title: Chapter 29 Xenozoonoses The Risk of Infection after Xenotransplantation

text: Immunological and technical advances have led to tremendous increases in the number of people potentially able to benefit from allotransplantation. Ironically, it is the success of the field that has led to a renewed interest in xenotransplantation during the past several decades. To a large part, this has occurred because of the great scarcity of human organ and tissue donors. However, it has expanded to include the use of cells from animals into humans such as porcine islet cells for diabetes or extracorporeal perfusion of human blood through animal organs or cells. Similar to allotransplantation, issues regarding transmission of infections from the graft to the human recipient were brought up for consideration with these procedures in the 1990s (Michaels and Simmons, 1994; Chapman et al., 1995; Hammel et al., 1998; Fishman et al., 1998). A risk for infection exists with the use of any biologic agent regardless of whether it is from a human or an animal source. Accordingly, transmission of infections from human organs, tissues, or cells is a well-recognized cause of disease after allotransplantation (Ison and Grossi, 2013; Green and Michaels, 2012). As the human graft shortage continues, newer cellular therapies are explored. Thus, attention continues to be given to the potential use of xenogeneic organs, tissues, or cells for human maladies through xenotransplantation. The potential for novel zoonotic infections to emerge because of xenotransplantation (xenozoonoses or xenosis) led to a debate on whether the field should be permitted to progress. This chapter reviews the issues of xenotransplantation related to infections from animals to humans. Lessons learned from infections with prior nonhuman primate xenotransplantation and human allotransplantation are used to help inform about risks with newer xenogeneic procedures. In addition, information on known zoonoses is reviewed to better develop constructs to decrease the hazard of infection with these novel procedures.


title: Viruses and DemyeSinating Disease of the Centra! Nervous System

text: In MS, there are many mechanisms by which viruses can produce demyelinating diseases in humans and experimental demyelinating infections in animals.


title: A systematic review of MERS-CoV seroprevalence and RNA prevalence in dromedary camels: Implications for animal vaccination

text: Human infection with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is driven by recurring dromedary-to-human spill-over events, leading decision-makers to consider dromedary vaccination. Dromedary vaccine candidates in the development pipeline are showing hopeful results, but gaps in our understanding of the epidemiology of MERS-CoV in dromedaries must be addressed to design and evaluate potential vaccination strategies. We aim to bring together existing measures of MERS-CoV infection in dromedary camels to assess the distribution of infection, highlighting knowledge gaps and implications for animal vaccination. We systematically reviewed the published literature on MEDLINE, EMBASE and Web of Science that reported seroprevalence and/or prevalence of active MERS-CoV infection in dromedary camels from both cross-sectional and longitudinal studies. 60 studies met our eligibility criteria. Qualitative syntheses determined that MERS-CoV seroprevalence increased with age up to 80–100% in adult dromedaries supporting geographically widespread endemicity of MERS-CoV in dromedaries in both the Arabian Peninsula and countries exporting dromedaries from Africa. The high prevalence of active infection measured in juveniles and at sites where dromedary populations mix should guide further investigation – particularly of dromedary movement – and inform vaccination strategy design and evaluation through mathematical modelling.


title: Pentoxifylline inhibits replication of Japanese encephalitis virus: a comparative study with ribavirin

text: Abstract Several investigations have shown that pentoxifylline possesses broad-spectrum antiviral activity against a range of RNA and DNA viruses. However, its ability to inhibit Japanese encephalitis virus (JEV) replication has not yet been studied. The present study was designed to investigate the antiviral activity of pentoxifylline against JEV in vitro and in vivo. The activity of pentoxifylline against JEV was evaluated in vitro using cytopathic effect inhibition and plaque reduction assays. Pentoxifylline was able to inhibit JEV replication in a dose-dependent manner at a 50% inhibitory concentration (IC50) of 50.3μg/mL (0.00018μM) and a therapeutic index (TI) of 10. Experiments to study the mechanism of antiviral action of pentoxifylline using in vitro translation of viral mRNA suggested that the drug did not interfere either with early or late protein synthesis but most likely exerted its action on virus assembly and/or release. Furthermore, the in vivo study showed that pentoxifylline at a concentration of 100mg/kg and 200mg/kg body weight was able to protect completely mice challenged with 50×50% lethal dose (LD50) of JEV.


title: The SARS-Unique Domain (SUD) of SARS Coronavirus Contains Two Macrodomains That Bind G-Quadruplexes

text: Since the outbreak of severe acute respiratory syndrome (SARS) in 2003, the three-dimensional structures of several of the replicase/transcriptase components of SARS coronavirus (SARS-CoV), the non-structural proteins (Nsps), have been determined. However, within the large Nsp3 (1922 amino-acid residues), the structure and function of the so-called SARS-unique domain (SUD) have remained elusive. SUD occurs only in SARS-CoV and the highly related viruses found in certain bats, but is absent from all other coronaviruses. Therefore, it has been speculated that it may be involved in the extreme pathogenicity of SARS-CoV, compared to other coronaviruses, most of which cause only mild infections in humans. In order to help elucidate the function of the SUD, we have determined crystal structures of fragment 389–652 (“SUD(core)”) of Nsp3, which comprises 264 of the 338 residues of the domain. Both the monoclinic and triclinic crystal forms (2.2 and 2.8 Å resolution, respectively) revealed that SUD(core) forms a homodimer. Each monomer consists of two subdomains, SUD-N and SUD-M, with a macrodomain fold similar to the SARS-CoV X-domain. However, in contrast to the latter, SUD fails to bind ADP-ribose, as determined by zone-interference gel electrophoresis. Instead, the entire SUD(core) as well as its individual subdomains interact with oligonucleotides known to form G-quadruplexes. This includes oligodeoxy- as well as oligoribonucleotides. Mutations of selected lysine residues on the surface of the SUD-N subdomain lead to reduction of G-quadruplex binding, whereas mutations in the SUD-M subdomain abolish it. As there is no evidence for Nsp3 entering the nucleus of the host cell, the SARS-CoV genomic RNA or host-cell mRNA containing long G-stretches may be targets of SUD. The SARS-CoV genome is devoid of G-stretches longer than 5–6 nucleotides, but more extended G-stretches are found in the 3′-nontranslated regions of mRNAs coding for certain host-cell proteins involved in apoptosis or signal transduction, and have been shown to bind to SUD in vitro. Therefore, SUD may be involved in controlling the host cell's response to the viral infection. Possible interference with poly(ADP-ribose) polymerase-like domains is also discussed.


Impact of influenza A (H3N2) seasonal outbreak on the pattern of vaccination uptake in healthcare workers


title: Translating COVID-19 Pandemic Surge Theory to Practice in the Emergency Department: How to Expand Structure

text: Multiple professional societies, nongovernment and government agencies have studied the science of sudden onset disaster mass casualty incidents to create and promote surge response guidelines. The COVID-19 pandemic has presented the health-care system with challenges that have limited science to guide the staff, stuff, and structure surge response. This study reviewed the available surge science literature specifically to guide an emergency department’s surge structural response using a translational science approach to answer the question: How does the concept of sudden onset mass casualty incident surge capability apply to the process to expand COVID-19 pandemic surge structure response? The available surge structural science literature was reviewed to determine the application to a pandemic response. The on-line ahead of print and print COVID-19 scientific publications, as well as gray literature were studied to learn the best available COVID-19 surge structural response science. A checklist was created to guide the emergency department team’s COVID-19 surge structural response.


title: Biochemical serum profiles in dogs experimentally infected with Angiostrongylus vasorum (Baillet, 1866)

text: The biochemical profiles of crossbred dogs experimentally infected with the parasite Angiostrongylus vasorum were studied. Two groups of five dogs were experimentally inoculated with 50 and 100 third stage infective larvae (L(3)) of A. vasorum per kilogram of body weight. A third group of five uninfected animals were used as control. Serum from these animals were used for biochemical tests to measure total and fractioned proteins, urea, creatinine and to determine the activities of aspartate (AST), alanine (ALT) aminotransferase, gamma-glutamyl transferase (GGT), alkaline phosphatase (PAL) and creatine kinase isoenzyme MB (CK-MB). The α-1, α-2 and β-globulins fractions showed alterations during acute phase of the infection. No modifications were observed in the biochemical profiles of ALT, AST, GGT, PAL, urea and creatinine. CK-MB was shown to be a good early indicator of cardiac injury in dogs experimentally infected with A. vasorum.


title: A review for natural polysaccharides with anti-pulmonary fibrosis properties, which may benefit to patients infected by 2019-nCoV

text: Pulmonary fibrosis (PF) is a lung disease with highly heterogeneous and mortality rate, but its therapeutic options are now still limited. Corona virus disease 2019 (COVID-19) has been characterized by WHO as a pandemic, and the global number of confirmed COVID-19 cases has been more than 8.0 million. It is strongly supported for that PF should be one of the major complications in COVID-19 patients by the evidences of epidemiology, viral immunology and current clinical researches. The anti-PF properties of naturally occurring polysaccharides have attracted increasing attention in last two decades, but is still lack of a comprehensively understanding. In present review, the resources, structural features, anti-PF activities, and underlying mechanisms of these polysaccharides are summarized and analyzed, which was expected to provide a scientific evidence supporting the application of polysaccharides for preventing or treating PF in COVID-19 patients.


title: The outbreak of SARS-CoV-2 pneumonia calls for viral vaccines

text: The outbreak of 2019-novel coronavirus disease (COVID-19) that is caused by SARS-CoV-2 has spread rapidly in China, and has developed to be a Public Health Emergency of International Concern. However, no specific antiviral treatments or vaccines are available yet. This work aims to share strategies and candidate antigens to develop safe and effective vaccines against SARS-CoV-2.


title: S-layer proteins of Lactobacillus acidophilus inhibits JUNV infection

text: Abstract It has been previously described that S-layer binds to the C-type lectin DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN, CD209). It was also shown that DC-SIGN is a cell-surface adhesion factor that enhances viral entry of several virus families. Among those, Junin virus (JUNV) entry is enhanced in cells expressing DC-SIGN and for that reason surface-layer protein (S-layer) of Lactobacillus acidophilus ATCC 4365 was evaluated as a possible JUNV inhibitor. Experiments using 3T3 cells stably expressing DC-SIGN, showed an almost complete inhibition of JUNV infection when they were treated with S-layer in a similar extend as the inhibition shown by mannan. However no inhibition effect was observed in 3T3 wild type cells or in 3T3 cells expressing liver/lymph node-specific ICAM-3 grabbing nonintegrin (L-SIGN or DC-SIGNR or CD209L). Treatments with S-layer during different times in the infection demonstrated that inhibition was only observed when S-layer was presented in early stages of the viral infection. This inhibition does not involve the classic recognition of mannose by this C-type lectin as the S-layer showed no evidence to be glycosylated. In fact, the highly basic nature of the S-layer (pI>9.5) seems to be involved in electrostatic interactions between DC-SIGN and S-layer, since high pH abolished the inhibitory effect on infection cause by the S-layer. In silico analysis predicts a Ca2+-dependant carbohydrate recognition domain in the SlpA protein. This novel characteristic of the S-layer, a GRAS status protein, contribute to the pathogen exclusion reported for this probiotic strain and may be applied as an antiviral agent to inhibit several kinds of viruses.


title: The challenges in developing effective canine infectious respiratory disease vaccines

text: OBJECTIVES: Canine infectious respiratory disease (CIRD) is a disease of multifactorial aetiology, where multiple pathogens act sequentially or synergistically to cause disease. It is common within large dog populations, such as those in re‐homing or training kennels. Vaccines are vital in its management of CIRD, but they often fail to prevent disease. Recently, a number of novel pathogens have been identified in CIRD outbreaks and represent new targets for vaccination. KEY FINDINGS: Innate immune responses provide a vital first line of defence against the infectious agents involved in the development of CIRD. Once breeched, adaptive mucosal immunity is necessary to prevent infection and limit spread. Current vaccines target only a few of the agents involved in CIRD. Evidence, from the limited amount of published data, indicates that although vaccinating against these agents reduces infection rates, duration of shedding and severity of disease, it does not induce sterilising immunity; and this has important consequences for the management of the disease, and the future of CIRD vaccine development. SUMMARY: In the process of considering the development of novel CIRD vaccines, this paper focuses on the immunological mechanisms that provide protection for the respiratory tract, the current recommendations for canine vaccination, and the challenges surrounding existing CIRD vaccines, and their future development.


title: Demographic, clinical, and outcomes of confirmed cases of Middle East Respiratory Syndrome coronavirus (MERS-CoV) in Najran, Kingdom of Saudi Arabia (KSA); A retrospective record based study

text: Abstract Introduction MERS is caused by a viral infection, which was first identified in KSA, 2012. MERS-CoV infection consequences with either hospitalization or death. Methods All positive MERS-CoV cases that diagnosed in and reported to a referral hospital in Najran, KSA from March/2014 to December/2018 were revised retrospectively. We identified patients from infection control department and medical records. Demographic, clinical, and outcome data were collected. Results Of the 54 positive MERS-CoV cases, 3 cases were excluded because no available data. Therefore, the final number of the included cases in the study was 51 cases (94.4). Most of the patients were Saudi 36 (70.6%), and majority of cases were reported in the winter 18 (35.3) season. Fever 47 (92.2%), cough 44 (86.3%), and shortness of breath 37 (72.5%) were reported as most common symptoms. Most patients had DM and hypertension. Overall mortality rate was 37.3%, and interestingly the mortality rate dropped sharply over 5 years. In logistic regression analysis, Season and Chronic Kidney disease patients were the only two variables statistically significantly associated with death. The odds of death the patients infected by MERS-CoV during Autumn and Winter season were 4.09 times higher than those patients who infected during Spring and Summer season (OR = 4.09, CI 1.18-14.15, P < 0.026). Compared with MERS-CoV patients who had Non-Chronic kidney diseases, the odds of death the MERS-CoV patients who had chronic kidney diseases were 18.08 times higher (OR = 18.08, CI -2.01-162.99, P < 0.01). Conclusion The mortality rate of MERS-CoV infection was high. Further studies with large sample sizes are needed to explore the reasons behind the decrease in the mortality rate over the time period.


title: Trees as Nature-Based Solutions

text: In the search for ways to address sustainability challenges, there is growing interest in nature-based solutions. Among these are calls to plant a trillion trees globally, which has been met with mixed responses. In this Voices, we ask researchers about the potential role of trees in mitigating and adapting to global change, as well as doing so in a way that does not compromise other Sustainable Development Goals.


Chloroquine-induced first-episode psychosis in a patient self-medicated for covid-19


2019-nCoV pandemic: A disruptive and stressful atmosphere for Indian academic fraternity


title: Severe acute respiratory syndrome mimicking acute abdomen

text: Severe acute respiratory syndrome (SARS) is a novel epidemic disease. The clinical presentation can sometimes be very non‐specific. The present study reports a case of SARS, which presented as acute abdomen, warranting laparotomy. The atypical presentation in the present case reminded us of the importance of strict infection control measures in all surgery‐related specialist workplaces.


title: Protective effect of Xuebijing injection on myocardial injury in patients with sepsis: a randomized clinical trial

text: Abstract OBJECTIVE To investigate the protective effect and possible mechanism of Xuebijing Injection on myocardial injury in patients with sepsis, and to evaluate its prognostic implications. METHODS Patients with septic myocardial injury were recruited, and were randomly divided into two groups: treatment group and control group. All patients in two groups received conventional cluster treatment, the patients in treatment group additional received Xuebijing injection dissolved in 0.9% sodium chloride injection, and the patients in control group received the same amount of 0.9% sodium chloride injection. At the beginning of treatment and 3, 7 and 10-day after treatment, laboratory indicators of cardiac troponin I (cTnI), N-terminal proB-type natriuretic peptide (NT-proBNP) and procalcitonin (PCT) were respectively tested in venous blood. The patient's length of stay in Intensive Care Unit (ICU) and the mortality in 28 days were recorded. RESULTS At 3, 7 and 10-day after treatment, the improvements of cTnI, NT-proBNP and PCT in treatment group were better than those in control group, and the differences were statistically significant (P < 0.05). The mortality of treatment group in 28 days was not significantly different from that of control group (P > 0.05). The ICU length of stay of treatment group was shorter than that of control group (P > 0.05). CONCLUSION Xuebijing injection could improve the levels of cTnI, NT-proBNP and PCT in patients with septic myocardial injury. and it had a protective effect on myocardial injury.


title: Management of a COVID-19 outbreak in a Hotel in Tenerife, Spain

text: Abstract Since the first accounts of SARS-CoV-2, authorities have encountered numerous unprecedented situations threatening public health. This rapid communication addresses events that led to the quarantining of a hotel in Tenerife, Spain and the effectiveness of the rapidly implemented control measures. In total, eight cases have been associated with the hotel. Due to the international nature of the guests, had these timely precautions not been in place, a multinational cluster might have formed.


title: A high-flow portable biological aerosol trap (HighBioTrap) for rapid microbial detection

text: Abstract Bioaerosols exposure can lead to many adverse health effects and even result in death if highly infectious agents involved. Apparently, there is a great need for rapid detection of bioaerosols, for which air sampling often is the first critical step. However, currently available samplers often either require an external power and/or with low sampling flow rate, thus falling short of providing a practical solution when response time is of great concern. Here, we have designed and evaluated a new portable high volume bioaerosol sampler named as HighBioTrap through optimizing its operating parameters. The sampler was operated at a sampling flow rate of 1200L/min, with an impaction velocity of about 10.2m/s (S/W = 1.5, T/W = 1), while the weight of the sampler is about 1.9kg. The performances of the HighBioTrap sampler were tested both in lab controlled and natural environments (outdoor and indoor environments in a university building) along with the reference sampler-the BioStage impactor using aerosolized Polystyrene (PS) uniform microspheres of various sizes, aerosolized bacteria and also ambient air particles. The microbial community structures of collected culturable bacterial aerosol particles both by the HighBioTrap and the BioStage impactor in the natural environments were analyzed using gene sequence method. Experimental results with PS particles showed the HighBioTrap has a cutoff size of ~ 2µm. The widely used impactor design equation was found to be not applicable for predicting the performance of the HighBioTrap due to its large Reynolds number. When sampling aerosolized individual Pseudomonas fluorescens and Bacillus subtilis bacterial particles, the HighBioTrap had physical collection efficiencies of 10% and 20%, respectively. Despite the higher desiccation effects introduced by higher flow rate, the HighBioTrap was shown to obtain a higher microbial diversity than the BioStage impactor for both in outdoor and indoor environments given the same sampling time (p < 0.01). Our data also showed that most of the desiccation effects might have occurred between 3 and 5min of the sampling and an impaction velocity of around 10m/s might be a close-to-optimal impaction velocity for collecting most environmental bacterial aerosols while maximally preserving their culturability. This work contributes to our understanding of microbial sampling stress (impaction velocity and sampling time), while developing a portable high volume sampler. The HighBioTrap sampler could find its great efficiencies in qualitative microbial aerosol detection and analysis, such as investigation of microbial aerosol diversity for a particular environment, or when the low level of pathogens is present and detection time is of great concern.


title: Chapter 6 Developing Phytocompounds from Medicinal Plants as Immunomodulators

text: Abstract Imbalance or malfunction of the immune systems is associated with a range of chronic diseases including autoimmune diseases, allergies, cancers and others. Various innate and adaptive immune cells that are integrated in this complex networking system may represent promising targets for developing immunotherapeutics for treating specific immune diseases. A spectrum of phytochemicals have been isolated, characterized and modified for development and use as prevention or treatment of human diseases. Many cytotoxic drugs and antibiotics have been developed from phytocompounds, but the application of traditional or new medicinal plants for use as immunomodulators in treating immune diseases is still relatively limited. In this review, a selected group of medicinal herbs, their derived crude or fractionated phytoextracts and the specific phytochemicals/phytocompounds isolated from them, as well as categorized phytocompound groups with specific chemical structures are discussed in terms of their immunomodulatory bioactivities. We also assess their potential for future development as immunomodulatory or inflammation-regulatory therapeutics or agents. New experimental approaches for evaluating the immunomodulatory activities of candidate phytomedicines are also discussed.


title: Oxidative stress in multiple sclerosis: Central and peripheral mode of action

text: Accumulating evidence suggests that oxidative stress plays a major role in the pathogenesis of multiple sclerosis (MS). Reactive oxygen species (ROS), which if produced in excess lead to oxidative stress, have been implicated as mediators of demyelination and axonal damage in both MS and its animal models. One of the most studied cell populations in the context of ROS-mediated tissue damage in MS are macrophages and their CNS companion, microglia cells. However, and this aspect is less well appreciated, the extracellular and intracellular redox milieu is integral to many processes underlying T cell activation, proliferation and apoptosis. In this review article we discuss how oxidative stress affects central as well as peripheral aspects of MS and how manipulation of ROS pathways can potentially affect the course of the disease. It is our strong belief that the well-directed shaping of ROS pathways has the potential to ameliorate disease progression in MS.


title: Process mapping of vaccines: Understanding the limitations in current response to emerging epidemic threats

text: Vaccination remains the most successful and effective mechanism of pathogen control. However, their development and deployment in epidemic settings have been limited, and the 2015 Ebola outbreak in West Africa identified several bottlenecks linked to a lack of investment in pathogen research, infrastructure or regulation. Shortly after this outbreak, the UK Government established the UK Vaccine Network to ensure the UK is better prepared to respond to pathogens outbreaks of epidemic potential. As part of their work, the network commissioned the creation of a Vaccine Development Tool (http://www.vaccinedevelopment.org.uk/) to serve as a guide to the key stages in vaccine development. The tool also set out to capture the key, rate-limiting bottlenecks in the development of vaccines against emerging infectious disease such that corrective action could be taken, be it through research, funding, infrastructure and policy, both in the UK and internationally. The main research bottlenecks were related to understanding pathogen biology, identification of appropriate animal models and investment in the manufacturing sciences, especially into process development. Infrastructure gaps in GMP manufacturing and fill-finish were also identified and limitations in GMO regulation and regulatory and ethical approvals, especially for outbreak pathogens required new policy initiatives. The UK Vaccine Network has since begun work to correct for these limitations with a series of funding calls and development programmes. This paper seeks to summarise the Vaccine Development Tool and its key findings.


title: Reorganization and expansion of the nidoviral family Arteriviridae

text: The family Arteriviridae presently includes a single genus Arterivirus. This genus includes four species as the taxonomic homes for equine arteritis virus (EAV), lactate dehydrogenase-elevating virus (LDV), porcine respiratory and reproductive syndrome virus (PRRSV), and simian hemorrhagic fever virus (SHFV), respectively. A revision of this classification is urgently needed to accommodate the recent description of eleven highly divergent simian arteriviruses in diverse African nonhuman primates, one novel arterivirus in an African forest giant pouched rat, and a novel arterivirus in common brushtails in New Zealand. In addition, the current arterivirus nomenclature is not in accordance with the most recent version of the International Code of Virus Classification and Nomenclature. Here we outline an updated, amended, and improved arterivirus taxonomy based on current data. Taxon-specific sequence cut-offs are established relying on a newly established open reading frame 1b phylogeny and pairwise sequence comparison (PASC) of coding-complete arterivirus genomes. As a result, the current genus Arterivirus is replaced by five genera: Equartevirus (for EAV), Rodartevirus (LDV + PRRSV), Simartevirus (SHFV + simian arteriviruses), Nesartevirus (for the arterivirus from forest giant pouched rats), and Dipartevirus (common brushtail arterivirus). The current species Porcine reproductive and respiratory syndrome virus is divided into two species to accommodate the clear divergence of the European and American “types” of PRRSV, both of which now receive virus status. The current species Simian hemorrhagic fever virus is divided into nine species to accommodate the twelve known simian arteriviruses. Non-Latinized binomial species names are introduced to replace all current species names to clearly differentiate them from virus names, which remain largely unchanged.


title: Metagenomic analysis of the RNA fraction of the fecal virome indicates high diversity in pigs infected by porcine endemic diarrhea virus in the United States

text: BACKGROUND: Emergence and re-emergence of porcine epidemic diarrhea virus (PEDV) in North America, Asia and Europe has caused severe economic loss to the global swine industry. However, the virome of PEDV infected pigs and its effect on disease severity remains unknown. The advancements of sequencing technology have made it possible to characterize the entire microbiome of different body sites for any host. METHODS: The objective of this study was to characterize the RNA virome in PEDV-positive pigs using the hypothesis-free metagenomics approach based on next-generation sequencing. Specifically, 217 PEDV-positive swine fecal swab samples collected from diarrheic piglets over 17 US states during 2015–2016 were analyzed. RESULTS: A Kraken algorithm-based bioinformatics analysis revealed the presence of up to 9 different RNA genera besides PEDV (Alphacoronavirus genus), including Mamastrovirus (52%, 113/217), Enterovirus (39%, 85/217), Sapelovirus (31%, 67/217), Posavirus (30%, 66/217), Kobuvirus (23%, 49/217), Sapovirus (13%, 28/217), Teschovirus (10%, 22/217), Pasivirus (9%, 20/217), and Deltacoronavirus (3%, 6/217). There were 58 out of 217 piglets (27%) have PEDV infection alone whereas the remaining 159 (73%) shed 2 up to 9 different viruses. CONCLUSION: These findings demonstrated that PEDV infected diarrheic pigs had an extensive RNA viral flora consisting of four different families: Astroviridae, Picornaviridae, Caliciviridae, and Coronaviridae.


title: Effects of pre- and postpartum nutrition on reproduction in spring calving cows and calf feedlot performance

text: Crossbred, spring-calving cows (yr 1, n = 136; yr 2, n = 113; yr 3, n = 113) were used in a 3-yr experiment to evaluate the influence of supplemental protein prepartum and grazing subirrigated meadow postpartum on pregnancy rates and calf feedlot performance. A 2 × 2 factorial arrangement of treatments was used in a switchback design. From December 1 to February 28, cows grazed dormant upland range in 8 pastures (32 ± 2 ha each). The equivalent of 0.45 kg of supplement/cow per d (42% CP) was provided to half of the cows on a pasture basis 3 d/wk. For 30 d before the beginning of breeding (May 1 to May 31), half of the cows grazed a common subirrigated meadow (58 ha), and the remainder was fed grass hay in a drylot. Cow BW and BCS were monitored throughout the year, and steer calf performance was determined until slaughter. Feeding supplement prepartum improved (P = 0.01 to P < 0.001) BCS precalving (5.1 vs. 4.7) and prebreeding (5.1 vs. 4.9) and increased (P = 0.02) the percentage of live calves at weaning (98.5 vs. 93.6%) but did not affect (P = 0.46) pregnancy rate (93 vs. 90%). Calves born to dams fed supplement prepartum had similar (P = 0.29) birth weight (37 vs. 36 kg) but greater (P = 0.02) weaning weight (218 vs. 211 kg). However, steer feedlot DMI (8.53 vs. 8.48 kg), ADG (1.6 vs. 1.6 kg), and carcass weight (369 vs. 363 kg) were not affected (P = 0.23 to P = 0.89) by prepartum supplementation. Allowing cows to graze subirrigated meadow postpartum improved (P < 0.001) BCS prebreeding (5.2 vs. 4.9) but did not affect (P = 0.88) pregnancy rate (92 vs. 91%). Allowing cows to graze subirrigated meadow increased (P = 0.01) calf weaning weight (218 vs. 211 kg) but not (P = 0.62 to P = 0.91) feedlot DMI (8.4 vs. 8.3 kg), ADG (1.6 vs. 1.6 kg), or carcass weight (363 vs. 362 kg) of their steer calves. Increased percentage of live calves at weaning as a result of feeding supplemental protein increased net returns at weaning and after finishing in the feedlot. Net returns were increased by allowing cows to graze subirrigated meadow postpartum regardless of whether calves were marketed at weaning or after finishing in the feedlot.


title: Genetic diversity and phylogenetic analysis of Feline Coronavirus sequences from Portugal

text: Abstract The distribution of FCoV Types I and II in a Portuguese cat population was studied by a RT-PCR assay targeting the 3′-end of the viral RNA. For a period of 3 years, 120 samples were collected and 57 were found positive for FCoV RNA. Within the positive samples the presence of FCoV Type I was found in 79%. Type II was only detected in 3.5% in animals with Feline Infectious Peritonitis. The remaining 17.5% could not be differentiated. These viral sequences, comprising a region within gene S were further subjected to a heteroduplex mobility assay (HMA) detecting the presence of viral quasispecies in 17% of the samples. Phylogenetic analysis for FCoV Type I revealed high genetic diversity between the Portuguese sequences and other previously characterized strains, while Type II tree showed a higher genetic homogeneity. This study confirmed the presence of FCoV Types I and II circulating in Portugal and detected high genetic diversity between circulating strains suggesting that the virus persists within the host as mixed viral populations.


title: Elevated levels of myeloperoxidase, pro-inflammatory cytokines and chemokines in naturally acquired upper respiratory tract infections

text: Upper respiratory tract infections (URTIs) are characterised by a neutrophilic mucosal infiltration. The purpose of this study was to investigate the time course of release of the cytokines/chemokines interleukins (IL) IL-1β, IL-1ra, tumour necrosis factor-α (TNF-α), IL-6, IL-8, interferon-γ (IFN-γ) and monocyte chemotactic protein (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1), myeloperoxidase (MPO) and bradykinin in nasal secretions of patients with a naturally acquired URTI. A total of 117 healthy adult volunteers were recruited for baseline nasal lavages, 39 of whom developed URTI symptoms within 6 months and returned to our centre within 48 h. Lavages were performed daily during the symptomatic period and 3 weeks thereafter, with symptoms no longer present. Compared to baseline, significantly elevated concentrations of total protein, bradykinin, IL-1β, TNF-α, IL-6, IL-8, MCP-1, IFN-γ, MPO and sICAM-1 were detected in nasal lavage fluids of symptomatic patients, whereas IL-1ra remained unaltered. All studied variables reached baseline 3 weeks after the URTI. Naturally acquired URTI represent a limited, neutrophilic inflammatory reaction, orchestrated by the release of pro-inflammatory cytokines and chemokines.


COVID-19 – Where should we go now?


title: Investigation of interaction between two neutralizing monoclonal antibodies and SARS virus using biosensor based on imaging ellipsometry

text: Two neutralizing human scFv, b1 and h12 were identified initially using ELISA,employing highly purified virus as the coating antigen. The biosensor technique based on imaging ellipsometry was employed directly to detect two neutralizing monoclonal antibodies and serial serum samples from 10 SARS patients and 12 volunteers who had not SARS. Further, the kinetic process of interaction between the antibodies and SARS-CoV was studied using the real-time function of the biosensor. The biosensor is consistent with ELISA that the antibody h12 showed a higher affinity in encountering the virus than antibody b1. The affinity of antibody b1 and antibody h12 was 9.5 × 10(6) M(−1) and 1.36 × 10(7) M(− 1), respectively. As a label free method, the biosensor based on imaging ellipsometry proved to be a more competent mechanism for measuring serum samples from SARS patients and the affinity between these antibodies and the SARS coronavirus.


title: Phlorotannins

text: Abstract Natural marine-derived compounds show excellent biological activities. Isolation, characterization and applications of marine derived compounds show a promising way to develop novel drugs to treat various diseases. Phlorotannins are one of the main compounds which are commonly isolated from the brown seaweeds. The structural unit of phlorotannins is made-up of polyphenolic units. Due to the unique structures, phlorotannins show a variety of biological activities such as antibacterial, antioxidant, anti-inflammatory, antiproliferative, antitumor, antidiabetics, radio protective, antiadipogenic, and anti-allergic effects. In the current chapter, we have discussed general information on phlorotannins, extraction procedure and their biological activities in detail. From the scientific literature, phlorotannins can be potentially useful in the development of pharmaceuticals, nutraceuticals and cosmeceuticals.


Dynamics of antibodies to SARS-CoV-2 in a case with SARS-CoV-2 infection


title: Deciphering the involvement of innate immune factors in the development of the host response to PRRSV vaccination

text: Abstract The natural response of pigs to porcine reproductive and respiratory syndrome virus (PRRSV) infections and vaccinations needs to be altered so that better protection is afforded against both homologous and heterologous challenges by this pathogen. To address this problem, real-time gene expression assays were coupled with cytokine Elispot and protein analyses to assess the nature of the anti-PRRSV response of pigs immunized with modified live virus (MLV) vaccine. Although T helper 1 (Th1) immunity was elicited in all vaccinated animals, as evidenced by the genesis of PRRSV-specific interferon-gamma secreting cells (IFNG SC), the overall extent of the memory response was variable and generally weak. Peripheral blood mononuclear cells (PBMC) isolated from these pigs responded to PRRSV exposure with a limited increase in their expression of the Th1 immune markers, IFNG, tumor necrosis factor-alpha and interleukin-15 (IL15), and a reduction in the quantity of mRNAs encoding the innate and inflammatory proteins, IL1B, IL8 and IFNA. Efforts to enhance Th1 immunity, by utilizing an expression plasmid encoding porcine IFNA (pINA) as an adjuvant, resulted in a temporary increase in the frequency of PRRSV-specific IFNG SC but only minor changes overall in the expression of Th1 associated cytokine or innate immune marker mRNA by virus-stimulated PBMC. Administration of pINA, however, did correlate with decreased IL1B secretion by cultured, unstimulated PBMC but had no effect on their ability to release IFNG. Thus, while exogenous addition of IFNA during PRRSV vaccination has an impact on the development of a Th1 immune response, other alterations will be required for substantial boosting of virus-specific protection.


title: High levels of unreported intraspecific diversity among RNA viruses in faeces of neonatal piglets with diarrhoea

text: BACKGROUND: Diarrhoea is a major cause of death in neonate pigs and most of the viruses that cause it are RNA viruses. Next Generation Sequencing (NGS) deeply characterize the genetic diversity among rapidly mutating virus populations at the interspecific as well as the intraspecific level. The diversity of RNA viruses present in faeces of neonatal piglets suffering from diarrhoea in 47 farms, plus 4 samples from non-diarrhoeic piglets has been evaluated by NGS. Samples were selected among the cases submitted to the Veterinary Diagnostic Laboratories of Infectious Diseases of the Universitat Autònoma de Barcelona (Barcelona, Spain) and Universidad de León (León, Spain). RESULTS: The analyses identified the presence of 12 virus species corresponding to 8 genera of RNA viruses. Most samples were co-infected by several viruses. Kobuvirus and Rotavirus were more commonly reported, with Sapovirus, Astrovirus 3, 4 and 5, Enterovirus G, Porcine epidemic diarrhoea virus, Pasivirus and Posavirus being less frequently detected. Most sequences showed a low identity with the sequences deposited in GenBank, allowing us to propose several new VP4 and VP7 genotypes for Rotavirus B and Rotavirus C. CONCLUSIONS: Among the cases analysed, Rotaviruses were the main aetiological agents of diarrhoea in neonate pigs. Besides, in a small number of cases Kobuvirus and Sapovirus may also have an aetiological role. Even most animals were co-infected in early life, the association with enteric disease among the other examined viruses was unclear. The NGS method applied successfully characterized the RNA virome present in faeces and detected a high level of unreported intraspecific diversity.


title: Saccharomyces cerevisiae: a versatile eukaryotic system in virology

text: The yeast Saccharomyces cerevisiae is a well-established model system for understanding fundamental cellular processes relevant to higher eukaryotic organisms. Less known is its value for virus research, an area in which Saccharomyces cerevisiae has proven to be very fruitful as well. The present review will discuss the main achievements of yeast-based studies in basic and applied virus research. These include the analysis of the function of individual proteins from important pathogenic viruses, the elucidation of key processes in viral replication through the development of systems that allow the replication of higher eukayotic viruses in yeast, and the use of yeast in antiviral drug development and vaccine production.


title: Urgent Peritoneal Dialysis in Patients With COVID-19 and Acute Kidney Injury: A Single-Center Experience in a Time of Crisis in the United States

text: At Montefiore Medical Center, in The Bronx, NY, the first case of coronavirus disease 2019 (COVID-19) was admitted on March 11, 2020. At the height of the pandemic, there were 855 patients with COVID-19 admitted on April 13, 2020. Due to high demand for dialysis and shortages of staff and supplies, we started an urgent peritoneal dialysis (PD) program. From April 1(st) to April 22(nd), 30 patients were started on PD. Of those 30 patients, 14 died during their hospitalization, 8 were discharged, and 8 were still hospitalized as of May 14, 2020. Although the PD program was successful in its ability to provide much-needed kidney replacement therapy (KRT) when hemodialysis was not available, challenges to delivering adequate PD dosage included difficulties in providing nurse training and availability of supplies. Providing adequate clearance and ultrafiltration for patients in intensive care units was especially difficult due to high prevalence of hypercatabolic state, volume overload, and prone positioning. PD was more easily performed in non-critically ill patients outside the intensive care unit. Despite these challenges, we demonstrate that urgent PD is a feasible alternative to hemodialysis in situations with critical resource shortages.


title: Frailty and mortality in hospitalized older adults with COVID-19: retrospective observational study

text: ABSTRACT Objectives To determine the association between frailty and short-term mortality in older adults hospitalized for coronavirus disease 2019 (COVID-19). Design Retrospective single-center observational study. Setting and participants: N = 81 patients with COVID-19 confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR), at the Geriatrics department of a general hospital in Belgium. Measure ments: Frailty was graded according to the Rockwood Clinical Frailty Scale (CFS). Demographic, biochemical and radiological variables, co-morbidities, symptoms and treatment were extracted from electronic medical records. Results Participants (N = 48 women, 59%) had a median age of 85 years (range 65 – 97 years), median CFS score of 7 (range 2 – 9), and 42 (52%) were long-term care residents. Within six weeks, eighteen patients died. Mortality was significantly but weakly associated with age (Spearman r = 0.241, P = 0.03) and CFS score (r = 0.282, P = 0.011), baseline lactate dehydrogenase (LDH) (r = 0.301, P = 0.009), lymphocyte count (r = -0.262, P = 0.02) and RT-PCR cycle threshold (Ct, r = -0.285, P = 0.015). Mortality was not associated with long-term care residence, dementia, delirium or polypharmacy. In multivariable logistic regression analyses, CFS, LDH and RT-PCR Ct (but not age) remained independently associated with mortality. Both age and frailty had poor specificity to predict survival. A multivariable model combining age, CFS, LDH and viral load significantly predicted survival. Conclusions and implications Although their prognosis is worse, even the oldest and most severely frail patients may benefit from hospitalization for COVID-19, if sufficient resources are available.


SOMALIA: Covid‐19 Hampers Progress


title: Lowered yields of virus-induced interferon production in leukocyte cultures and risk of recurrent respiratory infections in children

text: Abstract Objective: To study the correlation between the yield of virus-induced interferon (IFN) production in leukocyte cultures and the risk of recurrent respiratory infections. Methods: A sample of 71 consecutive children enrolled in the Finnish Otitis Media Cohort Study were selected. Children suffering from frequently recurring respiratory infections (FRRIs) were defined as the highest quintile of the entire cohort of 329 children, as regards the number of upper respiratory infections (URIs) and/or episodes of acute otitis media (AOM) during the follow-up period from 2 to 24 months. Results: In the sample of 71 children, there were 18 children with FRRI (≥9 URI and/or ≥4 AOM). Leukocyte cultures, prepared from blood drawn from these 18 children at 6 months of age, produced lower yields of IFN than those of the remaining 53 children, when stimulated with adenovirus (P<0.001), coronavirus (P<0.001) or rhinovirus (P=0.002). The difference in IFN yields was even greater (P<0.001 with all three viruses) if the comparison was made between children with FRRI and those with no or maximally one URI during the follow-up period. When the IFN production capacity induced by rhinovirus was measured at the age of 24 months, a statistically significant difference between the children with FRRI and the others was also seen (P=0.002). Influenza A virus-induced IFN production capacity did not differ between the groups at either age (P=0.209). Conclusions: Lowered IFN responses in children suffering from recurrent URIs and/or AOM may, in a subgroup of the children, be due to a genetic property of the child. However, because of the great interindividual variations, we cannot use the IFN production capacity as such for prediction of forthcoming respiratory infections and/or otitis media.


title: Preserving Organizational Resilience, Patient Safety, and Staff Retention during COVID-19 Requires a Holistic Consideration of the Psychological Safety of Healthcare Workers

text: During the COVID-19 pandemic, healthcare workers are fighting a lethal virus with acute shortages of Personal Protective Equipment (PPE). These unprecedented circumstances have amplified the sources of emotional distress and worker burnout. However, many healthcare organizations (HCOs) in the United States, have opted for a “stoic approach” to healthcare worker support, i.e., no additional support beyond federal and state policy protections for the licensing and liability of healthcare workers. In this scenario, a key public health concern is sustaining an adequate healthcare workforce, both by way of quantity (adequate numbers) and quality (maximizing clinician resilience to provide safe care to large volumes of patients under challenging conditions). Therefore, it is imperative for HCO leaders to recognize that a limited view of worker psychological safety, without due consideration for the broader emotional distress created by the pandemic, could have the effect of restricting organizational resilience and adversely impacting patient safety and staff retention during and beyond the pandemic. This paper uses the organizational resilience framework to discuss the potential impact of a stoic approach to healthcare worker support on patient safety and staff retention in a hospital intensive care unit (ICU) during COVID-19. The discussion in turn, helps to develop recommendations for HCOs to overcome these challenges.


title: Illinois rolls out COVID‐19 MH crisis hotline as cases climb

text: After another deadly 24 hours in Illinois, Gov. J.B. Pritzker announced a new program to connect scared and depressed Illinois residents to badly needed mental health services, Block Club Chicago reported April 11. In the 24 hours in question, 81 people died from COVID‐19 and 1,293 new confirmed cases were reported. Hoping to help those in need of mental and physical health care during the crisis, the state has created programs that will help people from afar. Call4Calm, a free emotional support text line, was created to serve Illinois residents “swimming in the stress and uncertainty” caused by COVID‐19, Pritzker said. To connect with a counselor, people can text “TALK” to 552020 or text “HABLAR” to the same number for counseling in Spanish. Users will remain anonymous, and the state has partnered with mental health organizations to have counselors respond. Once a resident texts the hotline, they'll get a call from a licensed counselor within 24 hours. The program was announced as the state reached 19,180 confirmed COVID‐19 cases, said Dr. Ngozi Ezike, director of the Illinois Department of Public Health.


title: A Call for Consistency in the Official Naming of the Disease Caused by Severe Acute Respiratory Syndrome Coronavirus 2 in Non-English Languages

text: We investigated the adoption of World Health Organization (WHO) naming of COVID-19 into the respective languages among the Group of Twenty (G20) countries, and the variation of COVID-19 naming in the Chinese language across different health authorities. On May 7, 2020, we identified the websites of the national health authorities of the G20 countries to identify naming of COVID-19 in their respective languages, and the websites of the health authorities in mainland China, Hong Kong, Macau, Taiwan and Singapore and identify their Chinese name for COVID-19. Among the G20 nations, Argentina, China, Italy, Japan, Mexico, Saudi Arabia and Turkey do not use the literal translation of COVID-19 in their official language(s) to refer to COVID-19, as they retain “novel” in the naming of this disease. China is the only G20 nation that names COVID-19 a pneumonia. Among Chinese-speaking jurisdictions, Hong Kong and Singapore governments follow the WHO’s recommendation and adopt the literal translation of COVID-19 in Chinese. In contrast, mainland China, Macau, and Taiwan refer to COVID-19 as a type of pneumonia in Chinese. We urge health authorities worldwide to adopt naming in their native languages that are consistent with WHO’s naming of COVID-19.


title: Respiratory viral infections in children with asthma: do they matter and can we prevent them?

text: BACKGROUND: Asthma is a major public health problem with a huge social and economic burden affecting 300 million people worldwide. Viral respiratory infections are the major cause of acute asthma exacerbations and may contribute to asthma inception in high risk young children with susceptible genetic background. Acute exacerbations are associated with decreased lung growth or accelerated loss of lung function and, as such, add substantially to both the cost and morbidity associated with asthma. DISCUSSION: While the importance of preventing viral infection is well established, preventive strategies have not been well explored. Good personal hygiene, hand-washing and avoidance of cigarette smoke are likely to reduce respiratory viral infections. Eating a healthy balanced diet, active probiotic supplements and bacterial-derived products, such as OM-85, may reduce recurrent infections in susceptible children. There are no practical anti-viral therapies currently available that are suitable for widespread use. SUMMARY: Hand hygiene is the best measure to prevent the common cold. A healthy balanced diet, active probiotic supplements and immunostimulant OM-85 may reduce recurrent infections in asthmatic children.


title: Disinfection technology of hospital wastes and wastewater: Suggestions for disinfection strategy during coronavirus Disease 2019 (COVID-19) pandemic in China

text: Abstract Hospitals are important sources of pollutants resulted from diagnostic, laboratory and research activities as well as medicine excretion by patients, which include active component of drugs and metabolite, chemicals, residues of pharmaceuticals, radioactive markers, iodinated contrast media, etc. The discharge of hospital wastes and wastewater, especially those without appropriate treatment would expose the public in danger of infection. In particular, under the Coronavirus Disease 2019 (COVID-19) pandemic context in China, it is of great significance to reduce the health risks to the public and environment. In this study, technologies of different types of hospital wastes and wastewater disinfection have been summarized. Liquid chlorine, sodium hypochlorite, chlorine dioxide, ozone, and ultraviolet irradiation disinfection are commonly used for hospital wastewater disinfection. While incineration, chemical disinfection, and physical disinfection are commonly used for hospital wastes disinfection. In addition, considering the characteristics of various hospital wastes, the classification and selection of corresponding disinfection technologies are discussed. On this basis, this study provides scientific suggestions for management, technology selection, and operation of hospital wastes and wastewater disinfection in China, which is of great significance for development of national disinfection strategy for hospital wastes and wastewater during COVID-19 pandemic.


title: Ebola or Not? Evaluating the Ill Traveler From Ebola-Affected Countries in West Africa

text: Background. The 2014–2015 Ebola epidemic in West Africa had global impact beyond the primarily affected countries of Guinea, Liberia, and Sierra Leone. Other countries, including the United States, encountered numerous patients who arrived from highly affected countries with fever or other signs or symptoms consistent with Ebola virus disease (EVD). Methods. We describe our experience evaluating 25 travelers who met the US Centers for Disease Control and Prevention case definition for a person under investigation (PUI) for EVD from July 20, 2014 to January 28, 2015. All patients were triaged and evaluated under the guidance of institutional protocols to the emergency department, outpatient tropical medicine clinic, or Emory's Ebola treatment unit. Strict attention to infection control and early involvement of public health authorities guided the safe evaluation of these patients. Results. None were diagnosed with EVD. Respiratory illnesses were common, and 8 (32%) PUI were confirmed to have influenza. Four patients (16%) were diagnosed with potentially life-threatening infections or conditions, including 3 with Plasmodium falciparum malaria and 1 with diabetic ketoacidosis. Conclusions. In addition to preparing for potential patients with EVD, Ebola assessment centers should consider other life-threatening conditions requiring urgent treatment, and travelers to affected countries should be strongly advised to seek pretravel counseling. Furthermore, attention to infection control in all aspects of PUI evaluation is paramount and has presented unique challenges. Lessons learned from our evaluation of potential patients with EVD can help inform preparations for future outbreaks of highly pathogenic communicable diseases.


title: Positive effects of COVID-19 control measures on influenza prevention

text: Abstract Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now become a pandemic threat to the whole world. At the same time, influenza virus has been active, with influenza virus and SARS-CoV-2 sharing the same transmission routes. This article aims to alert clinicians of the presence of co-infection with these two viruses and to describe the effect of the measures taken to fight COVID-19 on influenza prevention and control.


title: Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome

text: The recent emergence of the Middle East respiratory syndrome (MERS)-CoV, a close relative of the Severe Acute respiratory syndrome (SARS)-CoV, both of which caused a lethal respiratory infection in humans, reinforces the need for further understanding of coronavirus pathogenesis and the host immune response. These viruses have evolved diverse strategies to evade and block host immune responses, facilitating infection and transmission. Pathogenesis following infection with these viruses is characterized by a marked delay in the induction of Type I interferon (IFN I) and, subsequently, by a poor adaptive immune response. Therapies that expedite IFN I induction as well as interventions that antagonize immunoevasive virus proteins are thus promising candidates for immune modulation.


No Respite From Union Organizing During Pandemic


title: Role of endocytosis and cathepsin-mediated activation in Nipah virus entry

text: Abstract The recent discovery that the Nipah virus (NiV) fusion protein (F) is activated by endosomal cathepsin L raised the question if NiV utilize pH- and protease-dependent mechanisms of entry. We show here that the NiV receptor ephrin B2, virus-like particles and infectious NiV are internalized from the cell surface. However, endocytosis, acidic pH and cathepsin-mediated cleavage are not necessary for the initiation of infection of new host cells. Our data clearly demonstrate that proteolytic activation of the NiV F protein is required before incorporation into budding virions but not after virus entry.


title: Untapped potential: The utility of drylands for testing eco-evolutionary relationships between hosts and parasites

text: Drylands comprise over 41% of all terrestrial surface area and are home to approximately 35.5% of the world's population; however, both free-living and parasitic fauna of these regions remain relatively understudied. Yet, the very conditions that make these regions challenging to study – extreme environmental conditions and low population density for various organisms – also make them potentially untapped natural laboratories for examining eco-evolutionary relationships between hosts and parasites. Adaptations and ecological patterns illustrated by desert parasite communities can serve as exemplars within the extremes regarding the evolution of virulence, breadth of host spectra, and lifecycle strategies. This review provides relevant examples for each of these three topics using parasites from dryland regions in order to encourage future empirical tests of hypotheses regarding parasite ecology and evolution within dryland ecosystems and stimulate wider investigation into the parasitofauna of arid regions in general. As global climate changes and anthropogenic disturbance increases, desertification is a growing problem which has been labeled as a threat to global health. Thus, deserts not only provide useful natural laboratories in which to study parasite transmission but understanding parasite transmission within these habitats becomes increasingly important as larger, likely highly resource insecure, populations are projected to live on the margins of desert regions in the future.


title: Computer aided selection of candidate vaccine antigens

text: Immunoinformatics is an emergent branch of informatics science that long ago pullulated from the tree of knowledge that is bioinformatics. It is a discipline which applies informatic techniques to problems of the immune system. To a great extent, immunoinformatics is typified by epitope prediction methods. It has found disappointingly limited use in the design and discovery of new vaccines, which is an area where proper computational support is generally lacking. Most extant vaccines are not based around isolated epitopes but rather correspond to chemically-treated or attenuated whole pathogens or correspond to individual proteins extract from whole pathogens or correspond to complex carbohydrate. In this chapter we attempt to review what progress there has been in an as-yet-underexplored area of immunoinformatics: the computational discovery of whole protein antigens. The effective development of antigen prediction methods would significantly reduce the laboratory resource required to identify pathogenic proteins as candidate subunit vaccines. We begin our review by placing antigen prediction firmly into context, exploring the role of reverse vaccinology in the design and discovery of vaccines. We also highlight several competing yet ultimately complementary methodological approaches: sub-cellular location prediction, identifying antigens using sequence similarity, and the use of sophisticated statistical approaches for predicting the probability of antigen characteristics. We end by exploring how a systems immunomics approach to the prediction of immunogenicity would prove helpful in the prediction of antigens.


ARE CORONAVIRUS-LIKE PARTICLES SEEN IN DIARRHŒA STOOLS REALLY VIRUSES?


title: Follow-up Study on Pulmonary Function and Lung Radiographic Changes in Rehabilitating Severe Acute Respiratory Syndrome Patients After Discharge

text: Objectives To follow-up on the changes in lung function and lung radiographic pictures of severe acute respiratory syndrome (SARS) patients discharged from Xiaotangshan Hospital in Beijing (by regularly receiving examination), and to analyze retrospectively the treatment strategy in these patients. Methods Surviving SARS patients were seen at least twice within 3 months after discharge and underwent SARS-associated coronavirus (SARS-CoV) IgG antibody testing, pulmonary function testing, and chest radiography and/or high-resolution CT (HRCT) examinations at Chinese PLA General Hospital. The treatments received at Xiaotangshan Hospital were analyzed retrospectively and were correlated to later status. Results Positive SARS-Co virus IgG antibody results were seen in 208 of 258 patients, with 21.3% (55 of 258 patients) still having a pulmonary diffusion abnormality (Dlco < 80% of predicted). By comparing the 155 survivors with positive SARS-CoV IgG antibody results and Dlco ≥ 80% predicted with the 50 patients with negative SARS-CoV IgG results, we found that 53 patients with positive SARS-CoV IgG results and a lung diffusion abnormality had endured a much longer course of fever and received larger doses of glucocorticoid, as well as higher ratios of oxygen inhalation and noninvasive ventilation treatment. For these patients, 51 of 53 patients with positive SARS-CoV IgG results and a lung diffusion abnormality underwent pulmonary function testing after approximately 1 month. Dlco improved in 80.4% of patients (41 of 51 patients). Of the patients with a lung diffusion abnormality, 40 of 51 patients showed lung fibrotic changes in the lung image examination and 22 patients (55%) showed improvement in lung fibrotic changes 1 month later. Conclusion These findings suggest that lung fibrotic changes caused by SARS disease occurred mostly in severely sick patients and may be self-rehabilitated. Dlco scores might be more sensitive than HRCT when evaluating lung fibrotic changes.


title: Diagnostic tools for tackling febrile illness and enhancing patient management

text: Abstract Most patients with acute infectious diseases develop fever, which is frequently a reason to visit health facilities in resource-limited settings. The symptomatic overlap between febrile diseases impedes their diagnosis on clinical grounds. Therefore, the World Health Organization promotes an integrated management of febrile illness. Along this line, we present an overview of endemic and epidemic etiologies of fever and state-of-the-art diagnostic tools used in the field. It becomes evident that there is an urgent need for the development of novel technologies to fulfill end-users' requirements. This need can be met with point-of-care and near-patient diagnostic platforms, as well as e-Health clinical algorithms, which co-assess test results with key clinical elements and biosensors, assisting clinicians in patient triage and management, thus enhancing disease surveillance and outbreak alerts. This review gives an overview of diagnostic technologies featuring a platform based approach: (i) assay (nucleic acid amplification technologies are examined); (ii) cartridge (microfluidic technologies are presented); (iii) instrument (various detection technologies are discussed); and at the end proposes a way that such technologies can be interfaced with electronic clinical decision-making algorithms towards a broad and complete diagnostic ecosystem.


title: Impact of a viral respiratory epidemic on the practice of medicine and rehabilitation: Severe acute respiratory syndrome

text: Lim PA, Ng YS, Tay BK. Impact of a viral respiratory epidemic on the practice of medicine and rehabilitation: severe acute respiratory syndrome. Arch Phys Med Rehabil 2004;85:1365–70. Severe acute respiratory syndrome (SARS) is a new respiratory viral epidemic that originated in China but has affected many parts of the world, with devastating impact on economies and the practice of medicine and rehabilitation. A novel coronavirus has been implicated, with transmission through respiratory droplets. Rehabilitation was significantly affected by SARS, because strict infection control measures run counter to principles such as multidisciplinary interactions, patients encouraging and learning from each other, and close physical contact during therapy. Immunocompromised patients who may silently carry SARS are common in rehabilitation and include those with renal failure, diabetes, and cancer. Routine procedures such as management of feces and respiratory secretions (eg, airway suctioning, tracheotomy care) have been classified as high risk. Personal protection equipment presented not only a physical but also a psychologic barrier to therapeutic human contact. Visitor restriction to decrease chances of disease transmission are particularly difficult for long-staying rehabilitation patients. At the height of the epidemic, curtailment of patient movement stopped all transfers for rehabilitation, and physiatrists had to function as general internists. Our experiences strongly suggest that rehabilitation institutions should have emergency preparedness plans because such epidemics may recur, whether as a result of nature or of bioterrorism.


title: Are non‐allergenic environmental factors important in asthma?

text: OBJECTIVE: To review the roles of viral respiratory tract infections, environmental tobacco smoke and air pollution in asthma. DATA SOURCES: MEDLINE (1992‐1995) searches were conducted for publications on asthma, environmental tobacco smoke, ozone, nitrogen dioxide and particulates. STUDY SELECTION: Representative original experimental and epidemiological studies and reviews of viral infections in asthma. DATA SYNTHESIS: Respiratory virus infections are the most common and important trigger of asthma attacks in children and probably also in adults. Their role in promoting development of asthma is not so clear. Exposure to environmental tobacco smoke is almost certainly responsible for some cases of childhood asthma, and can also trigger symptoms of bronchoconstriction in adults with asthma. Exposure to ozone or nitrogen dioxide is associated with symptoms, impaired lung function, bronchial hyperresponsiveness and hospital presentations for asthma. These pollutants may also act as cofactors in the development of allergen‐specific bronchial hyperresponsiveness. CONCLUSIONS: Research on preventing upper respiratory viral infections may reduce asthma morbidity. The move to non‐smoking workplaces is welcome, but new interventions are needed to prevent young women taking up smoking and subsequently exposing their children. The ambient air quality guideline for ozone should be revised and a health‐based guideline for respirable particulates introduced.


title: Impact of Thiol–Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin-Converting Enzyme 2 Receptor

text: [Image: see text] The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an ongoing pandemic of coronavirus disease (COVID-19), which started in 2019. This is a member of Coronaviridae family in the genus Betacoronavirus, which also includes SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). The angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV and SARS-CoV-2 to enter the host cells. In particular, the interaction of viral spike proteins with ACE2 is a critical step in the viral replication cycle. The receptor-binding domain of the viral spike proteins and ACE2 have several cysteine residues. In this study, the role of thiol–disulfide balance on the interactions between SARS-CoV/CoV-2 spike proteins and ACE2 was investigated using molecular dynamics simulations. The study revealed that the binding affinity was significantly impaired when all of the disulfide bonds of both ACE2 and SARS-CoV/CoV-2 spike proteins were reduced to thiol groups. The impact on the binding affinity was less severe when the disulfide bridges of only one of the binding partners were reduced to thiols. This computational finding possibly provides a molecular basis for the differential COVID-19 cellular recognition due to the oxidative stress.


title: The Use of Ibuprofen to Treat Fever in COVID-19: A Possible Indirect Association with Worse Outcome?

text: Fever has been reported as a common symptom occurring in COVID-19 illness. Over the counter antipyretics such as ibuprofen and acetaminophen are often taken by individuals to reduce the discomfort of fever. Recently, the safety of ibuprofen in COVID-19 patients has been questioned due to anecdotal reports of worsening symptoms in previously healthy young adults. Studies show that ibuprofen demonstrates superior efficacy in fever reduction compared to acetaminophen. As fever may have benefit in shortening the duration of viral illness, it is plausible to hypothesize that the antipyretic efficacy of ibuprofen may be hindering the benefits of a fever response when taken during the early stages of COVID-19 illness.


title: 2′-5′-Oligoadenylate synthetase 1 polymorphisms are associated with tuberculosis: a case-control study

text: BACKGROUND: 2′-5′-Oligoadenylate synthetase 1 (OAS1) plays an important role in inflammatory immune reactions. OAS1 polymorphisms have been associated with increased susceptibility to various diseases. We investigated the association of polymorphisms in OAS1 with tuberculosis (TB). METHODS: A total of 1215 TB cases and 1114 healthy controls were enrolled from two independent studies. Genotyping was conducted using the improved multiplex ligase detection reaction (iMLDR) method. Associations between OAS1 polymorphisms (rs2240190, rs1131454, 10,774,671 and 11,066,453) and TB risk were established based on distributions of allelic frequencies using different genetic models. RESULTS: Significant association was observed between rs10774671, rs1131454 and TB. In the initial study, the G allele of rs10774671 was a significantly protective factor against TB (P = 0.006) and the genotype of GG differed significantly between TB patients and controls under the codominant model (P = 0.008) after Bonferroni correction. In the validation study, we also observed that the rs10774671 G allele (P = 0.001) and GG genotype (P = 0.001) were associated with TB. In addition, we found that the rs1131454 G allele (P = 0.004) and GG genotype (P = 0.001) were protective against TB in the Chinese Han population. CONCLUSIONS: We report novel associations of polymorphisms in OAS1 with TB in the Chinese Tibetan and Han populations. Similar studies in different populations and functional studies are warranted to confirm our results.


Dolutegravir plus lamivudine for hiv treatment: Does the historical genotype really matter?


title: Construction and immunogenicity analysis of Lactobacillus plantarum expressing a porcine epidemic diarrhea virus S gene fused to a DC-targeting peptide

text: Abstract Porcine epidemic diarrhea virus (PEDV) is one of the most important causative pathogens of swine diarrhea, which is widely prevalent throughout the world and is responsible for significant economic losses in the commercial pig industry, both domestic and abroad. The spike (S) protein in the PEDV capsid structure can carry the major B lymphocyte epitope, which induces production of neutralizing antibodies and provides immunoprotective effects. Moreover, the conserved region encoded by the S gene can be considered a target for establishing a new diagnostic method and is a new candidate for vaccine design. In this study, use of anchorin pgsA' allowed the fusion protein of S-DCpep to express on the surface of recombinant Lactobacillus plantarum (NC8-pSIP409-pgsA'-S-DCpep) NC8 strain. Mice were immunized by lavage administration of the recombinant NC8-pSIP409-pgsA'-S-DCpep, which was observed to induce DC activation and high production of sIgA and IgG antibodies in experimental animals, while also eliciting production of significantly more IgA+B220+ B cells. More importantly, secretion of cytokines IFN-γ, IL-4 and IL-17 in mice that were vaccinated with NC8-pSIP409-pgsA'-S-DCpep was remarkably increased. The results of our study suggest that NC8-pSIP409-pgsA'-S-DCpep potently triggers cellular and humoral immune responses. The obtained experimental results can provide a theoretical basis that lays the foundation for production of a novel oral vaccine against PED.


title: Identification of pathogens and virulence profile of Rhodococcus equi and Escherichia coli strains obtained from sand of parks

text: The identification of pathogens of viral (Rotavirus, Coronavirus), parasitic (Toxocara spp.) and bacterial (Escherichia coli, Salmonella spp., Rhodococcus equi) origin shed in feces, and the virulence profile of R. equi and E. coli isolates were investigated in 200 samples of sand obtained from 40 parks, located in central region of state of Sao Paulo, Brazil, using different diagnostic methods. From 200 samples analyzed, 23 (11.5%) strains of R. equi were isolated. None of the R. equi isolates showed a virulent (vapA gene) or intermediately virulent (vapB gene) profiles. Sixty-three (31.5%) strains of E. coli were identified. The following genes encoding virulence factors were identified in E. coli: eae, bfp, saa, iucD, papGI, sfa and hly. Phylogenetic classification showed that 63 E. coli isolates belonged to groups B1 (52.4%), A (25.4%) and B2 (22.2%). No E. coli serotype O157:H7 was identified. Eggs of Toxocara sp. were found in three parks and genetic material of bovine Coronavirus was identified in one sample of one park. No Salmonella spp. and Rotavirus isolates were identified in the samples of sand. The presence of R. equi, Toxocara sp, bovine Coronavirus and virulent E. coli isolates in the environment of parks indicates that the sanitary conditions of the sand should be improved in order to reduce the risks of fecal transmission of pathogens of zoonotic potential to humans in these places.


title: Progress and Prospects on Vaccine Development against SARS-CoV-2

text: In December 2019, the outbreak of pneumonia caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a serious pandemic in China and other countries worldwide. So far, more than 460,000 confirmed cases were diagnosed in nearly 190 countries, causing globally over 20,000 deaths. Currently, the epidemic is still spreading and there is no effective means to prevent the infection. Vaccines are proved to be the most effective and economical means to prevent and control infectious diseases. Several countries, companies, and institutions announced their programs and progress on vaccine development against the virus. While most of the vaccines are under design and preparation, there are some that have entered efficacy evaluation in animals and initial clinical trials. This review mainly focused on the progress and our prospects on field of vaccine development against SARS-CoV-2.


title: Parasite zoonoses and wildlife: One health, spillover and human activity

text: Abstract This review examines parasite zoonoses and wildlife in the context of the One Health triad that encompasses humans, domestic animals, wildlife and the changing ecosystems in which they live. Human (anthropogenic) activities influence the flow of all parasite infections within the One Health triad and the nature and impact of resulting spillover events are examined. Examples of spillover from wildlife to humans and/or domestic animals, and vice versa, are discussed, as well as emerging issues, particularly the need for parasite surveillance of wildlife populations. Emphasis is given to Trypanosoma cruzi and related species in Australian wildlife, Trichinella, Echinococcus, Giardia, Baylisascaris, Toxoplasma and Leishmania.


title: Bat Rabies in France: A 24-Year Retrospective Epidemiological Study

text: Since bat rabies surveillance was first implemented in France in 1989, 48 autochthonous rabies cases without human contamination have been reported using routine diagnosis methods. In this retrospective study, data on bats submitted for rabies testing were analysed in order to better understand the epidemiology of EBLV-1 in bats in France and to investigate some epidemiological trends. Of the 3176 bats submitted for rabies diagnosis from 1989 to 2013, 1.96% (48/2447 analysed) were diagnosed positive. Among the twelve recognised virus species within the Lyssavirus genus, two species were isolated in France. 47 positive bats were morphologically identified as Eptesicus serotinus and were shown to be infected by both the EBLV-1a and the EBLV-1b lineages. Isolation of BBLV in Myotis nattereri was reported once in the north-east of France in 2012. The phylogenetic characterisation of all 47 French EBLV-1 isolates sampled between 1989 and 2013 and the French BBLV sample against 21 referenced partial nucleoprotein sequences confirmed the low genetic diversity of EBLV-1 despite its extensive geographical range. Statistical analysis performed on the serotine bat data collected from 1989 to 2013 showed seasonal variation of rabies occurrence with a significantly higher proportion of positive samples detected during the autumn compared to the spring and the summer period (34% of positive bats detected in autumn, 15% in summer, 13% in spring and 12% in winter). In this study, we have provided the details of the geographical distribution of EBLV-1a in the south-west of France and the north-south division of EBLV-1b with its subdivisions into three phylogenetic groups: group B1 in the north-west, group B2 in the centre and group B3 in the north-east of France.


title: Quantitative analysis of human blood serum using vibrational spectroscopy

text: Abstract Analysis of bodily fluids using vibrational spectroscopy has attracted increasing attention in recent years. In particular, infrared spectroscopic screening of blood products, particularly blood serum, for disease diagnostics has been advanced considerably, attracting commercial interests. However, analyses requiring quantification of endogenous constituents or exogenous agents in blood are less well advanced. Recent advances towards this end are reviewed, focussing on infrared and Raman spectroscopic analyses of human blood serum. The importance of spectroscopic analysis in the native aqueous environment is highlighted, and the relative merits of infrared absorption versus Raman spectroscopy are considered, in this context. It is argued that Raman spectroscopic analysis is more suitable to quantitative analysis in liquid samples, and superior performance for quantification of high and low molecular weight components, is demonstrated. Applications for quantitation of viral loads, and therapeutic drug monitoring are also discussed.


title: SARS-CoV-2 Risk Management in Clinical Psychiatry: A Few Considerations on How to Deal With an Unrivaled Threat

text: The pandemic spread of the corona virus SARS-CoV-2 has even-handedly shattered national and international health systems and economies almost in an instant. As numbers of infections and COVID-19–related deaths rise from day to day, fears and uncertainties on how to deal with this unknown threat are extremely present both for individuals and societies as a whole. In this manuscript, we aim to exemplarily describe the bullet points concerning (a) the internal risk management, (b) the organizational and structural changes, and (c) the communicational strategies applied in a Psychiatric University Hospital in the Southern part of Germany. The authors are well aware about the fact that almost none of these considerations may be considered as evidence-based at the moment. However, the authors trust that these reflections and experiences may be useful as an orientation for similar risk constellations in other afflicted countries due to the temporal delay of the pandemic course.


title: Application of three duplex real-time PCR assays for simultaneous detection of human seasonal and avian influenza viruses

text: This study was performed to develop real-time PCR (qPCR) for detection of human seasonal and avian influenza viruses in duplex format. First duplex qPCR detects haemagglutinin (HA) gene of influenza virus A(H1N1)pdm09 and HA gene of influenza virus A(H3N2), the second reaction detects neuraminidase (NA) gene of influenza virus A(H3N2) and NA gene of influenza virus A(H1N1)pdm09 and A(H5N1), and the third reaction detects HA gene of influenza A(H5N1) and nonstructural protein gene of influenza B virus. Primers and probes were designed using multiple alignments of target gene sequences of different reference strains. Assays were optimised for identical thermocycling conditions. Their specificity was confirmed by conventional PCR and monoplex qPCR with nucleic acids isolated from different influenza viruses and other respiratory pathogens. Plasmid constructs with a fragment of specific gene were used to assess sensitivity of the assay. The limit of detection ranged from 27 to 96 cDNA copies/reaction. Clinical specimens (n = 107) have been tested using new assays, immunofluorescence and monoplex qRT-PCR. It has been shown that developed assays have been capable of rapid and accurate simultaneous detection and differentiation of influenza viruses. They are more sensitive than immunofluorescence and at least as sensitive as monoplex qRT-PCR.


title: Characterization of heparin and severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) spike glycoprotein binding interactions

text: Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has resulted in a pandemic and continues to spread around the globe at an unprecedented rate. To date, no effective therapeutic is available to fight its associated disease, COVID-19. Our discovery of a novel insertion of glycosaminoglycan (GAG)-binding motif at S1/S2 proteolytic cleavage site (681–686 (PRRARS)) and two other GAG-binding-like motifs within SARS-CoV-2 spike glycoprotein (SGP) led us to hypothesize that host cell surface GAGs may interact SARS-CoV-2 SGPs to facilitate host cell entry. Using a surface plasmon resonance direct binding assay, we found that both monomeric and trimeric SARS-CoV-2 SGP bind more tightly to immobilized heparin (K(D) = 40 pM and 73 pM, respectively) than the SARS-CoV and MERS-CoV SGPs (500 nM and 1 nM, respectively). In competitive binding studies, the IC(50) of heparin, tri-sulfated non-anticoagulant heparan sulfate, and non-anticoagulant low molecular weight heparin against SARS-CoV-2 SGP binding to immobilized heparin were 0.056 μM, 0.12 μM, and 26.4 μM, respectively. Finally, unbiased computational ligand docking indicates that heparan sulfate interacts with the GAG-binding motif at the S1/S2 site on each monomer interface in the trimeric SARS-CoV-2 SGP, and at another site (453–459 (YRLFRKS)) when the receptor-binding domain is in an open conformation. The current study serves a foundation to further investigate biological roles of GAGs in SARS-CoV-2 pathogenesis. Furthermore, our findings may provide additional basis for further heparin-based interventions for COVID-19 patients exhibiting thrombotic complications.


“Please doctor, could you tell him that I love him?”: letter from plastic surgeons at the COVID-19 warfront


Managing neonates with respiratory failure due to SARS-CoV-2 – Authors' reply


title: Hypoxia induced up-regulation of tissue factor is mediated through extracellular RNA activated Toll-like receptor 3-activated protein 1 signalling

text: Sterile Inflammation (SI), a condition where damage associated molecular patterns (DAMPs) released from dying cells, leads to TLR (Toll-like receptor) activation and triggers hypoxemia in circulation leading to venous thrombosis (VT) through tissue factor (TF) activation, but its importance under acute hypoxia (AH) remains unexplored. Thus, we hypothesized that eRNA released from dying cells under AH activates TF via the TLR3-ERK1/2-AP1 pathway, leading to VT. Animals were exposed to stimulate hypoxia for 0–24 h at standard temperature and humidity. RNaseA and DNase1 were injected immediately before exposure. TLR3 gene silencing was performed through in vivo injection of TLR3 siRNA. 80 μg/kg BW of isolated eRNA and eDNA were injected 6 h prior to sacrifice. Antigens of TF pathway were determined by ELISA and TF activity by a chromogenic assay. AH exposure significantly induced release of SI markers i.e. eRNA, eDNA, HMGB1 and upregulated TLR3, ERK1/2 (Extracellular signal-regulated kinases), AP1 (Activator Protein-1) and TF, whereas RNaseA pre-treatment diminished the effect of AH, thus inhibiting TF expression as well as activity during AH. Hence, we propose a possible mechanism of AH-induced TF activation and thrombosis where RNaseA can become the novel focal point in ameliorating therapy for AH induced thrombosis.


title: High-Resolution Analysis of Coronavirus Gene Expression by RNA Sequencing and Ribosome Profiling

text: Members of the family Coronaviridae have the largest genomes of all RNA viruses, typically in the region of 30 kilobases. Several coronaviruses, such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and Middle East respiratory syndrome-related coronavirus (MERS-CoV), are of medical importance, with high mortality rates and, in the case of SARS-CoV, significant pandemic potential. Other coronaviruses, such as Porcine epidemic diarrhea virus and Avian coronavirus, are important livestock pathogens. Ribosome profiling is a technique which exploits the capacity of the translating ribosome to protect around 30 nucleotides of mRNA from ribonuclease digestion. Ribosome-protected mRNA fragments are purified, subjected to deep sequencing and mapped back to the transcriptome to give a global “snap-shot” of translation. Parallel RNA sequencing allows normalization by transcript abundance. Here we apply ribosome profiling to cells infected with Murine coronavirus, mouse hepatitis virus, strain A59 (MHV-A59), a model coronavirus in the same genus as SARS-CoV and MERS-CoV. The data obtained allowed us to study the kinetics of virus transcription and translation with exquisite precision. We studied the timecourse of positive and negative-sense genomic and subgenomic viral RNA production and the relative translation efficiencies of the different virus ORFs. Virus mRNAs were not found to be translated more efficiently than host mRNAs; rather, virus translation dominates host translation at later time points due to high levels of virus transcripts. Triplet phasing of the profiling data allowed precise determination of translated reading frames and revealed several translated short open reading frames upstream of, or embedded within, known virus protein-coding regions. Ribosome pause sites were identified in the virus replicase polyprotein pp1a ORF and investigated experimentally. Contrary to expectations, ribosomes were not found to pause at the ribosomal frameshift site. To our knowledge this is the first application of ribosome profiling to an RNA virus.


title: Children with multiple viral respiratory infections are older than those with single viruses

text: AIM: To study the clinical impact of multiple viral respiratory infections compared to single infections. METHODS: Demographic data from 37 multiple infection periods in children <5 years of age were compared to data from 193 episodes with single infections. Clinical data derived from patient records of the multiple infection episodes were further compared to data from 93 matched control episodes with single infections. RESULTS: The mean age of patients with multiple viral findings was 12.7 months, compared to 5.7 months for those with single findings (p < 0.01). Wheezing was the most common diagnosis in both groups, except among children who were only infected with the coronavirus. No differences were found regarding duration of hospitalisation, oxygen treatment or admittance to the intensive care unit. CONCLUSION: Children with multiple viral findings in their respiratory secretions were older than those with a single detected virus. Otherwise, no major differences in comorbidity, presentation or clinical outcome were observed between the two groups.


title: Development of real-time PCR assays for detection and quantification of human bocavirus

text: Abstract Background Human bocavirus (HBoV) is a parvovirus that has been recently detected in patients with respiratory illness. Objectives We developed a sensitive, specific, and quantitative real-time PCR assay based on the TaqMan method for HBoV detection and quantification in respiratory specimens. Study design Three individual real-time PCR assays were designed to amplify HBoV NS1, NP-1, and VP1 genes. For clinical evaluation, 506 nasal aspirates obtained from patients with acute respiratory tract infections during December 2006 to May 2007 were tested. Results Each assay had a broad dynamic range (50×107 to 5×107 copies of plasmid DNA) and high inter- and intra-assay reproducibility. The detection limit of each assay was 10 genome copies per reaction, and no crossreactivity with other major respiratory viruses or bacteria was detected. Clinical evaluation revealed that 11 (2.1%) of 506 patients diagnosed with upper respiratory tract infections, pneumonia, bronchitis, pharyngitis, or sinusitis had HBoV detected by all three assays, with viral loads ranging from 8.2×104 to 8.1×109 copies/ml of specimen. Conclusions The three assays for HBoV diagnosis and quantification are highly sensitive, specific real-time tools for the reliable epidemiological and pathogenetic study of HBoV infection.


title: Hospital preparedness for COVID-19 pandemic: experience from department of medicine at Veterans Affairs Connecticut Healthcare System

text: The 2019–2020 pandemic Coronavirus Disease 2019 (COVID-19) has inundated hospital systems globally, as they prepare to accommodate surge of patients requiring advanced levels of care. Pandemic preparedness has not been this urgently and widely needed in the last several decades. According to epidemiologic predictions, the peak of this pandemic has still not been reached, and hospitals everywhere need to ensure readiness to care for more patients than they usually do, and safety for healthcare workers who strive to save lives. We share our hospital-wide rapid preparedness and response to COVID-19 to help provide information to other healthcare systems globally.


title: Chronic liver disease: current concepts of disease mechanisms

text: Optimal management of chronic liver disease requires an understanding of aetiological factors or conditions initiating and sustaining tissue damage. Injury may derive initially from toxin or xenobiotic exposure (direct, biotransformation adducts, hypersensitivity responses or immune‐mediated mechanisms), infectious organisms, inborn errors of metabolism, or pathological accumulations of transition metals (iron or copper), endotoxins or membranocytolytic bile acids. Secondarily, cells and mediators associated with inflammation, pathological expression of major histocompatibility foci on hepatocytes and biliary epithelia, aberrant initiation of apoptosis, modification of the extracellular matrix, and depletion of natural antioxidants can each play pivotal roles. Cholestatic liver injury derived from extrahepatic mechanical obstruction or intrahepatic cholestasis (many causes) can induce membrane damage subsequent to accumulation of membranocytolytic bile acids, copper retention, and membrane peroxidation. This paper reviews contemporary issues of chronic hepatocellular injury and hepatic fibrosis with the aim of broadening the clinical perspective of treatment strategies.


title: High-resolution CT for identify patients with smear-positive, active pulmonary tuberculosis

text: Abstract Purpose This study evaluates the use of high-resolution computed tomography (HRCT) to differentiate smear-positive, active pulmonary tuberculosis (PTB) from other pulmonary infections in the emergency room (ER) setting. Methods One hundred and eighty-three patients diagnosed with pulmonary infections in an ER were divided into an acid fast bacillus (AFB) smear-positive, active PTB group (G1=84) and a non-AFB smear-positive, pulmonary infection group (G2=99). HRCT images from a 64-Multidetector CT were analyzed, retrospectively, for the morphology, number, and segmental distribution of pulmonary lesions. Results Utilizing multivariate analysis, five variables were found to be independent risk factors predictive of G1: (1) consolidation involving the apex segment of right upper lobe, posterior segment of the right upper lobe, or apico-posterior segment of the left upper lobe; (2) consolidation involving the superior segment of the right or left lower lobe; (3) presence of a cavitary lesion; (4) presence of clusters of nodules; (5) absence of centrilobular nodules. A G1 prediction score was generated based on these 5 criteria to help differentiate G1 from G2. The area under the receiver operating characteristic (ROC) curve was 0.96±0.012 in our prediction model. With an ideal cut-off point score of 3, the specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) are 90.9%, 96.4%, 90.0% and 96.8%, respectively. Conclusion The use of this AFB smear-positive, active PTB prediction model based on 5 key HRCT findings may help ER physicians determine whether or not isolation is required while awaiting serial sputum smear results in high risk patients.


title: Emerging Viruses in the Felidae: Shifting Paradigms

text: The domestic cat is afflicted with multiple viruses that serve as powerful models for human disease including cancers, SARS and HIV/AIDS. Cat viruses that cause these diseases have been studied for decades revealing detailed insight concerning transmission, virulence, origins and pathogenesis. Here we review recent genetic advances that have questioned traditional wisdom regarding the origins of virulent Feline infectious peritonitis (FIP) diseases, the pathogenic potential of Feline Immunodeficiency Virus (FIV) in wild non-domestic Felidae species, and the restriction of Feline Leukemia Virus (FeLV) mediated immune impairment to domestic cats rather than other Felidae species. The most recent interpretations indicate important new evolutionary conclusions implicating these deadly infectious agents in domestic and non-domestic felids.


title: Inhibition of enterovirus 71 replication and viral 3C protease by quercetin

text: BACKGROUND: Enterovirus 71 (EV71) is one of the major causative agents of hand, foot, and mouth disease (HFMD), which is sometimes associated with severe central nervous system disease in children. There is currently no specific medication for EV71 infection. Quercetin, one of the most widely distributed flavonoids in plants, has been demonstrated to inhibit various viral infections. However, investigation of the anti-EV71 mechanism has not been reported to date. METHODS: The anti-EV71 activity of quercetin was evaluated by phenotype screening, determining the cytopathic effect (CPE) and EV71-induced cells apoptosis. The effects on EV71 replication were evaluated further by determining virus yield, viral RNA synthesis and protein expression, respectively. The mechanism of action against EV71 was determined from the effective stage and time-of-addition assays. The possible inhibitory functions of quercetin via viral 2Apro, 3C(pro) or 3D(pol) were tested. The interaction between EV71 3C(pro) and quercetin was predicted and calculated by molecular docking. RESULTS: Quercetin inhibited EV71-mediated cytopathogenic effects, reduced EV71 progeny yields, and prevented EV71-induced apoptosis with low cytotoxicity. Investigation of the underlying mechanism of action revealed that quercetin exhibited a preventive effect against EV71 infection and inhibited viral adsorption. Moreover, quercetin mediated its powerful therapeutic effects primarily by blocking the early post-attachment stage of viral infection. Further experiments demonstrated that quercetin potently inhibited the activity of the EV71 protease, 3C(pro), blocking viral replication, but not the activity of the protease, 2A(pro), or the RNA polymerase, 3D(pol). Modeling of the molecular binding of the 3C(pro)-quercetin complex revealed that quercetin was predicted to insert into the substrate-binding pocket of EV71 3C(pro), blocking substrate recognition and thereby inhibiting EV71 3C(pro) activity. CONCLUSIONS: Quercetin can effectively prevent EV71-induced cell injury with low toxicity to host cells. Quercetin may act in more than one way to deter viral infection, exhibiting some preventive and a powerful therapeutic effect against EV71. Further, quercetin potently inhibits EV71 3C(pro) activity, thereby blocking EV71 replication.