiloxane (PDMS) microfluidic flow channel to hybridize with immobilized DNA from the West Nile Virus. We demonstrate that a reduction of channel height, while keeping a fixed volumetric flow rate or a fixed flow velocity, enhances mass transport of target DNA to the capture probes. Compared to a passive hybridization, the DNA hybridization in the microfluidic flow channel generates higher fluorescence intensities for lower concentration of target DNA during the same fixed period of time. Within a fixed 2min time period the fastest DNA hybridization at a 50pM concentration of target DNA is achieved with a continuous flow of target DNA at the highest flow rate and the lowest channel height.


title: Novel Circovirus from Mink, China

text: A long-established epidemic of enteritis, caused by an unidentified pathogen distinct from parvovirus, has now been recognized in mink. In 2013, we identified a novel circovirus by degenerate PCR and fully sequenced its genome. This virus differs substantially from currently known members of the genus Circovirus and represents a new species.


COVID-19 y Argumentum ad ignorantiam o «no todo vale»


title: Collectins: Innate Immune Pattern Recognition Molecules

text: Collectins are collagen-containing C-type (calcium-dependent) lectins which are important pathogen pattern recognising innate immune molecules. Their primary structure is characterised by an N-terminal, triple-helical collagenous region made up of Gly-X-Y repeats, an a-helical coiled-coil trimerising neck region, and a C-terminal C-type lectin or carbohydrate recognition domain (CRD). Further oligomerisation of this primary structure can give rise to more complex and multimeric structures that can be seen under electron microscope. Collectins can be found in serum as well as in a range of tissues at the mucosal surfaces. Mannanbinding lectin can activate the complement system while other members of the collectin family are extremely versatile in recognising a diverse range of pathogens via their CRDs and bring about effector functions designed at the clearance of invading pathogens. These mechanisms include opsonisation, enhancement of phagocytosis, triggering superoxidative burst and nitric oxide production. Collectins can also potentiate the adaptive immune response via antigen presenting cells such as macrophages and dendritic cells through modulation of cytokines and chemokines, thus they can act as a link between innate and adaptive immunity. This chapter describes the structure-function relationships of collectins, their diverse functions, and their interaction with viruses, bacteria, fungi and parasites.


title: Advax augments B and T cell responses upon influenza vaccination via the respiratory tract and enables complete protection of mice against lethal influenza virus challenge

text: Abstract Administration of influenza vaccines via the respiratory tract has potential benefits over conventional parenteral administration, inducing immunity directly at the site of influenza exposure as well as being needle free. In this study, we investigated the suitability of Advax™, a stable particulate polymorph of inulin, also referred to as delta inulin, as a mucosal adjuvant for whole inactivated influenza vaccine (WIV) administered either as a liquid or dry powder formulation. Spray freeze-drying produced Advax-adjuvanted WIV powder particles in a size range (1–5 μm) suitable for inhalation. The physical and biological characteristics of both WIV and Advax remained unaltered both by admixing WIV with Advax and by spray freeze drying. Upon intranasal or pulmonary immunization, both liquid and dry powder formulations containing Advax induced significantly higher systemic, mucosal and cellular immune responses than non-adjuvanted WIV formulations. Furthermore, pulmonary immunization with Advax-adjuvanted WIV led to robust memory B cell responses along with an increase of lung localization factors i.e. CXCR3, CD69, and CD103. A less pronounced but still positive effect of Advax was seen on memory T cell responses. In contrast to animals immunized with WIV alone, all animals pulmonary immunized with a single dose of Advax-adjuvanted WIV were fully protected with no visible clinical symptoms against a lethal dose of influenza virus. These data confirm that Advax is a potent mucosal adjuvant that boosts vaccine-induced humoral and cellular immune responses both in the lung and systemically with major positive effects on B-cell memory and complete protection against live virus. Hence, respiratory tract immunization, particularly via the lungs, with Advax-adjuvanted WIV formulation as a liquid or dry powder is a promising alternative to parenteral influenza vaccination.


title: PPE shortages leaving staff at risk and urgent care system in jeopardy

text: A poll by the BDA of dentists staffing the emerging network of Urgent Dental Care centres suggests a third of sites in England remain inactive, with more than half reporting that their operational status is being impacted by a lack of Personal Protective Equipment (PPE)


title: Leveraging Lifestyle Medicine Interest Groups Through the COVID-19 Pandemic

text: Lifestyle medicine domains, despite accounting for more than 78% of chronic disease risk, are infrequently taught as a part of the medical curriculum. Aspects such as nutrition are taught in less than 25% of medical schools, a statistic that continues to decline, and less than 20% of practicing physicians were required to take even a single course in exercise counseling during their medical school training. To combat this lack of training, the American College of Lifestyle Medicine annually awards the Donald A. Pegg scholarship to fund the development of Lifestyle Medicine Interest Groups (LMIGs) across medical schools worldwide. This scholarship was initiated in 2016 and utilizes private funds to support the development and expansion of LMIGs with the aim of increasing awareness of lifestyle medicine among training practitioners. There are four award winners per year. To date there are sixteen Pegg Award winners. This article will showcase the four 2019-2020 Donald A. Pegg award recipients and their impact on the LMIGs at their institutions. Furthermore, it highlights the ingenuity and adaptation of these LMIGs during the COVID-19 pandemic.


title: Preparative purification of glycyrrhizin extracted from the root of liquorice using high-speed counter-current chromatography

text: Abstract Glycyrrhizin is one of the main bioactive components in liquorice (Glycyrrhiza uralensis Fisch) which has recently been found to be highly active in inhibiting replication of the severe acute respiratory syndrome (SARS)-associated virus. The separation and purification of glycyrrhizin from a methanol–water (70:30 (v/v)) extract of liquorice roots was achieved using high-speed counter-current chromatography. The separation was performed at a preparative scale in a one-step separation with a two-phase solvent system composed of ethyl acetate–methanol–water (5:2:5 (v/v)). The lower phase was used as the mobile phase in the head-to-tail elution mode. The present method yielded 42.2mg glycyrrhizin at 96.8% purity from 130mg of the crude exact with 95.2% recovery as determined by HPLC analysis.


title: Mechanism of Inhibition of Enveloped Virus Membrane Fusion by the Antiviral Drug Arbidol

text: The broad-spectrum antiviral arbidol (Arb) inhibits cell entry of enveloped viruses by blocking viral fusion with host cell membrane. To better understand Arb mechanism of action, we investigated its interactions with phospholipids and membrane peptides. We demonstrate that Arb associates with phospholipids in the micromolar range. NMR reveals that Arb interacts with the polar head-group of phospholipid at the membrane interface. Fluorescence studies of interactions between Arb and either tryptophan derivatives or membrane peptides reconstituted into liposomes show that Arb interacts with tryptophan in the micromolar range. Interestingly, apparent binding affinities between lipids and tryptophan residues are comparable with those of Arb IC50 of the hepatitis C virus (HCV) membrane fusion. Since tryptophan residues of membrane proteins are known to bind preferentially at the membrane interface, these data suggest that Arb could increase the strength of virus glycoprotein's interactions with the membrane, due to a dual binding mode involving aromatic residues and phospholipids. The resulting complexation would inhibit the expected viral glycoprotein conformational changes required during the fusion process. Our findings pave the way towards the design of new drugs exhibiting Arb-like interfacial membrane binding properties to inhibit early steps of virus entry, i.e., attractive targets to combat viral infection.


title: Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19

text: Abstract Background Several studies have described the clinical characteristics of patients with novel coronavirus (SARS-CoV-2) infected pneumonia (COVID-19), indicating severe patients tended to have higher neutrophil to lymphocyte ratio (NLR). Whether baseline NLR could be an independent predictor of in-hospital death in Chinese COVID-19 patients remains to be investigated. Methods A cohort of patients with COVID-19 admitted to the Zhongnan Hospital of Wuhan University from January 1 to February 29 was retrospectively analyzed. The baseline data of laboratory examinations, including NLR, were collected. Univariate and multivariate logistic regression models were developed to assess the independent relationship between the baseline NLR and in-hospital all-cause death. A sensitivity analysis was performed by converting NLR from a continuous variable to a categorical variable according to tertile. Interaction and stratified analyses were conducted as well. Results 245 COVID-19 patients were included in the final analyses, and the in-hospital mortality was 13.47%. Multivariate analysis demonstrated that there was 8% higher risk of in-hospital mortality for each unit increase in NLR (Odds ratio [OR] = 1.08; 95% confidence interval [95% CI], 1.01 to 1.14; P = 0.0147). Compared with patients in the lowest tertile, the NLR of patients in the highest tertile had a 15.04-fold higher risk of death (OR = 16.04; 95% CI, 1.14 to 224.95; P = 0.0395) after adjustment for potential confounders. Notably, the fully adjusted OR for mortality was 1.10 in males for each unit increase of NLR (OR = 1.10; 95% CI, 1.02 to 1.19; P = 0.016). Conclusions NLR is an independent risk factor of the in-hospital mortality for COVID-19 patients especially for male. Assessment of NLR may help identify high risk individuals with COVID-19.


title: Haddon Matrix for Kidney Transplantation during COVID‐19 Pandemic: A Problem Solving Framework for Present and Future

text: Novel coronavirus disease 2019 (COVID‐19) pandemic is a public health emergency with several million worldwide and a quarter of a million and soon half a million deaths including a third in the United States alone (as of May 10, 2020).(1) It affects kidney transplantation and has caused mortality in waitlist dialysis and transplant patients.(2,3) This inevitably raises questions about the practicality and direction of transplant surgeries during this critical period.


title: Reverse Transcription Recombinase Polymerase Amplification Assay for the Detection of Middle East Respiratory Syndrome Coronavirus

text: The emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the eastern Mediterranean and imported cases to Europe has alerted public health authorities. Currently, detection of MERS-CoV in patient samples is done by real-time RT-PCR. Samples collected from suspected cases are sent to highly-equipped centralized laboratories for screening. A rapid point-of-care test is needed to allow more widespread mobile detection of the virus directly from patient material. In this study, we describe the development of a reverse transcription isothermal Recombinase Polymerase Amplification (RT-RPA) assay for the identification of MERS-CoV. A partial nucleocapsid gene RNA molecular standard of MERS-coronavirus was used to determine the assay sensitivity. The isothermal (42°C) MERS-CoV RT-RPA was as sensitive as real-time RT-PCR (10 RNA molecules), rapid (3-7 minutes) and mobile (using tubescanner weighing 1kg). The MERS-CoV RT-RPA showed cross-detection neither of any of the RNAs of several coronaviruses and respiratory viruses affecting humans nor of the human genome. The developed isothermal real-time RT-RPA is ideal for rapid mobile molecular MERS-CoV monitoring in acute patients and may also facilitate the search for the animal reservoir of MERS-CoV.


title: Clinical Features of COVID-19-Related Liver Damage

text: Abstract Background & Aims Some patients with SARS-CoV-2 infection have abnormal liver function. We aimed to clarify the features of COVID-19-related liver damage to provide references for clinical treatment. Methods We performed a retrospective, single-center study of 148 consecutive patients with confirmed COVID-19 (73 female, 75 male; mean age, 50 years) at the Shanghai Public Health Clinical Center from January 20 through January 31, 2020. Patient outcomes were followed until February 19, 2020. Patients were analyzed for clinical features, laboratory parameters (including liver function tests), medications, and length of hospital stay. Abnormal liver function was defined as increased levels of alanine and aspartate aminotransferase, gamma glutamyltransferase, alkaline phosphatase, and total bilirubin. Results Fifty-five patients (37.2%) had abnormal liver function at hospital admission; 14.5% of these patients had high fever (14.5%), compared with 4.3% of patients with normal liver function (P=.027). Patients with abnormal liver function were more likely to be male, and had higher levels of procalcitonin and C-reactive protein. There was no statistical difference between groups in medications taken before hospitalization; a significantly higher proportion of patients with abnormal liver function (57.8%) had received lopinavir/ritonavir after admission compared to patients with normal liver function (31.3%). Patients with abnormal liver function had longer mean hospital stays (15.09±4.79 days) than patients with normal liver function (12.76±4.14 days) (P=.021). Conclusions More than one third of patients admitted to the hospital with SARS-CoV-2 infection have abnormal liver function, and this is associated with longer hospital stay. A significantly higher proportion of patients with abnormal liver function had received lopinavir/ritonavir after admission; these drugs should be given with caution.


title: Antibodies on demand: a fast method for the production of human scFvs with minimal amounts of antigen

text: BACKGROUND: Antibodies constitute a powerful tool to study protein function, protein localization and protein-protein interactions, as well as for diagnostic and therapeutic purposes. High-throughput antibody development requires faster methodologies with lower antigen consumption. RESULTS: Here, we describe a novel methodology to select human monoclonal recombinant antibodies by combining in vitro protein expression, phage display antibody libraries and antibody microarrays. The application of this combination of methodologies permitted us to generate human single-chain variable fragments (scFvs) against two proteins: green fluorescent protein (GFP) and thioredoxin (Trx) in a short time, using as low as 5 μg of purified protein. These scFvs showed specific reactivity against their respective targets and worked well by ELISA and western blot. The scFvs were able to recognise as low as 31 ng of protein of their respective targets by western blot. CONCLUSION: This work describes a novel and miniaturized methodology to obtain human monoclonal recombinant antibodies against any target in a shorter time than other methodologies using only 5 μg of protein. The protocol could be easily adapted to a high-throughput procedure for antibody production.


title: Role of Pharmacists in Responding to Humanitarian Crisis

text: Abstract Medical and pharmaceutical responses are crucial for saving precious lives during any humanitarian crisis. These responses include provision of both supplies as well as skilled human resource. Increasing number of humanitarian crisis situations are happening due to natural (owing to global warming, climatic change, and natural geographic processes) as well as global sociopolitical scenario with rising number of unresolved conflicts, economic turmoils, and international disputes. Hence, health professional's response to humanitarian crisis have evolved as a permanent feature of the global health-care scene. Pharmacists as the essential member of health care team, are incorporated in the health system network globally, also including their presence in the emergency conditions. The role of pharmacist is transforming globally to patient-centered approach. Similarly, in emergency medicine, pharmacists have not only struggled to advance their role in the logistic management but also focussed on rationality and safety, in accordance with the needs of the population.


title: Chapter 13 Recent Advances and Future Needs in Environmental Virology

text: Publisher Summary The detection of viruses in water and other environmental samples constitutes special challenges. The standard method of detection of viral pathogens in environmental samples uses assays in mammalian cell culture. The infected cell cultures undergo observable morphological changes called cytopathogenic effects (CPEs) that are used for the detection of viruses. Even though many viruses are culturable in several cell lines and are thus detectable by the development of CPEs in cell culture, there are several viruses, like enteric waterborne adenoviruses types 40 and 41, which are difficult to culture and do not produce clear and consistent CPE. Other viruses, like waterborne caliciviruses, have not yet been successfully grown in cell cultures. Conventional cell culture assays for the detection of viruses in environmental samples have limited sensitivity and can be labor-intensive and timeconsuming. Two advances, the PCR and microarrays, have spurred the study of viruses and should be further applied to the field of environmental virology. The ability of both DNA viruses and RNA viruses to rapidly evolve means new and emerging viral pathogens will need to be addressed. Pathogen discovery and characterization, occurrence in the environment, exposure pathways, and health outcomes via environmental exposure need to be addressed. This will likely follow a new microbial risk framework that will require focused research on some important properties of viral disease transmission. The future will require models that examine community risks and provide explicit links between the models currently under development for environmental exposure and infectious disease.


title: Coronavirus HKU1 Infection in the United States

text: In 2005, a new human coronavirus, HCoV-HKU1, was identified in Hong Kong. We screened respiratory specimens collected from December 16, 2001, to December 15, 2002, from children <5 years of age who tested negative for respiratory syncytial virus, parainfluenza viruses, influenza virus, and adenovirus for HCoV-HKU1 by reverse transcription–polymerase chain reaction. Overall, 1,048 respiratory specimens from 851 children were tested, and 9 HCoV-HKU1–positive children (1%) were identified, 2 of whom had 2 positive specimens. Children who had HCoV-HKU1 infection had evidence of either upper or lower respiratory tract infection or both. Two patients had disease beyond the respiratory tract. HCoV-HKU1 was identified from December 2001 to February 2002. Sequence analyses suggest that a single strain was circulating. HCoV-HKU1 is therefore likely circulating in the United States and is associated with upper and lower respiratory tract disease.


title: Diabetes Mellitus, Hypertension, and Death among 32 Patients with MERS-CoV Infection, Saudi Arabia

text: Diabetes mellitus and hypertension are recognized risk factors for severe clinical outcomes, including death, associated with Middle East respiratory syndrome coronavirus infection. Among 32 virus-infected patients in Saudi Arabia, severity of illness and frequency of death corresponded closely with presence of multiple and more severe underlying conditions.


title: Physiological Outcomes of an Internet Disease Management Program vs. In-person Counselling:A Randomized, Controlled Trial

text: ABSTRACT OBJECTIVE To compare physiological outcomes and satisfaction for followup care between an interactive diabetes internet program and Diabetes Education Centres. METHOD A randomized, controlled trial with outcomes of glycosylated hemoglobin (A1C), fasting blood glucose, total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol, lowdensity lipoprotein cholesterol and patient satisfaction. Enrollment was staggered, with individuals assessed at baseline, 3, 6 and 12 months. RESULTS Fifty-seven participants completed the study (20 control, 37 internet). Physiological outcomes were not statistically different between the 2 groups. However, within-group comparisons demonstrated a significant improvement in the internet group's A1C, TG and satisfaction levels from baseline to 3 and 6 months (p<0.0452, p<0.0428 and p<0.0138, respectively). CONCLUSION Although the trial was limited in sample size, it yielded significant findings for diabetes management, within group. Further research in using the internet program in other applications for diabetes management is needed.


title: Detection of central nervous system viral infections in adults in Manado, North Sulawesi, Indonesia

text: Central nervous system (CNS) viral infections are important causes of morbidity and mortality worldwide but the systematic survey of patients admitted to hospitals with CNS infections in many countries, including Indonesia, is limited. To obtain more information regarding the causes of CNS infections in Indonesia, this study was performed to detect and identify viral agents associated with CNS infections amongst in-patients at a referral hospital in Manado, North Sulawesi, Indonesia. Adult patients admitted to R.D. Kandou General Hospital with presumed CNS infection were enrolled. Cerebrospinal fluid, serum, and throat swab samples were collected and tested using molecular, serological, and virus isolation assays. A confirmed viral etiology was established in three and a probable/possible in 11 out of 74 patients. The most common was herpes simplex virus 1 (7/74, 9.5%), followed by Epstein-Barr virus (2/74, 2.7%), cytomegalovirus (1/74, 1.4%), enterovirus D68 (1/74, 1.4%), rhinovirus A (1/74, 1.4%), dengue virus (1/64, 1.6%), and Japanese encephalitis virus (1/64, 1.6%). There were 20 fatal cases (27.0%) during hospitalization in which eight were associated with viral causes. We identified herpes simplex virus 1 as the most common cause of CNS infection among adults in North Sulawesi with most of the cases remaining undiagnosed. Our study highlights the challenges in establishing the etiology of viral CNS infections and the importance of using a wide range of molecular and serological detection methods to identify CNS viruses.