title: The significance of aminopeptidases and haematopoietic cell differentiation

text: Abstract Aminopeptidases are a group of enzymes found on the cell surface and in the cytoplasmic compartments of many peripheral blood cell types and their progenitors. Their functional roles include the hydrolysis of several biologically active peptides and growth factors and some have proved to be of diagnostic and prognostic value in leukaemia. These enzymes may also be found in serum as a consequence of non-haematopoietic related diseases and so have been used as indicators of liver damage. Haematopoietic cells in the bone marrow go through a process of growth and differentiation before being released into the peripheral circulation where they fulfill many functional roles. The enzyme activities of some aminopeptidases have been shown to modulate the growth of these cells. In addition, the activities of these enzymes themselves can be regulated by haematopoietic growth factors. However, the mechanisms that regulate their expression and activity are not fully understood. In this report the current literature has been reviewed for evidence of expression, regulation and clinical significance.


title: Seeking Membranes: Positive-Strand RNA Virus Replication Complexes

text: How much do we really understand about how +RNA viruses usurp and transform the intracellular architecture of host cells when they replicate?


title: Increased dispersion and solubility of carbon nanotubes noncovalently modified by the polysaccharide biopolymer, chitosan: MD simulations

text: In order to explain the solubility of carbon nanotubes (CNT), including single walled CNTs, wrapped with chitosan of a 60% degree of deacetylation, MD simulations were applied to represent three chitosan concentrations, using two pristine CNTs (pCNT–pCNT), and one and two CNTs wrapped (pCNT–cwCNT and cwCNT–cwCNT). The CNT aggregation was observed in pCNT–pCNT and pCNT–cwCNT due to van der Waals interactions between tube–tube aromatic rings, and inter-CNT bridging by chitosan, respectively. At higher chitosan concentrations, such that most to all of CNTs were wrapped with chitosan, charge–charge repulsion was found to separate robustly the cwCNTs and lead to a well dispersed solution.


title: Fish Viruses

text: Viral pathogens impact both wild and farmed fish. In some cases, outbreaks of these diseases in populations of fish can lead to the near extinction of a particular race of sockeye salmon or such severe losses as to put commercial aquaculture ventures out of business. The importance of fish viruses to the aquaculture industry has increased the number of reported new virus isolations and the host range of previously characterized viruses. Currently, the fish viruses are represented in 14 of the families listed for vertebrate viruses by the International Committee on the Taxonomy of Viruses. The fish viruses containing DNA genomes are listed in the families Iridoviridae, Adenoviridae, and Herpesvirdae and those with RNA genomes are listed in the families Picornaviridae, Birnaviridae, Reoviridae, Rhabdoviridae, Orthomyxoviridae, Paramyxoviridae, Caliciviridae, Togaviridae, Nodaviridae, Retroviridae, and Coronaviridae. Many of these viruses have grown optimally at the temperature of the host (8–15 °C). A few of the viruses can cross the species barrier and infect other fish species, cattle, pigs, and humans. As the need of aquacultured fish grows and the industry brings into culture more diverse species of fish, it is likely that there will be new virus isolations and some will be subsequently classified as new genera or even families.


title: Chronic viral infections of the central nervous system: Aspects specific to multiple sclerosis

text: Abstract The involvement of a viral infection in the physiopathology of multiple sclerosis has been said to cause certain viruses to target the central nervous system and induce neuroinflammation leading to cell dysfunction, as seen, for example, by demyelination or neuronal death. The most recent results of the literature have focused on the Herpes family viruses (HHV-6 and HHV-4/Epstein-Barr virus) and their possible role in the development of multiple sclerosis. Even if no virus has been identified so far as the multiple sclerosis etiological agent, our aim here is to show that some viruses may be responsible for triggering or sustaining neurological diseases. This is particularly the case for Paramyxoviruses, in the late appearance of functional alterations, Picornaviruses, in inducing a breakdown of immune tolerance, epitope spreading and demyelination, and Herpes viruses in inducing T and B lymphocyte activation, T lymphocytes dysregulation and autoimmunity after their reactivation. Therefore, “common” viruses can play a role as potential modulators of the immune and nervous systems which, in the specific context of dysimmunity and genetic susceptibility, stimulate a favorable background to the development of multiple sclerosis. Tracing and studying viruses in multiple sclerosis patients may improve our understanding of their actual involvement in multiple sclerosis physiopathology.


title: Insights into the Roles of Cyclophilin A During Influenza Virus Infection

text: Cyclophilin A (CypA) is the main member of the immunophilin superfamily that has peptidyl-prolyl cis-trans isomerase activity. CypA participates in protein folding, cell signaling, inflammation and tumorigenesis. Further, CypA plays critical roles in the replication of several viruses. Upon influenza virus infection, CypA inhibits viral replication by interacting with the M1 protein. In addition, CypA is incorporated into the influenza virus virions. Finally, Cyclosporin A (CsA), the main inhibitor of CypA, inhibits influenza virus replication through CypA-dependent and -independent pathways. This review briefly summarizes recent advances in understanding the roles of CypA during influenza virus infection.


title: Comparative Histopathology and Immunohistochemistry of QX-like, Massachusetts and 793/B Serotypes of Infectious Bronchitis Virus Infection in Chickens

text: Summary The aim of this study was to compare experimentally the pathogenicity and tissue distribution of the recently emerged QX-like strain of infectious bronchitis virus (IBV) with the widespread M41 and 793/B serotypes of the virus. Histopathological and immunohistochemical methods were employed to define the main sites of virus replication. One-day-old specific pathogen free chickens were inoculated with five different QX-like strains, or with the M41 and 793/B IBV strains and monitored for 42 days post-infection. Tracheal lesions developed in all infected birds, confirming the ability of all of the tested strains to induce respiratory disease. Replication of the isolates in the alimentary tract was detected, but the infection did not cause significant gut lesions. Four of the five QX-like IBV strains induced severe kidney lesions. Dilation of the oviduct with accumulation of serum-like fluid in the lumen of this structure, reported previously from field cases of QX-like IBV infection, was observed following experimental infection with all of the five QX-like strains. Microscopical and immunohistochemical examination of the affected oviducts did not help to elucidate the pathogenesis of this lesion.


title: Global efforts on vaccines for COVID-19: Since, sooner or later, we all will catch the coronavirus

text: COVID-19 is an emerging infectious disease that has turned into a pandemic. It spreads through droplet transmission of the new coronavirus SARS-CoV-2. It is an RNA virus displaying a spike protein as the major surface protein with significant sequence similarity to SARS-CoV which causes severe acute respiratory syndrome. The receptor binding domain of the spike protein interacts with the human angiotensin converting enzyme 2 and is considered as the antigenic determinant for stimulating an immune response. While multiple candidate vaccines are currently under different stages of development, there are no known therapeutic interventions at the moment. This review describes the key genetic features that are being considered for generating vaccine candidates by employing innovative technologies. It also highlights the global efforts being undertaken to deliver vaccines for COVID-19 through unprecedented international cooperation and future challenges post development.


title: Coronavirus infection in intensively managed cattle with respiratory disease

text: BACKGROUND: A detailed laboratory investigation identified bovine coronavirus (BCoV) as the aetiological agent in an outbreak of respiratory disease at a semi‐intensive beef cattle feedlot in south‐east Australia. The outbreak caused 30% morbidity in the resident population and also affected two cohorts of cattle that were newly introduced to the property. METHODS: At slaughter, pulmonary consolidation and inflammatory lesions in the trachea were identified in 15 of 49 animals. Pasteurella multocida or Histophilus somni was cultured from 3 of 7 animals with lesions. Histopathological examination revealed multifocal non‐suppurative bronchointerstitial pneumonia with formation of epithelial syncytial cells, sometimes associated with suppurative bronchopneumonia. RESULTS: BCoV was detected in nasal swabs and pulmonary lesions using real‐time reverse transcriptase–polymerase chain reaction (qRT‐PCR) assay and virus isolation. There was serological evidence of previous exposure to bovine viral diarrhoea virus, bovine respiratory syncytial virus and bovine parainfluenza virus type 3, but not to bovine herpesvirus type 1. None of these viral pathogens or Mycoplasma bovis was identified by qRT‐PCR. CONCLUSION: This is believed to be the first report of BCoV in association with bovine respiratory disease complex in Australia.


title: Sustained effects of faculty leadership development modules for clinical instructors of core competences education in Taiwan: a four-year explanatory case study

text: BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) core competencies (CC) in general medicine-based primary care are essential for junior medical trainees. In this country, a regular faculty development (FD) program aimed at training faculty in instructing (teaching and assessing) these CC had operated. However, leadership was not emphasized. In a new intervention module, the roles and associated responsibilities of clinical instructors to conduct, design, and lead CC-based education were emphasis. AIMS: This follow-up explanatory case study compares the effectiveness of intervention module with that of the previous regular module. METHODS: The regular group (n = 28) comprised clinical instructors who participated in the FD module during the 2013–2014 year while the intervention group (n = 28) was composed of 2015–2016 participants. Prior to the formal (hands-on) training, participants in the intervention group were asked to study the online materials of the regular module. These participants then received a 30-h hands-on training in conducting, designing, and leading skills. Finally, they prepared a 10-h reflective end-of-module presentation of their real-world practices. RESULTS: Following the training, a higher degree improvement in participants self-reported familiarity with CC education, self-confidence in their ability to deliver CC education and sustained involve CC education were noted among the intervention FD group, compared with the regular FD group. In the intervention group, senior academicians (associate and full professor) are more substantially involved in designing and leading CC-based courses than junior academicians (lecturers and assistant professors). Among non-teaching award winners of in the intervention FD group, the follow-up degree of sustained involvement in delivering, designing and leading CC-based courses was significantly higher than that of the regular group. CONCLUSIONS: Our study demonstrated that leadership training in the intervention FD modules substantially motivated clinical instructors to become leaders in CC education.


title: Survival on uncommon fomites of feline calicivirus, a surrogate of noroviruses

text: BACKGROUND: Norovirus (NoV) transmission occurs mainly through food and fomites. Contaminated human fingers can transfer the virus to inanimate objects, which may then spread the virus to susceptible persons. However, no information is available on the survival of NoVs on fomites, which may be of importance in the transmission of NoVs in institutional settings such as hospitals and nursing homes. METHODS: In the absence of any in vitro cultivation system for NoVs, feline calicivirus (FCV) was used as a surrogate. Several fomites such as computer mouse, keyboard keys, telephone wire, telephone receiver, telephone buttons, and brass disks representing faucets and door handle surfaces were artificially contaminated with known amounts of FCV. Samples were taken at regular time intervals, and virus was titrated in feline kidney cells to determine its survival on these surfaces. RESULTS: Survivability of FCV varied with fomite type. The virus survived for up to 3 days on telephone buttons and receivers, for 1 or 2 days on computer mouse, and for 8 to 12 hours on keyboard keys and brass. The time for 90% virus reduction was <4 hours on computer keys, mouse, brass, and telephone wire; 4 to 8 hours on telephone receiver; and 12 to 24 hours on telephone buttons. CONCLUSION: The results of this study confirm that FCV (and perhaps NoV) can survive on fomites such as computers, telephones, and faucets and may be transmitted to humans using these contaminated materials. This may necessitate regular cleaning or disinfection of these items, especially in hospitals and nursing homes and after known outbreaks of NoVs.


title: Vaccination of calves using the BRSV nucleocapsid protein in a DNA prime–protein boost strategy stimulates cell-mediated immunity and protects the lungs against BRSV replication and pathology

text: Respiratory syncytial virus (RSV) is a major cause of respiratory disease in both cattle and young children. Despite the development of vaccines against bovine (B)RSV, incomplete protection and exacerbation of subsequent RSV disease have occurred. In order to circumvent these problems, calves were vaccinated with the nucleocapsid protein, known to be a major target of CD8(+) T cells in cattle. This was performed according to a DNA prime–protein boost strategy. The results showed that DNA vaccination primed a specific T-cell-mediated response, as indicated by both a lymphoproliferative response and IFN-γ production. These responses were enhanced after protein boost. After challenge, mock-vaccinated calves displayed gross pneumonic lesions and viral replication in the lungs. In contrast, calves vaccinated by successive administrations of plasmid DNA and protein exhibited protection against the development of pneumonic lesions and the viral replication in the BAL fluids and the lungs. The protection correlated to the cell-mediated immunity and not to the antibody response.


THE COURAGE TO RETURN TO EVERYDAY LIFE AT THE TIME OF COVID-19: THE POINT OF VIEW OF INFLAMMATORY BOWEL DISEASE PATIENTS NEEDING ENDOSCOPY.


title: Impact of admission screening for meticillin-resistant Staphylococcus aureus on the length of stay in an emergency department

text: Summary Preventing and controlling meticillin-resistant Staphylococcus aureus (MRSA) includes early detection and isolation. In the emergency department (ED), such measures have to be balanced with the requirement to treat patients urgently and transfer quickly to an acute hospital bed. We assessed, in a busy and overcrowded ED, the contribution made to a patient's stay by previous MRSA risk group identification and by selective rescreening of those patients who were previously documented in the research hospital as being MRSA positive. Patients with a previous diagnosis of MRSA colonisation were flagged automatically as ‘risk group’ (RG) on their arrival in the ED and were compared with ‘non-risk group’ (NRG), i.e. not previously demonstrated in the research hospital to be infected or colonised with MRSA. Over an 18 month period, there were 16 456 admissions via the ED, of which 985 (6%) were RG patients. The expected median times to be admitted following a request for a ward bed for NRG and RG patients were 10.4 and 12.9h, respectively. Female sex, age >65 years, and RG status all independently predicted a statistically significantly longer stay in the ED following a request for a hospital bed. We consider that national and local policies for MRSA need to balance the welfare of patients in the ED with the need to comply with best practice, when there are inadequate ED and inpatient isolation facilities. Patients with MRSA requiring emergency admission must have a bed available for them.


title: Construction and Rescue of a Molecular Clone of Deformed Wing Virus (DWV)

text: European honey bees are highly important in crop pollination, increasing the value of global agricultural production by billions of dollars. Current knowledge about virulence and pathogenicity of Deformed wing virus (DWV), a major factor in honey bee colony mortality, is limited. With this study, we close the gap between field research and laboratory investigations by establishing a complete in vitro model for DWV pathogenesis. Infectious DWV was rescued from a molecular clone of a DWV-A genome that induces DWV symptoms such as crippled wings and discoloration. The expression of DWV proteins, production of infectious virus progeny, and DWV host cell tropism could be confirmed using newly generated anti-DWV monoclonal antibodies. The recombinant RNA fulfills Koch’s postulates circumventing the need of virus isolation and propagation of pure virus cultures. In conclusion, we describe the development and application of a reverse genetics system for the study of DWV pathogenesis.


title: Forecasting Brazilian and American COVID-19 cases based on artificial intelligence coupled with climatic exogenous variables

text: The novel coronavirus disease (COVID-19) is a public health problem once according to the World Health Organization up to June 24th, 2020, more than 9.1 million people were infected, and more than 470 thousand have died worldwide. In the current scenario, the Brazil and the United States of America present a high daily incidence of new cases and deaths. Therefore, it is important to forecast the number of new cases in a time window of one week, once this can help the public health system developing strategic planning to deals with the COVID-19. The application of the forecasting artificial intelligence (AI) models has the potential of deal with dynamical behavior of time-series like of COVID-19. In this paper, Bayesian regression neural network, cubist regression, k-nearest neighbors, quantile random forest, and support vector regression, are used stand-alone, and coupled with the recent pre-processing variational mode decomposition (VMD) employed to decompose the time series into several intrinsic mode functions. All AI techniques are evaluated in the task of time-series forecasting with one, three, and six-days-ahead the cumulative COVID-19 cases in five Brazilian and American states, with a high number of cases up to April 28th, 2020. Previous cumulative COVID-19 cases and exogenous variables as daily temperature and precipitation were employed as inputs for all forecasting models. The models’ effectiveness are evaluated based on the performance criteria. In general, the hybridization of VMD outperformed single forecasting models regarding the accuracy, specifically when the horizon is six-days-ahead, the hybrid VMD–single models achieved better accuracy in 70% of the cases. Regarding the exogenous variables, the importance ranking as predictor variables is, from the upper to the lower, past cases, temperature, and precipitation. Therefore, due to the efficiency of evaluated models to forecasting cumulative COVID-19 cases up to six-days-ahead, the adopted models can be recommended as a promising models for forecasting and be used to assist in the development of public policies to mitigate the effects of COVID-19 outbreak.


Enfoque “PIT CREW” en la asistencia de pacientes COVID-19


title: Modeling Heterogeneity in Direct Infectious Disease Transmission in a Compartmental Model

text: Mathematical models have been used to understand the transmission dynamics of infectious diseases and to assess the impact of intervention strategies. Traditional mathematical models usually assume a homogeneous mixing in the population, which is rarely the case in reality. Here, we construct a new transmission function by using as the probability density function a negative binomial distribution, and we develop a compartmental model using it to model the heterogeneity of contact rates in the population. We explore the transmission dynamics of the developed model using numerical simulations with different parameter settings, which characterize different levels of heterogeneity. The results show that when the reproductive number, [Formula: see text] , is larger than one, a low level of heterogeneity results in dynamics similar to those predicted by the homogeneous mixing model. As the level of heterogeneity increases, the dynamics become more different. As a test case, we calibrated the model with the case incidence data for severe acute respiratory syndrome (SARS) in Beijing in 2003, and the estimated parameters demonstrated the effectiveness of the control measures taken during that period.


title: Emerging human infectious diseases and the links to global food production

text: Infectious diseases are emerging globally at an unprecedented rate while global food demand is projected to increase sharply by 2100. Here, we synthesize the pathways by which projected agricultural expansion and intensification will influence human infectious diseases and how human infectious diseases might likewise affect food production and distribution. Feeding 11 billion people will require substantial increases in crop and animal production that will expand agricultural use of antibiotics, water, pesticides and fertilizer, and contact rates between humans and both wild and domestic animals, all with consequences for the emergence and spread of infectious agents. Indeed, our synthesis of the literature suggests that, since 1940, agricultural drivers were associated with >25% of all — and >50% of zoonotic — infectious diseases that emerged in humans, proportions that will likely increase as agriculture expands and intensifies. We identify agricultural and disease management and policy actions, and additional research, needed to address the public health challenge posed by feeding 11 billion people.


title: Contributions of the S2 spike ectodomain to attachment and host range of infectious bronchitis virus

text: Abstract The spike protein is the major viral attachment protein of the avian coronavirus infectious bronchitis virus (IBV) and ultimately determines viral tropism. The S1 subunit of the spike is assumed to be required for virus attachment. However, we have previously shown that this domain of the embryo- and cell culture adapted Beaudette strain, in contrast to that of the virulent M41 strain, is not sufficient for binding to chicken trachea (Wickramasinghe et al., 2011). In the present study, we demonstrated that the lack of binding of Beaudette S1 was not due to absence of virus receptors on this tissue nor due to the production of S1 from mammalian cells, as S1 proteins expressed from chicken cells also lacked the ability to bind IBV-susceptible embryonic tissue. Subsequently, we addressed the contribution of the S2 subunit of the spike in IBV attachment. Recombinant IBV Beaudette spike ectodomains, comprising the entire S1 domain and the S2 ectodomain, were expressed and analyzed for binding to susceptible embryonic chorio-allantoic membrane (CAM) in our previously developed spike histochemistry assay. We observed that extension of the S1 domain with the S2 subunit of the Beaudette spike was sufficient to gain binding to CAM. A previously suggested heparin sulfate binding site in Beaudette S2 was not required for the observed binding to CAM, while sialic acids on the host tissues were essential for the attachment. To further elucidate the role of S2 the spike ectodomains of virulent IBV M41 and chimeras of M41 and Beaudette were analyzed for their binding to CAM, chicken trachea and mammalian cell lines. While the M41 spike ectodomain showed increased attachment to both CAM and chicken trachea, no binding to mammalian cells was observed. In contrast, Beaudette spike ectodomain had relatively weak ability to bind to chicken trachea, but displayed marked extended host range to mammalian cells. Binding patterns of chimeric spike ectodomains to these tissues and cells indicate that S2 subunits most likely do not contain an additional independent receptor-binding site. Rather, the interplay between S1 and S2 subunits of spikes from the same viral origin might finally determine the avidity and specificity of virus attachment and thus viral host range.


title: Messaging Mask Wearing During the COVID-19 Crisis: Ideological Differences

text: As the U.S. Government works to slow the spread of the novel coronavirus, messaging is important in getting individuals to comply with public health recommendations, especially as the response from the public seems to be polarized along partisan and ideological lines. Using a recent Centers for Disease Control recommendation of wearing facemasks, I use Regulatory Focus Theory to predict that conservatives will be more responsive to messages related to promotion, while liberals are more responsive to messages related to prevention. Using a pre-registered experimental design, I find no evidence that prevention messages influence attitudes toward mask wearing. Promotion messages, however, cause conservatives to become less supportive of mask wearing, in contrast to theoretical predictions. These findings suggest that, related to messaging about mask wearing, strong ideological differences do not emerge related to the focus of the message.


title: DCGR: feature extractions from protein sequences based on CGR via remodeling multiple information

text: BACKGROUND: Protein feature extraction plays an important role in the areas of similarity analysis of protein sequences and prediction of protein structures, functions and interactions. The feature extraction based on graphical representation is one of the most effective and efficient ways. However, most existing methods suffer limitations from their method design. RESULTS: We introduce DCGR, a novel method for extracting features from protein sequences based on the chaos game representation, which is developed by constructing CGR curves of protein sequences according to physicochemical properties of amino acids, followed by converting the CGR curves into multi-dimensional feature vectors by using the distributions of points in CGR images. Tested on five data sets, DCGR was significantly superior to the state-of-the-art feature extraction methods. CONCLUSION: The DCGR is practically powerful for extracting effective features from protein sequences, and therefore important in similarity analysis of protein sequences, study of protein-protein interactions and prediction of protein functions. It is freely available at https://sourceforge.net/projects/transcriptomeassembly/files/Feature%20Extraction. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-019-2943-x) contains supplementary material, which is available to authorized users.


title: Two immunocompromised patients with diffuse alveolar hemorrhage as a complication of severe COVID-19

text: Abstract Diffuse alveolar hemorrhage (DAH) is a severe and potentially life-threatening disease manifestation. Besides autoimmune diseases such as anti-neutrophil cytoplasmatic antibody (ANCA) associated vasculitis and anti-glomerular basement membrane (anti-GBM) syndrome pulmonary viral infections are also known to be culprits of DAH. The coronavirus disease 2019 (COVID-19) pandemic confronts healthcare providers all around the world with an unprecedented number of viral lung infections with a great variance in symptoms and severity. Hemoptysis being the key symptome of DAH has so far been reported to be rare. We present two cases of immunocompromised patients with rapidly developing hypoxemic respiratory failure and evidence of DAH in the context of SARS-CoV-2 infection.


title: Research and urology at a time of COVID‐19

text: COVID‐19 has brought a lot of medical research and surgical training to a halt. Here the author investigates the impact of the suspension on the future of patient‐centred research and the career prospects of healthcare professionals, along with an insider insight into the work at the NHS Nightingale, London.


title: The role of viral nucleic acid recognition in dendritic cells for innate and adaptive antiviral immunity

text: Abstract Dendritic cells which are located at the interface of innate and adaptive immunity are targets for infection by many different DNA and RNA viruses. Dendritic cell subpopulations express specific nucleic acid recognition receptors belonging to the Toll-like receptor family (TLR3, 7, 8, 9) and the cytosolic RNA helicase family (RIG-I, MDA5, LGP2). Activation of dendritic cells by viral DNA and RNA via these receptors is essential for triggering the innate antiviral immune response and shaping the ensuing adaptive antiviral immunity. This review will summarize our current knowledge of viral nucleic acid recognition and signaling by Toll-like receptors and RNA helicases focusing on recent evidence for their specific functions in antiviral defense in vivo.


title: Towards a Coronavirus-Based HIV Multigene Vaccine

text: Human immunodeficiency virus (HIV) infection represents one of the major health threats in the developing world. The costly treatment of infected individuals with multiple highly efficient anti-HIV drugs is only affordable in industrialized countries. Thus, an efficient vaccination strategy is required to prevent the further spread of the infection. The molecular biology of coronaviruses and particular features of the human coronavirus 229E (HCoV 229E) indicate that HCoV 229E-based vaccine vectors can become a new class of highly efficient vaccines. First, the receptor of HCoV 229E, human aminopeptidase N (hAPN or CD13) is expressed mainly on human dendritic cells (DCs) and macrophages indicating that targeting of HCoV 229E-based vectors to professional antigen presenting cells can be achieved by receptor-mediated transduction. Second, HCoV 229E structural genes can be replaced by multiple transcriptional units encoding various antigens. These virus-like particles (VLPs) containing HCoV 229E-based vector RNA have the ability to transduce human DCs and to mediate heterologous gene expression in these cells. Finally, coronavirus infections are associated with mainly respiratory and enteric diseases, and natural transmission of coronaviruses occurs via mucosal surfaces. In humans, HCoV 229E causes common cold by infecting the upper respiratory tract. HCoV 229E infections are mainly encountered in children and re-infection occurs frequently in adults. It is thus most likely that pre-existing immunity against HCoV 229E will not significantly impact on the vaccination efficiency if HCoV 229E-based vectors are used in humans.


title: Identification of Human Adenovirus in Respiratory Samples with Luminex Respiratory Virus Panel Fast V2 Assay and Real-Time Polymerase Chain Reaction

text: In order to compare the last version of the Respiratory Virus Panel (RVP) Fast assay for human Adenovirus (hAdv) detection with a specific real-time polymerase chain reaction (qPCR), which is considered the gold standard for hAdv detection, nasopharyngeal samples collected from 309 children (age range, four months to eight years) with respiratory tract infection were tested using the RVP Fast v2 assay (Luminex Molecular Diagnostics, Inc., Toronto, ON, Canada) and a specific TaqMan qPCR to identify hAdv DNA. The RVP Fast v2 assay detected 30/61 (49.2%) hAdv infections that had been identified by real-time qPCR, demonstrating a significantly lower detection rate (p < 0.001). The sensitivity of the RVP Fast v2 assay in comparison to qPCR was lower in younger children (42.9% vs. 57.7%; Cohen’s kappa coefficient, 0.53); in samples with co-infections (40.0% vs. 56.7%; Cohen’s kappa coefficient, 0.52); and in samples with hAdv type C (45.9% vs. 57.1%; Cohen’s kappa coefficient, 0.60). Samples with lower viral loads were associated with a significantly lower sensitivity of the RVP Fast v2 assay (35.1% vs. 68.2%, p = 0.01; Cohen’s kappa coefficients, 0.49). The RVP Fast v2 assay has important limitations for the detection of hAdv and cannot be used to evaluate whether hAdvs are the main etiologic agent responsible for an outbreak or when epidemiological studies are performed.


title: Analysis of 25% Duty-Cycle Up-Conversion Passive Mixer for UWB Transmitter

text: The performance of differential up-conversion passive mixer operating in the 3–5 GHz band for UWB transmitter driven by 25% duty-cycle clocks is studied and analyzed. A reasonably accurate LTI equivalent circuit accounting for harmonics is derived. We have demonstrated that the conversion gain, input and output impedances of the proposed LTI equivalent circuit matches those of the LTV up-conversion passive mixer. The LTI model can be used to define the reachable design space. The mixer input and output impedance can be tuned by varying resistor at the mixer output allowing for impedance match to connected circuits. We have shown how each design parameters impacts critical performance of the up-conversion passive mixer. Simulations of the proposed up-conversion passive mixer show -3.68 dB of conversion gain, 15.9 dBm of OIP3, 116.7dBm of OIP2 and a NF as low as 5.2 dB while consuming 1.5 pW. Furthermore linearity and ports isolation performances due to voltage threshold mismatch variation of ±60mV shows an OIP3 greater than 15.85dBm and an LO_RF isolation smaller than -51.9dB.


“Closed” Supraglottic Airway-Guided Intubation During the COVID-19 Pandemic: A Glo Germ Follow-up


title: Rescheduling Non- Urgent Care in Radiology: Implementation during the COVID-19 Pandemic

text: OBJECTIVE To meet hospital preparedness for the coronavirus disease 2019 pandemic, the Centers for Disease Control and Prevention and ACR recommended delay of all nonemergent tests and elective procedures. The purpose of this article is to report our experience for rescheduling nonemergent imaging and procedures during the pandemic at our tertiary, academic institution. METHODS We rescheduled the nonemergent imaging and procedures in our hospitals and outpatient centers from March 16 to May 4, 2020. We created a tiered priority system to reschedule patients for whom imaging could be delayed with minimal clinical impact. The radiologists performed detailed chart reviews for decision making. We conducted daily virtual huddles with discussion of rescheduling strategies and issue tracking. RESULTS Using a snapshot during the rescheduling period, there was a 53.4% decrease in imaging volume during the period of March 16 to April 15, 2020, compared with same time period in 2019. The total number of imaging studies decreased from 38,369 in 2019 to 17,891 in 2020 during this period. Although we saw the largest reduction in outpatient imaging (72.3%), there was also a significant decrease in inpatient (40.5%) and emergency department (48.9%) imaging volumes. DISCUSSION The use of multiple communication channels was critical in relaying the information to all our stakeholders, patients, referring physicians, and the radiology workforce. Teamwork, quick adoption, and adaptation of changing strategies was important given the fluidity of the situation.


title: Viral models of multiple sclerosis: Neurodegeneration and demyelination in mice infected with Theiler's virus

text: Abstract Multiple sclerosis (MS) is a complex inflammatory disease of unknown etiology that affects the central nervous system (CNS) white matter, and for which no effective cure exists. Indeed, whether the primary event in MS pathology affects myelin or axons of the CNS remains unclear. Animal models are necessary to identify the immunopathological mechanisms involved in MS and to develop novel therapeutic and reparative approaches. Specifically, viral models of chronic demyelination and axonal damage have been used to study the contribution of viruses in human MS, and they have led to important breakthroughs in our understanding of MS pathology. The Theiler's murine encephalomyelitis virus (TMEV) model is one of the most commonly used MS models, although other viral models are also used, including neurotropic strains of mouse hepatitis virus (MHV) that induce chronic inflammatory demyelination with similar histological features to those observed in MS. This review will discuss the immunopathological mechanisms involved in TMEV-induced demyelinating disease (TMEV-IDD). The TMEV model reproduces a chronic progressive disease due to the persistence of the virus for the entire lifespan in susceptible mice. The evolution and significance of the axonal damage and neuroinflammation, the importance of epitope spread from viral to myelin epitopes, the presence of abortive remyelination and the existence of a brain pathology in addition to the classical spinal cord demyelination, are some of the findings that will be discussed in the context of this TMEV-IDD model. Despite their limitations, viral models remain an important tool to study the etiology of MS, and to understand the clinical and pathological variability associated with this disease.


Fear and Understanding in the Time of COVID-19


title: Antibody responsiveness during immunization and challenge of genetically modified antibody responder mice with murine hepatitis virus 3

text: Summary The aim of this study was to evaluate some immunological patterns involved in natural and acquired resistance against MHV3 using the original model of genetically modified lines of mice selected for high (HIII) and low (LIII) antibody responsiveness. As previously shown, a lower pre-existing anti-MHV antibody level was found in susceptible HIII mice as compared to resistant LIII mice. Mortality rates of the F1 (H×L) hybrids and F2 and backcross segregants reflected co-dominance of both characters and the survivors had higher pre-existing anti-MHV antibody titers. The present data show that both lines had the potential to synthesize antibodies and that the resistance acquired by the susceptible HIII mice paralleled the antibody synthesis. Nevertheless, higher antibody titers were necessary to confer resistance in HIII mice than in LIII ones. When compared to uvMHV3, a single immunization with a related infectious MHV strain induced a higher antibody synthesis and led the HIII mice to resist the MHV3 challenge. A direct correlation between the antibody level and resistance to infection was always observed in HIII mice. Although mounting a Th2 response as indicated by IgG1 responses, they were also able to readily synthesize large amounts of IgG2a antibodies after immunization or during infection, reflecting a Th1 response. The transfer of anti-MHV antibodies to susceptible HIII mice was capable of conferring resistance to MHV3, providing the antibodies were present before virus infection and in large amounts. The resistance and the survival time of these animals increased with the level of antibody administered. If these direct and clear data suggest that HIII mice can acquire resistance through antibodies, the basis of the resistance of the resistant LIII mice may rely on mechanisms less dependent on antibodies.


title: COVID-19 Pandemic Impact on Decreased Imaging Utilization: A Single Institutional Experience

text: RATIONALE AND OBJECTIVES: Predictive models and anecdotal articles suggest radiology practices were losing 50-70% of their normal imaging volume during the COVID-19 pandemic. Using actual institutional data, we investigated the change in imaging utilization and revenue during this public health crisis. MATERIALS AND METHODS: Imaging performed within the 8-week span between March 8-April 30, 2020 was categorized into the COVID-19 healthcare crisis timeframe. The first week of this date range and the 10 weeks prior were used to derive the normal practice expected volume. A rolling seven-day total value was used for volume tracking and comparison. Total imaging utilization was derived and organized by patient setting (outpatient, inpatient, emergency) and imaging modality (X-ray, CT, Mammography, MRI, Nuclear Medicine/PET, US). The three highest volume hospitals were analyzed. Revenue information was collected from the hospital billing system. RESULTS: System-wide imaging volume decreased by 55% between April 7-13, 2020. Outpatient exams decreased by 68% relative to normal practice. Emergency exams decreased by 48% and inpatient exams declined by 31%. Mammograms and nuclear medicine scans were the most affected modalities, decreasing by 93% and 61%, respectively. The main campus hospital experienced less relative imaging volume loss compared to the other smaller and outpatient-driven hospitals. At its lowest point, the technical component revenue from main campus imaging services demonstrated a 49% negative variance from normal practice. CONCLUSION; The trends and magnitude of the actual imaging utilization data presented will help inform evidence-based decisions for more accurate volume predictions, policy changes, and institutional preparedness for current and future pandemics.


title: Upper-Respiratory Viral Infection, Biomarkers, and COPD Exacerbations

text: Background Respiratory viruses frequently are recovered in the upper-respiratory tract during acute exacerbations of COPD (AECOPD), but their role as contributing pathogens remains unclear. The usefulness of procalcitonin and C-reactive protein as indicators of the presence or absence of viral infection in this setting also needs to be evaluated. Methods The study was of a prospective cohort of patients with COPD admitted to the ED for AECOPD. Reverse transcriptase-polymerase chain reaction (RT-PCR) for 14 respiratory viruses was performed on nasopharyngeal swabs collected at admission and after recovery in stable condition. Results Eighty-six patients (mean age, 72 years; male, 64%) were included. During AECOPD, upper-respiratory viral infections were detected in 44 (51%) patients: picornavirus in 22, metapneumovirus in seven, coronavirus in eight, influenza A/B in two, parainfluenza in two, and respiratory syncytial virus in three. A dual infection was present in three patients. After recovery, viruses were detected in only eight (11%) of 71 patients (P < .001 compared with AECOPD phase). In five of these patients, no virus had been identified during the initial exacerbation, thus suggesting a new viral infection acquired during follow-up. During AECOPD, procalcitonin and C-reactive protein levels did not differ significantly between patients with or without a proven viral infection. Conclusions Prevalence of upper-respiratory viral infection, as detected from nasopharyngeal swab by RT-PCR, is high in AECOPD and low after clinical recovery, suggesting that AECOPD frequently are triggered by viral infections initiated in the upper-respiratory tract. In our study, serum procalcitonin and C-reactive protein did not discriminate virus-associated exacerbations from others. Trial registration clinicaltrials.gov; Identifier: NCT00448604.


Correction for Dietz et al., “2019 Novel Coronavirus (COVID-19) Pandemic: Built Environment Considerations To Reduce Transmission”


title: Antigens under cover—The preservation and demasking of selected antigens for successful poststaining immunocytochemistry of effusion, brain smears, and lymph node aspirates

text: BACKGROUND: In clinical cytology, the applicability of an ancillary test such as immunocytochemistry is too often limited by low sample volume, poor cell representation, and sample preservation. Diagnosticians often read Romanowsky‐stained cytology, although specific techniques such as immunocytochemistry are often essential for a definitive diagnosis. OBJECTIVES: The goal of the present study aimed to investigate if immunocytochemistry on previously‐stained cytologic specimens was possible. Different pretreatments were examined to determine which treatment preserved antigenicity best. METHODS: One hundred and twenty‐two impression smears and 64 fine‐needle aspirate preparations of brain and lymph nodes were processed and evaluated microscopically. The impact of staining cytologic preparations with a modified Wright's stain, using a destaining method, performing a coverslipping and decoverslipping process, and subjecting smears to a microwave treatment (MWT) were examined for the immunolabeling of selected nuclear, cytoplasmic, and plasmalemmal antigens, as well as intracellular feline coronavirus (FCoV). Biotinylated secondary antibodies were used, and the bound primary antibody was visualized using an ABC amplification kit. RESULTS: Cellular antigens were reliably detected with immunocytochemistry after smears were stained with a Romansky stain and were coverslipped early after staining and stayed coverslipped until immediately before immunolabeling. The staining intensity reached the same levels as that of the controls if the films underwent MWT in citrate buffer. In contrast, FCoV antigen detection was abolished after any physicochemical interference. CONCLUSIONS: Poststaining immunocytochemistry represents a practical tool for additional investigations on prestained cytologic specimens when searching for cellular antigens. Paired untreated samples should be kept in case the workup requires testing for more vulnerable viral antigens.


title: Discovery and genetic analysis of novel coronaviruses in least horseshoe bats in southwestern China

text: To investigate bat coronaviruses (CoVs), we collected 132 rectal swabs and urine samples from five bat species in three countries in southwestern China. Seven CoVs belonging to distinct groups of severe acute respiratory syndrome (SARS)-like CoVs and α-CoVs were detected in samples from least horseshoe bats. Samples from other bat species were negative for these viruses, indicating that the least horseshoe bat represents one of the natural reservoirs and mixers for strains of CoVs and has a pivotal role in the evolution and dissemination of these viruses. The genetic and evolutionary characteristics of these strains were described. Whole-genome sequencing of a new isolate (F46) from a rectal swab from a least horseshoe bat showed that it contained 29 699 nucleotides, excluding the poly (A) tail, with 13 open reading frames (ORFs). Phylogenetic and recombination analyses of F46 provided evidence of natural recombination between bat SARS-like CoVs (Rs3367 and LYRa11) or SARS-CoV (BJ01), suggesting that F46 could be a new recombinant virus from SARS-like CoVs or SARS-CoVs.


title: Diagnostic Testing for Severe Acute Respiratory Syndrome–Related Coronavirus-2: A Narrative Review

text: Diagnostic testing to identify persons infected with severe acute respiratory syndrome–related coronavirus-2 (SARS–CoV-2) infection is central to control the global pandemic of COVID-19 that began in late 2019. In a few countries, the use of diagnostic testing on a massive scale has been a cornerstone of successful containment strategies. In contrast, the United States, hampered by limited testing capacity, has prioritized testing for specific groups of persons. Real-time reverse transcriptase polymerase chain reaction–based assays performed in a laboratory on respiratory specimens are the reference standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging. Although excellent tools exist for the diagnosis of symptomatic patients in well-equipped laboratories, important gaps remain in screening asymptomatic persons in the incubation phase, as well as in the accurate determination of live viral shedding during convalescence to inform decisions to end isolation. Many affluent countries have encountered challenges in test delivery and specimen collection that have inhibited rapid increases in testing capacity. These challenges may be even greater in low-resource settings. Urgent clinical and public health needs currently drive an unprecedented global effort to increase testing capacity for SARS–CoV-2 infection. Here, the authors review the current array of tests for SARS–CoV-2, highlight gaps in current diagnostic capacity, and propose potential solutions.


title: Extracting Possibly Representative COVID-19 Biomarkers from X-ray Images with Deep Learning Approach and Image Data Related to Pulmonary Diseases

text: PURPOSE: While the spread of COVID-19 is increased, new, automatic, and reliable methods for accurate detection are essential to reduce the exposure of the medical experts to the outbreak. X-ray imaging, although limited to specific visualizations, may be helpful for the diagnosis. In this study, the problem of automatic classification of pulmonary diseases, including the recently emerged COVID-19, from X-ray images, is considered. METHODS: Deep Learning has proven to be a remarkable method to extract massive high-dimensional features from medical images. Specifically, in this paper, the state-of-the-art Convolutional Neural Network called Mobile Net is employed and trained from scratch to investigate the importance of the extracted features for the classification task. A large-scale dataset of 3905 X-ray images, corresponding to 6 diseases, is utilized for training MobileNet v2, which has been proven to achieve excellent results in related tasks. RESULTS: Training the CNNs from scratch outperforms the other transfer learning techniques, both in distinguishing the X-rays between the seven classes and between Covid-19 and non-Covid-19. A classification accuracy between the seven classes of 87.66% is achieved. Besides, this method achieves 99.18% accuracy, 97.36% Sensitivity, and 99.42% Specificity in the detection of COVID-19. CONCLUSION: The results suggest that training CNNs from scratch may reveal vital biomarkers related but not limited to the COVID-19 disease, while the top classification accuracy suggests further examination of the X-ray imaging potential.


title: Immunological aspects of coronavirus disease during pregnancy: an integrative review

text: OBJECTIVE To review the immunological aspects of the 2019 coronavirus disease (COVID-19) in pregnancy, based on the scientific evidence currently available METHODS An integrative review was performed by two independent researchers, based on the literature available in the MEDLINE (via PubMed) and LILACS databases, using the descriptors "pregnancy" and "COVID-19" This search included articles published up until 14th April 2020 published in English, Spanish or Portuguese After reading the articles available in their entirety, those related specifically to the immunological aspects of the disease in pregnancy were selected We initially found a total of 62 articles;52 were accessed in full-text, and 5 were finally selected RESULTS Pregnant women are more affected by respiratory diseases possibly because of physiological, immune, and anatomical changes Some studies highlight the important shift to a T-helper lymphocyte type 2 (Th2) immune response in pregnancy, as a potential contributor to the severity in cases of COVID-19 Additionally, the cytokine storm present in severe cases leads to an increased inflammatory state, which may deteriorate the clinical prognosis in this population Therefore, pregnant women may represent a vulnerable group to COVID-19 infection, primarily due to the immune imbalance in the maternal-fetal interface CONCLUSION Maternal immune response probably plays an important role in the pathophysiology of this infection, although some details remain unsolved Although further studies are needed to deeply investigate the immunological aspects of the disease in pregnancy, our findings may provide insights into the possible immune mechanisms involved in the pathophysiology of COVID-19 in pregnancy


title: Interactome analysis of the lymphocytic choriomeningitis virus nucleoprotein in infected cells reveals ATPase Na(+)/K(+) transporting subunit Alpha 1 and prohibitin as host-cell factors involved in the life cycle of mammarenaviruses

text: Several mammalian arenaviruses (mammarenaviruses) cause hemorrhagic fevers in humans and pose serious public health concerns in their endemic regions. Additionally, mounting evidence indicates that the worldwide-distributed, prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV), is a neglected human pathogen of clinical significance. Concerns about human-pathogenic mammarenaviruses are exacerbated by of the lack of licensed vaccines, and current anti-mammarenavirus therapy is limited to off-label use of ribavirin that is only partially effective. Detailed understanding of virus/host-cell interactions may facilitate the development of novel anti-mammarenavirus strategies by targeting components of the host-cell machinery that are required for efficient virus multiplication. Here we document the generation of a recombinant LCMV encoding a nucleoprotein (NP) containing an affinity tag (rLCMV/Strep-NP) and its use to capture the NP-interactome in infected cells. Our proteomic approach combined with genetics and pharmacological validation assays identified ATPase Na(+)/K(+) transporting subunit alpha 1 (ATP1A1) and prohibitin (PHB) as pro-viral factors. Cell-based assays revealed that ATP1A1 and PHB are involved in different steps of the virus life cycle. Accordingly, we observed a synergistic inhibitory effect on LCMV multiplication with a combination of ATP1A1 and PHB inhibitors. We show that ATP1A1 inhibitors suppress multiplication of Lassa virus and Candid#1, a live-attenuated vaccine strain of Junín virus, suggesting that the requirement of ATP1A1 in virus multiplication is conserved among genetically distantly related mammarenaviruses. Our findings suggest that clinically approved inhibitors of ATP1A1, like digoxin, could be repurposed to treat infections by mammarenaviruses pathogenic for humans.


Providing simultaneous COVID-19-sensitive and dementia-sensitive care as we transition from crisis care to ongoing care


title: Coronavirus disease 2019: acute Fanconi syndrome precedes acute kidney injury

text: BACKGROUND: Recent data have shown that severe acute respiratory syndrome coronavirus 2 can infect renal proximal tubular cells via Angiotensin Converting Enzyme 2 (ACE2) . Our objective was to determine whether Fanconi syndrome is a frequent clinical feature in coronavirus disease 2019 (COVID-19) patients. METHODS: A retrospective cohort of 42 laboratory-confirmed COVID-19 patients without history of kidney disease hospitalized in University Hospital of Nancy was investigated. Patients were admitted to the intensive care unit (ICU) (n = 28) or the Medical department (n = 14) and were screened at least once for four markers of proximal tubulopathy. RESULTS: The mean (standard deviation) follow-up was 19.7 (±12.2) days. Of the patients, 75% (30/40) showed at least two proximal tubule abnormalities (incomplete Fanconi syndrome). The main disorders were proteinuria (88%, n = 35), renal phosphate leak defined by renal phosphate threshold/glomerular filtration rate (TmPi/GFR) <0.77 (55%, n = 22), hyperuricosuria (43%, n = 17) and normoglycaemic glycosuria (30%, n = 12). At the time of the first renal evaluation, ICU patients presented more frequent (96 versus 62%, P = 0.0095) and more severe (844 ± 343 versus 350 ± 221 mg/g, P = 0.0001) proteinuria, and a trend for an increased number of proximal tubule abnormalities (P = 0.038). During follow-up, they presented a lower nadir of serum phosphate [median (interquartile range) 0.68 (0.43–0.76) versus 0.77 (0.66–1.07) mmol/L, P = 0.044] and Acute kidney Injury (AKI) during the hospitalization (P = 0.045). Fanconi syndrome preceded severe AKI KDIGO Stages 2 and 3 in 88% (7/8) of patients. Proximal tubular abnormalities (such as proteinuria, TmPi/GFR and glycosuria in five, two and two patients, respectively) were not detected anymore in recovering patients before hospital discharge. CONCLUSION: Incomplete Fanconi syndrome is highly frequent in COVID-19 patients and precedes AKI or disappears during the recovery phase.


title: Isolation of the subunits of the coronavirus envelope glycoprotein E2 by hydroxyapatite high-performance liquid chromatography

text: Abstract The coronavirus glycoprotein E2, which is responsible for virus attachment to cell receptors and virus-induced cell fusion, was purified by solubilization of virions with Triton X-114 and phase fractionation. Native E2 and tryptic subunits of the glycoprotein were separated by size-exclusion high-performance liquid chromatography (HPLC). Two distinct 90 kD E2 subunits, which had identified elecrophoretic mobilities when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were separated by hydroxyapetite HPLC in the presence of sodium dodecyl sulfate.


title: Clinical and Laboratory Findings of the First Imported Case of Middle East Respiratory Syndrome Coronavirus to the United States

text: Background. The Middle East respiratory syndrome coronavirus (MERS-CoV) was discovered September 2012 in the Kingdom of Saudi Arabia (KSA). The first US case of MERS-CoV was confirmed on 2 May 2014. Methods. We summarize the clinical symptoms and signs, laboratory and radiologic findings, and MERS-CoV–specific tests. Results. The patient is a 65-year-old physician who worked in a hospital in KSA where MERS-CoV patients were treated. His illness onset included malaise, myalgias, and low-grade fever. He flew to the United States on day of illness (DOI) 7. His first respiratory symptom, a dry cough, developed on DOI 10. On DOI 11, he presented to an Indiana hospital as dyspneic, hypoxic, and with a right lower lobe infiltrate on chest radiography. On DOI 12, his serum tested positive by real-time reverse transcription polymerase chain reaction (rRT-PCR) for MERS-CoV and showed high MERS-CoV antibody titers, whereas his nasopharyngeal swab was rRT-PCR negative. Expectorated sputum was rRT-PCR positive the following day, with a high viral load (5.31 × 10(6) copies/mL). He was treated with antibiotics, intravenous immunoglobulin, and oxygen by nasal cannula. He was discharged on DOI 22. The genome sequence was similar (>99%) to other known MERS-CoV sequences, clustering with those from KSA from June to July 2013. Conclusions. This patient had a prolonged nonspecific prodromal illness before developing respiratory symptoms. Both sera and sputum were rRT-PCR positive when nasopharyngeal specimens were negative. US clinicians must be vigilant for MERS-CoV in patients with febrile and/or respiratory illness with recent travel to the Arabian Peninsula, especially among healthcare workers.


title: Experiments to prove continuing microbial ingress from Space to Earth

text: A wide range of evidence for pointing to our cosmic origins is close to the point of being overwhelming. Yet the long-entrenched paradigm of Earth-centered biology appears to prevail in scientific culture. A matter of crucial importance is to carry out a decisive experiment that is long overdue—establishing empirically beyond any doubt that extraterrestrial microbiota reaches the surface of the Earth at the present day. Such an experiment may of course happen naturally by the appearance of pandemics of new disease as discussed in an earlier chapter.


Reply to Dutheil et al.


MEDICATION UNMASKED BRUGADA SYNDROME AND CARDIAC ARREST IN A COVID-19 PATIENT


title: The impact of COVID-19 lockdown on food priorities. Results from a preliminary study using social media and an online survey with Spanish consumers

text: This preliminary study describes the impact of the COVID-19 health crisis on people’s interests, opinions, and behaviour towards food. Here, the evolution of people’s internet searches, the characteristics of the most watched YouTube videos, and Tweeted messages in relation to COVID-19 and food was studied. Additionally, an online questionnaire (Spanish population, n = 362) studied changes in food shopping habits during the lockdown, motivations behind the changes, and perceived reliability of the information received from media. Results showed initial trending searches and most watched YouTube videos were about understanding what COVID-19 is and how the illness can progress and spread. When the official statement of a pandemic was released, trending searches in relation to food and shopping increased. Data retrieved from Twitter also showed an evolution from shopping concerns to the feeling of uncertainty for the oncoming crisis. The answers to the online questionnaire showed reduction of shopping frequency but no changes in shopping location. Products purchased with higher frequency were pasta and vegetables (health motivations), others were purchased to improve their mood (nuts, cheese, and chocolates). Reduced purchasing was attributed to products with a short shelf-life (fish, seafood) or because they were unhealthy and contributed to gained body weight (sugary bakery goods) or mood (desserts). Statements made by experts or scientists were considered by consumers to be the most reliable.


The Impressive and Rapidly Expanding Knowledge Base on SARS


title: Selective Inhibition of Enterovirus A Species Members’ Reproduction by Furano[2, 3‐d]pyrimidine Nucleosides Revealed by Antiviral Activity Profiling against (+)ssRNA Viruses

text: The rational design of broad‐spectrum antivirals requires data on antiviral activity of compounds against multiple viruses, which are often not available. We have developed a panel of (+)ssRNA viruses composed of Enterovirus and Flavivirus genera members allowing to study these activity spectra. Antiviral activity profiling of a set of nucleoside analogues revealed N (4)‐hydroxycytidine as an efficient inhibitor of replication of coxsackieviruses and other enteroviruses, but ineffective against tick‐borne encephalitis virus. Furano[2, 3‐d]pyrimidine nucleosides with n‐pentyl or n‐hexyl tails showed selective inhibition of Enterovirus A representatives. 5‐(Tetradec‐1‐yn‐1‐yl)‐uridine showed selective inhibition of tick‐borne encephalitis virus at the micromolar level.


title: The useful face‐protective shield “ORIGAMI” for gastrointestinal endoscopy during the COVID‐19 pandemic

text: Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) related disease, called coronavirus disease 2019 (COVID‐19), is mainly transmitted through droplets, aerosols, and direct contact.


title: CD4(+) T-cell subsets and host defense in the lung

text: CD4(+) T-helper subsets are lineages of T cells that have effector function in the lung and control critical aspects of lung immunity. Depletion of these cells experimentally or by drugs or human immunodeficiency virus (HIV) infection in humans leads to the development of opportunistic infections as well as increased rates of bacteremia with certain bacterial pneumonias. Recently, it has been proposed that CD4(+) T-cell subsets may also be excellent targets for mucosal vaccination to prevent pulmonary infections in susceptible hosts. Here we review recent findings that increase our understanding of T-cell subsets and their effector cytokines in the context of pulmonary infection.


title: Respiratory disease and virus shedding in rhesus macaques inoculated with SARS-CoV-2

text: An outbreak of a novel coronavirus, now named SARS-CoV-2, causing respiratory disease and a ∼2% case fatality rate started in Wuhan, China in December 2019. Following unprecedented rapid global spread, the World Health Organization declared COVID-19 a pandemic on March 11, 2020. Although data on disease in humans are emerging at a steady pace, certain aspects of the pathogenesis of SARS-CoV-2 can only be studied in detail in animal models, where repeated sampling and tissue collection is possible. Here, we show that SARS-CoV-2 causes respiratory disease in infected rhesus macaques, with disease lasting 8-16 days. Pulmonary infiltrates, a hallmark of human disease, were visible in lung radiographs of all animals. High viral loads were detected in swabs from the nose and throat of all animals as well as in bronchoalveolar lavages; in one animal we observed prolonged rectal shedding. Taken together, the rhesus macaque recapitulates moderate disease observed in the majority of human cases. The establishment of the rhesus macaque as a model of COVID-19 will increase our understanding of the pathogenesis of this disease and will aid development and testing of medical countermeasures.


title: Population-Level Interest and Telehealth Capacity of US Hospitals in Response to COVID-19: Cross-Sectional Analysis of Google Search and National Hospital Survey Data

text: BACKGROUND: As the novel coronavirus disease (COVID-19) is widely spreading across the United States, there is a concern about the overloading of the nation’s health care capacity. The expansion of telehealth services is expected to deliver timely care for the initial screening of symptomatic patients while minimizing exposure in health care facilities, to protect health care providers and other patients. However, it is currently unknown whether US hospitals have the telehealth capacity to meet the increasing demand and needs of patients during this pandemic. OBJECTIVE: We investigated the population-level internet search volume for telehealth (as a proxy of population interest and demand) with the number of new COVID-19 cases and the proportion of hospitals that adopted a telehealth system in all US states. METHODS: We used internet search volume data from Google Trends to measure population-level interest in telehealth and telemedicine between January 21, 2020 (when the first COVID-19 case was reported), and March 18, 2020. Data on COVID-19 cases in the United States were obtained from the Johns Hopkins Coronavirus Resources Center. We also used data from the 2018 American Hospital Association Annual Survey to estimate the proportion of hospitals that adopted telehealth (including telemedicine and electronic visits) and those with the capability of telemedicine intensive care unit (tele-ICU). Pearson correlation was used to examine the relations of population search volume for telehealth and telemedicine (composite score) with the cumulative numbers of COVID-19 cases in the United States during the study period and the proportion of hospitals with telehealth and tele-ICU capabilities. RESULTS: We found that US population–level interest in telehealth increased as the number of COVID-19 cases increased, with a strong correlation (r=0.948, P<.001). We observed a higher population-level interest in telehealth in the Northeast and West census region, whereas the proportion of hospitals that adopted telehealth was higher in the Midwest region. There was no significant association between population interest and the proportion of hospitals that adopted telehealth (r=0.055, P=.70) nor hospitals having tele-ICU capability (r=–0.073, P=.61). CONCLUSIONS: As the number of COVID-19 cases increases, so does the US population’s interest in telehealth. However, the level of population interest did not correlate with the proportion of hospitals providing telehealth services in the United States, suggesting that increased population demand may not be met with the current telehealth capacity. Telecommunication infrastructures in US hospitals may lack the capability to address the ongoing health care needs of patients with other health conditions. More practical investment is needed to deploy the telehealth system rapidly against the impending patient surge.


title: Immunomodulators as an antimicrobial tool

text: The spectrum of infectious diseases has shifted in the past 50 years to include those caused by microbes that cause disease predominantly in immunocompromised individuals. This phenomenon has underscored the dependence of microbial virulence on the immune status of the host. The limited efficacy of the available antimicrobial armamentarium in immunocompromised individuals, combined with increasing resistance to these agents, has led to an urgent need for new therapies for infectious diseases. Immunomodulation represents a novel approach to antimicrobial therapy that depends on bolstering host immunity, rather than direct antimicrobial activity. Immunomodulators can be divided into those that are specific to pathogens (pathogen-specific) and those that are not specific to pathogens (non-specific). However, to date only a few immunomodulators have been evaluated for their efficacy as antimicrobial tools.


title: Illuminating the Gateway of Gene Silencing: Perspective of RNA Interference Technology in Clinical Therapeutics

text: A novel laboratory revolution for disease therapy, the RNA interference (RNAi) technology, has adopted a new era of molecular research as the next generation “Gene-targeted prophylaxis.” In this review, we have focused on the chief technological challenges associated with the efforts to develop RNAi-based therapeutics that may guide the biomedical researchers. Many non-curable maladies, like neurodegenerative diseases and cancers have effectively been cured using this technology. Rapid advances are still in progress for the development of RNAi-based technologies that will be having a major impact on medical research. We have highlighted the recent discoveries associated with the phenomenon of RNAi, expression of silencing molecules in mammals along with the vector systems used for disease therapeutics.


title: Heterogeneity in spike protein genes of porcine epidemic diarrhea viruses isolated in Korea

text: Abstract Porcine epidemic diarrhea virus (PEDV) has plagued the domestic swine industry in Korea causing significant economic impacts on pig production nationwide. In the present study, we determined the complete nucleotide sequences of the spike (S) glycoprotein genes of seven Korean PEDV isolates. The entire S genes of all isolates were found to be nine nucleotides longer in length than other PEDV reference strains. This size difference was due to the combined presence of notable 15bp insertion and 6bp deletion within the N-terminal region of the S1 domain of the Korean isolates. In addition, the largest number of amino acid variations was accumulated in the S1 N-terminal region, leading to the presence of hypervariability in the isolates. Sequence comparisons at the peptide level of the S proteins revealed that all seven Korean isolates shared diverse similarities ranging from a 93.6% to 99.6% identity with each other but exhibited a 92.2% to 93.7% identity with other reference strains. Collectively, the sequence analysis data indicate the diversity of the PEDV isolates currently prevalent in Korea that represents a heterogeneous group. Phylogenetic analyses showed two separate clusters, in which all Korean field isolates were grouped together in the second cluster (group 2). The results indicate that prevailing isolates in Korea are phylogenetically more closely related to each other rather than other reference strains. Interestingly, the tree topology based on the nucleotide sequences representing the S1 domain or the S1 N-terminal region most nearly resembled the full S gene-based phylogenetic tree. Therefore, our data implicates a potential usefulness of the partial S protein gene including the N-terminal region in unveiling genetic relatedness of PEDV isolates.


title: Posttraumatic stress symptoms of health care workers during the corona virus disease 2019

text: Corona virus disease 2019 (COVID‐19) outbreak has attracted worldwide attention. The COVID‐19 outbreak is unique in its rapid transmission and results in heavy stress for the front‐line health care workers (HCWs). The current study aimed to exam posttraumatic stress symptoms (PTSSs) of HCWs fighting for the COVID‐19 and to evaluate their sleep quality after 1‐month stressful suffering. Three hundred seventy‐seven HCWs working in different provinces of China participated in the survey between February 1 and 5. The demographic information was collected first. Posttraumatic Stress Disorder Checklist for DSM‐5 (PCL‐5) and the Pittsburgh Sleep Quality Index (PSQI) were selected to measure PTSSs and sleep quality. Results showed that 1 month after the outbreak, the prevalence of PTSSs was 3.8% in HCWs. Female HCWs were more vulnerable to PTSSs with hazard ratio of 2.136 (95% CI = 1.388–3.286). HCWs with higher exposure level also significantly rated more hyperarousal symptoms (hazard ratio = 4.026, 95% CI = 1.233–13.140). There was a significant difference of sleep quality between participants with and without PTSSs (z value = 6.014, p < .001) and among different groups with various contact frequencies (chi‐square = 7.307, p = .026). Path analysis showed that there was a significant indirect effect from exposure level to PTSSs through sleep quality (coefficient = 1.750, 95% CI of Boostroop test = 0.543–2.998). In summary, targeted interventions on sleep contribute to the mental recovery during the outbreak of COVID‐19. Understanding the mental health response after a public health emergency might help HCWs and communities prepare for a population's response to disaster.


title: Disaster risk reduction in conflict contexts: Lessons learned from the lived experiences of Rohingya refugees in Cox's bazar, Bangladesh

text: Bangladesh is currently hosting more than one million stateless Rohingya refugees, who fled from the Rakhine State to avoid serious crimes against humanity persecuted by the Myanmar Army. The newly arrived Rohingyas were accommodated in overcrowded refugee camps in Cox's Bazar District (CBD). The camps are highly vulnerable to landslides, tropical cyclones, flash-flooding, and communicable disease outbreak. Although a number of improvement measures are ongoing, however, no study to date has addressed Rohingyas' self-adopted strategies to mitigate disaster risks. Consequently, this paper aims to explore how refugees cope with risks associated with environmental hazards in the Kutupalong Rohingya Camp in CBD. A mixed-methods research strategy incorporating both quantitative household questionnaire survey and qualitative focus group discussions (FGDs) techniques were applied. In total 250 Rohingya refugees were selected for the questionnaire survey using a stratified random sampling method from camps 17 and 19, and two FGDs (male and female-only) were carried out in camp 13 involving 21 Rohingya participants. Results derived from the study show that responding to early warning systems, storing dried food and medicine, utilising available resources, relocating to safer shelters, and keeping hopes high were some of the coping strategies practised by the respondents. Literacy level imposed a significant impact over respondents' perception to accept various measures. For instance, the probability of storing dried food in preparation for disasters was 4 times higher among literate Rohingya compared to their illiterate counterparts. Similarly, for literate respondents, the probability was 20 times higher to store medicine than for illiterate. Guaranteed distribution of shelter strengthening kits among all refugee households, inclusion of disaster risk awareness and preparedness trainings, ensuring safe and dignified return in Myanmar, and global and regional cooperation to address the refugee crisis are some of the propositions recommended in this study for improving Rohingyas' future adaptation strategies in a humanitarian context.


title: A serological survey to evaluate contemporary prevalence of viral agents and Mycoplasma pulmonis in laboratory mice and rats in western Europe

text: To evaluate current prevalence rates of 24 viruses and of the bacterium Mycoplasma pulmonis, the authors retrospectively surveyed serological data obtained from laboratory mice and rats housed in more than 100 western European institutions. Serum samples were submitted to the authors' institution for testing between January 2007 and June 2008. The prevalence of an infection was defined as the percentage of tested samples that yielded positive results for a specific agent. In mice, the most commonly detected infectious agents were murine norovirus (prevalence of 31.8%), mouse hepatitis virus (5.5%), mouse rotavirus (1.7%) and parvoviruses (1.0%). In rats, parvoviruses (12.1%) and M. pulmonis (3.6%) were the most prevalent infectious agents. Most rodent parvovirus infections could be attributed to mouse parvovirus in mice and to rat minute virus or to Kilham rat virus in rats. These data suggest the importance of up-to-date animal health monitoring programs and should stimulate the scientific community to further improve the microbiological quality of laboratory rodents.


title: Prebiotic and probiotic supplementation prevents rhinovirus infections in preterm infants: A randomized, placebo-controlled trial

text: Background Simple and safe strategies for the prevention of viral respiratory tract infections (RTIs) are needed. Objective We hypothesized that early prebiotic or probiotic supplementation would reduce the risk of virus-associated RTIs during the first year of life in a cohort of preterm infants. Methods In this randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov no. NCT00167700), 94 preterm infants (gestational age, ≥32 + 0 and ≤36 + 6 weeks; birth weight, >1500 g) treated at Turku University Hospital, Turku, Finland, were allocated to receive oral prebiotics (galacto-oligosaccharide and polydextrose mixture, 1:1), a probiotic (Lactobacillus rhamnosus GG, ATCC 53103), or placebo (microcrystalline cellulose) between days 3 and 60 of life. The primary outcome was the incidence of clinically defined virus-associated RTI episodes confirmed from nasal swabs by using nucleic acid testing. Secondary outcomes were the severity and duration of RTIs. Results A significantly lower incidence of RTIs was detected in infants receiving prebiotics (rate ratio [RR], 0.24; 95% CI, 0.12-0.49; P < .001) or probiotics (RR, 0.50; 95% CI, 0.28-0.90; P = .022) compared with those receiving placebo. Also, the incidence of rhinovirus-induced episodes, which comprised 80% of all RTI episodes, was found to be significantly lower in the prebiotic (RR, 0.31; 95% CI, 0.14-0.66; P = .003) and probiotic (RR, 0.49; 95% CI, 0.24-1.00; P = .051) groups compared with the placebo group. No differences emerged among the study groups in rhinovirus RNA load during infections, duration of rhinovirus RNA shedding, duration or severity of rhinovirus infections, or occurrence of rhinovirus RNA in asymptomatic infants. Conclusions Gut microbiota modification with specific prebiotics and probiotics might offer a novel and cost-effective means to reduce the risk of rhinovirus infections.


title: Clinical features and outcomes of pregnant women suspected of coronavirus disease 2019

text: Summary Background 2019 novel coronavirus disease (COVID-19) has become a worldwide pandemic. Under such circumstance pregnant women are also affected significantly. Objective This study aims to observe the clinical features and outcomes of pregnant women who have been confirmed with COVID-19. Methods The research objects were 55 cases of suspected COVID-19 pregnant women who gave a birth from Jan 20th 2020 to Mar 5th 2020 in our hospital-a big birth center delivering about 30,000 babies in the last 3 years. These cases were subjected to pulmonary CT scan and routine blood test, manifested symptoms of fever, cough, chest tightness or gastrointestinal symptoms. They were admitted to an isolated suite, with clinical features and newborn babies being carefully observed. Among the 55 cases, 13 patients were assigned into the confirmed COVID-19 group for being tested positive sever acute respiratory syndrome coronavirus 2(SARS-CoV-2) via maternal throat swab test, and the other 42 patients were assigned into the control group for being ruled out COVID-19 pneumonia based on new coronavirus pneumonia prevention and control program(the 7th edition). Results There were 2 fever patients during the prenatal period and 8 fever patients during the postpartum period in the confirmed COVID-19 group. In contrast, there were 11 prenatal fever patients and 20 postpartum fever patients in the control group (p>0.05). Among 55 cases, only 2 case had cough in the confirmed group. The imaging of pulmonary CT scan showed ground- glass opacity (46.2%, 6/13), patch-like shadows(38.5%, 5/13), fiber shadow(23.1%, 3/13), pleural effusion (38.5%, 5/13)and pleural thickening(7.7%, 1/13), and there was no statistical difference between the confirmed COVID-19 group and the control group (p>0.05). During the prenatal and postpartum period, there was no difference in the count of WBC, Neutrophils and Lymphocyte, the radio of Neutrophils and Lymphocyte and the level of CRP between the confirmed COVID-19 group and the control group(p<0.05). 20 babies (from confirmed mother and from normal mother) were subjected to SARS-CoV-2 examination by throat swab samples in 24 h after birth and no case was tested positive. Conclusion The clinical symptoms and laboratory indicators are not obvious for asymptomatic and mild COVID-19 pregnant women. Pulmonary CT scan plus blood routine examination are more suitable for finding pregnancy women with asymptomatic or mild COVID-19 infection, and can be used screening COVID-19 pregnant women in the outbreak area of COVID-19 infection.


title: Development of Dual TaqMan Based One-Step rRT-PCR Assay Panel for Rapid and Accurate Diagnostic Test of MERS-CoV: A Novel Human Coronavirus, Ahead of Hajj Pilgrimage

text: BACKGROUND: Coronaviruses (CoVs) are large ribonucleic acid (RNA) viruses causing primarily respiratory disease in humans. A novel human coronavirus, subsequently named middle east respiratory syndrome coronavirus (MERS-CoV), was first reported in Saudi Arabia in September of 2012. With increasing numbers of infections and deaths from MERS-CoV, development of a rapid and reliable kit was crucial to prevent further spread of MERS-CoV. OBJECTIVES: In this study, we present two real-time reverse-transcription polymerase chain reaction (rRT-PCR) assays for in-house rapid and sensitive diagnostic testing of MERS-CoV, detecting the regions upstream of the envelope gene (upE) and open reading frame (ORF) 1b, respectively, for initial screening and final confirmation of MERS-CoV infection, as recommended by the world health organization (WHO). MATERIALS AND METHODS: In this experimental study, acquiring patient samples was difficult; thus, according to WHO recommendations and standard protocols, we synthesized RNA sequences of upE and ORF1b genes as the template signatures and TaqMan based-diagnostic rRT-PCR assays were carried out using these synthetic genes for detection of MERS-CoV. In this research, we also inaugurated a cell-free system to transcribe these RNA sequences using the DNA templates synthesized. RESULTS: The upE and ORF1b based one-step rRT-PCR assays were optimized by testing several times via different synthetic RNAs, and validation results were highly successful. The sensitivity obtained for upE was fewer than ten copies of RNA template per reaction and for ORF1b was 50 or fewer copies per reaction. CONCLUSIONS: This study showed that the developed rRT-PCR assays are rapid, reliable, reproducible, specific, sensitive, and simple tools for detection of MERS-CoV. Finally, a kit consisting of two assay signatures and controls was assembled, which can be distributed to public health laboratories in Iran to support international MERS-CoV surveillance and public health response.


title: Recent advances in understanding viral evasion of type I interferon

text: The type I interferon (IFN) system mediates a wide variety of antiviral effects and represents an important first barrier to virus infection. Consequently, viruses have developed an impressive diversity of tactics to circumvent IFN responses. Evasion strategies can involve preventing initial virus detection, via the disruption of the Toll‐like receptors or the retinoic acid inducible gene I (RIG‐I) ‐like receptors, or by avoiding the initial production of the ligands recognized by these receptors. An alternative approach is to preclude IFN production by disarming or degrading the transcription factors involved in the expression of IFN, such as interferon regulatory factor 3 (IRF3)/IRF7, nuclear factor‐κB (NF‐κB), or ATF‐2/c‐jun, or by inducing a general block on host cell transcription. Viruses also oppose IFN signalling, both by disturbing the type I IFN receptor and by impeding JAK/STAT signal transduction upon IFN receptor engagement. In addition, the global expression of IFN‐stimulated genes (ISGs) can be obstructed via interference with epigenetic signalling, and specific ISGs can also be selectively targeted for inhibition. Finally, some viruses disrupt IFN responses by co‐opting negative regulatory systems, whereas others use antiviral mechanisms to their own advantage. Here, we review recent developments in this field.


title: Risk factors associated with Streptococcus pneumonia carriage in children under five years old with acute respiratory infection in Niger

text: INTRODUCTION: Streptococcus pneumonia is a leading cause of bacterial pneumonia, meningitis and sepsis in children, and pneumococcal carriage is an important source of horizontal spread of these pathogens within the community. METHODS: A questionnaire was addressed to parents for the collection of sociodemographic and medical information. Nasopharyngeal swabbing was processed using a molecular method. We used logistic regression models to examine independent associations between pneumococcal carriage and potential risk factors. All associations with a p-value of < 0.25 in the bivariate regression analyses were subsequently entered in the multivariate regression model. RESULTS: A total of 637 children aged 1 to 59 months admitted for acute respiratory infection were included. The rate of respiratory virus carriage was 76%, whereas that of bacteria was 47% and that of bacteria-virus co-colonization was 42%. A bivariate analysis showed that carriage was not related to gender, father's or mother's education level, father's occupation, type of housing or lighting, or passive exposure to cigarette smoking in the house. It was also not linked to complete vaccination with PCV-13 or PPSV-23 and antibiotic treatment prior to hospitalization. A multivariate analysis showed that carriage was related to age greater than 3 months, maternal occupation, house flooring type, and co-colonization of another bacterium and virus. CONCLUSION: These results can be helpful to understand the dynamics of pneumococcal nasopharyngeal colonization; they confirm the interest of vaccinating infants before the age of 3 months with appropriate vaccine to prevent spread nasopharyngeal colonization and pneumococcal diseases in children.


SARS‐CoV‐2 vaccination—A plea for fast and coordinated action


title: Toward Nanotechnology-Enabled Approaches against the COVID-19 Pandemic

text: [Image: see text] The COVID-19 outbreak has fueled a global demand for effective diagnosis and treatment as well as mitigation of the spread of infection, all through large-scale approaches such as specific alternative antiviral methods and classical disinfection protocols. Based on an abundance of engineered materials identifiable by their useful physicochemical properties through versatile chemical functionalization, nanotechnology offers a number of approaches to cope with this emergency. Here, through a multidisciplinary Perspective encompassing diverse fields such as virology, biology, medicine, engineering, chemistry, materials science, and computational science, we outline how nanotechnology-based strategies can support the fight against COVID-19, as well as infectious diseases in general, including future pandemics. Considering what we know so far about the life cycle of the virus, we envision key steps where nanotechnology could counter the disease. First, nanoparticles (NPs) can offer alternative methods to classical disinfection protocols used in healthcare settings, thanks to their intrinsic antipathogenic properties and/or their ability to inactivate viruses, bacteria, fungi, or yeasts either photothermally or via photocatalysis-induced reactive oxygen species (ROS) generation. Nanotechnology tools to inactivate SARS-CoV-2 in patients could also be explored. In this case, nanomaterials could be used to deliver drugs to the pulmonary system to inhibit interaction between angiotensin-converting enzyme 2 (ACE2) receptors and viral S protein. Moreover, the concept of “nanoimmunity by design” can help us to design materials for immune modulation, either stimulating or suppressing the immune response, which would find applications in the context of vaccine development for SARS-CoV-2 or in counteracting the cytokine storm, respectively. In addition to disease prevention and therapeutic potential, nanotechnology has important roles in diagnostics, with potential to support the development of simple, fast, and cost-effective nanotechnology-based assays to monitor the presence of SARS-CoV-2 and related biomarkers. In summary, nanotechnology is critical in counteracting COVID-19 and will be vital when preparing for future pandemics.


title: COVID-19-associated mild encephalitis/encephalopathy with a reversible splenial lesion

text: • We demonstrated the first patient with COVID-19 developing an isolated SCC lesion on brain MRI, suggestive of mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). • We showed that cerebellar ataxia could be developed as the initial manifestation of COVID-19. • MERS can be considered as a differential diagnosis for neurological symptoms of COVID-19, especially when patients develop transient cerebellar ataxia or disorientation.


title: Mutations in the 3c and 7b genes of feline coronavirus in spontaneously affected FIP cats

text: Abstract Feline infectious peritonitis (FIP) is the most frequent lethal infectious disease in cats. However, understanding of FIP pathogenesis is still incomplete. Mutations in the ORF 3c/ORF 7b genes are proposed to play a role in the occurrence of the fatal FIPV biotype. Here, we investigated 282 tissue specimens from 28 cats that succumbed to FIP. Within one cat, viral sequences from different organs were similar or identical, whereas greater discrepancies were found comparing sequences from various cats. Eleven of the cats exhibited deletions in the 3c gene, resulting in truncated amino acid sequences. The 7b gene was affected by deletions only in one cat. In three of the FIP cats, coronavirus isolates with both intact 3c genes as well as 7b genes of full length could also be detected. Thus, deletions or stop codons in the 3c sequence seem to be a frequent but not compelling feature of FIPVs.


title: Molecular Characterizations of Subcellular Localization Signals in the Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus

text: The nucleolus is a dynamic subnuclear structure, which is crucial to the normal operation of the eukaryotic cell. The porcine epidemic diarrhea virus (PEDV), coronavirus nucleocapsid (N) protein, plays important roles in the process of virus replication and cellular infection. Virus infection and transfection showed that N protein was predominately localized in the cytoplasm, but also found in the nucleolus in Vero E6 cells. Furthermore, by utilizing fusion proteins with green fluorescent protein (GFP), deletion mutations or site-directed mutagenesis of PEDV N protein, coupled with live cell imaging and confocal microscopy, it was revealed that, a region spanning amino acids (aa), 71–90 in region 1 of the N protein was sufficient for nucleolar localization and R87 and R89 were critical for its function. We also identified two nuclear export signals (NES, aa221–236, and 325–364), however, only the nuclear export signal (aa325–364) was found to be functional in the context of the full-length N protein. Finally, the activity of this nuclear export signal (NES) was inhibited by the antibiotic Lepomycin B, suggesting that N is exported by a chromosome region maintenance 1-related export pathway.


title: How Much Drool Is Too Much?

text: Abstract A 3-year-old boy presented to the emergency department with a chief complaint of “lethargy” and was found to have ptosis with eventual respiratory failure and need for emergent intubation. There is a broad differential for a patient with respiratory failure, and careful physical examination and history are imperative to reduce morbidity and prevent mortality. After further evaluation and workup, the diagnosis is ultimately revealed.


title: Clinical and CT features of early-stage patients with COVID-19: a retrospective analysis of imported cases in Shanghai, China

text: Since December 2019, some patients with novel corona virus infectious disease (COVID-19) emerged in Wuhan, Hubei, China [1]. The pathogen analysis discovered a new type of coronavirus from infected airway epithelial cells [2] and named as sever acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) [3]. At the time of Chinese people were heading home for celebrating the Spring Festival, many latent cases left Wuhan, which led to the emergence of imported COVID-19 cases across the mainland of China and some other countries [4, 5]. Shanghai is one of the major cities with imported cases [4, 5].


title: Synthesis and Biological Activity of Several Modified 5α-Androstanolone Derivatives

text: Several new N-containing epiandrosterone derivatives modified by phenylacetic acid chloride were synthesized for biological activity studies. Compounds with antiviral activity were discovered among them and 3β-hydroxy-1′-aryl-3′-methyl-5′-androstano[17,16-d]pyrazolines prepared by us earlier.


Mayo Clinic Strategies for COVID-19 Rapid Appraisal System for COVID-19 Medical Information


title: Comparative safety of vaccine adjuvants: a summary of current evidence and future needs

text: Improved use of highly pure antigens to improve vaccine safety has led to reduced vaccine immunogenicity and efficacy. This has led to the need to use adjuvants to improve vaccine immunogenicity. The ideal adjuvant should maximize vaccine immunogenicity without compromising tolerability or safety or posing undue risk. Unfortunately, adjuvant research has lagged behind other vaccine areas such as antigen discovery, with the consequence that only a very limited number of adjuvants based on aluminum salts, monophosphoryl lipid A and oil emulsions are currently approved for human use. Recent strategic initiatives to support adjuvant development by the National Institutes of Health should translate into greater adjuvant choices in the future. Mechanistic studies have been valuable in better understanding adjuvant action but mechanisms of adjuvant toxicity are less well understood. The inflammatory or danger-signal model of adjuvant action implies that increased vaccine reactogenicity is the inevitable price for improved immunogenicity. Hence, adjuvant reactogenicity may be avoidable only if it is possible to separate inflammation from adjuvant action. The biggest remaining challenge in the adjuvant field is to decipher the potential relationship between adjuvants and rare vaccine adverse reactions such as narcolepsy, macrophagic myofasciitis or Alzheimer’s disease. While existing adjuvants based on aluminum salts have a strong safety record, there is an ongoing need for new adjuvants and for more intensive research into adjuvants and their effects.


title: Small islands and pandemic influenza: Potential benefits and limitations of travel volume reduction as a border control measure

text: BACKGROUND: Some island nations have explicit components of their influenza pandemic plans for providing travel warnings and restricting incoming travellers. But the potential value of such restrictions has not been quantified. METHODS: We developed a probabilistic model and used parameters from a published model (i.e., InfluSim) and travel data from Pacific Island Countries and Territories (PICTs). RESULTS: The results indicate that of the 17 PICTs with travel data, only six would be likely to escape a major pandemic with a viral strain of relatively low contagiousness (i.e., for R(0 )= 1.5) even when imposing very tight travel volume reductions of 99% throughout the course of the pandemic. For a more contagious viral strain (R(0 )= 2.25) only five PICTs would have a probability of over 50% to escape. The total number of travellers during the pandemic must not exceed 115 (for R(0 )= 3.0) or 380 (for R(0 )= 1.5) if a PICT aims to keep the probability of pandemic arrival below 50%. CONCLUSION: These results suggest that relatively few island nations could successfully rely on intensive travel volume restrictions alone to avoid the arrival of pandemic influenza (or subsequent waves). Therefore most island nations may need to plan for multiple additional interventions (e.g., screening and quarantine) to raise the probability of remaining pandemic free or achieving substantial delay in pandemic arrival.


title: Concomitant neurological symptoms observed in a patient diagnosed with coronavirus disease 2019

text: There has been a global outbreak of coronavirus disease 2019 (COVID‐19) since December 2019. In clinical practice, not only fever and respiratory tract symptoms but also multiple organ symptoms are observed in patients diagnosed with COVID‐19. Herein, we report a rare case of a patient diagnosed with COVID‐19 who manifested with concomitant neurological symptoms. The patient developed fever and respiratory symptoms at disease onset, followed by muscle soreness, and subsequently altered consciousness and psychiatric symptoms, with positive signs based on neurological examination. The patient tested positive for the severe acute respiratory syndrome corona virus 2 (SARS‐CoV‐2) nucleic acid (throat swab). Further, chest computed tomography (CT) revealed typical COVID‐19 findings, and head CT did not reveal significant abnormalities. The patient recovered after treatment and was discharged. This rare case indicates that SARS‐CoV‐2 can invade the central nervous system, thus causing neurological symptoms and signs. This article is protected by copyright. All rights reserved.