title: Probiotics and COVID‐19: is there any link?

text: Understanding mechanisms of the novel SARS‐CoV2 infection and progression, can provide potential novel targets for prevention and/or treatment. This could be achieved via the inhibition of viral entry and/or replication, or by suppression the immunologic response that is provoked by the infection (known as the cytokine storm). Probiotics are defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”. There is scarcity of evidence about the relationship between COVID‐19 and gut microbiota. So, whether or not these supplements can prevent or ameliorate COVID‐19 associated symptoms is not fully understood. The aim of this paper is to provide an indirect evidence about the utility of probiotics in combating COVID‐19 or its associated symptoms, through the review of its antiviral and anti‐inflammatory properties in vitro, animal models, and human trials.


title: Melanoma defies ‘lockdown’: ongoing detection during Covid‐19 in central London

text: The COVID‐19 pandemic has presented significant challenges for Dermatology services, particularly the diagnosis and management of malignant melanoma (MM). Early detection and definitive surgical treatment are key to improving MM prognosis, and in England there is a suspected skin cancer referral pathway that facilitates specialist Dermatology assessment within two weeks. Here, we describe the impact of COVID‐19 on MM detection, based on data from the a Dermatology Department in central London.


title: Immunoblot analysis for IgE-reactive components of fetal calf serum in dogs that developed allergic reactions after non-rabies vaccination

text: Abstract We previously demonstrated the presence of IgE directed to fetal calf serum (FCS) in the sera from dogs that developed allergic reactions after vaccination. In this study, by an immunoblot analysis, we investigated the IgE-reactive components of FCS using sera from 16 dogs that exhibited allergic reactions after vaccination. The immunoblot analysis revealed that several FCS proteins of approximately 25-, 50-, 66-, 75-, 120-, and 175-kDa strongly reacted with IgE in the sera from dogs that showed post-vaccination allergic reactions. The 66-kDa band was detected in the sera from 14 of the 16 dog serum samples analyzed in the immunoblot analysis for FCS, and it was speculated to be albumin based on its molecular weight; however, serum IgE reactivity to bovine serum albumin could be detected in only four of the 14 dog samples. These findings demonstrated that a variety of FCS components including albumin could function as allergens in dogs that developed allergic reactions after vaccination.


title: In vitro inhibition of human influenza A virus replication by chloroquine

text: Chloroquine is a 9-aminoquinolone with well-known anti-malarial effects. It has biochemical properties that could be applied to inhibit viral replication. We report here that chloroquine is able to inhibit influenza A virus replication, in vitro, and the IC50s of chloroquine against influenza A viruses H1N1 and H3N2 are lower than the plasma concentrations reached during treatment of acute malaria. The potential of chloroquine to be added to the limited range of anti-influenza drugs should be explored further, particularly since antiviral drugs play a vital role in influenza pandemic preparedness.


title: Hosting of mass gathering sporting events during the 2013–2016 Ebola virus outbreak in West Africa: experience from three African countries

text: • Mass gatherings at sporting events attract millions of international and national host-country travellers, who may put themselves at risk of acquiring local endemic infectious diseases. • The 2013–2016 Ebola virus disease (EVD) outbreak in West Africa that resulted in over 28 637 cases and 11 315 deaths required that countries holding these events put in place public health programmes for enhanced surveillance and specific response plans for any suspected cases of EVD. • Three major sports events were held in Africa during the EVD outbreak, attended by athletes from numerous African countries including Liberia, Sierra Leone, and Guinea, the three countries most affected by EVD: the African Youth Games (Botswana), Africa Cup of Nations (Equatorial Guinea), and All-Africa Games (Republic of Congo). • A large range of infectious diseases other than EVD were considered with respect to the differential diagnosis of acute febrile illnesses and for the provision of laboratory diagnostics and treatment options. • The experience from these three mass gathering events during the Ebola epidemic illustrates that these events can be held safely provided that countries put measures in place for enhanced surveillance and response systems for communicable diseases.


title: Nucleocapsid proteins from other swine enteric coronaviruses differentially modulate PEDV replication

text: Abstract Porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV) and porcine deltacoronavirus (PDCoV) share tropism for swine intestinal epithelial cells. Whether mixing of viral components during co-infection alters pathogenic outcomes or viral replication is not known. In this study, we investigated how different coronavirus nucleocapsid (CoV N) proteins interact and affect PEDV replication. We found that PDCoV N and TGEV N can competitively interact with PEDV N. However, the presence of PDCoV or TGEV N led to very different outcomes on PEDV replication. While PDCoV N significantly suppresses PEDV replication, overexpression of TGEV N, like that of PEDV N, increases production of PEDV RNA and virions. Despite partial interchangeability in nucleocapsid oligomerization and viral RNA synthesis, endogenous PEDV N cannot be replaced in the production of infectious PEDV particles. Results from this study give insights into functional compatibilities and evolutionary relationship between CoV viral proteins during viral co-infection and co-evolution.


title: Post-traumatic Stress Disorder Among Health Care Providers Two Years Following the Israeli Attacks Against Gaza Strip in August 2014: Another Call for Policy Intervention

text: • We assessed the level of PTSD among 244 doctors & nurses after two years after the 2014 war against Gaza Strip. • Results showed a high level of PTSD among 89.3% of participants two years after the war. • Female health care providers and nurses participants have higher level of PTSD. • Highest level of PTSD subscales was Intrusion followed by Avoidance and Hyper-arousal. • Intervention programs to reduce stress and trauma among participants are recommended.


title: Early signs that COVID-19 is being contained in Australia

text: • The COVID-19 pandemic is overwhelming many national healthcare networks. • Case fatality from COVID-19 infection in Australia is between 0.4% to 3.0%. • Strict public health measures were enforced to control this outbreak in Australia. • Australia is on its way joining China and South Korea in ‘flattening the curve’.


Prevalence of respiratory virus infections using multiplex real-time PCR in Korean nationwide reference laboratory (2015 annual report)


title: What’s new in the renin-angiotensin system?: Angiotensin-converting enzyme-2: a molecular and cellular perspective

text: Angiotensin-converting enzyme-2 (ACE2) is the first human homologue of ACE to be described. ACE2 is a type I integral membrane protein which functions as a carboxypeptidase, cleaving a single hydrophobic/basic residue from the C-terminus of its substrates. ACE2 efficiently hydrolyses the potent vasoconstrictor angiotensin II to angiotensin (1–7). It is a consequence of this action that ACE2 participates in the renin-angiotensin system. However, ACE2 also hydrolyses dynorphin A (1–13), apelin-13 and des-Arg(9) bradykinin. The role of ACE2 in these peptide systems has yet to be revealed. A physiological role for ACE2 has been implicated in hypertension, cardiac function, heart function and diabetes, and as a receptor of the severe acute respiratory syndrome coronavirus. This paper reviews the biochemistry of ACE2 and discusses key findings such as the elucidation of crystal structures for ACE2 and testicular ACE and the development of ACE2 inhibitors that have now provided a basis for future research on this enzyme.


title: Systems modeling in support of evidence-based disaster planning for rural areas

text: Abstract The objective of this communication is to introduce a conceptual framework for a study that applies a rigorous systems approach to rural disaster preparedness and planning. System Dynamics is a well-established computer-based simulation modeling methodology for analyzing complex social systems that are difficult to change and predict. This approach has been applied for decades to a wide variety of issues of healthcare and other types of service capacity and delivery, and more recently, to some issues of disaster planning and mitigation. The study will use the System Dynamics approach to create computer simulation models as “what-if” tools for disaster preparedness planners. We have recently applied the approach to the issue of hospital surge capacity, and have reached some preliminary conclusions – for example, on the question of where in the hospital to place supplementary nursing staff during a severe infectious disease outbreak—some of which we had not expected. Other hospital disaster preparedness issues well suited to System Dynamics analysis include sustaining employee competence and reducing turnover, coordination of medical care and public health resources, and hospital coordination with the wider community to address mass casualties. The approach may also be applied to preparedness issues for agencies other than hospitals, and could help to improve the interactions among all agencies represented in a community's local emergency planning committee. The simulation models will support an evidence-based approach to rural disaster planning, helping to tie empirical data to decision-making. Disaster planners will be able to simulate a wide variety of scenarios, learn responses to each and develop principles or best practices that apply to a broad spectrum of disaster scenarios. These skills and insights would improve public health practice and be of particular use in the promotion of injury and disease prevention programs and practices.


title: Global patterns in coronavirus diversity

text: Since the emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrom Coronavirus (MERS-CoV) it has become increasingly clear that bats are important reservoirs of CoVs. Despite this, only 6% of all CoV sequences in GenBank are from bats. The remaining 94% largely consist of known pathogens of public health or agricultural significance, indicating that current research effort is heavily biased towards describing known diseases rather than the ‘pre-emergent’ diversity in bats. Our study addresses this critical gap, and focuses on resource poor countries where the risk of zoonotic emergence is believed to be highest. We surveyed the diversity of CoVs in multiple host taxa from twenty countries to explore the factors driving viral diversity at a global scale. We identified sequences representing 100 discrete phylogenetic clusters, ninety-one of which were found in bats, and used ecological and epidemiologic analyses to show that patterns of CoV diversity correlate with those of bat diversity. This cements bats as the major evolutionary reservoirs and ecological drivers of CoV diversity. Co-phylogenetic reconciliation analysis was also used to show that host switching has contributed to CoV evolution, and a preliminary analysis suggests that regional variation exists in the dynamics of this process. Overall our study represents a model for exploring global viral diversity and advances our fundamental understanding of CoV biodiversity and the potential risk factors associated with zoonotic emergence.


title: 46 How can biomarkers be used to differentiate between infection and non-infectious causes of inflammation?

text: Abstract: Diagnosis of sepsis is based on recognition of systemic inflammation and organ failure in the context of an inciting infection. Since none of the diagnostic criteria are specific to sepsis, it is easy to confound sepsis with noninfectious causes of systemic inflammation, including pancreatitis, cardiac ischemia, bowel perforation, vasculitis, and pulmonary embolism amongst others. Two widely used biomarkers, C-reactive protein and procalcitonin, have proven promising in sepsis diagnosis. Each has found varying success in the clinical context, with some centers relying heavily on these markers and others eschewing their use almost entirely. In this chapter, we present the evidence for their use in the diagnosis of sepsis and management of antibiotic therapy in the intensive care unit context.


title: Recommendations for management of diabetic foot ulcers during COVID‐19 outbreak

text: COVID‐19 pandemia began in Wuhan, China, in December 2019. A total of 1 878 489 people were infected and 119 044 people were lost because of the disease and its complications by 15 April. Severe morbidity and mortality complications are mostly seen in elderly and patients having comorbidities. Diabetic foot ulcers (DFUs) are one of severe complications of diabetes mellitus and it may require urgent surgical interventions. In this paper, we aimed to create a management algorithm to prevent the unexpected complications that may occur in the patients and health care workers during the evaluation of COVID‐19 in DFU patients who require urgent surgical intervention. We advise the use of thorax computerised tomography for preoperative screening in all DFU patients with severe signs of infection and especially those requiring urgent surgery for both the detection of the possible undiagnosed COVID‐19 in the patient for the need for close follow‐up and protection of the surgical and anaesthesiology team.


title: B-03 Métapneumovirus humain : un virus à ne pas négliger

text: Introduction et objectifs Le métapneumovirus humain (hMPV) – famille des Paramyxoviridae – a été identifié aux Pays-Bas en 2001. Ce virus est responsable de bronchiolites VRS-like (Virus Respiratoire Syncitial) chez l’enfant, avec le même caractère saisonnier. Il est aussi à l’origine d’infections respiratoires chez les personnes âgées. L’objectif est de mieux décrire l’épidémiologie des infections à hMPV et montrer l’intérêt de détecter ce virus en routine. Matériels et méthodes Au laboratoire de Virologie du CHU, hMPV est recherché en systématique par immuno-fluorescence indirecte sur les sécrétions nasales, les aspirations trachéales ou les liquides de lavage broncho-alvéolaire des patients. Parallèlement, six virus sont recherchés : Grippe A et B, VRS et Virus parainfluenzae (VP) 1, 2 et 3. Nous avons inclus les prélèvements de tout patient au cours de 2 saisons épidémiques : octobre 2007 à avril 2008 et octobre 2008 à janvier 2009. Les résultats positifs ont été recensés et colligés dans le tableau pour les 2 périodes étudiées : Prélèvements Oct. 2007/ Avr. 2008 Oct. 2008/ Jan. 2009 Total Positifs N % (positifs) N % (positifs) N Grippe A 27 14,8 38 20,0 65 Grippe B 17 9,3 2 1,0 19 VP 1,2,3 2 1,1 9 4,8 11 VRS 108 59,4 132 69,4 240 hMPV 28 15,4 9 4,8 37 Négatifs 583 / 334 / 917 Total 765 / 524 / 1289 Résultats Globalement, le VRS représente 64,5 % des prélèvements positifs, la grippe A 17,5 %. hMPV est, en terme de fréquence, le 3e virus isolé avec 10 % de prélèvements positifs. Sa prévalence sur la période 07/08 est de 3,6 % et sur 08/09 de 1,7 % (saison incomplète). L’âge médian observé est de 4 mois (extrêmes : 1-864) pour 07/08 et de 6 mois (extrêmes : 1-219) pour 08/09. Néanmoins, 71 % des prélèvements reviennent négatifs. En effet, les rhinovirus, coronavirus et adénovirus ne sont pas recherchés en routine. Conclusion Ainsi, 37 cas d’hMPV ont pu être recensés entraînant la mise en place de précautions complémentaires (gouttelettes et contact). Les nourrissons sont principalement touchés. Sans cette détection, les patients n’auraient probablement pas été isolés facilitant, de fait, la transmission nosocomiale du virus.


title: Ginkgolic acid inhibits fusion of enveloped viruses

text: Ginkgolic acids (GA) are alkylphenol constituents of the leaves and fruits of Ginkgo biloba. GA has shown pleiotropic effects in vitro, including: antitumor effects through inhibition of lipogenesis; decreased expression of invasion associated proteins through AMPK activation; and potential rescue of amyloid-β (Aβ) induced synaptic impairment. GA was also reported to have activity against Escherichia coli and Staphylococcus aureus. Several mechanisms for this activity have been suggested including: SUMOylation inhibition; blocking formation of the E1-SUMO intermediate; inhibition of fatty acid synthase; non-specific SIRT inhibition; and activation of protein phosphatase type-2C. Here we report that GA inhibits Herpes simplex virus type 1 (HSV-1) by inhibition of both fusion and viral protein synthesis. Additionally, we report that GA inhibits human cytomegalovirus (HCMV) genome replication and Zika virus (ZIKV) infection of normal human astrocytes (NHA). We show a broad spectrum of fusion inhibition by GA of all three classes of fusion proteins including HIV, Ebola virus (EBOV), influenza A virus (IAV) and Epstein Barr virus (EBV). In addition, we show inhibition of a non-enveloped adenovirus. Our experiments suggest that GA inhibits virion entry by blocking the initial fusion event. Data showing inhibition of HSV-1 and CMV replication, when GA is administered post-infection, suggest a possible secondary mechanism targeting protein and DNA synthesis. Thus, in light of the strong effect of GA on viral infection, even after the infection begins, it may potentially be used to treat acute infections (e.g. Coronavirus, EBOV, ZIKV, IAV and measles), and also topically for the successful treatment of active lesions (e.g. HSV-1, HSV-2 and varicella-zoster virus (VZV)).


Hydroxychloroquine, COVID‐19 and diabetes. Why it is a different story


title: A Generalized Discrete Dynamic Model for Human Epidemics

text: A discrete dynamic model for human epidemics was developed in present study. The model included major parameters as transmission strength and its decline parameters, mean incubation period, hospitalization time, non-hospitalization daily mortality, non-hospitalization daily recovery rate, and hospitalization proportion, etc. Sensitivity analysis of the model indicated the total cumulative cases significantly increased with initial transmission strength, hospitalization time. The total cumulative cases significantly decreased with transmission strength’s decline and hospitalization proportion, and linearly decreased with non-hospitalization daily mortality and non-hospitalization daily recovery rate. In a certain range, the total cumulative cases significantly increased with mean incubation period. Sensitivity analysis demonstrated that dynamic change of transmission strength is one of the most important and controllable factors. In addition, reducing the delay for hospitalization is much effective in weakening disease epidemic. Non-hospitalization recovery rate is of importance for enhancing immunity to recover from the disease.


Guideline for isolation precautions in hospitals


title: Quantitative proteomics identifies serum response factor binding protein 1 as a host factor for hepatitis C virus entry

text: Hepatitis C virus (HCV) enters human hepatocytes through a multistep mechanism involving, among other host proteins, the virus receptor CD81. How CD81 governs HCV entry is poorly characterized and CD81 protein interactions after virus binding remain elusive. We have developed a quantitative proteomics protocol to identify HCV-triggered CD81 interactions and found 26 dynamic binding partners. At least six of these proteins promote HCV infection as indicated by RNA interference. We further characterized serum response factor binding protein 1 (SRFBP1), which is recruited to CD81 during HCV uptake and supports HCV infection in hepatoma cells and primary human hepatocytes. SRFBP1 facilitates host cell penetration by all seven HCV genotypes, but not of vesicular stomatitis virus and human coronavirus. Thus, SRFBP1 is an HCV specific, pan-genotypic host entry factor. These results demonstrate the use of quantitative proteomics to elucidate pathogen entry and underscore the importance of host protein-protein interactions during HCV invasion.


“COVID‐Mask”: an atypical livedoid manifestation of COVID‐19 observed in a northern Italy hospital


title: The use of renin angiotensin system inhibitor on mortality in patients with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis

text: BACKGROUND: and Aims; To investigate the association between use of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin-receptor blocker (ARB) and outcomes of hypertensive COVID-19 patients, a systematic review and meta-analysis were performed. METHODS: We systematically searched PubMed, EuropePMC, ProQuest, and Cochrane Central Databases using the terms “(COVID-19 OR SARS-CoV-2) AND (angiotensin converting enzyme OR angiotensin receptor blocker)”. The primary and second outcomes were mortality (non-survivor) and severe COVID-19, respectively. RESULTS: Totally, 7410 patients were included from 15 studies. Pooled analysis showed that the use of ACEI/ARB was not associated with mortality (OR 0.73 [0.38, 1.40], p = 0.34; I(2): 81%) and severity (OR 1.03 [0.73, 1.45], p = 0.87; I(2): 65%). Pooled adjusted OR showed no risk/benefit associated with ACEI/ARB use in terms of mortality (OR 0.83 [0.54, 1.27], p = 0.38; I(2): 0%). Subgroup analysis showed that the use of ARB was associated with reduced mortality (OR 0.51 [0.29, 0.90], p = 0.02; I(2): 22%) but not ACEI subgroup (OR 0.68 [0.39, 1.17], p = 0.16; I(2): 0%). Meta-regression showed that the association between ACEI/ARB use and mortality in patients with COVID-19 do not varies by gender (p = 0.104). GRADE showed a very low certainty of evidence for effect of ACEI/ARB on mortality and severity. The certainty of evidence was very low for both ACEI and ARB subgroups. CONCLUSION: Administration of a renin angiotensin system (RAS) inhibitor, was not associated with increased mortality or severity of COVID-19 in patients with hypertension. Specifically, ARB and not ACEI use, was associated with lower mortality.


title: COVID-19: an FY1 on the frontline

text: The global spread of COVID-19 has put increased pressure on the NHS. The Government has put in a number of strategies to cope with this pandemic, which includes increasing funding for the NHS. However, increased funding itself will not ease the workload. With a number of our staff isolating from work due to COVID-19, we as the workforce have to step out of comfort zones and work in unfamiliar specialties. These are unprecedented times and are placing strains on our health service. Nonetheless, we as healthcare professionals have taken oaths that we are honouring and will continue to do so, till this virus is put to rest.


title: Updates in the Relationship Between Human Rhinovirus and Asthma

text: Human rhinovirus (HRV) is a nonenveloped, single stranded RNA virus belonging to the family Picornaviridae. HRV infections can cause both upper and lower respiratory illnesses in children and adults. Lower respiratory illnesses are more likely to occur in specific high risk groups, including infants, and children and adults with asthma. The relationships between rates of infection and the risk of clinical illness and exacerbation are not completely understood. Recent studies employing polymerase chain reaction and other molecular techniques indicate that there are new branches on the HRV family tree, and one characteristic of recently detected viruses is that they cannot be detected by standard tissue culture. Here we review the current literature and discuss new advances in understanding the link between HRV and asthma.


title: Restricting Daily Chest Radiography in the Intensive Care Unit: Implementing Evidence-Based Medicine to Decrease Utilization

text: PURPOSE: In this study, the authors applied evidence-based medicine to decrease the utilization of routine chest radiography in adult intensive care units and used time-driven activity-based costing to demonstrate cost savings. METHODS: A multidisciplinary team was formed with representatives from radiology, surgery, internal medicine, and nursing. The process of performing a portable chest radiographic examination was mapped, and time trials were performed by the radiology technologists and radiology resident. This information was used to determine the cost of performing portable intensive care unit (ICU) chest radiographic studies. The clinical team changed resident education, ordering protocols, and workflows to discontinue the use of routine daily chest radiography, emphasizing that it should be ordered only in specific situations, such as on admission or after central line placement. In addition, as a balancing measure, the team tracked complications such as unplanned extubations and ventilator days. RESULTS: Changing ordering practices in the adult ICUs to align with established evidence-based guidelines resulted in a 37% decrease in the utilization of portable chest radiography between June and December, without a concomitant increase in unplanned extubations or ventilator days. In addition, a proportionate cost savings was realized, as demonstrated by the application of time-driven activity-based costing. CONCLUSIONS: This performance improvement initiative successfully increased the value of care delivered to ICU patients by aligning institutional clinical practice with evidence-based medicine. This resulted in decreased utilization and the cost associated with delivering care without a concomitant increase in complications.


title: Clinical characteristics of older patients infected with COVID-19: A descriptive study

text: Abstract Objectives Since the outbreak of 2019 novel coronavirus (COVID-19), which has spread in the world rapidly. Population have a susceptibility to COVID-19, older people were more susceptible to have a variety diseases than younger, including COVID-19 infection with no doubt. This study focused on older patients with COVID-19 infection and analyzed the epidemiological and clinical characteristics of them. Methods We collected information on confirmed older patient transferred by Beijing Emergency Medical Service (EMS) to the designated hospitals from Jan 20 to Feb 29, 2020. The information including demographic, epidemiological, clinical, classification of severity and outcomes. All cases were categorized into three groups and compared the difference between aged 50–64 years, 65–79 years and older than 80 years. Results 56.7 % of elderly confirmed patients were male, fever (78.3 %), cough (56.7 %), dyspnea (30.0 %), and fatigue (23.3 %) were common symptoms of COVID-19 infection. Classification of severity has statistically significant differences between the three groups, compared with middle-aged patients and aged 65–79 years group, older than 80 years group had significant statistical differences in contacted to symptomatic case in 14 days. As of Feb 29, 38.3 % patients had discharged and 53.3 % patients remained in hospital in our study, the fatality of COVID-19 infection in elderly was 8.3 %. Conclusions The COVID-19 infection is generally susceptible with a relatively high fatality rate in older patients, we should pay more attention to the elderly patients with COVID-19 infection.


Communication with Patients and Families Regarding Healthcare-Associated Exposure to Coronavirus 2019: A Checklist to Facilitate Disclosure


title: Biophotonic telemedicine for disease diagnosis and monitoring during pandemics: overcoming COVID-19 and shaping the future of healthcare

text: • Infection prevention and control (IPC) strategies against coronavirus disease 2019 (COVID-19) include social distancing and isolating infected patients. • Telemedicine has become a common clinical practice for early disease diagnostics and monitoring. • Optical and biophotonic technologies have potential to improve treatment outcome and increase survival rates by advancing telemedicine.


title: Global analysis of an epidemic model with nonmonotone incidence rate

text: Abstract In this paper we study an epidemic model with nonmonotonic incidence rate, which describes the psychological effect of certain serious diseases on the community when the number of infectives is getting larger. By carrying out a global analysis of the model and studying the stability of the disease-free equilibrium and the endemic equilibrium, we show that either the number of infective individuals tends to zero as time evolves or the disease persists.


title: Does world heritage list really induce more tourists? Evidence from Macau

text: It is commonly believed that being listed on the World Heritage List (WHL) results in attracting more tourists. However, this assumption has not been generally subject to rigorous econometric approach in the existing literature. To fill this gap, we assess the impact of the accreditation World Heritage status on the “Historic Centre of Macau” in 2005 on visitor numbers to the territory to identify the real effect of WHL on fostering tourism. In doing so, because of the policy restrictions on the mainland Chinese tourists, such tourists have been excluded from the analysis. The empirical results indicate that there is no significant effect of WHL on promoting tourism other than possibly a short-run tourism-enhancing impact. Notably, this effect is particularly relevant to Asian tourists. This paper discusses these results in the wider context of econometric analyses of tourism.


title: Cyclophilin 40 alters UVA-induced apoptosis and mitochondrial ROS generation in keratinocytes

text: The CyP40 protein encoded by PPID gene is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. The CyP40 protein has been shown to possess PPIase activity and, similar to other family members, can bind to the immunosuppressant drug cyclosporin A (CsA). In this study, we created keratinocyte cell lines with CyP40 being stably knocked down using viral particles containing shRNA for CyP40 which knocked down the expression level of CyP40 transcripts by 90 to 99%. The proliferation rates of the cell lines with silenced CyP40 were decreased compared to the control cells. After UVA irradiation, the rate of apoptosis was found to be significantly lower in CyP40 silenced cell lines than it was in control cells. Moreover, mitochondrial membrane potential (MMP) was found to be less dissipated and mitochondrial permeability transition pore (MPTP) less active in cells with knocked down CyP40 than in control cells after UVA irradiation. Also, less mitochondrial superoxide was detected in the cells with silenced CyP40 compared to control cells after UVA exposure. Moreover, silencing of CyP40 partially modulates expression of key genes involved in mitochondrial pore formation including CyPD, ANTs and VDAC family members. The ability of CyP40 to regulate UV induced apoptosis implicates this protein as a potential target for therapy in cancer cells.


The COVID-19 pandemic: Technology use to support the wellbeing of children


title: Procalcitonin in severe acute respiratory syndrome (SARS)

text: Abstract Objective and methods. The role of procalcitonin (PCT) in severe acute respiratory syndrome (SARS) has not been highlighted so far. We described retrospectively eight cases of sepsis from pneumonia of various microbiological aetiologies including two due to SARS, compared their PCT concentrations and provided further descriptors of SARS as a viral pneumonia. Results. Like any viral pneumonia, patients with SARS had low PCT levels in contrast to bacterial or fungal pneumonia. Conclusions. In the setting of pneumonia with a finding of low PCT, testing for SARS should be considered, especially if there is a positive travel or contact history. During a SARS epidemic, we also strongly advocate isolating all suspected community acquired pneumonia with a low PCT level.


title: Viral infections in allergy and immunology: How allergic inflammation influences viral infections and illness

text: Viral respiratory tract infections are associated with asthma inception in early life and asthma exacerbations in older children and adults. Although how viruses influence asthma inception is poorly understood, much research has focused on the host response to respiratory viruses and how viruses can promote; or how the host response is affected by subsequent allergen sensitization and exposure. This review focuses on the innate interferon-mediated host response to respiratory viruses and discusses and summarizes the available evidence that this response is impaired or suboptimal. In addition, the ability of respiratory viruses to act in a synergistic or additive manner with TH2 pathways will be discussed. In this review we argue that these 2 outcomes are likely linked and discuss the available evidence that shows reciprocal negative regulation between innate interferons and TH2 mediators. With the renewed interest in anti-TH2 biologics, we propose a rationale for why they are particularly successful in controlling asthma exacerbations and suggest ways in which future clinical studies could be used to find direct evidence for this hypothesis.


title: Dissection and identification of regions required to form pseudoparticles by the interaction between the nucleocapsid (N) and membrane (M) proteins of SARS coronavirus

text: Abstract When expressed in mammalian cells, the nucleocapsid (N) and membrane (M) proteins of the severe acute respiratory syndrome coronavirus (SARS-CoV) are sufficient to form pseudoparticles. To identify region(s) of the N molecule required for pseudoparticle formation, we performed biochemical analysis of the interaction of N mutants and M in HEK293 cells. Using a peptide library derived from N, we found that amino acids 101–115 constituted a novel binding site for M. We examined the ability of N mutants to interact with M and form pseudoparticles, and our observations indicated that M bound to NΔ(101–115), N1–150, N151–300, and N301–422, but not to N1–150Δ(101–115). However, pseudoparticles were formed when NΔ(101–115) or N301–422, but not N1–150 or N151–300, were expressed with M in HEK293 cells. These results indicated that the minimum portion of N required for the interaction with M and pseudoparticle formation consists of amino acids 301–422.


title: Feline Coronavirus in Multicat Environments

text: Feline infectious peritonitis (FIP), a fatal disease in cats worldwide, is caused by FCoV infection, which commonly occurs in multicat environments. The enteric FCoV, referred to as feline enteric virus (FECV), is considered a mostly benign biotype infecting the gut, whereas the FIP virus biotype is considered the highly pathogenic etiologic agent for FIP. Current laboratory tests are unable to distinguish between virus biotypes of FCoV. FECV is highly contagious and easily spreads in multicat environments; therefore, the challenges to animal shelters are tremendous. This review summarizes interdisciplinary current knowledge in regard to virology, immunology, pathology, diagnostics, and treatment options in the context of multicat environments.


title: Human Coronavirus NL63, France

text: The human coronavirus NL63 (HCoV-NL63) was first identified in the Netherlands, and its circulation in France has not been investigated. We studied HCoV-NL63 infection in hospitalized children diagnosed with respiratory tract infections. From November 2002 to April 2003, we evaluated 300 respiratory specimens for HCoV-NL63. Of the 300 samples, 28 (9.3%) were positive for HCoV-NL63. The highest prevalence was found in February (18%). The main symptoms were fever (61%), rhinitis (39%), bronchiolitis (39%), digestive problems (33%), otitis (28%), pharyngitis (22%), and conjunctivitis (17%). A fragment of the spike protein gene was sequenced to determine the variety of circulating HCoV-NL63. Phylogenetic analysis indicated that strains with different genetic markers cocirculate in France.


title: Humoral and Cellular Immune Responses in Turkey Poults Infected with Turkey Coronavirus

text: Abstract The objective of the present study was to elucidate the kinetics of humoral and cellular immune responses of turkey poults infected with turkey coronavirus (TCV). Turkey poults were orally inoculated with TCV at 10 d of age, and the immune responses were analyzed at 1, 3, 7, 14, 21, 28, 42, and 63 d postinfection (PI) in three different experiments. Total Ig to TCV was initially detected at 7 and 14 d PI in Experiments 1 and 3. In addition, Ig gradually increased from 7 to 21 d PI and remained at 80 immunofluroescent antibody assay (IFA) titers or more thereafter. Lymphocyte proliferation responses of spleen cells to concanavalin A were higher in TCV-infected turkeys than in noninfected control turkeys with significant differences (P < 0.05) being noted at 14 and 63 d PI in Experiment 2 and at 3 and 28 d PI in Experiment 3. Strong IFA staining response to TCV antigen was observed in intestines of turkeys at 1, 3, and 7 d PI, and the response declined from 14 to 28 d PI in Experiment 3. In Experiment 3, the IgG isotype antibody response to TCV was markedly increased after 21 d PI and remained high until 63 d PI. The IgM isotype antibody response to TCV was 1.40 and 0.91 at 7 and 14 d PI, respectively. The IgA isotype antibody response to TCV was very low as detected at 7 (0.13), 14 (0.20), and 21 (0.17) d PI. Turkeys infected with TCV had significantly higher (P < 0.05) antibody response to sheep erythrocytes than noninfected controls at 7 d PI. Virus-specific lymphocyte proliferation response of spleen cells was significantly stimulated (P < 0.05) at 63 d PI in Experiment 3. The proportion of the CD4+ subpopulation of T lymphocytes was significantly increased (P < 0.05) at 1, 7, and 21 d PI in Experiment 3. The results indicate that humoral and cellular immunities to TCV are elicited in turkeys following infection with TCV.


title: Clinical, virological and epidemiological characteristics of rhinovirus infections in early childhood: A comparison between non-hospitalised and hospitalised children

text: Abstract Background Several studies have been published regarding the epidemiology and clinical significance of the different rhinovirus (RV) species (-A, -B and -C). However, data on RV types and the associations with clinical outcome in young children are limited. Here, we investigated the clinical, virological and epidemiological characteristics of RV infections in young children with mild or asymptomatic infection (non-hospitalised children) and in symptomatic young children admitted to the hospital. Objectives The aim of this study was to evaluate associations between different characteristics of RV infections and clinical outcome in young children. Study design RV-infected children were retrospectively selected from a Dutch birth cohort (EUROPA-study) and from hospitalised children admitted to the hospital because of respiratory symptoms. In total 120 RV-typed samples could be selected from 65 non-hospitalised and 49 hospitalised children between November 2009 and December 2012. Results RV-A was the predominant species in both study populations, followed closely by RV-C. RV-B was observed only sporadically. The distribution of the RV species was comparable in non-hospitalised and hospitalised children. In children with respiratory distress who required ICU-admission the distribution of RV species did not differ significantly from the non-hospitalised children. No predominant RV type was present in non-hospitalised nor hospitalised children. However, hospitalised children were younger, had more often an underlying illness, a higher RV load and more frequently a bacterial co-infection. Conclusions Clinical outcome of RV infected young children was not related to RV species or types, but may more likely be influenced by multiple (host-specific) factors.


title: Evolution of infectious bronchitis virus in Taiwan: Positively selected sites in the nucleocapsid protein and their effects on RNA-binding activity

text: Abstract RNA recombination has been shown to underlie the sporadic emergence of new variants of coronavirus, including the infectious bronchitis virus (IBV), a highly contagious avian pathogen. We have demonstrated that RNA recombination can give rise to a new viral population, supported by the finding that most isolated Taiwanese (TW) IBVs, similar to Chinese (CH) IBVs, exhibit a genetic rearrangement with the American (US) IBV at the 5’ end of the nucleocapsid (N) gene. Here, we further show that positive selection has occurred at two sites within the putative crossover region of the N-terminal domain (NTD) of the TW IBV N protein. Based on the crystal structure of the NTD, the stereographic positions of both predicted selected sites do not fall close to the RNA-binding groove. Surprisingly, converting either of the two residues to the amino acid present in most CH IBVs resulted in significantly reduced affinity of the N protein for the synthetic RNA repeats of the viral transcriptional regulatory sequence. These results suggest that modulating the amino acid residue at either selected site may alter the conformation of the N protein and affect the viral RNA–N interaction. This study illustrates that the N protein of the current TW IBV variant has been shaped by both RNA recombination and positive selection and that the latter may promote viral survival and fitness, potentially by increasing the RNA-binding capacity of the N protein.


Reply to Karagoz et al


title: Hazard to man and the environment posed by the use of urban waste compost: a review

text: Abstract This review presents the current state of knowledge on the relationship between the environment and the use of municipal waste compost in terms of health risk assessment. The hazards stem from chemical and microbiological agents whose nature and magnitude depend heavily on the degree of sorting and on the composting methods. Three main routes of exposure can be determined and are quantified in the literature: (i) The ingestion of soil/compost mixtures by children, mostly in cases of pica, can be a threat because of the amount of lead, chromium, cadmium, PCDD F and fecal streptococci that can be absorbed. (ii) Though concern about contamination through the food chain is weak when compost is used in agriculture, some authors anticipate accumulation of pollutants after several years of disposal, which might lead to future hazards. (iii) Exposure is also associated with atmospheric dispersion of compost organic dust that convey microorganisms and toxicants. Data on hazard posed by organic dust from municipal composts to the farmer or the private user is scarce. To date, microorganisms are only measured at composting plants, thus raising the issue of extrapolation to environmental situations. Lung damage and allergies may occur because of organic dust, Gram negative bacteria, actinomycetes and fungi. Further research is needed on the risk related to inhalation of chemical compounds.


title: Severe Acute Respiratory Syndrome Historical, Epidemiologic, and Clinical Features

text: Severe acute respiratory syndrome coronavirus (SARS-CoV), emerged from China and rapidly spread worldwide. Over 8098 people fell ill and 774 died before the epidemic ended in July 2003. Bats are likely an important reservoir for SARS-CoV. SARS-like CoVs have been detected in horseshoe bats and civet cats. The main mode of transmission of SARS-CoV is through inhalation of respiratory droplets. Faeco-oral transmission has been recorded. Strict infection control procedures with respiratory and contact precautions are essential. Fever and respiratory symptoms predominate, and diarrhea is common. Treatment involves supportive care. There are no specific antiviral treatments or vaccines available.


Corrigendum to: “Letter: Neurosurgery and Coronavirus (COVID-19) Epidemic: Doing our Part” by Pesce et al. Neurosurgery, nyaa115, https://doi.org/10.1093/neuros/nyaa115


title: The impact of COVID‐19 on food retail and food service in Canada: Preliminary assessment

text: COVID‐19 has imposed a series of unique challenges on the food retail and food service sectors in Canada. Almost overnight, the roughly 30% of the food dollar that Canadians have been spending on food away from home has shifted to retail.


title: The role of microRNAs in respiratory viral infection: friend or foe?

text: MicroRNAs (miRNAs) have emerged as a class of regulatory RNAs in host–pathogen interactions. Aberrant miRNA expression seems to play a central role in the pathology of several respiratory viruses, promoting development and progression of infection. miRNAs may thus serve as therapeutic and prognostic factors for respiratory viral infectious disease caused by a variety of agents. We present a comprehensive review of recent findings related to the role of miRNAs in different respiratory viral infections and discuss possible therapeutic opportunities aiming to attenuate the burden of viral infections. Our review supports the emerging concept that cellular and viral‐encoded miRNAs might be broadly implicated in human respiratory viral infections, with either positive or negative effects on virus life cycle. Copyright © 2016 John Wiley & Sons, Ltd.


COVID 2019 – ROLE OF FACULTY MEMBERS TO KEEP MENTAL ACTIVENESS OF STUDENTS


title: 2009 H1N1 Influenza: A Twenty-First Century Pandemic With Roots in the Early Twentieth Century

text: Abstract A swine-origin H1N1 triple-reassortant influenza A virus found to be a distant relative of the 1918 “Spanish flu” virus emerged in April 2009 to give rise to the first influenza pandemic of the 21st century. Although disease was generally mild and similar to seasonal influenza, severe manifestations including respiratory failure were noted in some, particularly those with underlying conditions such as asthma, pregnancy and immunosuppression. Children and younger adults accounted for most cases, hospitalizations and deaths. A reverse transcriptase-polymerase chain reaction assay was superior to antigen-based rapid tests for diagnosis. All 2009 H1N1 pandemic influenza strains were susceptible to 1 or more neuraminidase inhibitors. Monovalent, unadjuvanted 2009 H1N1 vaccines were licensed in the United States in September 2009 and initially targeted to younger individuals, pregnant women, caretakers of infants and healthcare providers. The 2009 H1N1 pandemic highlights the need for modernization of influenza vaccines, improved diagnostics and more rigorous evaluation of mitigation strategies.


title: Antimicrobial Decision Making for Enteric Diseases of Cattle

text: Diarrhea in neonatal and adult cattle is common and can be caused by several etiologic agents. As diagnostic testing is not always readily available, practitioners must often decide on a course of treatment based on knowledge of the likely pathogen and their own clinical experience. Antimicrobials have long been used to treat diarrhea in adults and neonates; however, there is increased pressure to prevent unnecessary use of antibiotics in food animal species. This article reviews existing data on the use of antibiotics given to cattle with enteric diseases to decide when they are necessary and which antimicrobials should be used.


title: The emerging role of ACE2 in physiology and disease

text: The renin–angiotensin–aldosterone system (RAAS) is a key regulator of systemic blood pressure and renal function and a key player in renal and cardiovascular disease. However, its (patho)physiological roles and its architecture are more complex than initially anticipated. Novel RAAS components that may add to our understanding have been discovered in recent years. In particular, the human homologue of ACE (ACE2) has added a higher level of complexity to the RAAS. In a short period of time, ACE2 has been cloned, purified, knocked‐out, knocked‐in; inhibitors have been developed; its 3D structure determined; and new functions have been identified. ACE2 is now implicated in cardiovascular and renal (patho)physiology, diabetes, pregnancy, lung disease and, remarkably, ACE2 serves as a receptor for SARS and NL63 coronaviruses. This review covers available information on the genetic, structural and functional properties of ACE2. Its role in a variety of (patho)physiological conditions and therapeutic options of modulation are discussed. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


title: Impact and seasonality of human rhinovirus infection in hospitalized patients for two consecutive years

text: Abstract Objectives To report epidemiological features, clinical characteristics, and outcomes of human rhinovirus (HRV) infections in comparison with other community acquired respiratory virus (CRV) infections in patients hospitalized for two consecutive years. Methods This was a cross-sectional study. Clinical, epidemiological, and laboratory data of patients hospitalized with acute respiratory syndrome in a tertiary care hospital from 2012 to 2013 were reviewed. Results HRV was the most common CRV observed (36%, 162/444) and was present in the majority of viral co-detections (69%, 88/128), mainly in association with human enterovirus (45%). Most HRV-infected patients were younger than 2 years (57%). Overall, patients infected with HRV had a lower frequency of severe acute respiratory infection than those infected with other CRVs (60% and 84%, respectively, p =0.006), but had more comorbidities (40% and 27%, respectively; p =0.043). However, in the adjusted analysis this association was not significant. The mortality rate within the HRV group was 3%. Detection of HRV was more prevalent during autumn and winter, with a moderately negative correlation between viral infection frequency and temperature (r =−0.636, p <0.001) but no correlation with rainfall (r =−0.036, p =0.866). Conclusion HRV is usually detected in hospitalized children with respiratory infections and is often present in viral co-detections. Comorbidities are closely associated with HRV infections. These infections show seasonal variation, with predominance during colder seasons.


title: Medical implication in the Bible and its relevance to modern medicine

text: Abstract The Holy Bible, as the root of Western civilization, has imposed great influence in the fields far beyond religion. In this thesis, the author intended to reveal the medical implication in the Holy Bible and its relevance to the modern medical science by exploring the biblical medical information and comparing it with the current medical theory and practice. The conclusion of the exploration is surprising yet inspiring: the Holy Bible, as an ancient religious book, contains rich medical information around themes such as sexual relations, dietary guidelines, hygiene, etc., which is not at odds, but in harmony with the modern medicine.


title: Godzilla in the corridor: The Ontario SARS crisis in historical perspective

text: Summary Ontario nurses were employed as the front-line workers when SARS descended upon Toronto in March 2003. Once the crisis had subsided, many nurses remarked that SARS had forever altered their chosen profession; employment, which they once viewed as relatively safe, had been transformed into potentially life-threatening. This discussion provides descriptions of these expressions through nurses who experienced the crisis and chose to go on the public record. Secondly, it compares the subjective perceptions of those nurses to those held by nurses who worked through historical epidemics of unknown or contested epidemiology. The historical literature on nursing in yellow fever, cholera and influenza epidemics has been employed to offer insight. The goal is to determine whether the SARS outbreak was a unique experience for nurses or whether similar experiences were shared by nurses in the past? In summary, the reactions of nurses when confronted with the possibility of contracting a deadly disease remain altogether human, not dissimilar in past or present. Nurses’ responses to SARS can be usefully studied within a larger historical vision of crisis nursing, and information or impressions from earlier crises are potentially of interest to the nursing profession.


title: Mucosal Immunization Induces a Higher Level of Lasting Neutralizing Antibody Response in Mice by a Replication-Competent Smallpox Vaccine: Vaccinia Tiantan Strain

text: The possible bioterrorism threat using the variola virus, the causative agent of smallpox, has promoted us to further investigate the immunogenicity profiles of existing vaccines. Here, we study for the first time the immunogenicity profile of a replication-competent smallpox vaccine (vaccinia Tiantan, VTT strain) for inducing neutralizing antibodies (Nabs) through mucosal vaccination, which is noninvasive and has a critical implication for massive vaccination programs. Four different routes of vaccination were tested in parallel including intramuscular (i.m.), intranasal (i.n.), oral (i.o.), and subcutaneous (s.c.) inoculations in mice. We found that one time vaccination with an optimal dose of VTT was able to induce anti-VTT Nabs via each of the four routes. Higher levels of antiviral Nabs, however, were induced via the i.n. and i.o. inoculations when compared with the i.m. and s.c. routes. Moreover, the i.n. and i.o. vaccinations also induced higher sustained levels of Nabs overtime, which conferred better protections against homologous or alternating mucosal routes of viral challenges six months post vaccination. The VTT-induced immunity via all four routes, however, was partially effective against the intramuscular viral challenge. Our data have implications for understanding the potential application of mucosal smallpox vaccination and for developing VTT-based vaccines to overcome preexisting antivaccinia immunity.


title: COVID-19 When Leadership Calls

text: Abstract From the minute our organization received our first presumptive positive COVID-19 patient, and throughout our journey, many challenges and obstacles have been presented for health care leadership. Priorities are rapidly shifting, anxiety and fear are present, and knowing where to focus support is a challenge. As I sit and reflect on lessons learned throughout this experience, I can't help but continue to focus on frontline leadership and their important role in this entire process.


title: SARS-CoV-2 Spike protein variant D614G increases infectivity and retains sensitivity to antibodies that target the receptor binding domain

text: Virus genome sequence variants that appear over the course of an outbreak can be exploited to map the trajectory of the virus from one susceptible host to another. While such variants are usually of no functional significance, in some cases they may allow the virus to transmit faster, change disease severity, or confer resistance to antiviral therapies. Since the discovery of SARS-CoV-2 as the cause of COVID-19, the virus has spread around the globe, and thousands of SARS-CoV-2 genomes have been sequenced. The rate of sequence variation among SARS-CoV-2 isolates is modest for an RNA virus but the enormous number of human-to-human transmission events has provided abundant opportunity for selection of sequence variants. Among these, the SARS-CoV-2 Spike protein variant, D614G, was not present in the presumptive common ancestor of this zoonotic virus but was first detected in late January in Germany and China. The D614G variant steadily increased in frequency and now constitutes >97% of isolates world-wide, raising the question whether D614G confers a replication advantage to SARS-CoV-2. Structural models predict that D614G would disrupt contacts between the S1 and S2 domains of the Spike protein and cause significant shifts in conformation. Using single-cycle vectors we showed that D614G is three to nine-fold more infectious than the ancestral form on human lung and colon cell lines, as well as on other human cell lines rendered permissive by ectopic expression of human ACE2 and TMPRSS2, or by ACE2 orthologues from pangolin, pig, dog, or cat. Nonetheless, monoclonal antibodies targeting the receptor binding domain of the SARS-CoV-2 Spike protein retain full neutralization potency. These results suggest that D614G was selected for increased human-to-human transmission, that it contributed to the rapidity of SARS-CoV-2 spread around the world, and that it does not confer resistance to antiviral therapies targeting the receptor binding domain.


title: Novel Dynamic Structures of 2019-nCoV with Nonlocal Operator via Powerful Computational Technique

text: In this study, we investigate the infection system of the novel coronavirus (2019-nCoV) with a nonlocal operator defined in the Caputo sense. With the help of the fractional natural decomposition method (FNDM), which is based on the Adomian decomposition and natural transform methods, numerical results were obtained to better understand the dynamical structures of the physical behavior of 2019-nCoV. Such behaviors observe the general properties of the mathematical model of 2019-nCoV. This mathematical model is composed of data reported from the city of Wuhan, China.


title: Evaluation of the performance of DiaSorin molecular Pneumocystis jirovecii-CMV multiplex real-time PCR assay from bronchoalveolar lavage samples

text: Abstract The aim of this study was to evaluate the performance of the DiaSorin Molecular PJ-CMV multiplex real-time PCR (PJ-CMV PCR) assay (DiaSorin Molecular LLC, USA) in bronchoalveolar lavage (BAL) samples compared to direct immunofluorescence assay (IFA) for the detection of Pneumocystis jirovecii and assess CMV and P. jirovecii co-infection rate in immunosuppressed patients with suspected pneumonia. A total of 125 BAL samples from immunosuppressed patients submitted for PJP-IFA were tested. Surplus samples were saved and further tested by using the PJ-CMV PCR assay. Among the 125 samples, P. jirovecii was detected in 31.2% (39/125) and in 40% (50/125) of the specimens using IFA and PJ-CMV PCR respectively. Eleven of the PJ-CMV PCR positive samples were negative by direct IFA for P. jirovecii. All samples positive by direct IFA were also positive by PJ-CMV PCR. Using the direct IFA as a gold standard, the PJ-CMV PCR sensitivity, specificity, positive predictive value and negative predictive value for detection of P. jirovecii were 100%, 87.2%, 78% and 100%, respectively. However, after reviewing the clinical diagnosis, the specificity and PPV increased to 100%. Of the 50 P. jirovecii samples positive by PJ-CMV PCR, 18 (36%) were also positive for CMV by the PJ-CMV PCR. The co-infection rate was found to be 37.5% (6/16) and 35.2% (12/34) in HIV infected and non-HIV infected patients. This study indicated that the DiaSorin Molecular PJ-CMV multiplex real-time PCR assay has higher sensitivity than direct IFA for detection of P. jirovecii and provides rapid detection of PJ and CMV infection in BAL samples.


title: Direct RNA sequencing and early evolution of SARS-CoV-2

text: Fundamental aspects of SARS-CoV-2 biology remain to be described, having the potential to provide insight to the response effort for this high-priority pathogen. Here we describe the first native RNA sequence of SARS-CoV-2, detailing the coronaviral transcriptome and epitranscriptome, and share these data publicly. A data-driven inference of viral genetic features and evolutionary rate is also made. The rapid sharing of sequence information throughout the SARS-CoV-2 pandemic represents an inflection point for public health and genomic epidemiology, providing early insights into the biology and evolution of this emerging pathogen.


title: Plausible mechanisms of Niclosamide as an antiviral agent against COVID-19

text: Abstract Corona virus disease 2019 (COVID-19) pandemic caused 18 440 deaths world wide as of 25 March 2020 and posing a serious threat to public health. There is a need, therefore, for effective therapeutic strategies to cure this disease. However, high attrition rates, substantial costs and slow pace are the major limitations of novel drug discovery. Drug repurposing, by employing ‘old’ drugs to treat ‘new’ diseases is an attractive approach in drug discovery. Niclosamide (NIC) is an approved anti-helminthic drug with diverse antiviral mechanisms. In this work we hypothesize, the potential antiviral mechanisms of NIC against COVID-19.


title: Community Under Stress: Trust, Reciprocity, and Community Collective Efficacy During SARS Outbreak

text: The study of epidemics is almost non-existent in sociological literature, even though such outbreaks can have detrimental effects on communities. The occurrence of SARS (Severe Acute Respiratory Syndrome) in 2003 provides a rare opportunity to understand the social functioning of a community during the outbreak of an epidemic. To evaluate the extensive social impact of such an outbreak, we focus on the effects of perceived collective efficacy. Specifically, we focus on how the collective efficacy of a community, measured by trust and reciprocal relations, is related to collective action in places where SARS occurred and those where SARS did not occur. The study is based on a unique data set, the 2003 Taiwan Social Image Survey, collected during the outbreak of SARS in Taiwan. Our findings show that community collective efficacy, measured by trust and reciprocity, is not associated with community collective action when an outbreak of an epidemic occurs.


title: Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study

text: Background: Nearly 30,000 patients with coronavirus disease-2019 (COVID-19) have been hospitalized in New York City as of April 14th, 2020. Data on the epidemiology, clinical course, and outcomes of critically ill patients with COVID-19 in this setting are needed. Methods: We prospectively collected clinical, biomarker, and treatment data on critically ill adults with laboratory-confirmed-COVID-19 admitted to two hospitals in northern Manhattan between March 2nd and April 1st, 2020. The primary outcome was in-hospital mortality. Secondary outcomes included frequency and duration of invasive mechanical ventilation, frequency of vasopressor use and renal-replacement-therapy, and time to clinical deterioration following hospital admission. The relationship between clinical risk factors, biomarkers, and in-hospital mortality was modeled using Cox-proportional-hazards regression. Each patient had at least 14 days of observation. Results: Of 1,150 adults hospitalized with COVID-19 during the study period, 257 (22%) were critically ill. The median age was 62 years (interquartile range [IQR] 51-72); 170 (66%) were male. Two-hundred twelve (82%) had at least one chronic illness, the most common of which were hypertension (63%; 162/257) and diabetes mellitus (36%; 92/257). One-hundred-thirty-eight patients (54%) were obese, and 13 (5%) were healthcare workers. As of April 14th, 2020, in-hospital mortality was 33% (86/257); 47% (122/257) of patients remained hospitalized. Two-hundred-one (79%) patients received invasive mechanical ventilation (median 13 days [IQR 9-17]), and 54% (138/257) and 29% (75/257) required vasopressors and renal-replacement-therapy, respectively. The median time to clinical deterioration following hospital admission was 3 days (IQR 1-6). Older age, hypertension, chronic lung disease, and higher concentrations of interleukin-6 and d-dimer at admission were independently associated with in-hospital mortality. Conclusions: Critical illness among patients hospitalized with COVID-19 in New York City is common and associated with a high frequency of invasive mechanical ventilation, extra-pulmonary organ dysfunction, and substantial in-hospital mortality.


title: Epidemiological and ecological modelling reveal diversity in upper respiratory tract microbial population structures from a cross-sectional community swabbing study

text: Respiratory tract infections (RTI) are responsible for over 4 million deaths per year worldwide with pathobiont carriage a required precursor to infection. Through a cross-sectional community-based nasal self-swabbing study we sought to determine carriage epidemiology for respiratory pathogens amongst bacteria (Streptococcus pneumoniae, Haemophilus influenza, Moraxella catarrhalis, Staphylococcus aureus, Pseudomonas aeruginosa and Neisseria meningitidis) and viruses (RSV, Influenza viruses A and B, Rhinovirus/Enterovirus, Coronavirus, Parainfluenza viruses 1-3 and Adenovirus (ADV)). Carriage of bacterial and viral species was shown to vary with participant age, recent RTI and the presence of other species. The spatial structure of microbial respiratory communities was less nested (more disordered) in the young (0-4 years) and those with recent RTI. Species frequency distributions were flatter than random expectation in young individuals (X2 = 20.42, p = 0.002), indicating spatial clumping of species consistent with facilitative relationships amongst them. Deviations from a neutral model of ecological niches were observed for samples collected in the summer and from older individuals (those aged 5-17, 18-64 and ≥65 years) but not in samples collected from winter, younger individuals (those aged 0-4 years), individuals with recent RTI and individuals without recent RTI, demonstrating the importance of both neutral and niche processes in respiratory community assembly. The application of epidemiological methods and ecological theory to sets of respiratory tract samples has yielded novel insights into the factors that drive microbial community composition, such as seasonality and age, as well as species patterns and interactions within the nose.


title: Disseminated Conidiobolus incongruus in a dog: A case report and literature review

text: Conidiobolomycosis is a rare fungal disease of both humans and animals, occurring mainly in tropical and subtropical climates. We describe a disseminated fungal infection in a young, apparently immunocompetent dog who initially presented for antibiotic resistant pneumonia. Histopathology and mycology identified a Conidiobolus sp., further confirmed as Conidiobolus incongruus through DNA sequencing of D1/D2 regions. This is the first report of this species causing disease in dogs and the fifth reported infection in animals.


title: Epidemiology, pathological aspects and genome heterogeneity of feline morbillivirus in Italy

text: Abstract Feline morbillivirus (FeMV) is an emerging morbillivirus first described in cats less than a decade ago. FeMV has been associated with chronic kidney disease of cats characterized by tubulointerstitial nephritis (TIN), although this aspect is still controversial and not demonstrated with certainty. To investigate FeMV prevalence and genomic characteristics, an epidemiological survey was conducted in a total number of 127 household cats originating from two Italian regions, Abruzzi and Emilia-Romagna. A total number of 69 cats originating from three feline colonies were also enrolled for the study. Correlation with TIN was investigated by employing a total number of 35 carcasses. Prevalence of FeMV RNA was higher in urine samples collected from cats of colonies (P = 31.8%, CI 95% 22.1–43.6) compared to household cats (P = 8.66%, CI 95% 4.9–14.9) and in young and middle-aged cats while prevalence of FeMV Abs was higher in old cats. Sequences obtained straight from infected biological samples, either partial or complete, cluster into two clades within FeMV genotype 1, distantly related to FeMV genotype 2. Immunohistochemistry analysis of kidney sections of FeMV RNA positive cats revealed immunoreactivity within epithelial cells of renal tubuli and inflammatory cells. However, statistically significant association between FeMV and renal damages, including TIN, was not demonstrated (p= 0.0695, Fisher exact test). By virus histochemistry performed with FeMV-negative feline tissues and a FeMV isolate, tropism for different cellular types such as inflammatory cells residing in blood vessels of kidney and brain, airway epithelial cells, alveolar macrophages and to a lesser extent, the central nervous system, was demonstrated. Additional studies are warranted in order to establish viral tropism and immune response during the early phases of infection and to disentangle the role of FeMV in co-infection processes.


title: Preparing intensive care for the next pandemic influenza

text: Few viruses have shaped the course of human history more than influenza viruses. A century since the 1918–1919 Spanish influenza pandemic—the largest and deadliest influenza pandemic in recorded history—we have learned much about pandemic influenza and the origins of antigenic drift among influenza A viruses. Despite this knowledge, we remain largely underprepared for when the next major pandemic occurs. While emergency departments are likely to care for the first cases of pandemic influenza, intensive care units (ICUs) will certainly see the sickest and will likely have the most complex issues regarding resource allocation. Intensivists must therefore be prepared for the next pandemic influenza virus. Preparation requires multiple steps, including careful surveillance for new pandemics, a scalable response system to respond to surge capacity, vaccine production mechanisms, coordinated communication strategies, and stream-lined research plans for timely initiation during a pandemic. Conservative models of a large-scale influenza pandemic predict more than 170% utilization of ICU-level resources. When faced with pandemic influenza, ICUs must have a strategy for resource allocation as strain increases on the system. There are several current threats, including avian influenza A(H5N1) and A(H7N9) viruses. As humans continue to live in closer proximity to each other, travel more extensively, and interact with greater numbers of birds and livestock, the risk of emergence of the next pandemic influenza virus mounts. Now is the time to prepare and coordinate local, national, and global efforts.


title: Suspected Case of COVID-19 Associated Pancreatitis in a Child

text: The world has been challenged by SARS CoV-2, a new virus causing pneumonia and acute respiratory distress syndrome, with common symptoms of COVID-19 in pediatric patients including both respiratory and GI symptoms. There is a lack of literature implicating COVID-19 in pancreatitis, yet viruses are generally understood to be a cause of pancreatitis in children. We present a case of a previously well 7-year-old girl, who presented to the Emergency Department with a chief complaint of abdominal pain and anorexia. She was diagnosed with acute pancreatitis with an abnormal lipase, ultrasound and computed tomography, and was found to be COVID-19 positive by polymerase chain reaction. Our case suggests that, in the current pandemic, consideration for SARS CoV-2 testing in children with gastrointestinal symptoms and pancreatitis may be considered. Additionally, this case highlights the need for appropriate personal protective equipment for providers, even when COVID is not initially on the differential


title: The severe acute respiratory syndrome coronavirus 3a is a novel structural protein

text: Abstract The severe acute respiratory syndrome coronavirus (SARS-CoV) 3a protein is one of the opening reading frames in the viral genome with no homologue in other known coronaviruses. Expression of the 3a protein has been demonstrated during both in vitro and in vivo infection. Here we present biochemical data to show that 3a is a novel coronavirus structural protein. 3a was detected in virions purified from SARS-CoV infected Vero E6 cells although two truncated products were present predominantly instead of the full-length protein. In Vero E6 cells transiently transfected with a cDNA construct for expressing 3a, a similar cleavage was observed. Furthermore, co-expression of 3a, membrane and envelope proteins using the baculovirus system showed that both full-length and truncated 3a can be assembled into virus-like particles. This is the first report that demonstrated the incorporation of 3a into virion and showed that the SARS-CoV encodes a novel coronavirus structural protein.


La psychiatrie française confrontée à l’inédit : la crise de la COVID-19


title: Similar virus spectra and seasonality in paediatric patients with acute respiratory disease, Ghana and Germany

text: Abstract Epidemiological differences between tropical and temperate regions regarding viruses causing acute respiratory infection are poorly understood. This is in part because methodological differences limit the comparability of data from these two regions. Using identical molecular detection methods, we tested 1174 Ghanaian and 539 German children with acute respiratory infections sampled over 12 months for the 15 most common respiratory viruses by PCR. A total 43.2% of the Ghanaian and 56.6% of the German children tested positive for at least one respiratory virus. The pneumoviruses respiratory syncytial virus and human metapneumovirus were most frequently detected, in 13.1% and 25.1% within the Ghanaian and German children, respectively. At both study sites, pneumoviruses were more often observed at younger ages (p <0.001). In the Ghanaian rainy season, enveloped viruses were detected twice as often as non-enveloped viruses (prevalence rate ratio (PR) 2.0, 95% CI 1.7–2.4). In contrast, non-enveloped viruses were more frequent during the Ghanaian dry season (PR 0.6, 95% CI 0.4–0.8). In Germany, enveloped viruses were also more frequently detected during the relatively colder winter season (PR 1.6, 95% CI 1.2–2.1) and non-enveloped viruses during summer (PR 0.7, 95% CI 0.5–0.9). Despite a distance of about 5000 km and a difference of 44° latitude separating Germany and Ghana, virus spectra, age associations and seasonal fluctuation showed similarities between sites. Neither respiratory viruses overall, nor environmentally stable (non-enveloped) viruses in particular were more frequent in tropical Ghana. The standardization of our sampling and laboratory testing revealed similarities in acute respiratory infection virus patterns in tropical and temperate climates.


title: Quantification of recombinant core-like particles of bluetongue virus using immunosorbent electron microscopy

text: Abstract Immunosorbent electron microscopy was used to quantify recombinant baculovirus-generated bluetongue virus (BTV) core-like particles (CLP) in either purified preparations or lysates of recombinant baculovirus-infected cells. The capture antibody was an anti-BTV VP7 monoclonal antibody. The CLP concentration in purified preparations was determined to be 6.6×1015 particles/l. CLP concentration in lysates of recombinant baculovirus-infected cells was determined at various times post-infection and shown to reach a value of 3×1015 particles/l of culture medium at 96 h post-infection. The results indicated that immunosorbent electron microscopy, aided by an improved particle counting method, is a simple, rapid and accurate technique for the quantification of virus and virus-like particles produced in large scale in vitro systems.


title: Highlights of the 30th International Conference on Antiviral Research

text: Abstract The 30th International Conference on Antiviral Research (ICAR) was held in Atlanta, GA, USA from May 18 to 21, 2017. This report provides an account of award lectures, invited keynote addresses and oral presentations during the meeting. The 2017 Gertrude Elion Memorial Lecture Award by Michael Sofia highlighted one of the most important accomplishments in recent drug discovery in antiviral research, the identification of the hepatitis C virus direct-acting antiviral sofosbuvir and new alternatives to combat hepatitis B virus (HBV) infection. The Antonín Holý Lecture Award by David Chu on medicinal chemistry provided an overview of early developments of nucleoside analogs for the treatment of HIV and varicella zoster virus infection and how this knowledge serves to develop new drugs targeting HBV. Priscilla Yang gave the first ISAR Women in Science lecture. She reported on pharmacological validation of new antiviral targets for dengue, Zika and other flaviviruses. The William Prusoff Young Investigator Lecture Award by Maaike Everts described the Alabama Drug Discovery Alliance and the Antiviral Drug Discovery and Development Consortium, and how they are helping to accelerate the development of new antivirals. The 30th ICAR was a success in promoting new discoveries in antiviral drug development and research. The 31st ICAR will be held in Porto, Portugal, June 11–15, 2018.


title: The Fine Balance: Adapting Clinical Research into COVID‐19 Response

text: Quality clinical research remains a high priority during the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) coronavirus disease (COVID‐19) pandemic response, however, the logistical barriers of conducting research across institutions with differing departmental policy responses and varying resources is a documented problem.


title: Iron Transport Tocopheryl Polyethylene Glycol Succinate in Animal Health and Diseases

text: Gut health is the starting place for maintaining the overall health of an animal. Strategies to maintain gut health are, thus, an important part in achieving the goal of improving animal health. A new strategy to do this involves two molecules: the iron transport protein ovotransferrin (IT) and α-tocopheryl polyethylene glycol succinate (TPGS), which result in the novel formulation of ITPGS. These molecules help reduce gut pathogens, while enhancing the absorption and bioavailability of therapeutic drugs, phytomedicines, and nanomedicines. This, in turn, helps to maintain normal health in animals. Maintaining the gastrointestinal tract (GIT) in its normal condition is key for successful absorption and efficacy of any nutrient. A compromised GIT, due to an imbalance (dysbiosis) in the GIT microbiome, can lead to an impaired GI barrier system with impaired absorption and overall health of the animal. The molecules in ITPGS may address the issue of poor absorption by keeping the GI system healthy by maintaining the normal microbiome and improving the absorption of nutrients through multiple mechanisms involving antioxidative, anti-inflammatory, immunomodulatory, and antimicrobial activities. The ITPGS technology can allow the dose of active pharmaceutical or herbal medicine to be significantly reduced in order to attain equal or better efficacy. With complimentary actions between IT and TPGS, ITPGS presents a novel approach to increase the bioavailability of drugs, phytoconstituents, nutrients, and nanomedicines by enhanced transport to the tissues at the site of action, while reducing gut pathogen load. The ITPGS approach appears to be a novel strategy for maintaining the health of animals by manipulation of microbiota.


title: Application of CareDose 4D combined with Karl 3D technology in the low dose computed tomography for the follow-up of COVID-19

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) is a highly infectious disease caused by the new coronavirus. Previous studies have shown that the chest CT examination plays an important role in the diagnosis and monitoring of COVID-19. However, some patients with COVID-19 had low white blood cell counts and reduced lymphocyte ratios. Multiple CT examinations may cause radiation damages as well as increase the apoptosis of peripheral blood lymphocytes. A new low-dose CT method should be developed because the regular CT may aggravate the disease. METHOD: Sixty cases were randomly divided into the study group (n = 30) and control group (n = 30). The lung window was reconstructed by Karl 3D iterative technique in the study group. The image quality was subjectively evaluated by two senior chest group diagnostic physicians using a 5-point double-blind method. The value of CT measurement and its standard deviation (SD) was used as an objective evaluation criteria. The volume of CT dose index (CTDI(vol)), dose length product (DLP) and effective dose (ED) from the two groups were compared and analyzed statistically. RESULT: There was no significant difference in the occurrence rates of ground glass opacities, consolidation, crazy-paving pattern, fiber cable shadow and axial interstitial thickening between the study group and control group (p > 0.05). In addition, no significant difference was found for the subjective score of overall image quality and image noise level (SD) between the two groups (p > 0.05). However, significant differences was found in CTDI(vol), DLP, and ED between the study group and the control group (p < 0.05). The effective dose of the study group was reduced by 76% compared to the control group. CONCLUSION: CareDose 4D low-dose scanning combined with Karl 3D iterative reconstruction technology can not only greatly reduce the radiation dose, but also provide images that meet the diagnostic criteria of COVID-19, which can be used as a routine method for the follow-up of COVID-19 patients.


title: Chapter 15 Innate Humoral Defense Factors

text: Abstract Although innate immunity came into the research spotlight in the late 1990s when its instructive role in the adaptive immune response was recognized, innate humoral defense factors have a much older history. The exocrine secretions of the body contain a plethora of distinct soluble factors (lysozyme, lactoferrin, peroxidases, proline-rich proteins, histatins, etc.) that protect the body from mucosal microbial pathogens. More recent studies have established that the humoral arm of innate immunity contains a heterogeneous group of pattern-recognition molecules (e.g., pentraxins, collectins, and ficolins), which perform diverse host-defense functions, such as agglutination and neutralization, opsonization, control of inflammation, and complement activation and regulation. These pattern-recognition molecules, which act as functional predecessors of antibodies (“ante-antibodies”), and the classic soluble innate defense factors form an integrated system with complementary specificity, action, and tissue distribution, and they are the subject of this chapter.


title: Factors Affecting the Disaster Response Competency of Emergency Medical Technicians in South Korea

text: Abstract Purpose This study explored the factors influencing disaster response competency, that is, demographic and disaster-related characteristics, personal disaster (household and workplace) preparedness, disaster risk perception, and self-efficacy in handling disasters among emergency medical technicians in South Korea. Methods The study follows a descriptive, cross-sectional design and uses a self-reported questionnaire. Emergency medical technicians, amounting to 1,020 in all, currently working in firefighting organizations from four South Korean cities (Busan, Daegu, Daejeon, and Ulsan) participated in the study. Results Disaster risk perception, self-efficacy for disaster, participation experience in disaster education/training, and personal disaster (household and workplace) preparedness predicted the disaster response competency of emergency medical technicians in South Korea. Conclusion There is a need for an antidisaster program to enhance the disaster risk perception, self-efficacy, personal disaster (household and workplace) preparedness, and the disaster education/training participation rate toward enhancing disaster response competency of emergency medical technicians in South Korea.


title: Hydrogen Europe paper on the hydrogen sector after Covid-19

text: The Hydrogen Europe industry association has published a paper analysing the hydrogen sector post-Covid-19, which outlines the need for and rationale behind rapid action as a result of the impact of the Covid-19 pandemic.


COVID-19, Aging and Mental Health: Lessons from the First Six Months


title: Development of an RT-PCR diagnostic test for an avian astrovirus

text: Abstract Astroviruses are small round viruses that cause enteric disease in the young of several species. Detection and diagnosis of astrovirus infection in non-human hosts relies heavily on electron microscopy and fluorescent antibody tests. Recently, our laboratory isolated and sequenced an avian astrovirus from poult enteritis mortality syndrome affected turkeys. These studies describe the development of RT-PCR methods, which specifically detect regions of the viral capsid and polymerase genes, and demonstrate their use in detecting astrovirus infection in commercial turkey flocks.


title: Sulfated polymannuroguluronate TGC161 ameliorates leukopenia by inhibiting CD4(+) T cell apoptosis

text: Polysaccharides have aroused considerable interest due to their diverse biological activities and low toxicity. In this study, we evaluated the effect of marine polysaccharide sulfated polymannuroguluronate (TGC161) on the leukopenia induced by chemotherapy. It is found that TGC161 ameliorates the leukopenia. Besides, TGC161 would promote CD4(+) T cell differentiation and maturation in the thymus, but does not have a significant effect on precursor cells in bone marrow. Furthermore, TGC161 inhibits CD4(+) T cell apoptosis in vitro. Collectively, our findings offer a natural and harmless polysaccharide to ameliorate leukopenia.


title: Proteins with RNA Chaperone Activity: A World of Diverse Proteins with a Common Task—Impediment of RNA Misfolding

text: Proteins with RNA chaperone activity are ubiquitous proteins that play important roles in cellular mechanisms. They prevent RNA from misfolding by loosening misfolded structures without ATP consumption. RNA chaperone activity is studied in vitro and in vivo using oligonucleotide- or ribozyme-based assays. Due to their functional as well as structural diversity, a common chaperoning mechanism or universal motif has not yet been identified. A growing database of proteins with RNA chaperone activity has been established based on evaluation of chaperone activity via the described assays. Although the exact mechanism is not yet understood, it is more and more believed that disordered regions within proteins play an important role. This possible mechanism and which proteins were found to possess RNA chaperone activity are discussed here.


title: A case of Listeria monocytogenes meningitis complicated by Hydrocephalus and Intraventricular hemorrhage: A review of treatment options and outcomes

text: Listeria monocytogenes is a gram-positive bacillus known to cause various human infections including central nervous system infections. The most common central nervous system manifestations are meningitis and rhomboencephalitis, however rare complications including hydrocephalus and intracerebral hemorrhage can occur and are associated with increased mortality and incidence of lasting neurologic sequelae. The mortality ranges from 17 % to greater than 30 % in patients with neurological involvement [[1], [2], [3]]. Various case reports have studied the differing treatment approaches and outcomes of patients who experienced these complications, and there is still no consensus on optimal treatment approaches. In this paper, we report a case of Listeria meningitis complicated by both acute hydrocephalus and intracerebral hemorrhage and analyze the factors that led to a favorable outcome by reviewing the existing literature.


title: Halitunal, an unusual diterpene aldehyde from the marine alga Halimeda tuna

text: Abstract Halituna( 1 ), a novel diterpene aldehyde possessing a unique cyclopentadieno[c]pyran ring system, has been isolated from the marine alga Halimeda tuna. The structure of 1 was elucidated by spectroscopic techniques. Halitunal shows antiviral activity against murine coronavirus A59 in-vitro.


title: Suitability of canine herpesvirus as a vector for oral bait vaccination of foxes

text: Abstract Studies were conducted to evaluate the feasibility of using canine herpesvirus (CHV) as a vaccine vector for bait-delivered oral vaccination of wild foxes. To test the viability of CHV in baits, CHV was freeze-dried, incorporated into different baits, stored, and the remaining viral infectivity tested in cell culture after varying periods of time at different storage temperatures. Experimental baits (mouse carcasses) and commercial baits (FOXOFF and PROBAIT) were prepared with either liquid or freeze-dried CHV and tested in two fox trials for their capacity to induce CHV-specific antibodies following oral baiting. Freeze-drying and storage temperatures below 0°C had a stabilizing effect to virus infectivity. When stored at −20°C, freeze-dried CHV retained its full infectivity for up to 3 months in PROBAIT baits, the remaining infectivity in FOXOFF baits was 100-fold less. Oral baiting with CHV induced antiviral serum antibodies in all vaccinated foxes (20/20). None of the vaccinated foxes became ill or shed infectious virus into the environment although viral DNA was detected in body secretions as evaluated by PCR. The results indicate that CHV can be freeze-dried and stored over extended periods of time without loosing much of its infectivity. This is the first report of CHV being used for oral bait vaccination of foxes. It appears that CHV is well suited for use as a recombinant vector for wild canids.


title: Identification of pyrvinium pamoate as an anti-tuberculosis agent in vitro and in vivo by SOSA approach amongst known drugs

text: Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) bacteria, is a leading infectious cause of mortality worldwide. The emergence of drug-resistant M. tb has made control of TB more difficult. The selective optimization of side activities (SOSA) approach uses old drugs for new pharmacological targets. In the present study by using SOSA approach, we have successfully identified pyrvinium pamoate (PP) which is capable of inhibiting the growth of mycobacteria, including M. tb H37Rv, Mycobacterium smegmatis, Bacille Calmette-Guérin (BCG), M. tb H37Ra, and drug-resistant M. tb clinical isolates in vitro from 1280 known drugs library. The MIC(99) of PP, the minimum inhibitory concentration that inhibits more than 99% of M. tb H37Rv and the drug-resistant M. tb clinical isolates, ranges from 1.55 to 4.8 µg/mL. Importantly, PP could reduce the bacterial colony-forming units (CFUs) in lung, spleen and liver tissues, and effectively inhibit inflammatory response in M. tb H37Rv, multidrug-resistant (MDR) M. tb and extensively drug-resistant (XDR) M.tb-infected mice. Our results clearly show that the PP has the potential application for treatment of TB.


title: Benzotriazole: An overview on its versatile biological behavior

text: Discovered in late 1960, azoles are heterocyclic compounds class which constitute the largest group of available antifungal drugs. Particularly, the imidazole ring is the chemical component that confers activity to azoles. Triazoles are obtained by a slight modification of this ring and similar or improved activities as well as less adverse effects are reported for triazole derivatives. Consequently, it is not surprising that benzimidazole/benzotriazole derivatives have been found to be biologically active. Since benzimidazole has been widely investigated, this review is focused on defining the place of benzotriazole derivatives in biomedical research, highlighting their versatile biological properties, the mode of action and Structure Activity Relationship (SAR) studies for a variety of antimicrobial, antiparasitic, and even antitumor, choleretic, cholesterol-lowering agents.


title: COVID-19 and immunosuppression: a review of current clinical experiences and implications for ophthalmology patients taking immunosuppressive drugs

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 in Wuhan city, Hubei province, China. This is the third and largest coronavirus outbreak since the new millennium after SARS in 2002 and Middle East respiratory syndrome (MERS) in 2012. Over 3 million people have been infected and the COVID-19 has caused more than 217 000 deaths. A concern exists regarding the vulnerability of patients who have been treated with immunosuppressive drugs prior or during this pandemic. Would they be more susceptible to infection by the SARS-CoV-2 and how would their clinical course be altered by their immunosuppressed state? This is a question the wider medical fraternity—including ophthalmologists, rheumatologists, gastroenterologist and transplant physicians among others—must answer. The evidence from the SARS and MERS outbreak offer some degree of confidence that immunosuppression is largely safe in the current COVID-19 pandemic. Preliminary clinical experiences based on case reports, small series and observational studies show the morbidity and mortality rates in immunosuppressed patients may not differ largely from the general population. Overwhelmingly, current best practice guidelines worldwide recommended the continuation of immunosuppression treatment in patients who require them except for perhaps high-dose corticosteroid therapy and in patients with associated risk factors for severe COVID-19 disease.


title: Crystal structure, vibrational and optic properties of 2-N-methylamino-3-methylpyridine N-oxide – Its X-ray and spectroscopic studies as well as DFT quantum chemical calculations

text: Abstract The crystal and molecular structure and physicochemical properties of 2-N-methylamino-3-methylpyridine N-oxide (MA3MPO) have been studied. MA3MPO was synthesized from 2-amino-3-methylpyridine by several steps to form colorless crystals suitable for crystallographic analysis. The data reveal that MA3MPO crystallizes in the monoclinic space group P21/n. The studied compound contains a nearly flat triply substituted pyridine skeleton whose structure is stabilized by an intramolecular N–H⋅⋅⋅O hydrogen bond. The N-oxide molecules are connected together by weak C–H⋯O hydrogen bonds, an acceptor of which is the oxygen atom from the N-oxide group. This leads to creation of two-dimensional network of hydrogen bonds. Its IR, Raman, UV–Vis and luminescence spectra have been measured and analyzed on the basis of DFT and NBO quantum chemical calculations in which the B3LYP/6-311++G(d,p) approach was applied. The distribution of the electron levels in the studied compound has been analyzed in terms of the possibility of its participation in the ligand-to-lanthanide ion energy transfer.


title: Headaches and the N95 face‐mask amongst healthcare providers

text: Background: During the 2003 severe acute respiratory distress syndrome epidemic, healthcare workers mandatorily wore the protective N95 face‐mask. Methods: We administered a survey to healthcare workers to determine risk factors associated with development of headaches (frequency, headache subtypes and duration of face‐mask wear) and the impact of headaches (sick days, headache frequency and use of abortive/preventive headache medications). Results: In the survey, 212 (47 male, 165 female) healthcare workers of mean age 31 years (range, 21–58) participated. Of the 79 (37.3%) respondents who reported face‐mask‐associated headaches, 26 (32.9%) reported headache frequency exceeding six times per month. Six (7.6%) had taken sick leave from March 2003 to June 2004 (mean 2 days; range 1–4 days) and 47 (59.5%) required use of abortive analgesics because of headache. Four (2.1%) took preventive medications for headaches during this period. Multivariate logistic regression showed that pre‐existing headaches [P = 0.041, OR = 1.97 (95% CI 1.03–3.77)] and continuous use of the N95 face‐mask exceeding 4 h [P = 0.053, OR = 1.85 (95% CI 0.99–3.43)] were associated with development of headaches. Conclusions: Healthcare providers may develop headaches following the use of the N95 face‐mask. Shorter duration of face‐mask wear may reduce the frequency and severity of these headaches.


Lung Surfactant for Pulmonary Barrier Restoration in Patients With COVID-19 Pneumonia


title: Tandem leader proteases of Grapevine leafroll-associated virus-2: Host-specific functions in the infection cycle

text: Abstract Several viruses in the genus Closterovirus including Grapevine leafroll-associated virus-2 (GLRaV-2), encode a tandem of papain-like leader proteases (L1 and L2) whose functional profiles remained largely uncharacterized. We generated a series of the full-length, reporter-tagged, clones of GLRaV-2 and demonstrated that they are systemically infectious upon agroinfection of an experimental host plant Nicotiana benthamiana. These clones and corresponding minireplicon derivatives were used to address L1 and L2 functions in GLRaV-2 infection cycle. It was found that the deletion of genome region encoding the entire L1–L2 tandem resulted in a ~100-fold reduction in minireplicon RNA accumulation. Five-fold reduction in RNA level was observed upon deletion of L1 coding region. In contrast, deletion of L2 coding region did not affect RNA accumulation. It was also found that the autocatalytic cleavage by L2 but not by L1 is essential for genome replication. Analysis of the corresponding mutants in the context of N. benthamiana infection launched by the full-length GLRaV-2 clone revealed that L1 or its coding region is essential for virus ability to establish infection, while L2 plays an accessory role in the viral systemic transport. Strikingly, when tagged minireplicon variants were used for the leaf agroinfiltration of the GLRaV-2 natural host, Vitis vinifera, deletion of either L1 or L2 resulted in a dramatic reduction of minireplicon ability to establish infection attesting to a host-specific requirement for tandem proteases in the virus infection cycle.


Letter to the Editor on “An Imperative Need for Research on the Role of Environmental Factors in Transmission of Novel Coronavirus (COVID-19)”, Back to Basics