title: Umbrella Visualization: A method of analysis dedicated to glycan flexibility with UnityMol

text: Abstract N-glycosylation is a post-translational modification heavily impacting protein functions. Some alterations of glycosylation, such as sialic acid hydrolysis, are related to protein dysfunction. Because of their high flexibility and the many reactive groups of the glycan chains, studying glycans with in vitro methods is a challenging task. Molecular dynamics is a useful tool and probably the only one in biology able to overcome this problem and gives access to conformational information through exhaustive sampling. To better decipher the impact of N-glycans, the analysis and visualization of their influence over time on protein structure is a prerequisite. We developed the Umbrella Visualization, a graphical method that assigns the glycan intrinsic flexibility during a molecular dynamics trajectory. The density plot generated by this method brought relevant informations regarding glycans dynamics and flexibility, but needs further development in order to integrate an accurate description of the protein topology and its interactions. We propose here to transform this analysis method into a visualization mode in UnityMol. UnityMol is a molecular editor, viewer and prototyping platform, coded in C#. The new representation of glycan chains presented in this study takes into account both the main positions adopted by each antenna of a glycan and their statistical relevance. By displaying the collected data on the protein surface, one is then able to investigate the protein/glycan interactions.


COVID-19: Interpretation of morbidity and mortality data


title: Dynamics of coagulopathy in patients with different COVID-19 severity

text: With the progress of COVID-19 studies, it became evident that SARS-CoV-2 infection is often associated with thrombotic complications. The goal of our present study was to evaluate which component of clot formation process including endothelial function, platelets aggregation and plasma coagulation, as well as endogenous fibrinolysis in patients with COVID-19 correlates with the severity of the disease. We prospectively included 58 patients with COVID-19 and 47 healthy volunteers as a control group that we recruited before the pandemic started. It turns out that plasma coagulation with subsequent platelet aggregation, but not endothelial function, correlates with the severity of the COVID-19. IL-6 blockade may play a beneficial role in COVID-19 induced coagulopathy.


Emergence of the Middle East Respiratory Syndrome Coronavirus


title: Ovine rotavirus strain LLR-85-based bovine rotavirus candidate vaccines: Construction, characterization and immunogenicity evaluation

text: Abstract Group A bovine rotaviruses (BRVs) are the most important cause of diarrheal diseases in neonatal calves and cause significant morbidity and mortality in the young animals, and epidemiologic surveillance of bovine rotavirus G genotypes conducted in various cattle populations throughout the world has shown that approximately 90% of the bovine rotavirus isolates belong to G6 and G10. Based on the modified Jennerian approach to immunization, we constructed and characterized a reassortant rotavirus stain, which bears a single bovine rotavirus VP7 gene encoding G genotype 6 specificity while the remaining 10 genes are derived from the ovine attenuated rotavirus LLR-85. The reassortant rotavirus strain, named as R191, and its parental virus strain LLR-85 were combined as bivalent vaccine candidates to inoculate the colostrums-deprived neonatal calves for evaluation of the immunogenicity. The calves were orally inoculated with the reassortant R191 (group 1), the parental rotavirus LLR-85 (group 2), or combined the R191 and LLR-85 (group 3), and serum specimens were detected to determine the immune response of IgG and IgA antibodies. Results showed that seroconversion to positivity for IgG and IgA antibodies occurred at postinoculation day (PID) 10 in all of the inoculated calves, and the highest titers of the serum IgG (range 1:800 to 1:6400) and IgA (range 1:800 to 1:3200) antibodies were obtained at PID 21 for all calves. Meanwhile, virus shedding was detected after inoculation, showing that the inoculated virus was positive in 2 of 77 fecal specimens (2.6%) collected from the inoculated calves during the first 7 days of oral inoculation with the rotavirus vaccine candidates. The results suggested that the rotavirus strains R191 and LLR-85 are promising bivalent vaccine candidates for the prevention of bovine G6 and G10 rotavirus infection.


title: Estimating number of cases and spread of coronavirus disease (COVID-19) using critical care admissions, United Kingdom, February to March 2020

text: An exponential growth model was fitted to critical care admissions from two surveillance databases to determine likely coronavirus disease (COVID-19) case numbers, critical care admissions and epidemic growth in the United Kingdom before the national lockdown. We estimate, on 23 March, a median of 114,000 (95% credible interval (CrI): 78,000–173,000) new cases and 258 (95% CrI: 220–319) new critical care reports, with 527,000 (95% CrI: 362,000–797,000) cumulative cases since 16 February.


Priority plan for invasive cardiac electrophysiology procedures during the coronavirus disease 2019 (COVID‐19) pandemic


Oral ulceration as presenting feature of paediatric inflammatory multisystem syndrome associated with COVID-19


title: Mandell, Douglas, and Bennett's principles and practice of infectious diseases GL Mandell

text: Unknown


title: Chapter 1 The Nature of Viruses

text: Publisher Summary This chapter discusses the animal virology that defines human development, which is shaped by at least three major recurring elements: environmental changes, human conflicts, and infectious diseases. It states that the origins of veterinary medicine are rooted in efforts to maintain the health of animals for food and fiber production and animals essential for work-related activities. The early phase of virology was one of skepticism and uncertainty because of the limited tools available to define the filterable agents. Even with filtration, there were differences among the agents as to their size as defined by filter retention. The bacterial viruses assisted in defining some of the basic principles of genetics through the study of mutations and the inheritance of phenotypic changes. Veterinary virology began as a discipline focusing on the effects of viral infections on animals of agricultural significance. Control of these infections relied on advances in understanding the disease process, in the characterization of the viruses, in the development of the fields of immunology and diagnostic technologies, and in the establishment of regulations controlling the movement of production animals. Initial experiences confirmed that eradication of some infectious diseases from defined areas could be achieved with a test and slaughter program, even in the absence of an effective vaccine. This chapter also explores characteristics of viruses, viral morphology, and taxonomy.


title: Knowledge, Attitude and practices regarding vector-borne diseases in Western Jamaica

text: BACKGROUND: Outbreaks of vector-borne diseases such as dengue, and malaria can overwhelm health systems in resource-poor countries. Environmental management strategies that reduce/eliminate vector breeding sites combined with improved personal prevention strategies can help to significantly reduce transmission of these infections. OBJECTIVE: This study was conducted to assess the knowledge, attitudes and practices (KAPs) of residents in Western Jamaica regarding control of mosquito vectors and protection from mosquito bites. METHODS: A cross-sectional study was conducted between May and August 2010 among patients or family members of patients waiting to be seen at hospitals in Western Jamaica. Participants completed an interviewer-administered questionnaire on sociodemographic factors and KAPs regarding vector-borne diseases. KAP scores were calculated and categorized as high or low based on number of correct/positive responses. Logistic regression analyses were conducted to identify predictors of KAP and linear regression analysis conducted to determine if knowledge and attitude scores predicted practice scores. RESULTS: Three-hundred and sixty-one people (85 males and 276 females) participated in the study. Most participants (87%) scored low on knowledge and practice items (78%). Conversely, 78% scored high on attitudes items. By multivariate logistic regression, housewives were 82% less likely to have high attitude scores than laborers, and homeowners were 65% less likely to have high attitude scores than renters. Participants from households with 1–2 children were 3.4 times more likely to have high attitude scores compared to those from households with no children. Participants from households ≥5 people were 65% less likely to have high practice scores compared to those from households with <5. By multivariable linear regression knowledge and attitude scores were significant predictors of practice score. CONCLUSION: The study revealed poor knowledge of vector-borne diseases and poor prevention practices among participants. It identified specific groups that can be targeted with vector-control and personal protection interventions to decrease transmission of the infections.


title: Cardiac Surgery in North America and COVID-19: Regional Variability in Burden and Impact

text: Abstract Objective The COVID-19 pandemic has resulted in an increase in hospital resource utilization and the need to defer non-urgent cardiac surgery procedures. The present study aims to report the regional variations of North American adult cardiac surgical case volume and case mix through the first wave of the COVID-19 pandemic. Methods A survey was sent to recruit participating adult cardiac surgery centers in North America. Data in regard to changes in institutional and regional cardiac surgical case volume and mix were analyzed. Results Our study comprises 67 adult cardiac surgery institutions with diverse geographic distribution across North America, representing annualized case volumes of 60,452 in 2019. Non-urgent surgery was stopped during the month of March 2020 in the majority of centers (96%) resulting in a decline to 45% of baseline with significant regional variation. Hospitals with a high burden of hospitalized patients with COVID-19 demonstrated similar trends of decline in total volume as centers in low burden areas. As a proportion of total surgical volume, there was a relative increase of coronary artery bypass grafting surgery (High +7.2% vs. Low +4.2%, p=0.550), extracorporeal membrane oxygenation (High +2.5% vs. Low 0.4%, p=0.328) and heart transplantation (High +2.7% vs. Low 0.4%, p=0.090), and decline in valvular cases (High -7.6% vs. Low -2.6%, p=0.195). Conclusions The present study demonstrates the impact of COVID-19 on North American cardiac surgery institutions as well as help associate region and COVID-19 burden with the impact on cardiac surgery volumes and case mix.


title: Detection of SARS-CoV-2 neutralizing antibodies with a cell-free PCR assay

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to more than 4 million confirmed infections worldwide and over 300,000 deaths. While Remdesivir has recently received FDA emergency use authorization for treatment of SARS-CoV-2 infection, convalescent plasma (CP) with high titers of SARS-CoV-2 neutralizing antibodies (NAbs) from recovered donors remains a promising and widely accessible method to mitigate severe disease symptoms. Here, we describe the development and validation of a cell-free neutralization PCR assay using SARS-CoV-2 spike protein S1 and human ACE2 receptor-DNA conjugates. By comparing with samples collected prior to the outbreak, we confirmed that NAbs were specifically detected in COVID-19 cases. Using our unique assay, the NAb signals are detectable as early as 10 days after onset of symptoms and continue to rise, plateauing after 18 days. Notably, we showed that the use of a licensed pathogen reduction technology to inactivate potentially contaminating infectious pathogens in CP did not alter NAb signals, paving a path to safely administer effective CP therapies. The described neutralization PCR assay can serve as a qualification tool to easily identify suitable CP donors of a potentially lifesaving therapy. In addition, this assay tool is readily deployable in standard laboratories with biosafety level 2 capability, and can yield results within 2–3 hrs. This advancement can facilitate research on factors driving diverse COVID-19 disease manifestations, help evaluate the impact of various CP processing protocols on CP therapeutic efficacy and assist in accelerating vaccine efficacy assessment.


Cardiopulmonary Resuscitation during the Coronavirus Crisis – important updates for the cardiothoracic and vascular anesthesia community


title: Mass spectrometry based proteomic studies on viruses and hosts – A review

text: Abstract In terms of proteomic research in the 21st century, the realm of virology is still regarded as an enormous challenge mainly brought by three aspects, namely, studying on the complex proteome of the virus with unexpected variations, developing more accurate analytical techniques as well as understanding viral pathogenesis and virus–host interaction dynamics. Progresses in these areas will be helpful to vaccine design and antiviral drugs discovery. Mass spectrometry based proteomics have shown exceptional display of capabilities, not only precisely identifying viral and cellular proteins that are functionally, structurally, and dynamically changed upon virus infection, but also enabling us to detect important pathway proteins. In addition, many isolation and purification techniques and quantitative strategies in conjunction with MS can significantly improve the sensitivity of mass spectrometry for detecting low-abundant proteins, replenishing the stock of virus proteome and enlarging the protein–protein interaction maps. Nevertheless, only a small proportion of the infectious viruses in both of animal and plant have been studied using this approach. As more virus and host genomes are being sequenced, MS-based proteomics is becoming an indispensable tool for virology. In this paper, we provide a brief review of the current technologies and their applications in studying selected viruses and hosts.


title: Prevalence of feline coronavirus in two cat populations in Malaysia

text: The prevalence of feline coronavirus (FCoV) was studied in two catteries in Malaysia. Rectal swabs or faecal samples were collected from a total of 44 clinically healthy Persian purebred and mix-breed cats. RNA extracted from the faecal material was subjected to a reverse transcription-polymerase chain reaction (RT-PCR) using primers flanking for a conserved region of the virus genome. The overall prevalence of FCoV infection was 84% and the infection rate was higher in Persian purebred cats (96%) than mix-breed cats (70%). There was no significant association between the age or gender of tested cats and shedding the virus. This study is the first PCR-based survey for FCoV in Malaysia and showed the ubiquitous presence of FCoV in Malaysian cat colonies.


title: Ibis T5000: a universal biosensor approach for microbiology

text: We describe a new technology, the Ibis T5000, for the identification of pathogens in clinical and environmental samples. The Ibis T5000 couples nucleic acid amplification to high-performance electrospray ionization mass spectrometry and base-composition analysis. The system enables the identification and quantification of a broad set of pathogens, including all known bacteria, all major groups of pathogenic fungi and the major families of viruses that cause disease in humans and animals, along with the detection of virulence factors and antibiotic resistance markers.


Online-Only Abstracts


title: Murine coronavirus-induced oligodendrocyte apoptosis is mediated through the activation of the Fas signaling pathway

text: Abstract We previously showed that infection of rat oligodendrocytes by ultraviolet light-inactivated mouse hepatitis virus (MHV) resulted in apoptosis, suggesting that the apoptosis is triggered during cell entry. To further characterize the earliest apoptotic signaling events, here we treated cells with an antibody specific to the MHV receptor prior to and during virus infection or with an antibody specific to MHV spike protein following virus binding. Both treatments blocked virus infection and apoptosis, indicating that virus–receptor binding is necessary but not sufficient for the apoptosis induction. Furthermore, virus infection significantly increased the formation of the “death–receptor complexes” consisting of Fas, Fas-associated death domain and procaspase-8, but did not induce the complexes involving the tumor necrosis factor receptor and its associated death domain, demonstrating the specific activation of the Fas signaling pathway. Moreover, virus infection did not alter the abundance of the individual proteins of the complexes, suggesting that the activation of the Fas signaling pathway was at the post-translational level. Treatment with a Fas/Fc chimera, which blocks Fas-Fas ligand-mediated apoptosis, inhibited the formation of the complexes and blocked the activation of caspase-8 and apoptosis in MHV-infected cells. It also inhibited the release of cytochrome c from mitochondria and the activation of caspase-9. These results demonstrate that oligodendrocyte apoptosis is triggered by MHV infection during cell entry through the activation of the Fas signaling pathway.


title: Hereditary and acquired angioedema: Problems and progress: Proceedings of the third C1 esterase inhibitor deficiency workshop and beyond

text: Hereditary angioedema (HAE), a rare but life-threatening condition, manifests as acute attacks of facial, laryngeal, genital, or peripheral swelling or abdominal pain secondary to intra-abdominal edema. Resulting from mutations affecting C1 esterase inhibitor (C1-INH), inhibitor of the first complement system component, attacks are not histamine-mediated and do not respond to antihistamines or corticosteroids. Low awareness and resemblance to other disorders often delay diagnosis; despite availability of C1-INH replacement in some countries, no approved, safe acute attack therapy exists in the United States. The biennial C1 Esterase Inhibitor Deficiency Workshops resulted from a European initiative for better knowledge and treatment of HAE and related diseases. This supplement contains work presented at the third workshop and expanded content toward a definitive picture of angioedema in the absence of allergy. Most notably, it includes cumulative genetic investigations; multinational laboratory diagnosis recommendations; current pathogenesis hypotheses; suggested prophylaxis and acute attack treatment, including home treatment; future treatment options; and analysis of patient subpopulations, including pediatric patients and patients whose angioedema worsened during pregnancy or hormone administration. Causes and management of acquired angioedema and a new type of angioedema with normal C1-INH are also discussed. Collaborative patient and physician efforts, crucial in rare diseases, are emphasized. This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder.


title: Ambulatory Care Practice in the COVID‐19 Era: Redesigning Clinical Services and Experiential Learning

text: The Coronavirus Disease (COVID ‐19) has created a variety of challenges for healthcare professionals, including ambulatory care clinical pharmacists. High‐quality remote and minimal‐contact care has become a necessity. Ambulatory care clinical pharmacists around the nation have adjusted their practice. In many cases, this included implementation of telehealth programs for comprehensive medication management. The redesign of ambulatory care Advanced Pharmacy Practice Experiences (APPE) also required quick adaptation. In this paper, we describe the clinical practice and experiential education challenges encountered by an ambulatory care clinical pharmacist workgroup in a COVID ‐19 “hotspot,” with an emphasis on solutions and guidance. We discuss how to adapt ambulatory care clinical pharmacy practices including methods of minimal‐contact care, reimbursement opportunities, tracking outcomes, and restructuring ambulatory care APPE. As ambulatory care clinical pharmacists continue to expand the services they provide in response to COVID ‐19, we also describe opportunities to promote pharmacists as providers during times of pandemic and into the future. This article is protected by copyright. All rights reserved.


Early Mortality Risk Stratification after SARS-CoV-2 Infection


title: Chimeric coronavirus-like particles carrying severe acute respiratory syndrome coronavirus (SCoV) S protein protects mice against challenge with SCoV

text: We tested the efficacy of coronavirus-like particles (VLPs) for protecting mice against severe acute respiratory syndrome coronavirus (SCoV) infection. Coexpression of SCoV S protein and E, M and N proteins of mouse hepatitis virus in 293T or CHO cells resulted in the efficient production of chimeric VLPs carrying SCoV S protein. Balb/c mice inoculated with a mixture of chimeric VLPs and alum twice at an interval of four weeks were protected from SCoV challenge, as indicated by the absence of infectious virus in the lungs. The same groups of mice had high levels of SCoV-specific neutralizing antibodies, while mice in the negative control groups, which were not immunized with chimeric VLPs, failed to manifest neutralizing antibodies, suggesting that SCoV-specific neutralizing antibodies are important for the suppression of viral replication within the lungs. Despite some differences in the cellular composition of inflammatory infiltrates, we did not observe any overt lung pathology in the chimeric-VLP-treated mice, when compared to the negative control mice. Our results show that chimeric VLP can be an effective vaccine strategy against SCoV infection.


title: The patient’s pathway for breast cancer in the COVID‐19 era: An Italian single‐center experience

text: COVID‐19 has been declared a pandemic by the World Health Organization. As of April 1, 2020, Italy was the country with the second highest number of cases in the world. The spread of COVID‐19 has required a rapid reorganization of health service delivery in face of the pandemic. Breast cancer units have reprioritized their workload to guarantee the health of oncologic patients at the highest risk and regular screening activities. However, at the end of the pandemic emergency, many benign and reconstructive cases will return to our attention and their surgical treatment will be necessary as soon as possible.


title: Streptococcus zooepidemicus: An emerging canine pathogen

text: Abstract Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) has caused several outbreaks of haemorrhagic pneumonia in dogs in recent years. This highly contagious and often fatal disease is characterised by sudden onset of clinical signs including pyrexia, dyspnoea and haemorrhagic nasal discharge. Post mortem examination typically reveals pulmonary haemorrhage and pleural effusion. Histopathology demonstrates fibrino-suppurative, necrotising and haemorrhagic pneumonia in most cases. The pathogenesis of S. zooepidemicus infection in dogs is incompletely understood. Bacterial virulence factors as well as host factors may contribute to the severe outcome. S. zooepidemicus occasionally causes zoonotic infections with potentially serious consequences. Canine vaccines for S. zooepidemicus are currently not available and prevention of the disease therefore relies on limiting bacterial spread by implementing stringent control measures in kennels. Further research, particularly sequence analysis of canine strains, is required to gain insights into epidemiology and pathogenesis of this emerging disease.


title: Effects of curcumin in treatment of experimental pulmonary fibrosis: A comparison with hydrocortisone

text: Abstract To compare curcumin with hydrocortisone for treating bleomycin-induced pulmonary fibrosis (BLMPF), four groups of rats were injected with 1.5mg/kg bleomycin intratracheally. Then the Group HC rats were treated with three injections of 2mg/kg hydrocortisone i.p.; Group CH and CL rats, respectively, were orally given 500 or 250mg/kg curcumin daily; and Group PC rats were given deionized water alone. After 28 days of treatment, lung samples were examined by H-E staining, Masson's staining and immunohistochemical analyses and pulmonary type I collagen (Col-I), inducible nitric oxide synthetase (iNOS) and transforming growth factor-β1 (TGF-β1) were determined by Western blotting and real-time RT PCR analyses. The results showed that (1) Group PC rats had histopathological characteristics of BLMPF with significant increase in their protein/mRNA expressions of Col-I (+114%/+173%), iNOS (+146%/+523%) and TGF-β1 (+476%/+527%) (P <0.01); (2) in Group HC, CH and CL rats, protein/mRNA expressions of Col-I (−39%/−52%, −31%/−57%, −33%/−58%), iNOS (−31%/−51%, −31%/−79%, −31%/−47%) and TGF-β1 (−64%/−78%, −75%/−74%, −81%/−79%) were significantly lower than Group PC (P <0.05); (3) except for levels of TGF-β1 protein, there was no significant difference among Group CH, CL and HC rats (P >0.05). It suggests that curcumin may play a similar role as hydrocortisone in preventing BLMPF.


title: Towards appropriate mainstreaming of “Theory of Change” approaches into agricultural research for development: Challenges and opportunities

text: Abstract Food insecurity persists in many parts of Africa and Asia, despite ongoing agricultural research for development (AR4D) interventions. This is resulting in a growing demand for alternative approaches to designing and evaluating interventions in complex systems. Theory of Change (ToC) is an approach which may be useful because it enables stakeholders to present and test their theories and assumptions about why and how impact may occur, ideally within an environment conducive to iterative reflection and learning. However, ToC is yet to be appropriately mainstreamed into development by donors, researchers and practitioners. We carried out a literature review, triangulated by interviews with 26 experts in African and Asian food security, consisting of researchers, advisors to programs, and donors. Although 17 (65%) of the experts had adopted ToC, their responses and the literature revealed four challenges to mainstreaming: (i) different interpretations of ToC; (ii) incoherence in relationships among the constituent concepts of ToC; (iii) confused relationships between ToC and project “logframes”; and (iv) limitations in necessary skills and commitment for enacting ToC. A case study of the evolution of a ToC in a West African AR4D project over 4 years which exemplified these challenges is presented. Five recommendations arise to assist the mainstreaming of ToC: (i) select a type of ToC suited to the relative complexity of the problem and focal system of interest; (ii) state a theory or hypotheses to be tested as the intervention progresses; (iii) articulate the relationship between the ToC and parallel approaches (e.g. logframe); (iv) accept that a ToC is a process, and (v) allow time and resources for implementers and researchers to develop ToC thinking within projects. Finally, we suggest that communities of practice should be established among AR4D and donor organisations to test, evaluate and improve the contribution that ToCs can make to sustainable food security and agricultural development.


Emerging infections and sensationalism: in Aesop's fable, the boy who cried wolf had a dreadful fate


COVID-19 in a lung transplant Recipient


In Reference to Anosmia and Ageusia: Common Findings in COVID‐19 Patients


Prevalence of Anxiety and Depression among the Healthcare Workers in Nepal during the COVID-19 Pandemic


Public responses to the novel 2019 coronavirus (2019‐nCoV) in Japan: Mental health consequences and target populations


title: Rare Presentation of Pulmonary Embolism Amidst Coronavirus Disease 2019 Era: Utility of Multiorgan Ultrasonography

text: Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is the underlying cause of a global crisis that the entire world is facing. It is a highly contagious viral infection, which is why social distancing seems to be effective. Its ability to survive on various surfaces and aerosolize necessitates very meticulous precautions, including airborne isolation for severely ill patients requiring mechanical ventilation. However, these patients may need routine diagnostic investigations including chest computed tomography and chest tomography angiogram scans (CT and CTA) to rule out other potential differential diagnoses and guide management. In this case, we focus on the utility of multiorgan ultrasonography (MOU) at the bedside to diagnose and manage pulmonary embolism (PE) in COVID-19 patients.


title: High-cell-density cultivations to increase MVA virus production

text: Abstract Increasing the yield and the productivity in cell culture-based vaccine manufacturing using high-cell-density (HCD) cultivations faces a number of challenges. For example, medium consumption should be low to obtain a very high concentration of viable host cells in an economical way but must be balanced against the requirement that accumulation of toxic metabolites and limitation of nutrients have to be avoided. HCD cultivations should also be optimized to avoid unwanted induction of apoptosis or autophagy during the early phase of virus infection. To realize the full potential of HCD cultivations, a rational analysis of the cultivation conditions of the appropriate host cell line together with the optimal infection conditions for the chosen viral vaccine strain needs to be performed for each particular manufacturing process. We here illustrate our strategy for production of the modified vaccinia Ankara (MVA) virus isolate MVA-CR19 in the avian suspension cell line AGE1.CR.pIX at HCD. As a first step we demonstrate that the adjustment of the perfusion rate strictly based on the measured cell concentration and the glucose consumption rate of cells enables optimal growth in a 0.8 L bioreactor equipped with an ATF2 system. Concentrations up to 57 × 106 cells/mL (before infection) were obtained with a viability exceeding 95%, and a maximum specific cell growth rate of 0.019 h−1 (doubling time = 36.5 h). However, not only the cell-specific MVA-CR19 virus yield but also the volumetric productivity was reduced compared to infections at conventional-cell-density (CCD). To facilitate optimization of the virus propagation phase at HCD, a larger set of feeding strategies was analyzed in small-scale cultivations using shake flasks. Densities up to 63 × 106 cells/mL were obtained at the end of the cell growth phase applying a discontinuous perfusion mode (semi-perfusion) with the same cell-specific perfusion rate as in the bioreactor (0.060 nL/(cell d)). At this cell concentration, a medium exchange at time of infection was required to obtain expected virus yields during the first 24 h after infection. Applying an additional fed-batch feeding strategy during the whole virus replication phase resulted in a faster virus titer increase during the first 36 h after infection. In contrast, a semi-continuous virus harvest scheme improved virus accumulation and recovery at a rather later stage of infection. Overall, a combination of both fed-batch and medium exchange strategies resulted in similar cell-specific virus yields as those obtained for CCD processes but 10-fold higher MVA-CR19 titers, and four times higher volumetric productivity.


title: Geographical structure of bat SARS-related coronaviruses

text: Abstract Bats are the natural reservoirs of severe acute respiratory syndrome coronavirus (SARS-CoV) which caused the outbreak of human SARS in 2002–2003. We introduce the genetic diversity of SARS-related coronaviruses (SARSr-CoVs) discovered in bats and provide insights on the bat origin of human SARS. We also analyze the viral geographical structure that may improve our understanding of the evolution of bat SARSr-CoVs.


title: AVNP2 protects against cognitive impairments induced by C6 glioma by suppressing tumour associated inflammation in rats

text: Abstract Glioblastoma is a kind of malignant tumour and originates from the central nervous system. In the last century, some researchers and clinician have noticed that the psychosocial and neurocognitive functioning of patients with malignant gliomas can be impaired. Many clinical studies have demonstrated that part of patients, adults or children, diagnosed with glioblastoma will suffer from cognitive deficiency during their clinical course, especially in long-term survivors. Many nanoparticles (NPs) can inhibit the biological functions of tumours by modulating tumour-associated inflammation, which provokes angiogenesis and tumour growth. As one of the best antiviral nanoparticles (AVNPs), AVNP2 is the 2nd generation of AVNP2 that have been conjugated to graphite-graphene for improving physiochemical performance and reducing toxicity. AVNP2 inactivates viruses, such as the H1N1 and H5N1influenza viruses and even the SARS coronavirus, while it inhibits bacteria, such as MRSA and E. coli. As antimicrobials, nanoparticles are considered to be one of the vectors for the administration of therapeutic compounds. Yet, little is known about their potential functionalities and toxicities to the neurotoxic effects of cancer. Herein, we explored the functionality of AVNP2 on inhibiting C6 in glioma-bearing rats. The novel object-recognition test and open-field test showed that AVNP2 significantly improved the neuro-behaviour affected by C6 glioma. AVNP2 also alleviated the decline of long-term potentiation (LTP) and the decreased density of dendritic spines in the CA1 region induced by C6. Western blot assay and immunofluorescence staining showed that the expressions of synaptic-related proteins (PSD-95 and SYP) were increased, and these findings were in accordance with the results mentioned above. It revealed that the sizes of tumours in C6 glioma-bearing rats were smaller after treatment with AVNP2. The decreased expression of inflammatory factors (IL-1β, IL-6 and TNF-α) by Western blotting assay and ELISA, angiogenesis protein (VEGF) by Western blotting assay and other related proteins (BDNF, NF-ĸB, iNOS and COX-2) by Western blotting assay in peri-tumour tissue indicated that AVNP2 could control tumour-associated inflammation, thus efficiently ameliorating the local inflammatory condition and, to some extent, inhibiting angiogenesis in C6-bearing rats. In conclusion, our results suggested that AVNP2 could have an effect on the peri-tumor environment, obviously restraining the growth progress of gliomas, and eventually improving cognitive levels in C6-bearing rats.


title: Distinct Patterns of IFITM-Mediated Restriction of Filoviruses, SARS Coronavirus, and Influenza A Virus

text: Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM1, 2, and 3) are recently identified viral restriction factors that inhibit infection mediated by the influenza A virus (IAV) hemagglutinin (HA) protein. Here we show that IFITM proteins restricted infection mediated by the entry glycoproteins (GP(1,2)) of Marburg and Ebola filoviruses (MARV, EBOV). Consistent with these observations, interferon-β specifically restricted filovirus and IAV entry processes. IFITM proteins also inhibited replication of infectious MARV and EBOV. We observed distinct patterns of IFITM-mediated restriction: compared with IAV, the entry processes of MARV and EBOV were less restricted by IFITM3, but more restricted by IFITM1. Moreover, murine Ifitm5 and 6 did not restrict IAV, but efficiently inhibited filovirus entry. We further demonstrate that replication of infectious SARS coronavirus (SARS-CoV) and entry mediated by the SARS-CoV spike (S) protein are restricted by IFITM proteins. The profile of IFITM-mediated restriction of SARS-CoV was more similar to that of filoviruses than to IAV. Trypsin treatment of receptor-associated SARS-CoV pseudovirions, which bypasses their dependence on lysosomal cathepsin L, also bypassed IFITM-mediated restriction. However, IFITM proteins did not reduce cellular cathepsin activity or limit access of virions to acidic intracellular compartments. Our data indicate that IFITM-mediated restriction is localized to a late stage in the endocytic pathway. They further show that IFITM proteins differentially restrict the entry of a broad range of enveloped viruses, and modulate cellular tropism independently of viral receptor expression.


title: Coding-Complete Genome Sequences of Two SARS-CoV-2 Isolates from Egypt

text: This report announces the complete genome sequences of two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolates detected in Egypt. The isolates were obtained from oropharyngeal swab specimens from two Egyptians in Upper and Lower Egypt. Sequence analysis showed mutations that differentiate Egyptian strains from the reference strain 2019-nCoV WHU01.


title: Test, test, test for COVID-19 antibodies: the importance of sensitivity, specificity and predictive powers

text: Abstract SARS-CoV-2 antibody tests of varying specificity and sensitivity are now available. For informing individuals whether they have had COVID-19, they need to be very accurate. For measuring population prevalence of past infection, the numbers of false positives and negatives need to be roughly equal. With a series of worked examples for a notional population of 100,000 people, we show that even test systems with a high specificity can yield a large number of false positive results, especially where the population prevalence is low. For example, at a true population prevalence of 5%, using a test with 99% sensitivity and specificity, 16% of positive results will be false and thus 950 people will be incorrectly informed they have had the infection. Further confirmatory testing may be needed. Giving false reassurance upon which personal or societal decisions might be based could be harmful for individuals, undermine public confidence and foster further outbreaks.


title: Case series of coronavirus (SARS-CoV-2) in a military recruit school: clinical, sanitary and logistical implications

text: INTRODUCTION: A new coronavirus, called Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2), has emerged from China in late 2019 and has now caused a worldwide pandemic. The impact of COVID-19 has not been described so far in a military setting. We therefore report a case series of infected patients in a recruit school in Switzerland and the herein associated challenges. METHODS: Retrospective review of COVID-19 cases among Swiss Armed Forces recruits in the early weeks of SARS-CoV-2 pandemic in the canton of Ticino, the southernmost canton of Switzerland. Positive cases were defined with two positive PCR testing for SARS-CoV-2 from nasopharyngeal swabs. Serological testing was performed with a commercially available kit according to manufacturers’ instructions. RESULTS: The first case was likely contaminated while skiing during weekend permission. He became symptomatic 4 days later, tested positive for SARS-CoV-2 and was put into isolation. He showed complete symptom resolution after 48 hours. Quarantine was ordered for all recruits with close contact in the past 2 days, a total of 55 persons out of 140 in the company. Seven out of nine recruits in one particular quarantine room became mildly symptomatic. SARS-CoV-2 PCR was positive in one of them. Seven days after initial diagnosis, the index patient and the other one from the quarantine retested positive for SARS-CoV-2, although they had been completely asymptomatic for over 96 hours. Serological testing revealed positive for both patients. All others showed negative IgM and IgG. CONCLUSIONS: Young healthy recruits often showed a mild course of COVID-19 with rapid symptom decline but were persistent SARS-CoV-2 carriers. This illustrates how asymptomatic patients may be responsible for covert viral transmission. An early and prolonged establishment of isolation and quarantine for patients and close contacts is essential to slow down the spread of SARS-CoV-2, especially in the confined space of a military environment.


title: From Anonymous to Public Enemy: How Does a Mosquito Become a Feared Arbovirus Vector?

text: The past few decades have seen the emergence of several worldwide arbovirus epidemics (chikungunya, Zika), the expansion or recrudescence of historical arboviruses (dengue, yellow fever), and the modification of the distribution area of major vector mosquitoes such as Aedes aegypti and Ae. albopictus, raising questions about the risk of appearance of new vectors and new epidemics. In this opinion piece, we review the factors that led to the emergence of yellow fever in the Americas, define the conditions for a mosquito to become a vector, analyse the recent example of the new status of Aedes albopictus from neglected mosquito to major vector, and propose some scenarios for the future.


title: Serum and fecal profiles of aromatic microbial metabolites reflect gut microbiota disruption in critically ill patients: a prospective observational pilot study

text: BACKGROUND: High serum levels of certain aromatic microbial metabolites (AMM) are associated with severity and mortality in critically ill patients. Omics-based studies suggest gut dysbiosis and reduced microbiome diversity in critical conditions. However, the landscape of gut microbial metabolites is still to be outlined, not to mention the interplay correlation between the metabolome and gut microbiome in critically ill patients. The aim of this study was to analyze the association between serum and fecal levels of AMM and compare them with the composition of gut microbiota in critically ill patients in the acute and chronic stages. METHODS: In this prospective observational pilot study, we analyzed the temporal dynamics of the gut microbiome and the AMM spectrum across two distinct subgroups—acute critical ill (ACI) patients with nosocomial pneumonia and chronically critically ill (CCI) patients (9 subjects each group)—as well as performed comparison with 23 healthy volunteers. The AMM levels for each patient were measured using GC-MS in simultaneously taken serum and fecal samples (SFS). These parameters were compared with 16S rRNA fecal microbiome profiles. RESULTS: The observed proportions of bacterial taxa suggest a significant gut dysbiosis in the ACI and the CCI patients. Stronger imbalance in microbiome composition and dynamics observed in the ACI patients compared to the CCI ones resonates with a higher severity in the former group. The total levels of AMM in serum samples were higher for the ACI patients than for the CCI patients (3.7 (1.4–6.3) and 1.1 (1.0–1.6) μM, respectively; p = 0.0003). The qualitative composition of the SFS was also altered. We discovered significant associations between gut microbial taxa levels and metabolite concentrations in blood serum as well as in feces in each of the ACI and the CCI patients. CONCLUSIONS: Aromatic microbial metabolite profiles in the gut and the serum are interlinked and reflect a disruption of the gut microbial community in critically ill patients.


title: Could Ergothioneine Aid in the Treatment of Coronavirus Patients?

text: Infection with SARS-CoV-2 causes the coronavirus infectious disease 2019 (COVID-19), a pandemic that has, at present, infected more than 11 million people globally Some COVID-19 patients develop a severe and critical illness, spurred on by excessive inflammation that can lead to respiratory or multiorgan failure Numerous studies have established the unique array of cytoprotective properties of the dietary amino acid ergothioneine Based on studies in a range of in vitro and in vivo models, ergothioneine has exhibited the ability to modulate inflammation, scavenge free radicals, protect against acute respiratory distress syndrome, prevent endothelial dysfunction, protect against ischemia and reperfusion injury, protect against neuronal damage, counteract iron dysregulation, hinder lung and liver fibrosis, and mitigate damage to the lungs, kidneys, liver, gastrointestinal tract, and testis, amongst many others When compiled, this evidence suggests that ergothioneine has a potential application in the treatment of the underlying pathology of COVID-19 We propose that ergothioneine could be used as a therapeutic to reduce the severity and mortality of COVID-19, especially in the elderly and those with underlying health conditions This review presents evidence to support that proposal


title: Virus Hunters: Catching Bugs in the Field

text: Densely populated areas in rural China require constant vigilance and state-of-the-art technology to stop new pandemics in their tracks. Hurdles are not only scientific in some parts of the developing world.


title: Lack of Middle East Respiratory Syndrome Coronavirus Transmission from Infected Camels

text: To determine risk for Middle East respiratory syndrome coronavirus transmission from camels to humans, we tested serum from 191 persons with various levels of exposure to an infected dromedary herd. We found no serologic evidence of human infection, suggesting that zoonotic transmission of this virus from dromedaries is rare.


title: COVID19 inhibitors: A prospective therapeutics

text: Abstract The inhibition of viral targets might provide new therapies for coronavirus disease abbreviated as COVID-19. The rational drug design identified as much of the recent discoveries of potent drugs molecule against any targets. This results in an improvement in bindings for better potency and selectivity. The drugs containing ethanolamine/propylamine fragments along with heterocycles have shown potential antiviral results. Similarly, there is the possibility of controlling the COVID-19 infection by nucleotide analogues. Here we also highlight drugs ACEIs/ARBs inhibitory discussing both their advantages and disadvantages. The class of compounds/antibodies inhibiting interleukin-6 works in antirheumatoid drugs are found useful in alleviating overactive inflammatory responses in the lungs of the patient. These inclusion based approaches counter some of the side-effects associated with the heterocycles and also potentiate the efficacy of the molecules. In this review article, design strategies for some of the drugs effective against SARS-CoV-2 are represented. The review also focuses on the listing of drugs that are currently testing under clinical trials for the COVID-19 virus with their mechanism of action. This conversation undertakes the opportunity to do a bit for the newer researchers working in this arena.


title: COVID-19 occurring during Natalizumab treatment: a case report in a patient with extended interval dosing approach

text: Abstract Background The novel Coronavirus SARS-CoV-2, which was identified after a recent outbreak in Wuhan, China, in December 2019, has generated a global pandemic impacting over 200 countries around the world. Recent reports suggest that ACE2, which is the target protein to invade the host, has a ubiquitous presence in human organs, including lung parenchyma, gastrointestinal tract, nasal mucosa, renal and urinary tract, airway epithelia, lymphoid tissues, reproductive organs, vascular endothelium and neurons. In this scenario, neurologists are particularly involved into considering even more specific therapeutic strategies according to the available data during the pandemic. In particular, MS patients are usually receiving disease-modifying therapies (DMTs) with immunosuppressant or immunomodulatory effects, which increase the risk of infections and morbidity, compared with the general population. Development of PML or other serious opportunistic infections during treatment with natalizumab forces to consider whether de-risking strategies are needed in this particular context and how to manage a high-efficacy treatment. Methods In this paper we report on a patient treated with natalizumab for relapsing MS who developed COVID-19 and recovered in a few days without complications. Results After recovery natalizumab has been administered in the window of the extended interval dosing (EID), without reporting any worsening or new symptoms. Discussion This case supports the opportunity to avoid discontinuing or delaying the retreatment over 8 weeks in patients recovered from a recent COVID-19.


title: Lung pathology of severe acute respiratory syndrome (SARS): a study of 8 autopsy cases from Singapore

text: Abstract Severe acute respiratory syndrome (SARS) is an infectious condition caused by the SARS-associated coronavirus (SARS-CoV), a new member in the family Coronaviridae. To evaluate the lung pathology in this life-threatening respiratory illness, we studied postmortem lung sections from 8 patients who died from SARS during the spring 2003 Singapore outbreak. The predominant pattern of lung injury in all 8 cases was diffuse alveolar damage. The histology varied according to the duration of illness. Cases of 10 or fewer days’ duration demonstrated acute-phase diffuse alveolar damage (DAD), airspace edema, and bronchiolar fibrin. Cases of more than 10 days’ duration exhibited organizing-phase DAD, type II pneumocyte hyperplasia, squamous metaplasia, multinucleated giant cells, and acute bronchopneumonia. In acute-phase DAD, pancytokeratin staining was positive in hyaline membranes along alveolar walls and highlighted the absence of pneumocytes. Multinucleated cells were shown to be both type II pneumocytes and macrophages by pancytokeratin, thyroid transcription factor-1, and CD68 staining. SARS-CoV RNA was identified by reverse transcriptase-polymerase chain reaction in 7 of 8 cases in fresh autopsy tissue and in 8 of 8 cases in formalin-fixed, paraffin-embedded lung tissue, including the 1 negative case in fresh tissue. Understanding the pathology of DAD in SARS patients may provide the basis for therapeutic strategies. Further studies of the pathogenesis of SARS may reveal new insight into the mechanisms of DAD.


title: Workforce Considerations, Training, and Diseases in the Middle East

text: Evaluating and providing global health assistance, humanitarian aid, and medical missions to Middle Eastern countries can be rewarding and challenging. A broad spectrum of financial capabilities supports effective health care delivery and infrastructure. Middle East tension can make obtaining a visa difficult. Personal safety considerations may hinder efforts to develop and carry out clinical and educational programs. Several Middle East countries have sophisticated and modern health care systems. Medical education and specialty training compares with that of Western medicine. The Middle East has a proud heritage as the foundation of many fundamental and modern medical and surgical principles.


title: Ebola: werknemers in de frontlijn: Infectieziekten en Arbeid

text: Ebola is de zoveelste zoönose die de Nederlandse samenleving treft binnen een paar jaar tijd. Denk maar aan de Mexicaanse griep, het Schmallenbergvirus, H5N8 aviaire influenza, MERS-CoV(16), Q-koorts en de ziekte van Lyme. De schaal waarop Nederlandse UMC’s en andere ketenpartners zich voorbereiden op een mogelijke introductie van ebola is ongeëvenaard. Sinds augustus 2014 houden vele duizenden professionals, beleidsmakers, et cetera, zich intensief bezig met de voorbereidingen. Uniek bij deze ebola-uitbraak is de grote aandacht voor de bedrijfsgeneeskunde. Was er bij eerdere zoönosen minimaal aandacht voor bedrijfsgeneeskundige aspecten, bij ebola zijn veilige arbeidsomstandigheden een centraal thema – terecht, want werknemers staan hier in de frontlijn. Never waste a good crisis. Wellicht is dit een uitgelezen kans om het thema veilige arbeidsomstandigheden en biologische agentia weer eens bij klanten op de agenda te zetten, ook in andere sectoren.


title: Incremental Validity of Coronaphobia: Coronavirus Anxiety explains Depression, Generalized Anxiety, and Death Anxiety

text: The adverse psychological effects of COVID-19 have increased globally. Moreover, the psychological toll may be worsening for this health crisis due to the growing numbers of mass deaths and unemployment levels. Coronaphobia, a relatively new pandemic-related construct, has been shown to be strongly related to functional impairment and psychological distress. However, the extent to which coronaphobia is uniquely accountable for the psychological distress experienced during the COVID-19 crisis has not been systematically investigated. The current study examined this question of incremental validity using online data from 453 adult MTurk workers in the U.S. The results of a series of hierarchical multiple regression analyses demonstrated that coronaphobia explained additional variance in depression, generalized anxiety, and death anxiety, above sociodemographics, COVID-19 factors, and the vulnerability factors of neuroticism, health anxiety, and reassurance-seeking behaviors. These findings suggest that health professionals should be aware of coronaphobia as this expression of pandemic-related stress has reliably demonstrated incremental validity in accounting for major indicators of psychological distress.


title: 100% peer review in radiation oncology: is it feasible?

text: PURPOSE: Peer review has been proposed as a strategy to ensure patient safety and plan quality in radiation oncology. Despite its potential benefits, barriers commonly exist to its optimal implementation in daily clinical routine. Our purpose is to analyze peer-review process at our institution. METHODS AND MATERIALS: Based on our group peer-review process, we quantified the rate of plan changes, time and resources needed for this process. Prospectively, data on cases presented at our institutional peer-review conference attended by physicians, resident physicians and physicists were collected. Items such as time to present per case, type of patient (adult or pediatric), treatment intent, dose, aimed technique, disease location and receipt of previous radiation were gathered. Cases were then analyzed to determine the rate of major change, minor change and plan rejection after presentation as well as the median time per session. RESULTS: Over a period of 4 weeks, 148 cases were reviewed. Median of attendants was six physicians, three in-training-physicians and one physicist. Median time per session was 38 (4–72) minutes. 59.5% of cases presented in 1–4 min, 32.4% in 5–9 min and 8.1% in ≥ 10 min. 79.1% of cases were accepted without changes, 11.5% with minor changes, 6% with major changes and 3.4% were rejected with indication of new presentation. Most frequent reason of change was contouring corrections (53.8%) followed by dose or fractionation (26.9%). CONCLUSION: Everyday group consensus peer review is an efficient manner to recollect clinical and technical data of cases presented to ensure quality radiation care before initiation of treatment as well as ensuring department quality in a feedback team environment. This model is feasible within the normal operation of every radiation oncology Department.


title: Differential innate immune responses induced by classical and variant infectious bronchitis viruses in specific pathogen free chicks

text: Abstract Avian infectious bronchitis virus (IBV) continues to cause serious economic losses in global chicken production. Concurrent circulation of both classic and variant IBVs have been identified in most parts of the world, raising major challenges to global prevention and control efforts. Therefore, immunopathogenesis, particularly early host responses, needs to be better understood for effective control of diseases caused by different strains of IBVs. We investigated differing immunopathogenesis in chickens following infection with IS/885/00-like (885), QX-like (QX) and M41 IBV strains. We confirmed that the histopathological changes, proinflammatory and innate immune gene responses were induced to different magnitudes, depending on the IBV strain. Results indicated that upregulation of proinflammatory cytokines (such as IL-6 and IL-1β) and lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF) expression is induced by IBV M41 in the trachea and by IBV 885 and QX in the kidney, which mainly coincides with tracheal and renal histopathological lesions respectively caused by these strains. In addition, elevated levels of TLR3, MDA5 and IFN-β expression occurred concurrently with greater lesion severity in IBV infected trachea and kidney tissues. Overall, this study reports marked differences in the activation of early host responses by pathogenic IBV strains.


title: Establishment of a recombinase polymerase amplification (RPA) assay for the detection of Brucella spp. Infection

text: Abstract Brucellosis is a worldwide re-emerging zoonosis. It has an economic impact due to abortion and loss of fertility in livestock. In this study, Real-time recombinase polymerase amplification (RT-RPA-BP26) targeting Brucella spp. bp26 gene and Lateral flow dipstick (LFD-RPA-IS711) combined with SYBR- Green recombinase polymerase amplification (RPA) targeting insertion sequence IS711 region of Brucella spp. bp26 gene, was developed to detect Brucella spp. from different sample types in domestic animals. The sensitivity and specificity of the two developed RPAs were compared with real-time PCR, PCR, and Rose Bengal Plate Test (RBPT). The analytical sensitivity and detection limit of Real-time RPA and LFD RPA were four and six copies per reaction respectively. The detection of six colony forming units (CFU) of the bacteria-bearing construct with the target sequence was within 20 min at 40 °C for Real-time RPA and 37 °C for LFD RPA. The LFD RPA could work at temperatures between 30 and 35 °C and could be completed within 10–30 min. No significant differences were observed when comparing the results from Real-time RPA and LFD RPA to Real-time PCR and PCR. Both methods showed no cross reactivity with Chlamydia abortus, Toxoplasma gondii, Salmonella typhimurium, and Escherichia coli. In conclusion, RPA is a useful and convenient field and point of care test for brucellosis.


title: Phage display technique identifies the interaction of severe acute respiratory syndrome coronavirus open reading frame 6 protein with nuclear pore complex interacting protein NPIPB3 in modulating Type I interferon antagonism

text: Abstract Background/Purpose Severe acute respiratory syndrome coronavirus (SARS-CoV) proteins including ORF6 inhibit Type I interferon (IFN) signaling. Methods This study identified SARS-CoV ORF6-interacting proteins using the phage displayed human lung cDNA libraries, and examined the association of ORF6–host factor interaction with Type I IFN antagonism. After the fifth round of biopanning with Escherichia coli-synthesized ORF6-His tagged protein, the relative binding affinity of phage clones to ORF6 was determined using direct enzyme-linked immunosorbent assay. Results The highest affinity clone to ORF6 displayed the C-terminal domain of NPIPB3 (nuclear pore complex interacting protein family, member B3; also named as phosphatidylinositol-3-kinase-related kinase SMG-1 isoform 1 homolog). The coimmunoprecipitation assay demonstrated the direct binding of ORF6 to the C-terminal domain of NPIPB3 in vitro. Confocal imaging revealed a close colocalization of SARS-CoV ORF6 protein with NPIPB3 in human promonocytes. The dual luciferase reporter assay showed that the C-terminal domain of NPIPB3 attenuated the antagonistic activity of SARS-CoV ORF6 on IFN-β-induced ISRE (IFN stimulated response element)-responsive firefly luciferase activity. In addition, confocal imaging and Western blotting assays revealed that the increases in STAT-1 nuclear translocation and phosphorylation occurred in the transfected cells expressing both genes of ORF6 and NPIPB3, but not in the ORF6-expressing cells in response to IFN-β. Conclusion The overexpression of NPIPB3 restored the IFN-β responses in SARS-CoV ORF6 expressing cells, indicating that the interaction of SARS CoV ORF6 and NPIPB3 reduced Type I IFN antagonism by SARS-CoV ORF6.


title: Expression, crystallization and preliminary crystallographic study of the functional mutant (N60K) of nonstructural protein 9 from Human coronavirus HKU1

text: Human coronavirus HKU1 (HCoV-HKU1), which mainly causes acute self-limited respiratory-tract infections, belongs to group A of the Betacoronavirus genus. Coronavirus genomes encode 16 nonstructural proteins (nsp1–16), which assemble into a large replication–transcription complex mediating virus propagation. Nonstructural protein 9, which binds to the single-stranded DNA/RNA, has been shown to be indispensible for viral replication. Interestingly, a functional mutant (N60K) of nsp9 was identified to compensate for a 6 nt insertion mutation of the 3′-untranslated region (UTR), which is critical for viral RNA synthesis. It has been proposed that the N60K mutation may cause certain conformational changes of nsp9 to rescue the defective insertion mutant. To further investigate the underlying structural mechanism, the N60K mutant of nsp9 from HCoV-HKU1 was successfully crystallized in this study. The crystals diffracted to 2.6 Å resolution and belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 31.9, b = 85.0, c = 95.0 Å. Two molecules were identified per asymmetric unit.


title: Nafamostat Mesylate Blocks Activation of SARS-CoV-2: New Treatment Option for COVID-19

text: The currently unfolding coronavirus pandemic threatens health systems and economies worldwide.….


title: Epidemiology of COVID-19 in older persons, Wuhan, China

text: BACKGROUND: The epidemiological characteristics of older patients with COVID-19 was far from clear. OBJECTIVE: To explore the epidemiology of older patients with COVID-19 in Wuhan, China. DESIGN: A retrospective cross-sectional study. SETTING: A population-based study. SUBJECTS: The resident older patients (older than 65 years old) diagnosed with COVID-19. METHODS: Citywide case series reported to Wuhan Center for Disease Control and Prevention from 12 December 2019 to 17 March 2020 were included. The epidemic curves were constructed by dates of disease onset. RESULTS: 14238 confirmed COVID-19 cases were older persons. The number of male cases were slightly less than female cases (1:1.01). The attack rate of COVID-19 in the older persons was 11.49‰ in Wuhan. There was a rapid increase of disease at the early stage of the epidemic and then a gradual and steady decrease was performed. 3,723 (26.15%) and 734 (5.16%) patients were diagnosed as severe and critical cases, respectively. The attributable crude fatality ratio of COVID-19 in the older population was 222.57/100,000, and the crude fatality ratio of COVID was 19.37%. The proportion of severe and critical cases, and fatality ratio were both higher in downtown area and increased with age. CONCLUSIONS: The older persons are sensitive to COVID-19. The proportion of severe and critical cases and fatality ratio are higher than that in children and younger adults. Strengthen the protection and control strategies for the older adults is of priorities. More detailed epidemiological and clinical information should be measured in further studies.


title: Assembling evidence for identifying reservoirs of infection

text: Many pathogens persist in multihost systems, making the identification of infection reservoirs crucial for devising effective interventions. Here, we present a conceptual framework for classifying patterns of incidence and prevalence, and review recent scientific advances that allow us to study and manage reservoirs simultaneously. We argue that interventions can have a crucial role in enriching our mechanistic understanding of how reservoirs function and should be embedded as quasi-experimental studies in adaptive management frameworks. Single approaches to the study of reservoirs are unlikely to generate conclusive insights whereas the formal integration of data and methodologies, involving interventions, pathogen genetics, and contemporary surveillance techniques, promises to open up new opportunities to advance understanding of complex multihost systems.


title: Contingency Plan for the Intensive Care Services for the COVID-19 pandemic

text: Abstract In January 2020, the Chinese authorities identified a new virus of the Coronaviridae family as the cause of several cases of pneumonia of unknown aetiology. The outbreak was initially confined to Wuhan City, but then spread outside Chinese borders. On 31 January 2020, the first case was declared in Spain. On 11 March 2020, The World Health Organization (WHO) declared the coronavirus outbreak a pandemic. On 16 March 2020, there were 139 countries affected. In this situation, the Scientific Societies SEMICYUC and SEEIUC, have decided to draw up this Contingency Plan to guide the response of the Intensive Care Services. The objectives of this plan are to estimate the magnitude of the problem and identify the necessary human and material resources. This is to provide the Spanish Intensive Medicine Services with a tool to programme optimal response strategies.


title: An uncommon cold

text: The covid-19 virus isn't the first coronavirus to jump from animals to humans. What can we learn from previous encounters, asks Anthony King


title: Essential Long‐Term Care Workers Commonly Hold Second Jobs and Double‐ or Triple‐Duty Caregiving Roles

text: OBJECTIVES: Long‐term care (LTC) facilities are particularly dangerous places for the spread of COVID‐19 given that they house vulnerable high‐risk populations. Transmission‐based precautions to protect residents, employees, and families alike must account for potential risks posed by LTC workersʼ second jobs and unpaid care work. This observational study describes the prevalence of their (1) second jobs, and (2) unpaid care work for dependent children and/or adult relatives (double‐ and triple‐duty caregiving) overall and by occupational group (registered nurses [RNs], licensed practical nurses [LPNs], or certified nursing assistants [CNAs]). DESIGN: A descriptive secondary analysis of data collected as part of the final wave of the Work, Family and Health Study. SETTING: Thirty nursing home facilities located throughout the northeastern United States. PARTICIPANTS: A subset of 958 essential facility‐based LTC workers involved in direct patient care. MEASUREMENTS: We present information on LTC workersʼ demographic characteristics, health, features of their LTC occupation, additional paid work, wages, and double‐ or triple‐duty caregiving roles. RESULTS: Most LTC workers were CNAs, followed by LPNs and RNs. Overall, more than 70% of these workers agreed or strongly agreed with this statement: “When you are sick, you still feel obligated to come into work.” One‐sixth had a second job, where they worked an average of 20 hours per week, and more than 60% held double‐ or triple‐duty caregiving roles. Additional paid work and unpaid care work characteristics did not significantly differ by occupational group, although the prevalence of second jobs was highest and accompanying work hours were longest among CNAs. CONCLUSION: LTC workers commonly hold second jobs along with double‐ and triple‐duty caregiving roles. To slow the spread of COVID‐19, both the paid and unpaid activities of these employees warrant consideration in the identification of appropriate clinical, policy, and informal supports.


title: Advax Delta Inulin Adjuvant Overcomes Immune Immaturity In Neonatal Mice Thereby Allowing Single–Dose Influenza Vaccine Protection

text: Neonates are at high risk for influenza morbidity and mortality due to immune immaturity and lack of priming by prior exposure. Inactivated influenza vaccines are ineffective in infants under six months and to provide protection in older children generally require two doses given a month apart. This leaves few options for rapid protection of infants, e.g. during an influenza pandemic. We investigated whether Advax™, a novel polysaccharide adjuvant based on delta inulin microparticles could help overcome neonatal immune hypo-responsiveness and also whether it was possible to obtain single-dose influenza vaccine protection of babies against lethal infection. Inactivated influenza A/H1N1 vaccine (iH1N1) combined with Advax™ adjuvant administered as a single immunization to 7-day-old mouse pups significantly enhanced serum influenza-specific IgM, IgG1, IgG2a and IgG2b levels in association with a 3–4 fold increase in the frequency of splenic influenza-specific IgM and IgG antibody secreting cells versus pups immunized with iH1N1 alone. Pups immunized with Advax-adjuvanted iH1N1 had significantly higher influenza-stimulated splenocyte production of IFN-γ, IL-2, IL-4, and IL-10 and a 3–10 fold higher frequency of T cells IFN-γ secreting IL-2, IL-4 or IL-17 by ELISPOT. Immunisation with iH1N1+Advax adjuvant induced robust protection against influenza virus challenge 3 weeks post-immunization, whereas pups immunized with iH1N1 alone had no protection. Protection by Advax-adjuvanted iH1N1 was mediated by serum antibody and memory B cells rather than memory T cells as protection was lost in neonatal µMT mice that are B-cell deficient. Hence, Advax adjuvant overcame neonatal immune hypo-responsiveness and enabled single-dose protection of pups against otherwise lethal influenza infection, thereby supporting development of Advax™ as a neonatal vaccine adjuvant.


title: Thin-section CT assessment of spontaneous pneumomediastinum in interstitial lung disease: Correlation with serial changes in lung parenchymal abnormalities

text: Summary Purpose The purpose of this study was to analyze thin-section computed tomography (CT) appearances of interstitial lung diseases before and at the time of detection of pneumomediastinum, and to evaluate the relationship between pneumomediastinum and parenchymal changes on thin-section CT. Materials & methods We reviewed CT images before and at the time of detection of pneumomediastinum in 13 patients with idiopathic pulmonary fibrosis (8 patients) and collagen vascular diseases (5 patient). The extent of the total area of reticular opacity, increased opacity (ground-glass opacity and consolidation), and honeycombing were scored, and these scores were compared before and at the time of detection of pneumomediastinum. We also divided patients into two groups according to therapy received. Patients in group 1 experienced pneumomediastinum after or during treatment with corticosteroids or immunosuppressive agents for acute or subacute exacerbation of interstitial lung disease. Patients in group 2 experienced pneumomediastinum without therapy. Results The mean score of all patients for honeycombing significantly increased at the time of detection of pneumomediastinum ( P = 0.003 ). In group 1, the extent of increasing opacity had been decreased significantly at the time of detection of pneumomediastinum ( P = 0.028 ). In group 2, the mean CT score of reticular opacity, increasing opacity, and honeycombing significantly increased at the time of detection of pneumomediastinum ( P = 0.028 , 0.018, and 0.018, respectively). Conclusions Spontaneous pneumomediastinum associated with interstitial lung disease appears to have a tendency to occur under conditions of altered of parenchymal interstitial lesions.


title: RNA chaperone activity of the tombusviral p33 replication protein facilitates initiation of RNA synthesis by the viral RdRp in vitro

text: Small plus-stranded RNA viruses do not code for RNA helicases that would facilitate the proper folding of viral RNAs during replication. Instead, these viruses might use RNA chaperones as shown here for the essential p33 replication protein of Tomato bushy stunt virus (TBSV). In vitro experiments demonstrate that the purified recombinant p33 promotes strand separation of a DNA/RNA duplex. In addition, p33 renders dsRNA templates sensitive to single-strand specific S1 nuclease, suggesting that p33 can destabilize highly structured RNAs. We also demonstrate that the RNA chaperone activity of p33 facilitates self-cleavage by a ribozyme in vitro. In addition, purified p33 facilitates in vitro RNA synthesis on double-stranded (ds)RNA templates up to 5-fold by a viral RNA-dependent RNA polymerase. We propose that the RNA chaperone activity of p33 facilitates the initiation of plus-strand synthesis as well as affects RNA recombination. Altogether, the TBSV RNA chaperone might perform similar biological functions to the helicases of other RNA viruses with much larger coding capacity.


title: Research Note: Lyophilization of hyperimmune egg yolk: effect on antibody titer and protection of broilers against Campylobacter colonization

text: Abstract Oral administration of antibodies is a promising strategy against various infectious diseases. Previously, it was demonstrated that passive immunization by providing hyperimmune egg yolk through the feed reduces Campylobacter jejuni colonization in broilers. Campylobacteriosis is the most commonly reported bacterial foodborne zoonosis worldwide, and poultry products are the number one origin of these bacteria for human infection. To date, no effective control measures exist to limit Campylobacter colonization in the chicken's intestinal tract. Here, the effect of lyophilization of hyperimmune egg yolk on protection of broilers against C. jejuni was investigated. During an in vivo trial, broiler chickens were prophylactically given feed with lyophilized hyperimmune or non-immunized egg yolk powder starting from day 1 after hatch. At day 11, broilers were inoculated with C. jejuni according to a seeder model. Five days later, all broilers were euthanized and cecal content was examined for C. jejuni colonization. No decrease in C. jejuni colonization was found. The freeze-drying resulted in a 16-fold decrease of the antibody titer in the yolk powder compared to the fresh yolks, presumably caused by structural changes in the antibodies. In conclusion, applying freeze-dried hyperimmune egg yolk failed to protect broilers against C. jejuni colonization, possibly because lyophilization affected the antibodies' functionality.


title: Design and synthesis of new tripeptide-type SARS-CoV 3CL protease inhibitors containing an electrophilic arylketone moiety

text: Abstract We describe here the design, synthesis and biological evaluation of a series of molecules toward the development of novel peptidomimetic inhibitors of SARS-CoV 3CLpro. A docking study involving binding between the initial lead compound 1 and the SARS-CoV 3CLpro motivated the replacement of a thiazole with a benzothiazole unit as a warhead moiety at the P1′ site. This modification led to the identification of more potent derivatives, including 2i, 2k, 2m, 2o, and 2p, with IC50 or K i values in the submicromolar to nanomolar range. In particular, compounds 2i and 2p exhibited the most potent inhibitory activities, with K i values of 4.1 and 3.1nM, respectively. The peptidomimetic compounds identified through this process are attractive leads for the development of potential therapeutic agents against SARS. The structural requirements of the peptidomimetics with potent inhibitory activities against SARS-CoV 3CLpro may be summarized as follows: (i) the presence of a benzothiazole warhead at the S1′-position; (ii) hydrogen bonding capabilities at the cyclic lactam of the S1-site; (iii) appropriate stereochemistry and hydrophobic moiety size at the S2-site and (iv) a unique folding conformation assumed by the phenoxyacetyl moiety at the S4-site.


title: Evidence-based guidelines for managing patients with primary ER+ HER2− breast cancer deferred from surgery due to the COVID-19 pandemic

text: Many patients with ER+ HER2− primary breast cancer are being deferred from surgery to neoadjuvant endocrine therapy (NeoET) during the COVID-19 pandemic. We have collated data from multiple international trials of presurgical endocrine therapy in order to provide guidance on the identification of patients who may have insufficiently endocrine-sensitive tumors and should be prioritised for early surgery or neoadjuvant chemotherapy rather than NeoET during or in the aftermath of the COVID-19 pandemic for safety or when surgical activity needs to be prioritized. For postmenopausal patients, our data provide strong support for the use of ER and PgR status at diagnosis for triaging of patients into three groups in which (taking into account clinical factors): (i) NeoET is likely to be inappropriate (Allred ER <6 or ER 6 and PgR <6) (ii) a biopsy for Ki67 analysis (on-treatment Ki67) could be considered after 2–4 weeks of NeoET (a: ER 7 or 8 and PgR <6 or b: ER 6 or 7 and PgR ≥6) or (iii) NeoET is an acceptable course of action (ER 8 and PgR ≥6). Cut-offs for percentage of cells positive are also given. For group (ii), a high early on-treatment level of Ki67 (>10%) indicates a higher priority for early surgery. Too few data were available for premenopausal patients to provide a similar treatment algorithm. These guidelines should be helpful for managing patients with early ER+ HER2− breast cancer during and in the aftermath of the COVID-19 crisis.


Covid-19 Pandemic Experience: Can It Serve as a Clarion Call to Establish or Revamp a Specialty Known as ‘Infectious Diseases Physiotherapy’?


title: Role of regulatory T cells in coronavirus-induced acute encephalitis

text: Abstract C57BL/6 mice infected with mouse hepatitis virus, strain JHM (JHMV) develop a rapidly fatal acute encephalitis. Previously, we showed that this disease is partially CD4 T cell-mediated since infection with a recombinant JHMV (rJ) mutated in only a single immunodominant CD4 T cell epitope (epitope M133, rJ.MY135Q) results in a nonlethal disease. Increased mortality correlated with a greater number of JHMV-specific CD4 T cells in the brains of rJ compared to rJ.MY135Q-infected mice. Here, we extend these results to show that the diminished number of virus-specific T cells correlates with a reduced cytokine/chemokine response in the infected brain. We also show that regulatory CD4 T cells (Tregs) are critical for mild disease in rJ.MY135Q-infected mice because their depletion results in increased mortality. Further, a relative paucity of Tregs characterizes lethal infection because adoptive transfer of Tregs into rJ-infected mice increases survival from 0% to 50%. These results support the notion that clinical disease in coronavirus-induced acute encephalitis results from a balance between factors critical for virus clearance, such as virus-specific effector T cells and anti-inflammatory elements, such as Tregs. These findings also show that unlike chronic infections, in which an excessive number of Tregs contributes to pathogen persistence, Tregs in the setting of acute encephalitis may help to limit immunopathological disease without delaying virus clearance.


title: The time is now: moving toward virus-specific T cells after allogeneic hematopoietic stem cell transplantation as the standard of care

text: Abstract Adoptive immunotherapy—in particular, T-cell therapy—has recently emerged as a useful strategy with the potential to overcome many of the limitations of antiviral drugs for the treatment of viral complications after hematopietic stem cell transplantation. In this review, we briefly summarize the current methods for virus-specific T-cell isolation or selection and we report results from clinical trials that have used these techniques, focusing specifically on the strategies aimed to broaden the application of this technology.


title: Rapid detection of Acinetobacter baumannii and molecular epidemiology of carbapenem-resistant A. baumannii in two comprehensive hospitals of Beijing, China

text: Acinetobacter baumannii is an important opportunistic pathogen associated with a variety of nosocomial infections. A rapid and sensitive molecular detection in clinical isolates is quite needed for the appropriate therapy and outbreak control of A. baumannii. Group 2 carbapenems have been considered the agents of choice for the treatment of multiple drug-resistant A. baumannii. But the prevalence of carbapenem-resistant A. baumannii (CRAB) has been steadily increasing in recent years. Here, we developed a loop-mediated isothermal amplification (LAMP) assay for the rapid detection of A. baumannii in clinical samples by using high-specificity primers of the bla(OXA-51) gene. Then we investigated the OXA-carbapenemases molecular epidemiology of A. baumannii isolates in two comprehensive hospitals in Beijing. The results showed that the LAMP assay could detect target DNA within 60 min at 65°C. The detection limit was 50 pg/μl, which was about 10-fold greater than that of PCR. Furthermore, this method could distinguish A. baumannii from the homologous A. nosocomialis and A. pittii. A total of 228 positive isolates were identified by this LAMP-based method for A. baumannii from 335 intensive care unit patients with clinically suspected multi-resistant infections in two hospitals in Beijing. The rates of CRAB are on the rise and are slowly becoming a routine phenotype for A. baumannii. Among the CRABs, 92.3% harbored both the bla(OXA-23) and bla(OXA-51) genes. Thirty-three pulsotypes were identified by pulsed-field gel electrophoresis, and the majority belonged to clone C. In conclusion, the LAMP method developed for detecting A. baumannii was faster and simpler than conventional PCR and has great potential for both point-of-care testing and basic research. We further demonstrated a high distribution of class D carbapenemase-encoding genes, mainly OXA-23, which presents an emerging threat in hospitals in China.


title: The peptide specificities of the autoantibodies elicited by mouse hepatitis virus A59

text: Abstract Synthetic decapeptides (N =206) covering the entire sequence of mouse liver fumarylacetoacetate hydrolase (FAH) were used to analyze the specificities of the autoantibodies (autoAb) elicited towards this enzyme in mice infected with mouse hepatitis virus (MHV). These autoAb bound mainly to N- and C-terminal FAH peptides, the most reactive sequences being 1–50 and 390–420, respectively. Surprisingly, although FAH sequence 1–50 shares a high degree of homology with various MHV proteins, the C-terminal portion does not. Moreover, whereas the autoAb reacted with homologous peptides surrounding residues 70, 160 and 360, non-similar sequences around residues 130, 210, 240, 250, and 300 were also recognized, indicating that autoAb were not restricted to epitopes with sequence homologies. There was also a lack of correlation between the amount of anti-MHV or anti-FAH antibodies produced and the reactivity towards the peptides. Moreover, the spectrum of peptides recognized by the autoAb of a given mouse did not change significantly with time, which suggests that the MHV-elicited autoimmune response does not induce an epitope recognition spreading. Finally, anti-FAH Ab produced after immunization with rat liver FAH recognized essentially the same mouse FAH regions than autoAb from MHV-infected mice. Results indicated that the induction of the autoAb is not only related to molecular or structural mimicry, but rather supports the Danger model, in which any aggression, in this case the MHV infection, is susceptible to trigger the production of autoAb.


title: Diagnostics of Dairy and Beef Cattle Diarrhea

text: Calf diarrhea is a multifactorial disease related to a combination of host and pathogen factors. The most common pathogens found in diarrheic calves are cryptosporidium, rotavirus, coronavirus, Salmonella, attaching and effacing E coli and F5 (K99) Escherichia coli. Increased mortality and morbidity are often due to the presence of more than one pathogen. This article includes a discussion of key information to obtain a clinical history, the pathogens, pathology findings, and diagnostic methods.


title: Vaccinology at the beginning of the 21st century

text: Today, the main challenges for vaccinologists include improving vaccines against as yet undefeated pathogens, rapid identification and response to emerging diseases and successful intervention in chronic diseases in which ongoing immune responses are insufficient. Reverse genetics and reverse vaccinology are now used to generate rapidly new vaccine strains and to mine whole genomes in the search for promising antigens. The rational design of adjuvants has become possible as a result of the discovery of the receptors that recognize microbial patterns and lead to dendritic cell activation. Antigen-loaded dendritic cells, DNA in naked, formulated or viral form, and other delivery systems are used to maximize immune responses. Although work on the ‘easy’ vaccines has already been completed, it is hoped that a combination of conceptual and technical innovation will enable the development of more complex and sophisticated vaccines in the future.


title: Who’s afraid of the big bad wolf? The experience of an Oral Medicine Unit in the time of Corona‐Virus.

text: To cope with the emergency from COVID‐19 (2019‐nCoV) and to increase the supply of intensive care beds, all over the world it was necessary to remodel or suspend the deferred and non‐urgent inpatient and outpatient activities, including those provided by the dental clinics.


title: Importance of homo-dimerization of Fanconi-associated nuclease 1 in DNA flap cleavage

text: Abstract Fanconi-associated nuclease 1 (FAN1) removes interstrand DNA crosslinks (ICLs) through its DNA flap endonuclease and exonuclease activities. Crystal structures of human and bacterial FAN1 bound to a DNA flap have been solved. The Pseudomonas aeruginosa bacterial FAN1 and human FAN1 (hFAN1) missing a flexible loop are monomeric, while intact hFAN1 is homo-dimeric in structure. Importantly, the monomeric and dimeric forms of FAN1 exhibit very different DNA binding modes. Here, we interrogate the functional differences between monomeric and dimeric forms of FAN1 and provide an explanation for the discrepancy in oligomeric state between the two hFAN1 structures. Specifically, we show that the flexible loop in question is needed for hFAN1 dimerization. While monomeric and dimeric bacterial or human FAN1 proteins cleave a short 5′ flap strand with similar efficiency, optimal cleavage of a long 5′ flap strand is contingent upon protein dimerization. Our study therefore furnishes biochemical evidence for a role of hFAN1 homodimerization in biological processes that involve 5′ DNA Flap cleavage.


Reumataxi: Una experiencia solidaria en tiempos de COVID-19


title: Light as a potential treatment for pandemic coronavirus infections: A perspective

text: Abstract The recent outbreak of COVID-19, which continues to ravage communities with high death tolls and untold psychosocial and catastrophic economic consequences, is a vivid reminder of nature's capacity to defy contemporary healthcare. The pandemic calls for rapid mobilization of every potential clinical tool, including phototherapy—one of the most effective treatments used to reduce the impact of the 1918 “Spanish influenza” pandemic. This paper cites several studies showing that phototherapy has immense potential to reduce the impact of coronavirus diseases, and offers suggested ways that the healthcare industry can integrate modern light technologies in the fight against COVID-19 and other infections. The evidence shows that violet/blue (400–470 nm) light is antimicrobial against numerous bacteria, and that it accounts for Niels Ryberg Finsen's Nobel-winning treatment of tuberculosis. Further evidence shows that blue light inactivates several viruses, including the common flu coronavirus, and that in experimental animals, red and near infrared light reduce respiratory disorders, similar to those complications associated with coronavirus infection. Moreover, in patients, red light has been shown to alleviate chronic obstructive lung disease and bronchial asthma. These findings call for urgent efforts to further explore the clinical value of light, and not wait for another pandemic to serve as a reminder. The ubiquity of inexpensive light emitting lasers and light emitting diodes (LEDs), makes it relatively easy to develop safe low-cost light-based devices with the potential to reduce infections, sanitize equipment, hospital facilities, emergency care vehicles, homes, and the general environment as pilot studies have shown.


Strengthening what we already have: collaborations to prevent medication shortages amid COVID‐19


title: Skin fragility syndrome in a cat with cholangiohepatitis and hepatic lipidosis

text: A case of acquired skin fragility syndrome associated with hepatic disease in a 9-year-old, spayed female, domestic shorthair cat is described. The cat was admitted to the veterinary hospital of the University of São Paulo (Brazil) with a 6-week history of vomiting, inappetence and weight loss. Remarkable signs were weakness, lethargy and profound jaundice that had been present for 10 days according to the owner. On completion of the physical examination, when the cat was gently manipulated for blood collection the thoracic limb and interscapular skin tore. Liver enzymes and bilirubin levels were all above the normal range. On histological examination of skin and liver, Masson's trichrome stain showed collagen fibre alteration and major hepatocyte abnormalities. Findings were consistent with feline skin fragility syndrome associated with cholangiohepatitis and hepatic lipidosis.


title: Prevención y tratamiento del Covid-19 en la población pediátrica desde una perspectiva familiar y comunitaria

text: Resumen Partiendo del informe sobre la situación de COVID-19 en España, del 3 de abril de 2020, los casos confirmados ascienden a 117.710, de los que 343 tienen una edad inferior a 14 años (< del 1%). Es fundamental conocer la especificidad de este proceso en la población infantil, así como las recomendaciones específicas para una adecuada prevención y cuidado de los niños durante la Pandemia por el COVID-19. Este artículo tiene como objetivo es analizar la evidencia científica sobre las recomendaciones específicas para la atención pediátrica en casos de COVID-19 desde el ámbito familiar y comunitario. Se han seleccionado y analizado las principales recomendaciones y medidas preventivas en los entornos de atención primaria de salud y el domicilio desde un enfoque integrador dónde se incluyen los aspectos biopsicosociales del niño durante el confinamiento. La importancia de los cuidados de la infancia frente a la enfermedad, radican sobre todo en asegurar las correctas medidas de prevención del contagio por la condición de actuar como posibles portadores durante un período de incubación de hasta 21 días. La recomendación es que los niños participen activamente en las acciones preventivas habituales para la contención de la expansión de la enfermedad. A nivel domiciliario, el aislamiento supone un importante reto para las familias dónde se presentan manifestaciones de incertidumbre, miedo e indefensión ante los cambios y entre las recomendaciones se encuentran establecer rutinas orden mediante horarios de actividades y ocio unido a las medidas de higiene. Dada la rapidez con la que se ha producido la pandemia por COVID-19, existen pocas evidencias del impacto en niños en España por el momento. Es necesario desarrollar estudios específicos sobre prevención y tratamiento en la edad pediátrica para mejorar las recomendaciones disponibles. Abstract Based on the report on the situation of COVID-19 in Spain, dated April 3, 2020, the confirmed cases amount to 117,710, of which 343 are under 14 years of age (<1%). It is essential to know the specificity of this process in the child population, as well the specific recommendations for proper prevention and care of children during the COVID-19 Pandemic. Our objective is to analyze the scientific evidence on the specific recommendations for pediatric care in cases of COVID-19 from the family and community settings. The main recommendations and preventive measures in primary health care settings and at home have been selected and analyzed from an integrative approach that includes the biopsychosocial aspects of the child during confinement. The importance of caring for children in the face of the disease lies above all in ensuring the correct measures for the prevention of contagion due to the condition of acting as possible carriers during an incubation period of up to 21 days. The recommendation is that children actively participate in routine preventive actions to contain the spread of the disease. At the household level, isolation is an important challenge for families where there are manifestations of uncertainty, fear and helplessness in the face of changes and among the recommendations are establishing routines and order through schedules of activities and leisure together with hygiene measures. Given the rapidity with which the COVID-19 pandemic has occurred, there is little evidence at the moment. Research on prevention and treatment in the pediatric age needs to be developed to improve the available recommendations.


title: Characteristics and serological patterns of COVID‐19 convalescent plasma donors: optimal donors and timing of donation

text: BACKGROUND: The lack of effective treatments against the 2019 coronavirus disease (COVID‐19) has led to the exploratory use of convalescent plasma for treating COVID‐19. Case reports and case series have shown encouraging results. This study investigated SARS‐CoV‐2 antibodies and epidemiological characteristics in convalescent plasma donors, to identify criteria for donor selection. METHODS: Recovered COVID‐19 patients, aged 18‐55 years, who had experienced no symptoms for more than 2 weeks, were recruited. Donor characteristics such as disease presentations were collected and SARS‐CoV‐2 N‐specific IgM, IgG, and S‐RBD‐specific IgG levels were measured by enzyme‐linked immunosorbent assay (ELISA). RESULTS: Whereas levels of N‐specific IgM antibody declined after recovery, S‐RBD‐specific and N‐specific IgG antibodies increased after 4 weeks from the onset of symptoms, with no significant correlation to age, sex, or ABO blood type. Donors with the disease presentation of fever exceeding 38.5°C or lasting longer than 3 days exhibited higher levels of S‐RBD‐specific IgG antibodies at the time of donation. Of the 49 convalescent plasma donors, 90% had an S‐RBD‐specific IgG titer of ≥1:160 and 78% had a titer of ≥1:640 at the time of plasma donation. Of the 30 convalescent plasma donors, who had donated plasma later than 28 days after the onset of symptoms and had a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C, 100% had an S‐RBD‐specific IgG titer of ≥1:160 and 93% had a titer of ≥1:640. CONCLUSION: This study indicates that the S‐RBD‐specific IgG antibody reaches higher levels after 4 weeks from the onset of COVID‐19 symptoms. We recommend the following selection criteria for optimal donation of COVID‐19 convalescent plasma: 28 days after the onset of symptoms and with a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C. Selection based on these criteria can ensure a high likelihood of achieving sufficiently high S‐RBD‐specific IgG titers.


title: Gastritis, Enteritis, and Colitis in Horses

text: The gastrointestinal system of horses is affected by a large variety of inflammatory infectious and noninfectious conditions. The most prevalent form of gastritis is associated with ulceration of the pars esophagea. Although the diagnostic techniques for alimentary diseases of horses have improved significantly over the past few years, difficulties still exist in establishing the causes of a significant number of enteric diseases in this species. This problem is compounded by several agents of enteric disease also being found in the intestine of clinically normal horses, which questions the validity of the mere detection of these agents in the intestine.


title: Organization and Finance of China’s Health Sector: Historical Antecedents for Macroeconomic Structural Adjustment

text: China has exploded onto the world economy over the past few decades and is undergoing rapid transformation toward relatively more services. The health sector is an important part of this transition. This article provides a historical account of the development of health care in China since 1949. It also focuses on health insurance and macroeconomic structural adjustment to less saving and more consumption. In particular, the question of how health insurance impacts precautionary savings is considered. Multivariate analysis using data from 1990 to 2012 is employed. The household savings rate is the dependent variable in 3 models segmented for rural and urban populations. Independent variables include out-of-pocket health expenditures, health insurance payouts, housing expenditure, education expenditure, and consumption as a share of gross domestic product (GDP). Out-of-pocket health expenditures were positively correlated with household savings rates. But health insurance remains weak, and increased payouts by health insurers have not been associated with lower levels of household savings so far. Housing was positively correlated, whereas education had a negative association with savings rates. This latter finding was unexpected. Perhaps education is perceived as investment and a substitute for savings. China’s shift toward a more service-oriented economy includes growing dependence on the health sector. Better health insurance is an important part of this evolution. The organization and finance of health care is integrally linked with macroeconomic policy in an environment constrained by prevailing institutional convention. Problems of agency relationships, professional hegemony, and special interest politics feature prominently, as they do elsewhere. China also has a dual approach to medicine relying heavily on providers of traditional Chinese medicine. Both of these segments will take part in China’s evolution, adding another layer of complexity to policy.