title: COVID-19 Disease: Perspectives in Low- and Middle-Income Countries

text: Abstract Pandemics such as COVID-19 bring significant challenges for all health services, especially those in low-to low-middle income countries, where access to supplement and expand services may be difficult. For these countries with a limited workforce the loss of key workers to the illness itself or the need to self-isolate following contact can paralyse service delivery. This article looks at some of the issues that may arise and strategies to overcome them. It includes a case study from Viet Nam illustrating the need for a rapid integrated response to contact and prevent further outbreaks. Caring for COVID-19 patients is a heavily dependent on the skills and expertise of the nurses. There is therefore a need to share nursing interventions that can be implemented without major resource implications in all hospital departments.


title: Crimean-Congo Hemorrhagic Fever: Current Scenario in India

text: India is considered as a hot spot for emerging infectious diseases. In the recent past many infectious diseases of emerging and re-emerging nature have entered this subcontinent and affected a large number of populations. A few examples are Nipah, Avian influenza, Pandemic influenza, severe acute respiratory syndrome corona virus and Chikungunya virus. These diseases have not only affected human and animal health but also economy of the country on a very large scale. During December 2010, National Institute of Virology, Pune detected Crimean-Congo hemorrhagic fever virus specific IgG antibodies in livestock serum samples from Gujarat and Rajasthan states. Subsequently, during January 2011 Crimean-Congo hemorrhagic fever virus was confirmed in a nosocomial outbreak, in Ahmadabad, Gujarat, India. Retrospective investigation of suspected human samples confirmed that the virus was present in Gujarat state, earlier to this outbreak. This disease has a case fatality rate ranging from 5 to 80 %. Earlier presence of hemagglutination inhibition antibodies have been detected in animal sera from Jammu and Kashmir, the western border districts, southern regions and Maharashtra state of India. The evidences of virus activity and antibodies were observed during and after the outbreak in human beings, ticks and domestic animals (buffalo, cattle, goat and sheep) from Gujarat State of India. During the year 2012, this virus was again reported in human beings and animals. Phylogenetic analysis showed that all the four isolates of 2011, as well as the S segment from specimen of 2010 and 2012 were highly conserved and clustered together in the Asian/Middle East genotype IV. The S segment of South-Asia 2 type was closest to a Tajikistan strain TADJ/HU8966 of 1990. The present scenario in India suggests the need to look seriously into various important aspects of this zoonotic disease, which includes diagnosis, intervention, patient management, control of laboratory acquired and nosocomial infection, tick control, livestock survey and this, should be done in priority before it further spreads to other states. Being a high risk group pathogen, diagnosis is a major concern in India where only a few Biosafety level 3 laboratories exist and it needs to be addressed immediately before this disease becomes endemic in India.


title: “Smart” Antimicrobial Nanocomplexes with Potential to Decrease Surgical Site Infections (SSI)

text: The emergence of resistant pathogens is a burden on mankind and threatens the existence of our species. Natural and plant-derived antimicrobial agents need to be developed in the race against antibiotic resistance. Nanotechnology is a promising approach with a variety of products. Biosynthesized silver nanoparticles (AgNP) have good antimicrobial activity. We prepared AgNPs with trans-cinnamic acid (TCA) and povidone–iodine (PI) with increased antimicrobial activity. We synthesized also AgNPs with natural cinnamon bark extract (Cinn) in combination with PI and coated biodegradable Polyglycolic Acid (PGA) sutures with the new materials separately. These compounds (TCA-AgNP, TCA-AgNP-PI, Cinn-AgNP, and Cinn-AgNP-PI) and their dip-coated PGA sutures were tested against 10 reference strains of microorganisms and five antibiotics by zone inhibition with disc- and agar-well-diffusion methods. The new compounds TCA-AgNP-PI and Cinn-AgNP-PI are broad spectrum microbicidal agents and therefore potential coating materials for sutures to prevent Surgical Site Infections (SSI). TCA-AgNP-PI inhibits the studied pathogens stronger than Cinn-AgNP-PI in-vitro and on coated sutures. Dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-Vis), Fourier Transform infrared spectroscopy (FT-IR), Raman, X-ray diffraction (XRD), microstructural analysis by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) confirmed the composition of TCA-AgNP-PI and Cinn-AgNP-PI. Smart solutions involving hybrid materials based on synergistic antimicrobial action have promising future perspectives to combat resistant microorganisms.


title: A pantropic canine coronavirus genetically related to the prototype isolate CB/05

text: Abstract We report the genetic and biological characterisation of a novel pantropic canine coronavirus (CCoV), strain 450/07, which caused the death of a 60-day-old miniature pinscher. At the genetic level, this virus was strictly related to the prototype strain CB/05, but displayed some unique features. After experimental infection with the new pantropic isolate, most inoculated dogs showed diarrhoea and acute lymphopenia. Gross lesions and histological changes were mainly evident in the gut and lymphoid tissues, although some animals showed remarkable changed also in parenchymatous organs. The viral RNA was detected in the faeces and/or internal organs of most pups. These findings seem to indicate that strain 450/07 is able to spread to internal organs (mainly lymphoid tissues), causing lymphopenia but inducing a mild disease.


EU-Wide Access to High-quality, Affordable Precision Diagnostics: An EHA Position Paper


title: How a global social lockdown helps to unlock time for sleep

text: Summary The SARS-CoV-2 pandemic related social lockdown has helped unlock time to give more room to sleep. Although daily stress during lockdown increased, and sleep quality decreased, sleep behaviour was generally healthier, as two novel research papers show.


title: Products in a Pandemic: Liability for Medical Products and the Fight against COVID-19

text: A multitude of medical products are being developed and produced as part of efforts to tackle COVID-19. They are varied in nature and range from test kits to tracing apps, protective equipment, ventilators, medicines and, of course, vaccines. The design, testing and manufacture of many of these products differs from production in normal times due to the urgency of the situation and the rapid increase in demand created by the pandemic. This article considers the legal issues arising as a result of the production of emergency products, particularly from a products liability perspective. To what extent do existing concepts under the European Product Liability Directive, such as defect, causation and the various defences, permit the pandemic to be taken into account when a Court is considering issues of liability? What is the impact on liability of the modified regulatory regime? In light of that discussion, the case for alternative responses is examined from a comparative and European perspective, including the issue of Government indemnities for the manufacturers of products, legal exemptions from liability and alternative no-fault compensation schemes.


title: Review of practical recommendations for otolaryngologists and head and neck surgeons during the COVID-19 pandemic: Recommendations for otolaryngologists during the COVID-19 pandemic

text: INTRODUCTION: Otolaryngologists are at very high risk of COVID-19 infection while performing examination or surgery. Strict guidelines for these specialists have not already been provided, while currently available recommendations could presumably change in course of COVID-19 pandemic as the new data increases. OBJECTIVES: This study aimed to synthesize evidence concerning otolaryngology during COVID‐19 pandemic. It presents a review of currently existing guidelines and recommendations concerning otolaryngological procedures and surgeries during COVID-19 pandemic, and provides a collective summary of all crucial information for otolaryngologists. It summarizes data concerning COVID-19 transmission, diagnosis, and clinical presentation highlighting the information significant for otolaryngologists. METHODS: The Medline and Web of Science databases were searched without time limit using terms ‘‘COVID-19”, “SARS-CoV-2” in conjunction with “head and neck surgery”, “otorhinolaryngological manifestations”. RESULTS: Patients in stable condition should be consulted using telemedicine options. Only emergency consultations and procedures should be performed during COVID-19 pandemic. Mucosa-involving otolaryngologic procedures are considered high risk procedures and should be performed using enhanced PPE (N95 respirator and full face shield or powered air-purifying respirator, disposable gloves, surgical cap, gown, shoe covers). Urgent surgeries for which there is not enough time for SARS-CoV-2 screening are also considered high risk procedures. These operations should be performed in a negative pressure operating room with high-efficiency particulate air filtration. Less urgent cases should be tested for COVID-19 twice, 48 hours preoperatively in 24 hours’ interval. CONCLUSIONS: This review serves as a collection of current recommendations for otolaryngologists for how to deal with their patients during COVID-19 pandemic.


title: Practical pathology of aging mice

text: Old mice will have a subset of lesions as part of the progressive decline in organ function that defines aging. External and palpable lesions will be noted by the research, husbandry, or veterinary staff during testing, cage changing, or physical exams. While these readily observable lesions may cause alarm, not all cause undue distress or are life-threatening. In aging research, mice are maintained until near end of life that, depending on strain and genetic manipulation, can be upwards of 33 months. Aging research has unique welfare issues related to age-related decline, debilitation, fragility, and associated pain of chronic diseases. An effective aging research program includes the collaboration and education of the research, husbandry, and veterinary staff, and of the members of the institution animal care and use committee. This collaborative effort is critical to humanely maintaining older mice and preventing excessive censorship due to non-lethal diseases. Part of the educational process is becoming familiar with how old mice appear clinically, at necropsy and histopathologically. This baseline knowledge is important in making the determination of humane end points, defining health span, contributing causes of death and effects of interventions. The goal of this paper is to introduce investigators to age-associated diseases and lesion patterns in mice from clinical presentation to pathologic assessment. To do so, we present and illustrate the common clinical appearances, necropsy and histopathological lesions seen in subsets of the aging colonies maintained at the University of Washington.


title: Biophysical approaches for exploring lipopeptide-lipid interactions

text: Abstract In recent years, lipopeptides (LPs) have attracted a lot of attention in the pharmaceutical industry due to their broad-spectrum of antimicrobial activity against a variety of pathogens and their unique mode of action. This class of compounds has enormous potential for application as an alternative to conventional antibiotics and for pest control. Understanding how LPs work from a structural and biophysical standpoint through investigating their interaction with cell membranes is crucial for the rational design of these biomolecules. Various analytical techniques have been developed for studying intramolecular interactions with high resolution. However, these tools have been barely exploited in lipopeptide-lipid interactions studies. These biophysical approaches would give precise insight on these interactions. Here, we reviewed these state-of-the-art analytical techniques. Knowledge at this level is indispensable for understanding LPs activity and particularly their potential specificity, which is relevant information for safe application. Additionally, the principle of each analytical technique is presented and the information acquired is discussed. The key challenges, such as the selection of the membrane model are also been briefly reviewed.


Tracking Mental Health and Symptom Mentions on Twitter During COVID-19


title: COVID-19 from mysterious enemy to an environmental detection process: a critical review

text: The recent global emergence of an unusual viral pneumonia of COVID-19 epidemic was firstly started in Wuhan city, Hubei province in China in December 2019. Regrettably, it is still sweeping the planet, and it cannot be controlled up till now. By May 2020, the unexpected spread of this disaster had caused more than 3,759,967 cases and 259,474 deaths in 114 countries from Asia to the Middle East, Europe, and the USA. Considering its fatal nature, it has evolved as a major challenge for the world. This is necessitating a quick and steep intervention in order to save millions of people’s lives across the globe. The knowledge about the nature and evolution of the COVID-19 virus in water, soils, and other environmental compartments can be addressed through wastewater and sewage. Wastewater-based epidemiology approach can be used as an early indicator of the infection within a specific population. The basic aim of this review article is trying to provide a prompt, and valuable reference guides about COVID-19. Some important questions were addressed, such as, its origin, transmission, clinical symptoms, diagnosis, environmental aspects, and the possible indoors and outdoors airborne transmission minimization strategies that may benefit specialists.


title: Novel Diubiquitin Probes Expand the Chemical Toolkit to Study DUBs

text: Linkage-specific DUBs employ different mechanisms to recognize and cleave polyubiquitin chains of specific linkage types. In this issue of Cell Chemical Biology, Flierman et al. (2016) develop a new family of novel non-hydrolyzable diubiquitin probes that will be valuable tools to study how DUBs achieve specificity.


title: Collective Bargaining During Times of Crisis: Recommendations from the COVID‐19 Pandemic

text: The COVID‐19 dramatically changed employment across sectors in 2020. This Viewpoint essay examines public sector labor relations during the pandemic and describes the impact bargaining process used to protect public employees. We draw on our own experience in impact bargaining negotiations and the public labor relations, conflict management, and civil service reform literatures to develop recommendations for public union labor leaders in times of crisis. We suggest that public unions have an important role in crisis management, but must act strategically in order to develop good working relationships with leadership and successfully negotiate employee protections in uncertain times. This article is protected by copyright. All rights reserved.


title: Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations

text: Abstract Background and aims High prevalence of diabetes makes it an important comorbidity in patients with COVID-19. We sought to review and analyze the data regarding the association between diabetes and COVID-19, pathophysiology of the disease in diabetes and management of patients with diabetes who develop COVID-19 infection. Methods PubMed database and Google Scholar were searched using the key terms ‘COVID-19’, ‘SARS-CoV-2’, ‘diabetes’, ‘antidiabetic therapy’ up to April 2, 2020. Full texts of the retrieved articles were accessed. Results There is evidence of increased incidence and severity of COVID-19 in patients with diabetes. COVID-19 could have effect on the pathophysiology of diabetes. Blood glucose control is important not only for patients who are infected with COVID-19, but also for those without the disease. Innovations like telemedicine are useful to treat patients with diabetes in today’s times.


title: Low-fidelity Venezuelan equine encephalitis virus polymerase mutants to improve live-attenuated vaccine safety and efficacy

text: During RNA virus replication, there is the potential to incorporate mutations that affect virulence or pathogenesis. For live-attenuated vaccines, this has implications for stability, as replication may result in mutations that either restore the wild-type phenotype via reversion or compensate for the attenuating mutations by increasing virulence (pseudoreversion). Recent studies have demonstrated that altering the mutation rate of an RNA virus is an effective attenuation tool. To validate the safety of low-fidelity mutations to increase vaccine attenuation, several mutations in the RNA-dependent RNA-polymerase (RdRp) were tested in the live-attenuated Venezuelan equine encephalitis virus vaccine strain, TC-83. Next generation sequencing after passage in the presence of mutagens revealed a mutant containing three mutations in the RdRp, TC-83 3x, to have decreased replication fidelity, while a second mutant, TC-83 4x displayed no change in fidelity, but shared many phenotypic characteristics with TC-83 3x. Both mutants exhibited increased, albeit inconsistent attenuation in an infant mouse model, as well as increased immunogenicity and complete protection against lethal challenge of an adult murine model compared with the parent TC-83. During serial passaging in a highly permissive model, the mutants increased in virulence but remained less virulent than the parent TC-83. These results suggest that the incorporation of low-fidelity mutations into the RdRp of live-attenuated vaccines for RNA viruses can confer increased immunogenicity whilst showing some evidence of increased attenuation. However, while in theory such constructs may result in more effective vaccines, the instability of the vaccine phenotype decreases the likelihood of this being an effective vaccine strategy.


title: Is the discovery of the novel human betacoronavirus 2c EMC/2012 (HCoV-EMC) the beginning of another SARS-like pandemic?

text: Summary Fouchier et al. reported the isolation and genome sequencing of a novel coronavirus tentatively named “human betacoronavirus 2c EMC/2012 (HCoV-EMC)” from a Saudi patient presenting with pneumonia and renal failure in June 2012. Genome sequencing showed that this virus belongs to the group C species of the genus betacoronavirus and phylogenetically related to the bat coronaviruses HKU4 and HKU5 previously found in lesser bamboo bat and Japanese Pipistrelle bat of Hong Kong respectively. Another patient from Qatar with similar clinical presentation and positive RT-PCR test was reported in September 2012. We compare and contrast the clinical presentation, laboratory diagnosis and management of infection due to this novel coronavirus and that of SARS coronavirus despite the paucity of published information on the former. Since 70% of all emerging infectious pathogens came from animals, the emergence of this novel virus may represent another instance of interspecies jumping of betacoronavirus from animals to human similar to the group A coronavirus OC43 possibly from a bovine source in the 1890s and the group B SARS coronavirus in 2003 from bat to civet and human. Despite the apparently low transmissibility of the virus at this stage, research preparedness against another SARS-like pandemic is an important precautionary strategy.


title: Recherche de virus en microscopie électronique dans les selles d'enfants atteints de gastro-entérite aiguë hivernale

text: Summary During two successive winters, faecal extracts from 110 children under 3 years of age were examined by electron microscopy with negative contrast. In a first group of 22 children hospitalised for various medical disorders, no virus particles were detected. In the second group of 88 children with acute gastroenteritis, we found viruses in 31,8 % of the faecal extracts, Rotavirus were detected in 22,7 % of the specimens and various particles (Adenovirus, Astrovirus, Coronavirus) in 9,1 % of the specimens.


HUMAN CORONAVIRUS-NL63 INFECTION IS NOT ASSOCIATED WITH ACUTE KAWASAKI DISEASE


title: Psychiatric burdens or stress during hospitalization and concerns after discharge in patients with severe acute respiratory syndrome coronavirus-2 isolated in a tertiary care hospital

text: • Quarantined inpatients with SARS-CoV-2 have psychiatric burdens. • Some inpatients had discrimination, prejudice, and suspension and dismissal from work. • Implementation of necessary measures is needed to minimize the risk of long-term social isolation and potential risk of suicide.


title: Antiviral efficacy of nanoparticulate vacuolar ATPase inhibitors against influenza virus infection

text: BACKGROUND: Influenza virus infections are a major public health concern worldwide. Conventional treatments against the disease are designed to target viral proteins. However, the emergence of viral variants carrying drug-resistant mutations can outpace the development of pathogen-targeting antivirals. Diphyllin and bafilomycin are potent vacuolar ATPase (V-ATPase) inhibitors previously shown to have broad-spectrum antiviral activity. However, their poor water solubility and potential off-target effect limit their clinical application. METHODS: In this study, we report that nanoparticle encapsulation of diphyllin and bafilomycin improves the drugs’ anti-influenza applicability. RESULTS: Using PEG-PLGA diblock copolymers, sub-200 nm diphyllin and bafilomycin nanoparticles were prepared, with encapsulation efficiency of 42% and 100%, respectively. The drug-loaded nanoparticles have sustained drug release kinetics beyond 72 hours and facilitate intracellular drug delivery to two different influenza virus-permissive cell lines. As compared to free drugs, the nanoparticulate V-ATPase inhibitors exhibited lower cytotoxicity and greater in vitro antiviral activity, improving the therapeutic index of diphyllin and bafilomycin by approximately 3 and 5-fold, respectively. In a mouse model of sublethal influenza challenge, treatment with diphyllin nanoparticles resulted in reduced body weight loss and viral titer in the lungs. In addition, following a lethal influenza viral challenge, diphyllin nanoparticle treatment conferred a survival advantage of 33%. CONCLUSIONS: These results demonstrate the potential of the nanoparticulate V-ATPase inhibitors for host-targeted treatment against influenza.


title: Development of a real-time RT-PCR assay for detection of resistance to oseltamivir in influenza A pandemic (H1N1) 2009 virus using single nucleotide polymorphism probes

text: Abstract Resistance to oseltamivir in pandemic (H1N1) 2009 influenza A virus is linked to an amino acid change from histidine (H) to tyrosine (Y) at position 275 in the neuraminidase protein (NA). A real-time one step RT-PCR assay using single nucleotide polymorphism (SNP) probes was developed to detect this mutation in respiratory specimens. The limit of detection was 47.6 copies/reaction for wild-type H275 RNA and 52.9 copies/reaction for the mutant H275Y RNA. The assay did not cross-react with other respiratory pathogens. The clinical sensitivity and specificity of the assay was compared to the gold standard Sanger sequencing method using 25 sensitive, 15 resistant and 20 negative samples. The sensitivity and specificity was 88.0% and 100% respectively with the SOIV_Osel_SEN probe designed to detect the H275 allele and 100% for the SOIV_Osel_RES probe detecting the 275Y allele. The sensitivity of the assay using nine admixtures of sensitive and resistant alleles was 88.9% and 77.8% with the SOIV_Osel_SEN probe and SOIV_Osel_RES probe respectively. The presence of mixed sensitive and resistant alleles in patient samples and mixtures of in vitro RNA were detected reproducibly. This assay can be used for screening of original samples for oseltamivir resistance without the need for culture and phenotypic testing.


title: Kinetics of cell migration to the dermis and hypodermis in dogs vaccinated with antigenic compounds of Leishmania braziliensis plus saponin

text: Abstract The search for new immunobiologicals against canine visceral leishmaniasis (CVL) has intensified in the last decade. However, it still remains to be elucidated that mechanisms of the innate immune response in situ after immunization (a.i.). The aim of this study was to investigate the kinetics of cell migration in the skin dogs with distinct antigenic compounds of the LBSap vaccine. Our major findings indicated that saponin adjuvant alone or combined with Leishmania braziliensis antigen induced strong local acute inflammatory reaction. However, these reactions not progressed to ulcerated lesions. Overall, the cell profile found in Sap and LBSap was composed of neutrophils, lymphocytes and eosinophils. There was also increased production of iNOS in Sap and LBSap groups. Thus, we can conclude that dogs immunized by LBSap and the saponin adjuvant elicited a potential innate-immune activations status compatible with effective control of the resistance to infection by Leishmania and contributing to a better understanding of the innate-immunity events induced by the LBSap vaccine.


title: Risk factors for adverse outcomes of Indigenous infants hospitalized with bronchiolitis

text: BACKGROUND: Hospitalized bronchiolitis imposes a significant burden among infants, particularly among Indigenous children. Traditional or known risk factors for severe disease are well described, but there are limited data on risks for prolonged hospitalization and persistent symptoms. Our aims were to determine factors (clinical and microbiological) associated with (i) prolonged length of stay (LOS); (ii) persistent respiratory symptoms at 3 weeks; (iii) bronchiectasis up to ∼24 months post‐hospitalisation; and (iv) risk of respiratory readmissions within 6 months. METHODS: Indigenous infants hospitalized with bronchiolitis were enrolled at Royal Darwin Hospital between 2008 and 2013. Standardized forms were used to record clinical data. A nasopharyngeal swab was collected at enrolment to identify respiratory viruses and bacteria. RESULTS: The median age of 232 infants was 5 months (interquartile range 3–9); 65% male. On multivariate regression, our 12 point severity score (including accessory muscle use) was the only factor associated with prolonged LOS but the effect was modest (+3.0 hr per point, 95%CI: 0.7, 5.1, P = 0.01). Presence of cough at 3 weeks increased the odds of bronchiectasis (OR 3.0, 95%CI: 1.1, 7.0, P = 0.03). Factors associated with respiratory readmissions were: previous respiratory hospitalization (OR 2.3, 95%CI: 1.0, 5.4, P = 0.05) and household smoke (OR 2.6, 95%CI: 1.0, 6.3, P = 0.04). CONCLUSION: Increased severity score is associated with prolonged LOS in Indigenous children hospitalized with bronchiolitis. As persistent symptoms at 3 weeks post‐hospitalization are associated with future diagnosis of bronchiectasis, optimising clinical care beyond hospitalization is needed to improve long‐term respiratory outcomes for infants at risk of respiratory disease. Pediatr Pulmonol. 2016;51:613–623. © 2015 Wiley Periodicals, Inc.


title: Effect of diethylcarbamazine on testing serum samples for retroviral antibodies

text: Abstract Previous investigations have revealed that in vivo use of diethylcarbamazine (N,N-diethyl-4-methyl-1-piperazine carboxamide; DEC), the mainstay of prevention and therapy for filariases, results in increased titers of antibody to feline oncornavirus-associated cell membrane antigen (FOCMA) in feline leukemia virus (FeLV)-infected cats.In the present study, the effect of in vitro DEC on detection of serum antibodies to retroviruses was investigated. The addition of DEC (5 mg ml−1, pH 7·3–7·4) to the serum diluent resulted in detection of antibody to FOCMA by indirect membrane immunofluorescence in five of five FeLV-infected cats, whereas samples from all five cats tested negative without the addition of DEC. In vitro DEC also increased the absorbance values generated by enzyme immunoassay human immunodeficiency virus type 1 (HIV-1) antibody testing of samples from (a) persons with AIDS-related disease; (b) persons with helper T-lymphocytes < 500 mm−3 blood; and (c) persons testing positive for antibody to HIV-1 env- but not gag-related antigens as determined by radioimmunoprecipitation and sodium dodecyl sulfate polyacrylamide gel electrophoresis ( RIP-SDS PAGE ). We conclude that in vitro as well as in vivo use of DEC may alter results of antibody testing for retroviruses.


title: Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis

text: BACKGROUND: The prevalence and prognosis of digestive system involvement, including gastrointestinal symptoms and liver injury, in patients with COVID-19 remains largely unknown. We aimed to quantify the effects of COVID-19 on the digestive system. METHODS: In this systematic review and meta-analysis, we systematically searched PubMed, Embase, and Web of Science for studies published between Jan 1, 2020, and April 4, 2020. The websites of WHO, CDC, and major journals were also searched. We included studies that reported the epidemiological and clinical features of COVID-19 and the prevalence of gastrointestinal findings in infected patients, and excluded preprints, duplicate publications, reviews, editorials, single case reports, studies pertaining to other coronavirus-related illnesses, and small case series (<10 cases). Extracted data included author; date; study design; country; patient demographics; number of participants in severe and non-severe disease groups; prevalence of clinical gastrointestinal symptoms such as vomiting, nausea, diarrhoea, loss of appetite, abdominal pain, and belching; and digestive system comorbidities including liver disease and gastrointestinal diseases. Raw data from studies were pooled to determine effect estimates. FINDINGS: We analysed findings from 35 studies, including 6686 patients with COVID-19, that met inclusion criteria. 29 studies (n=6064) reported gastrointestinal symptoms in patients with COVID-19 at diagnosis, and the pooled prevalence of digestive system comorbidities was 4% (95% CI 2–5; range 0–15; I(2)=74%). The pooled prevalence of digestive symptoms was 15% (10–21; range: 2–57; I(2)=96%) with nausea or vomiting, diarrhoea, and loss of appetite being the three most common symptoms. The pooled prevalence of abnormal liver functions (12 studies, n=1267) was 19% (9–32; range 1–53; I(2)=96%). Subgroup analysis showed patients with severe COVID-19 had higher rates of gastrointestinal symptoms (odds ratio [OR] 1·60 [95% CI 1·09–2·36]; p=0·0020; I(2)=44%) and liver injury (2·20 [1·60–3·02]; p<0·00001; I(2)=36%) compared with those with non-severe disease. Patients in Hubei province, where the initial COVID-19 outbreak occurred, were more likely to present with abnormal liver functions (p<0·0001) compared with those outside of Hubei. Paediatric patients with COVID-19 had a similar prevalence of gastrointestinal symptoms to those of adult patients. 10% (95% CI 4–19; range 3–23; I(2)=97%) of patients presented with gastrointestinal symptoms alone without respiratory features. Patients who presented with gastrointestinal system involvement had delayed diagnosis (standardised mean difference 2·85 [95% CI 0·22–5·48]; p=0·030; I(2)=73%). Patients with gastrointestinal involvement had a higher prevalence of complication (OR 2·51 [95% CI 1·62–3·89]; p<0·0001; I(2)=0%). INTERPRETATION: Our study showed that digestive symptoms and liver injury are not uncommon in patients with COVID-19. Increased attention should be paid to the care of this unique group of patients. FUNDING: None.


title: Can You Catch It? Lessons Learned and Modification of ED Triage Symptom- and Travel-Screening Strategy

text: INTRODUCTION Efficient identification and isolation of patients with communicable diseases limits exposure to health care workers, other patients, and visitors. In August 2014, our team developed and implemented an algorithm to triage suspected cases of Ebola virus disease in a midwestern United States emergency department and outpatient clinics based on patient travel history and symptoms. Here, we present the lessons learned and modifications to update the tool. METHODS Two strategies were developed and utilized to properly identify, isolate, and inform on patients with suspected highly hazardous communicable diseases: 1) a robust electronic symptom and travel screen with decision support tools in the electronic medical record, and 2) the availability of workflow protocols for Ebola virus disease, Middle East Respiratory Syndrome (MERS), and coronavirus 2019 (COVID-19) once a person under investigation is identified. After action reports provided opportunities to modify the algorithm and improve the identification and isolation processes. RESULTS Since our screening and travel electronic medical record inception 5 years ago, modifications changed iteratively to further enhance the screening process. Since 2018, staff have identified 5 patients at risk for MERS; in all cases, identification occurred during the check-in process. Exposure investigations in the emergency department decreased significantly after algorithm implementation in January 2019, from 30 in 2018 to 0 in 2019. DISCUSSION Although highly hazardous communicable diseases like Ebola virus disease and MERS are of concern due to their mortality rates and limited treatment options, these same concepts may be applied to the early identification and isolation of patients suspected of having more common communicable diseases like measles and influenza, emphasizing the importance of protocol-based screening in the healthcare environment.


title: Camphor-based symmetric diimines as inhibitors of influenza virus reproduction

text: Abstract Influenza is a continuing world-wide public health problem that causes significant morbidity and mortality during seasonal epidemics and sporadic pandemics. The purpose of the study was synthesis and investigation of antiviral activity of camphor-based symmetric diimines and diamines. A set of C2-symmetric nitrogen-containing camphor derivatives have been synthesized. The antiviral activity of these compounds was studied against rimantadine- and amantadine-resistant influenza virus A/California/7/09 (H1N1)pdm09 in MDCK cells. The highest efficacy in virus inhibiting was shown for compounds 2a–e with cage moieties bound by aliphatic linkers. The therapeutic index (selectivity index) for 2b exceeded that for reference compounds amantadine, deitiforin and rimantadine almost 10-fold. As shown by structure–activity analysis, the length of the linker has a dramatic effect on the toxicity of compounds. Compound 2e with –C12H24– linker exhibited the lowest toxicity (CTD50 =2216μM). Derivatives of camphor, therefore, can be considered as prospective antiinfluenza compounds active against influenza viruses resistant to adamantane-based drugs.


Infectious Disease Outbreaks: The Need For an All-in Approach


title: Challenges of Oral Medicine Specialistsat the time of COVID‐19 Pandemic

text: The novel coronavirus disease 2019 (COVID-19) had caused major disruptions in medical and dental care across the world, affecting secondary care services that had to rapidly adapt to new circumstances. Postponed and delayed oral medicine (OM) care, deferring non-urgent follow-ups in case of patients because of COVID-19 crisis, and limited access to health care, may have lead serious consequences fororal and systemic health (Arduino et al, 2020; Jones et al, 2020). Deferred diagnosis of a malignant conditionwhen suspected or even dysplasia in oralleucoplakia cases vastly implies the clinical outcome, influencing treatment and prognosis, subsequently(Meng et al, 2020).Suspended routine care provision for patients with other, less severe conditions (hyposalivation, oral lichen planus,oral candidiasis, and recurrentaphthous stomatitis - RAS)could have a significant impact on the patients' well-being and quality of life, if oral medicine cases are not managed consistently and timely. Chronic autoimmune disorders with oral manifestations, such asmucous membrane pemphigoid orpemphigus vulgaris,can be exacerbated as a result of delayed OM follow-ups, dental care and self-management or even interruptionof long-term(pharmaco)therapy(Martins-Chaves et al, 2020; Kasperkiewicz et al, 2).


Welche Probenmaterialien für den Nachweis von SARS-CoV-2?


Hand hygiene and the novel coronavirus pandemic: The role of healthcare workers


title: Safety protocols for dental practices in the COVID-19 era

text: Aim Aim of this paper was to provide safety and operatory protocols for providing dental care during the COVID19 pandemic. Data sources The protocol is based on summarising the existing literature, published on different aspects of dealing with the pandemic situation. This protocol was established as an international collaboration among three dental universities: Hadassah School of Dental Medicine Israel, the University of Rochester Medical Centre USA, and the University of Pennsylvania USA. The details of the virus-transmission and its impact on dental care are discussed. Additionally, safety and operatory protocols for urgent and emergency dental care are detailed with a special focus on endodontic and surgical dental care. Conclusions A protocol detailing the safety and operatory measures to be taken while giving the dental care in the COVID-era is provided. The primary aim is to prevent any cross-contamination while allowing the provision of urgent and emergency dental care. Aerosol-producing and other elective procedures should be avoided.


title: Recent advances on the role of host factors during non-poliovirus enteroviral infections

text: Non-polio enteroviruses are emerging viruses known to cause outbreaks of polio-like infections in different parts of the world with several cases already reported in Asia Pacific, Europe and in United States of America. These outbreaks normally result in overstretching of health facilities as well as death in children under the age of five. Most of these infections are usually self-limiting except for the neurological complications associated with human enterovirus A 71 (EV-A71). The infection dynamics of these viruses have not been fully understood, with most inferences made from previous studies conducted with poliovirus. Non-poliovirus enteroviral infections are responsible for major outbreaks of hand, foot and mouth disease (HFMD) often associated with neurological complications and severe respiratory diseases. The myriad of disease presentations observed so far in children calls for an urgent need to fully elucidate the replication processes of these viruses. There are concerted efforts from different research groups to fully map out the role of human host factors in the replication cycle of these viral infections. Understanding the interaction between viral proteins and human host factors will unravel important insights on the lifecycle of this groups of viruses. This review provides the latest update on the interplay between human host factors/processes and non-polio enteroviruses (NPEV). We focus on the interactions involved in viral attachment, entry, internalization, uncoating, replication, virion assembly and eventual egress of the NPEV from the infected cells. We emphasize on the virus- human host interplay and highlight existing knowledge gaps that needs further studies. Understanding the NPEV-human host factors interactions will be key in the design and development of vaccines as well as antivirals against enteroviral infections. Dissecting the role of human host factors during NPEV infection cycle will provide a clear picture of how NPEVs usurp the human cellular processes to establish an efficient infection. This will be a boost to the drug and vaccine development against enteroviruses which will be key in control and eventual elimination of the viral infections.


Wuhan-like virus discovered seven years ago


title: Self-assembling protein nanoparticles in the design of vaccines

text: For over 100 years, vaccines have been one of the most effective medical interventions for reducing infectious disease, and are estimated to save millions of lives globally each year. Nevertheless, many diseases are not yet preventable by vaccination. This large unmet medical need demands further research and the development of novel vaccines with high efficacy and safety. Compared to the 19th and early 20th century vaccines that were made of killed, inactivated, or live-attenuated pathogens, modern vaccines containing isolated, highly purified antigenic protein subunits are safer but tend to induce lower levels of protective immunity. One strategy to overcome the latter is to design antigen nanoparticles: assemblies of polypeptides that present multiple copies of subunit antigens in well-ordered arrays with defined orientations that can potentially mimic the repetitiveness, geometry, size, and shape of the natural host-pathogen surface interactions. Such nanoparticles offer a collective strength of multiple binding sites (avidity) and can provide improved antigen stability and immunogenicity. Several exciting advances have emerged lately, including preclinical evidence that this strategy may be applicable for the development of innovative new vaccines, for example, protecting against influenza, human immunodeficiency virus, and respiratory syncytial virus. Here, we provide a concise review of a critical selection of data that demonstrate the potential of this field. In addition, we highlight how the use of self-assembling protein nanoparticles can be effectively combined with the emerging discipline of structural vaccinology for maximum impact in the rational design of vaccine antigens.


Onco-gynecologic surgery in the COVID-19 era: Risks and precautions—A position paper from FRANCOGYN, SCGP, SFCO, and SFOG


title: Guidelines for the Evaluation and Treatment of Pneumonia

text: Pneumonia is a common cause of respiratory infection, accounting for more than 800,000 hospitalizations in the United States annually. Presenting symptoms of pneumonia are typically cough, pleuritic chest pain, fever, fatigue, and loss of appetite. Children and the elderly have different presenting features of pneumonia, which include headache, nausea, abdominal pain, and absence of one or more of the prototypical symptoms. Knowledge of local bacterial pathogens and their antibiotic susceptibility and resistance profiles is the key for effective pharmacologic selection and treatment of pneumonia.


Who gets the ventilator? Important legal rights in a pandemic


Safer countries through global health security


title: Antiviral escin derivatives from the seeds of Aesculus turbinata Blume (Japanese horse chestnut)

text: Abstract Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and high fatality of piglets, influencing the swine industry. Japanese horse chestnut (seed of Aesculus turbinata) contains many saponin mixtures, called escins, and has been used for a long time as a traditional medicinal plant. Structure-activity relationship (SAR) studies on escins have revealed that acylations at C-21 and C-22 with angeloyl or tigloyl groups were important for their cytotoxic effects. However, the strong cytotoxicity of escins makes them hard to utilize for other diseases and to develop as nutraceuticals. In this research, we investigated whether escin derivatives 1–7 (including new compounds 2, 3, 5 and 6), without the angeloyl or tigloyl groups and with modified glycosidic linkages by hydrolysis, have PEDV inhibitory effects with less cytotoxicity. Compounds 1–7 had no cytotoxicity at 20μM on VERO cells, while compounds 8–10 showed strong cytotoxicity at similar concentrations on PEDV. Our results suggest that escin derivatives showed strong inhibitory activities on PEDV replication with lowered cytotoxicity. These studies propose a method to utilize Japanese horse chestnut for treating PEDV and to increase the diversity of its bioactive compounds.


Person-to-person transmission of influenza A (H5N1)


Covid-19: medical schools are urged to fast-track final year students


title: Infectious Diseases among Refugee Children

text: In recent years, there has been a substantial increase in refugee and asylum-seeking adults, adolescents and children to high-income countries. Infectious diseases remain the most frequently identified medical diagnosis among U.S.-bound refugee children. Medical screening and immunization are key strategies to reduce the risk of infectious diseases in refugee, internationally adopted, and immigrant children. Notable infectious diseases affecting refugee and other newly arriving migrants include latent or active tuberculosis, human immunodeficiency virus type 1 (HIV), hepatitis B, hepatitis C, vaccine-preventable diseases, malaria, and other parasitic infections. The U.S. Centers for Disease Control and Prevention and the American Academy of Pediatrics have published guidelines for health assessment of newly arriving immigrant, refugee, and internationally adopted children. Although, data on the health risks and needs of refugee exists in some high-income countries, there is an urgent need to develop robust evidence-informed guidance on screening for infectious diseases and vaccination strategies on a broader scale to inform national policies. Innovative approaches to reach migrant communities in the host nations, address health and other complex barriers to improve access to high-quality integrated health services, and strong advocacy to mobilize resources to improve health, safety, and wellbeing for refugee children and their families are urgent priorities.


title: Polysomes Bypass a 50 Nucleotide Coding Gap less Efficiently than Monosomes Due to Attenuation of a 5’ mRNA Stem Loop and Enhanced Drop-off

text: Efficient translational bypassing of a 50 nt non-coding gap in a phage T4 topoisomerase subunit gene (gp60) requires several recoding signals. Here we investigate the function of the mRNA stem loop 5′ of the take-off codon, as well as the importance of ribosome loading density on the mRNA for efficient bypassing. We show that polysomes are less efficient at mediating bypassing than monosomes, both in vitro and in vivo, due to their preventing formation of a stem loop 5′ of the take-off codon and allowing greater peptidyl-tRNA drop off. A ribosome profiling analysis of phage T4 infected E. coli yielded protected mRNA fragments within the normal size range derived from ribosomes stalled at the take-off codon. However, ribosomes at this position also yielded some 53 nucleotide fragments, 16 longer. These were due to protection of the nucleotides that form the 5′ stem loop. NMR shows that the 5′ stem loop is highly dynamic. The importance of different nucleotides in the 5′ stem loop is revealed by mutagenesis studies. These data highlight the significance of the 5′ stem loop for the 50 nt bypassing, and further enhance appreciation of relevance of the extent of ribosome loading for recoding.


Similar environmental survival patterns of Streptococcus pyogenes strains of different epidemiologic backgrounds and clinical severity


title: Construction and Immunogenicity of Novel Chimeric Virus-Like Particles Bearing Antigens of Infectious Bronchitis Virus and Newcastle Disease Virus

text: Infectious bronchitis virus (IBV) and Newcastle disease virus (NDV) are two poultry pathogens seriously affecting the poultry industry. Here, IBV S1 and the ectodomain of NDV F proteins were separately linked with the trans-membrane and carboxy-terminal domain of IBV S protein (S(TMCT)), composing rS and rF; thus, a novel chimeric infectious bronchitis-Newcastle disease (IB-ND) virus-like particles (VLPs) vaccine containing the rS, rF, and IBV M protein was constructed. Under the transmission electron microscope (TEM), VLPs possessing similar morphology to natural IBV were observed. To evaluate the immunogenicity of chimeric IB-ND VLPs, specific pathogen-free (SPF) chickens were immunized with three increasing doses (50, 75, and 100 μg protein of VLPs). Results of ELISAs detecting IBV and NDV specific antibodies and IL-4 and IFN-γ T cell cytokines indicated that vaccination with chimeric IB-ND VLPs could efficiently induce humoral and cellular immune responses. In the challenge study, chimeric IB-ND VLPs (100 μg protein) provided 100% protection against IBV or NDV virulent challenge from death, and viral RNA levels in tissues and swabs were greatly reduced. Collectively, chimeric IB-ND VLPs are highly immunogenic and could provide complete protection from an IBV or NDV virulent challenge. Chimeric IB-ND VLPs are an appealing vaccine candidate and a promising vaccine platform bearing multivalent antigens.


title: Bloom Energy powers two California sites in fast pandemic response

text: In California, Bloom Energy completed two rapid-deployment fuel cell microgrid projects in early April to support patients affected by Covid-19. Bloom Energy Servers provide electricity with almost zero particulate emissions, ensuring that Covid-19 patients with severe respiratory issues can breathe clean air. The crisis has overwhelmed existing hospitals, necessitating the deployment of secondary locations to treat patients, and these new locations need reliable power.


title: Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection

text: BACKGROUND: CTCF is a key insulator-binding protein, and mammalian genomes contain numerous CTCF sites, many of which are organized in tandem. RESULTS: Using CRISPR DNA-fragment editing, in conjunction with chromosome conformation capture, we find that CTCF sites, if located between enhancers and promoters in the protocadherin (Pcdh) and β-globin clusters, function as an enhancer-blocking insulator by forming distinct directional chromatin loops, regardless whether enhancers contain CTCF sites or not. Moreover, computational simulation in silico and genetic deletions in vivo as well as dCas9 blocking in vitro revealed balanced promoter usage in cell populations and stochastic monoallelic expression in single cells by large arrays of tandem CTCF sites in the Pcdh and immunoglobulin heavy chain (Igh) clusters. Furthermore, CTCF insulators promote, counter-intuitively, long-range chromatin interactions with distal directional CTCF sites, consistent with the cohesin “loop extrusion” model. Finally, gene expression levels are negatively correlated with CTCF insulators located between enhancers and promoters on a genome-wide scale. Thus, single CTCF insulators ensure proper enhancer insulation and promoter activation while tandem CTCF topological insulators determine balanced spatial contacts and promoter choice. CONCLUSIONS: These findings have interesting implications on the role of topological chromatin insulators in 3D genome folding and developmental gene regulation.


title: Endotracheal Surfactant Combined With Budesonide for Neonatal ARDS

text: Acute respiratory distress syndrome (ARDS) is a clinical condition characterized by acute diffuse inflammatory lung injury and severe hypoxemia. In 2017, the Montreux Consensus defined diagnostic criteria for ARDS in the neonatal period. The management of ARDS includes strict adherence to lung-protective ventilation strategies and therapeutic agents to improve gas exchange. We report two similar cases of premature infants with gestational ages of 23 and 24 weeks diagnosed with neonatal ARDS according to the Montreux definition. These patients developed acute worsening of oxygenation on the 30th and 28th day of life, respectively, while they were ventilated on volume-guarantee assist/control mode. Chest X-rays revealed bilateral diffuse opacity, there were no cardiogenic origins for pulmonary edema, and their oxygenation indexes were >8. Both cases fulfilled the neonatal ARDS criteria and the patients' clinical conditions were associated with late onset neonatal sepsis. After lung recruitment maneuver, the infants began HFO volume-guarantee ventilation and received surfactant treatment. Since they showed a poor short-term response, intratracheal surfactant of 100 mg/kg plus budesonide of 0.25 mg/kg were administered and their oxygenation indexes were reduced stepwise. Both patients survived and were discharged home with spontaneous breathing of room air. Neonatal ARDS is generally an underdiagnosed condition associated with sepsis, pneumonia, and meconium aspiration. Impaired surfactant activity and reduced lung compliance play important roles in its pathophysiology. To our knowledge, this is the first case report indicating the possible therapeutic role of budesonide plus surfactant in ARDS treatment. Since ARDS is an entity not recognized in newborns, we want to emphasize neonatal ARDS diagnosis and underline that the combination of budesonide and surfactant may be a novel therapeutic option in the treatment of ARDS.


title: CD13/Aminopeptidase N overexpression by basic fibroblast growth factor mediates enhanced invasiveness of 1F6 human melanoma cells

text: CD13/Aminopeptidase N (CD13) is known to play an important role in tumour cell invasion. We examined whether basic fibroblast growth factor (bFGF) is involved in the regulation of CD13 expression in human melanoma cells. 1F6 human melanoma cells were stably transfected with constructs encoding either the 18 kDa (18kD) or all (ALL) bFGF isoform proteins. We observed highly increased CD13 mRNA and protein expression in the 1F6 clones regardless of the overexpression of either the 18kD or all isoform proteins. Neutral aminopeptidase activity was increased five-fold and could be inhibited by bestatin and the CD13-neutralising antibody WM15. The enhanced invasion through Matrigel, but not migration in a wound assay, was efficiently abrogated by both bestatin and WM15. Upregulation of CD13 expression was the result of increased epithelial and myeloid promoter activity up to 4.5-fold in 1F6-18kD and 1F6-ALL clones. Interestingly, in a panel of human melanoma cell lines, a significant correlation (r(2)=0.883, P<0.05) between bFGF and CD13 mRNA and protein expression was detected. High bFGF and CD13 expression were clearly related with an aggressive phenotype. Taken together, our data indicate that high bFGF expression upregulates CD13 expression in human melanoma cells by activating both the myeloid and the epithelial CD13 promoter. In addition, we show that high bFGF and CD13 expression results in enhanced invasive capacity and metastatic behaviour of human melanoma cells.


title: Applications of machine learning techniques to a sensor-network-based prosthesis training system

text: Abstract In the past, the utilization of the limb prosthesis has improved the daily life of amputees or patients with movement disorders. However, a leg-amputee has to take a series of training after wearing a limb prosthesis, and the training results determine whether a patient can use the limb prosthesis correctly in her/his daily life. Limb prosthesis vendors thus desire to offer the leg-amputee a complete and well-organized training process, but they often fail to do so owing to the factors such as the limited support of human resource and financial condition of the amputee. This work proposes a prosthesis training system that the amputees can borrow or buy from the limb prosthesis vendors and train themselves at home. Instant feedback messages provided by the prosthesis training system are used to correct their walking postures during the self-training process. An embedded chip is used as a core to establish a body area sensor network for the prosthesis training system. RFID readers and tags are employed to acquire the 3D positioning information of the amputee's limbs in this work to assist in diagnosing the amputee's walking problem. A series of simulations were conducted and the simulation results exhibit the effectiveness and practicability of the proposed prosthesis training system.


title: Oligonucleotide aptamers: potential novel molecules against viral hepatitis

text: Viral hepatitis, as an international public health concern, seriously affects communities and health system. In recent years, great strides have been taken for development of new potential tools against viral hepatitis. Among these efforts, a valuable strategy introduced new molecules called “aptamers”. Aptamers as potential alternatives for antibodies could be directed against any protein in infected cells and any components of viral particles. In this review, we will focus on recent advances in the diagnosis and treatment of viral hepatitis based on aptamer technology. In recent years, various types of aptamers including RNA and DNA were introduced against viral hepatitis. Some of these aptamers can be utilized for early and precise diagnosis of hepatitis infections and other group selected as therapeutic tools against viral targets. Designing diagnostic and therapeutic platforms based on aptamer technology is a promising approach in viral infections. The obtained aptamers in the recent years showed obvious potential for use as diagnostic and therapeutic tools against viral hepatitis. Although some modifications to increase the biostability and half-life of aptamers are underway, it seems these molecules will be a favorable substitute for monoclonal antibody in near future.


title: Ischaemic stroke and SARS-CoV-2 infection: A causal or incidental association?

text: Abstract Introduction Ischaemic stroke has been reported in patients with COVID-19, particularly in more severe cases. However, it is unclear to what extent this is linked to systemic inflammation and hypercoagulability secondary to the infection. Materials and methods We describe the cases of 4 patients with ischaemic stroke and COVID-19 who were attended at our hospital. Patients are classified according to the likelihood of a causal relationship between the hypercoagulable state and ischaemic stroke. We also conducted a review of studies addressing the possible mechanisms involved in the aetiopathogenesis of ischaemic stroke in these patients. Results The association between COVID-19 and stroke was probably causal in 2 patients, who presented cortical infarcts and had no relevant arterial or cardioembolic disease, but did show signs of hypercoagulability and systemic inflammation in laboratory analyses. The other 2 patients were of advanced age and presented cardioembolic ischaemic stroke; the association in these patients was probably incidental. Conclusions Systemic inflammation and the potential direct action of the virus may cause endothelial dysfunction, resulting in a hypercoagulable state that could be considered a potential cause of ischaemic stroke. However, stroke involves multiple pathophysiological mechanisms; studies with larger samples are therefore needed to confirm our hypothesis. The management protocol for patients with stroke and COVID-19 should include a complete aetiological study, with the appropriate safety precautions always being observed.


title: Human monoclonal antibodies by immortalization of memory B cells

text: The administration of hyper immune sera to prevent or treat life-threatening infections is a remarkable milestone in medicine and biotechnology that has been achieved more than a century ago. Yet, the therapeutic use of monoclonal antibodies in this field has developed slowly over the last decades. Here we compare and contrast current methods to generate human monoclonal antibodies and highlight the advantages of exploiting the human antibody repertoire using a novel method that allows efficient immortalization and cloning of human memory B cells. This method, which has been successfully applied to isolate broadly neutralizing antibodies against SARS and H5N1 influenza viruses, is expected to accelerate the development of therapeutics in the field of infectious diseases not only by providing neutralizing antibodies for passive serotherapy, but also by generating relevant information for vaccine design.


title: Current and future antiviral therapy of severe seasonal and avian influenza

text: The currently circulating H3N2 and H1N1 subtypes of influenza A virus cause a transient, febrile upper respiratory illness in most adults and children (“seasonal influenza”), but infants, the elderly, immunodeficient and chronically ill persons may develop life-threatening primary viral pneumonia or complications such as bacterial pneumonia. By contrast, avian influenza viruses such as the H5N1 virus that recently emerged in Southeast Asia can cause severe disease when transferred from birds to previously healthy people (“avian influenza”). Most H5N1 patients present with fever, cough and shortness of breath that progress rapidly to adult respiratory distress syndrome. In seasonal influenza, viral replication remains confined to the respiratory tract, but limited studies indicate that H5N1 infections are characterized by systemic viral dissemination, high cytokine levels and multiorgan failure. Gastrointestinal infection and encephalitis also occur. The licensed anti-influenza drugs (the M2 ion channel blockers, amantadine and rimantadine, and the neuraminidase inhibitors, oseltamivir and zanamivir) are beneficial for uncomplicated seasonal influenza, but appropriate dosing regimens for severe seasonal or H5N1 viral infections have not been defined. Treatment options may be limited by the rapid emergence of drug-resistant viruses. Ribavirin has also been used to a limited extent to treat influenza. This article reviews approaches to therapy, including licensed drugs and treatments under development, including high-dose oseltamivir; parenterally administered neuraminidase inhibitors, peramivir and zanamivir; dimeric forms of zanamivir; the RNA polymerase inhibitor T-705; a ribavirin prodrug, viramidine; polyvalent and monoclonal antibodies; and combination therapies.


title: Species‐specific clinical characteristics of human coronavirus infection among otherwise healthy adolescents and adults

text: Human coronavirus (HCoV) is a known cause of influenza‐like illness (ILI). In a multisite, observational, longitudinal study of ILI among otherwise healthy adolescents and adults, 12% of subjects were PCR‐positive for HCoV. The distribution of species was as follows: HCoV‐OC43 (34%), HCoV‐229E (28%), HCoV‐NL63 (22%), and HCoV‐HKU1 (16%). We did not observe species‐specific differences in the clinical characteristics of HCoV infection, with the exception of HCoV‐HKU1, for which the severity of gastrointestinal symptoms trended higher on the fourth day of illness.


title: Cyclophilin A as a target in the treatment of cytomegalovirus infections

text: BACKGROUND: Viruses are obligate parasites that depend on the cellular machinery of the host to regenerate and manufacture their proteins. Most antiviral drugs on the market today target viral proteins. However, the more recent strategies involve targeting the host cell proteins or pathways that mediate viral replication. This new approach would be effective for most viruses while minimizing drug resistance and toxicity. METHODS: Cytomegalovirus replication, latency, and immune response are mediated by the intermediate early protein 2, the main protein that determines the effectiveness of drugs in cytomegalovirus inhibition. This review explains how intermediate early protein 2 can modify the action of cyclosporin A, an immunosuppressive, and antiviral drug. It also links all the pathways mediated by cyclosporin A, cytomegalovirus replication, and its encoded proteins. RESULTS: Intermediate early protein 2 can influence the cellular cyclophilin A pathway, affecting cyclosporin A as a mediator of viral replication or anti-cytomegalovirus drug. CONCLUSION: Cyclosporin A has a dual function in cytomegalovirus pathogenesis. It has the immunosuppressive effect that establishes virus replication through the inhibition of T-cell function. It also has an anti-cytomegalovirus effect mediated by intermediate early protein 2. Both of these functions involve cyclophilin A pathway.


title: An insertion unique to SARS-CoV-2 exhibits superantigenic character strengthened by recent mutations

text: Multisystem Inflammatory Syndrome in Children (MIS-C) associated with Coronavirus Disease 2019 (COVID-19) is a newly recognized condition in which children with recent SARS-CoV-2 infection present with a constellation of symptoms including hypotension, multiorgan involvement, and elevated inflammatory markers. These symptoms and the associated laboratory values strongly resemble toxic shock syndrome, an escalation of the cytotoxic adaptive immune response triggered upon the binding of pathogenic superantigens to MHCII molecules and T cell receptors (TCRs). Here, we used structure-based computational models to demonstrate that the SARS-CoV-2 spike (S) exhibits a high-affinity motif for binding TCR, interacting closely with both the α- and β-chains variable domains’ complementarity-determining regions. The binding epitope on S harbors a sequence motif unique to SARS-CoV-2 (not present in any other SARS coronavirus), which is highly similar in both sequence and structure to bacterial superantigens. Further examination revealed that this interaction between the virus and human T cells is strengthened in the context of a recently reported rare mutation (D839Y/N/E) from a European strain of SARS-CoV-2. Furthermore, the interfacial region includes selected residues from a motif shared between the SARS viruses from the 2003 and 2019 pandemics, which has intracellular adhesion molecule (ICAM)-like character. These data suggest that the SARS-CoV-2 S may act as a superantigen to drive the development of MIS-C as well as cytokine storm in adult COVID-19 patients, with important implications for the development of therapeutic approaches.


title: Is the anti-psychotic, 10-(3-(dimethylamino)propyl)phenothiazine (promazine), a potential drug with which to treat SARS infections? Lack of efficacy of promazine on SARS-CoV replication in a mouse model

text: Phenothiazine and derivatives were tested for inhibition of SARS-CoV replication. Phenothiazine slightly inhibited SARS-CoV replication in a neutral red (NR) uptake assay. Adding a propylamino group to give promazine reduced virus yields (VYR assay) with an EC(90) = 8.3 ± 2.8 µM, but without selectivity. Various substitutions in the basic phenothiazine structure did not promote efficacy. Phenazine ethosulfate was the most potent compound by VYR assay (EC(90) = 6.1 ± 4.3 µM). All compounds were toxic (IC(50) = 6.6–74.5 µM) except for phenoxathiin (IC(50) = 858 ± 208 µM) and 10-(alpha-diethylamino-propionyl) phenothiazine·HCl (IC(50) = 195 ± 71.2 µM). Consequently, none were selective inhibitors of SARS-CoV replication (SI values <1–3.3 µM). These data portended the poor efficacy of promazine in a SARS-CoV mouse lung replication model. Intraperitoneal treatment with promazine using a prophylactic (−4 h)/therapeutic regimen of 1, 10, or 50 mg/(kg day) did not reduce virus lung titers at day 3, yet prolonged virus replication to 14 days. Similar therapeutic promazine doses were not efficacious. Thus, promazine did not affect SARS-CoV replication in vitro or in vivo, nor were any other phenothiazines efficacious in reducing virus replication. Therefore, treating SARS infections with compounds like promazine is not warranted.


title: MERS-CoV: Ein aktueller Überblick

text: The following article gives a current overview of the newly emerging Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Since first time in summer 2012 in some countries in the Arabian Peninsula there were a number of severe infections of the respiratory tract caused by the new coronavirus. The majority of cases of illness were reported from Saudi Arabia, in Germany several imported cases of the disease have been reported. After beginning with flu-like-symptoms usually follows a pneumonia with a transition to an acute respiratory distress syndrome. The mortality rate is estimated at 55%. In the travel medical advice it should be elucidated about the disease and for that reason it is of great importance also for occupational medicine.


Prescribing Parenteral Nutrition in Acute Hospital setting during COVID-19: The Singapore experience


title: International Experience of US Pediatricians and Level of Comfort Caring for Immigrant Children and Children Traveling Internationally

text: OBJECTIVE: To determine if international experience is associated with greater comfort in providing care to U.S. children who are immigrants, refugees, and traveling internationally. STUDY DESIGN: Following enrollment into the 2018 American Board of Pediatrics Maintenance of Certification program, general pediatricians and subspecialists received a voluntary, online survey with questions about their experience and self-reported comfort caring for immigrant, refugee, and internationally traveling children and prior international experiences. Using multivariable logistic regression, we examined how prior international experiences, and other personal characteristics, were associated with self-reported comfort. RESULTS: A total of 5461 eligible participants completed the survey; 76.3%, (n=4168) reported caring for immigrant children, 35.8% (n=1957) cared for refugee children, and 79.8% (n=4358) cared for children traveling internationally. High levels of comfort caring for immigrant children were reported by 68.5% (n=3739), for refugee children by 50.1% (n=2738), and for children traveling internationally by 72.7% (n=3968). One-third of respondents (34.1%, n=1866) reported past international experiences. In multivariable analysis, respondents with prior international experience and of Hispanic origin were significantly more likely to report high levels of comfort caring for all 3 populations. CONCLUSIONS: The majority of pediatricians report caring for children in the United States who are immigrants, refugees, and traveling internationally, and prior international experience was associated with greater comfort with care. Training programs and professional organizations should consider ways to encourage a more diverse workforce and to support all pediatricians in achieving the skills and confidence required to care for children in our highly mobilized society.


title: Microfluidic-based biosensors toward point-of-care detection of nucleic acids and proteins

text: This article reviews state-of-the-art microfluidic biosensors of nucleic acids and proteins for point-of-care (POC) diagnostics. Microfluidics is capable of analyzing small sample volumes (10(−9)–10(−18) l) and minimizing costly reagent consumption as well as automating sample preparation and reducing processing time. The merger of microfluidics and advanced biosensor technologies offers new promises for POC diagnostics, including high-throughput analysis, portability and disposability. However, this merger also imposes technological challenges on biosensors, such as high sensitivity and selectivity requirements with sample volumes orders of magnitude smaller than those of conventional practices, false response errors due to non-specific adsorption, and integrability with other necessary modules. There have been many prior review articles on microfluidic-based biosensors, and this review focuses on the recent progress in last 5 years. Herein, we review general technologies of DNA and protein biosensors. Then, recent advances on the coupling of the biosensors to microfluidics are highlighted. Finally, we discuss the key challenges and potential solutions for transforming microfluidic biosensors into POC diagnostic applications.


title: Detection and monitoring of virus infections by real-time PCR

text: Abstract The employment of polymerase chain reaction (PCR) techniques for virus detection and quantification offers the advantages of high sensitivity and reproducibility, combined with an extremely broad dynamic range. A number of qualitative and quantitative PCR virus assays have been described, but commercial PCR kits are available for quantitative analysis of a limited number of clinically important viruses only. In addition to permitting the assessment of viral load at a given time point, quantitative PCR tests offer the possibility of determining the dynamics of virus proliferation, monitoring of the response to treatment and, in viruses displaying persistence in defined cell types, distinction between latent and active infection. Moreover, from a technical point of view, the employment of sequential quantitative PCR assays in virus monitoring helps identifying false positive results caused by inadvertent contamination of samples with traces of viral nucleic acids or PCR products. In this review, we provide a survey of the current state-of-the-art in the application of the real-time PCR technology to virus analysis. Advantages and limitations of the RQ-PCR methodology, and quality control issues related to standardization and validation of diagnostic assays are discussed.


Public interest in EU policymaking after COVID-19: five short-term lessons from a consumer perspective


Circulating plasma levels of angiotensin II and aldosterone in patients with coronavirus disease 2019 (COVID-19): A preliminary report


title: Using primary literature on SARS‐CoV‐2 to promote student learning about evolution

text: The ongoing COVID‐19 pandemic caused by SARS‐CoV‐2 has caused widespread deaths, illnesses, and societal disruption. I describe here how I pivoted a discussion‐based senior biology capstone course to include a multiweek module surrounding one primary literature paper on the evolution of SARS‐CoV‐2 and the subsequent scientific discourse about the paper. Using a gradual reveal of the paper following the CREATE method (consider, read, elucidate, and think of the next experiment), I challenged students to learn new evolutionary principles and critically analyze the data surrounding the evolution and transmission of SARS‐CoV‐2 presented in the paper. I also provide general advice for implementing this module in future courses.


title: De Nora technology supports the fight against the spread of coronavirus

text: Industrie De Nora SpA, a provider of electrodes and coatings for electrochemical processes, is helping to fight against the spread of coronavirus.


COVID‐19: Finding silver linings for dental education


title: Genetic control of anti‐idiotypic vaccination against coronavirus infection

text: The idiotypic network can be experimentally altered to induce protective immune responses against microbial pathogens. Both internal image and noninternal image anti‐idiotypic (anti‐Id) antibodies have been shown to trigger antigen (Ag)‐specific immune responses. Therefore, mechanisms of anti‐Id vaccination appear to go beyond structural mimicry of Ag, but remain undefined. Using the neurotropic murine coronavirus animal model, we have previously shown that a polyclonal noninternal image anti‐Id (Ab2) could vaccinate BALB/c mice. To characterize its mode of action, we have examined the immune modulating capability of this Ab2 in vivo in strains of mice with different H‐2 haplotypes. Even though only internal image anti‐Id are expected to induce non‐genetically restricted immunity, this noninternal image Ab2 induced protective immunity in four of eight genetically different strains of mice susceptible to coronavirus infection. These were BALB/c (H‐2(d)), DBA/1 (H‐2(d)), DBA/1 (H‐2(q)), and SWR (H‐2(q)) mice. Protection was generally correlated with the induction of specific antiviral Ab (Ab3) that showed biological properties, such as virus neutralization in vitro, similar to the initial Ab1. To evaluate the genetic implication of the H‐2 haplotypes in protection, congenic mice were also tested. Vaccination profiles suggest that cooperation between background gene(s) of the BALB/c mouse with H‐2(d) and H‐2(q) loci is necessary for an optimal protective immune response, although the main genetic element(s) regulating the antiviral response to Ab2 inoculation appeared to be located outside the major histocompatibility complex. These results are consistent with the ability of Ab2 to induce protective antiviral antibodies in genetically different animals by biological mimicry.


title: Point‐of‐care lung ultrasound in patients with COVID‐19 – a narrative review

text: Ultrasound imaging of the lung and associated tissues may play an important role in the management of patients with COVID‐19–associated lung injury. Compared with other monitoring modalities, such as auscultation or radiographic imaging, we argue lung ultrasound has high diagnostic accuracy, is ergonomically favourable and has fewer infection control implications. By informing the initiation, escalation, titration and weaning of respiratory support, lung ultrasound can be integrated into COVID‐19 care pathways for patients with respiratory failure. Given the unprecedented pressure on healthcare services currently, supporting and educating clinicians is a key enabler of the wider implementation of lung ultrasound. This narrative review provides a summary of evidence and clinical guidance for the use and interpretation of lung ultrasound for patients with moderate, severe and critical COVID‐19–associated lung injury. Mechanisms by which the potential lung ultrasound workforce can be deployed are explored, including a pragmatic approach to training, governance, imaging, interpretation of images and implementation of lung ultrasound into routine clinical practice.


ACE in the hole


title: The Common Cold: Potential for Future Prevention or Cure

text: The common cold is the most frequent, although generally mild, human disease. Human Rhinoviruses are the prevalent causative agents, but other viruses are also implicated. Being so common, viral colds, have significant implications on public health and quality of life, but may also be life-threatening for vulnerable groups of patients. Specific diagnosis and treatment of the common cold still remain unmet needs. Molecular diagnostic techniques allow specific detection of known pathogens as well as the identification of newly emerging viruses. Although a number of medications or natural treatments have been shown to have some effect, either on the number or on the severity of common colds, no single agent is considerably effective. Virus-specific management remains in most cases a challenging potential as many factors have to be taken into account, including the diversity of the viral genomes, the heterogeneity of affected individuals, as well as the complexity of this long standing host-virus relationship.


title: World in lockdown

text: Around a fifth of the global population is in lockdown as covid-19 cases continue to rise, reports Jessica Hamzelou


title: Characteristics of patients with coronavirus disease (COVID‐19) confirmed using an IgM‐IgG antibody test

text: Coronavirus disease (COVID‐19), caused by a novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has rapidly developed into a pandemic since it was first reported in December 2019. Nucleic acid testing is the standard method for the diagnosis of viral infections. However, this method reportedly has a low positivity rate. To increase the sensitivity of COVID‐19 diagnoses, we developed an IgM‐IgG combined assay and tested it in patients with suspected SARS‐CoV‐2 infection. In total, 56 patients were enrolled in this study and SARS‐CoV‐2 was detected by using both IgM‐IgG antibody and nucleic acid tests. Clinical and laboratory data were collected and analyzed. Our findings suggest that patients who develop severe illness might experience longer virus exposure times and develop a more severe inflammatory response. The IgM‐IgG test is an accurate and sensitive diagnostic method. A combination of nucleic acid and IgM‐IgG testing is a more sensitive and accurate approach for diagnosis and early treatment of COVID‐19.


title: The Management of Respiratory Infections During Pregnancy

text: Respiratory infections that complicate pregnancy are encountered frequently, and they encompass a broad range of disorders. Although respiratory infections usually are not seen more commonly in pregnancy, they often result in greater morbidity and mortality secondary to the physiologic adaptations that occur during pregnancy. Pregnant patients who have one of these disorders require a higher level of surveillance and intervention.


SARS‐CoV‐2 as a trigger of neurodegeneration: thinking ahead


title: Large-Scale Air Medical Operations in the Age of Coronavirus Disease 2019: Early Leadership Lessons From the Front Lines of British Columbia

text: Abstract In late 2019, a novel coronavirus was identified as the cause of a cluster of atypical pneumonia cases in Wuhan, China. It subsequently spread throughout China and around the world, quickly becoming a public health emergency. In March 2020, the World Health Organization declared coronavirus disease 2019 a pandemic. This article explores the preparation and early experiences of a large Canadian critical care transport program during the coronavirus disease 2019 pandemic focused on 6 broad strategic objectives centered around staff welfare, regular and transparent communication, networking, evidenced-based approach to personal protective equipment, agile mission planning, and an expedited approach to clinical practice and policy updates and future state modeling.


Conservative management of Covid-19 patients – emergency palliative care in action


title: Global Sentiments Surrounding the COVID-19 Pandemic on Twitter: Analysis of Twitter Trends

text: BACKGROUND: With the World Health Organization’s pandemic declaration and government-initiated actions against coronavirus disease (COVID-19), sentiments surrounding COVID-19 have evolved rapidly. OBJECTIVE: This study aimed to examine worldwide trends of four emotions—fear, anger, sadness, and joy—and the narratives underlying those emotions during the COVID-19 pandemic. METHODS: Over 20 million social media twitter posts made during the early phases of the COVID-19 outbreak from January 28 to April 9, 2020, were collected using “wuhan,” “corona,” “nCov,” and “covid” as search keywords. RESULTS: Public emotions shifted strongly from fear to anger over the course of the pandemic, while sadness and joy also surfaced. Findings from word clouds suggest that fears around shortages of COVID-19 tests and medical supplies became increasingly widespread discussion points. Anger shifted from xenophobia at the beginning of the pandemic to discourse around the stay-at-home notices. Sadness was highlighted by the topics of losing friends and family members, while topics related to joy included words of gratitude and good health. CONCLUSIONS: Overall, global COVID-19 sentiments have shown rapid evolutions within just the span of a few weeks. Findings suggest that emotion-driven collective issues around shared public distress experiences of the COVID-19 pandemic are developing and include large-scale social isolation and the loss of human lives. The steady rise of societal concerns indicated by negative emotions needs to be monitored and controlled by complementing regular crisis communication with strategic public health communication that aims to balance public psychological wellbeing.


Coronavirus disease-2019: A brief compilation of facts


title: Plasmonic/magnetic molybdenum trioxide and graphitic carbon nitride quantum dots-based fluoroimmunosensing system for influenza virus

text: A novel magnetic/plasmonic-assisted fluoro-immunoassay system is developed for the detection of influenza virus using magnetic-derivatized plasmonic molybdenum trioxide quantum dots (MP-MoO(3) QDs) as the plasmonic/magnetic agent and fluorescent graphitic carbon nitride quantum dots (gCNQDs) as the monitoring probe. Specific antibody against influenza A virus was conjugated onto the surface of MP-MoO(3) QDs and gCNQDs, respectively. In the presence of influenza A virus (as the test virus), a core-satellite immunocomplex is formed between the antibody-conjugated nanomaterials (Ab-MP-MoO(3) QDs and Ab-gCNQDs) and their interaction resulted in the modulation and gradual enhancement of the fluorescence intensity of the detection probe with the influenza virus concentration-dependent increase. In addition, PL change without influenza A virus was not observed. Limits of detection of 0.25 and 0.9 pg/mL were achieved for Influenza virus A/New Caledonia (20/99/IVR/116) (H1N1) detection in deionized water and human serum, respectively. Clinically isolated influenza virus A/Yokohama (110/2009) (H3N2) was detected in the range of 45 – 25,000 PFU/mL, with a limit of detection ca 45 PFU/mL (as opposed to a minimum of 5000 PFU/mL for a commercial test kit). This developed biosensor provides a robust, sensitive as well as a selective platform for influenza virus detection.


title: The presence of contaminations in sewage sludge – The current situation

text: Abstract Sewage sludge/biosolids are by-wastes of municipal and industrial wastewater treatment. As sources of nutrients (C, N, P) they are widely used in intensive farming where large supplementation of organic matter to maintain fertility and enhance crop yields is needed. However, according to the report of European Commission published in 2010, only 39% of produced sewage sludge is recycled into agriculture in the European Union. This situation occurs mainly due to the fact, that the sewage sludge may contain a dangerous volume of different contaminants. For over decades, a great deal of attention has been focused on total concentration of few heavy metals and pathogenic bacteria Salmonella and Escherichia coli. The Sewage Sludge Directive (86/278/EEC) regulates the allowable limits of Zn, Cu, Ni, Pb, Cd, Cr and Hg and pathogens and allows for recovery of sludge on land under defined sanitary and environmentally sound conditions. In this paper, a review on quality of sewage sludge based on the publications after 2010 has been presented. Nowadays there are several papers focusing on new serious threats to human health and ecosystem occurring in sewage sludge – both chemicals (such as toxic trace elements – Se, Ag, Ti; nanoparticles; polyaromatic hydrocarbons; polychlorinated biphenyl; perfluorinated surfactants, polycyclic musks, siloxanes, pesticides, phenols, sweeteners, personal care products, pharmaceuticals, benzotriazoles) and biological traits (Legionella, Yersinia, Escherichia coli O157:H7).


title: Loop‐mediated isothermal amplification (LAMP): a versatile technique for detection of micro‐organisms

text: Loop‐mediated isothermal amplification (LAMP) amplifies DNA with high specificity, efficiency and rapidity under isothermal conditions by using a DNA polymerase with high displacement strand activity and a set of specifically designed primers to amplify targeted DNA strands. Following its first discovery by Notomi et al. (2000 Nucleic Acids Res 28: E63), LAMP was further developed over the years which involved the combination of this technique with other molecular approaches, such as reverse transcription and multiplex amplification for the detection of infectious diseases caused by micro‐organisms in humans, livestock and plants. In this review, available types of LAMP techniques will be discussed together with their applications in detection of various micro‐organisms. Up to date, there are varieties of LAMP detection methods available including colorimetric and fluorescent detection, real‐time monitoring using turbidity metre and detection using lateral flow device which will also be highlighted in this review. Apart from that, commercialization of LAMP technique had also been reported such as lyophilized form of LAMP reagents kit and LAMP primer sets for detection of pathogenic micro‐organisms. On top of that, advantages and limitations of this molecular detection method are also described together with its future potential as a diagnostic method for infectious disease.


title: Surgical tracheostomies in Covid-19 patients: Important considerations and the “5Ts” of safety

text: Abstract The coronavirus disease (covid19) pandemic (caused by the SARS-CoV-2 virus) is the greatest healthcare challenge in a generation. Clinicians are modifying the way they approach day-to-day procedures. Safety and reduction transmission risk is paramount. Surgical tracheostomies in covid19 patients are aerosol generating procedures linked with a significant risk of viral contamination. Here, we describe our local approach for these procedures, introducing the “5Ts” of safe tracheostomy practice: Theatre set-up, Team Briefing, Transfer of patient, Tracheostomy Procedure, Team Doffing and de-brief. We identify the critical steps of the procedure and explain how we overcome the risks linked with breaking the transfer circuit to link the patient to the theatre ventilator. We explain our technique to reduce secretion spillage when opening the trachea. We emphasise the importance of closed tracheal suctioning and mouth suctioning prior to patient transfer. We highlight the importance of maintaining a closed circuit throughout the procedure and describe tips on how to achieve this. We summarise the steps in our protocol in an “easy to reproduce” way. Finally, we emphasise the importance of communication in a constantly changing environment and challenging circumstances.


title: Chapter 16 Knowledge-Based Crisis and Emergency Management

text: Contributor: Maurits van den Berg Image: Evgeny Dubinchuk – https://stock.adobe.com/be_en/images/large-flames-of-forest-fire/24003771?prev_url=detail Icon in page corners: Fire icon by Nicolas Vicent, from the Noun Project (https://thenounproject.com/search/?q=firei=91161)


title: Inter-laboratory study to characterize the detection of serum antibodies against porcine epidemic diarrhoea virus

text: Abstract Porcine epidemic diarrhea virus (PEDV) has caused extensive economic losses to pig producers in many countries. It was recently introduced, for the first time, into North America and outbreaks have occurred again in multiple countries within Europe as well. To assess the properties of various diagnostic assays for the detection of PEDV infection, multiple panels of porcine sera have been shared and tested for the presence of antibodies against PEDV in an inter-laboratory ring trial. Different laboratories have used a variety of “in house” ELISAs and also one commercial assay. The sensitivity and specificity of each assay has been estimated using a Bayesian analysis applied to the ring trial results obtained with the different assays in the absence of a gold standard. Although different characteristics were found, it can be concluded that each of the assays used can detect infection of pigs at a herd level by either the early European strains of PEDV or the recently circulating strains (INDEL and non-INDEL). However, not all the assays seem suitable for demonstrating freedom from disease in a country. The results from individual animals, especially when the infection has occurred within an experimental situation, show more variation.


Health-system reforms to control tuberculosis in China


title: Human genetic basis of fulminant viral hepatitis

text: In rare cases, hepatitis A virus (HAV) and hepatitis B virus (HBV) can cause fulminant viral hepatitis (FVH), characterized by massive hepatocyte necrosis and an inflammatory infiltrate. Other viral etiologies of FVH are rarer. FVH is life-threatening, but the patients are typically otherwise healthy, and normally resistant to other microbes. Only a small minority of infected individuals develop FVH, and this is the key issue to be addressed for this disease. In mice, mouse hepatitis virus 3 (MHV3) infection is the main model for dissecting FVH pathogenesis. Susceptibility to MHV3 differs between genetic backgrounds, with high and low mortality in C57BL6 and A/J mice, respectively. FVH pathogenesis in mice is related to uncontrolled inflammation and fibrinogen deposition. In humans, FVH is typically sporadic, but rare familial forms also exist, suggesting that there may be causal monogenic inborn errors. A recent study reported a single-gene inborn error of human immunity underlying FVH. A patient with autosomal recessive complete IL-18BP deficiency was shown to have FVH following HAV infection. The mechanism probably involves enhanced IL-18- and IFN-γ-dependent killing of hepatocytes by NK and CD8 T cytotoxic cells. Proof-of-principle that FVH can be genetic is important clinically, for the affected patients and their families, and immunologically, for the study of immunity to viruses in the liver. Moreover, the FVH-causing IL18BP genotype suggests that excessive IL-18 immunity may be a general mechanism underlying FVH, perhaps through the enhancement of IFN-γ immunity.


title: Evaluation of recombinant fowlpox virus expressing infectious bronchitis virus S1 gene and chicken interferon-γ gene for immune protection against heterologous strains

text: Abstract A recombinant fowlpox virus (rFPV-IFNγS1) that co-expressed the infectious bronchitis virus (IBV) S1 gene and the chicken interferon-γ gene has been constructed. To evaluate the efficacy of the recombinant fowlpox virus vaccine against heterotypic IBV strains, 60 4-week-old Specific-Pathogen-Free (SPF) chickens were inoculated with this vaccine and 3 weeks post inoculation challenged with the homotypic IBV strain LX4 and the heterotypic IBV strains LHB, LHLJ04XI, LTJ95I and LSC99I. Antibodies against IBV were detected in vaccinated chickens 1-week post inoculation. The number of CD4+ and CD8+ T-lymphocytes in the peripheral blood increased rapidly in the vaccinated groups challenged with strains LX4, LHB and LHLJ04XI. There were significant differences in the number of CD4+ and CD8+ T-lymphocytes between the vaccinated groups challenged with strains LTJ95I and LSC99I and all the control groups. The morbidity was below 30% in vaccinated groups challenge with strains LX4, LHB and LHLJ04XI, but was 40% greater than that in the other groups. In addition, the lesions and the amount of virus shedding were less severe in the vaccinated groups challenged by strains LX4, LHB and LHLJ04XI when compared with the other groups, but there was no significant difference in the average body weight of the chickens in all groups (all p >0.05). These results indicate that the rFPV-IFNγS1 protected chickens against challenge with homotypic IBV strain LX4 and heterotypic strains LHLJ04XI and LHB.


title: Viral-associated exacerbations of asthma and COPD

text: Exacerbations of asthma and chronic obstructive pulmonary disease are major burdens on the healthcare system, and contribute significantly to the mortality and morbidity associated with these diseases. Upper respiratory viral infections are associated with the majority of such disease exacerbations. The past few years have seen advances in the mechanisms by which viral infections induce pro-inflammatory chemokine production, and in our understanding of host antiviral and anti-inflammatory defence pathways that might regulate responses to infection. A more comprehensive understanding of the molecular basis of these processes could elucidate new therapeutic approaches to reduce the devastating impact that these exacerbations have on quality of life and healthcare costs.


IF-03 Clinical Effectiveness of Oseltamivir or Zanamivir for Influenza A/H1N1 Virus with or without H274Y Mutation


title: Infections and foreign bodies in ENT

text: Abstract Infections of the ear, nose and throat are common. The majority of these infections are managed by the primary care physicians and they settle with conservative and medical management. However, a small group can progress to become troublesome and develop complications to the extent that they may require surgical intervention. Some of the infections can lead to life-threatening complications therefore awareness and correct diagnosis along with appropriate management is paramount. Foreign bodies in the ear, nose and throat are commonly encountered. The location and type of foreign body can have an implication on the urgency of action and the possible complications. In this article the common ENT infections and foreign bodies and their management are discussed.


title: A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing

text: An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 290,000 people since the end of 2019, killed over 12,000, and caused worldwide social and economic disruption(1,2). There are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Unfortunately, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To illuminate this, we cloned, tagged and expressed 26 of the 29 viral proteins in human cells and identified the human proteins physically associated with each using affinity- purification mass spectrometry (AP-MS), which identified 332 high confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays. The identification of host dependency factors mediating virus infection may provide key insights into effective molecular targets for developing broadly acting antiviral therapeutics against SARS-CoV-2 and other deadly coronavirus strains.