title: Expanding the size limit of RNA viruses: Evidence of a novel divergent nidovirus in California sea hare, with a ~35.9 kb virus genome

text: While RNA viruses thrive with massive structural and functional diversity, their genomes size variation is particularly low, ranging only from ~2-to-33 kb. Here, I present the characterization of RNA sequences corresponding to the first virus associated with Aplysia californica. Genome structure and domain architecture suggest that the identified virus is a novel member of Nidovirales. The proposed aplysia californica nido-like virus (AcNV), with a genome sequence of ca.35,906 nt, represents the longest ever recorded RNA virus yet. Phylogenetic insights indicate that AcNV clusters in a major phylloclade of unclassified invertebrate nidoviruses, Roniviridae, and Mesoniviridae. Basal branching in this emerging cluster could indicate that AcNV is a member of a novel divergent clade within Nidovirales. Further, virus RNA detection in multiple independent studies suggests that AcNV is neurotropic with a broad cell/tissue/organ tropism, supported by AcNV occurrence in diverse organs, including the first detection of a Nidovirales in single specific neurons. Highlights -RNA virus genomes reported in the literature are limited at ca. 33.4 kb -A novel nidovirus was identified in the gastropod mollusk Aplysia californica -The aplysia californica nido-like virus (AcNV) presents a 35.9 kb RNA genome -AcNV has a broad tropism, is enriched in the CNS, and accumulates in neurons -The unique features of A. californica enables single-neuron virus dynamics of AcNV


title: Cross-Regulation of Two Type I Interferon Signaling Pathways in Plasmacytoid Dendritic Cells Controls Anti-malaria Immunity and Host Mortality

text: Type I interferon (IFN) is critical for controlling pathogen infection; however, its regulatory mechanisms in plasmacytoid cells (pDCs) still remain unclear. Here, we have shown that nucleic acid sensors cGAS-, STING-, MDA5-, MAVS-, or transcription factor IRF3-deficient mice produced high amounts of type I IFN-α and IFN-β (IFN-α/β) in the serum and were resistant to lethal plasmodium yoelii YM infection. Robust IFN-α/β production was abolished when gene encoding nucleic acid sensor TLR7, signaling adaptor MyD88, or transcription factor IRF7 was ablated or pDCs were depleted. Further, we identified SOCS1 as a key negative regulator to inhibit MyD88-dependent type I IFN signaling in pDCs. Finally, we have demonstrated that pDCs, cDCs, and macrophages were required for generating IFN-α/β-induced subsequent protective immunity. Thus, our findings have identified a critical regulatory mechanism of type I IFN signaling in pDCs and stage-specific function of immune cells in generating potent immunity against lethal YM infection.


title: Ritter reaction-mediated syntheses of 2-oxaadamantan-5-amine, a novel amantadine analog

text: Two alternative syntheses of 2-oxaadamantan-5-amine, a novel analog of the clinically approved drug amantadine, are reported. The compound has been tested as an anti-influenza A virus agent and as an NMDA receptor antagonist. While the compound was not antivirally active, it displayed moderate activity as an NMDA receptor antagonist.


title: IL-15 INDEPENDENT MAINTENANCE OF VIRUS-SPECIFIC CD8(+) T CELLS IN THE CNS DURING CHRONIC INFECTION

text: The role of IL-15 in T cell survival was examined during chronic CNS coronavirus infection. Similar numbers of virus-specific CD8(+) T cells were retained in the CNS of IL-15(−/−)and wt mice, consistent with loss of IL-2/15 receptor (CD122) expression. IL-15 deficiency also had no affect on IL-7 receptor (CD127) expression, Bcl-2 upregulation, granzyme B expression, or IFN-γ secretion in CNS persisting CD8(+) T cells. Furthermore, CD8(+) T cell division in the CNS was reduced compared to spleen. CD8(+) T cells in the persistently infected CNS are thus characterized by IL-15 independent, low level proliferation and an activated/memory phenotype.


Invasive pulmonary aspergillosis in severe COVID-19 pneumonia


title: Transcription analysis of the porcine alveolar macrophage response to porcine circovirus type 2

text: BACKGROUND: Porcine circovirus type 2 (PCV2) is the causal agent of postweaning multisystemic wasting syndrome (PMWS), which has severely impacted the swine industry worldwide. PCV2 triggers a weak and atypical innate immune response, but the key genes and mechanisms by which the virus interferes with host innate immunity have not yet been elucidated. In this study, genes that control the response of primary porcine alveolar macrophages (PAMs), the main target of PCV2, were profiled in vitro. RESULTS: PAMs were successfully infected by PCV2-WH strain, as evidenced quantitative real-time polymerase chain reaction (qPCR) and immunofluorescence assay (IFA) results. Infection-related differential gene expression was investigated using pig microarrays from the US Pig Genome Coordination Program and validated by real-time PCR and enzyme-linked immunosorbent assay (ELISA). Microarray analysis at 24 and 48 hours post-infection (HPI) revealed 266 and 175 unique genes, respectively, that were differentially expressed (false discovery rate <0.05; fold-change >2). Only six genes were differentially expressed between 24 and 48 HPI. The up-regulated genes were principally related to immune response, cytokine activity, locomotion, regulation of cell proliferation, apoptosis, cell growth arrest, and antigen procession and presentation. The down-regulated genes were mainly involved in terpenoid biosynthesis, carbohydrate metabolism, translation, proteasome degradation, signal transducer activity, and ribosomal proteins, which were representative of the reduced vital activity of PCV2-infected cells. CONCLUSIONS: PCV2 infection of PAMs causes up-regulation of genes related to inflammation, indicating that PCV2 may induce systematic inflammation. PCV2 persistently induced cytokines, mainly through the Toll-like receptor (TLR) 1 and TLR9 pathways, which may promote high levels of cytokine secretion. PCV2 may prevent apoptosis in PAMs by up-regulating SERPINB9 expression, possibly to lengthen the duration of PCV2 replication-permissive conditions. The observed gene expression profile may provide insights into the underlying immunological response and pathological changes that occur in pigs following PCV2 infection.


title: 3D-printed contact-free devices designed and dispatched against the COVID19 pandemic: the 3D COVID initiative

text: Abstract Contacts with public devices such as elevator buttons, beepers, telephones, computer mice and keyboards can contribute to spread viral diseases. Here we report our experience in designing, producing and dispatching three 3D-printed objected intending to lower the risks of COVID19 contamination by limiting direct contacts: (1) fixed hand-free door openers, (2) door hooks and (3) button pushers. These devices were produced in industrial quantities and made available for free for Greater Paris University Hospitals and various state institutions as part of the 3D COVID project. In this short technical note, we describe the sequential organisation of the design and production and highlight the advantages of additive manufacturing in dealing with specific aspects of sanitary crises.


title: Regulation of Cytokine Production by the Unfolded Protein Response; Implications for Infection and Autoimmunity

text: Protein folding in the endoplasmic reticulum (ER) is an essential cell function. To safeguard this process in the face of environmental threats and internal stressors, cells mount an evolutionarily conserved response known as the unfolded protein response (UPR). Invading pathogens induce cellular stress that impacts protein folding, thus the UPR is well situated to sense danger and contribute to immune responses. Cytokines (inflammatory cytokines and interferons) critically mediate host defense against pathogens, but when aberrantly produced, may also drive pathologic inflammation. The UPR influences cytokine production on multiple levels, from stimulation of pattern recognition receptors, to modulation of inflammatory signaling pathways, and the regulation of cytokine transcription factors. This review will focus on the mechanisms underlying cytokine regulation by the UPR, and the repercussions of this relationship for infection and autoimmune/autoinflammatory diseases. Interrogation of viral and bacterial infections has revealed increasing numbers of examples where pathogens induce or modulate the UPR and implicated UPR-modulated cytokines in host response. The flip side of this coin, the UPR/ER stress responses have been increasingly recognized in a variety of autoimmune and inflammatory diseases. Examples include monogenic disorders of ER function, diseases linked to misfolding protein (HLA-B27 and spondyloarthritis), diseases directly implicating UPR and autophagy genes (inflammatory bowel disease), and autoimmune diseases targeting highly secretory cells (e.g., diabetes). Given the burgeoning interest in pharmacologically targeting the UPR, greater discernment is needed regarding how the UPR regulates cytokine production during specific infections and autoimmune processes, and the relative place of this interaction in pathogenesis.


title: Can vitamins and/or supplements provide hope against coronavirus?

text: Severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) quickly became a global pandemic and has been responsible, so far, for infecting 5.8 million and claiming the lives of more than 350,000. While certain medications initially garnered attention as potential treatment options, further studies failed to demonstrate great promise but did demonstrate the need to reduce the cytokine storm experienced by patients with this potentially life-threatening virus. Unfortunately, there is no cure on the horizon, but members of the medical community are beginning to evaluate the potential role of vitamins and supplements as potential treatment options or addition to other treatments. The goal of this narrative review is to evaluate current and ongoing clinical trials of vitamins and supplements, alone or in combination with each other or other therapies, for the treatment of coronavirus disease-2019 (COVID-19).


title: In-hospital Use of Statins is Associated with a Reduced Risk of Mortality among Individuals with COVID-19

text: Summary Statins are lipid-lowering therapeutics with favorable anti-inflammatory profiles and have been proposed as an adjunct therapy for COVID-19. However, statins may increase the risk of SARS-CoV-2 viral entry by inducing ACE2 expression. Here, we performed a retrospective study on 13,981 patients with COVID-19 in Hubei Province, China, among which 1,219 received statins. Based on a Cox model with time-varying exposure, as well as a mixed-effect Cox model after propensity score-matching, we found that the risk for 28-day all-cause mortality was 5.2% and 9.4% in the matched statin and non-statin groups, respectively, with a hazard ratio 0.58. These results imply the potential benefits of statin therapy in hospitalized subjects with COVID-19. Further, they give support for the completion of on-going prospective studies and randomized controlled trials involving statin treatment for COVID-19, which are needed to further validate the utility of this class of drugs to combat the mortality of this pandemic.


title: The impact of influenza infection on young children, their family and the health care system

text: BACKGROUND: Influenza is a major cause of respiratory illness in young children. Assessing the impact of infection on children and the community is required to guide immunisation policies. OBJECTIVES: To describe the impact of laboratory‐proven influenza in young children and to compare its impact with that of other respiratory viruses on the child, their family and the health care system. METHODS: Preschool children presenting for care or admission to a tertiary paediatric hospital during the 2008‐2014 influenza seasons were tested for respiratory virus by polymerase chain reaction and culture. Parental surveys were used to determine the impact of infection on illness duration, medication use, absenteeism and health service utilisation. Multivariate regression analyses were used to assess the impact of influenza and to evaluate the association between influenza status and outcomes. RESULTS: Among 1191 children assessed, 238 had influenza. Among children with influenza, 87.8% were administered antipyretics and 40.9% antibiotics. 28.6% had secondary complications. 65.4% of children missed school/day care, and 53.4% of parents missed work. When influenza and other viruses were compared, significant differences were noted including duration of illness (influenza: 9.54 days, other viruses: 8.50 days; P = 0.005) and duration of absenteeism for both the child (23.1 vs 17.3 hours; P = 0.015) and their parents (28.5 vs 22.7 hours; P = 0.012). CONCLUSIONS: Influenza infection in young children has a significant impact on medication use, absenteeism and the use of health care service. Significant differences are identified when compared with other ILI. These data demonstrate that influenza prevention strategies including immunisation are likely to have wide and significant impacts.


title: Phosphonylated Acyclic Guanosine Analogues with the 1,2,3-Triazole Linker

text: A novel series of {4-[(2-amino-6-chloro-9H-purin-9-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates and {4-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates as acyclic analogues of guanosine were synthesized and assessed for antiviral activity against a broad range of DNA and RNA viruses and for their cytostatic activity toward three cancerous cell lines (HeLa, L1210 and CEM). They were devoid of antiviral activity; however, several phosphonates were found slightly cytostatic against HeLa cells at an IC(50) in the 80–210 µM range. Compounds (1R,2S)-17k and (1S,2S)-17k showed the highest inhibitory effects (IC(50) = 15–30 µM) against the proliferation of murine leukemia (L1210) and human T-lymphocyte (CEM) cell lines.


title: Comparing COVID-19 and the 1918–19 influenza pandemics in United Kingdom

text: Abstract We compare the COVID-19 pandemic and 1918-19 influenza pandemic in United Kingdom. We found that the on-going COVID-19 wave of infection matched the major wave of the 1918-19 influenza pandemic surprisingly well, both reached similar magnitude (in term of estimated weekly new infections) and spent the same duration above 5 cases per 1000 inhabitants, for the past two months. We discussed the similar characteristics between these two pandemics.


title: COVID-19–Related Collapsing Glomerulopathy in a Kidney Transplant Recipient

text: We report a case of a kidney transplant recipient who presented with acute kidney injury and nephrotic-range proteinuria in a context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Kidney biopsy revealed collapsing glomerulopathy. Droplet-based digital PCR did not detect the presence of SARS-CoV-2 RNA in the biopsy fragment, and the virus was barely detectable in the plasma at the time of the biopsy. SARS-CoV-2 RNAemia peaked several days later, followed by a seroconversion despite the absence of circulating CD19-positive lymphocytes at admission due to rituximab-based treatment of antibody-mediated rejection 3 months earlier. Genotyping for the two risk alleles of the apolipoprotein L1 (APOL1) gene revealed that the donor carried the low-risk G0/G2 genotype. This case illustrates that COVID-19 may promote a collapsing glomerulopathy in kidney allografts with a low-risk APOL1 genotype, in the absence of detectable SARS-CoV2 RNA in the kidney, and that podocyte injury may precede SARS-CoV2 RNAemia.


Ejercitarse en tiempos del COVID-19: ¿qué recomiendan los expertos hacer entre cuatro paredes?


title: Rôle des animaux vertébrés dans l’épidémiologie des zoonoses

text: Résumé Les zoonoses, distinguées ici des maladies humaines d’origine animale, représentent un ensemble d’entités pathologiques dont les agents responsables circulent régulièrement entre l’espèce humaine et de nombreuses espèces de vertébrés. L’analyse de divers exemples, quelles que soient les voies de transmission et les causes favorisantes de la contamination, met en avant une régulière rareté du passage direct du réservoir animal vers l’espèce humaine, à opposer à la diversité et surtout à la gravité possible des évolutions sanitaires ultérieures possibles, parfois liées à des comportements humains peu adaptés. D’un point de vue pratique, il semblerait plus pertinent de se pencher d’abord sur un meilleur contrôle de la diffusion des agents pathogènes au sein des populations humaines que d’agir a priori sur le réservoir animal, qu’il soit domestique ou sauvage, source potentielle de ces agents pathogènes mais selon des modalités difficiles à anticiper. La relation entre biodiversité et santé est abordée à l’occasion de la discussion. Summary Zoonoses, to be distinguished here from human diseases with an animal origin, represent a large quantity of pathological entities the corresponding pathogens of which are regularly shared between human beings and many different vertebrates species. Working on selected examples and situations, whatever the contamination routes and the facilitating reasons, puts into light a real rarity of a direct transmission from the animal reservoir to human beings. On the opposite, the diversity and the possible severity of some of the sanitary consequences, quite often in relation to human behaviours, must be stressed. On a practical point of view, it seems more adapted to try first to improve the control of pathogens diffusion within human populations after a contamination than to try to start to work first on the reservoir, be it domestic or wild, the potential source of these pathogens, but following routes quite difficult to anticipate. The relationship between biodiversity and health is discussed.


title: Rapid and Long-Term Immunity Elicited by DNA-Encoded Antibody Prophylaxis and DNA Vaccination Against Chikungunya Virus

text: Background. Vaccination and passive antibody therapies are critical for controlling infectious diseases. Passive antibody administration has limitations, including the necessity for purification and multiple injections for efficacy. Vaccination is associated with a lag phase before generation of immunity. Novel approaches reported here utilize the benefits of both methods for the rapid generation of effective immunity. Methods. A novel antibody-based prophylaxis/therapy entailing the electroporation-mediated delivery of synthetic DNA plasmids encoding biologically active anti–chikungunya virus (CHIKV) envelope monoclonal antibody (dMAb) was designed and evaluated for antiviral efficacy, as well as for the ability to overcome shortcomings inherent with conventional active vaccination and passive immunotherapy. Results. One intramuscular injection of dMAb produced antibodies in vivo more rapidly than active vaccination with an anti-CHIKV DNA vaccine. This dMAb neutralized diverse CHIKV clinical isolates and protected mice from viral challenge. Combination of dMAb and the CHIKV DNA vaccine afforded rapid and long-lived protection. Conclusions. A DNA-based dMAb strategy induced rapid protection against an emerging viral infection. This method can be combined with DNA vaccination as a novel strategy to provide both short- and long-term protection against this emerging infectious disease. These studies have implications for pathogen treatment and control strategies.


title: AJN On the Web.

text: Objectives In late December, 2019, an outbreak of coronavirus disease (COVID-19) in Wuhan, China was caused by a novel coronavirus, newly named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) We aimed to quantify severity of COVID-19 infection on High-Resolution CT and to determine its relationship with clinical parameters Materials and Methods From Jan 11, 2020, to Feb 5, 2020, the clinical, laboratory and HRCT features of 42 patients (26-75 years, 25 males) with COVID-19 were analyzed The initial and follow-up CT obtained a mean of 4 5 days and 11 6 days from the illness onset were retrospectively assessed for the severity and progression of pneumonia Correlations among clinical parameters, initial CT features and progression of opacifications were evaluated with Spearman correlation and linear regression analysis Results Thirty-five (83%) patients exhibited a progressive process according to CT features during the early stage from onset Follow-up CT findings showed progressive opacifications, consolidation, interstitial thickening, fibrous strips and air bronchograms, compared to initial CT (all p<0 05) Before regular treatments, there was a moderate correlation between the days from onset and sum score of opacifications (R=0 68, p<0 01) The C-reactive protein, erythrocyte sedimentation rate and lactate dehydrogenase showed significantly positive correlation with the severity of pneumonia assessed on initial CT (R range 0 36-0 75, p<0 05) The highest temperature and the severity of opacifications assessed on initial CT were significantly related to the progression of opacifications on follow-up CT (p=0 001-0 04) Conclusions Patients with the COVID-19 infection usually presented with typical ground-grass opacities and other CT features, which showed significant correlations with some clinical and laboratory measurements Follow-up CT images often demonstrated progressions during the early stage from illness onset Corresponding author: Xiaoming Li, MD, PhD, Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, 430030, Wuhan, China lilyboston2002@ 163 com;Wenzhen Zhu, MD, PhD, Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, 430030, Wuhan, China zhuwenzhen8612@163 com Ying Xiong and Dong Sun contributed equally and share the first authorship This work was supported, in part, by the National Natural Science Foundation of China (grant numbers: 81730049, 81930045, 31630025 and 81601480) Copyright © 2020 Wolters Kluwer Health, Inc All rights reserved


title: Telemedicine in the Era of COVID-19: The Virtual Orthopaedic Examination

text: With the onset of the COVID-19 pandemic, the shifting of clinical care to telemedicine visits has been hastened. Because of current limitations in resources, many elective surgeons have been forced to venture into utilizing telemedicine, in which the standards for orthopaedic examinations have not previously been fully developed. We report our experience with protocols and methods to standardize these visits to maximize the benefit and efficiency of the virtual orthopaedic examination. At the time of scheduling, patients are asked to prepare for their virtual visit and are given a checklist. In addition to confirming audiovisual capabilities prior to the visit, patients are given specific instructions on camera positioning, body positioning, setting, and attire to improve the efficiency of the visit. During the examination, digital tools can be utilized as needed. In the setting of outpatient injury evaluations, a systematic virtual examination can aid in triaging and managing common musculoskeletal conditions. With the rapid incorporation of telehealth visits, as well as the unknown future with regard to the pandemic, the utilization and capabilities of telemedicine will continue to expand. Future directions include the development of validated, modified examination techniques and new technology that will allow for improved interactive physical examinations, as we rapidly move forward into the realm of telemedicine due to unexpected necessity.


title: Depression, Anxiety and Stress during COVID-19: Associations with Changes in Physical Activity, Sleep, Tobacco and Alcohol Use in Australian Adults

text: The novel coronavirus (COVID-19) has enforced dramatic changes to daily living including economic and health impacts. Evidence for the impact of these changes on our physical and mental health and health behaviors is limited. We examined the associations between psychological distress and changes in selected health behaviors since the onset of COVID-19 in Australia. An online survey was distributed in April 2020 and included measures of depression, anxiety, stress, physical activity, sleep, alcohol intake and cigarette smoking. The survey was completed by 1491 adults (mean age 50.5 ± 14.9 years, 67% female). Negative change was reported for physical activity (48.9%), sleep (40.7%), alcohol (26.6%) and smoking (6.9%) since the onset of the COVID-19 pandemic. Significantly higher scores in one or more psychological distress states were found for females, and those not in a relationship, in the lowest income category, aged 18–45 years, or with a chronic illness. Negative changes in physical activity, sleep, smoking and alcohol intake were associated with higher depression, anxiety and stress symptoms. Health-promotion strategies directed at adopting or maintaining positive health-related behaviors should be utilized to address increases in psychological distress during the pandemic. Ongoing evaluation of the impact of lifestyle changes associated with the pandemic is needed.


title: Detection of Canine Distemper Virus in Blood Samples by Reverse Transcription Loop‐Mediated Isothermal Amplification

text: Reverse transcription loop‐mediated isothermal amplification (RT‐LAMP) was used to detect canine distemper virus (CDV) genomic RNA. A set of four primers, two outer and two inner, were designed from CDV genomic RNA targeting the nucleocapsid protein gene. The optimal reaction time and temperature for LAMP were determined to be 60 min at 65°C. The relative sensitivity and specificity of RT‐LAMP was found to be 100% and 93.3%, respectively, based on 50 canine blood samples and using RT‐PCR as the gold standard. The detection limit of the RT‐LAMP method was 100 times lower than with RT‐PCR (10‐1TCID50 ml(−1) versus 10TCID50 ml(−1)). In addition to the advantage resulting from the visual detection of the end‐product, the LAMP method is fast, requiring only 1 h to complete the assay. The LAMP method is a viable alternative to RT‐PCR for diagnosing CDV infection in dogs. The LAMP method might be useful as an on site diagnostic assay for detecting CDV.


title: Preventing healthcare-associated transmission of the Middle East Respiratory Syndrome (MERS): Our Achilles heel

text: Summary Middle East Respiratory Syndrome (MERS) coronavirus is the most recent among the Coronaviridae family to jump species and infect humans. Major healthcare associated MERS outbreaks have occurred in the Middle East and Korea that affected both patients and healthcare workers. These outbreaks were characterized by intra and inter-hospital spread and were exacerbated specifically by overcrowding, delayed diagnosis and appropriate use of personal protective equipment. Recent experience with this virus emphasizes the importance of compliance with infection control practices and with other interventions addressing patient triage, placement and flow within and between healthcare facilities. Our Achilles heel remains compliance with the best infection prevention practices and their harmonization with patient flow. Both infection prevention compliance and maintenance of patient flow are critical in preventing healthcare-associated transmission of many of these emerging infectious diseases, including MERS.


title: Environmental persistence of porcine coronaviruses in feed and feed ingredients

text: Porcine Epidemic Diarrhea Virus (PEDV), Porcine Delta Corona Virus (PDCoV), and Transmissible Gastroenteritis Virus (TGEV) are major threats to swine health and contaminated feed plays a role in virus transmission. The objective of our study was to characterize inactivation of PEDV, PDCoV, and TGEV in various feed ingredient matrices. Samples of complete feed, spray dried porcine plasma, meat meal, meat and bone meal, blood meal, corn, soybean meal, and corn dried distillers grains with solubles were weighed (5 g/sample) into scintillation vials and inoculated with 1 mL of PEDV, PDCoV, or TGEV. Samples were incubated at room temperature for up to 56 days. Aliquots were removed at various time points followed by preparing serial 10-fold dilutions and inoculating in cell cultures to determine the amount of surviving virus. Inactivation kinetics were determined using the Weibull model, which estimates a delta value indicating the time necessary to reduce virus concentration by 1 log. Delta values of various ingredients were compared and analyzed as to their nutrient composition. Soybean meal had the greatest delta value (7.50 days) for PEDV (P < 0.06) as compared with all other ingredients. High delta values (P < 0.001) were observed in soybean meal for PDCoV (42.04 days) and TGEV (42.00 days). There was a moderate correlation between moisture content and the delta value for PDCoV (r = 0.49, P = 0.01) and TGEV (r = 0.41, P = 0.02). There was also a moderate negative correlation between TGEV survival and ether extract content (r = -0.51, P = 0.01). In conclusion, these results indicate that the first log reduction of PDCoV and TGEV takes the greatest amount of time in soybean meal. In addition to this, moisture and ether content appear to be an important determinant of virus survival in feed ingredients.


title: Web-based participatory surveillance of infectious diseases: the Influenzanet participatory surveillance experience

text: To overcome the limitations of the state-of-the-art influenza surveillance systems in Europe, we established in 2008 a European-wide consortium aimed at introducing an innovative information and communication technology approach for a web-based surveillance system across different European countries, called Influenzanet. The system, based on earlier efforts in The Netherlands and Portugal, works with the participation of the population in each country to collect real-time information on the distribution of influenza-like illness cases through web surveys administered to volunteers reporting their symptoms (or lack of symptoms) every week during the influenza season. Such a large European-wide web-based monitoring infrastructure is intended to rapidly identify public health emergencies, contribute to understanding global trends, inform data-driven forecast models to assess the impact on the population, optimize the allocation of resources, and help in devising mitigation and containment measures. In this article, we describe the scientific and technological issues faced during the development and deployment of a flexible and readily deployable web tool capable of coping with the requirements of different countries for data collection, during either a public health emergency or an ordinary influenza season. Even though the system is based on previous successful experience, the implementation in each new country represented a separate scientific challenge. Only after more than 5 years of development are the existing platforms based on a plug-and-play tool that can be promptly deployed in any country wishing to be part of the Influenzanet network, now composed of The Netherlands, Belgium, Portugal, Italy, the UK, France, Sweden, Spain, Ireland, and Denmark.


All eyes on Coronavirus—What do we need to know as ophthalmologists


title: Drug screening identifies gemcitabine inhibiting rotavirus through alteration of pyrimidine nucleotide synthesis pathway

text: Although rotavirus infection is usually acute and self-limiting, it can cause chronic infection with severe diseases in immunocompromised patients, including organ transplantation recipients and cancer patients irrespective of pediatric or adult patients. Since no approved medication against rotavirus infection is available, this study screened a library of safe-in-man broad-spectrum antivirals. We identified gemcitabine, a widely used anti-cancer drug, as a potent inhibitor of rotavirus infection. We confirmed this effect in 2D cell cultures and 3D cultured human intestinal organoids with both laboratory-adapted rotavirus strains and five clinical isolates. Supplementation of UTP or uridine largely abolished the anti-rotavirus activity of gemcitabine, suggesting its function through inhibition of pyrimidine biosynthesis pathway. Our results support repositioning of gemcitabine for treating rotavirus infection, especially for infected cancer patients.


title: Endovascular stroke treatment during the COVID-19 pandemic

text: The COVID-19 pandemic has added an additional layer of complexity to endovascular treatment (EVT) for acute ischaemic stroke. Drawing on recently published guidelines, this article provides a conceptual framework for EVT in the COVID-19 era, outlining key principles for ensuring safe and timely EVT while minimizing the risk of infectious exposure for health-care workers and patients.


Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Oman: Current Situation and Going Forward


Posibles factores protectores de la infección por SARS-CoV-2 en una paciente vulnerable: a propósito de un caso


title: Panmicrobial Oligonucleotide Array for Diagnosis of Infectious Diseases

text: To facilitate rapid, unbiased, differential diagnosis of infectious diseases, we designed GreeneChipPm, a panmicrobial microarray comprising 29,455 sixty-mer oligonucleotide probes for vertebrate viruses, bacteria, fungi, and parasites. Methods for nucleic acid preparation, random primed PCR amplification, and labeling were optimized to allow the sensitivity required for application with nucleic acid extracted from clinical materials and cultured isolates. Analysis of nasopharyngeal aspirates, blood, urine, and tissue from persons with various infectious diseases confirmed the presence of viruses and bacteria identified by other methods, and implicated Plasmodium falciparum in an unexplained fatal case of hemorrhagic feverlike disease during the Marburg hemorrhagic fever outbreak in Angola in 2004–2005.


title: Viable supply chain model: integrating agility, resilience and sustainability perspectives—lessons from and thinking beyond the COVID-19 pandemic

text: Viability is the ability of a supply chain (SC) to maintain itself and survive in a changing environment through a redesign of structures and replanning of performance with long-term impacts. In this paper, we theorize a new notion—the viable supply chain (VSC). In our approach, viability is considered as an underlying SC property spanning three perspectives, i.e., agility, resilience, and sustainability. The principal ideas of the VSC model are adaptable structural SC designs for supply–demand allocations and, most importantly, establishment and control of adaptive mechanisms for transitions between the structural designs. Further, we demonstrate how the VSC components can be categorized across organizational, informational, process-functional, technological, and financial structures. Moreover, our study offers a VSC framework within an SC ecosystem. We discuss the relations between resilience and viability. Through the lens and guidance of dynamic systems theory, we illustrate the VSC model at the technical level. The VSC model can be of value for decision-makers to design SCs that can react adaptively to both positive changes (i.e., the agility angle) and be able to absorb negative disturbances, recover and survive during short-term disruptions and long-term, global shocks with societal and economical transformations (i.e., the resilience and sustainability angles). The VSC model can help firms in guiding their decisions on recovery and re-building of their SCs after global, long-term crises such as the COVID-19 pandemic. We emphasize that resilience is the central perspective in the VSC guaranteeing viability of the SCs of the future. Emerging directions in VSC research are discussed.


title: Internet of things (IoT) applications to fight against COVID-19 pandemic

text: Abstract Background and aim The current global challenge of COVID-19 pandemic has surpassed the provincial, radical, conceptual, spiritual, social, and pedagogical boundaries. Internet of Things (IoT) enabled healthcare system is useful for proper monitoring of COVID-19 patients, by employing an interconnected network. This technology helps to increase patient satisfaction and reduces readmission rate in the hospital. Methods Searched the databases of Google Scholar, PubMed, SCOPUS and ResearchGate using the keywords “Internet of things” or “IoT” and “COVID-19”. Further inputs are also taken from blogs and relevant reports. Results IoT implementation impacts on reducing healthcare cost and improve treatment outcome of the infected patient. Therefore, this present study based research is attempted to explore, discuss, and highlight the overall applications of the well-proven IoT philosophy by offering a perspective roadmap to tackle the COVID-19 pandemic. Finally, twelve significant applications of IoT are identified and discussed. It has ultimately forced the researchers, academicians, and scientists to propose some productive solutions to overcome or confront this pandemic. Conclusions IoT is helpful for an infected patient of COVID-19 to identify symptoms and provides better treatment rapidly. It is useful for patient, physician, surgeon and hospital management system.


title: Characteristics of air pollutant dispersion around a high-rise building

text: A numerical wind tunnel model was proposed. The computed results of the pollutant diffusion around a typical Hong Kong high-rise building model (at a linear scale of 1:30), were found to show a similar trend to the outcomes of self-conducted experimental measurements that the pathways of pollutant migration for windward and leeward pollutant emission are different. For the case with windward pollutant emission at the 3rd floor within a re-entry, the pollutant migrated downwards due to the downwash created by the wind. In contrast, for the case with leeward pollution emission, dispersion is dominated by intense turbulent mixing in the near wake and characterized by the upward migration of the pollutant in the leeward re-entry. The simulated results of haze-fog (HF) studies confirm that the pathway of pollutant migration is dominated by wind–structure interaction and buoyancy effect only plays a minor role in the dispersion process.


title: Nanomedicines for the Delivery of Antimicrobial Peptides (AMPs)

text: Microbial infections are still among the major public health concerns since several yeasts and fungi, and other pathogenic microorganisms, are responsible for continuous growth of infections and drug resistance against bacteria. Antimicrobial resistance rate is fostering the need to develop new strategies against drug-resistant superbugs. Antimicrobial peptides (AMPs) are small peptide-based molecules of 5–100 amino acids in length, with potent and broad-spectrum antimicrobial properties. They are part of the innate immune system, which can represent a minimal risk of resistance development. These characteristics contribute to the description of these molecules as promising new molecules in the development of new antimicrobial drugs. However, efforts in developing new medicines have not resulted in any decrease of drug resistance yet. Thus, a technological approach on improving existing drugs is gaining special interest. Nanomedicine provides easy access to innovative carriers, which ultimately enable the design and development of targeted delivery systems of the most efficient drugs with increased efficacy and reduced toxicity. Based on performance, successful experiments, and considerable market prospects, nanotechnology will undoubtedly lead a breakthrough in biomedical field also for infectious diseases, as there are several nanotechnological approaches that exhibit important roles in restoring antibiotic activity against resistant bacteria.


title: Predicting the effects of parasite co-infection across species boundaries

text: It is normal for hosts to be co-infected by parasites. Interactions among co-infecting species can have profound consequences, including changing parasite transmission dynamics, altering disease severity and confounding attempts at parasite control. Despite the importance of co-infection, there is currently no way to predict how different parasite species may interact with one another, nor the consequences of those interactions. Here, we demonstrate a method that enables such prediction by identifying two nematode parasite groups based on taxonomy and characteristics of the parasitological niche. From an understanding of the interactions between the two defined groups in one host system (wild rabbits), we predict how two different nematode species, from the same defined groups, will interact in co-infections in a different host system (sheep), and then we test this experimentally. We show that, as predicted, in co-infections, the blood-feeding nematode Haemonchus contortus suppresses aspects of the sheep immune response, thereby facilitating the establishment and/or survival of the nematode Trichostrongylus colubriformis; and that the T. colubriformis-induced immune response negatively affects H. contortus. This work is, to our knowledge, the first to use empirical data from one host system to successfully predict the specific outcome of a different co-infection in a second host species. The study therefore takes the first step in defining a practical framework for predicting interspecific parasite interactions in other animal systems.


title: Significant alterations of biodistribution and immune responses in Balb/c mice administered with adenovirus targeted to CD40(+) cells

text: CD40 ligation has been shown to promote antigen-presenting functions of dendritic cells, which express CD40 receptor. Here we reported significantly altered biodistribution and immune responses with the use of CD40-targeted adenovirus. Compared with unmodified adenovirus 5, the CD40-targeted adenovirus following intravenous administration (i.v.) resulted in increased transgene expressions in the lung and thymus, which normally do not take up significant amounts of adenovirus. Intradermal injection saw modified adenovirus being mainly processed in local draining lymph nodes and skin. Following intranasal administration (i.n.), neither unmodified nor targeted viruses were found to be in the liver or spleen, which predominantly took up the virus following i.v. administration. However, inadvertent infection of the brain was found with unmodified adenoviruses, with the second highest gene expression among 14 tissues examined. Importantly, such undesirable effects were largely ablated with the use of targeted vector. Moreover, the targeted adenovirus elicited more sustained antigen-specific cellular immune responses (up to 17-fold) at later time points (30 days post boosting), but also significantly hampered humoral responses irrespective of administration routes. Additional data suggest the skewed immune responses induced by the targeted adenoviruses were not due to the identity of the transgene but more likely a combination of overall transgene load and CD40 stimulation. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/sj.gt.3303085) contains supplementary material, which is available to authorized users.


title: Deep Learning Based Drug Screening for Novel Coronavirus 2019-nCov

text: A novel coronavirus, called 2019-nCoV, was recently found in Wuhan, Hubei Province of China, and now is spreading across China and other parts of the world. Although there are some drugs to treat 2019-nCoV, there is no proper scientific evidence about its activity on the virus. It is of high significance to develop a drug that can combat the virus effectively to save valuable human lives. It usually takes a much longer time to develop a drug using traditional methods. For 2019-nCoV, it is now better to rely on some alternative methods such as deep learning to develop drugs that can combat such a disease effectively since 2019-nCoV is highly homologous to SARS-CoV. In the present work, we first collected virus RNA sequences of 18 patients reported to have 2019-nCoV from the public domain database, translated the RNA into protein sequences, and performed multiple sequence alignment. After a careful literature survey and sequence analysis, 3C-like protease is considered to be a major therapeutic target and we built a protein 3D model of 3C-like protease using homology modeling. Relying on the structural model, we used a pipeline to perform large scale virtual screening by using a deep learning based method to accurately rank/identify protein–ligand interacting pairs developed recently in our group. Our model identified potential drugs for 2019-nCoV 3C-like protease by performing drug screening against four chemical compound databases (Chimdiv, Targetmol-Approved_Drug_Library, Targetmol-Natural_Compound_Library, and Targetmol-Bioactive_Compound_Library) and a database of tripeptides. Through this paper, we provided the list of possible chemical ligands (Meglumine, Vidarabine, Adenosine, d-Sorbitol, d-Mannitol, Sodium_gluconate, Ganciclovir and Chlorobutanol) and peptide drugs (combination of isoleucine, lysine and proline) from the databases to guide the experimental scientists and validate the molecules which can combat the virus in a shorter time. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12539-020-00376-6) contains supplementary material, which is available to authorized users.


Ivermectin and COVID-19: a report in Antiviral Research, widespread interest, an FDA warning, two letters to the editor and the authors' responses


title: Virologic and serologic surveillance for human, swine and avian influenza virus infections among pigs in the north-central United States

text: Influenza virus infection in pigs is both an animal health problem and a public health concern. As such, surveillance and characterization of influenza viruses in swine is important to the veterinary community and should be a part of human pandemic preparedness planning. Studies in 1976/1977 and 1988/1989 demonstrated that pigs in the U.S. were commonly infected with classical swine H1N1 viruses, whereas human H3 and avian influenza virus infections were very rare. In contrast, human H3 and avian H1 viruses have been isolated frequently from pigs in Europe and Asia over the last two decades. From September 1997 through August 1998, we isolated 26 influenza viruses from pigs in the north-central United States at the point of slaughter. All 26 isolates were H1N1 viruses, and phylogenetic analyses of the hemagglutinin and nucleoprotein genes from 11 representative viruses demonstrated that these were classical swine H1 viruses. However, monoclonal antibody analyses revealed antigenic heterogeneity among the HA proteins of the 26 viruses. Serologically, 27.7% of 2,375 pigs tested had hemagglutination-inhibiting antibodies against classical swine H1 influenza virus. Of particular significance, however, the rates of seropositivity to avian H1 (7.6%) and human H3 (8.0%) viruses were substantially higher than in previous studies.


title: Potentiation of bradykinin actions by analogues of the bradykinin potentiating nonapeptide BPP(9α)

text: Synthetic analogues of the bradykinin potentiating nonapeptide BPP(9α) indicate significantly different structural requirements for potentiation of the bradykinin (BK)-induced smooth muscle contraction (GPI) and the inhibition of isolated somatic angiotensin I-converting enzyme (ACE). The results disprove the ACE inhibition as the only single mechanism and also the direct interaction of potentiating peptides with the bradykinin receptors in transfected COS-7 cells as molecular mechanism of potentiation. Our results indicate a stimulation of inositol phosphates (IP(n)) formation independently from the B(2) receptor. Furthermore, the results with La(3+) support the role of extracellular Ca(2+) and its influx through corresponding channels. The missing effect of calyculin on the GPI disproves the role of phosphatases in the potentiating action. These experimental studies should not only contribute to a better understanding of the potentiating mechanisms but also incorporate a shift in the research towards the immune system, in particular towards the immunocompetent polymorphonuclear leukocytes. The chemotaxis of these cells can be potentiated most likely by exclusive inhibition of the enzymatic degradation of bradykinin. Thus the obtained results give evidence that the potentiation of the bradykinin action can occur by different mechanisms, depending on the system and on the applied potentiating factor.


title: Genetic Epidemiology of Acute Respiratory Distress Syndrome: Implications for Future Prevention and Treatment

text: The genetic susceptibility to the development of and variable outcomes in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) has become a topic of great interest in the pulmonary and critical care community. Published studies of variable genetic susceptibility to ALI/ARDS already have identified some important candidate genes and potential gene-environment interactions. This article reviews these recent studies, features of the current approach, and implications for future prevention and treatment in ALI. The challenges and potential contributions of genetic epidemiology to the future prevention and treatment in ALI are discussed.


title: A nursing informatics response to COVID‐19: perspectives from five regions of the world

text: The 21st century has seen several infectious disease outbreaks that have turned into epidemics and pandemics including Severe Acute Respiratory Syndrome (SARS) which began in Asia in 2003 (Poon, Guan, Nicholls, Yuen, & Peiris, 2004), followed by H1N1 that emerged in Mexico and the United States in 2009 (Belongia et al., 2010). Next came the lesser known Middle East Respiratory Syndrome (MERS) originating in Saudi Arabia in 2012 (Assiri et al., 2013), after which the Ebola outbreak in West Africa took place from 2014 to 2016, with a more recent occurrence in the Democratic Republic of Congo from 2018 to 2019 (Malvy, McElroy, de Clerck, Günther, & van Griensven, 2019). To date, the coronavirus (COVID‐19) outbreak that started in Wuhan, in the Hubei province of China, in late December 2019 seems to be eclipsing all of these previous infectious diseases in terms of its global reach and impact (Wang, Horby, Hayden, & Gao, 2020). After being declared by the World Health Organization (WHO) as a public health emergency on 30 January 2020 (World Health Organization, 2020c), it was elevated to a pandemic status on 11 March 2020 (World Health Organization, 2020d). As of 28 April 2020, there are more than 2.9 million cases and 202,597 deaths reported worldwide (World Health Organization, 2020b).


title: Influence of Pooled Colostrum or Colostrum Replacement on IgG and Evaluation of Animal Plasma in Milk Replacer

text: Abstract Newborn Holstein (n=48) and Jersey (n=30) calves were studied to compare absorption of immunoglobulin G (IgG) from maternal colostrum (n=39) or colostrum replacement containing an Ig concentrate derived from bovine serum (n=39). Calves were also fed milk replacer with (n=38) or without (n=40) animal plasma (20% of crude protein) to 29 d of age to determine effect of plasma protein on IgG status, health, and growth. Calves were fed maternal colostrum or colostrum replacement at 1.5 and 13.5h of age and provided a total of 250 or 249 and 180 or 186g of IgG for Holsteins and Jerseys fed maternal colostrum or colostrum replacement, respectively. Milk replacer (12.5% DM) was fed at 31% of metabolic birth weight (2 feedings/d). Plasma was sampled at 0h, 24h, and weekly to determine IgG by turbidimetric immunoassay. At blood collection, calves were weighed and measured to determine growth. Health scores, fecal scores, and grain intake were measured daily. Plasma IgG at 24h did not differ between calves fed maternal colostrum (13.78±0.39g/L) and colostrum replacement (13.96±0.38g/L). Average daily gain, withers height, hip height, body length, heart girth, health, and incidence of diarrhea were not different between treatment groups. Calves fed maternal colostrum used feed more efficiently than calves fed colostrum replacement. Plasma IgG and performance were not affected by the addition of animal plasma to milk replacer. The colostrum replacement used in this study provided adequate IgG for newborn calves. Animal plasma was an acceptable source of protein but did not enhance growth or immunity under the conditions of this study.


title: Middle East respiratory syndrome coronavirus transmission among health care workers: Implication for infection control

text: BACKGROUND: Many outbreaks of Middle East respiratory syndrome coronavirus (MERS-CoV) have occurred in health care settings and involved health care workers (HCWs). We describe the occurrence of an outbreak among HCWs and attempt to characterize at-risk exposures to improve future infection control interventions. METHODS: This study included an index case and all HCW contacts. All contacts were screened for MERS-CoV using polymerase chain reaction. RESULTS: During the study period in 2015, the index case was a 30-year-old Filipino nurse who had a history of unprotected exposure to a MERS-CoV–positive case on May 15, 2015, and had multiple negative tests for MERS-CoV. Weeks later, she was diagnosed with pulmonary tuberculosis and MERS-CoV infection. A total of 73 staff were quarantined for 14 days, and nasopharyngeal swabs were taken on days 2, 5, and 12 postexposure. Of those contacts, 3 (4%) were confirmed positive for MERS-CoV. An additional 18 staff were quarantined and had MERS-CoV swabs. A fourth case was confirmed positive on day 12. Subsequent contact investigations revealed a fourth-generation transmission. Only 7 (4.5%) of the total 153 contacts were positive for MERS-CoV. CONCLUSIONS: The role of HCWs in MERS-CoV transmission is complex. Although most MERS-CoV–infected HCWs are asymptomatic or have mild disease, fatal infections can occur and HCWs can play a major role in propagating health care facility outbreaks. This investigation highlights the need to continuously review infection control guidance relating to the role of HCWs in MERS-CoV transmission in health care outbreaks, especially as it relates to the complex questions on definition of risky exposures, who to test, and the frequency of MERS-CoV testing; criteria for who to quarantine and for how long; and clearance and return to active duty criteria.


title: Bovine coronavirus in neonatal calf diarrhoea in Iran

text: Partial gene sequencing for the bovine coronavirus at the World Genebank is available for many countries, which are distributed unevenly in five continents, but so far, no sequencing of strains has been recorded in Iran. One hundred ninety‐four stool samples from calves with diarrhoea less than one‐month old were collected from five different geographical regions of country in order to detect coronavirus and characterize it if coronavirus was found. Samples were screened for the presence of BCoV by using a commercially available ELISA kit. Furthermore, RT‐PCR was carried out on positive samples for confirmation of the presence of N and S specific genes. Sequencing and phylogenetic analysis was carried out following RT‐PCR tests. 7.2% of samples, were positive for BCoV and all stool samples from the South‐West, Northeast and West regions of Iran were negative. The results showed that all the strains of coronavirus identified in Iran were completely in independent clusters and that they did not stand in the same cluster as any of the strains identified in other parts of the world. The strains from Iran were quite different from strains in other parts of the world but from the point of similarity these viruses showed some similarities to the European strains, such as those found in France, Croatia, Denmark and Sweden.


title: Bayesian Analysis of Severe Acute Respiratory Syndrome: The 2003 Hong Kong Epidemic

text: This paper analyzes data arising from a Severe Acute Respiratory Syndrome (SARS) epidemic in Hong Kong in 2003 involving 1755 cases. A discrete time stochastic model that uses a back‐projection approach is proposed. Markov Chain Monte Carlo (MCMC) methods are developed for estimation of model parameters. The algorithm is further extended to integrate numerically over unobserved variables of the model. Applying the method to SARS data from Hong Kong, a value of 3.88 with a posterior standard deviation of 0.09 was estimated for the basic reproduction number. An estimate of the transmission parameter at the beginning of the epidemic was also obtained as 0.149 with a posterior standard deviation of 0.003. A reduction in the transmission parameter during the course of the epidemic forced the effective reproduction number to cross the threshold value of one, seven days after control interventions were introduced. At the end of the epidemic, the effective reproduction number was as low as 0.001 suggesting that the epidemic was brought under control by the intervention measures introduced. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)


title: Development of a Dose‐Response Model for SARS Coronavirus

text: In order to develop a dose‐response model for SARS coronavirus (SARS‐CoV), the pooled data sets for infection of transgenic mice susceptible to SARS‐CoV and infection of mice with murine hepatitis virus strain 1, which may be a clinically relevant model of SARS, were fit to beta‐Poisson and exponential models with the maximum likelihood method. The exponential model (k= 4.1 × l0(2)) could describe the dose‐response relationship of the pooled data sets. The beta‐Poisson model did not provide a statistically significant improvement in fit. With the exponential model, the infectivity of SARS‐CoV was calculated and compared with those of other coronaviruses. The does of SARS‐CoV corresponding to 10% and 50% responses (illness) were estimated at 43 and 280 PFU, respectively. Its estimated infectivity was comparable to that of HCoV‐229E, known as an agent of human common cold, and also similar to those of some animal coronaviruses belonging to the same genetic group. Moreover, the exponential model was applied to the analysis of the epidemiological data of SARS outbreak that occurred at an apartment complex in Hong Kong in 2003. The estimated dose of SARS‐CoV for apartment residents during the outbreak, which was back‐calculated from the reported number of cases, ranged from 16 to 160 PFU/person, depending on the floor. The exponential model developed here is the sole dose‐response model for SARS‐CoV at the present and would enable us to understand the possibility for reemergence of SARS.


title: Heart Transplantation in the Era of the SARS‐CoV‐2 Pandemic: Is It Safe and Feasible?

text: As the SARS‐CoV‐2 pandemic continues to unfold, the number of heart transplants completed in the United States has been declining steadily. The current case series examines the immediate short‐term outcomes of 7 heart transplant recipients transplanted during the SARS‐CoV‐2 pandemic. We hope to illustrate that with proper preparation, planning, and testing, heart transplantation can be continued during a pandemic. We assessed 7 patients transplanted from March 4, 2020 to April 15, 2020. The following endpoints were noted: in‐hospital survival, in‐hospital freedom from rejection, in‐hospital non‐fatal major cardiac adverse events (NF‐MACE), severe primary graft dysfunction, hospital length of stay, and ICU length of stay. There were no expirations throughout the hospital admission. In addition, there were no patients with NF‐MACE or treated rejection, and 1 patient developed severe primary graft dysfunction. Average length of stay was 17.2 days with a standard deviation of 5.9 days. ICU length of stay was 7.7 days with a standard deviation of 2.3 days. Despite the decreasing trend in completed heart transplants due to SARS‐CoV‐2, heart transplantation appears to be feasible in the immediate short term. Further follow up is needed, however, to assess the impact of SARS‐CoV‐2 on post‐heart transplant outcomes months after transplantation.


title: Nature of a lockdown

text: Going out into the natural world is good for your health and mind, and you can still get some of the same benefits even when stuck inside, says Graham Lawton


title: Marketing innovations during a global crisis: A study of China firms’ response to COVID-19

text: As a worldwide disaster, the COVID-19 crisis is profoundly affecting the development of the global economy and threatening the survival of firms worldwide. It seems unavoidable that this natural disruption has hit the global economy and produced a huge crisis for firms. This study explores how firms in China are innovating their marketing strategies by critically identifying the typology of firms’ marketing innovations using two dimensions, namely, motivation for innovations and the level of collaborative innovations. This research also explores the influence of the external environment, internal advantages (e.g., dynamic capabilities and resource dependence), and characteristics of firms on Chinese firms’ choice and implementation of marketing innovation strategies. It provides valuable insights for firms to respond successfully to similar crisis events in the future.


title: Two RNA-binding sites in plant fibrillarin provide interactions with various RNA substrates

text: Fibrillarin, one of the major proteins of the nucleolus, plays several essential roles in ribosome biogenesis including pre-rRNA processing and 2′-O-ribose methylation of rRNA and snRNAs. Recently, it has been shown that fibrillarin plays a role in virus infections and is associated with viral RNPs. Here, we demonstrate the ability of recombinant fibrillarin 2 from Arabidopsis thaliana (AtFib2) to interact with RNAs of different lengths and types including rRNA, snoRNA, snRNA, siRNA and viral RNAs in vitro. Our data also indicate that AtFib2 possesses two RNA-binding sites in the central (138–179 amino acids) and C-terminal (225–281 amino acids) parts of the protein, respectively. The conserved GCVYAVEF octamer does not bind RNA directly as suggested earlier, but may assist with the proper folding of the central RNA-binding site.


title: Mechano-genomic regulation of coronaviruses and its interplay with ageing

text: Coronaviruses employ various nuclear signalling mechanisms for their propagation. Here we link replication of coronaviruses, including SARS-CoV-2, the coronavirus disease 2019 (COVID-19)-causing virus, with cytoskeleton-dependent signalling and 3D genome organization. This link could provide novel insights into the high coronavirus pathogenicity in certain cellular states, particularly those associated with ageing.


title: Generation of human antibody fragments recognizing distinct epitopes of the nucleocapsid (N) SARS-CoV protein using a phage display approach

text: BACKGROUND: Severe acute respiratory syndrome (SARS)-CoV is a newly emerging virus that causes SARS with high mortality rate in infected people. Successful control of the global SARS epidemic will require rapid and sensitive diagnostic tests to monitor its spread, as well as, the development of vaccines and new antiviral compounds including neutralizing antibodies that effectively prevent or treat this disease. METHODS: The human synthetic single-chain fragment variable (scFv) ETH-2 phage antibody library was used for the isolation of scFvs against the nucleocapsid (N) protein of SARS-CoV using a bio panning-based strategy. The selected scFvs were characterized under genetics-molecular aspects and for SARS-CoV N protein detection in ELISA, western blotting and immunocytochemistry. RESULTS: Human scFv antibodies to N protein of SARS-CoV can be easily isolated by selecting the ETH-2 phage library on immunotubes coated with antigen. These in vitro selected human scFvs specifically recognize in ELISA and western blotting studies distinct epitopes in N protein domains and detect in immunohistochemistry investigations SARS-CoV particles in infected Vero cells. CONCLUSION: The human scFv antibodies isolated and described in this study represent useful reagents for rapid detection of N SARS-CoV protein and SARS virus particles in infected target cells.


title: Incidental typical COVID-19 appearance on the lung bases, visualized at abdominal CT for a patient that presented with abdominal pain and nausea

text: This is a case report of a 55-year-old male patient, medically free presented to the emergency department at our hospital, King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia. The patient presented with generalized abdominal pain and nausea only, without fever or any respiratory symptoms. On a computed tomography scan examination of the abdomen to rule out bowel ischemia, an incidental finding of a typical appearance of COVID-19 pneumonia was found at the visualized lung bases. The diagnosis of COVID-19 was confirmed afterward by laboratory testing. Conclusion: Typical COVID-19 findings can be suggested on lung bases at abdominal CT.


title: Structure and Assembly of Complex Viruses

text: Viral particles consist essentially of a proteinaceous capsid protecting a genome and involved also in many functions during the virus life cycle. In simple viruses, the capsid consists of a number of copies of the same, or a few different proteins organized into a symmetric oligomer. Structurally complex viruses present a larger variety of components in their capsids than simple viruses. They may contain accessory proteins with specific architectural or functional roles; or incorporate non-proteic elements such as lipids. They present a range of geometrical variability, from slight deviations from the icosahedral symmetry to complete asymmetry or even pleomorphism. Putting together the many different elements in the virion requires an extra effort to achieve correct assembly, and thus complex viruses require sophisticated mechanisms to regulate morphogenesis. This chapter provides a general view of the structure and assembly of complex viruses.


title: Anticoagulation clinic drive-up service during COVID-19 pandemic in Qatar

text: Coronavirus Disease 2019 (COVID-19) is a pandemic affecting many countries worldwide. Given the increasing incidence especially in elderly and individuals with comorbid conditions, it is advised by health authorities to stay home if possible, maintain social distancing and stay away from those who are sick or could be infected. Patients with comorbidities especially cardiovascular disease are at higher risk of getting infected with COVID-19 and have worse prognosis. Among efforts to safely manage warfarin patients during this pandemic, we introduced a hospital drive-up anticoagulation testing service. This service can reduce the risk of exposure of anticoagulation patients to COVID-19 by reducing the contact time with the different personnel at the hospital and by maintaining those patients at a safe distance from others


title: Neospora caninum: the First Demonstration of the Enteroepithelial Stages in the Intestines of a Naturally Infected Dog

text: Summary A 1.5-month-old Kangal breed puppy from a dairy cattle farm died after showing severe diarrhoea and incoordination. Necropsy examination revealed multifocal pulmonary consolidation and necrosis and fibrinohaemorrhagic enteritis. Microscopically, there was necrotic and purulent bronchopneumonia, myocarditis and non-purulent encephalitis. In the jejunum and ileum there was villous atrophy and crypt hyperplasia with oocyst-like and schizont-like structures in the epithelia. Immunohistochemically, Neospora caninum antigen was detected in association with the intestinal protozoal structures, degenerative neurons and areas of necrosis in the lungs and heart. Polymerase chain reaction confirmed that the organism was N. caninum and not Toxoplasma gondii. The seroprevalence for N. caninum was 74.2% (49/66 animals) for the cattle and 57.1% (4/7 animals) for dogs on this farm. This report documents fatal systemic neosporosis and enteroepithelial stages of N. caninum in a naturally infected puppy. To the authors' knowledge, this is the first definition of intestinal neosporosis in a naturally infected dog as well as the first evidence of fatal canine neosporosis in Turkey.


title: Supersize me: how whole-genome sequencing and big data are transforming epidemiology

text: In epidemiology, the identification of ‘who infected whom’ allows us to quantify key characteristics such as incubation periods, heterogeneity in transmission rates, duration of infectiousness, and the existence of high-risk groups. Although invaluable, the existence of many plausible infection pathways makes this difficult, and epidemiological contact tracing either uncertain, logistically prohibitive, or both. The recent advent of next-generation sequencing technology allows the identification of traceable differences in the pathogen genome that are transforming our ability to understand high-resolution disease transmission, sometimes even down to the host-to-host scale. We review recent examples of the use of pathogen whole-genome sequencing for the purpose of forensic tracing of transmission pathways, focusing on the particular problems where evolutionary dynamics must be supplemented by epidemiological information on the most likely timing of events as well as possible transmission pathways. We also discuss potential pitfalls in the over-interpretation of these data, and highlight the manner in which a confluence of this technology with sophisticated mathematical and statistical approaches has the potential to produce a paradigm shift in our understanding of infectious disease transmission and control.


title: Preparation and antibacterial efficacy of bamboo charcoal/polyoxometalate biological protective material

text: Abstract Nanocomposites based on Keggin-type polyoxometalate H5PV2Mo10O40 (POM) and porous bamboo charcoal (BC) were prepared by activation and immobilization processes. The physical properties of the BC/POM composites were examined using FTIR, UV–Vis spectroscope, 31P MAS-NMR, SEM and TEM. These techniques indicated that the POM was intact on the surface of the BC matrix after impregnation. The POM particle size was found to be less than 150nm based on TEM. The antibacterial effects of the BC/POM composites were assessed from the zone of inhibition, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and plate-counting method, and an excellent antibacterial performance was discovered.


title: Enterovirus D68 in Hospitalized Children: Sequence Variation, Viral Loads and Clinical Outcomes

text: BACKGROUND: An outbreak of enterovirus D68 (EV-D68) caused severe respiratory illness in 2014. The disease spectrum of EV-D68 infections in children with underlying medical conditions other than asthma, the role of EV-D68 loads on clinical illness, and the variation of EV-D68 strains within the same institution over time have not been described. We sought to define the association between EV-D68 loads and sequence variation, and the clinical characteristic in hospitalized children at our institution from 2011 to 2014. METHODS: May through November 2014, and August to September 2011 to 2013, a convenience sample of nasopharyngeal specimens from children with rhinovirus (RV)/EV respiratory infections were tested for EV-D68 by RT-PCR. Clinical data were compared between children with RV/EV-non-EV-D68 and EV-D68 infections, and among children with EV-D68 infections categorized as healthy, asthmatics, and chronic medical conditions. EV-D68 loads were analyzed in relation to disease severity parameters and sequence variability characterized over time. RESULTS: In 2014, 44% (192/438) of samples tested positive for EV-D68 vs. 10% (13/130) in 2011–13 (p<0.0001). PICU admissions (p<0.0001) and non-invasive ventilation (p<0.0001) were more common in children with EV-D68 vs. RV/EV-non-EV-D68 infections. Asthmatic EV-D68+ children, required supplemental oxygen administration (p = 0.03) and PICU admissions (p <0.001) more frequently than healthy children or those with chronic medical conditions; however oxygen duration (p<0.0001), and both PICU and total hospital stay (p<0.01) were greater in children with underlying medical conditions, irrespective of viral burden. By phylogenetic analysis, the 2014 EV-D68 strains clustered into a new sublineage within clade B. CONCLUSIONS: This is one of the largest pediatric cohorts described from the EV-D68 outbreak. Irrespective of viral loads, EV-D68 was associated with high morbidity in children with asthma and co-morbidities. While EV-D68 circulated before 2014, the outbreak isolates clustered differently than those from prior years.


COVID‐19 treatment in patients with comorbidities: Awareness of drug‐drug interactions


title: Discovery of New Hydroxyethylamine Analogs against 3CL(pro) Protein Target of SARS-CoV-2: Molecular Docking, Molecular Dynamics Simulation, and Structure–Activity Relationship Studies

text: [Image: see text] The novel coronavirus, SARS-CoV-2, has caused a recent pandemic called COVID-19 and a severe health threat around the world. In the current situation, the virus is rapidly spreading worldwide, and the discovery of a vaccine and potential therapeutics are critically essential. The crystal structure for the main protease (M(pro)) of SARS-CoV-2, 3-chymotrypsin-like cysteine protease (3CL(pro)), was recently made available and is considerably similar to the previously reported SARS-CoV. Due to its essentiality in viral replication, it represents a potential drug target. Herein, a computer-aided drug design (CADD) approach was implemented for the initial screening of 13 approved antiviral drugs. Molecular docking of 13 antivirals against the 3-chymotrypsin-like cysteine protease (3CL(pro)) enzyme was accomplished, and indinavir was described as a lead drug with a docking score of −8.824 and a XP Gscore of −9.466 kcal/mol. Indinavir possesses an important pharmacophore, hydroxyethylamine (HEA), and thus, a new library of HEA compounds (>2500) was subjected to virtual screening that led to 25 hits with a docking score more than indinavir. Exclusively, compound 16 with a docking score of −8.955 adhered to drug-like parameters, and the structure–activity relationship (SAR) analysis was demonstrated to highlight the importance of chemical scaffolds therein. Molecular dynamics (MD) simulation analysis performed at 100 ns supported the stability of 16 within the binding pocket. Largely, our results supported that this novel compound 16 binds with domains I and II, and the domain II–III linker of the 3CL(pro) protein, suggesting its suitability as a strong candidate for therapeutic discovery against COVID-19.


title: HOPS-dependent endosomal fusion required for efficient cytosolic delivery of therapeutic peptides and small proteins

text: Protein therapeutics represent a significant and growing component of the modern pharmacopeia, but their potential to treat human disease is limited because most proteins fail to traffic across biological membranes. Recently, we discovered that cell-permeant miniature proteins (CPMPs) containing a precisely defined, penta-arginine motif traffic readily to the cytosol and nucleus with efficiencies that rival those of hydrocarbon-stapled peptides active in animals and man. Like many cell-penetrating peptides (CPPs), CPMPs enter the endocytic pathway; the difference is that CPMPs are released efficiently from endosomes while other CPPs are not. Here, we seek to understand how CPMPs traffic from endosomes into the cytosol and what factors contribute to the efficiency of endosomal release. First, using two complementary cell-based assays, we exclude endosomal rupture as the primary means of endosomal escape. Next, using a broad spectrum of techniques, including an RNA interference (RNAi) screen, fluorescence correlation spectroscopy (FCS), and confocal imaging, we identify VPS39—a gene encoding a subunit of the homotypic fusion and protein sorting (HOPS) complex—as a critical determinant in the trafficking of CPMPs and hydrocarbon-stapled peptides to the cytosol. Although CPMPs neither inhibit nor activate HOPS function, HOPS activity is essential to efficiently deliver CPMPs to the cytosol. Subsequent multi-color confocal imaging studies identify CPMPs within the endosomal lumen, particularly within the intraluminal vesicles (ILVs) of Rab7+ and Lamp1+ endosomes that are the products of HOPS-mediated fusion. These results suggest that CPMPs require HOPS to reach ILVs—an environment that serves as a prerequisite for efficient endosomal escape.


title: Chapter Five A Review of the Use of Organic Amendments and the Risk to Human Health

text: Abstract Historically, organic amendments—organic wastes—have been the main source of plant nutrients, especially N. Their use allows better management of often-finite resources to counter changes in soils that result from essential practices for crop production. Organic amendments provide macro- and micronutrients, including carbon for the restoration of soil physical and chemical properties. Challenges from the use of organic amendments arise from the presence of heavy metals and the inability to control the transformations required to convert the organic forms of N and P into the minerals available to crops, and particularly to minimize the losses of these nutrients in forms that may present a threat to human health. Animal manure and sewage biosolids, the organic amendments in greatest abundance, contain components that can be hazardous to human health, other animals and plants. Pathogens pose an immediate threat. Antibiotics, other pharmaceuticals and naturally produced hormones may pose a threat if they increase the number of zoonotic disease organisms that are resistant to multiple antimicrobial drugs or interfere with reproductive processes. Some approaches aimed at limiting N losses (e.g. covered liquid or slurry storage, rapid incorporation into the soil, timing applications to minimize delay before plant uptake) also tend to favor survival of pathogens. Risks to human health, through the food chain and drinking water, from the pathogens, antibiotics and hormonal substances that may be present in organic amendments can be reduced by treatment before land application, such as in the case of sewage biosolids. Other sources, such as livestock and poultry manures, are largely managed by ensuring that they are applied at the rate, time and place most appropriate to the crops and soils. A more holistic approach to management is required as intensification of agriculture increases.


title: TGEV corona virus ORF4 encodes a membrane protein that is incorporated into virions

text: Abstract The coding potential of the open reading frame ORF4 (82 amino acids) of transmissible gastroenteritis virus (TGEV) has been confirmed by expression using a baculovirus vector. Five monoclonal antibodies (MAbs) raised against the 10K recombinant product immunoprecipitated a polypeptide of a similar size in TGEV-infected cells. Immunofluorescence assays performed both on insect and mammalian cells revealed that ORF4 was a membrane-associated protein, a finding consistent with the prediction of a membrane-spanning segment in ORF4 sequence. Two epitopes were localized within the last 21 C-terminal residues of the sequence through peptide scanning and analysis of the reactivity of a truncated ORF4 recombinant protein. Since the relevant MAbs were found to induce a cell surface fluorescence, these data suggest that ORF4 may be an integral membrane protein having a Cexo-Nendo orientation. Anti-ORF4 MAbs were also used to show that ORF4 polypeptide may be detected in TGEV virion preparations, with an estimated number of 20 molecules incorporated per particle. Comparison of amino acid sequence data provided strong evidence that other coronaviruses encode a polypeptide homologous to TGEV ORF4. Our results led us to propose that ORF4 represents a novel minor structural polypeptide, tentatively designated SM (small membrane protein).


title: Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study

text: OBJECTIVE: To investigate the occurrence of olfactory and gustatory dysfunctions in patients with laboratory-confirmed COVID-19 infection. METHODS: Patients with laboratory-confirmed COVID-19 infection were recruited from 12 European hospitals. The following epidemiological and clinical outcomes have been studied: age, sex, ethnicity, comorbidities, and general and otolaryngological symptoms. Patients completed olfactory and gustatory questionnaires based on the smell and taste component of the National Health and Nutrition Examination Survey, and the short version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS). RESULTS: A total of 417 mild-to-moderate COVID-19 patients completed the study (263 females). The most prevalent general symptoms consisted of cough, myalgia, and loss of appetite. Face pain and nasal obstruction were the most disease-related otolaryngological symptoms. 85.6% and 88.0% of patients reported olfactory and gustatory dysfunctions, respectively. There was a significant association between both disorders (p < 0.001). Olfactory dysfunction (OD) appeared before the other symptoms in 11.8% of cases. The sQO-NS scores were significantly lower in patients with anosmia compared with normosmic or hyposmic individuals (p = 0.001). Among the 18.2% of patients without nasal obstruction or rhinorrhea, 79.7% were hyposmic or anosmic. The early olfactory recovery rate was 44.0%. Females were significantly more affected by olfactory and gustatory dysfunctions than males (p = 0.001). CONCLUSION: Olfactory and gustatory disorders are prevalent symptoms in European COVID-19 patients, who may not have nasal symptoms. The sudden anosmia or ageusia need to be recognized by the international scientific community as important symptoms of the COVID-19 infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00405-020-05965-1) contains supplementary material, which is available to authorized users.


title: Pseudomonas fluorescens contamination of a feline packed red blood cell unit and studies of canine units

text: BACKGROUND: While screening programs have reduced the risk of infectious disease transmission by donors in human and veterinary blood banking, bacterial contamination of blood products has emerged as a major complication in human medicine. OBJECTIVES: To describe a Pseudomonas fluorescens (Pf)-contaminated feline packed RBC (pRBC) unit and experimentally investigate Pf-contaminated canine pRBCs. METHODS: Canine pRBCs were inoculated with Pf-rich pRBCs from the sentinel feline unit and stored at 4°C or 20°C for 72 hours. Aliquots from the pRBCs were serially evaluated by microscopy, culture, and a eubacterial 16S rRNA real-time PCR assay. RESULTS: One Pf-contaminated feline unit turned black after 22 days of storage and was removed from the blood bank; a source was not found, and no other contaminated units were identified. Canine pRBCs spiked with 5 or 25 μL of the sentinel unit became culture- and/or 16S PCR-positive at ≥8 hours at 20°C and 48 hours at 4°C and developed a color change at ≥24 hours. Sensitivity studies indicated that without incubation, inoculation of ≥100 μL Pf-rich pRBCs was necessary for a positive 16S PCR test result. CONCLUSIONS: P. fluorescens grows in stored pRBCs slowly at 4°C and rapidly at 20°C. Screening of blood products for color change, estimating bacterial concentration with microscopy, and 16S PCR testing are simple and fast ways to detect bacteria in stored blood. Aseptic collection, temperature-controlled storage, and regular visual monitoring of stored units is recommended. Discolored units should not be transfused, but examined for bacterial contamination or other blood product quality problems.


title: Surgical Transplantation of Mouse Neural Stem Cells into the Spinal Cords of Mice Infected with Neurotropic Mouse Hepatitis Virus

text: Mice infected with the neurotropic JHM strain of mouse hepatitis virus (MHV) develop pathological and clinical outcomes similar to patients with the demyelinating disease Multiple Sclerosis (MS). We have shown that transplantation of NSCs into the spinal cords of sick mice results in a significant improvement in both remyelination and in clinical outcome. Cell replacement therapies for the treatment of chronic neurologic diseases are now a reality and in vivo models are vital in understanding the interactions between the engrafted cells and host tissue microenvironment. This presentation provides an adapted method for transplanting cells into the spinal cord of JHMV-infected mice. In brief, we provide a procedure for i) preparation of NSCs prior to transplant, ii) pre-operative care of mice, iii) exposure of the spinal cord via laminectomy, iv) stereotactic injection of NSCs, and iv) post-operative care.


title: Spatial Analysis of COVID-19 Clusters and Contextual Factors in New York City

text: Identifying areas with low access to testing and high case burden is necessary to understand risk and allocate resources in the COVID-19 pandemic. Using zip code level data for New York City, we analyzed testing rates, positivity rates, and proportion positive. A spatial scan statistic identified clusters of high and low testing rates, high positivity rates, and high proportion positive. Boxplots and Pearson correlations determined associations between outcomes, clusters, and contextual factors. Clusters with less testing and low proportion positive tests had higher income, education, and white population, whereas clusters with high testing rates and high proportion positive tests were disproportionately black and without health insurance. Correlations showed inverse associations of white race, education, and income with proportion positive tests, and positive associations with black race, Hispanic ethnicity, and poverty. We recommend testing and health care resources be directed to eastern Brooklyn, which has low testing and high proportion positives.


title: Knowledge, Attitudes and Practices (KAP) related to the Pandemic (H1N1) 2009 among Chinese General Population: a Telephone Survey

text: BACKGROUND: China is at greatest risk of the Pandemic (H1N1) 2009 due to its huge population and high residential density. The unclear comprehension and negative attitudes towards the emerging infectious disease among general population may lead to unnecessary worry and even panic. The objective of this study was to investigate the Chinese public response to H1N1 pandemic and provide baseline data to develop public education campaigns in response to future outbreaks. METHODS: A close-ended questionnaire developed by the Chinese Center for Disease Control and Prevention was applied to assess the knowledge, attitudes and practices (KAP) of pandemic (H1N1) 2009 among 10,669 responders recruited from seven urban and two rural areas of China sampled by using the probability proportional to size (PPS) method. RESULTS: 30.0% respondents were not clear whether food spread H1N1 virusand. 65.7% reported that the pandemic had no impact on their life. The immunization rates of the seasonal flu and H1N1vaccine were 7.5% and 10.8%, respectively. Farmers and those with lower education level were less likely to know the main transmission route (cough or talk face to face). Female and those with college and above education had higher perception of risk and more compliance with preventive behaviors. Relationships between knowledge and risk perception (OR = 1.69; 95%CI 1.54-1.86), and knowledge and practices (OR = 1.57; 95%CI 1.42-1.73) were found among the study subjects. With regard to the behavior of taking up A/H1N1 vaccination, there are several related factors found in the current study population, including the perception of life disturbed (OR = 1.29; 95%CI 1.11-1.50), the safety of A/H1N1 vaccine (OR = 0.07; 95%CI 0.04-0.11), the knowledge of free vaccination policy (OR = 7.20; 95%CI 5.91-8.78), the state's priority vaccination strategy(OR = 1.33; 95%CI 1.08-1.64), and taking up seasonal influenza vaccine behavior (OR = 4.69; 95%CI 3.53-6.23). CONCLUSIONS: This A/H1N1 epidemic has not caused public panic yet, but the knowledge of A/H1N1 in residents is not optimistic. Public education campaign may take the side effects of vaccine and the knowledge about the state's vaccination strategy into account.


title: Growth restriction of an experimental live attenuated human parainfluenza virus type 2 vaccine in human ciliated airway epithelium in vitro parallels attenuation in African green monkeys

text: Human parainfluenza viruses (HPIVs) are common causes of severe pediatric respiratory viral disease. We characterized wild-type HPIV2 infection in an in vitro model of human airway epithelium (HAE) and found that the virus replicates to high titer, sheds apically, targets ciliated cells, and induces minimal cytopathology. Replication of an experimental, live attenuated HPIV2 vaccine strain, containing both temperature sensitive (ts) and non-ts attenuating mutations, was restricted >30-fold compared to rHPIV2-WT in HAE at 32°C and exhibited little productive replication at 37°C. This restriction paralleled attenuation in the upper and lower respiratory tract of African green monkeys, supporting the HAE model as an appropriate and convenient system for characterizing HPIV2 vaccine candidates.


title: Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System: Celebrating the 20th Anniversary of the Discovery of ACE2

text: ACE2 (angiotensin-converting enzyme 2) has a multiplicity of physiological roles that revolve around its trivalent function: a negative regulator of the renin-angiotensin system, facilitator of amino acid transport, and the severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-CoV-2 receptor. ACE2 is widely expressed, including, in the lungs, cardiovascular system, gut, kidneys, central nervous system, and adipose tissue. ACE2 has recently been identified as the SARS-CoV-2 receptor, the infective agent responsible for coronavirus disease 2019, providing a critical link between immunity, inflammation, ACE2, and cardiovascular disease. Although sharing a close evolutionary relationship with SARS-CoV, the receptor-binding domain of SARS-CoV-2 differs in several key amino acid residues, allowing for stronger binding affinity with the human ACE2 receptor, which may account for the greater pathogenicity of SARS-CoV-2. The loss of ACE2 function following binding by SARS-CoV-2 is driven by endocytosis and activation of proteolytic cleavage and processing. The ACE2 system is a critical protective pathway against heart failure with reduced and preserved ejection fraction including, myocardial infarction and hypertension, and against lung disease and diabetes mellitus. The control of gut dysbiosis and vascular permeability by ACE2 has emerged as an essential mechanism of pulmonary hypertension and diabetic cardiovascular complications. Recombinant ACE2, gene-delivery of Ace2, Ang 1–7 analogs, and Mas receptor agonists enhance ACE2 action and serve as potential therapies for disease conditions associated with an activated renin-angiotensin system. rhACE2 (recombinant human ACE2) has completed clinical trials and efficiently lowered or increased plasma angiotensin II and angiotensin 1-7 levels, respectively. Our review summarizes the progress over the past 20 years, highlighting the critical role of ACE2 as the novel SARS-CoV-2 receptor and as the negative regulator of the renin-angiotensin system, together with implications for the coronavirus disease 2019 pandemic and associated cardiovascular diseases.


Fungal diseases as neglected pathogens: A wake-up call to public health officials


title: Evaluation of cystatin C activities against HIV

text: BACKGROUND & OBJECTIVES: Several host defense proteins known to possess antimicrobial activities are present on mucosal surfaces and are consequently found in body fluids of vertebrates. Naturally occurring protease inhibitors like cystatins, especially cystatin C (cys C), are abundantly present in human seminal plasma. Although its antiviral activity against herpes simplex virus (HSV) has been demonstrated, the role of this protein against HIV is not well studied. Therefore, the aim of the present study was to evaluate the anti-HIV activities of cys C, which is present innately in the male reproductive tract. METHODS: Protein-protein interaction of cys C with various HIV proteins was studied using a commercially available HIV blot and specific interaction with HIV protease was studied by dot-blot technique using commercially available cys C. To purify biologically active cys C from human seminal plasma to be used for subsequent experiments, gel-permeation chromatography followed by affinity chromatography was used. The HIV infectivity inhibition activity of the purified cystatin C was tested in TZM-bl cells. To study its activity on HIV protease, time-course enzyme kinetics studies were performed using spectrometric assay. RESULTS: Cystatin C reacted with some HIV proteins including HIV protease. Biologically active cys C was purified using gel permeation chromatography followed by affinity chromatography. When tested in TZM-bl cells, purified cystatin C demonstrated HIV-infectivity inhibitory activity (IC(50): 0.28 μM). Enzyme kinetic studies demonstrated that it abrogated the action of HIV protease on its substrate. INTERPRETATION & CONCLUSIONS: The present data demonstrate that cystatin C possesses anti-HIV activities. Molecular models need to be designed with this protein which would assist towards prevention/therapeutics against HIV.


title: Cell‐based therapy to reduce mortality from COVID‐19: Systematic review and meta‐analysis of human studies on acute respiratory distress syndrome

text: Severe cases of COVID‐19 infection, often leading to death, have been associated with variants of acute respiratory distress syndrome (ARDS). Cell therapy with mesenchymal stromal cells (MSCs) is a potential treatment for COVID‐19 ARDS based on preclinical and clinical studies supporting the concept that MSCs modulate the inflammatory and remodeling processes and restore alveolo‐capillary barriers. The authors performed a systematic literature review and random‐effects meta‐analysis to determine the potential value of MSC therapy for treating COVID‐19‐infected patients with ARDS. Publications in all languages from 1990 to March 31, 2020 were reviewed, yielding 2691 studies, of which nine were included. MSCs were intravenously or intratracheally administered in 117 participants, who were followed for 14 days to 5 years. All MSCs were allogeneic from bone marrow, umbilical cord, menstrual blood, adipose tissue, or unreported sources. Combined mortality showed a favorable trend but did not reach statistical significance. No related serious adverse events were reported and mild adverse events resolved spontaneously. A trend was found of improved radiographic findings, pulmonary function (lung compliance, tidal volumes, PaO(2)/FiO(2) ratio, alveolo‐capillary injury), and inflammatory biomarker levels. No comparisons were made between MSCs of different sources.


Social Work in the Time of the COVID-19 Pandemic: All in This Together?


title: Predicting the Growth and Trend of COVID-19 Pandemic using Machine Learning and Cloud Computing

text: Abstract The outbreak of COVID-19 Coronavirus, namely SARS-CoV-2, has created a calamitous situation throughout the world. The cumulative incidence of COVID-19 is rapidly increasing day by day. Machine Learning (ML) and Cloud Computing can be deployed very effectively to track the disease, predict growth of the epidemic and design strategies and policy to manage its spread. This study applies an improved mathematical model to analyse and predict the growth of the epidemic. An ML-based improved model has been applied to predict the potential threat of COVID-19 in countries worldwide. We show that using iterative weighting for fitting Generalized Inverse Weibull distribution, a better fit can be obtained to develop a prediction framework. This has been deployed on a cloud computing platform for more accurate and real-time prediction of the growth behavior of the epidemic. A data driven approach with higher accuracy as here can be very useful for a proactive response from the government and citizens. Finally, we propose a set of research opportunities and setup grounds for further practical applications.


title: Ebola virus disease: societal challenges and new treatments

text: Ebola virus disease (EVD) is a zoonotic disease that causes severe haemorrhagic fever, with high fatality rates of up to 90% in humans. Today, there is no effective treatment available. Person‐to‐person transmission occurs through exposure to blood or body fluids, which can threaten other household members and first‐line healthcare workers. The first cases of EVD in Guinea were identified on 22 March 2014. It was initially believed that this like previous outbreaks would be self‐limiting. However, lack of public health infrastructure, delays in virus detection and late implementation of control interventions contributed to widespread transmission of EVD in a region inexperienced in dealing with the disease. Socio‐cultural and economic factors probably also played a key role in the spread of the disease, resulting in the current large‐scale outbreak. Some promising candidate treatments for this disease are now being developed.