title: Principles of Molecular Organization, Expression, and Evolution of Closteroviruses: Over The Barriers

text: Publisher Summary This chapter focuses on the molecular organization, evolution, and expression of closterovirus genomes, as well as on their unique particle structure. The closterovirus group combines several positive-strand RNA viruses with very flexuous filamentous particles, of which beet yellows virus (BYV) is the type virus. Closteroviruses are distinct from other RNA viruses of plants in some important phenomenological aspects. They have genomes of up to 20 kilobases (kb), a value comparable only to those of the animal coronaviruses and toroviruses, which have the largest RNA genomes of all positive-strand RNA viruses. The existence of such genomes having a coding capacity several times that of an average RNA virus genome raises questions as to the trend whereby the long genomes have evolved and the possible novel functions they have acquired. The dramatic increase in the closterovirus genome coding capacity may be linked to the distinct ecological niche they occupy. Thus, closteroviruses are the only elongated plant viruses known so far to cause phloem-limited infections in plants and to persist in their insect vectors for many hours, in contrast to only minutes.


Proposed algorithm during COVID-19 pandemic for patient management in medical retina clinic


title: The successes and future prospects of the linear antisense RNA amplification methodology

text: It has been over a quarter of a century since the introduction of the linear RNA amplification methodology known as antisense RNA (aRNA) amplification. Whereas most molecular biology techniques are rapidly replaced owing to the fast-moving nature of development in the field, the aRNA procedure has become a base that can be built upon through varied uses of the technology. The technique was originally developed to assess RNA populations from small amounts of starting material, including single cells, but over time its use has evolved to include the detection of various cellular entities such as proteins, RNA-binding-protein-associated cargoes, and genomic DNA. In this Perspective we detail the linear aRNA amplification procedure and its use in assessing various components of a cell's chemical phenotype. This procedure is particularly useful in efforts to multiplex the simultaneous detection of various cellular processes. These efforts are necessary to identify the quantitative chemical phenotype of cells that underlies cellular function.


title: 15 What factors predispose patients to acute respiratory distress syndrome?

text: Abstract: Sepsis, pneumonia, and shock are the most common conditions predisposing to acute respiratory distress syndrome (ARDS) and certain host genetic variants have been associated with the development of ARDS. Risk modifiers include abuse of alcohol and tobacco, malnutrition, and obesity. The Lung Injury Prediction Score (LIPS) and the simplified Early Acute Lung Injury Score predict ARDS based on clinical and investigational criteria. Hospital-acquired ARDS may result from a medley factors of which high tidal volume ventilation, high oxygen concentration, and plasma transfusion are most commonly implicated. The Checklist for Lung Injury Prevention (CLIP) has been developed to ensure compliance with evidence-based practice that may affect ARDS occurrence. To date, no pharmacologic intervention has been shown to prevent ARDS


title: Molecular characterization of pathogenic 4/91-like and QX-like infectious bronchitis virus infecting commercial poultry farms in Indonesia

text: BACKGROUND AND AIM: Existing data on the characteristics of infectious bronchitis virus (IBV) gathered throughout Indonesia have been recognized to indicate variants similar to globally distributed vaccine strains. Despite past and current intensive vaccination programs, IBV infections in the country’s poultry industry have not been effectively controlled. Therefore, this study aimed to investigate the genotype of several isolates based on partial S1 gene sequences. In particular, the investigation is directed to focus on layer chickens in actively vaccinated farms indicating IBV symptoms. MATERIALS AND METHODS: Samples were isolated from ten different layer chicken flocks experiencing respiratory problem, drops in egg production, and a “penguin-like” stance, which were collected from commercial poultry farms in Central Java and Yogyakarta regions, Indonesia, within the periods of 2012-2018. Fragment of the S1 gene of IBV sampled from actively vaccinated commercial poultry farms was amplified using primer 5’-aca tgg taa ttt ttc aga tgg-3’ (forward) and 5’-cag att gct tac aac cac c-3’ (reverse) with the length of polymerase chain reaction (PCR) product at 383 bp. The sequence of samples was then compared with the sequence of reference S1 gene nucleotides of IBV from NCBI GenBank database. The amino acid analysis and multiple alignment sequence were conducted using Mega X. RESULTS: During necropsy, enlargement of the oviduct and swollen kidney were observed. Reverse transcription-PCR diagnosis of their 383 bp S1 gene showed that all samples were IBV positive. Phylogenetic analysis of the S1 gene discovered seven samples to be clustered as 4/91-like strains. Meanwhile, the remaining three samples were grouped in QX-like strain cluster. CONCLUSION: This study is a pioneering report providing molecular evidence of pathogenic QX-like and 4/91-like strains circulating in Indonesia. Findings discovered, in this study, strongly suggested the importance of improving protections by available IBV vaccines through updated circulating strain clusters. It is critical to ensure the delivery of an effective control measurement of and vaccination protocols against IBV infections in the country’s commercial poultry industry in particular and worldwide in general.


title: The Alarming Burden of Non‐Communicable Diseases in COVID‐19 New Normal: Implications on Oral Health

text: The coronavirus disease (COVID‐19) outbreak has triggered massive debates within dental professional organizations about prioritization of offered services, served groups, and required protective measures.(Volgenant et al., 2020) While navigating through the post‐outbreak era, we aim to demonstrate the importance of continuous global focus on the burden of non‐communicable diseases (NCDs) such as oral diseases. Oral diseases are the most prevalent NCDs worldwide consuming one‐fifth of out‐of‐pocket health expenditure and being recognized as the third most expensive condition to treat in Europe.(Peres et al., 2019) The World Health Organization (WHO) recommends prioritizing common risk factor approaches in all interventions targeting NCDs in order to draw attention to the multifaceted relationship between oral diseases and chronic conditions like diabetes, cardiovascular disease, and cancers.(Sheiham & Watt, 2000)


title: DNA microarrays for the diagnosis of infectious diseases

text: Abstract The diagnosis of bacterial infections relies on isolation of the bacterium, which is rarely achieved when needed for patient management. Furthermore, culture is poorly suited to the diagnosis of polymicrobial infections. Finally, a syndromic approach should target both bacteria and viruses causing the same syndrome. The detection of specific DNA sequences in clinical specimen, using DNA microarrays, is an alternative. Microarrays were first used as a diagnostic tool in 1993, to identify a hantavirus associated with an outbreak of acute respiratory diseases. The main advantage of microarrays is multiplexing, enabling exploration of the microbiota and pathogen detection in bacteremia, respiratory infections, and digestive infections: circumstance in which DNA arrays may lack sensitivity and provide false negatives. Enrichment of sampling can increase sensitivity. Furthermore, chips allow typing Streptococcus pneumoniae and detecting resistance in Staphylococcus aureus (MRSA) and Mycobacterium tuberculosis (rifampicin, isoniazid, fluoroquinolones). However, the cost and high technical requirements remain a problem for routine use of this bacterial infection diagnostic technology.


title: Nitric oxide inhalation as an interventional rescue therapy for COVID-19-induced acute respiratory distress syndrome

text: COVID-19 is an emerging disease of public health concern. While there is no specific recommended treatment for COVID-19, nitric oxide has the potential to be of therapeutic value for managing acute respiratory distress syndrome in patients with COVID-19. However, inhaled nitric oxide has not yet been formally evaluated. Given the extent of the COVID-19 pandemic, and the large numbers of hospitalized patients requiring respiratory support, clinical use of inhaled nitric oxide may become an alternate rescue therapy before extracorporeal membrane oxygenation for the management of acute respiratory distress syndrome in patients with COVID-19.


title: Let’s Be Gentle With Ourselves and Each Other

text: A nurse reflects on the many lessons the COVID-19 pandemic is teaching us.


AIRPORTS AND SERVICES: Coronavirus


title: Chapter 7 Pathogenesis of Virus Infections

text: Abstract Pathogenesis encompasses all the sequence of events accompanying acute and persistent infections. It includes entry of the virus into the body, multiplication and spread, the development of tissue damage, and the production of an immune response; the latter may contribute to the pathology of an infection. It includes the appearance of clinical signs and symptoms, the eventual resolution of the infection and, in most cases, virus elimination. Understanding viral disease pathogenesis requires knowledge of each of the stages of infection and an awareness of the underlying mechanisms. There may be variation from individual to individual in the severity and/or the duration of these events, but a sound working knowledge of a typical sequence associated with each infection is crucial in both making an accurate diagnosis and recommending the appropriate treatment.


title: Systems biology and the host response to viral infection

text: Will our increasing understanding of virus-host interactions translate into a new generation of antiviral therapeutics or steer us toward an expensive journey to nowhere?


title: Clinical Approach to Dermatologic Disease in Exotic Animals

text: Skin disease is an extremely common presenting complaint to the exotic animal practitioner. A systematic diagnostic approach is necessary in these cases to achieve a diagnosis and formulate an effective treatment plan. In all exotic species, husbandry plays a central role in the pathogenesis of cutaneous disease, so a thorough evaluation of the husbandry is critical for successful management. The clinical approach to skin disease in exotic animal patients is reviewed with specific focus on structure and function of the skin, diagnostic testing, and differential diagnoses for commonly encountered cutaneous diseases.


title: The effect of control strategies to reduce social mixing on outcomes of the COVID-19 epidemic in Wuhan, China: a modelling study

text: Summary Background In December, 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, emerged in Wuhan, China. Since then, the city of Wuhan has taken unprecedented measures in response to the outbreak, including extended school and workplace closures. We aimed to estimate the effects of physical distancing measures on the progression of the COVID-19 epidemic, hoping to provide some insights for the rest of the world. Methods To examine how changes in population mixing have affected outbreak progression in Wuhan, we used synthetic location-specific contact patterns in Wuhan and adapted these in the presence of school closures, extended workplace closures, and a reduction in mixing in the general community. Using these matrices and the latest estimates of the epidemiological parameters of the Wuhan outbreak, we simulated the ongoing trajectory of an outbreak in Wuhan using an age-structured susceptible-exposed-infected-removed (SEIR) model for several physical distancing measures. We fitted the latest estimates of epidemic parameters from a transmission model to data on local and internationally exported cases from Wuhan in an age-structured epidemic framework and investigated the age distribution of cases. We also simulated lifting of the control measures by allowing people to return to work in a phased-in way and looked at the effects of returning to work at different stages of the underlying outbreak (at the beginning of March or April). Findings Our projections show that physical distancing measures were most effective if the staggered return to work was at the beginning of April; this reduced the median number of infections by more than 92% (IQR 66–97) and 24% (13–90) in mid-2020 and end-2020, respectively. There are benefits to sustaining these measures until April in terms of delaying and reducing the height of the peak, median epidemic size at end-2020, and affording health-care systems more time to expand and respond. However, the modelled effects of physical distancing measures vary by the duration of infectiousness and the role school children have in the epidemic. Interpretation Restrictions on activities in Wuhan, if maintained until April, would probably help to delay the epidemic peak. Our projections suggest that premature and sudden lifting of interventions could lead to an earlier secondary peak, which could be flattened by relaxing the interventions gradually. However, there are limitations to our analysis, including large uncertainties around estimates of R 0 and the duration of infectiousness. Funding Bill & Melinda Gates Foundation, National Institute for Health Research, Wellcome Trust, and Health Data Research UK.


title: Determination of chemical changes in Isatis indigotica seeds carried after Chinese first spaceship with FTIR and 2D-IR correlation spectroscopy

text: Abstract Spaceflight represents a complex environmental condition. Space mutagenesis breeding has achieved and marked certain results over the years. This method was employed in our previous studies in order to obtain improved germplasm of Isatis indigotica. This study is to determine the chemical changes in I. indigotica seeds carried after Chinese first spaceship (Shenzhou I). Fourier transform infrared (FTIR), second derivative and two-dimensional infrared (2DIR) correlation spectroscopy were used in analysis. Not much differences between the two spectra were found except the peaks in the range of 1500–1200cm− 1 which was about 7cm− 1 different and indicated the absorption could be initialed from different bonds. SP4 showed different derivative compared with C4 in the second derivative spectra of 1200–800cm− 1. The stronger signal of 2DIR in SP4 indicated the protein content of the seed was changed after spaceflight. It is concluded that spaceflight provided an extreme condition that caused changes of chemical properties in I. indigotica.


title: Serum profiling of leptospirosis patients to investigate proteomic alterations

text: Abstract Leptospirosis is a zoonotic infectious disease of tropical, subtropical and temperate zones, which is caused by the pathogenic spirochetes of genus Leptospira. Although this zoonosis is generally not considered as fatal, the pathogen can eventually cause severe infection with septic shock, multi-organ failure and lethal pulmonary hemorrhages leading to mortality. In this study, we have performed a proteomic analysis of serum samples from leptospirosis patients (n=6), febrile controls (falciparum malaria) (n=8) and healthy subjects (n=18) to obtain an insight about disease pathogenesis and host immune responses in leptospiral infections. 2DE and 2D-DIGE analysis in combination with MALDI-TOF/TOF MS revealed differential expression of 22 serum proteins in leptospirosis patients compared to the healthy controls. Among the identified differentially expressed proteins, 8 candidates exhibited different trends compared to the febrile controls. Functional analysis suggested the involvement of differentially expressed proteins in vital physiological pathways, including acute phase response, complement and coagulation cascades and hemostasis. This is the first report of analysis of human serum proteome alterations in leptospirosis patients, which revealed several differentially expressed proteins, including α-1-antitrypsin, vitronectin, ceruloplasmin, G-protein signaling regulator, apolipoprotein A-IV, which have not been reported in context of leptospirosis previously. This study will enhance our understanding about leptospirosis pathogenesis and provide a glimpse of host immunological responses. Additionally, a few differentially expressed proteins identified in this study may further be investigated as diagnostic or prognostic serum biomarkers for leptospirosis. This article is part of a Special Issue entitled: Integrated omics.


title: Beyond traditional surveillance: applying syndromic surveillance to developing settings – opportunities and challenges

text: BACKGROUND: All countries need effective disease surveillance systems for early detection of outbreaks. The revised International Health Regulations [IHR], which entered into force for all 194 World Health Organization member states in 2007, have expanded traditional infectious disease notification to include surveillance for public health events of potential international importance, even if the causative agent is not yet known. However, there are no clearly established guidelines for how countries should conduct this surveillance, which types of emerging disease syndromes should be reported, nor any means for enforcement. DISCUSSION: The commonly established concept of syndromic surveillance in developed regions encompasses the use of pre-diagnostic information in a near real time fashion for further investigation for public health action. Syndromic surveillance is widely used in North America and Europe, and is typically thought of as a highly complex, technology driven automated tool for early detection of outbreaks. Nonetheless, low technology applications of syndromic surveillance are being used worldwide to augment traditional surveillance. SUMMARY: In this paper, we review examples of these novel applications in the detection of vector-borne diseases, foodborne illness, and sexually transmitted infections. We hope to demonstrate that syndromic surveillance in its basic version is a feasible and effective tool for surveillance in developing countries and may facilitate compliance with the new IHR guidelines.


title: CORONA-steps for tracheotomy in COVID-19 patients: A staff-safe method for airway management

text: • The recent outbreak of SARS‐CoV‐2 has assumed worldwide proportion. • Tracheostomy in intubated COVID-19 patients requires adjunctive safeguards. • A step-by-step approach named CORONA is proposed in order to recall essential recommendations during the surgical procedure. • The CORONA-method would allow a secure space in which health workers can guarantee their activity, safely.


COVID‐19: The personal and professional impact of one case


title: Reduced Physical Activity During COVID-19 Pandemic in Children with Congenital Heart Disease

text: Abstract Children with congenital heart disease (CHD) are at-risk for both COVID-19 and secondary cardiovascular outcomes. Their increased cardiovascular risk may be mitigated through physical activity, but public health measures implemented for COVID-19 can make physical activity challenging. We objectively measured the impact of the COVID-19 pandemic on physical activity, continuously measured by FitbitTM step-counts, in children with CHD. Step-counts were markedly lower in late March and early April 2020, compared to 2019 and to early March 2020. It is vital to understand how precautions for COVID-19 will impact the health of children with CHD, especially if they persist long-term.


title: Understanding Ebola virus and other zoonotic transmission risks through human–bat contacts: Exploratory study on knowledge, attitudes and practices in Southern Cameroon

text: The ecology of Ebola virus (EBV) remains largely unknown, but the previous detection of viral RNA and anti‐EBV antibodies in African bats suggests that they might play a role in the EBV reservoir. Moreover, African bats also carry other potentially zoonotic agents such as Henipah‐like viruses, coronaviruses and lyssaviruses. Today only little information is available on interactions between humans and bats. The objective of our exploratory study was to describe the extent and modes of contacts between humans and bats in southern Cameroon, considered as an area at risk for future EBV outbreaks. The survey was conducted in 11 villages of four distinct rural areas in southern Cameroon. A total of 135 respondents were interviewed using semi‐structured questionnaires, between February and May 2017. The study showed that direct contacts between bats and humans are relatively common. Bat bushmeat appeared to be an occasional meat resource; 40% of respondents consume bats with a median annual consumption of three, and 28% of respondents hunt them. About 22% of the respondents reported children catching bats. Indirect contact also appeared to be common; 55% of hunters use caves as shelters and 67% of interviewees eat fruits previously chewed by bats. Bat consumption varied significantly between regions (from 0% to 87%) and between pygmies and bantus in the extreme south‐east of Cameroon. The study revealed considerable diversity in practices among interviewees, most of them being subsistence cultivators and relying on self‐hunted bushmeat. Geographical diversity of contacts and perceptions regarding bats in Cameroon emphasizes the need to adjust zoonotic pathogen surveillance and education campaigns to the specificities of the communities and their context of interaction with wildlife.


title: Highlights from the 2014 International Symposium on HIV & Emerging Infectious Diseases (ISHEID): from cART management to the end of the HIV pandemic

text: The 2014 International Symposium on HIV and Emerging Infectious Diseases (ISHEID) provided a forum for investigators to hear the latest research developments in the clinical management of HIV and HCV infections as well as HIV cure research. Combined anti-retroviral therapy (c-ART) has had a profound impact on the disease prognosis and transformed this infection into a chronic disease. However, HIV is able to persist within the infected host and the pandemic is still growing. The main 2014 ISHEID theme was, hence “Together for a world without HIV and AIDS”. In this report we not only give details on this main topic but also summarize what has been discussed in the areas of HCV coinfection and present a short summary on currently emerging viral diseases.


title: Use of adenoviral vectors as veterinary vaccines

text: Vaccines are the most effective and inexpensive prophylactic tool in veterinary medicine. Ideally, vaccines should induce a lifelong protective immunity against the target pathogen while not causing clinical or pathological signs of diseases in the vaccinated animals. However, such ideal vaccines are rare in the veterinary field. Many vaccines are either of limited effectiveness or have harmful side effects. In addition, there are still severe diseases with no effective vaccines. A very important criterion for an ideal vaccine in veterinary medicine is low cost; this is especially important in developing countries and even more so for poultry vaccination, where vaccines must sell for a few cents a dose. Traditional approaches include inactivated vaccines, attenuated live vaccines and subunit vaccines. Recently, genetic engineering has been applied to design new, improved vaccines. Adenovirus vectors are highly efficient for gene transfer in a broad spectrum of cell types and species. Moreover, adenoviruses often induce humoral, mucosal and cellular immune responses to antigens encoded by the inserted foreign genes. Thus, adenoviruses have become a vector of choice for delivery and expression of foreign proteins for vaccination. Consequently, the market requirements for adenovirus vaccines are increasing, creating a need for production methodologies of concentrated vectors with warranted purity and efficacy. This review summarizes recent developments and approaches of adenovirus production and purification as the application of these vectors, including successes and failures in clinical applications to date.


title: Trends in US approvals: new biopharmaceuticals and vaccines

text: The efficient development and approval of new therapeutics and vaccines is vital to the health and welfare of patients. Tufts Center for the Study of Drug Development has collected and analyzed data for new protein therapeutics and vaccines approved in the USA during the past decade. Our results suggest trends toward longer clinical and approval phases for the therapeutics, particularly for oncology products. In this Opinion article, we discuss various legislative acts and FDA initiatives that might improve the efficiency of drug development and approval. Furthermore, few new vaccines have been approved in the past 10 years owing, at least in part, to the lack of incentives for the development of the products. We predict that this might change in the future as government and industry respond to the twin threats of the global spread of infectious diseases and potential bioterrorism.


title: Inflammasomes and their roles in the pathogenesis of viral hepatitis and their related complications: An updated systematic review

text: Abstract Inflammasomes are a set of innate receptors which are the responsible molecules for activation of pro-interleukin (IL)-1β and IL-18 and induction of inflammation. Due to the key roles of the inflammasomes in the induction of inflammation, it has been hypothesized that the molecules may be the main parts of immune responses against viral infections and the tissue damage. Because some cases of viral hepatitis infections, including hepatitis B and C, are diagnosed as chronic and may be associated with various complications such as liver cirrhosis and hepatocellular carcinoma (HCC), several studies focused on the roles played by the inflammation on the pathogenesis of viral hepatitis. Based on the roles played by inflammasomes in induction of inflammation, it has been hypothesized that inflammasomes may be the main parts of the puzzle of the viral hepatitis complications. This article reviews the roles of the inflammasomes in the pathogenesis of hepatitis B and C viral infections and their complications, liver cirrhosis, and HCC.


title: A core extended naphtalene diimide G-quadruplex ligand potently inhibits herpes simplex virus 1 replication

text: G-quadruplexes (G4s) are nucleic acids secondary structures, epigenetic regulators in cells and viruses. In herpes simplex virus 1 (HSV-1)-infected cells, G4s are massively present during viral replication. We here aimed at investigating the possibility to target the HSV-1 G4s by a core extended naphtalene diimide (c-exNDI) G4 ligand. Biophysical and biomolecular analysis proved that c-exNDI stabilized the HSV-1 G4s in a concentration dependent manner. In MS competition assays, c-exNDI preferentially recognized HSV-1 G4s over cellular telomeric G4s, the most represented G4s within cells; other less abundant cellular G4s were also recognized. Treatment of HSV-1 infected cells with c-exNDI at low nanomolar concentrations induced significant virus inhibition with no cytotoxicity. The mechanism of action was ascribed to G4-mediated inhibition of viral DNA replication, with consequent impairment of viral genes transcription. Our data suggest that the observed potent antiviral activity and low cytotoxicity mainly depend on a combination of c-exNDI affinity for HSV-1 G4s and their massive presence during infection. HSV-1 G4s may thus represent new effective antiviral targets: the fact that no current antiherpetic drug exploits them and their presence at the viral genome, responsible for both active and latent HSV infections, makes them particularly attracting.


title: A step towards gender equity to strengthen the pharmaceutical workforce during COVID-19

text: There is plenty of evidence to support that women leaders are needed in the health and pharmaceutical sectors, although most of the leadership positions in global health are predominantly occupied by men. This is a major challenge to global health policy. Gender diversity and inclusion within the pharmaceutical workforce is integral to optimal patient care. Women continue to be underrepresented in senior and leadership positions within pharmacy, despite outnumbering the men in the global pharmacy workforce. This commentary highlights the need towards gender equity and discusses the several key initiatives that are building momentum and making substantial progress towards this agenda in the pharmaceutical workforce.


title: The coronavirus spread: the Italian case

text: A model based on population growth, chaotic maps, and turbulent flows is applied to the spread of Coronavirus for each Italian region in order to obtain useful information and help to contrast it. We divide the regions into different risk categories and discuss anomalies. The worst cases are confined between the Appenine and the Alps mountain ranges but the situation seem to improve closer to the sea. The Veneto region gave the most efficient response so far and some of their resources could be diverted to other regions, in particular, more tests to the Lombardia, Liguria, Piemonte, Marche and V. Aosta regions, which seem to be worst affected. We noticed worrying anomalies in the Lazio, Campania and Sicilia regions to be monitored. We stress that the number of fatalities we predicted on March 12 has been confirmed daily by the bulletins. This suggests a change of strategy in order to reduce such number maybe moving the weaker population (and negative to the virus test) to beach resorts, which should be empty presently. The ratio deceased/positives on April 4, 2020 is 5.4% worldwide, 12.3% in Italy, 1.4% in Germany, 2.7% in the USA, 10.3% in the UK and 4.1% in China. These large fluctuations should be investigated starting from the Italian regions, which show similar large fluctuations.


title: Mass gathering and globalization of respiratory pathogens during the 2013 Hajj

text: Every year, more than 10 million pilgrims arrive in the Kingdom of Saudi Arabia for the Hajj or Umrah. Crowding conditions lead to high rates of respiratory infections among the pilgrims, representing a significant cause of morbidity and a major cause of hospitalization. Pre- and post-Hajj nasal specimens were prospectively obtained from a paired cohort (692 pilgrims) and from nonpaired cohorts (514 arriving and 470 departing pilgrims) from 13 countries. The countries of residence included Africa (44.2%), Asia (40.2%), the United States (8.4%) and Europe (7.2%). Nasal specimens were tested for 34 respiratory pathogens using RT-PCR. A total of 80 512 PCRs were performed. The prevalence of viruses and bacteria increased, from 7.4% and 15.4% before the Hajj to 45.4% and 31.0% after the Hajj, respectively, due to the acquisition of rhinovirus, coronaviruses (229E, HKU1, OC43), influenza A H1N1, Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus. We did not identify Middle East respiratory coronavirus carriage. At arrival, the prevalence of several viruses was clearly dependent on the pilgrim's country of origin. After Hajj participation, these viruses were isolated among pilgrims from all countries, with few exceptions. No significant differences were observed between paired and nonpaired cohort results. Our results strongly suggest that, given the particularly crowded conditions during the rituals, an international mass gathering such as the Hajj may contribute to the globalization of respiratory pathogens after the cross-contamination of pilgrims harbouring pathogens that easily spread among participants. Influenza and pneumococcal vaccination, face mask use and hand hygiene should be considered in the context of the Hajj.


title: Occupation-Related Respiratory Infections Revisited

text: Occupational pulmonary infectious diseases include tuberculosis (TB) and many viral pathogens, including influenza, coronavirus (severe acute respiratory syndrome or SARS), varicella, respiratory syncytial virus, and hantavirus. This review focuses on TB, influenza, and SARS, because the published literature is extensive for these 3 infections. The lessons from these 3 are relevant for all nosocomial pulmonary infectious diseases.


title: Detection of respiratory viruses in adult patients with perennial allergic rhinitis

text: Abstract Background The symptoms of allergic rhinitis may be worsened by a viral respiratory infection. However, there are few data on the presence of respiratory virus in patients with allergic rhinitis. Objective To evaluate whether patients with allergic rhinitis have an increased frequency of respiratory virus detection in a prospective case–control study. Methods Fifty-eight adult patients diagnosed with perennial allergic rhinitis were evaluated from September 2011 through June 2012. A control group of 61 adult patients without allergy was included. Multiplex polymerase chain reaction was used to detect respiratory viruses in nasal lavage samples. Results Respiratory viruses were detected in 25 of 58 patients (43.1%) with perennial allergic rhinitis, but in only 15 of 61 control patients (24.6%). In virus-positive samples, multiple viruses were detected in 9 of 25 patients (36.0%) with perennial allergic rhinitis but in only 2 of 15 control patients (12.5%). Rhinovirus was the most common virus in patients without allergy and those with allergic rhinitis. There were significant differences in the detection rates of overall and multiple respiratory viruses and rhinovirus between the 2 groups (P < .05). However, in patients with allergic rhinitis, there was no statistically significant association between the detection of respiratory viruses and symptom scores. Conclusion This study shows that there is a high prevalence of respiratory viruses, especially rhinovirus, in patients with allergic rhinitis. Subsequent studies are needed to determine the clinical significance of highly prevalent respiratory viruses in patients with allergic rhinitis.


title: Assembly of pseudorabies virus genome-based transfer vehicle carrying major antigen sites of S gene of transmissible gastroenteritis virus: Potential perspective for developing live vector vaccines

text: Abstract Two severe porcine infectious diseases, pseudorabies (PR) and transmissible gastroenteritis (TGE) caused by pseudorabies virus (PRV) and transmissible gastroenteritis virus (TGEV) respectively often result in serious economic loss in animal husbandry worldwide. Vaccination is the important prevention means against both infections. To achieve a PRV genome-based virus live vector, aiming at further TGEV/PRV bivalent vaccine development, a recombinant plasmid pUG was constructed via inserting partial PK and full-length gG genes of PRV strain Bartha K-61 amplified into pUC119 vector. In parallel, another recombinant pHS was generated by introducing a fragment designated S1 encoding the major antigen sites of S gene from TGEV strain TH-98 into a prokaryotic expression vector pPROEX HTc. The SV40 polyA sequence was then inserted into the downstream of S1 fragment of pHS. The continuous region containing S1fragment, SV40 polyA and four single restriction enzyme sites digested from pHS was subcloned into the downstream of gG promoter of pUG. In addition, a LacZ reporter gene was introduced into the universal transfer vector named pUGS-LacZ. Subsequently, a PRV genome-based virus live vector was generated via homologous recombination. The functionally effective vector was purified and partially characterized. Moreover, the potential advantages of this system are discussed.


title: Prevalence of comorbidities and their association with mortality in patients with COVID‐19: A Systematic Review and Meta‐analysis

text: AIMS: COVID‐19 is a global pandemic that as of the 4th May has registered over 3 585 711 confirmed cases and 248 780 deaths. This review aims to estimate the prevalence of both cardiometabolic and other co‐morbidities in patients with COVID‐19 infection, and to estimate the increased risk of severity and mortality in people with co‐morbidities. MATERIALS AND METHODS: Medline, Scopus and the World Health Organisation (WHO) website for Global research on COVID‐19 were searched from January 2019 up to April 23, 2020. Study inclusion was restricted to English language publications, original articles that reported prevalence of co‐morbidities in individuals with COVID‐19 disease, and case‐series >10 patients. 18 studies were selected for inclusion. Data were analysed using random effects meta‐analysis models. RESULTS: Eighteen studies with a total of 14 558 individuals were identified. The pooled prevalence for co‐morbidities in patients with COVID‐19 disease was 22.9% (95% CI: 15.8 to 29.9) for hypertension; 11.5% (9.7 to 13.4) for diabetes; and 9.7% (6.8 to 12.6) for cardiovascular disease (CVD). For chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), cerebrovascular disease, and cancer, the pooled prevalences were all less than 4%. With the exception of cerebrovascular disease, all other co‐morbidities had a significantly increased risk for having severe COVID‐19. In addition, the risk of mortality was significantly increased in individuals with CVD, COPD, CKD, cerebrovascular disease, and cancer. CONCLUSIONS: In individuals with COVID‐19, the presence of co‐morbidities (both cardiometabolic and other) is associated with a higher risk of severe COVID‐19 and mortality. These findings have important implications for the public health with regards to risk stratification and future planning. This article is protected by copyright. All rights reserved.


title: Exosomal vaccines containing the S protein of the SARS coronavirus induce high levels of neutralizing antibodies

text: Abstract Infection with the SARS-associated coronavirus (SARS-CoV) induces an atypical pulmonary disease with a high lethality rate. Although the initial SARS epidemic was contained, sporadic outbreaks of the disease still occur, suggesting a continuous need for a vaccine against this virus. We therefore explored exosome-based vaccines containing the spike S proteins of SARS-CoV. S-containing exosomes were obtained by replacing the transmembrane and cytoplasmic domains of the S protein by those of VSV-G. The immunogenicity and efficacy of the S-containing exosomes were tested in mice and compared to an adenoviral vector vaccine expressing the S protein. Both, S-containing exosomes and the adenoviral vector vaccine induced neutralizing antibody titers. After priming with the SARS-S exosomal vaccine and boosting with the adenoviral vector the neutralizing antibody titers exceeded those observed in the convalescent serum of a SARS patient. Both approaches were effective in a SARS-S-expressing tumor challenge model and thus warrant further investigation.


title: Guidance for Resumption of Routine Electrodiagnostic Testing during the COVID‐19 Pandemic

text: As the world accommodates to the COVID‐19 pandemic, routine in‐person medical services are resuming. The resumption of non‐urgent electrodiagnostic (EDX) testing faces unique challenges due to the long duration of the procedure and direct close contact with patients, including studies with risk of exposure to oropharyngeal secretions. We provide consensus guidance for resumption of EDX testing, addressing scheduling, patient arrival and registration, use of personal protective equipment, COVID‐19 screening and testing, the performance of EDX in outpatient and inpatient settings, cleaning and maintenance of the EDX equipment and laboratory, balancing trainee safety and training requirements, and patient care issues. These are broad recommendations which need to be adapted to local COVID‐19 risks, institutional guidelines and policies, and changing federal, state and local regulations, and to changes in the pandemic over time. This article is protected by copyright. All rights reserved.


title: Chemokine expression and viral infection of the central nervous system: Regulation of host defense and neuropathology

text: An effective host response against viral infection of the central nervous system (CNS) is the principal factor dictating the outcome of infection. It is the responsibility of the immune response to contain and control viral replication. Paradoxically, it is the immune response that may also contribute to the development of neuropathology. We have used mouse hepatitis virus (MHV), a positive-strand RNA virus, infection of the CNS to understand the dynamic interaction between viral replication, protection, and pathology with an emphasis on understanding how chemokines participate in these interrelated processes. Herein, we demonstrate the complexity of the chemokine response to MHV infection of the CNS and the delicate balance that exists between host defense and development of disease.


title: Degradation of thymic humoral factor 2 in human, rat and mouse blood: An experimental and theoretical study

text: The degradation of the immunomodulatory octapeptide, thymic humoral factor γ2 (THF-γ2, thymoctonan) has been studied in whole blood samples from human, rat and mouse. The peptide, Leu-Glu-Asp-Gly-Pro-Lys-Phe-Leu, was shown to be rapidly degraded by peptidases. The half-life of the intact peptide was less than 6 min at 37 °C in blood from the three species tested. The main fragments formed from THF-γ2 were found to be Glu-Asp-Gly-Pro-Lys-Phe-Leu (2–8), Asp-Gly-Pro-Lys-Phe-Leu (3–8) and Glu-Asp-Gly-Pro-Lys (2–6) in human and in rat blood and 2–8 and 2–6 in mouse blood. Analysis of the time course of degradation revealed a sequential removal of single amino acids from the N-terminus (aminopeptidase activities) in a process that was apparently unable to cleave the Gly-Pro bond (positions 4–5 in the peptide) together with an independent cleavage of the Lys-Phe bond (positions 6–7 in the peptide) to release the dipeptide Phe-Leu. This behaviour and the effects of inhibitors showed the involvement of metallo-exopeptidases in the N-terminal digestion and a phosphoramidon-sensitive metallo-endopeptidase in the cleavage of the Lys-Phe bond. The degradation patterns in human blood were modelled in terms of the competing pathways involved approximating to first-order kinetics, and an analytical solution obtained via the method of Laplace Transforms. The half-life of THF degradation in whole rat blood sample was found to be significantly lower than in human or mouse.


title: Post‐Acute Care Preparedness in a COVID‐19 World

text: Coronavirus disease 2019 (COVID‐19) has led to a surge of patients requiring post‐acute care. In order to support federal, state and corporate planning, we offer a four‐stage regionally oriented approach to achieving optimal systemwide resource allocation across a region's post‐acute service settings and providers over time. In the first stage, the post‐acute care system must, to the extent possible, help relieve acute hospitals of non‐COVID‐19 patients to create as much inpatient capacity as possible over the surge period. In the second stage after the initial surge as subsided, post‐acute providers must protect vulnerable populations from COVID‐19, prepare treat‐in‐place protocols for non‐COVID‐19 admissions, and create and formalize COVID‐19 specific settings. In the third stage after a vaccine has been developed or an effective prophylactic option is available, post‐acute care providers must assist with distribution and administration of vaccinations and prophylaxis, develop strategies to deliver non‐COVID‐19 related medical care, and begin to transition to the post‐COVID‐19 landscape. In the final stage, we must create health advisory bodies to review post‐acute sector's response, identify opportunities to improve performance going forward, and develop a pandemic response plan for post‐acute care providers.


title: Counting the cost of COVID-19

text: Coronavirus disease 2019 (COVID-19) is the name given by the World Health Organization (WHO) to the highly contagious and infectious disease caused by the Novel Corona Virus or SARS-CoV-2, which was first reported on 31 December 2019 in Wuhan city of the capital of China's Hubei province. Due to the rapid increase in the number of infections worldwide, the WHO in March 2020, declared COVID-19 as a pandemic. Historically, first coronavirus had surfaced in 1965 with symptoms of common cold. Since then five different strands of this virus have emerged, most lethal of them was the Severe Acute Respiratory Syndrome (SARS), which infected about eight thousand people, killing ten percent of them. The COVID-19 is not the most deadly pandemic world has ever witnessed as the Spanish influenza pandemic, during 1918–19, killed more than fifty million people. Indeed COVID-19 has turned out to be the most lethal of all coronaviruses as it has infected at least three million people killing more than two hundred thousands of them in the first 4 months of its spread. Many politicians and social scientists have dubbed the depression, being caused by COVID-19, worse than that caused by the Second World War. In this article, we shall analyze economic, social, cultural, educational and political impact of the COVID-19.


title: Viral and Bacterial Etiologies of Acute Respiratory Infections Among Children Under 5 Years in Senegal

text: Acute respiratory infections (ARIs) are the leading cause of infectious disease–related morbidity, hospitalization, and morbidity among children worldwide. This study aimed to assess the viral and bacterial causes of ARI morbidity and mortality in children under 5 years in Senegal. Nasopharyngeal samples were collected from children under 5 years who had ARI. Viruses and bacteria were identified using multiplex real-time reverse transcription-polymerase chain reaction and conventional biochemical techniques, respectively. Adenovirus was the most prevalent virus (50%; n = 81), followed by influenza virus (45.68%, n = 74), rhinovirus (40.12%; n = 65), enterovirus (25.31%; n = 41), and respiratory syncytial virus (16.05%; n = 26), whereas Streptococcus pneumoniae (17%; n = 29), Moraxella catarrhalis (15.43%; n = 25), and Haemophilus influenzae (8.02%; n = 13) were the most commonly isolated bacteria. Virus pathogens seem more likely to be more prevalent in our settings and were often associated with bacteria and S. pneumoniae (6%; 16) coinfection.


title: Induction of protective immunity against severe acute respiratory syndrome coronavirus (SARS-CoV) infection using highly attenuated recombinant vaccinia virus DIs

text: Abstract SARS-coronavirus (SARS-CoV) has recently been identified as the causative agent of SARS. We constructed a series of recombinant DIs (rDIs), a highly attenuated vaccinia strain, expressing a gene encoding four structural proteins (E, M, N and S) of SARS-CoV individually or simultaneously. These rDIs elicited SARS-CoV-specific serum IgG antibody and T-cell responses in vaccinated mice following intranasal or subcutaneous administration. Mice that were subcutaneously vaccinated with rDIs expressing S protein with or without other structural proteins induced a high level of serum neutralizing IgG antibodies and demonstrated marked protective immunity against SARS-CoV challenge in the absence of a mucosal IgA response. These results indicate that the potent immune response elicited by subcutaneous injection of rDIs containing S is able to control mucosal infection by SARS-CoV. Thus, replication-deficient DIs constructs hold promise for the development of a safe and potent SARS vaccine.


title: Japan ECMOnet for COVID-19: telephone consultations for cases with severe respiratory failure caused by COVID-19

text: Recently, the novel coronavirus disease 2019 (COVID-19) started spreading in Japan. Therefore, the number of patients with severe COVID-19 requiring extracorporeal membranous oxygenation (ECMO) is expected to increase. A working group has been formed to provide telephone consultation services for cases with severe respiratory failure caused by COVID-19 in Japan. During the first 13 days of the service, there were 12 consultations. For each consultation, we advised the patient on the initiation of ECMO and arranged transportation for patients with ECMO. Based on experience from the H1N1 influenza pandemic, transporting patients to experienced facilities is essential to obtain better outcomes.


title: Organelle dynamics and viral infections: at cross roads

text: Abstract Viruses are obligate intracellular parasites of the host cells. A commonly accepted view is the requirement of internal membranous structures for various aspects of viral life cycle. Organelles enable favourable intracellular environment for several viruses. However, studies reporting organelle dynamics upon viral infections are scant. In this review, we aim to summarize and highlight modulations caused to various organelles upon viral infection or expression of its proteins.


title: miR‐223: infection, inflammation and cancer

text: Expression of the microRNA miR‐223 is deregulated during influenza or hepatitis B infection and in inflammatory bowel disease, type 2 diabetes, leukaemia and lymphoma. Although this may also be the result of the disease per se, increasing evidence suggests a role for miR‐223 in limiting inflammation to prevent collateral damage during infection and in preventing oncogenic myeloid transformation. Validated targets for miR‐223 that have effects on inflammation and infection include granzyme B, IKKα, Roquin and STAT3. With regard to cancer, validated targets include C/EBPβ, E2F1, FOXO1 and NFI‐A. The effect of miR‐223 on these targets has been documented individually; however, it is more likely that miR‐223 affects multiple targets simultaneously for key processes where the microRNA is important. Such processes include haematopoietic cell differentiation, particularly towards the granulocyte lineage (where miR‐223 is abundant) and as cells progress down the myeloid lineage (where miR‐223 expression decreases). NF‐κB and the NLRP3 inflammasome are important inflammatory mechanisms that are dampened by miR‐223 in these cell types. The miRNA can also directly target viruses such as HIV, leading to synergistic effects during infection. Here we review the recent studies of miR‐223 function to show how it modulates inflammation, infection and cancer development.


title: Virus Taxonomy

text: Abstract Virus taxonomy is the classification of viruses into categories called taxa and the development and implementation of a standardized nomenclature for taxa. Whereas virus taxonomy has been a niche subspecialty over many decades, the field has recently gained importance due to the exponentially increasing number of new viruses discovered by next-generation sequencing methods. The expanded known global virome and associated viral genome sequence space gradually morph virus taxonomy from a phenotype-based and inherently subjective process, focussing on shared or distinct, often arbitrarily chosen biophysical characteristics of virions to a significant subspecialty of systematic evolutionary biology. Indeed, current virus classification is increasingly performed using ever more complex phylogenetic approaches that move researchers closer to a rudimentary understanding of the origin, evolution, relatedness, and diversification of viruses over eons.


title: A Conserved Histidine in the RNA Sensor RIG-I Controls Immune Tolerance to N(1)-2′O-Methylated Self RNA

text: The cytosolic helicase retinoic acid-inducible gene-I (RIG-I) initiates immune responses to most RNA viruses by detecting viral 5′-triphosphorylated RNA (pppRNA). Although endogenous mRNA is also 5′-triphosphorylated, backbone modifications and the 5′-ppp-linked methylguanosine ((m7)G) cap prevent immunorecognition. Here we show that the methylation status of endogenous capped mRNA at the 5′-terminal nucleotide (N(1)) was crucial to prevent RIG-I activation. Moreover, we identified a single conserved amino acid (H830) in the RIG-I RNA binding pocket as the mediator of steric exclusion of N(1)-2′O-methylated RNA. H830A alteration (RIG-I(H830A)) restored binding of N(1)-2′O-methylated pppRNA. Consequently, endogenous mRNA activated the RIG-I(H830A) mutant but not wild-type RIG-I. Similarly, knockdown of the endogenous N(1)-2′O-methyltransferase led to considerable RIG-I stimulation in the absence of exogenous stimuli. Studies involving yellow-fever-virus-encoded 2′O-methyltransferase and RIG-I(H830A) revealed that viruses exploit this mechanism to escape RIG-I. Our data reveal a new role for cap N(1)-2′O-methylation in RIG-I tolerance of self-RNA.


title: B cell homeostasis and follicle confines are governed by fibroblastic reticular cells

text: Fibroblastic reticular cells (FRCs) are known to inhabit T cell-rich areas of lymphoid organs where they function to coordinate T cell and dendritic cell interactions. However, in vivo manipulation of FRCs has been limited by a dearth of genetic tools targeting this lineage. Here, using a mouse model to conditionally ablate FRCs, we demonstrate their indispensable role in anti-viral T cell responses. Unexpectedly, FRC loss also attenuated humoral immunity due to impaired B cell viability and follicular organization. Follicle-resident FRCs established a favorable niche for B lymphocytes via production of the cytokine BAFF. Thus, our study indicates that adaptive immunity requires an intact FRC network and illuminates a subset of FRCs that controls B cell homeostasis and follicle identity.


title: Mutational and inhibitive analysis of SARS coronavirus 3C-like protease by fluorescence resonance energy transfer-based assays

text: Abstract The 3C-like protease (3CLpro) of severe acute respiratory syndrome coronavirus (SARS-CoV) plays key roles in viral replication and is an attractive target for anti-SARS drug discovery. In this report, a fluorescence resonance energy transfer (FRET)-based method was developed to assess the proteolytic activity of SARS-CoV 3CLpro. Two internally quenched fluorogenic peptides, 1NC and 2NC, corresponding to the N-terminal and the C-terminal autocleavage sites of SARS-CoV 3CLpro, respectively, were used as substrates. SARS-CoV 3CLpro seemed to work more efficiently on 1NC than on 2NC in trans-cleavage assay. Mutational analysis demonstrated that the His41 residue, the N-terminal 7 amino acids, and the domain III of SARS-CoV 3CLpro were important for the enzymatic activity. Antibodies recognizing domain III could significantly inhibit the enzymatic activity of SARS-CoV 3CLpro. The effects of class-specific protease inhibitors on the trans-cleavage activity revealed that this enzyme worked more like a serine protease rather than the papain protease.


title: Risk Factors for MERS-CoV Seropositivity among Animal Market and Slaughterhouse Workers, Abu Dhabi, United Arab Emirates, 2014–2017

text: Camel contact is a recognized risk factor for Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Because specific camel exposures associated with MERS-CoV seropositivity are not fully understood, we investigated worker–camel interactions and MERS-CoV seroprevalence. We assessed worker seroprevalence in 2 slaughterhouses and 1 live-animal market in Abu Dhabi, United Arab Emirates, during 2014–2017 and administered an epidemiologic survey in 2016 and 2017. Across 3 sampling rounds during 2014–2017, we sampled 100–235 workers, and 6%–19% were seropositive for MERS-CoV at each sampling round. One (1.4%) of 70 seronegative workers tested at multiple rounds seroconverted. On multivariable analyses, working as a camel salesman, handling live camels or their waste, and having diabetes were associated with seropositivity among all workers, whereas handling live camels and either administering medications or cleaning equipment was associated with seropositivity among market workers. Characterization of high-risk exposures is critical for implementation of preventive measures.


title: Novel Betacoronavirus in Dromedaries of the Middle East, 2013

text: In 2013, a novel betacoronavirus was identified in fecal samples from dromedaries in Dubai, United Arab Emirates. Antibodies against the recombinant nucleocapsid protein of the virus, which we named dromedary camel coronavirus (DcCoV) UAE-HKU23, were detected in 52% of 59 dromedary serum samples tested. In an analysis of 3 complete DcCoV UAE-HKU23 genomes, we identified the virus as a betacoronavirus in lineage A1. The DcCoV UAE-HKU23 genome has G+C contents; a general preference for G/C in the third position of codons; a cleavage site for spike protein; and a membrane protein of similar length to that of other betacoronavirus A1 members, to which DcCoV UAE-HKU23 is phylogenetically closely related. Along with this coronavirus, viruses of at least 8 other families have been found to infect camels. Because camels have a close association with humans, continuous surveillance should be conducted to understand the potential for virus emergence in camels and for virus transmission to humans.


title: Development and evaluation of an antigen-capture ELISA for detection of the UL24 antigen of the duck enteritis virus, based on a polyclonal antibody against the UL24 expression protein

text: Abstract An antigen-capture enzyme-linked immunosorbent assay (AC-ELISA) method was developed for the efficient detection of the UL24 antigen of the duck enteritis virus (DEV) using polyclonal antibodies. Ducks and rabbits were immunized, respectively, with expressed UL24 recombinant protein. The IgG antibodies against UL24 from ducks and rabbits were purified and used as the capture antibodies. The specificity of the optimized AC-ELISA was evaluated by use of DEV, duck hepatitis virus (DHV), duck hepatitis B virus (DHBV), gosling plague virus (GPV), Riemerella anatipestifer (R.A.), Escherichia coli (E. coli), Pasteurella multocida (P.M.) and Salmonella Enteritidis (S.E.). Only DEV specimens yielded a specific and strong signal. The limit of the sensitivity of this method for the detection of DEV was 46ng/100μl. Compared with PCR and virus isolation, the rate of agreement for the detection of experimentally infected sera was 100%. A comparative test used on clinical specimens between the neutralization test and the AC-ELISA showed that the proportions of true positives and true negatives by the AC-ELISA were 0.90 and 0.67 respectively. These results indicated that the AC-ELISA approach is rapid, sensitive, and reliable for specific detection of DEV antigen.


title: Temporal variation of human encounters and the number of locations in which they occur: a longitudinal study of Hong Kong residents

text: Patterns of social contact between individuals are important for the transmission of many pathogens and shaping patterns of immunity at the population scale. To refine our understanding of how human social behaviour may change over time, we conducted a longitudinal study of Hong Kong residents. We recorded the social contact patterns for 1450 individuals, up to four times each between May 2012 and September 2013. We found individuals made contact with an average of 12.5 people within 2.9 geographical locations, and spent an average estimated total duration of 9.1 h in contact with others during a day. Distributions of the number of contacts and locations in which contacts were made were not significantly different between study waves. Encounters were assortative by age, and the age mixing pattern was broadly consistent across study waves. Fitting regression models, we examined the association of contact rates (number of contacts, total duration of contact, number of locations) with covariates and calculated the inter- and intra-participant variation in contact rates. Participant age was significantly associated with the number of contacts made, the total duration of contact and the number of locations in which contact occurred, with children and parental-age adults having the highest rates of contact. The number of contacts and contact duration increased with the number of contact locations. Intra-individual variation in contact rate was consistently greater than inter-individual variation. Despite substantial individual-level variation, remarkable consistency was observed in contact mixing at the population scale. This suggests that aggregate measures of mixing behaviour derived from cross-sectional information may be appropriate for population-scale modelling purposes, and that if more detailed models of social interactions are required for improved public health modelling, further studies are needed to understand the social processes driving intra-individual variation.


title: Lack of Protection Against Ebola Virus from Chloroquine in Mice and Hamsters

text: The antimalarial drug chloroquine has been suggested as a treatment for Ebola virus infection. Chloroquine inhibited virus replication in vitro, but only at cytotoxic concentrations. In mouse and hamster models, treatment did not improve survival. Chloroquine is not a promising treatment for Ebola. Efforts should be directed toward other drug classes.


title: Animal Health Equipment Management

text: Proper health equipment management requires significant attention to detail. Establishing and following protocols during processing (eg, cleaning and disinfecting equipment at the end of the work day) is required to ensure a safe product that is free of defects and residues. Overall cleanliness of equipment and facilities is important not only from a food safety standpoint but many view these as an overall indicator of attention to detail in the entire production system. Ensuring that needles are changed, implant guns are managed properly, vaccine is handled in an acceptable manner, and that proper chute operation occurs is essential.


title: Seasonality of respiratory viruses causing hospitalizations for acute respiratory infections in children in Nha Trang, Vietnam

text: Abstract Background Acute respiratory infections (ARIs) are the most common causes of death in children under 5 years of age. While the etiology of most pneumonia and ARI episodes is undiagnosed, a broad range of ARI-causing viruses circulate widely in South East Asia. However, the patterns and drivers of the seasonal transmission dynamics are largely unknown. Here we identify the seasonal patterns of multiple circulating viruses associated with hospitalizations for ARIs in Nha Trang, Vietnam. Methods Hospital based enhanced surveillance of childhood ARI is ongoing at Khanh Hoa General Hospital in Nha Trang. RT-PCR was performed to detect 13 respiratory viruses in nasopharyngeal samples from enrolled patients. Seasonal patterns of childhood ARI hospital admissions of various viruses were assessed, as well as their association with rainfall, temperature, and dew point. Results Respiratory syncytial virus peaks in the late summer months, and influenza A in April to June. We find significant associations between detection of human parainfluenza 3 and human rhinovirus with the month's mean dew point. Using a cross-wavelet transform we find a significant out-of-phase relationship between human parainfluenza 3 and temperature and dew point. Conclusions Our results are important for understanding the temporal risk associated with circulating pathogens in Southern Central Vietnam. Specifically, our results can inform timing of routing seasonal influenza vaccination and for when observed respiratory illness is likely viral, leading to judicious use of antibiotics in the region.


title: Studies in a Murine Model Confirm the Safety of Griffithsin and Advocate Its Further Development as a Microbicide Targeting HIV-1 and Other Enveloped Viruses

text: Griffithsin (GRFT), a lectin from Griffithsia species, inhibits human immunodeficiency virus-1 (HIV-1) replication at sub-nanomolar concentrations, with limited cellular toxicity. However, in vivo safety of GRFT is not fully understood, especially following parenteral administration. We first assessed GRFT’s effects in vitro, on mouse peripheral blood mononuclear cell (mPBMC) viability, mitogenicity, and activation using flow-cytometry, as well as cytokine secretion through enzyme-linked immunosorbent assay (ELISA). Toxicological properties of GRFT were determined after a single subcutaneous administration of 50 mg/kg or 14 daily doses of 10 mg/kg in BALB/c mice. In the context of microbicide development, toxicity of GRFT at 2 mg/kg was determined after subcutaneous, intravaginal, and intraperitoneal administrations, respectively. Interestingly, GRFT caused no significant cell death, mitogenicity, activation, or cytokine release in mPBMCs, validating the usefulness of a mouse model. An excellent safety profile for GRFT was obtained in vivo: no overt changes were observed in animal fitness, blood chemistry or CBC parameters. Following GRFT treatment, reversible splenomegaly was observed with activation of certain spleen B and T cells. However, spleen tissues were not pathologically altered by GRFT (either with a single high dose or chronic doses). Finally, no detectable toxicity was found after mucosal or systemic treatment with 2 mg/kg GRFT, which should be further developed as a microbicide for HIV prevention.


title: A unique water optional health care personnel handwash provides antimicrobial persistence and residual effects while decreasing the need for additional products

text: BACKGROUND: The Centers for Disease Control and Prevention (CDC) has published guidelines for hand hygiene practices, recommending a handwash regimen that alternates between waterless alcohol products and antimicrobial or nonantimicrobial soap and water. The advent of an alcohol-based product that can be used with or without water (ie, water optional) to decontaminate the hands while providing immediacy of kill and antimicrobial persistence could reduce the confusion associated with handwash guidelines. Such a product has been developed, is alcohol-based (61%), and zinc pyrithione (ZPT) preserved (61% alcohol-ZPT) and has proven to be fully compliant with the Food and Drug Administration (FDA) and CDC guidelines. METHODS: FDA-required testing of the 61% alcohol-ZPT product for the health care personnel handwash indication was performed as outlined in the Tentative Final Monograph (TFM) for Health-Care Antiseptic Drug Products, employing waterless and water-aided product applications. It was next assessed for antimicrobial persistence and residual effects by comparing it, in separate waterless and water-aided applications, with commonly available handwashes containing various antimicrobials in a 5-day study employing 49 subjects, in which samples were collected immediately and at 4 hours and 8 hours postapplication. The skin conditioning properties of this formulation were investigated via appropriate methods. RESULTS: The 61% alcohol-ZPT product easily produced >3.0 log(10) reduction in the indicator strain (Serratia marcescens) following the first wash, exceeding the 2.0 log(10) FDA requirement. This level of performance was maintained through the tenth wash, surpassing the 3.0 log(10) FDA requirement for the handwash indication. For the assessment of persistence and residual effect in the waterless mode, the water-optional, 61% alcohol-ZPT product consistently produced log(10) reductions of nearly 3.5 or greater at every point over the entire study period. In the water-aided configuration, similar results were obtained as log(10) reductions of 2.5 were observed. The formulation is nonirritating, actually contributing to hand skin condition. CONCLUSIONS: The 61% alcohol-ZPT product exceeds all FDA criteria for the health care personnel handwash indication and is a significant advancement in the concept of skin antisepsis. It represents a single product suitable for use in all hand hygiene settings, demonstrating improved antimicrobial persistence and residual effects. The 61% alcohol-ZPT formulation contributes positively to overall hand conditioning, and a previously reported study has documented it to be virucidal for several DNA and RNA viruses.


title: Immunogenicity and protective efficacy in monkeys of purified inactivated Vero-cell SARS vaccine

text: BACKGROUND: In 2003, severe acute respiratory syndrome (SARS) resulted in hundreds of infections and deaths globally. We aim to assess immunogenicity and protective efficacy of purified inactivated Vero-cell SARS vaccine in monkeys. METHODS: The cultures of SARS coronavirus (SARS-CoV) BJ-01 strain infected Vero cells were inactivated with β-propiolactone. Sequential procedures, including ultrafiltration, gel filtration and ion exchange chromatography, were performed to obtain purified inactivated SARS vaccine. The purified SARS vaccine was analyzed with electron microscope, HPLC and Western blotting. We immunized three groups of cynomolgus macaques fascicularis with adjuvant-containing purified vaccine, purified vaccine and unpurified vaccine, respectively, and a fourth group served as a control. Antibody titers were measured by plaque reduction neutralization test. The vaccinated monkeys were challenged with SARS-CoV BJ-01 strain to observe protective efficacy. Additionally, three groups of rhesus monkeys were immunized with different doses of the purified inactivated SARS vaccine (0.5, 1 and 2 μg/time/monkey) on days 0 and 7, and the monkeys were challenged with SARS-CoV GZ-01 strain. We assessed the safety of the SARS vaccine and observed whether the antibody dependent enhancement (ADE) occurred under low levels of neutralizing antibody in rhesus. FINDINGS: The purity of SARS vaccine was 97.6% by HPLC identification and reacted with convalescent sera of SARS patients. The purified SARS vaccine induced high levels of neutralizing antibodies and prevented the replication of SARS-CoV in monkeys. Under low levels of neutralizing antibody, no exacerbation of clinical symptoms was observed when the immunized monkeys were challenged with SARS-CoV. In this preliminary animal trial, no side effects were detected when monkeys were immunized with purified SARS vaccine either at normal or large doses. INTERPRETATION: The purified inactivated SARS vaccine could induce high levels of neutralizing antibody, and protect the monkeys from the challenge of SARS-CoV. The SARS vaccine prepared in the study appeared to be safe in monkeys.


title: Dynamic profile for the detection of anti-SARS-CoV-2 antibodies using four immunochromatographic assays

text: Abstract In order to fight the SARS-CoV-2 pandemic infection, there is a growing need and demand for diagnostic tools that are complementary and different from the RT-PCR currently in use. Multiple serological tests are or will be very soon available but need to be evaluated and validated. We have thus tested 4 immunochromatographic tests for the detection of antibodies to SARS-CoV-2. In addition, we assessed the kinetics of antibody appearance using these assays in 22 patients after they were tested positive by RT-PCR. We observed great heterogeneity in antiboy detection post-symptom onset. The median antibody detection time was between 8 and 10 days according to the manufacturers. All the tests showed a sensitivity of 60 to 80% on day 10 and 100% on day 15. In addition, a single cross-reaction was observed with other human coronavirus infections. Thus, immunochromatographic tests for the detection of anti-SARS-CoV-2 antibodies may have their place for the diagnostic panel of COVID-19.


title: Observing and quantifying airflows in the infection control of aerosol- and airborne-transmitted diseases: an overview of approaches

text: Summary With concerns about the potential for the aerosol and airborne transmission of infectious agents, particularly influenza, more attention is being focused on the effectiveness of infection control procedures to prevent hospital-acquired infections by this route. More recently a number of different techniques have been applied to examine the temporal–spatial information about the airflow patterns and the movement of related, suspended material within this air in a hospital setting. Closer collaboration with engineers has allowed clinical microbiologists, virologists and infection control teams to assess the effectiveness of hospital isolation and ventilation facilities. The characteristics of human respiratory activities have also been investigated using some familiar engineering techniques. Such studies aim to enhance the effectiveness of such preventive measures and have included experiments with human-like mannequins using various tracer gas/particle techniques, real human volunteers with real-time non-invasive Schlieren imaging, numerical modelling using computational fluid dynamics, and small scale physical analogues with water. This article outlines each of these techniques in a non-technical manner, suitable for a clinical readership without specialist airflow or engineering knowledge.


title: Cardiac involvement in recovered COVID-19 patients identified by magnetic resonance imaging

text: Abstract Objective To evaluate cardiac involvement in recovered COVID-19 patients using cardiac MRI. Background Myocardial injury caused by COVID-19 was previously reported in hospitalized patients. It is unknown if there is sustained cardiac involvement after patients’ recovery from COVID-19. Methods Twenty-six recovered COVID-19 patients that reported cardiac symptoms and underwent MRI exams were retrospectively included. MRI protocols consisted of conventional sequences (cine, T2WI, LGE), and quantitative mapping sequences (T1, T2, and ECV mapping). Edema ratio and LGE were assessed in post-COVID-19 patients. Cardiac function, native T1/T2, and ECV were quantitatively evaluated and compared with controls. Results Fifteen patients (58%) had abnormal MRI findings on conventional MRI sequences: myocardial edema was found in 14 (54%) patients and LGE was found in 8 (31%) patients. Decreased RV functional parameters including EF, CI, and SV/ BSA were found in patients with positive conventional MRI findings. Using quantitative mapping, global native T1, T2, and ECV were all found to be significantly elevated in patients with positive conventional MRI findings, compared to patients without positive findings and controls (median [IQR], native T1 1271ms [1243-1298] vs 1237ms [1216-1262] vs 1224ms [1217-1245]; mean [SD], T2 42.7ms [3.1] vs 38.1ms [2.4] vs 39.1ms [3.1]; median [IQR], 28.2% [24.8-36.2] vs 24.8% [23.1-25.4] vs 23.7% [22.2-25.2]; p=0.002, p <0.001, and p =0.002, respectively). Conclusions Cardiac involvement was found in a proportion of the recovered COVID-19 patients. MRI manifestation included myocardial edema, fibrosis, and impaired RV function. Attention should be paid to the possible myocardial involvement in recovered COVID-19 patients with cardiac symptoms.


title: Prevalence and correlates of PTSD and depressive symptoms one month after the outbreak of the COVID-19 epidemic in a sample of home-quarantined Chinese university students

text: BACKGROUND: : When COVID-19 emerged in China in late 2019, most citizens were home-quarantined to prevent the spread of the virus. This study explored the prevalence of post-traumatic stress disorder (PTSD) and depression in a sample of home-quarantined college students to identify the psychological distress risk factors. METHOD: : The PTSD and depressive symptoms in the 2485 participants from 6 universities were investigated using online survey versions of the PTSD Checklist Civilian Version and the 9-question Patient Health Questionnaires (PHQ-9), and data on sleep durations, exposure, home-quarantine time and socio-demographic variables were also collected. RESULTS: : The PTSD and depression prevalence were found to be 2.7% and 9.0%. Subjectively, feeling extreme fear was the most significant risk factor for psychological distress, followed by short sleep durations, being in their graduating year (4(th) year) and living in severely afflicted areas. Sleep durations was a mediator between exposures and mental health problems. CONCLUSIONS: : The results suggested that the psychological consequences of the COVID-19 could be serious. Psychological interventions that reduce fear and improve sleep durations need to be made available to the home-quarantined university students, and graduating students and those in the worst-hit areas should be given priority focus.


title: Advice regarding COVID‐19 and use of immunomodulators, in patients with severe dermatological diseases

text: Coronavirus disease 2019 (COVID-19) is the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as named by the International Committee on Taxonomy of Viruses (ICTV). There is very limited evidence base to formulate specific advice for dermatology patients on immunomodulators with regards to COVID-19. The following is based on expert opinion, taking into account known risks of influenza (a negative sense single-stranded RNA virus) and other, positive-sense single-stranded, RNA virus infections (such as SARS, MERS, and the common cold). An Australia/New Zealand consensus document is in development.


title: Effect of Feline Interferon‐Omega on the Survival Time and Quality of Life of Cats with Feline Infectious Peritonitis

text: Background: There is no therapy with proven efficacy to treat cats with feline infectious peritonitis (FIP). Hypothesis: Feline interferon‐omega (FeIFN‐ω) prolongs survival time and increases quality of life in cats with FIP. Animals: Thirty‐seven privately owned cats were subjects of this study. Methods: The study was performed as a placebo‐controlled double‐blind trial. Feline infectious peritonitis was confirmed by histology or immunostaining of feline coronavirus (FCoV) antigen in effusion or tissue macrophages or both. The cats were randomly selected for treatment with either FeIFN‐to or a placebo. All cats received adjunctive treatment with glucocorticoids and antibiotics and passive immunization with Feliserin. Results: There was no statistically significant difference in the survival time of cats treated with FeIFN‐ω versus placebo or in any other variable evaluated (with the exception of the lymphocyte count). The cats survived between 3 and 200 days (median, 9 days). There was only 1 long‐term survivor (>3 months), and the cat was in the FeIFN‐ω group. Conclusion and Clinical Relevance: No effect of FeIFN‐ω on survival time or quality of life could be demonstrated in this study.


Reflections and new developments within the COVID‐19 pandemic


title: Effective factors in expansion of medical tourism in Iran

text: Background: Medical tourism (MT) refers to circumstances in which people travel for medical treatments. The present study focuses on determining factors affecting MT in Iran. Methods: The study uses a mixed method approach. Initially, through a qualitative study, 12 experts were interviewed deeply; then, 22 participants in three equal focus groups expressed their ideas about growth and development of MT in Iran. Based on the expressed ideas, 120 factors were identified and accordingly a structured questionnaire was developed. Some members from the focus groups confirmed the questionnaire’s face and content validity. The reliability of pertinent items was confirmed using Cronbach’s alpha=0.8. Afterwards, 61 eligible subjects filled out this questionnaire. Results: The findings showed that "healthcare quality" and "high level of expertise" are two most attractive factors in MT. However, other factors such as "healthcare costs", and "visa facilities" are among key factors as well. Also, the role of "the healthcare providers" was found to be more prominent than the roles of "the government" and "the general tourist services". Conclusion: Although some attractive MT factors are present currently, MT expansion to a desirable level in Iran requires a comprehensive plan of which its factors were discussed in this paper.


Chapter 88 Middle Ear and Eustachian Tube


title: Out Patient Department practices in orthopaedics amidst COVID-19: The evolving model

text: Severe Acute Respiratory Syndrome COVID-19 was declared as a pandemic on 11(th) March 2020 by the World Health Organization and consequent lockdown imposed in several areas resulted in a marked reduction in orthopaedic practice. Although some guidelines for patient care in orthopaedic practice have been published, overall, publications focusing exclusively on guidelines on starting orthopaedic outpatient departments (OPD) after the COVID-19 lockdown amidst the on-going pandemic are lacking. We hereby propose the evolving knowledge in changes in OPD management practices for orthopaedic surgeons in the COVID- 19 era. The emphasis on online registration (e-registration) should be given impetus and become the new norm supplemented by telephonic and spot registration for the uneducated patients. The review highlights the safety of patient and orthopaedic surgeons in OPD by screening and maintaining hygiene at various levels. The article also mentions the duties of the help desk, OPD hall supervisor and the new norms of Air Conditioning, ventilation, safe use of elevators, sanitization of OPD premises and biomedical waste disposal. The optimum and safe utilization of human & material resources, DO's and DON'Ts for patients & health staff have also been proposed. The reorganization of plaster room, the precaution during plastering, fracture clinic, dressing and injection room services are discussed as per evolving guidelines. This article will give deep insight into the OPD plan &telemedicine graphically also. The authors suggest updating and downward permeation of existing e-infrastructure of government health services that is up-gradation of existing tertiary level online registration services, a paperless model of OPD Consultation & dispensation. The future updating of Aarogya Setu App (https://mygov.in/aarogya-setu-app/). for convenient online OPD registration and dispensation has been discussed and proposed. This review will help in containing the spread of COVID 19 and build upon the health gains achieved after lockdown. The easy concept of CCCATTT has been introduced, and the OPD Plan has also been suggested. We have endeavoured to holistically detail an orthopaedic OPD setup and its upkeep in COVID-19 pandemic, but since the knowledge of COVID 19 is ever-evolving it needs replenishment by regular education for health staff.


Covid‐19 and exacerbation of psoriasis


title: Comparative genomic signature representations of the emerging COVID-19 coronavirus and other coronaviruses: High identity and possible recombination between Bat and Pangolin coronaviruses

text: Abstract Coronaviruses are responsible on respiratory diseases in animal and human. The combination of numerical encoding techniques and digital signal processing methods are becoming increasingly important in handling large genomic data. In this paper, we propose to analyze the SARS-CoV-2 genomic signature using the combination of different nucleotide representations and signal processing tools in the aim to identify its genetic origin. The sequence of SARS-CoV-2 was compared with 21 relevant sequences including bat, yak and pangolin coronavirus sequences. In addition, we developed a new algorithm to locate the nucleotide modifications. The results show that the Bat and Pangolin coronaviruses were the most related to SARS-CoV-2 with 96% and 86% of identity all along the genome. Within the S gene sequence, the Pangolin sequence presents local highest nucleotide identity. Those findings suggest genesis of SARS-Cov-2 through evolution from bat and pangolin strains. This study offers new ways to automatically characterize viruses.


title: Promoting Better Clinical Trials and Drug Information as Public Health Interventions for the COVID-19 Emergency in Italy

text: According to these authors from the Italian Medicines Agency, “evidence-informed prescribing and clinical trials were beaten off the mark by social media, rumors, and panic in the early phase of the COVID-19 pandemic.” In this article, they describe lessons learned to counteract misleading information and nudge the research community to do high-quality, informative multigroup trials.


title: Non-operative management of acute appendicitis in a pediatric patient with concomitant COVID-19 infection

text: INTRODUCTION: In late December 2019, reports emerged from Wuhan, China of a novel corovonavirus SARS-CoV-2, which caused severe acute respiratory distress syndrome referred to as COVID-19. As the virus spread, reports of severe perioperative complications, including fatalities, began to emerge in the literature. We present a case of a previously healthy patient who developed classic symptoms of appendicitis. The patient was also found to be positive for COVID-19. Given the risks to both the patient and surgical team, we elected to pursue a non-operative management strategy for this patient with appendicitis. MATERIALS AND METHODS: A 13 year old female with COVID-19 presented with a day of right lower quadrant abdominal pain. A computerized tomography (CT) scan diagnosed uncomplicated appendicitis. The patient was successfully treated non-operatively with antibiotics and discharged home. CONCLUSION: To our knowledge, this case illustrates the first report of a pediatric patient with concomitant appendicitis and COVID-19 infection. We have been able to utilize a non-operative management strategy to effectively treat the patient's acute appendicitis, while protecting her from the risks of undergoing a general anesthetic as well as the operative team. We hope this report can provide others with a potential management strategy for similar patients.


title: Dynamic network measures reveal the impact of cattle markets and alpine summering on the risk of epidemic outbreaks in the Swiss cattle population

text: BACKGROUND: Livestock herds are interconnected with each other via an intricate network of transports of animals which represents a potential substrate for the spread of epidemic diseases. We analysed four years (2012–2015) of daily bovine transports to assess the risk of disease transmission and identify times and locations where monitoring would be most effective. Specifically, we investigated how the seasonal dynamics of transport networks, driven by the alpine summering and traditional cattle markets, affect the risk of epidemic outbreaks. RESULTS: We found strong and consistent seasonal variation in several structural network measures as well as in measures for outbreak risk. Analysis of the consequences of excluding markets, dealers and alpine pastures from the network shows that markets contribute much more to the overall outbreak risk than alpine summering. Static descriptors of monthly transport networks were poor predictors of outbreak risk emanating from individual holdings; a dynamic measure, which takes the temporal structure of the network into account, gave better risk estimates. A stochastic simulation suggests that targeted surveillance based on this dynamic network allows a higher detection rate and smaller outbreak size at detection than compared to other sampling schemes. CONCLUSIONS: Dynamic measures based on time-stamped data—the outgoing contact chain—can give better risk estimates and could help to improve surveillance schemes. Using this measure we find evidence that even in a country with intense summering practice, markets continue being the prime risk factor for the spread of contagious diseases.


title: Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID‐19

text: The global pandemic of coronavirus disease 2019 (COVID‐19) is associated with the development of acute respiratory distress syndrome (ARDS), which requires ventilation in critically ill patients. The pathophysiology of ARDS results from acute inflammation within the alveolar space and prevention of normal gas exchange. The increase in proinflammatory cytokines within the lung leads to recruitment of leukocytes, further propagating the local inflammatory response. A consistent finding in ARDS is the deposition of fibrin in the air spaces and lung parenchyma. COVID‐19 patients show elevated D‐Dimers and fibrinogen. Fibrin deposits are found in the lungs of patients due to the dysregulation of the coagulation and fibrinolytic systems. Tissue factor (TF) is exposed on damaged alveolar endothelial cells and on the surface of leukocytes promoting fibrin deposition, while significantly elevated levels of plasminogen activator inhibitor 1 (PAI‐1) from lung epithelium and endothelial cells create a hypofibrinolytic state. Prophylaxis treatment of COVID‐19 patients with low molecular weight heparin (LMWH) is important to limit coagulopathy. However, to degrade pre‐existing fibrin in the lung it is essential to promote local fibrinolysis. In this review, we discuss the repurposing of fibrinolytic drugs, namely tissue‐type plasminogen activator (tPA), to treat COVID‐19 associated ARDS. tPA is an approved intravenous thrombolytic treatment, and the nebulizer form has been shown to be effective in plastic bronchitis and is currently in Phase II clinical trial. Nebulizer plasminogen activators may provide a targeted approach in COVID‐19 patients to degrade fibrin and improving oxygenation in critically ill patients.


title: Pathogenic characteristics of a QX-like infectious bronchitis virus strain SD in chickens exposed at different ages and protective efficacy of combining live homologous and heterologous vaccination

text: Continued reports of infections with infectious bronchitis virus (IBV) variants have occurred since its first isolation in the 1930s. Currently, QX-like IBVs are the predominant circulating genotype around the world. Here, the pathogenicity of QX-like IBV strain SD was characterized in chickens at different ages of exposure to the virus, and the protection efficacy of available vaccine combinations against IBV was evaluated. The results revealed that QX-like IBV strain SD was severely pathogenic in chickens, causing respiratory, urinary and reproductive infections, irrespective of age, based on clinical observations, viral distribution in tissues and a ciliostasis study. Severe respiratory signs, tracheal cilia injury, nephritis and abnormal development of the oviduct and ovarian follicles were evident throughout the experiment. A challenge experiment demonstrated that the homologous QX vaccine showed superior protection efficacy compared with other available vaccines, confirming the importance of IBV vaccine seed homology against the circulating IBV strains. Our findings aid an understanding of the pathogenicity of QX-like IBVs that may help to further control the infection.


title: A Small Region of Porcine Hemagglutinating Encephalomyelitis Virus Spike Protein Interacts with the Neural Cell Adhesion Molecule

text: OBJECTIVE: The spike (S) protein of porcine hemagglutinating encephalomyelitis virus (PHEV) may mediate infection by binding to a cellular neural cell adhesion molecule (NCAM). This study aimed to identify the crucial domain of the S1 subunit of the S protein that interacts with NCAM. METHODS: Three truncated segments (S(1-291), S(277-794) and S(548-868)) of the S gene of PHEV and the NCAM gene were cloned individually into the Escherichia coli expression vectors and yeast two-hybrid expression vectors. The interaction between S(1-291), S(277-794), S(548-868) and NCAM were detected by a GST pull-down experiment and yeast two-hybrid assay. RESULTS: Three fusion proteins (S(1-291), S(277-794) and S(548-868)) were screened for their interactions with NCAM by protein-protein interaction assays. The results of these assays clarified that S(277-794) interacted with NCAM, while S(1-291) and S(548-868) did not. CONCLUSIONS: A small fragment (258-amino-acid fragment, residues 291-548) on the PHEV S protein was posited to be the minimum number of amino acids necessary to interact with NCAM. This fragment may be the receptor-binding domain that mediates PHEV binding to NCAM.


The potential benefits of Chinese integrative medicine for pregnancy women during the COVID-19 pandemic


title: When science goes viral: The research response during three months of the COVID-19 outbreak

text: Here we present the results of a bibliometric survey of peer-reviewed and pre-print papers published in the English language on issues related to COVID-19 within the first three months since a cluster of a severe acute respiratory disease of unknown etiology was officially confirmed by the Chinese Center for Disease Control and Prevention on 31 December 2019. A systematic search using PubMed/Medline and Scopus databases and preprint servers was performed. The articles were classified according to their type, subject and country of origin. Up to 31 March 2020, a total of 2062 papers published in 578 peer-reviewed journals and 1425 preprints posted mostly on medRxiv (55.4%), were identified. The mean number of published journal papers and preprints per day in the considered period was 27 and 12, respectively, and reached a maximum of 51 and 46 per day in March, respectively. The identified articles, journal papers and preprints, mostly covered the epidemiology of COVID-19 (35.7%), clinical aspects of infection (21.0%), preventative measures (12.8%), treatment options (12.5%), diagnostics (12.2%), mathematical modeling of disease transmission and mitigation (9.6%), and molecular biology and pathogenesis of SARS-CoV-2 (8.7%). The majority of the journal papers were commentaries (38.5%), reviews (33.6%) and original research (21.3%), while preprints predominantly presented original results (89.8%). Chinese scientists contributed the highest share of original research and were responsible for 32.9% journal papers and 43.9% preprints published in the considered period. A high number of contributions was also seen from the United States, the United Kingdom, and Italy. The benefits and potential risks of such a massive publication output are discussed. The scientific response seen during the first 3 months of the COVID-19 outbreak is a demonstration of the capabilities of modern science to react rapidly to emerging global health threats by providing and discussing the essential information for understanding the etiological factor, its spread, preventative measures, and mitigation strategies.


title: Sub-basin prioritization for assessment of soil erosion susceptibility in Kangsabati, a plateau basin: A comparison between MCDM and SWAT models

text: Abstract Kangsabati basin located in tropical plateau region faces multiple problems of soil erosion susceptibility (SES), soil fertility deterioration, and sedimentation in reservoirs. Hence, identification of SES zones in thirty-eight sub-basins (SB) for basin prioritization is necessary. The present research addressed the issue by using four multi-criteria decision-making (MCDM) models: VlseKriterijumska optimizacija I Kompromisno Resenje (VIKOR), technique for order preference by similarity to ideal solution (TOPSIS), simple additive weighing (SAW), compound factor (CF). To determine the best fitted method from MCDM for erosion susceptibility (ES), a comparison has been made with Soil and Water Assessment Tool (SWAT), where fifteen morphometric parameters were considered for MCDM, and meteorological data, soil, slope and land use land cover (LULC) were considered for SWAT model. Two validation indices of percentage change and intensity change were used for evaluation and comparison of MCDM results. With SWAT model performance, SWAT calibration and uncertainty analysis programs (CUP) was used for sensitive analysis of SWAT parameters on flow discharge and sediment load simulation. The results showed that 23, 16, 18 SB have high ES; therefore they were given 1 to 3 ranks, whereas 31, 37, 21SB have low ES, hence given 38 to 36 rank as predicted by MCDM methods and SWAT. MCDM validation results depict that VIKOR and CF methods are more acceptable than TOPSIS and SAW. Calibration (flow discharge R2 0.86, NSE 0.75; sediment load R2 0.87, NSE 0.69) and validation (flow discharge R2 0.79, NSE 0.55; sediment load R2 0.79, NSE 0.76) of SWAT model indicated that simulated results are well fitted with observed data. Therefore, VIKOR reflects the significant role of morphometric parameters on ES, whereas SWAT reflects the significant role of LULC, slope, and soil on ES. However, it could be concluded that VIKOR is more effective MCDM method in comparison to SWAT prediction.


title: Other viruses causing gastroenteritis

text: Publisher Summary Besides the viruses producing the majority of human viral gastroenteritis, other viruses infect more rarely but are sometimes able to cause epidemics. In particular, they cause chronic infection in the immunocompromised. Some of these viruses discussed in this chapter are toroviruses, picobirnaviruses, enteroviruses, human immunodeficiency virus (HIV), herpesviruses, and coronaviruses. Toroviruses make up a genus of the Coronaviridae family. They are a well-described cause of diarrhea in calves and horses but may also infect sheep, goats, and pigs. Picobirnaviruses are related to members of the Birnaviridae family. They are found in the feces of HIV-infected patients with diarrhea more frequently than in HIV-infected patients without diarrhea, but a virus-specific immune response was not measurable. The genus Enterovirus is of the Picornaviridae family. All enteroviruses infect man via the gastrointestinal tract where they have their first site of replication, probably in lymphoid tissues of the pharynx and gut. HIV, the causative agent of the acquired immunodeficiency syndrome (AIDS), is a member of the Lentivirus genus of the Retroviridae family. Cytomegalovirus (CMV) and herpes simplex viruses, members of the Herpesviridae family, are found as the cause of colitis and esophagitis, mainly in HIV-infected patients. Coronavirus is another genus of the Coronaviridae family. Coronaviruses infect the respiratory and gastrointestinal tracts. They are a recognized cause of the common cold in man.