title: Knowledge, attitudes, practices, and burden during the covid-19 pandemic in people with Parkinson’s disease in Germany

text: Background: Adherence to measures that have been adopted during the COVID-19 pandemic is crucial to control the spread of the coronavirus. Methods: Semi-structured telephone interviews were performed with 99 patients with Parkinson’s disease (PD) and 21 controls to explore knowledge, attitudes, practices, and burden in order to elucidate nonadherence to preventive measures. Results: The majority of patients understood the preventive measures and felt sufficiently informed. Analysis of qualitative answers, however, showed that about 30% of patients had an insufficient level of knowledge, which was not associated with educational level, cognitive disorders, or depression. Changes in behaviour were reported by 73 patients (99% performed at least one specific preventive behavior, and 86.9% have reduced social contacts and stayed home). A closer analysis of qualitative answers showed that 27.3% of patients continued to meet relatives face-to-face almost daily. Anxiety and worries about the current situation were reported by 58.6% of patients; 31.3% complained about a decrease in their mobility since the beginning of the restrictions, mainly because of worsening of PD and because regular therapies (e.g., physiotherapy) were canceled. Conclusions: About 30% of PD patients are nonadherent to preventive measures. Use of simple dichotomous questions overestimates adherence to preventive measures in patients with PD.


Interruption of the European Association of Cardiothoracic Anaesthesiology (EACTA) Fellowship Program during the COVID-19 pandemic: consequences and solutions.


title: Modelling of reproduction number for COVID-19 in India and high incidence states

text: BACKGROUND: Since the onset of the COVID-19 in China, forecasting and projections of the epidemic based on epidemiological models have been in the centre stage. Researchers have used various models to predict the maximum extent of the number of cases and the time of peak. This yielded varying numbers. This paper aims to estimate the effective reproduction number (R) for COVID-19 over time using incident number of cases that are reported by the government. METHODS: Exponential Growth method to estimate reproduction rate R(0), and Time dependent method to calculate the effective reproduction number (dynamic) were used. “R0” package in R software was used to estimate these statistics. RESULTS: The basic reproduction number (R(0)) for India was estimated at 1.379 (95% CI: 1.375, 1.384). This was 1.450 (1.441, 1.460) for Maharashtra, 1.444 (1.430, 1.460) for Gujarat, 1.297 (1.284, 1.310) for Delhi and 1.405 (1.389, 1.421) for Tamil Nadu. In India, the R at the first week from March 2–8, 2020 was 3.2. It remained around 2 units for three weeks, from March 9–29, 2020. After March 2020, it started declining and reached around 1.3 in the following week suggesting a stabilisation of the transmissibility rate. CONCLUSION: The study estimated a baseline R(0) of 1.379 for India. It also showed that the R was getting stabilised from first week of April (R = 1.1), despite the increase in March. This suggested that in due course there will be a reversal of epidemic. However, these analyses should be revised periodically.


title: Viral Discovery and Sequence Recovery Using DNA Microarrays

text: Because of the constant threat posed by emerging infectious diseases and the limitations of existing approaches used to identify new pathogens, there is a great demand for new technological methods for viral discovery. We describe herein a DNA microarray-based platform for novel virus identification and characterization. Central to this approach was a DNA microarray designed to detect a wide range of known viruses as well as novel members of existing viral families; this microarray contained the most highly conserved 70mer sequences from every fully sequenced reference viral genome in GenBank. During an outbreak of severe acute respiratory syndrome (SARS) in March 2003, hybridization to this microarray revealed the presence of a previously uncharacterized coronavirus in a viral isolate cultivated from a SARS patient. To further characterize this new virus, approximately 1 kb of the unknown virus genome was cloned by physically recovering viral sequences hybridized to individual array elements. Sequencing of these fragments confirmed that the virus was indeed a new member of the coronavirus family. This combination of array hybridization followed by direct viral sequence recovery should prove to be a general strategy for the rapid identification and characterization of novel viruses and emerging infectious disease.


LOW FREQUENCY OF COVID-19 IN INFLAMMATORY BOWEL DISEASES


COVID-19 Shatters global automotive industry; Sales of metal powder take a nosedive amid wavering demand


title: Cybercrime in a time of coronavirus

text: An alert issued jointly by the US Department of Homeland Security's Cyber security and Infrastructure Security Agency (CISA) and the UK's National Cyber Security Centre (NCSC) warns that so-called advanced persistent threat (APT) groups are exploiting the Covid-19 pandemic to ramp up operations targeted against organisations involved in responses to the emergency at both national and international levels.


title: Visualising the expansion and spread of coronavirus disease 2019 by cartograms

text: Coronavirus disease 2019 (COVID-19) has emerged as a growing focus of global attention and a critical factor in public-health decision making. Towards fighting the COVID-19 outbreak, countries worldwide and international organisations have taken various actions, including promoting the transparency of and public access to disease data. In such public communications, maps have played an important role in that a map is worth a thousand words. Most of these have taken the form of a choropleth map. Here, we propose employing cartograms to visualise both the expansion and spread of COVID-19. We designed a combination of six circular cartograms containing the data of confirmed cases every 48 hours from 24 January to 3 February 2020. Such a design conveys both spatial and temporal information more intuitively and efficiently, so it can be expected to facilitate better public participation in the fight against COVID-19.


title: The impact of the COVID-19 pandemic on final year medical students in the United Kingdom: a national survey

text: BACKGROUND: The coronavirus disease (COVID-19) global pandemic has resulted in unprecedented public health measures. This has impacted the UK education sector with many universities halting campus-based teaching and examinations. The aim of this study is to identify the impact of COVID-19 on final year medical students’ examinations and placements in the United Kingdom (UK) and how it might impact their confidence and preparedness going into their first year of foundation training. METHODS: A 10-item online survey was distributed to final year medical students across 33 UK medical schools. The survey was designed by combining dichotomous, multiple choice and likert response scale questions. Participants were asked about the effect that the COVID-19 global pandemic had on final year medical written exams, electives, assistantships and objective structured clinical examinations (OSCEs). The survey also explored the student’s confidence and preparedness going into their first year of training under these new unprecedented circumstances. RESULTS: Four hundred forty students from 32 UK medical schools responded. 38.4% (n = 169) of respondents had their final OSCEs cancelled while 43.0% (n = 189) had already completed their final OSCEs before restrictions. 43.0% (n = 189) of assistantship placements were postponed while 77.3% (n = 340) had electives cancelled. The impact of COVID-19 on OSCEs, written examinations and student assistantships significantly affected students’ preparedness (respectively p = 0.025, 0.008, 0.0005). In contrast, when measuring confidence, only changes to student assistantships had a significant effect (p = 0.0005). The majority of students feel that measures taken during this pandemic to amend their curricula was necessary. Respondents also agree that assisting in hospitals during the outbreak would be a valuable learning opportunity. CONCLUSIONS: The impact on medical student education has been significant, particularly affecting the transition from student to doctor. This study showed the disruptions to student assistantships had the biggest effect on students’ confidence and preparedness. For those willing to assist in hospitals to join the front-line workforce, it is crucial to maintain their wellbeing with safeguards such as proper inductions, support and supervision.


title: On coughing and airborne droplet transmission to humans

text: Our understanding of the mechanisms of airborne transmission of viruses is incomplete. This paper employs computational multiphase fluid dynamics and heat transfer to investigate transport, dispersion, and evaporation of saliva particles arising from a human cough. An ejection process of saliva droplets in air was applied to mimic the real event of a human cough. We employ an advanced three-dimensional model based on fully coupled Eulerian–Lagrangian techniques that take into account the relative humidity, turbulent dispersion forces, droplet phase-change, evaporation, and breakup in addition to the droplet–droplet and droplet–air interactions. We computationally investigate the effect of wind speed on social distancing. For a mild human cough in air at 20 °C and 50% relative humidity, we found that human saliva-disease-carrier droplets may travel up to unexpected considerable distances depending on the wind speed. When the wind speed was approximately zero, the saliva droplets did not travel 2 m, which is within the social distancing recommendations. However, at wind speeds varying from 4 km/h to 15 km/h, we found that the saliva droplets can travel up to 6 m with a decrease in the concentration and liquid droplet size in the wind direction. Our findings imply that considering the environmental conditions, the 2 m social distance may not be sufficient. Further research is required to quantify the influence of parameters such as the environment’s relative humidity and temperature among others.


title: Species identification of trichomonads and associated coinfections in dogs with diarrhea and suspected trichomonosis

text: Abstract Trichomonads have been infrequently reported in the feces of dogs where their pathogenicity remains uncertain. It is currently unknown whether Tritrichomonas foetus or Pentatrichomonas hominis is identified more commonly in dogs with trichomonosis or how often these infections are accompanied by concurrent enteric infectious agents. The objective of this study was to determine the identity of trichomonads present in a series of 38 unsolicited canine diarrheic fecal samples submitted for T. foetus diagnostic polymerase chain reaction (PCR) testing between 2007 and 2010. We also examined each fecal sample for an association of trichomonosis with concurrent infection using a convenient real-time PCR panel for nine gastrointestinal pathogens. P. hominis, T. foetus, or both were identified by PCR in feces of 17, 1, and 1 dogs respectively. Feces from the remaining 19 dogs were PCR negative for T. foetus, P. hominis and using broader-spectrum Trichomonadida primers. The total number and specific identities of concurrent enteropathogens identified did not differ between fecal samples from dogs that were or were not identified by PCR as infected with trichomonads. These results suggest that P. hominis infection is more frequently identified than T. foetus infection in diarrheic dogs with trichomonosis and that concurrent enteropathogen infection is common in this population.


EU-China relations in the time of COVID-19


title: Porcine reproductive and respiratory syndrome virus nonstructural protein 2 contributes to NF-κB activation

text: BACKGROUND: Nuclear factor-kappaB (NF-κB) is an inducible transcription factor that plays a key role in inflammation and immune responses, as well as in the regulation of cell proliferation and survival. Previous studies by our group and others have demonstrated that porcine reproductive and respiratory syndrome virus (PRRSV) infection could activate NF-κB in MARC-145 cells and alveolar macrophages. The nucleocapsid (N) protein was identified as an NF-κB activator among the structural proteins encoded by PRRSV; however, it remains unclear whether the nonstructural proteins (Nsps) contribute to NF-κB activation. In this study, we identified which Nsps can activate NF-κB and investigated the potential mechanism(s) by which they act. RESULTS: By screening the individual Nsps of PRRSV strain WUH3, Nsp2 exhibited great potential to activate NF-κB in MARC-145 and HeLa cells. Overexpression of Nsp2 induced IκBα degradation and nuclear translocation of NF-κB. Furthermore, Nsp2 also induced NF-κB-dependent inflammatory factors, including interleukin (IL)-6, IL-8, COX-2, and RANTES. Compared with the Nsp2 of the classical PRRSV strain, the Nsp2 of highly pathogenic PRRSV (HP-PRRSV) strains that possess a 30 amino acid (aa) deletion in Nsp2 displayed greater NF-κB activation. However, the 30-aa deletion was demonstrated to not be associated with NF-κB activation. Further functional domain analyses revealed that the hypervariable region (HV) of Nsp2 was essential for NF-κB activation. CONCLUSIONS: Taken together, these data indicate that PRRSV Nsp2 is a multifunctional protein participating in the modulation of host inflammatory response, which suggests an important role of Nsp2 in pathogenesis and disease outcomes.


title: A New Ridge-Type Estimator for the Linear Regression Model: Simulations and Applications

text: The ridge regression-type (Hoerl and Kennard, 1970) and Liu-type (Liu, 1993) estimators are consistently attractive shrinkage methods to reduce the effects of multicollinearity for both linear and nonlinear regression models. This paper proposes a new estimator to solve the multicollinearity problem for the linear regression model. Theory and simulation results show that, under some conditions, it performs better than both Liu and ridge regression estimators in the smaller MSE sense. Two real-life (chemical and economic) data are analyzed to illustrate the findings of the paper.


title: In the eye of the storm: the right ventricle in COVID-19

text: The corona virus disease of 2019 pandemic caused by the SARS-CoV-2 virus continues to inflict significant morbidity and mortality around the globe. A variety of cardiovascular presentations of SARS-CoV-2 infection have been described so far. However, the impact of SARS-CoV-2 on the right ventricle is largely unknown. Due to its pathophysiologic relevance, the right ventricle finds itself in the eye of the storm of corona virus disease of 2019, placing it at higher risk of failure. Increased afterload from acute respiratory distress syndrome and pulmonary embolism, negative inotropic effects of cytokines, and direct angiotensin converting enzyme 2-mediated cardiac injury from SARS-CoV-2 are potential mechanisms of right ventricle dysfunction in corona virus disease of 2019. Early detection and treatment of right ventricle dysfunction may lead to decreased mortality and improved patient outcomes in corona virus disease of 2019.


title: Metapneumovirus and its place in childhood

text: Human metapneumovirus (hMPV) was recently identified as a cause of acute upper and lower respiratory tract infection in children and adults. The epidemiology is similar to that exhibited by respiratory syncytial virus, with most episodes occurring during the winter months. The virus likely has a worldwide distribution. Almost all children have been infected by five years of age. The suspicion of hMPV infection should be higher in infants or children presenting with symptoms compatible with a viral etiology and in whom screening tests for other common viral pathogens have been negative. Clinical manifestations may be subtle or severe, including life-threatening bronchiolitis or pneumonia. Fever, rhinorrhea, cough, retractions, tachypnea and wheezing are common findings. Bronchiolitis is perhaps the most common manifestation among hospitalized children. Currently, there is no antiviral treatment or vaccine available and management is simply supportive.


title: Usage of Over-the-Counter and Herbal Products in Common Cold in Poland: Findings from Consumer Survey

text: Upper respiratory tract infections are usually self-treated with synthetic and herbal over-the-counter products. The aim of the study was to assess the reasons for the purchase of those medications in Poland. We examined 413 adults, aged 18 and over (70.5 % of them were women) using a questionnaire. The findings demonstrate that oral synthetic products were used by 76 % of respondents, while herbal products by 30 %. Synthetic products were used mainly by educated people under 65 years of age, students, and the employed. Herbal products were used mainly by older people. In conclusion, synthetic products against common cold are perceived as more effective. Such medications are used by people who probably would like to recover and return to professional activity as quickly as possible. As they generally use more medications, they are at increased risk of adverse effects resulting from drug interactions, and they should be a target group for health education programs.


Letter: COVID-19 Pandemic—The Bystander Effect on Stroke Care in Michigan


title: Patients’ reported experiences and outcomes following surgical excision of lower limb osteomyelitis and microvascular free tissue reconstruction under ‘awake’ epidural anaesthesia and sedation()

text: BACKGROUND: Orthoplastic operations for lower limb osteomyelitis (LLOM) involving microvascular free tissue reconstructions (“free-flaps”) are usually performed under general anaesthesia (GA), with or without epidural anaesthesia (EA) due to concerns about the discomfort associated with prolonged surgery. However, our clinical experience supports “awake” epidural anaesthesia with sedation (EA + Sed) rather than EA + GA as a technique of choice for this type of surgery. METHODS: We used a standardised postoperative questionnaire to formally assess the experiences and outcomes for 50 patients who underwent free-flaps for LLOM under EA + Sed. FINDINGS: The mean duration of surgery was 522 min (8.7 h), range 240–875 min. There were no ITU admissions or flap failures. Postoperatively, fifty patients completed a standardised questionnaire about their experiences before the operation, in the anaesthetic room and theatre. 80% were aware of the procedure at least “some of the time”. 72.5% patients and 75% respectively, did not have any concerns in the anaesthetic room and theatre. Concerns expressed by the remaining patients were manageable. 97.5% of those patients who recalled their operation reported their overall experience as “comfortable” or “very comfortable”. 92% of respondents had undergone previous lower limb surgery under GA ± EA. In this subgroup, 91.3% reported the recovery after EA + Sed as “quicker” than GA, and 89.4% reported their experience with EA + Sed as “better”. All fifty patients (100%) were “satisfied” or “very satisfied” with their experience and all but one (98%) would recommend this technique to others. CONCLUSIONS: Our study showed that despite prolonged duration, the patients' reported experiences and outcomes were excellent when EA + Sed was used for orthoplastic operations involving free-flaps for LLOM. We recommend EA + Sed as the anaesthetic technique of choice for such patients.


title: Association between chest CT features and clinical course of Coronavirus Disease 2019

text: Abstract Purpose This retrospective study aims to illustrate the radiographic characteristics of Coronavirus Disease 2019 and the correlation with the clinical course. Methods 195 hospitalized patients confirmed as Coronavirus Disease 2019 at First Hospital of Changsha, Hunan Province from December 31, 2019 to February 20, 2020 were enrolled. Chest computed tomography scan, clinical data and laboratory tests results were collected accordingly. Variable characteristics were recorded, radiographic evolution and outcome were analyzed along with the time course. Representative laboratory tests results were analyzed based on the image findings. Results Majority of the patients showed bilateral (73.8%), multiple lobes involvements (75.9%), peripheral distribution (83.1%), ground-glass opacification (41.0%), increased vascular margins (63.1%), long axis parallelism (55.9%), patchy ground-glass opacities beneath the pleura (51.3%) and consolidation (45.6%). According to the repeated radiology analysis, patients of improving/stable group tended to have younger age compared with worsening group (45.3 ± 15.0 VS. 59.3 ± 13.5, P = 0.001). Based on the laboratory test results, patients with positive image findings shared elder age, 46.0 (35.0–60.0)VS.31.0 (12.0–37.0) P < 0.001, and higher chance developing fever(P < 0.05); higher level of lymphocytes, C-reactive protein, erythrocyte sedimentation rate and lactate dehydrogenase; lower level of white blood cells, neutrophil and albumin(P < 0.001). Conclusions There are several specific image changes along with the disease progression may be helpful in early recognition and differential diagnosis of Coronavirus Disease 2019. Comprehensive assessments of both imaging feature and laboratory test results may offer an intact knowledge of Coronavirus Disease 2019.


title: High titer MVA and influenza A virus production using a hybrid fed-batch/perfusion strategy with an ATF system

text: A cultivation strategy to increase the productivity of Modified Vaccinia Ankara (MVA) virus in high-cell density processes is presented. Based on an approach developed in shake flask cultures, this strategy was established in benchtop bioreactors, comprising the growth of suspension AGE1.CR.pIX cells to high cell densities in a chemically defined medium before infection with the MVA-CR19 virus strain. First, a perfusion regime was established to optimize the cell growth phase. Second, a fed-batch regime was chosen for the initial infection phase to facilitate virus uptake and cell-to-cell spreading. Afterwards, a switch to perfusion enabled the continuous supply of nutrients for the late stages of virus propagation. With maximum infectious titers of 1.0 × 10(10) IU/mL, this hybrid fed-batch/perfusion strategy increased product titers by almost one order of magnitude compared to conventional batch cultivations. Finally, this strategy was also applied to the production of influenza A/PR/8/34 (H1N1) virus considered for manufacturing of inactivated vaccines. Using the same culture system, a total number of 3.8 × 10(10) virions/mL was achieved. Overall, comparable or even higher cell-specific virus yields and volumetric productivities were obtained using the same cultivation systems as for the conventional batch cultivations. In addition, most viral particles were found in the culture supernatant, which can simplify further downstream operations, in particular for MVA viruses. Considering the current availability of well-described perfusion/cell retention technologies, the present strategy may contribute to the development of new approaches for viral vaccine production. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00253-019-09694-2) contains supplementary material, which is available to authorized users.


title: Mechanisms of viral entry: sneaking in the front door

text: Recent developments in methods to study virus internalisation are providing clearer insights into mechanisms used by viruses to enter host cells. The use of dominant negative constructs, specific inhibitory drugs and RNAi to selectively prevent entry through particular pathways has provided evidence for the clathrin-mediated entry of hepatitis C virus (HCV) as well as the caveolar entry of Simian Virus 40. Moreover, the ability to image and track fluorescent-labelled virus particles in real-time has begun to challenge the classical plasma membrane entry mechanisms described for poliovirus and human immunodeficiency virus. This review will cover both well-documented entry mechanisms as well as more recent discoveries in the entry pathways of enveloped and non-enveloped viruses. This will include viruses which enter the cytosol directly at the plasma membrane and those which enter via endocytosis and traversal of internal membrane barrier(s). Recent developments in imaging and inhibition of entry pathways have provided insights into the ill-defined entry mechanism of HCV, bringing it to the forefront of viral entry research. Finally, as high-affinity receptors often define viral internalisation pathways, and tropism in vivo, host membrane proteins to which viral particles specifically bind will be discussed throughout.


title: Respiratory Syncytial Virus Uses CX3CR1 as a Receptor on Primary Human Airway Epithelial Cultures

text: Respiratory syncytial virus (RSV) is the most frequent cause of lower respiratory disease in infants, but no vaccine or effective therapy is available. The initiation of RSV infection of immortalized cells is largely dependent on cell surface heparan sulfate (HS), a receptor for the RSV attachment (G) glycoprotein in immortalized cells. However, RSV infects the ciliated cells in primary well differentiated human airway epithelial (HAE) cultures via the apical surface, but HS is not detectable on this surface. Here we show that soluble HS inhibits infection of immortalized cells, but not HAE cultures, confirming that HS is not the receptor on HAE cultures. Conversely, a “non-neutralizing” monoclonal antibody against the G protein that does not block RSV infection of immortalized cells, does inhibit infection of HAE cultures. This antibody was previously shown to block the interaction between the G protein and the chemokine receptor CX3CR1 and we have mapped the binding site for this antibody to the CX3C motif and its surrounding region in the G protein. We show that CX3CR1 is present on the apical surface of ciliated cells in HAE cultures and especially on the cilia. RSV infection of HAE cultures is reduced by an antibody against CX3CR1 and by mutations in the G protein CX3C motif. Additionally, mice lacking CX3CR1 are less susceptible to RSV infection. These findings demonstrate that RSV uses CX3CR1 as a cellular receptor on HAE cultures and highlight the importance of using a physiologically relevant model to study virus entry and antibody neutralization.


title: Effectiveness of an education health programme about Middle East respiratory syndrome coronavirus tested during travel consultations

text: Abstract Objective We aimed to evaluate the level of knowledge of Middle East respiratory syndrome coronavirus (MERS-CoV) among Hajj pilgrims before and after an education health programme during international vaccine consultations in France. Study design A cross-sectional study was performed in the consultation for travel medicine and international vaccination in Reims University Hospital between July 2014 and October 2015. Methods Consecutive adults (>18 years old) who attended for pre-Hajj meningococcal vaccination were eligible to complete an anonymous questionnaire with closed answers to evaluate their level of knowledge about MERS-CoV. To evaluate the effectiveness of the information given during the consultation, the same questionnaire was completed by the Hajj pilgrim before and after the consultation, where the information about MERS-CoV was provided. Results Among 82 Hajj pilgrim adults enrolled in the study, less than 25% were aware of the routes of transmission, symptoms and preventive behaviours to adopt abroad or in case of fever. Pilgrims had a higher rate of correct responses on each question at the time they completed the second questionnaire, as compared with the first, with 11 of 13 questions answered significantly better after delivery of educational information about MERS-CoV. However, although the rate of correct answers to the questions about routes of transmission, symptoms, preventive behaviours to adopt in case of fever and time delay between return and potential MERS-CoV occurrence increased significantly after receiving the information, the rates remained below 50%. Conclusion Information given during travel consultations significantly increases the general level of knowledge, but not enough to achieve epidemic control.


title: Coronavirus: Schutzkleidung wird zentral bestellt und bezahlt: Infektionsschutz

text: KBV und GKV-Spitzenverband haben sich — endlich — auf eine Regelung zur Beschaffung, Verteilung und Finanzierung von Schutzkleidung für die vertragsärztlichen Praxen geeinigt. Die Ärzte sollen finanziell nicht belastet werden. Die Regelung ist zunächst befristet bis zum 10. Juni 2020.


title: Viral subversion of the host protein synthesis machinery

text: Viruses are fully reliant on the translation machinery of their host cells to produce the polypeptides that are essential for viral replication. Consequently, viruses recruit host ribosomes to translate viral mRNAs, typically using virally encoded functions to seize control of cellular translation factors and the host signalling pathways that regulate their activity. This not only ensures that viral proteins will be produced, but also stifles innate host defences that are aimed at inhibiting the capacity of infected cells for protein synthesis. Remarkably, nearly every step of the translation process can be targeted by virally encoded functions. This Review discusses the diverse strategies that viruses use to subvert host protein synthesis functions and regulate mRNA translation in infected cells.


title: MERS-CoV spike protein: Targets for vaccines and therapeutics

text: Abstract The disease outbreak caused by Middle East respiratory syndrome coronavirus (MERS-CoV) is still ongoing in the Middle East. Over 1700 people have been infected since it was first reported in September 2012. Despite great efforts, licensed vaccines or therapeutics against MERS-CoV remain unavailable. The MERS-CoV spike (S) protein is an important viral antigen known to mediate host-receptor binding and virus entry, as well as induce robust humoral and cell-mediated responses in humans during infection. In this review, we highlight the importance of the S protein in the MERS-CoV life cycle, summarize recent advances in the development of vaccines and therapeutics based on the S protein, and discuss strategies that can be explored to develop new medical countermeasures against MERS-CoV.


title: Infectious Complications Following Solid Organ Transplantation

text: Infections in solid organ transplant recipients are complex and heterogeneous. This article reviews the clinical syndromes that will likely be encountered in the intensive care unit and helps to guide in the therapy and management of these patients.


title: Adaptation of novel H7N9 influenza A virus to human receptors

text: The emergence of the novel H7N9 influenza A virus (IAV) has caused global concerns about the ability of this virus to spread between humans. Analysis of the receptor-binding properties of this virus using a recombinant protein approach in combination with fetuin-binding, glycan array and human tissue-binding assays demonstrates increased binding of H7 to both α2-6 and α2-8 sialosides as well as reduced binding to α2-3-linked SIAs compared to a closely related avian H7N9 virus from 2008. These differences could be attributed to substitutions Q226L and G186V. Analysis of the enzymatic activity of the neuraminidase N9 protein indicated a reduced sialidase activity, consistent with the reduced binding of H7 to α2-3 sialosides. However, the novel H7N9 virus still preferred binding to α2-3- over α2-6-linked SIAs and was not able to efficiently bind to epithelial cells of human trachea in contrast to seasonal IAV, consistent with its limited human-to-human transmission.


title: Analysis on Novel Coronavirus (COVID-19) Using Machine Learning Methods

text: In this paper, we are working on a pandemic of novel coronavirus (COVID-19). COVID-19 is an infectious disease, it creates severe damage in the lungs. COVID-19 causes illness in humans and has killed many people in the entire world. However, this virus is reported as a pandemic by the World Health Organization (WHO) and all countries are trying to control and lockdown all places. The main objective of this work is to solve the five different tasks such as I) Predicting the spread of coronavirus across regions. II) Analyzing the growth rates and the types of mitigation across countries. III) Predicting how the epidemic will end. IV) Analyzing the transmission rate of the virus. V) Correlating the coronavirus and weather conditions. The advantage of doing these tasks to minimize the virus spread by various mitigation, how well the mitigations are working, how many cases have been prevented by this mitigations, an idea about the number of patients that will recover from the infection with old medication, understand how much time will it take to for this pandemic to end, we will be able to understand and analyze how fast or slow the virus is spreading among regions and the infected patient to reduce the spread based clear understanding of the correlation between the spread and weather conditions. In this paper, we propose a novel Support Vector Regression method to analysis five different tasks related to novel coronavirus. In this work, instead of simple regression line we use the supported vectors also to get better classification accuracy. Our approach is evaluated and compared with other well-known regression models on standard available datasets. The promising results demonstrate its superiority in both efficiency and accuracy.


title: Clinical update on COVID‐19 in pregnancy: A review article

text: The data pertaining to the COVID‐19 pandemic has been rapidly evolving since the first confirmed case in December 2019. This review article presents a comprehensive analysis of the current data in relation to COVID‐19 and its effect on pregnant women, including symptoms, disease severity and the risk of vertical transmission. We also review the recommended management of pregnant women with suspected or confirmed COVID‐19 and the various pharmacological agents that are being investigated and may have a role in the treatment of this disease. At present, it does not appear that pregnant women are at increased risk of severe infection than the general population, although there are vulnerable groups within both the pregnant and nonpregnant populations, and clinicians should be cognizant of these high‐risk groups and manage them accordingly. Approximately 85% of women will experience mild disease, 10% more severe disease and 5% critical disease. The most common reported symptoms are fever, cough, shortness of breath and diarrhea. Neither vaginal delivery nor cesarean section confers additional risks, and there is minimal risk of vertical transmission to the neonate from either mode of delivery. We acknowledge that the true effect of the virus on both maternal and fetal morbidity and mortality will only be evident over time. We also discuss the impact of social isolation can have on the mental health and well‐being of both patients and colleagues, and as clinicians, we must be mindful of this and offer support as necessary.


title: Possible role of highly activated mucosal NK cells against viral respiratory infections in children undergoing haematopoietic stem cell transplantation

text: Infection is the leading cause of non-relapse-related mortality after allogeneic haematopoietic stem cell transplantation (HSCT). Altered functions of immune cells in nasal secretions may influence post HSCT susceptibility to viral respiratory infections. In this prospective study, we determined T and NK cell numbers together with NK activation status in nasopharyngeal aspirates (NPA) in HSCT recipients and healthy controls using multiparametric flow cytometry. We also determined by polymerase chain reaction (PCR) the presence of 16 respiratory viruses. Samples were collected pre-HSCT, at day 0, +10, +20 and +30 after HSCT. Peripheral blood (PB) was also analyzed to determine T and NK cell numbers. A total of 27 pediatric HSCT recipients were enrolled and 16 of them had at least one viral detection (60%). Rhinovirus was the most frequent pathogen (84% of positive NPAs). NPAs of patients contained fewer T and NK cells compared to healthy controls (p = 0.0132 and p = 0.120, respectively). Viral PCR + patients showed higher NK cell number in their NPAs. The activating receptors repertoire expressed by NK cells was also higher in NPA samples, especially NKp44 and NKp46. Our study supports NK cells relevance for the immune defense against respiratory viruses in HSCT recipients.


title: Influenza in the neonatal intensive care unit

text: Influenza has historically been an uncommon illness in the newborn period, although epidemic outbreaks in neonatal intensive care units have been described. There is currently significant concern about the possibility of a new pandemic of influenza in the near future. During a pandemic neonates are likely to be exposed, with significant illness more likely in pre-term newborns due to reduced levels of passively transferred protective maternal antibodies. While newer therapies have been shown to be effective in reducing the severity of illness in adults and children, such therapies are untried in neonates. Supportive care and measures to contain and prevent spread of infection may well be the most important measures in the event of a neonate acquiring influenza, including the avian variety.


title: Targeting Cytokine Storm to Manage Patients with COVID-19: A Mini-Review

text: Abstract Corona Virus Disease 2019 (COVID-19) pandemic is rapidly spreading all over the world. Excessive immune responses trigger life-threatening cytokine release syndrome (CRS) which can result in overproduction of pro-inflammatory cytokines including tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and IL-1β with different pro-inflammatory roles. Anecdotal evidence suggests that the modulation of systemic immune responses may have a potential role in the treatment of patients with COVID-19. Given the importance of the issue and the lack of therapeutic treatment or vaccine; anti-cytokine therapy such as IL-6, TNFα and IL-1 antagonists have been suggested for the alleviation of hyper-inflammation status in these patients. In this mini-review, we addressed the inflammatory pathways of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its relationship with the host cytokine storm. Furthermore, the proposed therapeutic options to reverse hyper-inflammation in infected patients were mentioned.


title: Severe acute respiratory distress syndrome (ARDS) induced by human adenovirus B21: Report on 2 cases and literature review

text: Abstract Severe pneumonia and ARDS caused by human adenovirus B21 infections (HAdV-B21) is a rare, but a devastating disease with rapid progression to multiorgan failure and death. However, only a few cases were reported so far. Infections appear associated with increased disease severity and higher mortality in infected critically ill patients. Possible factors contributing to infection are underlying psychiatric disease resulting in institutionalization of respective patients, and polytoxicomania. Controlled data on the therapy of severe adenovirus infections are lacking and remains experimental. In conclusion, data on HAdV-B21 infections causing severe pneumonia or ARDS are scarce. Controlled clinical trials on the therapy of adenovirus pneumonia are non existent and thus there is no established therapy so far. ICU physicians should be aware of this potentially devastating disease and further studies are needed.


title: A Serpin Shapes the Extracellular Environment to Prevent Influenza A Virus Maturation

text: Interferon-stimulated genes (ISGs) act in concert to provide a tight barrier against viruses. Recent studies have shed light on the contribution of individual ISG effectors to the antiviral state, but most have examined those acting on early, intracellular stages of the viral life cycle. Here, we applied an image-based screen to identify ISGs inhibiting late stages of influenza A virus (IAV) infection. We unraveled a directly antiviral function for the gene SERPINE1, encoding plasminogen activator inhibitor 1 (PAI-1). By targeting extracellular airway proteases, PAI-1 inhibits IAV glycoprotein cleavage, thereby reducing infectivity of progeny viruses. This was biologically relevant for IAV restriction in vivo. Further, partial PAI-1 deficiency, attributable to a polymorphism in human SERPINE1, conferred increased susceptibility to IAV in vitro. Together, our findings reveal that manipulating the extracellular environment to inhibit the last step in a virus life cycle is an important mechanism of the antiviral response.


title: Impact of the 2009 H1N1 Pandemic on Age-Specific Epidemic Curves of Other Respiratory Viruses: A Comparison of Pre-Pandemic, Pandemic and Post-Pandemic Periods in a Subtropical City

text: BACKGROUND: The 2009 H1N1 influenza pandemic caused offseason peaks in temperate regions but coincided with the summer epidemic of seasonal influenza and other common respiratory viruses in subtropical Hong Kong. This study was aimed to investigate the impact of the pandemic on age-specific epidemic curves of other respiratory viruses. METHODS: Weekly laboratory-confirmed cases of influenza A (subtypes seasonal A(H1N1), A(H3N2), pandemic virus A(H1N1)pdm09), influenza B, respiratory syncytial virus (RSV), adenovirus and parainfluenza were obtained from 2004 to 2013. Age-specific epidemic curves of viruses other than A(H1N1)pdm09 were compared between the pre-pandemic (May 2004 – April 2009), pandemic (May 2009 – April 2010) and post-pandemic periods (May 2010 – April 2013). RESULTS: There were two peaks of A(H1N1)pdm09 in Hong Kong, the first in September 2009 and the second in February 2011. The infection rate was found highest in young children in both waves, but markedly fewer cases in school children were recorded in the second wave than in the first wave. Positive proportions of viruses other than A(H1N1)pdm09 markedly decreased in all age groups during the first pandemic wave. After the first wave of the pandemic, the positive proportion of A(H3N2) increased, but those of B and RSV remained slightly lower than their pre-pandemic proportions. Changes in seasonal pattern and epidemic peak time were also observed, but inconsistent across virus-age groups. CONCLUSION: Our findings provide some evidence that age distribution, seasonal pattern and peak time of other respiratory viruses have changed since the pandemic. These changes could be the result of immune interference and changing health seeking behavior, but the mechanism behind still needs further investigations.


title: Metal complexes driven from Schiff bases and semicarbazones for biomedical and allied applications: a review

text: Abstract Schiff bases are versatile organic compounds which are widely used and synthesized by condensation reaction of different amino compound with aldehydes or ketones known as imine. Schiff base ligands are considered as privileged ligands as they are simply synthesized by condensation. They show broad range of application in medicine, pharmacy, coordination chemistry, biological activities, industries, food packages, dyes, and polymer and also used as an O2 detector. Semicarbazone is an imine derivative which is derived from condensation of semicarbazide and suitable aldehyde and ketone. Imine ligand–containing transition metal complexes such as copper, zinc, and cadmium have shown to be excellent precursors for synthesis of metal or metal chalcogenide nanoparticles. In recent years, the researchers have attracted enormous attention toward Schiff bases, semicarbazones, thiosemicarbazones, and their metal complexes owing to numerous applications in pharmacology such as antiviral, antifungal, antimicrobial, antimalarial, antituberculosis, anticancer, anti-HIV, catalytic application in oxidation of organic compounds, and nanotechnology. In this review, we summarize the synthesis, structural, biological, and catalytic application of Schiff bases as well as their metal complexes.


title: The World Goes Bats: Living Longer and Tolerating Viruses

text: For centuries, people believed that bats possessed sinister powers. Bats are thought to be ancestral hosts to many deadly viruses affecting humans including Ebola, rabies, and most recently SARS-CoV-2 coronavirus. However, bats themselves tolerate these viruses without ill effects. The second power that bats have is their longevity. Bats live much longer than similar-sized land mammals. Here we review how bats’ ability to control inflammation may be contributing to their longevity. The underlying mechanisms may hold clues to developing new treatments for age-related diseases. Now may be the time to use science to exploit the secret powers of bats for human benefit.


COVID-19: a complex multi-system disorder


title: Cerebrospinal fluid chemokine patterns in children with enterovirus 71-related encephalitis

text: Enterovirus 71 (EV71) is a major pathogen that causes hand, foot and mouth disease (HFMD) as well as neurological complications, such as encephalitis. The chemokines involved in the migration of leukocytes have increasingly been implicated in infectious diseases of the central nervous system. Few studies have evaluated the levels of chemokines in HMFD children with EV71-related encephalitis. In the present study, we evaluated the cerebrospinal fluid (CSF) levels of the chemokines IL-8, RANTES, MIG, MCP-1 and IP-10 in 99 children with EV71-related encephalitis and 22 children with febrile convulsion (FC). We found that the concentrations of IL-8, RANTES, MIG and IP-10 were significantly higher in HFMD children with encephalitis compared to patients with FC. Additionally, these four chemokines were dramatically reduced during convalescence. Inversely, the level of MCP-1 was lower in encephalitis patients than FC patients and was not significantly reduced during convalescence. Additionally, MIG was strongly correlated with IP-10 in encephalitis patients. Furthermore, the area under the ROC curve (AUC) of CSF MIG and IP-10 in distinguishing encephalitis from FC were 0.869 and 0.876, and the corresponding sensitivities/specificities were 67.7%/100.0% and 67.7%/95.5%, respectively. In conclusion, our results indicate that chemokines play important roles in the pathogenesis of EV71 infection.


title: Use of dialdehyde starch treated filters for protection against airborne viruses

text: Abstract In the event of a pandemic, the general public would use filters as protective devices. However, most commercial filters only remove airborne viruses physically without inactivating them, allowing reproduction on the surface and yielding the mask as a fomite. The objective of this study was to investigate the inactivation performance of dialdehyde starch (DAS) treated filters against airborne viruses. The viable removal efficiency by and relative survivability on the biocidal filters prepared with dialdehyde starch compared to untreated filters were investigated using MS2 bacteriophage at high relative humidity (80–90%) and room temperature. Experimental results showed no significant difference in viable removal efficiency and pressure drop between the treated and untreated filters for polypropylene filtering facepiece respirators. The pressure drop of DAS treated cellulose filters significantly decreased although there was no significant change in viable removal efficiency; the combination of these two factors resulted in an increase of filter quality. All biocidal filters showed a significantly lower relative survivability than untreated filters, and the relative survivability decreased as the concentration of DAS increased. The biocidal filter treated with 4% DAS presented an average of 30% survivability compared to the baseline of untreated filters. The results demonstrate that dialdehyde starch can be incorporated onto filters to provide an effective means for inactivating MS2 viruses through surface contact.


title: Chapter 15 Antiviral Vaccines: Challenges and Advances

text: Abstract Vaccination is the most effective means of preventing and controlling viral infections. The eradication of smallpox and the significant progress made toward polio eradication are clear examples of the great impact of antiviral vaccines. However, viral infections remain a major public health threat and a significant cause of death. Most of the antiviral vaccines introduced over the past century were empirically developed. Poliomyelitis, measles, mumps, and rubella are examples of diseases that are now largely controlled thanks to these empirically developed vaccines. However, there is a growing list of viral pathogens against which effective vaccines are yet to be developed. Recent technological advances will potentially provide us with new platforms that could be harnessed to develop vaccines against emerging and reemerging viral pathogens.


title: Coronaviruses and people with intellectual disability: an exploratory data analysis

text: BACKGROUND: Corona virus disease 2019 (COVID‐19) has been announced as a new coronavirus disease by the World Health Organization. At the time of writing this article (April 2020), the world is drastically influenced by the COVID‐19. Recently, the COVID‐19 Open Research Dataset (CORD‐19) was published. For researchers on ID such as ourselves, it is of key interest to learn whether this open research dataset may be used to investigate the virus and its consequences for people with an ID. METHODS: From CORD‐19, we identified full‐text articles containing terms related to the ID care and applied a text mining technique, specifically the term frequency–inverse document frequency analysis in combination with K‐means clustering. RESULTS: Two hundred fifty‐nine articles contained one or more of our specified terms related to ID. We were able to cluster these articles related to ID into five clusters on different topics, namely: mental health, viral diseases, diagnoses and treatments, maternal care and paediatrics, and genetics. CONCLUSION: The CORD‐19 open research dataset consists of valuable information about not only COVID‐19 disease but also ID and the relationship between them. We suggest researchers investigate literature‐based discovery approaches on the CORD‐19 and develop a new dataset that addresses the intersection of these two fields for further research.


title: Functional Protein Microarray Technology

text: Functional protein microarrays are emerging as a promising new tool for large-scale and high-throughput studies. In this article, we will review their applications in basic proteomics research, where various types of assays have been developed to probe binding activities to other biomolecules, such as proteins, DNA, RNA, small molecules, and glycans. We will also report recent progress of using functional protein microarrays in profiling protein posttranslational modifications, including phosphorylation, ubiquitylation, acetylation, and nitrosylation. Finally, we will discuss potential of functional protein microarrays in biomarker identification and clinical diagnostics. We strongly believe that functional protein microarrays will soon become an indispensible and invaluable tool in proteomics research and systems biology.


title: First Human Rabies Case in French Guiana, 2008: Epidemiological Investigation and Control

text: BACKGROUND: Until 2008, human rabies had never been reported in French Guiana. On 28 May 2008, the French National Reference Center for Rabies (Institut Pasteur, Paris) confirmed the rabies diagnosis, based on hemi-nested polymerase chain reaction on skin biopsy and saliva specimens from a Guianan, who had never travelled overseas and died in Cayenne after presenting clinically typical meningoencephalitis. METHODOLOGY/PRINCIPAL FINDINGS: Molecular typing of the virus identified a Lyssavirus (Rabies virus species), closely related to those circulating in hematophagous bats (mainly Desmodus rotundus) in Latin America. A multidisciplinary Crisis Unit was activated. Its objectives were to implement an epidemiological investigation and a veterinary survey, to provide control measures and establish a communications program. The origin of the contamination was not formally established, but was probably linked to a bat bite based on the virus type isolated. After confirming exposure of 90 persons, they were vaccinated against rabies: 42 from the case's entourage and 48 healthcare workers. To handle that emergence and the local population's increased demand to be vaccinated, a specific communications program was established using several media: television, newspaper, radio. CONCLUSION/SIGNIFICANCE: This episode, occurring in the context of a Department far from continental France, strongly affected the local population, healthcare workers and authorities, and the management team faced intense pressure. This observation confirms that the risk of contracting rabies in French Guiana is real, with consequences for population educational program, control measures, medical diagnosis and post-exposure prophylaxis.


title: Antiviral Lead Compounds from Marine Sponges

text: Marine sponges are currently one of the richest sources of pharmacologically active compounds found in the marine environment. These bioactive molecules are often secondary metabolites, whose main function is to enable and/or modulate cellular communication and defense. They are usually produced by functional enzyme clusters in sponges and/or their associated symbiotic microorganisms. Natural product lead compounds from sponges have often been found to be promising pharmaceutical agents. Several of them have successfully been approved as antiviral agents for clinical use or have been advanced to the late stages of clinical trials. Most of these drugs are used for the treatment of human immunodeficiency virus (HIV) and herpes simplex virus (HSV). The most important antiviral lead of marine origin reported thus far is nucleoside Ara-A (vidarabine) isolated from sponge Tethya crypta. It inhibits viral DNA polymerase and DNA synthesis of herpes, vaccinica and varicella zoster viruses. However due to the discovery of new types of viruses and emergence of drug resistant strains, it is necessary to develop new antiviral lead compounds continuously. Several sponge derived antiviral lead compounds which are hopedto be developed as future drugs are discussed in this review. Supply problems are usually the major bottleneck to the development of these compounds as drugs during clinical trials. However advances in the field of metagenomics and high throughput microbial cultivation has raised the possibility that these techniques could lead to the cost-effective large scale production of such compounds. Perspectives on biotechnological methods with respect to marine drug development are also discussed.


title: Living on the edge

text: Abstract This study examines the role that tourism plays for residents of Tap Mun, an island off the northeast coast of Hong Kong which is in its last stages of decline. Once it was a vibrant fishing and farming community, but today its economy is reliant on tourism. The majority of enterprises provide only a marginal income and most workers are seasonal. Yet, this business provides the residents with the economic rationale to remain on the island, and in doing so, enables them to retain their existing social networks, sense of place, and connection to their ancestral homes. Thus, the net social benefits of pursuing subsistence-level tourism outweigh the limited economic gains.


Pathogen-Inaktivierungssysteme für Thrombozytenkonzentrate: Stellungnahme


title: Evaluation of fixed sources of variation and estimation of genetic parameters for incidence of bovine respiratory disease in preweaned calves and feedlot cattle(2)

text: The primary objective of this study was to estimate variance components and heritability of bovine respiratory disease (BRD) incidence in beef calves before weaning and during the finishing phase. The second objective was to investigate the impact of BRD incidence and treatment frequency on performance and carcass traits. Bovine respiratory disease is the biggest and most costly health challenge facing the cattle industry. The 2 populations used consisted of 1,519 preweaned calves and 3,277 head of feedlot cattle. The incidence rate of BRD in preweaned calves was 11.39%, and among treated cattle, 82.1% were treated once, 13.9% were treated twice, and 4.0% were treated 3 times or more. The incidence of BRD (P = 0.35) and the number of treatments (P = 0.77) had no significant effect on weaning BW. Heritability estimates of the entire preweaned population for BRD resistance and number of treatments were 0.11 ± 0.06 and 0.08 ± 0.05, respectively. The genetic correlation estimates for BRD incidence with weaning BW and birth BW were low (−0.02 ± 0.32 and 0.07 ± 0.27, respectively). The same estimate for the number of BRD treatments with weaning BW and birth BW was 0.25 ± 0.35 and 0.30 ± 0.27, respectively. The observed BRD incidence rate for feedlot cattle was observed at 9.43%. Incidence of BRD significantly (P < 0.01) decreased overall and acclimation ADG by 0.06 ± 0.01 kg/d and 0.28 ± 0.03 kg/d, respectively. Carcass traits were also significantly (P < 0.05) affected by BRD incidence; untreated cattle had a 9.1 ± 1.7-kg heavier HCW. Results were similar in the analysis of treatment frequency. The heritability estimate of BRD incidence and the number of treatments were 0.07 ± 0.04 and 0.02 ± 0.03, respectively. Estimates of genetic correlations of BRD incidence with production traits were −0.63 ± 0.22 for acclimation ADG, −0.04 ± 0.23 for on-test ADG, −0.31 ± 0.21 for overall ADG, −0.39 ± 0.21 for final BW, −0.22 ± 0.22 for HCW, −0.03 ± 0.22 for LM area, 0.24 ± 0.25 for fat, and −0.43 ± 0.20 for marbling score. Similar results for the number of treatments and production traits were −1.00 ± 0.68 for acclimation ADG, −0.04 ± 0.39 for on-test ADG, −0.47 ± 0.41 for overall ADG, −0.66 ± 0.40 for final BW, −0.58 ± 0.45 for HCW, −0.12 ± 0.38 for LM area, 0.42 ± 0.50 for fat, and −0.32 ± 0.37 for marbling score. Because of the high economic cost associated with BRD incidence, even these modest estimates for heritability of BRD resistance should be considered for incorporation into beef cattle breeding programs.


title: Squalene-based multidrug nanoparticles for improved mitigation of uncontrolled inflammation in rodents

text: Uncontrolled inflammatory processes are at the root of numerous pathologies. Most recently, studies on confirmed COVID-19 cases have suggested that mortality might be due to virally induced hyperinflammation. Uncontrolled pro-inflammatory states are often driven by continuous positive feedback loops between pro-inflammatory signaling and oxidative stress, which cannot be resolved in a targeted manner. Here, we report on the development of multidrug nanoparticles for the mitigation of uncontrolled inflammation. The nanoparticles are made by conjugating squalene, a natural lipid, to adenosine, an endogenous immunomodulator, and then encapsulating α-tocopherol, as antioxidant. This resulted in high drug loading, biocompatible, multidrug nanoparticles. By exploiting the endothelial dysfunction at sites of acute inflammation, these multidrug nanoparticles delivered the therapeutic agents in a targeted manner, conferring survival advantage to treated animals in models of endotoxemia. Selectively delivering adenosine and antioxidants together could serve as a novel therapeutic approach for safe treatment of acute paradoxal inflammation.


title: Recovery from Mouse Hepatitis Virus Infection Depends on Recruitment of CD8+ Cells Rather Than Activation of Intrahepatic CD4+αβ−TCRinter or NK-T Cells

text: Abstract Mouse hepatitis virus (MHV) provides an excellent animal model for the study of the immunopathological mechanisms involved in hepatic viral diseases. We previously generated an attenuated viral variant, YAC-MHV3, which induces a subclinical disease and recovery within 15 days. In contrast, the L2-MHV3 strain induces the development of a fulminant hepatitis, leading to death within 3 days. In this paper, we document intrahepatic and splenic T cell subpopulations involved in the hepatitis process and viral elimination identified in attenuated or pathogenic MHV3-infected C57BL/6 mice. Percentages of intrahepatic CD4+ cells decreased in attenuated YAC-MHV3-infected mice, while they increased in mice infected with pathogenic L2-MHV3, compared with uninfected animals. Moreover, in YAC-MHV3-infected mice, the percentages of intrahepatic CD8+ cells slightly decreased at 24 h pi, then increased until 15 days pi. In contrast, the CD4/CD8 ratios of splenic lymphoid subpopulations increased in the first days of infection and returned to normal values at 15 days pi. Intrahepatic NK1.1+αβ − TCRinter cells decreased in both virally infected groups of mice, while CD4+αβ − TCRinter LFA-1high cells increased in L2-MHV3-infected mice, in contrast with what was seen in YAC-MHV3-infected mice. However, these cells became anergic following Con A or PHA stimulation. Ex vivo studies showed that only the intrahepatic CD8+ cells that were increased in YAC-MHV3-infected mice could be stimulated by lectins. In addition, in vitro viral infections revealed that L2-MHV3 viral infection led to an increase of intrahepatic CD4+αβ − TCRinter cells in the absence of CD8+ cells only. These results indicate that the attenuated phenotype of the YAC-MHV3 virus is related to two different mechanisms: the first involves no increase of intrahepatic CD4+αβ − TCRinter or NK-T cells, while the second favors the recruitment and activation of CD8+ cells in liver. The results are discussed in relation to the integrity of intrahepatic immune tolerance mechanisms and immune-mediated viral elimination.


title: News at a glance.

text: In science news around the world, the World Health Organization cautions governments against introducing "immunity passports that declare people immune to COVID-19 after they test positive for antibodies to the new coronavirus;the group notes a lack of evidence that people with such antibodies are protected from a second infection The U S National Institutes of Health ends a long-standing grant for research on how viruses spread from bats and other wildlife to humans after conservative politicians criticize the project's ties to a lab in Wuhan, China, that they blame, without evidence, for being the source of the COVID-19 virus The U S Food and Drug Administration advises physicians not to prescribe the antimalarial drugs chloroquine and hydroxychloroquine for COVID-19 patients outside of hospitals or clinical trials, citing safety concerns The U S Supreme Court gives hydrologic science top billing in a closely watched ruling affirming that the federal Clean Water Act covers groundwater pollution Donald Kennedy, former editor-in-chief of Science, dies at the age of 88 from COVID-19


title: Controlled, double-blind, randomized trial to assess the efficacy and safety of hydroxychloroquine chemoprophylaxis in SARS CoV2 infection in healthcare personnel in the hospital setting: A structured summary of a study protocol for a randomised controlled trial

text: BACKGROUND: SARS-CoV-2 infection presents a high transmission in the group of health professionals in Spain (12-15% infected). Currently there is no accepted chemoprophylaxis but hydroxychloroquine (HDQ) is known to inhibit the coronavirus in vitro. Our hypothesis is that oral administration of hydroxychloroquine to healthcare professionals can reduce the incidence and prevalence of infection as well as its severity in this group. METHODS: Design: Prospective, single center, double blind, randomised, controlled trial (RCT). Participants: Adult health-care professionals (18-65 years) working in areas of high exposure and high risk of transmission of SARS-COV-2 (COVID areas, Intensive Care Unit –ICUs-, Emergency, Anesthesia and all those performing aerosol-generating procedures) will be included. Exclusion criteria include previous infection with SARS CoV2 (positive SARS-CoV-2 PCR or IgG serology), pregnancy or lactation, any contraindication to hydroxychloroquine or evidence of unstable or clinically significant systemic disease. INTERVENTIONS: Patients will be randomized (1:1) to receive once-daily oral Hydroxychloroquine 200mg for two months (HC group) or placebo (P group) in addition to the protective measures appropriate to the level of exposure established by the hospital. A serological evaluation will be carried out every 15 days with PCR in case of seroconversion, symptoms or risk exposure. Primary outcome is the percentage of subjects presenting infection (seroconversion and/or PCR +ve) by the SARS-Cov-2 virus during the observation period. Additionally, both the percentage of subjects in each group presenting Pneumonia with severity criteria (Curb 65 ≥2) and that of subjects requiring admission to ICU will be determined. DISCUSSION: While awaiting a vaccine, hygiene measures, social distancing and personal protective equipment are the only primary prophylaxis measures against SARS-CoV-2, but they have not been sufficient to protect our healthcare professionals. Some evidence of the in vitro efficacy of hydroxychloroquine against this virus is known, along with some clinical data that would support the study of this drug in the chemoprophylaxis of infection. However, there are still no data from controlled clinical trials in this regard. If our hypothesis is confirmed, hydroxychloroquine can help professionals fight this infection with more guarantees. PARTICIPANTS: This is a single-center study that will be carried out at the Marqués de Valdecilla University Hospital. 450 health professionals working at the Hospital Universitario Marqués de Valdecilla in areas of high exposure and high risk of transmission of SARS COV2 (COVID hospital areas, Intensive Care Unit, Emergency, Anesthesia and all those performing aerosol-generating procedures) will be included. Inclusion criteria: 1) Health professionals aged between 18 and 65 years (inclusive) at the time of the first screening visit; 2) They must provide signed written informed consent and agree to comply with the study protocol; 3) Active work in high exposure areas during the last two weeks and during the following weeks. Exclusion criteria: 1) Previous infection with SARS CoV2 (positive coronavirus PCR or positive serology with SARS Cov2 negative PCR and absence of symptoms); 2) Current treatment with hydroxychloroquine or chloroquine; 3) Hypersensitivity, allergy or any contraindication for taking hydroxychloroquine, in the technical sheet; 4) Previous or current treatment with tamoxifen or raloxifene; 5) Previous eye disease, especially maculopathy; 6) Known heart failure (Grade III to IV of the New York Heart Association classification) or prolonged QTc; 7) Any type of cancer (except basal cell) in the last 5 years; 6) Refusal to give informed consent; 8) Evidence of any other unstable or clinically significant untreated immune, endocrine, hematological, gastrointestinal, neurological, neoplastic or psychiatric illness; 9) Antibodies positive for the human immunodeficiency virus; 10) Significant kidney or liver disease; 11) Pregnancy or lactation. INTERVENTION AND COMPARATOR: 1. Intervention: (n = 225): One 200 mg hydroxychloroquine sulfate coated tablet once daily for two months. 2. Comparator (control group) (n = 225): One hydroxychloroquine placebo tablet (identical to that of the drug) once daily for two months. MAIN OUTCOMES: number and percentage of healthcare personnel presenting symptomatic and asymptomatic infection (see “Diagnosis of SARS CoV2 infection” below) by the SARS-Cov2 virus during the study observation period (8 weeks) in both treatment arms; number and percentage of healthcare personnel in each group presenting with Pneumonia with severity criteria (Curb 65 ≥2) and number and percentage of healthcare personnel requiring admission to the Intensive Care Unit (ICU) in both treatment arms. DIAGNOSIS OF SARS COV2 INFECTION: Determination of IgA, IgM and IgG type antibodies against SARS-CoV-2 using the Anti-SARS-CoV-2 ELISA kit (EUROIMMUN Medizinische Labordiagnostika AG, Germany) every two weeks. In cases of seroconversion, a SARS-CoV-2 PCR will be performed to rule out / confirm an active infection (RT-PCR in One Step: RT performed with mastermix (Takara) and IDT probes, following protocol published and validated by the CDC Evaluation of COVID-19 in case of SARS-CoV-2 infection RANDOMISATION: Participants will be allocated to intervention and comparator groups according to a balanced randomization scheme (1: 1). The assignment will be made through a computer-generated numeric sequence for all participants BLINDING (MASKING): Both participants and investigators responsible for recruiting and monitoring participants will be blind to the assigned arm. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Taking into account the current high prevalence of infection in healthcare personnel in Spain (up to 15%), to detect a difference equal to or greater than 8% in the percentage estimates through a two-tailed 95% CI, with a statistical power of 80% and a dropout rate of 5%, a total of 450 participants will need to be included (250 in each arm). TRIAL STATUS: The protocol approved by the health authorities in Spain (Spanish Agency for Medicines and Health Products “AEMPS”) and the Ethics and Research Committee of Cantabria (CEIm Cantabria) corresponds to version 1.1 of April 2, 2020. Currently, recruitment has not yet started, with the start scheduled for the second week of May 2020. TRIAL REGISTRATION: Eudra CT number: 2020-001704-42 (Registered on 29 March 2020) FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


title: Chapter 7 Scientific Advances in the Diagnosis of Emerging and Reemerging Viral Human Pathogens

text: Abstract Despite scientific advances, the diagnosis of infectious diseases is primarily possible through vaccination and later by antibiotics. Emerging and reemerging pathologies are still considered to be dangerous to humanity because of the unique nature of these diseases: it is the encounter between two living organisms that have coexisted for millions of years within the people on the same planet without being previously recognized. These infectious agents, such as bacteria, viruses, fungi, or parasites, pose no threat to humans. In fact, only a few hundred are able to inflict damage to the human host. In addition, the spectrum of human disease caused by a particular pathogen varies considerably depending on the factors related to the ecological agent, the host, and the infectious agents. Several emerging or reemerging infectious agents are organisms that could be used in biological control. The differentiation of a natural epidemic from a bioterrorian event is based on several epidemiological indices as well as on the molecular characterization of the pathogen(s) involved. The role of pathologists is indeed very important. It is in this context that this chapter aims to discuss the various scientific advances, particularly molecular, in terms of diagnosis of these diseases; the new discoveries in the role of nanotechnologies and nanobiosensors; and also the implication of biomarkers, especially microRNAs (miRNAs), since it was reported that a single miRNA has the ultimate capacity to target multiple genes simultaneously. In a viral infection context, miRNAs have been connected with the interplay between host and pathogen and occupy a major role in the host–parasite interaction and pathogenesis. It is in this context that various molecular and nanomethods for the detection of emerging viruses and experimental validation of miRNAs during quelling viruses target transcripts will be discussed in this chapter.


title: Bushmeat Hunting, Deforestation, and Prediction of Zoonotic Disease

text: Understanding the emergence of new zoonotic agents requires knowledge of pathogen biodiversity in wildlife, human-wildlife interactions, anthropogenic pressures on wildlife populations, and changes in society and human behavior. We discuss an interdisciplinary approach combining virology, wildlife biology, disease ecology, and anthropology that enables better understanding of how deforestation and associated hunting leads to the emergence of novel zoonotic pathogens.


title: Reverse transcription-PCR assays for the differentiation of various US porcine epidemic diarrhea virus strains

text: Abstract Concurrently, several porcine epidemic diarrhea virus (PEDV) variants are circulating in US swine farms, including the original US and the spike insertion-deletion (S-INDEL) strains. In this study, reverse transcription (RT)-PCR assays for the detection and differentiation of different US PEDV variants were developed based on the differences in the S1 domain of the spike (S) gene. This assay successfully differentiated three PEDV strains: PC22A (the original US virulent), Iowa106 (S-INDEL), and PC177 (S-197DEL) that was derived from cell culture adaptation and has a 197 amino acid-deletion in the S1 domain. The assays did not amplify the porcine deltacoronavirus OH-FD22 strain or transmissible gastroenteritis virus Miller strain. It is the first report on the development of RT-PCR assays allowing the detection and differentiation of all major types of US PEDV variants.


title: Nanoparticles for mucosal vaccine delivery

text: Mucosal surfaces represent important routes of entry into the human body for the majority of pathogens, and they constitute unique sites for targeted vaccine delivery. Nanoparticle-based drug delivery systems are emerging technologies for delivering and improving the efficacy of mucosal vaccines. Recent studies have provided new insights into formulation and delivery aspects of importance for the design of safe and efficacious mucosal subunit vaccines based on nanoparticles. These include novel nanomaterials, their physicochemical properties and formulation approaches, nanoparticle interaction with immune cells in the mucosa, and mucosal immunization and delivery strategies. Here, we present recent progress in the application of nanoparticle-based approaches for mucosal vaccine delivery and discuss future research challenges and opportunities in the field.


title: Prediction of the Number of Patients Infected with COVID-19 Based on Rolling Grey Verhulst Models

text: The outbreak of a novel coronavirus (SARS-CoV-2) has caused a large number of residents in China to be infected with a highly contagious pneumonia recently. Despite active control measures taken by the Chinese government, the number of infected patients is still increasing day by day. At present, the changing trend of the epidemic is attracting the attention of everyone. Based on data from 21 January to 20 February 2020, six rolling grey Verhulst models were built using 7-, 8- and 9-day data sequences to predict the daily growth trend of the number of patients confirmed with COVID-19 infection in China. The results show that these six models consistently predict the S-shaped change characteristics of the cumulative number of confirmed patients, and the daily growth decreased day by day after 4 February. The predicted results obtained by different models are very approximate, with very high prediction accuracy. In the training stage, the maximum and minimum mean absolute percentage errors (MAPEs) are 4.74% and 1.80%, respectively; in the testing stage, the maximum and minimum MAPEs are 4.72% and 1.65%, respectively. This indicates that the predicted results show high robustness. If the number of clinically diagnosed cases in Wuhan City, Hubei Province, China, where COVID-19 was first detected, is not counted from 12 February, the cumulative number of confirmed COVID-19 cases in China will reach a maximum of 60,364–61,327 during 17–22 March; otherwise, the cumulative number of confirmed cases in China will be 78,817–79,780.


title: Acute respiratory failure in immunocompromised adults

text: Summary Acute respiratory failure occurs in up to half of patients with haematological malignancies and 15% of those with solid tumours or solid organ transplantation. Mortality remains high. Factors associated with mortality include a need for invasive mechanical ventilation, organ dysfunction, older age, frailty or poor performance status, delayed intensive care unit admission, and acute respiratory failure due to an invasive fungal infection or unknown cause. In addition to appropriate antibacterial therapy, initial clinical management aims to restore oxygenation and predict the most probable cause based on variables related to the underlying disease, acute respiratory failure characteristics, and radiographic findings. The cause of acute respiratory failure must then be confirmed using the most efficient, least invasive, and safest diagnostic tests. In patients with acute respiratory failure of undetermined cause, a standardised diagnostic investigation should be done immediately at admission before deciding whether to perform more invasive diagnostic procedures or to start empirical treatments. Collaborative and multidisciplinary clinical and research networks are crucial to improve our understanding of disease pathogenesis and causation and to develop less invasive diagnostic strategies and more targeted treatment options.


title: M gene analysis of canine coronavirus strains detected in Korea

text: The purpose of this study was to investigate the genetic features of canine coronavirus (CCV) strains detected in Korea. M gene sequences obtained for isolates from 22 dogs with enteritis over a 5-year period were evaluated. Sequence comparison revealed that the 22 Korean CCV strains had an 87.2 to 100% nucleotide homology. Comparing to the typical reference CCV strains (type II), the nucleotide sequence of Korean strains had homology ranged from 86.3% to 98.3% (89.1% to 99.2% for the amino acid sequence) and 87.7% to 97.8% (92.4% to 100% for the amino acid sequence) when compared to FCoV-like CCV strains (type I). Three amino acid variations in the M gene were characteristic for the Korean CCV strains. Phylogenetic analysis demonstrated that the 22 Korean CCV strains belonged to four typical CCV clusters (i.e., a unique Korean CCV cluster, a type II and transmissible gastroenteritis virus cluster, an intermediate cluster between type I and II, and a type I cluster). This study was the first to identify genetic differences of the M gene from Korean CCV strains and provided a platform for molecular identification of different Korean CCV strains.


title: Arsenic intoxication: general aspects and chelating agents

text: Arsenic (As) is widely used in the modern industry, especially in the production of pesticides, herbicides, wood preservatives, and semiconductors. The sources of As such as contaminated water, air, soil, but also food, can cause serious human diseases. The complex mechanism of As toxicity in the human body is associated with the generation of free radicals and the induction of oxidative damage in the cell. One effective strategy in reducing the toxic effects of As is the usage of chelating agents, which provide the formation of inert chelator–metal complexes with their further excretion from the body. This review discusses different aspects of the use of metal chelators, alone or in combination, in the treatment of As poisoning. Consideration is given to the therapeutic effect of thiol chelators such as meso-2,3-dimercaptosuccinic acid, sodium 2,3-dimercapto-1-propanesulfonate, 2,3-dimercaptopropanol, penicillamine, ethylenediaminetetraacetic acid, and other recent agents against As toxicity. The review also considers the possible role of flavonoids, trace elements, and herbal drugs as promising natural chelating and detoxifying agents.


title: Synthesis and Antiviral Activity of Several N-Containing 5α-STEROIDS

text: A study of the antiviral activity of several new hydrazones and amines and amides of 5α-steroids that were synthesized by us earlier found highly and moderately active compounds. The structures of the synthesized compounds were proven using IR, PMR, (13)C NMR, and mass spectral data.


title: Coronavirus: cerveau prédictif et gestion de la terreur

text: Résumé Les maladies infectieuses émergentes comme le Covid-19 représentent une menace majeure pour la santé mondiale. Lorsqu'ils sont confrontés à de nouveaux agents pathogènes, les individus génèrent de nombreuses croyances à propos du phénomène épidémique. Plusieurs études ont montré que les comportements individuels de protection dépendent largement de ces croyances. En raison de l'absence de traitement et de vaccin contre ces pathogènes émergents, le lien entre ces croyances et ces comportements représente un enjeu crucial pour les politiques de santé publique. Dans les prémisses de la pandémie de Covid-19, plusieurs études préliminaires ont souligné un retard dans la perception du risque par les individus, participant à une difficulté à mettre en place les mesures de précaution nécessaires : les individus avaient tendance à sous-estimer les risques associés au virus, et donc aussi l’importance des mesures de prévention. Au cours du pic de la pandémie, la saillance de la menace et des informations associées au risque de mortalité pourraient ensuite avoir transformé la manière dont les individus génèrent leurs croyances, entrainant des bouleversements dans la façon dont ils comprennent le monde. Nous proposons ici d’explorer l’évolution des croyances et des comportements au cours de la crise du Covid-19 en nous appuyant sur la théorie du codage prédictif et la théorie de la gestion de la terreur, deux conceptions influentes en sciences cognitives et en psychologie sociale. Abstract Emerging infectious diseases like Covid-19 cause a major threat to global health. When confronted with new pathogens, individuals generate several beliefs about the epidemic phenomenon. Many studies have shown that individual protective behaviors largely depend on these beliefs. Due to the absence of treatment and vaccine against these emerging pathogens, the relation between these beliefs and these behaviors represents a crucial issue for public health policies. In the premises of the Covid-19 pandemic, several preliminary studies have highlighted a delay in the perception of risk by individuals, which potentially holds back the implementing of the necessary precautionary measures: people underestimated the risks associated with the virus, and therefore also the importance of complying with sanitary guidelines. During the peak of the pandemic, the salience of the threat and of the risk of mortality could then have transformed the way people generate their beliefs. This potentially leads to upheavals in the way they understand the world. Here, we propose to explore the evolution of beliefs and behaviors during the Covid-19 crisis, using the theory of predictive coding and the theory of terror management, two influential frameworks in cognitive science and in social psychology.


title: The Clinical Presentation and Outcomes of Children Infected with Newly Identified Respiratory Tract Viruses

text: Numerous emerging respiratory tract viruses have been identified as significant causes of acute upper and lower respiratory tract illness in children. Human metapneumovirus is a paramyxovirus discovered in 2001 in the Netherlands, with a seasonal occurrence and spectrum of clinical illness most similar to the closely related respiratory syncytial virus. Several new members of the corona-virus family have been identified, including the truly novel agent of severe acute respiratory syndrome and others that probably have been circulating undetected. Avian influenza strains have caused numerous outbreaks with high mortality, including children, and are potential causes of pandemic influenza. Several zoonotic paramyxoviruses, including Nipah and Hendra viruses, have emerged as occasional causes of sever outbreaks of respiratory tract illness in children and adults.


title: Overview of the 3rd isirv-Antiviral Group Conference – advances in clinical management

text: This review highlights the main points which emerged from the presentations and discussions at the 3rd isirv-Antiviral Group Conference - advances in clinical management. The conference covered emerging and potentially pandemic influenza viruses and discussed novel/pre-licensure therapeutics and currently approved antivirals and vaccines for the control of influenza. Current data on approved and novel treatments for non-influenza respiratory viruses such as MERS-CoV, respiratory syncytial virus (RSV) and rhinoviruses and the challenges of treating immunocompromised patients with respiratory infections was highlighted.


title: How do epidemiologists know how many people will get Covid‐19?

text: Patrick Ball explains the SIR model


title: Identification of New Pathogens in the Intraocular Fluid of Patients With Uveitis

text: Purpose To determine infectious causes in patients with uveitis of unknown origin by intraocular fluids analysis. Design Case-control study. Methods Ocular fluids from 139 patients suspected of infectious uveitis, but negative for herpes simplex virus, varicella-zoster virus, cytomegalovirus, and Toxoplasma gondii by polymerase chain reaction and/or antibody analysis in intraocular fluids, were assessed for the presence of 18 viruses and 3 bacteria by real-time polymerase chain reaction (PCR). The ocular fluids from 48 patients with uveitis of known etiology or with cataract were included as controls. Results Positive PCR results were found for Epstein-Barr virus, for rubella virus, and for human herpesvirus 6 each in 1 patient and for human parechovirus in 4 patients. Of the human parechovirus–positive patients, 1 was immunocompromised and had panuveitis. The other 3 patients were immunocompetent and had anterior uveitis, all with corneal involvement. Conclusions Human parechovirus might be associated with infectious (kerato)uveitis.


title: Eight Year Prospective Study of Adenoviruses Infections in Hospitalized Children. Comparison with Other Respiratory Viruses

text: Human adenovirus (HAdV) cause upper and lower respiratory tract infections. However, there are few large prospective studies focused on HAdVs acute infections requiring hospitalization. From 2005 to 2013 a prospective study was conducted on children admitted with acute respiratory infections. Specimens of nasopharyngeal aspirate were taken for virological study by PCR and clinical data was recorded. HAdV specimens were genotyped. Frequency and clinical course of HAdV infections were compared with RSV, rhinovirus (RV), human bocavirus (HBoV) and influenza in the same population. HAdV was detected in 403 cases of 2371 confirmed viral infections (17.2%) , of which 154 were single virus infections (38%). We genotyped 154 HAdVs. The most frequent genotypes were HAdV-3 (24%), HAdV-6 (21%), and HAdV-5 (20%). A total of 262 children had fever (64.9%); 194 suffered hypoxia (48%), and 147 presented infiltrate in chest x-rays (36.4%). The most frequent diagnoses were recurrent wheezing or asthma (51.7%), bronchiolitis (18.3 %), and pneumonia (11.9%), and 46 (11.4%) episodes required prolonged hospitalization (>7 days) due to the severity. Adenovirus single infections were compared with single infections of 598 RSV, 494 RV, 83 influenza and 78 HBoV. Significant clinical differences were found between HAdV, RSV and RV infections.


title: Perspectives of Australian policy-makers on the potential benefits and risks of technologically enhanced communicable disease surveillance – a modified Delphi survey

text: BACKGROUND: Event-based social media monitoring and pathogen whole genome sequencing (WGS) will enhance communicable disease surveillance research and systems. If linked electronically and scanned systematically, the information provided by these technologies could be mined to uncover new epidemiological patterns and associations much faster than traditional public health approaches. The benefits of earlier outbreak detection are significant, but implementation could be opposed in the absence of a social licence or if ethical and legal concerns are not addressed. METHODS: A three-phase mixed-method Delphi survey with Australian policy-makers, health practitioners and lawyers (n = 44) was conducted to explore areas of consensus and disagreement over (1) key policy and practical issues raised by the introduction of novel communicable disease surveillance programmes; and (2) the most significant and likely risks from using social media content and WGS technologies in epidemiological research and outbreak investigations. RESULTS: Panellists agreed that the integration of social media monitoring and WGS technologies into communicable disease surveillance systems raised significant issues, including impacts on personal privacy, medicolegal risks and the potential for unintended consequences. Notably, their concerns focused on how these technologies should be used, rather than how the data was collected. Panellists held that social media users should expect their posts to be monitored in the interests of public health, but using those platforms to contact identified individuals was controversial. The conditions of appropriate use of pathogen WGS in epidemiological research and investigations was also contentious. Key differences amongst participants included the necessity for consent before testing and data-linkage, thresholds for action, and the legal and ethical importance of harms to individuals and commercial entities. The erosion of public trust was seen as the most significant risk from the systematic use of these technologies. CONCLUSIONS: Enhancing communicable disease surveillance with social-media monitoring and pathogen WGS may cause controversy. The challenge is to determine and then codify how these technologies should be used such that the balance between individual risk and community benefit is widely accepted. Participants agreed that clear guidelines for appropriate use that address legal and ethical concerns need to be developed in consultation with relevant experts and the broader Australian public. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12961-019-0440-3) contains supplementary material, which is available to authorized users.


title: Psychoneuroimmunology goes East: Development of the PNIRS China affiliate and its expansion into PNIRS Asia-Pacific

text: Abstract The Psychoneuroimmunology Research Society (PNIRS) created an official Chinese regional affiliate in 2012, designated PNIRS China . Now, just eight years later, the program has been so successful in advancing the science of psychoneuroimmunology that it has expanded to the whole of Asia-Oceania. In 2017, PNIRS China became PNIRS Asia-Pacific . Between 2012 and 2019, this outreach affiliate of PNIRS organized seven symposia at major scientific meetings in China as well as nine others in Taiwan, Japan, South Korea, Australia and New Zealand. This paper summarizes the remarkable growth of PNIRS Asia-Pacific . Here, regional experts who have been instrumental in organizing these PNIRS Asia-Pacific symposia briefly review and share their views about the past, present and future state of psychoneuroimmunology research in China, Taiwan, Australia and Japan. The newest initiative of PNIRS Asia-Pacific is connecting Asia-Pacific laboratories with those in Western countries through a simple web-based registration system. These efforts not only contribute to the efforts of PNIRS to serve a truly global scientific society but also to answer the imperative call of increasing diversity in our science.


title: Porcine epidemic diarrhea virus (PEDV) co-infection induced chlamydial persistence/stress does not require viral replication

text: Chlamydiae may exist at the site of infection in an alternative replicative form, called the aberrant body (AB). ABs are produced during a viable but non-infectious developmental state termed “persistence” or “chlamydial stress.” As persistent/stressed chlamydiae: (i) may contribute to chronic inflammation observed in diseases like trachoma; and (ii) are more resistant to current anti-chlamydial drugs of choice, it is critical to better understand this developmental stage. We previously demonstrated that porcine epidemic diarrhea virus (PEDV) co-infection induced Chlamydia pecorum persistence/stress in culture. One critical characteristic of persistence/stress is that the chlamydiae remain viable and can reenter the normal developmental cycle when the stressor is removed. Thus, we hypothesized that PEDV-induced persistence would be reversible if viral replication was inhibited. Therefore, we performed time course experiments in which Vero cells were C. pecorum/PEDV infected in the presence of cycloheximide (CHX), which inhibits viral but not chlamydial protein synthesis. CHX-exposure inhibited PEDV replication, but did not inhibit induction of C. pecorum persistence at 24 h post-PEDV infection, as indicated by AB formation and reduced production of infectious EBs. Interestingly, production of infectious EBs resumed when CHX-exposed, co-infected cells were incubated 48–72 h post-PEDV co-infection. These data demonstrate that PEDV co-infection-induced chlamydial persistence/stress is reversible and suggest that this induction (i) does not require viral replication in host cells; and (ii) does not require de novo host or viral protein synthesis. These data also suggest that viral binding and/or entry may be required for this effect. Because the PEDV host cell receptor (CD13 or aminopeptidase N) stimulates cellular signaling pathways in the absence of PEDV infection, we suspect that PEDV co-infection might alter CD13 function and induce the chlamydiae to enter the persistent state.


title: Identification of a Potential Peptide Inhibitor of SARS-CoV-2 Targeting its Entry into the Host Cells

text: BACKGROUND AND OBJECTIVE: Coronavirus disease (COVID-19) is an ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the incessant spread of the disease with substantial morbidity and mortality rates, there is an urgent demand for effective therapeutics and vaccines to control and diminish this pandemic. A critical step in the crosstalk between the virus and the host cell is the binding of SARS-CoV-2 spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor present on the surface of the host cells. Hence, inhibition of this interaction could be a promising strategy to combat the SARS-CoV-2 infection. METHODS: Docking and Molecular Dynamics (MD) simulation studies revealed that designed peptide maintains their secondary structure and provide a highly specific and stable binding (blocking) to SARS-CoV-2. RESULTS: We have designed a novel peptide that could inhibit SARS-CoV-2 spike protein interaction with ACE2, thereby blocking the cellular entry of the virus. CONCLUSION: Our findings suggest that computationally developed inhibitory peptide may be developed as an anti-SARS-CoV-2 agent for the treatment of SARS-CoV-2 infection. We further plan to pursue the peptide in cell-based assays and eventually for clinical trials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40268-020-00312-5) contains supplementary material, which is available to authorized users.


title: Tracheostomy in a patient with COVID-19: a case report

text: Some of coronavirus disease 2019 (COVID-19) patients with prolonged ventilation may require tracheostomy, which is an aerosol-generating procedure and poses a significant risk of viral transmission. We report our experience of the management of a patient with COVID-19 who underwent surgical tracheostomy and describe several essential infection control principles. In our patient, on the 14th day after intubation, an open tracheostomy was carried out because of the prolonged tracheal intubation and unsuccessful extubation attempts. Meticulous attention was paid during surgery to decrease the infection risk. Appropriate protection, infection control and teamwork are essential to perform open tracheostomy in COVID-19 positive patients safely with minimal risks to healthcare professionals.


title: Proteomic analysis of primary duck hepatocytes infected with duck hepatitis B virus

text: BACKGROUND: Hepatitis B virus (HBV) is a major cause of liver infection in human. Because of the lack of an appropriate cell culture system for supporting HBV infection efficiently, the cellular and molecular mechanisms of hepadnavirus infection remain incompletely understood. Duck heptatitis B virus (DHBV) can naturally infect primary duck hepatocytes (PDHs) that provide valuable model systems for studying hepadnavirus infection in vitro. In this report, we explored global changes in cellular protein expression in DHBV infected PDHs by two-dimension gel electrophoresis (2-DE) combined with MALDI-TOF/TOF tandem mass spectrometry (MS/MS). RESULTS: The effects of hepadnavirus infection on hepatocytes were investigated in DHBV infected PDHs by the 2-DE analysis. Proteomic profile of PDHs infected with DHBV were analyzed at 24, 72 and 120 h post-infection by comparing with uninfected PDHs, and 75 differentially expressed protein spots were revealed by 2-DE analysis. Among the selected protein spots, 51 spots were identified corresponding to 42 proteins by MS/MS analysis; most of them were matched to orthologous proteins of Gallus gallus, Anas platyrhynchos or other avian species, including alpha-enolase, lamin A, aconitase 2, cofilin-2 and annexin A2, etc. The down-regulated expression of beta-actin and annexin A2 was confirmed by Western blot analysis, and potential roles of some differentially expressed proteins in the virus-infected cells have been discussed. CONCLUSIONS: Differentially expressed proteins of DHBV infected PDHs revealed by 2-DE, are involved in carbohydrate metabolism, amino acid metabolism, stress responses and cytoskeleton processes etc, providing the insight to understanding of interactions between hepadnavirus and hepatocytes and molecular mechanisms of hepadnavirus pathogenesis.