title: Use of Aspergillus fumigatus real-time PCR in bronchoalveolar lavage samples (BAL) for diagnosis of invasive aspergillosis, including azole-resistant cases, in high risk haematology patients: the need for a combined use with galactomannan

text: Diagnosis of invasive aspergillosis (IA) is challenging, particularly in high-risk patients with lung lesions other than typical according to 2008-EORTC/MSG criteria. Even if microbiology is positive, they still remain unclassified according to 2008-EORTC/MSG. Quantitative polymerase chain reaction (qPCR) provides new mycological documentation of IA. This retrospective study assessed Aspergillus fumigatus real time qPCR (MycoGENIE®) in BAL to diagnose IA and identify azole-resistant strains. Clinical, radiological, and microbiological data from 114 hematology patients (69% HSCT recipients; 29% on mould active agents) from years 2012-2017 were collected; and 123 BAL samples were tested with qPCR (cutoff: Ct < 40) and galactomannan (GM, Platelia®, cutoff: 0.5 ODI). Patients were classified as proven/probable, possible, and no-IA. "Atypical-IA" referred to patients with lesions other than typical according to 2008-EORTC/MSG and positive mycology. Proven IA was diagnosed in two cases (1.6%), probable in 28 (22.8%), possible in 27 (22%), atypical in 14 (11.4%). qPCR was positive in 39 samples (31.7%). Sensitivity and specificity of qPCR for proven/probable IA (vs no-IA; atypical-IA excluded) were 40% (95% confidence interval [CI]: 23–59) and 69% (95%CI: 55–81), respectively. Sensitivity of qPCR was higher when combined with GM (83%, 95%CI: 65–94) and in those receiving mould-active agents at BAL (61%, 95%CI: 32–86). One sample had TR34/L98H mutation. In conclusion, in high-risk hematology patients with various lung lesions, A. fumigatus qPCR in BAL contributes to diagnosing IA, particularly if combined with GM and in patients receiving mould-active agents might allow detecting azole-resistant mutations in culture negative samples.


title: Enhancing workplace learning at the transition into practice. Lessons from a pandemic

text: Taking responsibility for prescribing is one of newly qualified doctors’ greatest stressors.(1) Despite being a routine task, prescribing insulin is particularly stress‐inducing. The global pandemic has made it more important to minimise transitioning students’ stress; yet there are fewer clinicians to support their accelerated transitions. We had planned an intervention during 9‐week ‘Clinical Assistantships’ immediately before qualifying. Students would write insulin ‘pre‐prescriptions’, which supervisors would endorse as prescriptions that were appropriate to dispense. A trained healthcare professional or person with diabetes (‘debriefer’) would conduct one‐to‐one Case Based discussions (CBDs) to help students learn reflectively from experience.


Pre-procedural COVID testing: The “New Normal.”


A summary of the rapid services changes made in response to staff psychological needs and maintaining care to those with cancer in light of COVID‐19


title: Missed or delayed diagnosis of ARDS: a common and serious problem

text: Clinical recognition of acute respiratory distress syndrome (ARDS) is delayed or missed entirely in a substantial proportion of patients. In the LUNG SAFE study, the largest international cohort of patients with ARDS, investigators were able to determine if ARDS was present, and at what stage the clinician made the diagnosis of ARDS. The diagnosis of ARDS was delayed or missed in two-thirds of patients, with the diagnosis missed entirely in 40% of patients, while ARDS recognition ranged from 51% in mild ARDS to 79% in severe cases. Failure to recognize ARDS in a timely fashion leads to failure to use strategies that improve survival in ARDS. Early diagnosis of ARDS may facilitate measures to abrogate progression of the lung injury, including protective mechanical ventilation, fluid restriction, and adjunctive measures proven to improve survival such as prone positioning. Information overload and a complex ‘syndrome’ diagnosis likely play key roles in ARDS under-recognition. Clinical under-recognition has important consequences particularly in terms of therapeutic options not considered. The development of approaches to enable more timely recognition has the potential to save lives.


Histopathologic Changes and SARS–CoV-2 Immunostaining in the Lung of a Patient With COVID-19


title: Emergency and essential surgical healthcare services during COVID-19 in low- and middle-income countries: A Perspective

text: The COVID-19 pandemic resulted in significant changes in health care systems worldwide, with low- and middle-income countries (LMIC) sustaining important repercussions. Specifically, alongside cancellation and postponements of non-essential surgical services, emergency and essential surgical care delivery may become affected due to the shift of human and material resources towards fighting the pandemic. For surgeries that do get carried through, new difficulties arise in protecting surgical personnel from contracting SARS-CoV-2. This scarcity in LMIC surgical ecosystems may result in higher morbidity and mortality, in addition to the COVID-19 toll. This paper aims to explore the potential consequences of COVID-19 on the emergency and essential surgical care in LMICs, to offer recommendations to mitigate damages and to reflect on preparedness for future crises. Reducing the devastating consequences of the COVID-19 pandemic on LMIC emergency and essential surgical services can be achieved through empowering communities with accurate information and knowledge on prevention, optimizing surgical material resources, providing quality training of health care personnel to treat SARS-CoV-2, and ensuring adequate personal protection equipment for workers on the frontline. While LMIC health systems are under larger strain, the experience from previous outbreaks may aid in order to innovate and adapt to the current pandemic. Protecting LMIC surgical ecosystems will be a pivotal process in ensuring that previous health system strengthening efforts are preserved, comprehensive care for populations worldwide are ensured, and to allow for future developments beyond the pandemic.


title: Perception of spokespersons' performance and characteristics in crisis communication: Experience of the 2003 severe acute respiratory syndrome outbreak in Taiwan

text: Background/Purpose To explore perception of spokespersons' performance and characteristics in response to the 2003 severe acute respiratory syndrome (SARS) outbreak. Methods This study was conducted from March to July, 2005, using semi-structured in-depth interviews to collect data. All interviews were audio-recorded and transcribed verbatim. A qualitative content analysis was employed to analyze the transcribed data. Interviewees included media reporters, media supervisors, health and medical institution executives or spokespersons, and social observers. Results Altogether, 35 interviewees were recruited for in-depth interviews, and the duration of the interview ranged from 1 hour to 2 hours. Results revealed that the most important characteristics of health/medical institutions spokespersons are professional competence and good interaction with the media. In contrast, the most important behaviors they should avoid are concealing the truth and misreporting the truth. Three major flaws of spokespersons' performance were identified: they included poor understanding of media needs and landscape; blaming the media to cover up a mistake they made in an announcement; and lack of sufficient participation in decision-making or of authorization from the head of organization. Conclusion Spokespersons of health and medical institutions play an important role in media relations during the crisis of a newly emerging infectious disease.


title: Infección por SARS-CoV-2 en el embarazo y posibilidad de transmisión al neonato: una revisión sistemática

text: Resumen En este trabajo se revisan los artículos publicados sobre COVID-19, embarazo y afectación del neonato hasta 30 de abril de 2020. Se han encontrado un total de 33 publicaciones que se refieren a 553 gestantes y 456 partos. Los síntomas más frecuentes en la embarazada fueron fiebre, tos y disnea. Cerca de dos tercios de los partos se realizaron por cesárea; el 5,9% de las mujeres requirieron ingreso en UCI y el 4% requirió ventilación mecánica. No se produjo ninguna muerte materna. Hubo prematuridad en el 22,3% de los partos y el neonato requirió ingreso en UCI en el 38,3%. Solo se informó de una muerte neonatal (0,4%) y de 13 casos de COVID-19 neonatal (3,4%). La información disponible no permite asegurar que la transmisión se produjera por vía trasplacentaria. Abstract Studies published on COVID-19, pregnancy and neonate disease until 30 April 2020 are revised. We found 33 articles including 553 pregnant women and 456 deliveries. The more frequent symptoms in the pregnant women were fever, cough and dyspnoea. About two thirds deliveries were carried out via Caesarean rate; 5.9% women were admitted in the ICU and 4% required mechanic ventilation. No maternal death was reported. Prematurity occurred in 22.3% deliveries and 38.3% neonates required admission in the ICU. Only one neonatal death was reported (0.4%) and 13 neonates (3.4%) suffered COVID-19. The available information does not allow to state whether transmission to neonates occurred transplacentarily.


title: Infectivity of attenuated poxvirus vaccine vectors and immunogenicity of a raccoonpox vectored rabies vaccine in the Brazilian Free-tailed bat (Tadarida brasiliensis)

text: Bats (Order Chiroptera) are an abundant group of mammals with tremendous ecological value as insectivores and plant dispersers, but their role as reservoirs of zoonotic diseases has received more attention in the last decade. With the goal of managing disease in free-ranging bats, we tested modified vaccinia Ankara (MVA) and raccoon poxvirus (RCN) as potential vaccine vectors in the Brazilian Free-tailed bat (Tadarida brasiliensis), using biophotonic in vivo imaging and immunogenicity studies. Animals were administered recombinant poxviral vectors expressing the luciferase gene (MVA-luc, RCN-luc) through oronasal (ON) or intramuscular (IM) routes and subsequently monitored for bioluminescent signal indicative of viral infection. No clinical illness was noted after exposure to any of the vectors, and limited luciferase expression was observed. Higher and longer levels of expression were observed with the RCN-luc construct. When given IM, luciferase expression was limited to the site of injection, while ON exposure led to initial expression in the oral cavity, often followed by secondary replication at another location, likely the gastric mucosa or gastric associated lymphatic tissue. Viral DNA was detected in oral swabs up to 7 and 9 days post infection (dpi) for MVA and RCN, respectively. While no live virus was detected in oral swabs from MVA-infected bats, titers up to 3.88 × 10(4) PFU/ml were recovered from oral swabs of RCN-infected bats. Viral DNA was also detected in fecal samples from two bats inoculated IM with RCN, but no live virus was recovered. Finally, we examined the immunogenicity of a RCN based rabies vaccine (RCN-G) following ON administration. Significant rabies neutralizing antibody titers were detected in the serum of immunized bats using the rapid fluorescence focus inhibition test (RFFIT). These studies highlight the safety and immunogenicity of attenuated poxviruses and their potential use as vaccine vectors in bats.


title: Comparison of the AdvanSure™ real-time RT-PCR and Seeplex® RV12 ACE assay for the detection of respiratory viruses

text: Abstract The AdvanSure™ RV real-time PCR kit (AdvanSure; LG Life Sciences, Korea) is based on multiplex real-time PCR and can simultaneously detect 14 respiratory viruses. We compared the performance of the AdvanSure assay with the Seeplex RV 12 ACE detection kit (Seeplex; Seegene, Seoul, South Korea), a multiplex end-point PCR assay. A total of 454 consecutive respiratory specimens were tested with both AdvanSure and Seeplex assays; AdvanSure detected 153 (33.7%) positive cases and Seeplex detected 145 (31.9%) positive cases. The positive percent agreement, negative percent agreement, and kappa value for the two assays were 87.2% (95% CI, 80.3–92.1), 91.1% (95% CI, 87.2–93.9), and 0.77 (95% CI, 0.70–0.83), respectively. Compared with the Seeplex assay, the AdvanSure assay had a shorter turnaround time (3h vs. 8h) and a shorter hands-on time (<1h vs 2h). In conclusion, the AdvanSure assay demonstrated comparable performance to the Seeplex assay.


title: Assessing Ebola-related web search behaviour: insights and implications from an analytical study of Google Trends-based query volumes

text: BACKGROUND: The 2014 Ebola epidemic in West Africa has attracted public interest worldwide, leading to millions of Ebola-related Internet searches being performed during the period of the epidemic. This study aimed to evaluate and interpret Google search queries for terms related to the Ebola outbreak both at the global level and in all countries where primary cases of Ebola occurred. The study also endeavoured to look at the correlation between the number of overall and weekly web searches and the number of overall and weekly new cases of Ebola. METHODS: Google Trends (GT) was used to explore Internet activity related to Ebola. The study period was from 29 December 2013 to 14 June 2015. Pearson’s correlation was performed to correlate Ebola-related relative search volumes (RSVs) with the number of weekly and overall Ebola cases. Multivariate regression was performed using Ebola-related RSV as a dependent variable, and the overall number of Ebola cases and the Human Development Index were used as predictor variables. RESULTS: The greatest RSV was registered in the three West African countries mainly affected by the Ebola epidemic. The queries varied in the different countries. Both quantitative and qualitative differences between the affected African countries and other Western countries with primary cases were noted, in relation to the different flux volumes and different time courses. In the affected African countries, web query search volumes were mostly concentrated in the capital areas. However, in Western countries, web queries were uniformly distributed over the national territory. In terms of the three countries mainly affected by the Ebola epidemic, the correlation between the number of new weekly cases of Ebola and the weekly GT index varied from weak to moderate. The correlation between the number of Ebola cases registered in all countries during the study period and the GT index was very high. CONCLUSION: Google Trends showed a coarse-grained nature, strongly correlating with global epidemiological data, but was weaker at country level, as it was prone to distortions induced by unbalanced media coverage and the digital divide. Global and local health agencies could usefully exploit GT data to identify disease-related information needs and plan proper communication strategies, particularly in the case of health-threatening events. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-015-0090-9) contains supplementary material, which is available to authorized users.


title: Cost-effectiveness of immediate versus delayed sequential bilateral cataract surgery in the Netherlands (the BICAT-NL study): study design of a prospective multicenter randomised controlled trial

text: BACKGROUND: Cataract surgery is one of the most frequently performed types of surgery. Most patients suffer from bilateral cataract and while cataract surgery of only one eye is effective in restoring functional vision, second-eye surgery leads to further improvements in health-related quality of life, and is cost-effective. At present, most patients undergo cataract surgery in both eyes on separate days as recommended in national guidelines, referred to as delayed sequential bilateral cataract surgery (DSBCS). An alternative procedure involves operating both eyes on the same day, but as separate procedures, known as immediately sequential bilateral cataract surgery (ISBCS). The aim of this study is to evaluate the effectiveness and costs of ISBCS compared to DSBCS, in order to test the hypothesis that ISBCS is non-inferior to DSBCS in terms of effectiveness and superior to ISBCS in terms of cost-effectiveness. METHODS/DESIGN: Multicenter non-inferiority randomised controlled clinical trial. Patients (18 years or older) with bilateral cataract and an indication for bilateral cataract surgery with an expected uncomplicated intraoperative and postoperative course are included in the study. Patients are randomly assigned to either ISBCS or DSBCS. The primary endpoint is the proportion of patients with a refractive outcome in the second eye within 1.0 dioptre from the target refraction, at 4 weeks after surgery. Secondary outcomes include corrected and uncorrected distance visual acuity, complications, patient reported outcomes (PROMs), cost-effectiveness, and budget impact. Follow-up visits are planned at 1 week after first-eye surgery and 4 weeks after second-eye surgery. At 3 months after first-eye surgery, the occurrence of complications is checked and patients fill in a final questionnaire. DISCUSSION: This study protocol describes the design of a multicenter non-inferiority randomised controlled trial. Current studies on ISBCS often lack information on safety regarding refractive outcomes. In addition, there is a lack of well-designed cost-effectiveness studies using established methods. The BICAT-NL study will provide more insight in refractive and cost-effectiveness outcomes for ISBCS compared to DSBCS. TRIAL REGISTRATION: This study was prospectively registered at Clinicaltrials.gov on January 17th 2018. (Identifier: NCT03400124.


title: Trends in Injuries, Illnesses, and Policies in Canadian Healthcare Workplaces

text: BACKGROUND: Analysis of workers’ compensation data and occupational health and safety trends in healthcare across Canada was conducted to provide insight concerning workplace injuries and prevention measures undertaken in the healthcare sector. METHODS: Timeloss claims data were collected for 1992–2002 from the Association of Workers’ Compensation Boards of Canada. Labour Force data from Statistics Canada were used to calculate injury rates. The Occupational Health and Safety Agency for Healthcare in British Columbia coordinated with provincial occupational health and safety agencies in Ontario, Quebec and Nova Scotia to analyze injury data and collate prevention measures in their regions. RESULTS: The national timeloss injury rate declined from 4.3 to 3.7 injuries per 100 personyears since 1998. Musculoskeletal injuries consistently comprised the majority of timeloss claims. Needlestick injuries, infectious diseases and stress-related claims infrequently resulted in timeloss claims although they are known to cause great concern in the workplace. Prevention measures taken in the various provinces related to safer equipment (lifts and electric beds), return-to-work programs, and violence prevention initiatives. Different eligibility criteria as well as adjudication policies confounded the comparison of injury rates across provinces. DISCUSSION: Since 2000, all provinces experienced healthcare restructuring and increased workload in an aging workforce. Despite these increased risks, injury rates have decreased. Attribution for these trends is complex, but there is reason to believe that focus on prevention can further decrease injuries. While occupational health is a provincial jurisdiction, harmonizing data in addition to sharing data on successful prevention measures and best practices may improve workplace conditions and thereby further reduce injury rates for higher risk healthcare sector occupations.


title: Evolutionary Dynamics in the RNA Bacteriophage Qβ Depends on the Pattern of Change in Selective Pressures

text: The rate of change in selective pressures is one of the main factors that determines the likelihood that populations can adapt to stress conditions. Generally, the reduction in the population size that accompanies abrupt environmental changes makes it difficult to generate and select adaptive mutations. However, in systems with high genetic diversity, as happens in RNA viruses, mutations with beneficial effects under new conditions can already be present in the population, facilitating adaptation. In this work, we have propagated an RNA bacteriophage (Qβ) at temperatures higher than the optimum, following different patterns of change. We have determined the fitness values and the consensus sequences of all lineages throughout the evolutionary process in order to establish correspondences between fitness variations and adaptive pathways. Our results show that populations subjected to a sudden temperature change gain fitness and fix mutations faster than those subjected to gradual changes, differing also in the particular selected mutations. The life-history of populations prior to the environmental change has great importance in the dynamics of adaptation. The conclusion is that in the bacteriophage Qβ, the standing genetic diversity together with the rate of temperature change determine both the rapidity of adaptation and the followed evolutionary pathways.


title: Psychotic relapse from COVID-19 quarantine, a case report

text: • The coronavirus disease 2019 (COVID-19), first reported on December 31(st), 2019 in China, has currently spread worldwide and became pandemic on March 11(th). • Besides causing an emotional impact in people affected, COVID-19 pandemic could specially affect people with previous mental health conditions, resulting in relapses or worsening of an already existing mental health condition because of high susceptibility to stress compared with the general population. • Worldwide, in different countries, among them Spain, it has been necessary to adopt confinement measures to preserve public health. These measures might represent to an extra stressful situation, particularly in vulnerable patients, such as those suffering from psychotic disorders. • This case report highlights the importance to developing specific support programs for this vulnerable population in an unprecedented situation such us the COVID-19 crisis. The role of telemedicine it has been suggested for that purpose.


Coronavirus et cerveau : une recherche originale démarre


title: A Critical HA1 Neutralizing Domain of H5N1 Influenza in an Optimal Conformation Induces Strong Cross-Protection

text: The highly pathogenic avian influenza (HPAI) H5N1 viruses, especially the laboratory-generated H5N1 mutants, have demonstrated the potential to cross the species barrier and infect mammals and humans. Consequently, the design of an effective and safe anti-H5N1 vaccine is essential. We previously demonstrated that the full-length hemagglutinin 1 (HA1) could induce significant neutralizing antibody response and protection. Here, we intended to identify the critical neutralizing domain (CND) in an optimal conformation that can elicit strong cross-neutralizing antibodies and protection against divergent H5N1 strains. We thus constructed six recombinant proteins covering different regions of HA1 of A/Anhui/1/2005(H5N1), each of which was fused with foldon (Fd) and Fc of human IgG. We found that the critical fragment fused with Fd/Fc (HA-13–263-Fdc, H5 numbering) that could elicit the strongest neutralizing antibody response is located in the N-terminal region of HA1 (residues 13–263), which covers the receptor-binding domain (RBD, residues 112–263). We then constructed three additional recombinants fused with Fd plus His tag (HA-13–263-Fd-His), Fc only (HA-13–263-Fc), and His tag only (HA-13–263-His), respectively. We found that the HA-13–263-Fdc, which formed an oligomeric conformation, induced the strongest neutralizing antibody response and cross-protection against challenges of two tested H5N1 virus strains covering clade 1: A/VietNam/1194/2004 (VN/1194) or clade 2.3.4: A/Shenzhen/406H/06 (SZ/406H), while HA-13–263-Fc dimer and HA-13–263-Fd-His trimer elicited higher neutralizing antibody response and protection than HA-13–263-His monomer. These results suggest that the oligomeric form of the CND containing the RBD can be further developed as an effective and safe vaccine for cross-protection against divergent strains of H5N1 viruses.


title: Baicalein, Ethyl Acetate, and Chloroform Extracts of Scutellaria baicalensis Inhibit the Neuraminidase Activity of Pandemic 2009 H1N1 and Seasonal Influenza A Viruses

text: This study rated antiviral activity of Scutellaria baicalensis Georgi (S. baicalensis) extracts against influenza A virus subtypes, for example, pandemic 2009 H1N1, seasonal H1N1 and H3N2. Ethyl acetate (EtOAc) and chloroform extracts inhibited in vitro neuraminidase (NA) enzymatic activity and viral replication more than methanol (MeOH) extract. EtOAc extract demonstrated NA inhibition IC(50) values ranging from 73.16 to 487.40 μg/mL and plaque reduction IC(50) values ranging from 23.7 to 27.4 μg/mL. Chloroform extract showed antiviral activities with plaque reduction IC(50) values ranging from 14.16 to 41.49 μg/mL Time-of-addition assay indicated that EtOAc and chloroform extracts also significantly inhibited virus yields after infection. HPLC analysis demonstrated that baicalin was dominant in the MeOH extract; baicalein and chrysin were rich in the EtOAc and chloroform extracts. Molecular simulation revealed baicalein hydrogen bonding with Glu277 as well as hydrophobic and Van der Waals interactions with Ile222, Arg224, Ser246, and Tyr347 in NA1 active sites of NA1. Baicalein inhibited in vitro replication of influenza A viruses pandemic 2009 H1N1 (IC(50) = 0.018 μM) and seasonal 2007 H1N1 using plaque reduction assays. A combination of low-dose baicalein with other anti-influenza agents could be applicable for development of alternative remedies treating influenza A virus infection.


title: Evaluation of Nutritional Risk and its Association With Mortality Risk in Severe and Critically Ill COVID‐19 Patients

text: BACKGROUND: The nutritional status of COVID‐19 patients is unknown. This study evaluates the clinical and nutritional characteristics of severe and critically ill patients infected with SARS‐CoV‐2, and investigates the relationship between nutritional risk and clinical outcomes. METHODS: A retrospective, observational study was conducted at West Campus of Union Hospital in Wuhan. Patients confirmed with SARS‐CoV‐2 infection by a nucleic acid‐positive test and identified as severe or critically ill, were enrolled in this study. Clinical data and outcomes information was collected and nutritional risk was assessed by using Nutritional Risk Screening 2002 (NRS). RESULTS: Totally, 413 patients were enrolled in this study, including 346 severe patients and 67 critically ill patients. Most patients, especially critically ill patients, had significant changes in nutrition‐related parameters and inflammatory markers. As for nutritional risk, the critically ill patients had significantly higher proportion of high NRS scores (P<0.001), which were correlated with inflammatory and nutrition‐related markers. Among 342 patients with NRS score ≥3, only 84 (25%) received nutritional support. The critically ill patients and the patients with higher NRS score had a higher risk of mortality and longer stay in hospital. In logistic regression models, one unit increased in NRS score was associated with the risk of mortality increased by 1.23 times (adjusted OR = 2.23, 95% CI: 1.10, 4.51, P = 0.026). CONCLUSIONS: Most severe and critically ill patients infected with SARS‐CoV‐2 are at nutritional risk. The patients with higher nutrition risk have worse outcome, and require nutritional therapy. This article is protected by copyright. All rights reserved


title: NMR assignment of the domain 513–651 from the SARS-CoV nonstructural protein nsp3

text: Sequence-specific NMR assignments of an internal domain of the protein nsp3, nsp3(513–651), which is a part of the SARS coronavirus (SARS-CoV) replicase polyprotein, have been determined, using triple-resonance NMR experiments with the uniformly [(13)C,(15)N]-labeled protein. The complete assignments (>99%) provide the basis for the ongoing three-dimensional structure determination.


title: Detection of viral antigens, particles, and early antibodies in diagnosis.

text: Immunoassays for the detection of viral antigens in clinical specimens and virus-specific IgM responses in serum have shortened the time required to make a laboratory diagnosis of several infections. A range of antigen detection systems are available, varying in sensitivity, complexity, and expense, and each may have a role to play depending upon the laboratory setting. Technical advancements to eliminate false-positive results in solid-phase IgM assays have provided an awareness of very early IgM responses in diseases such as rubella, hepatitis A, and mumps. When clinical specimens contain large numbers of virus particles, a rapid diagnosis is easily made using electron microscopy. Detection of antigens, virus particles, and IgM responses is creating increased demands for viral diagnostic services in primary care settings. Other approaches using sensitive probes for viral nucleic acids or enzymes will also serve as viable laboratory techniques in the future.


title: Broadly targeted triplex real-time PCR detection of influenza A, B and C viruses based on the nucleoprotein gene and a novel “MegaBeacon” probe strategy

text: Abstract A PCR assay that covers animal and human influenza A, B and C viruses, i.e., most of Orthomyxoviridae, is needed. Influenza types are distinguished based on differences in the nucleoprotein (NP) present in the virus. Conserved NP regions were therefore used to design a TaqMan®-based triplex reverse transcription real-time PCR method. Variability of influenza A within the probe target region mandated the development of a novel molecular beacon, the “Mega” molecular beacon (MegaBeacon; MegB), for the detection of influenza A with this method. MegaBeacon is a mismatch-tolerant molecular beacon that is also a TaqMan® probe. The triplex method (3QPCR-MegB) was evaluated with influenza A isolates covering 18 HxNx combinations, two influenza B isolates, and five Japanese influenza C isolates, as well as influenza A, B and C synthetic DNA targets. One to ten viral RNA and cDNA genome equivalents were detected per PCR reaction for influenza A, B and C. Seventy-one human nasopharyngeal aspirates from respiratory infections yielded 30 influenza A, 11 influenza B and 0 influenza C with 3QPCR-MegB, where immunofluorescence (IF) found 28 influenza A and 10 influenza B. 3QPCR-MegB was more mismatch-tolerant than a variant PCR with an influenza A TaqMan® probe (3QPCR) and is a sensitive and rational method to detect influenza viruses of animal and human origin. MegaBeacon probes hold promise for variable target nucleic acids.


title: COVID‐19 Screening with Chest CT in Acute Stroke Imaging: A Clinical Decision Model

text: BACKGROUND AND PURPOSE: Acute stroke patients may have undiagnosed coronavirus disease 2019 (COVID‐19) infection, transmissible to medical professionals involved in their care. Our aim was to determine the value of incorporating a chest computed tomography (CT) scan during acute stroke imaging, and the factors that influence this decision. METHODS: We constructed a probabilistic decision tree of the value of acquiring a chest CT scan or not, expressed in quality‐adjusted life months (QALM) of patients and medical professionals. The model was based on the chance of detecting infection by chest CT scan, the case fatality rates of COVID‐19 infection, the risk of COVID‐19 infection after exposure, the expected proportion of medical professionals exposed, and the exposure reduction derived from early disease detection. RESULTS: The decision to incorporate the chest CT scan was superior to not doing so (12.00 QALM vs 11.99 QALM, respectively), when the probability of patients having undetected COVID‐19 infection is 3.5%, potentially exposing 100% of medical professionals, and if early detection reduces exposure by 50%. The risk of developing symptomatic COVID‐19 infection following exposure casts uncertainty on the results, but this is offset by the potential for reducing exposure. CONCLUSIONS: We identified a measurable benefit of incorporating a chest CT into the urgent imaging protocol of acute stroke patients in reducing exposure of medical professionals without appropriate precautions. The clinical impact of this benefit, however, may not be materially significant.


title: Ribavirin inhibits Zika virus (ZIKV) replication in vitro and suppresses viremia in ZIKV-infected STAT1-deficient mice

text: Abstract Zika fever, a mosquito-borne infectious disease caused by Zika virus (ZIKV), is an epidemic disease for which no effective therapy has been established. The recent outbreaks of ZIKV in Brazil and French Polynesia have been linked to a considerable increase in the incidence of fetal microcephaly and other diseases such as Guillain-Barre syndrome. Because there is currently no specific therapy or vaccine, the early exploitation of a method to prevent expansion of ZIKV is a high priority. To validate commonly used antiviral drugs, we evaluated the effect of ribavirin, a drug used to treat hepatitis C with interferon-β (IFN-β), on ZIKV replication. In mammalian cells, we observed an inhibitory effect of ribavirin on ZIKV replication and ZIKV-induced cell death without cytotoxic effect. Furthermore, we found that STAT1-deficient mice, which lack type I IFN signaling, were highly sensitive to ZIKV infection and exhibited lethal outcome. Ribavirin abrogated viremia in ZIKV-infected STAT-1-deficient mice. These data suggest that the inhibition of viral RNA-dependent RNA polymerases may be effective for treatment of ZIKV infection. Our data provide a new insight into the mechanisms for inhibition of ZIKV replication and prevention of Zika fever.


title: “COVID-19 and Smoking: How and Why We Implemented a Tobacco Treatment Campaign”

text: Abstract Smoking is associated with one out of five deaths in the United States. Multi-modality tobacco treatment increases rates of successful cessation by at least 20%. The COVID-19 pandemic has put a halt to many inpatient and outpatient medical visits deemed non-essential, including tobacco treatment. The transition to telehealth has been wrought with challenges. While data on the association between COVID-19 and tobacco products is mixed, the overall health consequences of tobacco point towards increased risk of morbidity and mortality associated with the virus. This leaves smoking as one of the few readily modifiable risk factors in an environment understandably not set up to prioritize cessation. A military health facility on Fort Eustis in Virginia runs a successful tobacco treatment program and adapted it to pandemic times. This paper describes the process and lessons learned from this initiative. The model is applicable and scalable to government and civilian health centers as healthcare adapts to a new normal.


title: Coronaviruses: An RNA proofreading machine regulates replication fidelity and diversity

text: In order to survive and propagate, RNA viruses must achieve a balance between the capacity for adaptation to new environmental conditions or host cells with the need to maintain an intact and replication competent genome. Several virus families in the order Nidovirales, such as the coronaviruses (CoVs) must achieve these objectives with the largest and most complex replicating RNA genomes known, up to 32 kb of positive-sense RNA. The CoVs encode sixteen nonstructural proteins (nsp 1–16) with known or predicted RNA synthesis and modification activities, and it has been proposed that they are also responsible for the evolution of large genomes. The CoVs, including murine hepatitis virus (MHV) and SARS-CoV, encode a 3′-to-5′ exoribonuclease activity (ExoN) in nsp14. Genetic inactivation of ExoN activity in engineered SARS-CoV and MHV genomes by alanine substitution at conserved DE-D-D active site residues results in viable mutants that demonstrate 15- to 20-fold increases in mutation rates, up to 18 times greater than those tolerated for fidelity mutants of other RNA viruses. Thus nsp14-ExoN is essential for replication fidelity, and likely serves either as a direct mediator or regulator of a more complex RNA proofreading machine, a process previously unprecedented in RNA virus biology. Elucidation of the mechanisms of nsp14-mediated proofreading will have major implications for our understanding of the evolution of RNA viruses, and also will provide a robust model to investigate the balance between fidelity, diversity and pathogenesis. The discovery of a protein distinct from a viral RdRp that regulates replication fidelity also raises the possibility that RNA genome replication fidelity may be adaptable to differing replication environments and selective pressures, rather than being a fixed determinant.


title: Induction of neutralising antibodies and cellular immune responses against SARS coronavirus by recombinant measles viruses

text: Live attenuated recombinant measles viruses (rMV) expressing a codon-optimised spike glycoprotein (S) or nucleocapsid protein (N) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) were generated (rMV-S and rMV-N). Both recombinant viruses stably expressed the corresponding SARS-CoV proteins, grew to similar end titres as the parental strain and induced high antibody titres against MV and the vectored SARS-CoV antigens (S and N) in transgenic mice susceptible to measles infection. The antibodies induced by rMV-S had a high neutralising effect on SARS-CoV as well as on MV. Moreover, significant N-specific cellular immune responses were measured by IFN-γ ELISPOT assays. The pre-existence of anti-MV antibodies induced by the initial immunisation dose did not inhibit boost of anti-S and anti-N antibodies. Immunisations comprising a mixture of rMV-S and rMV-N induced immune responses similar in magnitude to that of vaccine components administered separately. These data support the suitability of MV as a bivalent candidate vaccine vector against MV and emerging viruses such as SARS-CoV.


title: Recombinant Protein Targeting and Opsonizing Spike Glycoprotein for Enhancing SARS-CoV-2 Phagocytosis

text: The present hypothesis suggests an innovative therapeutic strategy to cease Covid 19 infection. It is based on the inhibition of Spike glycoprotein and ACE-2 receptor interaction that provides the entry of virus in human host cells, by targeting the S protein with a recombinant molecule made of the ACE-2 receptor ectodomain and an opsonin, the formed complex would enhance its phagocytosis.


title: A Diverse Group of Previously Unrecognized Human Rhinoviruses Are Common Causes of Respiratory Illnesses in Infants

text: BACKGROUND: Human rhinoviruses (HRVs) are the most prevalent human pathogens, and consist of 101 serotypes that are classified into groups A and B according to sequence variations. HRV infections cause a wide spectrum of clinical outcomes ranging from asymptomatic infection to severe lower respiratory symptoms. Defining the role of specific strains in various HRV illnesses has been difficult because traditional serology, which requires viral culture and neutralization tests using 101 serotype-specific antisera, is insensitive and laborious. METHODS AND FINDINGS: To directly type HRVs in nasal secretions of infants with frequent respiratory illnesses, we developed a sensitive molecular typing assay based on phylogenetic comparisons of a 260-bp variable sequence in the 5' noncoding region with homologous sequences of the 101 known serotypes. Nasal samples from 26 infants were first tested with a multiplex PCR assay for respiratory viruses, and HRV was the most common virus found (108 of 181 samples). Typing was completed for 101 samples and 103 HRVs were identified. Surprisingly, 54 (52.4%) HRVs did not match any of the known serotypes and had 12–35% nucleotide divergence from the nearest reference HRVs. Of these novel viruses, 9 strains (17 HRVs) segregated from HRVA, HRVB and human enterovirus into a distinct genetic group (“C”). None of these new strains could be cultured in traditional cell lines. CONCLUSIONS: By molecular analysis, over 50% of HRV detected in sick infants were previously unrecognized strains, including 9 strains that may represent a new HRV group. These findings indicate that the number of HRV strains is considerably larger than the 101 serotypes identified with traditional diagnostic techniques, and provide evidence of a new HRV group.


title: Simultaneous HPLC analysis, with isocratic elution, of glycyrrhizin and glycyrrhetic acid in liquorice roots and confectionery products

text: Glycyrrhizin (1), the main active principle of Glycyrrhiza glabra (liquorice) roots, is extensively used in herbal medicines, in pharmaceutical preparations and confectionery products. A feasible and reliable method which allows the simultaneous analysis of 1 and its aglycone, 18β‐glycyrrhetic acid (2), by means of an isocratic HPLC procedure is described. The system uses a C(8) column as the stationary phase, and a mixture of acetonitrile, methanol, water and glacial acetic acid as the mobile phase. Good linearity was found in the concentration ranges 1–50 and 0.05–2.50 µg/mL for 1 and 2, respectively. A simple and rapid sample pre‐treatment, based on the extraction of the two analytes with a mixture of water and ethanol, was developed for the examination of liquorice confectionery products and root samples. The HPLC method was shown to be appropriate, in terms of precision and feasibility, for the quality control of the analytes in these matrices. Copyright © 2005 John Wiley & Sons, Ltd.


title: Identification of a novel protein encoded by the latency-related gene of bovine herpesvirus 1

text: The latency-related (LR) RNA encoded by bovine herpesvirus 1 (BHV-1) is abundantly expressed and alternatively spliced in trigeminal ganglia. A mutant BHV-1 strain that contains three stop codons at the beginning of LR open reading frame (ORF)-2 (LR mutant virus) does not express ORF-2 or an adjacent reading frame that lacks an initiating ATG (RF-C). Calves latently infected with wild-type (wt) BHV-1, but not with the LR mutant virus, reactivate from latency, indicating that proteins encoded by the LR gene regulate the latency-reactivation cycle. The LR gene also contains another large ORF (ORF-1) that is approximately 200 bp downstream of stop codons inserted at the N-terminus of ORF-2. To test whether the LR mutant virus can expresses ORF-1, the authors developed antiserum directed against ORF-1. The ORF-1 antiserum recognizes specific proteins in bovine cells productively infected with wt BHV-1. ORF-1 protein expression is reduced, but not blocked, when bovine cells are infected with the LR mutant virus. Confocal microscopy demonstrated ORF-1 is present in the cytoplasm and nucleus of productively infected cells, whereas RF-C or a fusion protein containing RF-C localizes to the cytoplasm. Trigeminal ganglia from calves latently infected with wt BHV-1 contain neurons specifically stained with the ORF-1 antiserum. These studies suggest ORF-1 expression may be important for the BHV-1 latency-reactivation cycle.


title: Forecasting versus projection models in epidemiology: The case of the SARS epidemics

text: Summary In this work we propose a simple mathematical model for the analysis of the impact of control measures against an emerging infection, namely, the severe acute respiratory syndrome (SARS). The model provides a testable hypothesis by considering a dynamical equation for the contact parameter, which drops exponentially with time, simulating control measures. We discuss the role of modelling in public health and we analyse the distinction between forecasting and projection models as assessing tools for the estimation of the impact of intervention strategies. The model is applied to the communities of Hong Kong and Toronto (Canada) and it mimics those epidemics with fairly good accuracy. The estimated values for the basic reproduction number, R 0, were 1.2 for Hong Kong and 1.32 for Toronto (Canada). The model projects that, in the absence of control, the final number of cases would be 320,000 in Hong Kong and 36,900 in Toronto (Canada). In contrast, with control measures, which reduce the contact rate to about 25% of its initial value, the expected final number of cases is reduced to 1778 in Hong Kong and 226 in Toronto (Canada). Although SARS can be a devastating infection, early recognition, prompt isolation, and appropriate precaution measures, can be very effective to limit its spread.


title: The impact of high-speed railway on tourism spatial structures between two adjoining metropolitan cities in China: Beijing and Tianjin

text: Abstract This study examines the impact of HSR services on the tourism spatial interactions between Beijing and Tianjin in China. Data were collected from official statistical reports. A method of derivation was developed and several indexes, such as tourism mean center, and tourism standard distance are further applied to measure temporal-spatial changes between the two adjoining cities. The results reveal the dynamic tourism spatial interaction between Beijing and Tianjin has been influenced by a range of factors including population, destination attractiveness, disposable income and income elasticity, changes in the domestic and international spatial structure of tourist flows and how destination management organizations react to the changes. The study has implications for both the research and practice of city transportation and tourism development.


Today's virtual teams: Adapting lessons learned to the pandemic context


title: Idiopathic toxic epidermal necrolysis in an adolescent

text: A 10‐year‐old girl, suspected 2 days prior to have streptococcal pharyngitis, presented with diffuse erythema, tense bullae, Nikolsky‐positive desquamation, as well as ulcerations of her oral and genital mucosa. She denied recent travel, sick contacts, or preceding and concurrent use of medications, including over‐the‐counter and herbal supplements. A comprehensive viral polymerase chain reaction (PCR) panel, Mycoplasma pneumoniae PCR and IgM, streptococcal molecular antigen test, urine culture, blood culture, and rheumatologic serologies were negative. Based on the patient's clinical presentation and biopsy results, she was diagnosed with idiopathic toxic epidermal necrolysis.


title: COVID 19: Disruptive impacts and transformative opportunities in undergraduate nurse education

text: • COVID 19. • Education. • Transformation. • Opportunities. • Challenges.


title: Stepwise evolution of two giant composite LTR-retrotransposon-like elements DA and Xiao

text: BACKGROUND: We recently discovered two composite long terminal repeat (LTR)-retrotransposon-like elements which we named DA (~300 kb) and Xiao (~30 kb), meaning big and small in Chinese respectively. Xiao and DA (three types of DA identified) were found to have been derived from several donor sites and have spread to 30 loci in the human genome, totaling to 5 Mb. Our bioinformatics analyses with the released human, chimp, rhesus macaque, orangutan, and marmoset genomic sequences indicate that DA and Xiao emerged ~25 million years (Myr) ago. RESULTS: To better understand the evolution of these two complex elements, we investigated various internal junctions of DA and Xiao as well as orthologous genomic sites of the 30 DA/Xiao loci in non-human primates including great apes, lesser apes, Old World monkeys, New World monkeys, and a prosimian. We found that Xiao and type I DA first emerged in the genome between 25 and 18 Myr ago, whereas type II and Type III DAs emerged between 14 and 7 Myr ago. Xiao and DA were most active in great apes, with their amplification peaking during 25-14 and 14-7 Myr ago, respectively. Neither DA nor Xiao seem to have been active in the human and chimp genomes during last 6 Myr. CONCLUSION: The study has led to a more accurate age determination of the DA and Xiao elements than our previous bioinformatics analyses, and indicates that the amplification activity of the elements coincided with that of group I HERV-Es during evolution. It has also illustrated an evolutionary path with stepwise structural changes for the elements during past 25 Myr, and in doing so has shed more light on these two intriguing and complex elements that have reshaped our genome.


title: Development of a DNA-based microarray for the detection of zoonotic pathogens in rodent species

text: Abstract The demand for diagnostic tools that allow simultaneous screening of samples for multiple pathogens is increasing because they overcome the limitations of other methods, which can only screen for a single or a few pathogens at a time. Microarrays offer the advantages of being capable to test a large number of samples simultaneously, screening for multiple pathogen types per sample and having comparable sensitivity to existing methods such as PCR. Array design is often considered the most important process in any microarray experiment and can be the deciding factor in the success of a study. There are currently no microarrays for simultaneous detection of rodent-borne pathogens. The aim of this report is to explicate the design, development and evaluation of a microarray platform for use as a screening tool that combines ease of use and rapid identification of a number of rodent-borne pathogens of zoonotic importance. Nucleic acid was amplified by multiplex biotinylation PCR prior to hybridisation onto microarrays. The array sensitivity was comparable to standard PCR, though less sensitive than real-time PCR. The array presented here is a prototype microarray identification system for zoonotic pathogens that can infect rodent species.


title: Análisis del impacto del confinamiento en el número de reproducción del SARS-Cov-2 en España

text: ABSTRACT Objective: The late 2019 COVID-19 outbreak has put the health systems of many countries to the limit of their capacity. The most affected European countries are, so far, Italy and Spain. In both countries (and others), the authorities decreed a lockdown, with local specificities. The objective of this work is to evaluate the impact of the measures undertaken in Spain to deal with the pandemic. Method: We estimated the number of cases and the impact of lockdown on the reproducibility number based on the hospitalization reports up to April 15th 2020. Results: The estimated number of cases shows a sharp increase until the lockdown, followed by a slowing down and then a decrease after full quarantine was implemented. Differences in the basic reproduction ratio are also significant, dropping from de 5.89 (95% confidence interval [95%CI]: 5.46-7.09) before the lockdown to 0.48 (95%CI: 0.15-1.17) afterwards. Conclusions: Handling a pandemic like COVID-19 is complex and requires quick decision making. The large differences found in the speed of propagation of the disease show us that being able to implement interventions at the earliest stage is crucial to minimise the impact of a potential infectious threat. Our work also stresses the importance of reliable up to date epidemiological data in order to accurately assess the impact of Public Health policies on viral outbreak. RESUMEN Objetivo: El brote de COVID-19 a finales de 2019 ha puesto los sistemas de salud de muchos países al límite de su capacidad. Los países europeos más afectados son, hasta ahora, Italia y España. En ambos (y en otros países), las autoridades decretaron un confinamiento, con especificidades locales. El objetivo de este trabajo es evaluar el impacto de las medidas adoptadas en España para hacer frente a la pandemia. Método: Estimamos el número de casos y el impacto del confinamiento en el número básico de reproducción según los informes de hospitalización hasta el 15 de abril de 2020. Resultados: El número estimado de casos muestra un fuerte aumento hasta el bloqueo, seguido de una desaceleración y luego una disminución tras la implementación del confinamiento total. Las diferencias en el número básico de reproducción también son muy significativas, cayendo de 5,89 (intervalo de confianza del 95% [IC95%]: 5,46-7,09) antes del bloqueo a 0,48 (IC95%: 0,15-1,17) después. Conclusiones: Gestionar una pandemia como la de COVID-19 es muy complejo y requiere una rápida toma de decisiones. Las grandes diferencias encontradas en la velocidad de propagación de la enfermedad muestran que poder implementar intervenciones en la etapa más temprana es crucial para minimizar el impacto de una potencial amenaza. Nuestro trabajo también indica la importancia de contar con datos epidemiológicos actualizados y confiables para evaluar con precisión el impacto de las políticas de salud pública en la pandemia.


title: Access to primary healthcare during lockdown measures for COVID-19 in rural South Africa: a longitudinal cohort study

text: OBJECTIVES: Public health interventions designed to interrupt COVID-19 transmission could have deleterious impacts on primary healthcare access. We sought to identify whether implementation of the nationwide lockdown (shelter-in-place) order in South Africa affected ambulatory clinic visitation in rural Kwa-Zulu Natal (KZN). DESIGN: Prospective, longitudinal cohort study SETTING: Data were analyzed from the Africa Health Research Institute Health and Demographic Surveillance System, which includes prospective data capture of clinic visits at eleven primary healthcare clinics in northern KwaZulu-Natal PARTICIPANTS: A total of 36,291 individuals made 55,545 clinic visits during the observation period. EXPOSURE OF INTEREST: We conducted an interrupted time series analysis with regression discontinuity methods to estimate changes in outpatient clinic visitation from 60 days before through 35 days after the lockdown period. OUTCOME MEASURES: Daily clinic visitation at ambulatory clinics. In stratified analyses we assessed visitation for the following sub-categories: child health, perinatal care and family planning, HIV services, non-communicable diseases, and by age and sex strata. RESULTS: We found no change in total clinic visits/clinic/day from prior to and during the lockdown (−6.9 visits/clinic/day, 95%CI −17.4, 3.7) or trends in clinic visitation over time during the lockdown period (−0.2, 95%CI −3.4, 3.1). We did detect a reduction in child healthcare visits at the lockdown (−7.2 visits/clinic/day, 95%CI −9.2, −5.3), which was seen in both children <1 and children 1–5. In contrast, we found a significant increase in HIV visits immediately after the lockdown (8.4 visits/clinic/day, 95%CI 2.4, 14.4). No other differences in clinic visitation were found for perinatal care and family planning, non-communicable diseases, or among adult men and women. CONCLUSIONS: In rural KZN, the ambulatory healthcare system was largely resilient during the national-wide lockdown order. A major exception was child healthcare visitation, which declined immediately after the lockdown but began to normalize in the weeks thereafter. Future work should explore efforts to decentralize chronic care for high-risk populations and whether catch-up vaccination programs might be required in the wake of these findings.


title: Differential induction of type I interferon by type I and type II feline coronaviruses in vitro

text: Abstract Feline infectious peritonitis (FIP) is a feline coronavirus (FCoV)-induced fatal disease in wild and domestic cats. There are two FCoV serotypes. Both type I and II FCoV can replicate in Felis catus whole fetus (fcwf)-4 cells, but the replicability of type I FCoV in feline cell lines is lower than that of type II FCoV, the reason for which is unclear. Inhibition of IFNβ production by non-structural and structural proteins, excluding spike protein has been reported in many coronavirus infections. In this study, we investigated whether IFNβ is involved in the difference in replicability in feline cell lines between types I and II FCoV. When fcwf-4 cells were infected with FCoV, the virus titer of type II FCoV in the culture supernatant was higher than that of type I FIPV. When the IFNβ expression level in FCoV-infected fcwf-4 cells was semi-quantitatively analyzed, infection with type I FIPV, excluding type I FIPV UCD-1, highly induced IFNβ expression. In contrast, induction of IFNβ by type II FCoV infection was significantly lower than that by type I FIPV. In addition, when fcwf-4 cells were adsorbed by FIPV and then stimulated with Poly(I:C), type II FCoV infection inhibited Poly(I:C)-induced IFNβ gene expression. Also, the proliferation of type I FIPV was enhanced by a IFN inhibitor. These findings clarified that, unlike type I FIPV, type II FCoV strongly inhibits IFNβ expression in infected cells. It was also suggested that the IFNβ-inducing ability is different among type I FIPV strains.


title: Critical adjustments in a department of orthopaedics through the COVID-19 pandemic

text: PURPOSE: SARS-CoV-2’s new scenario has forced health systems to work under extreme stress urging to perform a complete reorganization of the way our means and activities were organized. The orthopaedic and trauma units have rescheduled their activities to help SARS-CoV-2 units, but trauma patients require also treatment, and no standardized protocols have been established. METHODS: A single-centre cross-sectional study was performed in a tertiary hospital. Two different periods of time were analyzed: a two week period of time in March 2019 (pre-SARS-CoV-2) and the same period in March 2020 (SARS-CoV-2 pandemic time). Outpatient’s data, emergency activity, surgical procedures, and admissions were evaluated. Surgeons’ and patient’s opinion was also evaluated using a survey. RESULTS: A total of ~ 16k (15,953) patients were evaluated. Scheduled clinical appointments decreased by ~ 22%. Urgent consultations and discharge from clinics also descended (~ 37% and ~ 20% respectively). Telemedicine was used in 90% of outpatient clinical evaluations. No elective surgical procedures during SARS-CoV-2 time were scheduled, and subtracting the effect of elective surgeries, there was a reduction of inpatient surgeries, from ~ 85% to ~ 59%. Patients delayed trauma assistance more than 48 hours in 13 cases (35%). Pre-operative admission for hip fractures decreased in ten hours on average. Finally, surveys stated that patients were more in favour than surgeons were to this new way to evaluate orthopaedic and trauma patients based strongly on telemedicine. CONCLUSION: Detailed protocols should be standardized for surgical departments during the pandemic. This paper offers a general view in how this virus affects an orthopaedic unit and could serve as a protocol and example for orthopaedic and trauma units. Even in the worst scenario, an orthopaedic and trauma unit could offer an effective, efficient, and quality service. SARS-CoV-2 will set up a new paradigm for health care in orthopaedics and trauma.


title: Choosing Wisely® in Hematology: Have We Made a Difference?

text: PURPOSE OF REVIEW: The Choosing Wisely® initiative, led by the American Board of Internal Medicine Foundation in collaboration with national professional medical societies, aims to help patients choose care that is essential, free from harm, and evidence-based. The American Society of Hematology has advocated practices specific to hematology for physicians and patients to examine carefully. Here, we summarize various barriers to adopting these practices, interventions used to improve adoption, and challenges in measuring the effectiveness of these interventions. RECENT FINDINGS: The Choosing Wisely® campaign has become an international effort with more than 20 countries worldwide having embraced it. Such widespread interest indicates that the campaign initiated an important dialog between patients and physicians about overutilization of resources. Evidence showing the positive impact of interventions on adopting these practices is accumulating, but their effect on improving clinical outcomes is uncertain. SUMMARY: Decreasing overuse of resources is a cultural change in perspective for practitioners and patients alike. We believe that healthcare delivery is transitioning from being volume-based to value-based. As we continue to support the Choosing Wisely® campaign, we need to implement strategies to document and measure the influence of our value-based recommendations on physician practices, patient care and attitudes, and healthcare costs.


title: Diagnosis and Treatment of Pharyngitis in Children

text: Acute pharyngitis is one of the most common illnesses for which children visit primary care physicians. Most cases of acute pharyngitis in children are caused by viruses and are benign and self-limited. Group A beta-hemolytic streptococcus is the most important of the bacterial causes of acute pharyngitis. Strategies for diagnosis and treatment of acute pharyngitis are directed at distinguishing children with viral pharyngitis, who would not benefit from antimicrobial therapy, from children with group A beta-hemolytic streptococcal pharyngitis, for whom antimicrobial therapy would be beneficial. Making this distinction is crucial in attempting to minimize the unnecessary use of antimicrobial agents in children.


title: Factors associated with prolonged viral RNA shedding in patients with COVID-19

text: BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) is becoming a public health emergency. Data are limited on the duration and host factors related to viral shedding. METHODS: In this retrospective study, risk factors associated with severe acute respiratory coronavirus 2 (SARS-CoV-2) RNA shedding were evaluated in a cohort of 113 symptomatic patients from two hospitals outside Wuhan. RESULTS: The median duration of SARS-CoV-2 RNA detection was 17 days (Interquartile Range [IQR], 13–22 days) as measured from illness onset. When comparing patients with early (<15 days) and late viral RNA clearance (≥15 days after illness onset), prolonged SARS-CoV-2 RNA shedding was associated with male sex (p=0.009), old age (p=0.033), concomitated with hypertension (p=0.009), delayed admission to hospital after illness onset (p=0.001), severe illness at admission (p=0.049), invasive mechanical ventilation (p=0.006), and corticosteroid treatment (p=0.025). Patients with longer SARS-CoV-2 RNA shedding duration had slower recovery of body temperature (p<0.001) and focal absorption on radiograph images (p<0.001) than patients with early SARS-CoV-2 RNA clearance. Male sex (odds ratio [OR], 3.24 [95% CI, 1.31–8.02]), delayed hospital admission (OR, 1.30 [95% CI, 1.10–1.54]), and invasive mechanical ventilation (OR, 9.88 [95% CI, 1.11–88.02]) were independent risk factors for prolonged SARS-CoV-2 RNA shedding. CONCLUSIONS: Male sex, delayed admission to hospital after illness onset, and invasive mechanical ventilation were associated with prolonged SARS-CoV-2 RNA shedding. Hospital admission and general treatments should be started as soon as possible in symptomatic COVID-19 patients, especially male patients.


title: Covid-19 pneumonia, Takotsubo syndrome and left ventricle thrombi

text: Left ventricle thrombus is considered a rare complication of Takotsubo syndrome. However, both a stress condition predisposing to Takotsubo syndrome and coagulation abnormalities coexist in COVID-19. We describe a case of COVID-19 patient with Takotsubo.


title: Lack of cross-neutralization by SARS patient sera towards SARS-CoV-2

text: Despite initial findings indicating that SARS-CoV and SARS-CoV-2 are genetically related belonging to the same virus species and that the two viruses used the same entry receptor, angiotensin-converting enzyme 2 (ACE2), our data demonstrated that there is no detectable cross-neutralization by SARS patient sera against SARS-CoV-2. We also found that there are significant levels of neutralizing antibodies in recovered SARS patients 9–17 years after initial infection. These findings will be of significant use in guiding the development of serologic tests, formulating convalescent plasma therapy strategies, and assessing the longevity of protective immunity for SARS-related coronaviruses in general as well as vaccine efficacy.


COVID-19 contact tracing apps: the ‘elderly paradox’


title: Can antiglycolipid antibodies present in HIV‐infected individuals induce immune demyelination?

text: Of the eight clinically defined neuropathies associated with HIV infection, there is compelling evidence that acute and chronic inflammatory demyelinating polyneuropathy (IDPN) have an autoimmune pathogenesis. Many non‐HIV infected individuals who suffer from sensorymotor nerve dysfunction have autoimmune indicators. The immunopathogenesis of demyelination must involve neuritogenic components in myelin. The various antigens suspected to play a role in HIV‐seronegative IDPN include (i) P(2) protein; (ii) sulfatide (GalS); (iii) various gangliosides (especially GM(1)); (iv) galactocerebroside (GalC); and (v) glycoproteins or glycolipids with the carbohydrate epitope glucuronyl‐3‐sulfate. These glycoproteins or glycolipids may be individually targeted, or an immune attack may be raised against a combination of any of these epitopes. The glycolipids, however, especially GalS, have recently evoked much interest as mediators of immune events underlying both non‐HIV and HIV‐associated demyelinating neuropathies. The present review outlines the recent research findings of antiglycolipid antibodies present in HIV‐infected patients with and without peripheral nerve dysfunction, in an attempt to arrive at some consensus as to whether these antibodies may play a role in the immunopathogenesis of HIV‐associated inflammatory demyelinating polyneuropathy.


Les officinaux Prêts à participer au dépistage des patients infectés par le sars-CoV-2


The COVID-19 pandemic: The ‘black swan’ for mental health care and a turning point for e-health


title: Universal and Serial Laboratory Testing for SARS-CoV-2 at a Long-Term Care Skilled Nursing Facility for Veterans — Los Angeles, California, 2020

text: On March 28, 2020, two residents of a long-term care skilled nursing facility (SNF) at the Veterans Affairs Greater Los Angeles Healthcare System (VAGLAHS) had positive test results for SARS-CoV-2, the cause of coronavirus disease 2019 (COVID-19), by reverse transcription-polymerase chain reaction (RT-PCR) testing of nasopharyngeal specimens collected on March 26 and March 27. During March 29-April 23, all SNF residents, regardless of symptoms, underwent serial (approximately weekly) nasopharyngeal SARS-CoV-2 RT-PCR testing, and positive results were communicated to the county health department. All SNF clinical and nonclinical staff members were also screened for SARS-CoV-2 by RT-PCR during March 29-April 10. Nineteen of 99 (19%) residents and eight of 136 (6%) staff members had positive test results for SARS-CoV-2 during March 28-April 10; no further resident cases were identified on subsequent testing on April 13, April 22, and April 23. Fourteen of the 19 residents with COVID-19 were asymptomatic at the time of testing. Among these residents, eight developed symptoms 1-5 days after specimen collection and were later classified as presymptomatic; one of these patients died. This report describes an outbreak of COVID-19 in an SNF, with case identification accomplished by implementing several rounds of RT-PCR testing, permitting rapid isolation of both symptomatic and asymptomatic residents with COVID-19. The outbreak was successfully contained following implementation of this strategy.


title: Extreme reactive thrombocytosis in a healthy 6 year-old child

text: Abstract Thrombocytosis is usually found by chance in children. Reactive or secondary thrombocytosis is the more common form, with infectious diseases being the most prevalent cause of it. Regarding the number of platelets there are four degrees of thrombocytosis; in its extreme degree the number of platelets exceeds 1,000,000/mm3. We describe a case of extreme reactive thrombocytosis in a healthy 6-year-old child. He required critical care admission for diagnosis and treatment (maximum number of platelets 7,283,000/mm3). We review the different causes of thrombocytosis in childhood, the differential diagnosis, and the available treatments in case of extreme thrombocytosis.


title: Spatiotemporal Dynamics of COVID-19 epidemic in the State of Kuwait

text: Abstract Objectives The prompt understanding of the temporal and spatial patterns of the epidemic on a national level is a critical step for the timely allocation of surveillance resources. Therefore, we explored the temporal and spatiotemporal dynamics of the COVID-19 epidemic in Kuwait using daily confirmed case data collected between the 23rd of February and the 7th of May, 2020. Methods We quantified the epidemic progression using the time-dependent reproductive number (R(t)), while we used the spatiotemporal scan statistic model to identify local clustering events. We accounted for the variability in the transmission dynamics within and between two socioeconomic classes, including citizens-residents and migrant workers. Results Overall, the epidemic size in Kuwait continues to grow (R(t)s ≥ 2), indicating significant ongoing spread. Significant spreading and clustering events were detected among migrant workers due to their densely populated areas and poor living conditions. However, the government's aggressive intervention measures substantially lowered epidemic growth in migrant worker areas. Yet, at a later stage of the study period, we inferred active spreading and clustering events among both socioeconomic classes. Conclusions Our analyses unveiled deeper insights into the epidemiology of COVID-19 in Kuwait and provided an important platform for rapid guidance of decisions related to intervention activities.


title: The heterogeneity of public ex situ collections of microorganisms: Empirical evidence about conservation practices, industry spillovers and public goods

text: Abstract Public service (ex situ) micro-organism collections serve to secure genetic resources for unforeseen future needs, and importantly, to provide authenticated biomaterials for contemporaneous use in private and public entities and as upstream research materials. Hence, it is important to understand the functioning and strategic decisions of these providers of public good resources. 2 2 Here we refer to public goods in a general way as goods which are relatively costly to exclude others from using, and, whose consumption by one user does not in a significant way reduce the quantity of the good available for others to use. The existing literature tends to use case studies of individual collections. This paper uses a unique worldwide survey of microbial collections to analyse the heterogeneity among culture collections, and to empirically assess the economic and institutional conditions that contribute to this heterogeneity with respect to conservation choice and associated industry spillovers. Results suggest that in the short run public-private partnerships may indeed support knowledge accumulation with particularly strong public good properties. It is important to be aware of this strong tie, in order to steer also the long term conservation patrimony into one that offers not only short term usability but also resilience to future unforeseen needs e.g. of emerging crop plagues.


title: Equine faecal microbiota transplant: Current knowledge, proposed guidelines and future directions

text: While certainly not a novel concept, faecal microbiota transplant (FMT) has recently garnered renewed interest in veterinary medicine due to its remarkable success in treating recurrent Clostridium difficile infection (CDI) in man. There is a dearth of information on indications and efficacy of FMT for the treatment of gastrointestinal disorders in the horse; however, based on evidence in man and other veterinary species, and anecdotal reports in horses, FMT may be a useful treatment for selected cases of acute and chronic diarrhoea and inflammatory bowel disease (IBD) in the horse. In the absence of evidence, expert opinion is offered on case selection and FMT procedure. More research is needed to explore the efficacy, indications and optimal preparation, storage and delivery of FMT to horses.


title: Strategies and recommendations for the management of gastrointestinal surgery during the COVID-19 pandemic: experience shared by Chinese surgeons

text: Novel coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing public-health pandemic worldwide. Although SARS-CoV-2 has been known to spread primarily through respiratory droplets, recent evidence also supports fecal/oral as an additional route of transmission, raising concerns over gastrointestinal (GI) transmission of the infection. Herein, we, as the front-line Chinese GI surgeons, would like to share our experience and lessons in the combat against COVID-19. It is essential to create science-based, rational, and practical strategies during the outbreak of COVID-19. Here, we provide multi-institutional consensus on minimizing disease transmission while continuing to provide care from all aspects for patients in GI surgery, including outpatient clinics, inpatient units, gastrointestinal endoscopy centers, and adjustments in perioperative care. Our experiences and recommendations are worth sharing and may help to establish specific infection-control and outcome measures.


title: Replicative homeostasis II: Influence of polymerase fidelity on RNA virus quasispecies biology: Implications for immune recognition, viral autoimmunity and other "virus receptor" diseases

text: Much of the worlds' population is in active or imminent danger from established infectious pathogens, while sporadic and pandemic infections by these and emerging agents threaten everyone. RNA polymerases (RNA(pol)) generate enormous genetic and consequent antigenic heterogeneity permitting both viruses and cellular pathogens to evade host defences. Thus, RNA(pol )causes more morbidity and premature mortality than any other molecule. The extraordinary genetic heterogeneity defining viral quasispecies results from RNA(pol )infidelity causing rapid cumulative genomic RNA mutation a process that, if uncontrolled, would cause catastrophic loss of sequence integrity and inexorable quasispecies extinction. Selective replication and replicative homeostasis, an epicyclical regulatory mechanism dynamically linking RNApol fidelity and processivity with quasispecies phenotypic diversity, modulating polymerase fidelity and, hence, controlling quasispecies behaviour, prevents this happening and also mediates immune escape. Perhaps more importantly, ineluctable generation of broad phenotypic diversity after viral RNA is translated to protein quasispecies suggests a mechanism of disease that specifically targets, and functionally disrupts, the host cell surface molecules – including hormone, lipid, cell signalling or neurotransmitter receptors – that viruses co-opt for cell entry. This mechanism – "Viral Receptor Disease (VRD)" – may explain so-called "viral autoimmunity", some classical autoimmune disorders and other diseases, including type II diabetes mellitus, and some forms of obesity. Viral receptor disease is a unifying hypothesis that may also explain some diseases with well-established, but multi-factorial and apparently unrelated aetiologies – like coronary artery and other vascular diseases – in addition to diseases like schizophrenia that are poorly understood and lack plausible, coherent, pathogenic explanations.


title: The Use of Recombinant Feline Interferon Omega Therapy as an Immune-Modulator in Cats Naturally Infected with Feline Immunodeficiency Virus: New Perspectives

text: Type I interferons (IFNs) are well-known cytokines that, among their main functions, are key components of the host immune response against viral infections. Due to its immune modulation properties, they are commonly used in the therapeutic approach of various retroviral infections, namely human immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV). In HIV infection, it has been shown that IFN therapy limits early viral replication, particularly useful on post-exposure prophylaxis. In veterinary medicine, recombinant feline interferon omega (rFeIFN-ω) was the first interferon licensed for use in cats. Several studies have recently shown that this compound seems to stimulate the innate immunity, decreasing clinical signs and co-infections in naturally FIV-infected cats. More than summarizing the main conclusions about rFeIFN-ω in cats, this review emphasizes the immune-modulation properties of IFN therapy, opening new perspectives for its use in retroviral infections. Either in FIV-infected cats or in HIV individuals, type I IFNs seem to induce an innate immune-modulation and should not be overlooked as a therapeutic option in retroviral infections.


title: Prion Diseases as Transmissible Zoonotic Diseases

text: Prion diseases, also called transmissible spongiform encephalopathies (TSEs), lead to neurological dysfunction in animals and are fatal. Infectious prion proteins are causative agents of many mammalian TSEs, including scrapie (in sheep), chronic wasting disease (in deer and elk), bovine spongiform encephalopathy (BSE; in cattle), and Creutzfeldt–Jakob disease (CJD; in humans). BSE, better known as mad cow disease, is among the many recently discovered zoonotic diseases. BSE cases were first reported in the United Kingdom in 1986. Variant CJD (vCJD) is a disease that was first detected in 1996, which affects humans and is linked to the BSE epidemic in cattle. vCJD is presumed to be caused by consumption of contaminated meat and other food products derived from affected cattle. The BSE epidemic peaked in 1992 and decreased thereafter; this decline is continuing sharply owing to intensive surveillance and screening programs in the Western world. However, there are still new outbreaks and/or progression of prion diseases, including atypical BSE, and iatrogenic CJD and vCJD via organ transplantation and blood transfusion. This paper summarizes studies on prions, particularly on prion molecular mechanisms, BSE, vCJD, and diagnostic procedures. Risk perception and communication policies of the European Union for the prevention of prion diseases are also addressed to provide recommendations for appropriate government policies in Korea.


title: Potential COVID-19 infection in patients with severe multiple sclerosis treated with alemtuzumab

text: BACKGROUND: Management of disease-modifying therapies in Multiple Sclerosis (MS) during the COVID-19 pandemic is a controversial issue. Alemtuzumab is an immunosuppressive drug that induces lymphocytes depletion. In this study, we aimed to evaluate the frequency and severity of COVID-19 in a case series of patients treated with alemtuzumab in our center. METHODS: Ten patients with a diagnosis of relapsing-remitting MS were phoned and asked about symptoms suggestive and COVID-19 using a semi-structured questionnaire. RESULTS: The mean age was 43.7 ± 9.65 years old, and 8 (80%) were females. The mean time since disease diagnosis was 17.30 ± 8.59 years, and all were patients with relapsing-remitting MS. Mean time from the last dose of Alemtuzumab was 9.80 ± 6.64 months, and last lymphocyte count was 760 ± 231 / μL. Two patients (20%) developed symptoms highly suggestive of COVID-19. Disease duration was 2 and 7 days. None patient required hospital admission. Patients with COVID-19 symptoms had longer clinical course of MS. Conversely, we did not find statistically significant differences regarding age, EDSS, last lymphocyte count, and months since the last dose of alemtuzumab administered between patients having or not symptoms of COVID-19. CONCLUSIONS: Our data suggest that patients receiving alemtuzumab showed very mild symptoms of COVID-19. We speculate that immune reconstitution induced by treatment may induce positive changes in the immune system in the defense against SARS-CoV2. Further research about alemtuzumab and their role in COVID-infection is necessary to confirm these preliminary findings.


title: Characterization of a Pathogenic Full-Length cDNA Clone and Transmission Model for Porcine Epidemic Diarrhea Virus Strain PC22A

text: Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic alphacoronavirus. In the United States, highly virulent PEDV strains cause between 80 and 100% mortality in suckling piglets and are rapidly transmitted between animals and farms. To study the genetic factors that regulate pathogenesis and transmission, we developed a molecular clone of PEDV strain PC22A. The infectious-clone-derived PEDV (icPEDV) replicated as efficiently as the parental virus in cell culture and in pigs, resulting in lethal disease in vivo. Importantly, recombinant PEDV was rapidly transmitted to uninoculated pigs via indirect contact, demonstrating virulence and efficient transmission while replicating phenotypes seen in the wild-type virus. Using reverse genetics, we removed open reading frame 3 (ORF3) and replaced this region with a red fluorescent protein (RFP) gene to generate icPEDV-ΔORF3-RFP. icPEDV-ΔORF3-RFP replicated efficiently in vitro and in vivo, was efficiently transmitted among pigs, and produced lethal disease outcomes. However, the diarrheic scores in icPEDV-ΔORF3-RFP-infected pigs were lower than those in wild-type-virus- or icPEDV-infected pigs, and the virus formed smaller plaques than those of PC22A. Together, these data describe the development of a robust reverse-genetics platform for identifying genetic factors that regulate pathogenic outcomes and transmission efficiency in vivo, providing key infrastructural developments for developing and evaluating the efficacy of live attenuated vaccines and therapeutics in a clinical setting.


title: Chapter 1 Introduction to Animal Viruses

text: Abstract Viruses are infectious agents that are not cellular in nature. They consist of a nucleic acid genome packaged within a protein shell. Although relatively simple, viruses exhibit significant diversity in terms of size, genome organization, and capsid architecture. All viruses are obligate intracellular parasites as they must obtain energy and building blocks from the cell. They subvert many host cell processes for their own replication, and studying virus replication has provided detailed information about the basic workings of cells. At the cellular level, possible outcomes of infection range from production of virus particles without damage to the cell, to cell death, or occasionally cell transformation. In humans and animals the outcomes of infection range from inapparent (no disease) to considerable disease and death. Some viruses cause acute infections lasting for days or a few weeks while others infect their hosts for a lifetime. Viruses can evolve and rapidly adapt to changing conditions. Some viruses are easily replicated in cultured cells, while others require specific conditions only found in specialized cells within a human or animal. While this text focuses on viruses of humans and other animals, viruses infect organisms of all types, from bacteria to fungi to plants. Viruses are most often classified based on groups of genome and virion characteristics. Genome sequence comparisons provide an unbiased method for grouping and categorizing viruses.


title: A novel three-dimensional aerogel biochip for molecular recognition of nucleotide acids

text: Abstract Mesoporous aerogel was produced under regular atmospheric conditions using the sol–gel polymerization of tetraethyl orthosilicate with an ionic liquid as both solvent and active agent. This was then used to build a three-dimensional structure to recognize nucleotide acids. Fourier transformation infrared spectroscopy, scanning electron microscopy, 29Si solid-state nuclear magnetic resonance, and Brunauer–Emmett–Teller instruments were used to characterize this 3D aerogel, demonstrating that it had high porosity and large internal networking surface area that could capture nucleotide acids. The functionality of molecular recognition on nucleotide acids was demonstrated by immobilizing an oligonucleotide to probe its DNA target and confirming the tagged fluorescent signals by confocal laser scanning microscopy. The results indicated that the as-prepared 3D bioaerogel was capable of providing a very large surface area to capture and recognize human gene ATP5O.


title: Unfolded protein response pathways regulate Hepatitis C virus replication via modulation of autophagy

text: Abstract Background Hepatitis C virus (HCV) induces endoplasmic reticulum (ER) stress which, in turn, activates the unfolding protein response (UPR). UPR activates three distinct signalling pathways. Additionally, UPR induces autophagy (UPR-autophagy pathways). On the other hand, it has become clear that some positive-single-strand RNA viruses utilize autophagy. Some groups have used the siRNA silencing approach to show that autophagy is required for HCV RNA replication. However, the mechanism of induction of the UPR-autophagy pathways remain unclear in the cells with HCV. Method and results: we used a genome-length HCV RNA (strain O of genotype 1b) replication system (OR6) in hepatoma cells (HuH-7-derived OR6 cells). As control, we used OR6c cells from which the HCV genome had been removed by treatment with interferon-α. The UPR-autophagy pathways were activated to a greater degree in the OR6 cells as compared to the OR6c cells. Rapamycin, mTOR-independent autophagy inducer, activated HCV replication in the OR6 cells. On the other hand, HCV replication in the cells was inhibited by 3-methyladenine (3-MA), which is an inhibitor of autophagy. Salubrinal (Eukaryotic Initiation Factor 2(eIF2)-alpha phosphatase inhibitor), 3-ethoxy-5, 6-dibromosalicylaldehyde (X-box binding protein-1 (XBP-1) splicing inhibitor) and sp600125 (c-Jun N-terminal kinases (JNK) inhibitor) inhibited HCV replication and autophagy. Additionally, HCV replication and autophagy were inhibited more strongly by combination of these inhibitors. Conclusion Our results suggest that UPR-autophagy pathways exert an influence on HCV replication. Therefore, control these pathways may serve as a novel therapeutic strategy against replication of HCV.


title: Development of an inactivated vaccine candidate for SARS-CoV-2

text: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are currently no SARS-CoV-2-specific treatments or vaccines available due to the novelty of the virus. Hence, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here we developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against SARS-CoV-2 strains. Three immunizations using two different doses (3 μg or 6 μg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support clinical development of SARS-CoV-2 vaccines for humans.


title: REMOTE WORKING DURING THE PANDEMIC: A Q&A WITH GILLIAN ISAACS RUSSELL : Questions from the Editor and Editorial Board of the BJP

text: In this interview by email, Gillian Isaacs Russell, author of the influential Screen Relations: The Limits of Computer‐Mediated Psychoanalysis and Psychotherapy, responds to a set of questions from the BJP. The interview focuses on the impact of remote working during the coronavirus epidemic, starting with the question of whether an effective therapeutic process can occur without physical co‐presence. Isaacs Russell shares her immediate thoughts about the virtually overnight changes to our practice that came with the epidemic, and the work of the American Psychoanalytic Association's Covid‐19 Advisory Team, on which she sits. Her responses are informed by recent cross‐disciplinary and neuropsychological research on the digital age. She considers what happens to free association, evenly suspended attention and reverie when working by phone or online; the loss of the consulting room as a containing physical space for both clinician and patient; the relationship between place and time; and whether (and how) we can maintain a focus on transference and countertransference in the presence of the threat of death. The interview ends with her thoughts on whether we should assume that the landscape of analytic therapy will be permanently altered by Covid‐19, and with her hope that general awareness of the impact of trauma on our mental health has been raised.


title: Systematic review of COVID‐19 in children shows milder cases and a better prognosis than adults

text: AIM: The coronavirus disease 2019 (COVID‐19) pandemic has affected hundreds of thousands of people. Data on symptoms and prognosis in children are rare. METHODS: A systematic literature review was carried out to identify papers on COVID‐19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), using the MEDLINE and Embase databases between January 1 and March 18, 2020. RESULTS: The search identified 45 relevant scientific papers and letters. The review showed that children have so far accounted for 1%‐5% of diagnosed COVID‐19 cases, they often have milder disease than adults and deaths have been extremely rare. Diagnostic findings have been similar to adults, with fever and respiratory symptoms being prevalent, but fewer children seem to have developed severe pneumonia. Elevated inflammatory markers were less common in children, and lymphocytopenia seemed rare. Newborn infants have developed symptomatic COVID‐19, but evidence of vertical intrauterine transmission was scarce. Suggested treatment included providing oxygen, inhalations, nutritional support and maintaining fluids and electrolyte balances. CONCLUSIONS: The coronavirus disease 2019 has occurred in children, but they seemed to have a milder disease course and better prognosis than adults. Deaths were extremely rare.


SARS-CoV-2: “Three-steps” infection model and CSF diagnostic implication


title: Predicting and Evaluating the Epidemic Trend of Ebola Virus Disease in the 2014-2015 Outbreak and the Effects of Intervention Measures

text: We constructed dynamic Ebola virus disease (EVD) transmission models to predict epidemic trends and evaluate intervention measure efficacy following the 2014 EVD epidemic in West Africa. We estimated the effective vaccination rate for the population, with basic reproduction number (R(0)) as the intermediate variable. Periodic EVD fluctuation was analyzed by solving a Jacobian matrix of differential equations based on a SIR (susceptible, infective, and removed) model. A comprehensive compartment model was constructed to fit and predict EVD transmission patterns, and to evaluate the effects of control and prevention measures. Effective EVD vaccination rates were estimated to be 42% (31–50%), 45% (42–48%), and 51% (44–56%) among susceptible individuals in Guinea, Liberia and Sierra Leone, respectively. In the absence of control measures, there would be rapid mortality in these three countries, and an EVD epidemic would be likely recur in 2035, and then again 8~9 years later. Oscillation intervals would shorten and outbreak severity would decrease until the periodicity reached ~5.3 years. Measures that reduced the spread of EVD included: early diagnosis, treatment in isolation, isolating/monitoring close contacts, timely corpse removal, post-recovery condom use, and preventing or quarantining imported cases. EVD may re-emerge within two decades without control and prevention measures. Mass vaccination campaigns and control and prevention measures should be instituted to prevent future EVD epidemics.


title: Immunogenicity of a receptor-binding domain of SARS coronavirus spike protein in mice: Implications for a subunit vaccine

text: We studied the immunogenicity of an anti-SARS subunit vaccine comprised of the fragment of the SARS coronavirus (SARS-CoV) spike protein amino acids 318–510 (S318–510) containing the receptor-binding domain. The S protein fragment was purified from the culture supernatant of stably transformed HEK293T cells secreting a tagged version of the protein. The vaccine was given subcutaneously to 129S6/SvEv mice in saline, with alum adjuvant or with alum plus CpG oligodeoxynucleotides (ODN). Mice immunized with the adjuvanted antigen elicited strong antibody and cellular immune responses; furthermore, adding the CpG ODN to the alum resulted in increased IgG2a antibody titers and a higher number of INF-γ-secreting murine splenocytes. Mice vaccinated with S318–510 deglycosylated by PNGase F (dgS318–510) showed a lower neutralizing antibody response but had similar numbers of INF-γ-producing cells in the spleen. This finding suggests that carbohydrate is important for the immunogenicity of the S318–510 protein fragment and provide useful information for designing an effective and safe SARS subunit vaccine.


title: When Stay-at-Home Orders Leave Victims Unsafe at Home: Exploring the Risk and Consequences of Intimate Partner Violence during the COVID-19 Pandemic

text: The novel coronavirus pandemic (hereafter COVID-19) is likely to have unprecedented impacts on the incidence and impacts of crime and violence globally. This includes impacts to the risk, consequences, and decision-making of women experiencing violence by an intimate partner (hereafter IPV). Most importantly, the COVID-19 pandemic, and its impact on the risk of IPV is likely to differentially impact vulnerable populations, including minority women and those with long histories of victimization and mental health issues. This review paper explores the potential short- and long-term implications of COVID-19 on the risk of IPV, highlighting some of the most recent preliminary data. The economic impact of the COVID-19 pandemic, record levels of male unemployment, added stressors in the home, including the care and home schooling of children, and the social distancing measures required by the epidemiological response, may serve to undermine the decades of progress made in keeping women and children safe at home. Victim police reporting, help-seeking decisions, and social service utilization during the pandemic are likely to be impacted by stay-at-home orders and social distancing requirements. The paper concludes with a discussion of the implications for providing safety planning and self-care for victims and their children.


title: Respiratory Pathogens in Infants Diagnosed with Acute Lower Respiratory Tract Infection in a Tertiary Care Hospital of Western India Using Multiplex Real Time PCR

text: OBJECTIVE: To determine the frequency of respiratory pathogens in infants diagnosed with acute lower respiratory tract infections. METHODS: A prospective cross-sectional observational study was conducted in infants hospitalized with a diagnosis of acute lower respiratory tract infection (ALRTI), in a tertiary care hospital in a metropolitan city of Western India. Nasopharyngeal swabs were analyzed by multiplex real time polymerase chain reaction, for 18 viruses and 3 bacteria (H. influenzae type b, C. pneumoniae and M. pneumoniae). The entire data was entered in Microsoft excel sheet and frequencies were determined. RESULTS: One hundred eligible infants were enrolled. Pathogens were detected in 82 samples, which included Respiratory syncytial viruses (RSV) A / B (35.4%), Human rhinovirus (25.6%), Adenovirus (22%), Human Parainfluenza viruses (11%), Human bocavirus (9.8), Human metapneumovirus A / B (8.5%), Influenza A (H1N1) pdm 09 (6.1%), Parechovirus (3.7%), Human coronaviruses (3.66%), Haemophilus influenzae type b (6.1%), Chlamydia pneumoniae (2.4%) and Mycoplasma pneumoniae (2.4%). Influenza A (other than H1N1), Influenza B, Human Coronavirus 229E and Enterovirus were not detected. The rate of coinfection was 34% and rhinovirus was the most common of the multiple pathogens. CONCLUSIONS: Spectrum of viral etiologies of ALRTI is highlighted. Etiological diagnosis of ALRTI would enable specific antiviral therapy, restrict antibiotic use and help in knowing burden of disease.


When Physical Medicine and Rehabilitation Became Medicine—Life in the Time of Coronavirus Disease of 2019


title: Relative survival of Bacillus subtilis spores loaded on filtering facepiece respirators after five decontamination methods

text: This study determines the relative survival (RS) of Bacillus subtilis spores loaded on an N95 filtering facepiece respirator (FFR) after decontamination by five methods under worst‐case conditions. Relative survival was obtained by testing after decontamination and after storing the FFRs at 37°C and 95% relative humidity for 24 hours. The decontamination methods involved ethanol, bleach, ultraviolet irradiation (UVA 365 nm, UVC 254 nm), an autoclave, and a traditional electric rice cooker (TERC) that was made in Taiwan. Without decontamination, 59 ± 8% of the loaded spores survived for 24 hours. When 70% ethanol was added to the N95 FFR at a packing density of 0.23, the RS was 73 ± 5% initially and decayed to 22 ± 8% in 24 hours. Relative survival remained above 20% after 20 minutes of UVA irradiation. The other four decontamination measures achieved 99%‐100% biocidal efficacy, as measured immediately after the methods were applied to the test FFRs. Relative survival is a useful parameter for measuring sterilization or degree of disinfection. Bleach, UVC, an autoclave, and a TERC provide better biocidal efficacy than ethanol and UVA. Not only a higher filter quality but also a lower value of RS produced the most decontaminated FFR.