title: Broad neutralizing human monoclonal antibodies against influenza virus from vaccinated healthy donors

text: Abstract Human monoclonal antibodies (HuMAbs) prepared from patients with viral infections could provide information on human epitopes important for the development of vaccines as well as potential therapeutic applications. Through the fusion of peripheral blood mononuclear cells from a total of five influenza-vaccinated volunteers, with newly developed murine–human chimera fusion partner cells, named SPYMEG, we obtained 10 hybridoma clones stably producing anti-influenza virus antibodies: one for influenza A H1N1, four for influenza A H3N2 and five for influenza B. Surprisingly, most of the HuMAbs showed broad reactivity within subtype and four (two for H3N2 and two for B) showed broad neutralizing ability. Importantly, epitope mapping revealed that the two broad neutralizing antibodies to H3N2 derived from different donors recognized the same epitope located underneath the receptor-binding site of the hemagglutinin globular region that is highly conserved among H3N2 strains.


title: Urban planning of the endoplasmic reticulum (ER): How diverse mechanisms segregate the many functions of the ER

text: Abstract The endoplasmic reticulum (ER) is the biggest organelle in most cell types, but its characterization as an organelle with a continuous membrane belies the fact that the ER is actually an assembly of several, distinct membrane domains that execute diverse functions. Almost 20years ago, an essay by Sitia and Meldolesi first listed what was known at the time about domain formation within the ER. In the time that has passed since, additional ER domains have been discovered and characterized. These include the mitochondria-associated membrane (MAM), the ER quality control compartment (ERQC), where ER-associated degradation (ERAD) occurs, and the plasma membrane-associated membrane (PAM). Insight has been gained into the separation of nuclear envelope proteins from the remainder of the ER. Research has also shown that the biogenesis of peroxisomes and lipid droplets occurs on specialized membranes of the ER. Several studies have shown the existence of specific marker proteins found on all these domains and how they are targeted there. Moreover, a first set of cytosolic ER-associated sorting proteins, including phosphofurin acidic cluster sorting protein 2 (PACS-2) and Rab32 have been identified. Intra-ER targeting mechanisms appear to be superimposed onto ER retention mechanisms and rely on transmembrane and cytosolic sequences. The crucial roles of ER domain formation for cell physiology are highlighted with the specific targeting of the tumor metastasis regulator gp78 to ERAD-mediating membranes or of the promyelocytic leukemia protein to the MAM.


title: A SARS-CoV protein, ORF-6, induces caspase-3 mediated, ER stress and JNK-dependent apoptosis

text: Abstract Severe acute respiratory syndrome (SARS) coronavirus (CoV) spread from China to more than 30 countries, causing severe outbreaks of atypical pneumonia and over 800 deaths worldwide. CoV primarily infects the upper respiratory and gastrointestinal tract; however, SARS-CoV has a unique pathogenesis because it infects both the upper and lower respiratory tracts and leads to human respiratory diseases. SARS-CoV genome has shown containing 14 open reading frames (ORFs) and 8 of them encode novel proteins. Previous reports show that overexpression of ORF-3a, ORF-3b and ORF-7a induce apoptosis. In this report, we demonstrate that overexpression of ORF-6 also induces apoptosis and that Caspase-3 inhibitor and JNK inhibitor block ORF-6 induced apoptosis. Importantly, the protein level of ER chaperon protein, GRP94, was up-regulated when ORF-6 was overexpressed. All these data suggest that ORF-6 induces apoptosis via Caspase-3 mediated, ER stress and JNK-dependent pathways.


title: Stevens-Johnson Syndrome complicated by obstructive uropathy, pneumothorax, and pneumomediastinum: a case report and literature review

text: BACKGROUND: Stevens-Johnson Syndrome (SJS) is an acute mucocutaneous eruption with blisters of the skin and haemorrhagic erosions of mucous membranes. This report describes air-leak syndrome and obstructive uropathy occurring simultaneously in a teenage patient affected by SJS. CASE PRESENTATION: A 17-year-old Malay female with SJS suffered from bilateral pneumothoraces, pneumomediastinum, and obstructive uropathy as early complications of her disease. She required intubation, chest tube insertion, and bilateral ureteric stenting as part of her intensive care management. These extra-cutaneous complications of renal and pulmonary systems were likely secondary to widespread epithelial detachment. CONCLUSION: Despite paucity of cases in adult literature, post-renal causes for acute kidney injury must be considered in SJS, especially in the setting of gross haematuria. Bedside point-of-care ultrasonography may be a useful tool for excluding obstructive uropathy. Pneumothorax is a rare but documented complication of SJS in paediatric cases and, to a lesser extent, adult patients. Extra care should be exercised when caring for mechanically ventilated patients suffering from SJS.


title: Pneumonia aguda fibrinosa e organizante

text: Resumo O padrão histológico de Pneumonia Aguda Fibrinosa e Organizante (AFOP – Acute Fibrinous And Organizing Pneumonia), descrito por Beasley em 2002, caracteriza-se pela existência de fibrina intra-alveolar sob a forma de bolas de fibrina e pneumonia organizativa difusa. A apresentação clínica desta doença intersticial pulmonar pode ser aguda ou subaguda, diferindo no entanto dos outros padrões histológicos habitualmente associados a lesão pulmonar aguda – Lesão Alveolar Difusa (DAD), Pneumonia Organizativa (OP) e Pneumonia Eosinofílica (EP). A propósito deste tema, os autores fazem uma revisão da literatura e descrevem o caso clínico de um doente de 44 anos, com aspectos imagiológicos e evolução pouco habituais. Abstract The histologic pattern of Acute Fibrinous and Organizing Pneumonia (AFOP), described by Beasley in 2002, is characterized by the existence of intra alveolar fibrin in the form of fibrin “balls” and diffuse organizing pneumonia. Presenting symptoms of this interstitial pulmonary disease can be acute or subacute. However, it differs from the well-recognized histologic patterns of acute pulmonary lesion – Diffuse Alveolar Damage (DAD), Organizing Pneumonia (OP) and Eosinophilic Pneumonia (EP). The authors carry out a review of the literature concerning this topic and describe the clinical case of a 44-year-old patient with unusual imaging features and outcome.


Management of ICU nursing teams during the COVID-19 pandemic


COAGULACIÓN INTRAVASCULAR DISEMINADA COMO FORMA DE PRESENTACIÓN DE LA ENFERMEDAD POR CORONAVIRUS-19. CASO CLÍNICO


title: PA-X-associated early alleviation of the acute lung injury contributes to the attenuation of a highly pathogenic H5N1 avian influenza virus in mice

text: PA-X is a novel discovered accessory protein encoded by the PA mRNA. Our previous study demonstrated that PA-X decreases the virulence of a highly pathogenic H5N1 strain A/Chicken/Jiangsu/k0402/2010 in mice. However, the underlying mechanism of virulence attenuation associated with PA-X is still unknown. In this study, we compared two PA-X-deficient mutant viruses and the parental virus in terms of induction of pathology and manipulation of host response in the mouse lung, stimulation of cell death and PA nuclear accumulation. We first found that down-regulated PA-X expression markedly aggravated the acute lung injury of the infected mice early on day 1 post-infection (p.i.). We then determined that loss of PA-X expression induced higher levels of cytokines, chemokines and complement-derived peptides (C3a and C5a) in the lung, especially at early time point’s p.i. In addition, in vitro assays showed that the PA-X-deficient viruses enhanced cell death and increased expression of reactive oxygen species (ROS) in mammalian cells. Moreover, we also found that PA nuclear accumulation of the PA-X-null viruses accelerated in MDCK cells. These results demonstrate that PA-X decreases the level of complement components, ROS, cell death and inflammatory response, which may together contribute to the alleviated lung injury and the attenuation of the virulence of H5N1 virus in mice.


title: TMPRSS2: A potential target for treatment of influenza virus and coronavirus infections

text: Abstract Influenza virus and coronavirus epidemics or pandemics have occurred in succession worldwide throughout the early 21st century. These epidemics or pandemics pose a major threat to human health. Here, we outline a critical role of the host cell protease TMPRSS2 in influenza virus and coronavirus infections and highlight an antiviral therapeutic strategy targeting TMPRSS2.


title: The impacts of COVID-19 measures on global environment and fertility rate: double coincidence

text: The study aims to examine the effects of coronavirus disease-2019 (COVID-19) measures on global environment and fertility rate by using the data of 1980 to 2019. The results show that communicable diseases including COVID-19 measures decrease carbon emissions and increase the chances of fertility rates in an account of city-wide lockdown. The knowledge spillover substantially decreases carbon emissions, while high energy demand increases carbon emissions. Poverty incidence increases fertility rate in the short-run; however, in the long-run, the result only supported with vulnerable employment and food prices that lead to increase fertility rates worldwide. The study concludes that besides some high negative externalities associated with COVID-19 pandemic in the form of increasing death tolls and rising healthcare costs, the global world should have to know how to direct high mass carbon emissions and population growth through acceptance of preventive measures, which would be helpful to contain coronavirus pandemic at a global scale. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11869-020-00865-z) contains supplementary material, which is available to authorized users.


title: Avian influenza (H5N1): implications for intensive care

text: BACKGROUND: As influenza A/H5N1 spreads around the globe the risk of an epidemic increases. DISCUSSION: Review of the cases of influenza A/H5N1 reported to date demonstrates that it causes a severe illness, with a high proportion of patients (63%) requiring advanced organ support. Of these approx. 68% develop multiorgan failure, at least 54% develop acute respiratory distress syndrome, and 90% die. Disease progression is rapid, with a median time from presentation to hospital to requirement for advanced organ support of only 2 days. CONCLUSION: The infectious nature, severity and clinical manifestations of the disease and its potential for pandemic spread have considerable implications for intensive care in terms of infection control, patient management, staff morale and intensive care expansion.


title: Validity of the Common Cold Questionnaire (CCQ) in Asthma Exacerbations

text: BACKGROUND: The common cold questionnaire (CCQ) is used to discriminate those with and without a viral infection. Its usefulness in people with acute asthma is unknown. Our aim was to assess the ability of the CCQ to detect viral infection and to monitor recovery during a viral induced asthma exacerbation and confirmed by virological testing. METHODOLOGY/PRINCIPAL FINDINGS: We studied subjects (≥7 yrs) admitted to hospital with acute asthma and diagnosed as positive (n = 63), or negative to viral infection (n = 27) according to molecular and virological testing from respiratory samples. CCQ, asthma history and asthma control questionnaires were completed and repeated 4–6 weeks later. Sensitivity, specificity, and response to change of the CCQ were assessed by receiver operator curve (ROC) analysis and effect size calculation respectively. The CCQ did not discriminate between viral and non-viral infection for subjects with asthma (sensitivity = 76.2%; specificity = 29.6%). ROC analysis could not differentiate between positive or negative virus in subjects with asthma. The CCQ had a large response to change following recovery (effect size = 1.01). 39% of subjects recovering from viral exacerbation remained positive to virological testing at follow-up despite improvement in clinical symptoms. The CCQ reflected clinical improvement in these subjects, thus providing additional information to complement virological testing. CONCLUSIONS/SIGNIFICANCE: The CCQ is a useful instrument for monitoring response to viral infection in people with asthma. Reliable differentiation between viral and non-viral asthma exacerbations was not achieved with the CCQ and requires specific virological testing. When combined with virological testing, the CCQ should be a useful outcome measure for evaluating therapies in viral-induced asthma.


title: Chapter 21 Use of Host Factors in Microbial Forensics

text: Publisher Summary This chapter illustrates central elements of the host response in a simplified fashion and describes a few representative examples that have a high potential of providing evidence. It may aid an investigation to distinguish a perpetrator from a victim who has been exposed to a particular microorganism or by-product, such as a toxin. Considerable advances have been made in the forensic analysis of microbes and toxins. These advances include sequencing, genomics, and microscopy. An underdeveloped and underutilized area in microbial forensics is how the host interacts with microorganisms in a way that provides unique signatures for forensic use. For investigative and forensic purposes, an immediate goal is to distinguish a potential victim and innocent person from a perpetrator and to distinguish between a naturally acquired or intentional infection. Two principal methods that are sufficiently developed are characterization of the humoral immune response and identification of vaccine-induced immunity or antibiotics that may be present in a possible perpetrator. The primary aims of a microbial forensics investigation are to identify the biological agent, its source, and the individuals responsible for the event. Analytic approaches differ when the suspected biothreat agent is encountered in a container or the environment, as opposed to in vivoin a human, animal, or plant. Analyses of trace elements, pollens, growth media, latent fingerprints, and microbial and nonmicrobial nucleic acids are all applicable to the container and environmental sample.


Double-edged sword: Granulocyte colony stimulating factors in cancer patients during the COVID-19 era


title: In vivo growth of porcine reproductive and respiratory syndrome virus engineered nsp2 deletion mutants

text: Abstract Prior studies on PRRSV strain VR-2332 non-structural protein 2 (nsp2) had shown that as much as 403 amino acids could be removed from the hypervariable region without losing virus viability in vitro. We utilized selected nsp2 deletion mutants to examine in vivo growth. Young swine (4 pigs/group; 5 control swine) were inoculated intramuscularly with one of 4 nsp2 deletion mutants (rΔ727–813, rΔ543–726, rΔ324–523, rΔ324–726) or full-length recombinant virus (rVR-2332). Serum samples were collected on various days post-inoculation and analyzed by HerdChek* ELISA, PRRSV real time RT-PCR, gamma interferon (IFN-γ) ELISA, and nucleotide sequence analysis of the entire nsp2 coding region. Tracheobronchial lymph node weight compared to body weight was recorded for each animal and used as a clinical measurement of viral pathogenesis. Results showed that all deletion mutants grew less robustly than full-length recombinant virus, yet all but the large deletion virus (rΔ324–726) recovered to parental viral RNA levels by study end. Swine receiving the rΔ727–813 mutants had a significant decrease in lymph node enlargement compared to rVR-2332. While swine infection with rVR-2332 caused a rapid rise in serum IFN-γ levels, the IFN-γ protein produced by infection with 3 of the 4 deletion mutant viruses was significantly reduced, perhaps due to differences in viral growth kinetics. The rΔ543–726 nsp2 mutant virus, although growth impaired, mimicked rVR-2332 in inducing a host serum IFN-γ response but exhibited a 2-week delay. Targeted sequencing showed that all deletions were stable in the region coding for nsp2 after one swine passage. The data suggested that the selected nsp2 deletion mutants were growth attenuated in swine, altered the induction of serum IFN-γ, an innate cytokine of unknown function in PRRSV clearance, and pointed to a domain that may influence tracheobronchial lymph node size.


State of the art: coronaviruses


title: Silencing of SARS-CoV spike gene by small interfering RNA in HEK 293T cells

text: Abstract Two candidate small interfering RNAs (siRNAs) corresponding to severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike gene were designed and in vitro transcribed to explore the possibility of silencing SARS-CoV S gene. The plasmid pEGFP-optS, which contains the codon-optimized SARS-CoV S gene and expresses spike-EGFP fusion protein (S-EGFP) as silencing target and expressing reporter, was transfected with siRNAs into HEK 293T cells. At various time points of posttransfection, the levels of S-EGFP expression and amounts of spike mRNA transcript were detected by fluorescence microscopy, flow cytometry, Western blot, and real-time quantitative PCR, respectively. The results showed that the cells transfected with pEGFP-optS expressed S-EGFP fusion protein at a higher level compared with those transfected with pEGFP-S, which contains wildtype SARS-CoV spike gene sequence. The green fluorescence, mean fluorescence intensity, and SARS-CoV S RNA transcripts were found significantly reduced, and the expression of SARS-CoV S glycoprotein was strongly inhibited in those cells co-transfected with either EGFP- or S-specific siRNAs. Our findings demonstrated that the S-specific siRNAs used in this study were able to specifically and effectively inhibit SARS-CoV S glycoprotein expression in cultured cells through blocking the accumulation of S mRNA, which may provide an approach for studies on the functions of SARS-CoV S gene and development of novel prophylactic or therapeutic agents for SARS-CoV.


title: Engineering the PRRS virus genome: Updates and perspectives

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is endemic in most pig producing countries worldwide and causes enormous economic losses to the pork industry. Infectious clones for PRRSV have been constructed, and so far at least 14 different infectious clones are available representing both genotypes I and II. Two strategies have been taken for progeny reconstitution: RNA transfection and DNA transfection. Mutations, insertions, deletions, and replacements of the viral genome have been employed to study the structure function relationship, foreign gene expression, functional complementation, and virulence determinants. Essential regions and non-essential regions for viral replication have been identified in both the coding regions and non-encoding regions. Foreign sequences have successfully been inserted into the nsp2 and N regions and in the space between ORF1b and ORF2a. Chimeras between member viruses in the family Arteriviridae have also been constructed and utilized to study cell tropism and functional complementation. This review discusses the advances and utilization of PRRSV reverse genetics and its potential for future research.


title: Death and contagious infectious diseases: Impact of the COVID-19 virus on stock market returns

text: Abstract This study investigates whether contagious infectious diseases affect stock market outcomes. As a natural experiment, we use panel data regression analysis to measure the effect of the COVID-19 virus, which is a contagious infectious disease, on the Chinese stock market. The findings indicate that both the daily growth in total confirmed cases and in total cases of death caused by COVID-19 have significant negative effects on stock returns across all companies.


title: From the Trenches: Inpatient Management of COVID-19 in Pregnancy

text: ABSTRACT The novel coronavirus disease 2019 caused by the severe acute respiratory syndrome coronavirus 2 has become a pandemic. It has quickly swept across the globe leaving many clinicians to care for infected patients with limited information about the disease and best practices for care. Our goal is to share our experiences of caring for pregnant and postpartum women with novel coronavirus disease 2019 (COVID-19) in New York, the COVID-19 epicenter in the United States and review current guidelines. We offer a guide, focusing on inpatient management, including testing policies, admission criteria, medical management, care for the decompensating patient, as well as practical tips for inpatient antepartum service management.


title: Epidemiological evidence on Balkan nephropathy as a viral disease

text: Abstract Balkan nephropathy is a chronic kidney disease of a completely unknown etiology. Most epidemilogists believe that the disease has been caused by viruses, though all attempts to prove such a relationship have been fruitless. A common feature of most of the clues offered for elucidating the role of the viruses, is that they interfere with the epidemiological evidence on BN. Therefore, a hypothesis is put forward that the disease has been caused by slow viruses transmitted by rodents which contaminate food and articles in the house. Such an explanation fits most of the existing epidemiological data.


title: Structure-Based Design of Prefusion-Stabilized Filovirus Glycoprotein Trimers

text: Ebola virus causes severe hemorrhagic fever, often leading to death in humans. The trimeric fusion glycoprotein (GP) is the sole target for neutralizing antibodies and is the major focus of vaccine development. Soluble GP ectodomains are unstable and mostly monomeric when not fused to a heterologous trimerization domain. Here, we report structure-based designs of Ebola and Marburg GP trimers based on a stabilizing mutation in the hinge loop in refolding region 1 and substitution of a partially buried charge at the interface of the GP1 and GP2 subunits. The combined substitutions (T577P and K588F) substantially increased trimer expression for Ebola GP proteins. We determined the crystal structure of stabilized GP from the Makona Zaire ebolavirus strain without a trimerization domain or complexed ligand. The structure reveals that the stabilized GP adopts the same trimeric prefusion conformation, provides insight into triggering of GP conformational changes, and should inform future filovirus vaccine development.


title: Vitamin E and Selenium Levels are Within Normal Range in Pigs Diagnosed with Mulberry Heart Disease and Evidence for Viral Involvement in the Syndrome is Lacking

text: Mulberry heart disease (MHD) in pigs is characterized by lesions of acute haemorrhagic myocarditis and myocardial necrosis. The objectives of this study were to determine the levels of vitamin E and selenium and 13 other trace minerals in heart and liver tissues and to determine the prevalence of certain viral infections in heart tissues from MHD‐affected and MHD‐unaffected pigs and the vitamin E and selenium concentration in feed samples from selected farms with MHD. Based on the pathological examination, 114 pigs were separated into MHD lesion‐negative (L‐NEG) (n = 57) and MHD lesion‐positive (L‐POS) (n = 57) groups. Seventy‐three samples (40 L‐NEG and 33 L‐POS) were subjected to chemical analysis, and 66 (32 L‐NEG and 34 L‐POS) were subjected to PCR detection for viral pathogens. Lower (P < 0.05) levels of myocardial copper, lower (P < 0.05) levels of hepatic magnesium and higher (P < 0.05) levels of myocardial and hepatic sodium were detected in the L‐POS cases. Although lower (P < 0.05) levels of hepatic selenium were detected in L‐POS group, all were within the normal range. Analysis of feed samples (n = 22) revealed that selenium levels in all the samples were above the legal limit (0.3 ppm) for pigs. Vitamin E levels in all feed samples were above 20 IU/kg. Among the 66 pigs subjected to PCR detection, there were 19, 4, 13, 8, 2 and 1 animals positive for porcine circovirus type 2, porcine reproductive and respiratory syndrome virus, pan‐herpes virus, porcine enterovirus, pan‐pestivirus and porcine parvovirus, respectively. Clear evidence of viral association with L‐POS was lacking.


title: GTPase-activating protein-binding protein 1 (G3BP1) plays an antiviral role against porcine epidemic diarrhea virus

text: Abstract Porcine epidemic diarrhoea virus (PEDV) is a single-stranded, positive-sense RNA virus that belongs to the Coronaviridae. PEDV causes severe diarrhoea and dehydration in nursing piglets, which leads to significant economic losses to the swine industry worldwide. Stress granules (SGs) are sites of mRNA storage that are formed under various stress conditions including viral infections. Increasing evidence suggests that SGs function in antiviral innate immunity of host cells to limit virus replication. Ras-GTPase-activating protein (SH3 domain) binding protein 1 (G3BP1) is a key stress granule-resident protein that nucleates stress granule assembly. Depletion of G3BP1 inhibits SGs formation and overexpression of G3BP1 nucleates SGs assembly. We observed that knockdown of G3BP1 by silencing RNA significantly increased PEDV replication. Overexpression of exogenous G3BP1, on the other hand, lowered virus replication by 100-fold compared to vector control. An increase in the levels of mRNAs of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) was also observed in PEDV-infected G3BP1 depleted cells compared to PEDV-infected control cells. Taken together, our results suggest that G3BP1 plays an antiviral role and impairs PEDV replication.


title: A Human Lung Xenograft Mouse Model of Nipah Virus Infection

text: Nipah virus (NiV) is a member of the genus Henipavirus (family Paramyxoviridae) that causes severe and often lethal respiratory illness and encephalitis in humans with high mortality rates (up to 92%). NiV can cause Acute Lung Injury (ALI) in humans, and human-to-human transmission has been observed in recent outbreaks of NiV. While the exact route of transmission to humans is not known, we have previously shown that NiV can efficiently infect human respiratory epithelial cells. The molecular mechanisms of NiV-associated ALI in the human respiratory tract are unknown. Thus, there is an urgent need for models of henipavirus infection of the human respiratory tract to study the pathogenesis and understand the host responses. Here, we describe a novel human lung xenograft model in mice to study the pathogenesis of NiV. Following transplantation, human fetal lung xenografts rapidly graft and develop mature structures of adult lungs including cartilage, vascular vessels, ciliated pseudostratified columnar epithelium, and primitive “air” spaces filled with mucus and lined by cuboidal to flat epithelium. Following infection, NiV grows to high titers (10(7) TCID(50)/gram lung tissue) as early as 3 days post infection (pi). NiV targets both the endothelium as well as respiratory epithelium in the human lung tissues, and results in syncytia formation. NiV infection in the human lung results in the production of several cytokines and chemokines including IL-6, IP-10, eotaxin, G-CSF and GM-CSF on days 5 and 7 pi. In conclusion, this study demonstrates that NiV can replicate to high titers in a novel in vivo model of the human respiratory tract, resulting in a robust inflammatory response, which is known to be associated with ALI. This model will facilitate progress in the fundamental understanding of henipavirus pathogenesis and virus-host interactions; it will also provide biologically relevant models for other respiratory viruses.


title: The Modern Autopsy: What to Do if Infection Is Suspected

text: Deaths due to infectious diseases are common worldwide. The autopsy, although less frequently performed than previously, is important to our understanding of disease pathogenesis. The autopsy also provides critical information regarding potential disease outbreaks. To optimize the benefits of an autopsy, the pathologist should approach the autopsy with a well-constructed differential diagnosis that provides the framework for appropriate selection of diagnostic specimens and tests. Standard microbiologic cultures, although necessary and important, are often insufficient and must be supplemented by newer molecular methodologies.


title: The Molecular Biology of Frog Virus 3 and other Iridoviruses Infecting Cold-Blooded Vertebrates

text: Frog virus 3 (FV3) is the best characterized member of the family Iridoviridae. FV3 study has provided insights into the replication of other family members, and has served as a model of viral transcription, genome replication, and virus-mediated host-shutoff. Although the broad outlines of FV3 replication have been elucidated, the precise roles of most viral proteins remain unknown. Current studies using knock down (KD) mediated by antisense morpholino oligonucleotides (asMO) and small, interfering RNAs (siRNA), knock out (KO) following replacement of the targeted gene with a selectable marker by homologous recombination, ectopic viral gene expression, and recombinant viral proteins have enabled researchers to systematically ascertain replicative- and virulence-related gene functions. In addition, the application of molecular tools to ecological studies is providing novel ways for field biologists to identify potential pathogens, quantify infections, and trace the evolution of ecologically important viral species. In this review, we summarize current studies using not only FV3, but also other iridoviruses infecting ectotherms. As described below, general principles ascertained using FV3 served as a model for the family, and studies utilizing other ranaviruses and megalocytiviruses have confirmed and extended our understanding of iridovirus replication. Collectively, these and future efforts will elucidate molecular events in viral replication, intrinsic and extrinsic factors that contribute to disease outbreaks, and the role of the host immune system in protection from disease.


Clinical course of asthma in 4 cases of COVID-19 infection


title: Evaluation of inflammation and immunity in cats with spontaneous parvovirus infection: Consequences of recombinant feline interferon-ω administration

text: Abstract Administration of recombinant feline interferon-ω (rFeIFN) has been proposed for the prophylaxis of canine and feline parvovirosis. In the present study, the influence of the administration of rFeIFN on blood markers of inflammation (α-globulins, α1-acid glycoprotein) and immune system activation (γ-globulins, IgG, IgM, specific anti-feline parvovirus IgG or IgM) was evaluated in a cattery developing an outbreak of feline panleukopenia due to feline parvovirus (FPV) infection few days after initial administration of rFeIFN. Kittens (n =23) were injected with rFeIFN (1MU/kg subcutaneoulsy, once a day for 3 days) and their blood parameters were compared with those of 17 untreated cats. Cats that survived the outbreak were vaccinated and re-sampled 1 month after the last rFeIFN administration. Time of emergence of clinical signs and survival rate were not significantly different between the two groups. Controls and treated cats surviving the infection had high levels of γ-globulins, total- and anti-FPV specific IgGs, likely due to passive transfer of maternal immunity. Compared to controls, treated kittens had lower levels of α1-globulins and higher mean values of γ-globulins and immunoglobulins. Data from samples collected after vaccination revealed a higher level of γ-globulins, total- and anti-FPV specific IgGs in treated kittens, compared with controls, suggesting that rFeIFN stimulates antibody production. Based on this results, rFeIFN should be administered to the queen, to increase passive maternal immunity, or to kittens before introduction in a potentially contaminated environment.


title: An evaluation of potential reference genes for stability of expression in two salmonid cell lines after infection with either Piscirickettsia salmonis or IPNV

text: BACKGROUND: Due to the limited number of species specific antibodies against fish proteins, differential gene expression analyses are vital for the study of host immune responses. Quantitative real-time reverse transcription PCR (qRT-PCR) is one of the most powerful tools for this purpose. Nevertheless, the accuracy of the method will depend on the careful selection of genes whose expression are stable and can be used as internal controls for a particular experimental setting. FINDINGS: The expression stability of five commonly used housekeeping genes [beta-actin (ACTB), elongation factor 1-alpha (EF1A), ubiquitin (UBQ), glyceraldehyd-3-phosphate dehydrogenase (GAPDH) and tubulin alpha (TUBA)] were monitored in salmonid cell lines CHSE-214 and RTS11 after infection with two of the most fastidious fish pathogens, the facultative bacterium Piscirickettsia salmonis and the aquabirnavirus IPNV (Infectious Pancreatic Necrosis Virus). After geNorm analysis, UBQ and EF1A appeared as the most stable, although EF1A was slightly upregulated at late stages of P. salmonis infection in RTS11. ACTB instead, showed a good performance in each case, being always considered within the three most stable genes of the panel. In contrast, infection-dependent differential regulation of GAPDH and TUBA was also demonstrated. CONCLUSION: Based on the data presented here with the cell culture models CHSE-214 and RTS11, we suggest the initial choice of UBQ, ACTB and EF1A as reference genes in qRT-PCR assays for studying the effect of P. salmonis and IPNV on the host immune response.


title: 1-Year Pulmonary Function and Health Status in Survivors of Severe Acute Respiratory Syndrome

text: Study objectives To characterize the long-term pulmonary function and health status in a prospectively identified cohort of patients who survived the severe acute respiratory syndrome (SARS). Design Prospective follow-up cohort study. Setting University-affiliated hospital. Patients Ninety-four patients who recovered from SARS were assessed at a uniform time point of 1 year after hospital discharge. Measurements The study included the measurement of static and dynamic lung volumes, the determination of the diffusing capacity of the lung for carbon monoxide (Dlco), and a health status evaluation using the St. George Respiratory Questionnaire (SGRQ). Results Eleven patients (12%) had mild impairment of FVC, 20 (21%) had mild impairment of FEV1, 5 (5%) had mild impairment of the FEV1/FVC ratio, and 17 (18%) had mild impairment of the Dlco. There was one patient (1%) who had moderate impairment of FVC, one patient (1%) who had moderate impairment of the FEV1/FVC ratio, and three patients (3%) who had moderate impairment of the Dlco. No pulmonary function abnormalities were detected in 59 patients (63%). Mean scores were significantly higher (ie, worse) than the population norms in the activity (p < 0.001), impacts (p < 0.001), and total (p < 0.001) domains of the SGRQ. Conclusions One year after recovery from SARS, persistent pulmonary function impairment was found in about one third of patients. The health status of SARS survivors was also significantly worse compared with the healthy population. The main determinants of morbidity in recovered SARS patients need to be further defined.


title: Evaluation of the in-field efficacy of oregano essential oil administration on the control of neonatal diarrhea syndrome in calves

text: Abstract The objective of this study was to evaluate under field conditions, whether daily administration of oregano essential oil is effective in preventing and/or diminishing the severity of neonatal diarrhea syndrome in calves aged less than 15days. Ninety-one newborn calves from three dairy farms were assigned into two groups; “Eco” group (n=46) calves were drenched with Greek oregano (Origanum vulgare ssp. Hirtum) essential oil (ECODIAR® liquid 5%) at the dose of 12.5mg/kg body weight once per day until the age of 10days. “Conts” group (n=45) calves were left untreated and served as controls. All animals were monitored daily for the incidence of diarrhea until the age of 15days and their fecal score was recorded. Fecal samples were collected on days 3, 6 and 10 for microbiological and parasitological evaluation. Average fecal score throughout the experiment, incidence of diarrhea, duration and severity of diarrhea episodes were significantly lower in Eco group compared to the controls. Daily administration of oregano essential oil in calves for the first 10days of their life effectively diminishes the severity of naturally acquired diarrhea under field conditions and, under certain hygiene practices, possess a preventive effect against neonatal diarrhea syndrome.


title: Scenarios for the logistics services industry: A Delphi-based analysis for 2025

text: Abstract The logistics services industry will be significantly affected by future developments throughout the world. Therefore, developing future scenarios is an important basis for long-term strategy development. Nevertheless, research exposes that there is a lack of awareness among logistics researchers and practitioners about future scenarios. In this paper, we apply scenario planning and present the findings of an extensive Delphi-based scenario study on the future of the logistics services industry in the year 2025. The major contribution of our research is the development of probable and unforeseen scenarios of the future which may provide a valuable basis for strategy development in the logistics services industry.


title: Development and validation of IMMUNO-COV™: a high-throughput clinical assay for detecting antibodies that neutralize SARS-CoV-2

text: We here describe the development and validation of IMMUNO-COV™, a high-throughput clinical test to quantitatively measure SARS-CoV-2-neutralizing antibodies, the specific subset of anti-SARS-CoV-2 antibodies that block viral infection. The test measures the capacity of serum or purified antibodies to neutralize a recombinant Vesicular Stomatitis Virus (VSV) encoding the SARS-CoV-2 spike glycoprotein. This recombinant virus (VSV-SARS-CoV-2-S-Δ19CT) induces fusion in Vero cell monolayers, which is detected as luciferase signal using a dual split protein (DSP) reporter system. VSV-SARS-CoV-2-S-Δ19CT infection was blocked by monoclonal α-SARS-CoV-2-spike antibodies and by plasma or serum from SARS-CoV-2 convalescing individuals. The assay exhibited 100% specificity in validation tests, and across all tests zero false positives were detected. In blinded analyses of 230 serum samples, only two unexpected results were observed based on available clinical data. We observed a perfect correlation between results from our assay and 80 samples that were also assayed using a commercially available ELISA. To quantify the magnitude of the anti-viral response, we generated a calibration curve by adding stepped concentrations of α-SARS-CoV-2-spike monoclonal antibody to pooled SARS-CoV-2 seronegative serum. Using the calibration curve and a single optimal 1:100 serum test dilution, we reliably measured neutralizing antibody levels in each test sample. Virus neutralization units (VNUs) calculated from the assay correlated closely (p < 0.0001) with PRNTEC50 values determined by plaque reduction neutralization test against a clinical isolate of SARS-CoV-2. Taken together, these results demonstrate that the IMMUNO-COV™ assay accurately quantitates SARS-CoV-2 neutralizing antibodies in human sera and therefore is a potentially valuable addition to the currently available serological tests. The assay can provide vital information for comparing immune responses to the various SARS-CoV-2 vaccines that are currently in development, or for evaluating donor eligibility in convalescent plasma therapy studies.


title: Considerations on BVD eradication for the Irish livestock industry

text: Animal Health Ireland has produced clear guidelines for the control of Bovine Viral Diarrhoea (BVD) infection in Irish cattle herds. In the course of developing these guidelines it was clear that a framework for regional and/or national BVD control would be required to increase the uptake of BVD control at farm level and reduce the overall prevalence of the disease. This paper assessed the economic impact of BVD, epidemiological aspects of the disease to its control, models of BVD control, international experiences of BVD control programmes. The technical knowledge and test technology exists to eradicate BVD. Indeed, many countries have successfully and others are embarking on control of the disease. The identification and prompt elimination of PI cattle will form the basis of any control programme. The trade of such animals must be curtailed. Pregnant and potentially pregnant carrying PI foetuses pose a significant threat. International experience indicates systematic, well coordinated programmes have the most success, while voluntary programmes can make good initial progress but ultimately fail. The farming community must buy into any proposed programme, and without their support, failure is likely. To buy into the programme and create such a demand for BVD control, farmers must first be well informed. It is likely that stemming economic loss and improving productivity will be the primary motivator at individual farm level.


title: Probable primary polydipsia in a domestic shorthair cat

text: CASE SUMMARY: A 10-month-old neutered male domestic shorthair cat presented with a 4 month history of polyuria and polydipsia. After a thorough diagnostic work-up the only abnormal findings were hyposthenuria and an elevated random plasma osmolality level. Trial therapy with the oral and ophthalmic forms of desmopressin failed to concentrate urine. A modified water deprivation test confirmed the ability to concentrate urine above a urine specific gravity (USG) of 1.035. After transitioning the cat to a higher sodium diet and instituting several enrichment changes to the cat’s environment, average water consumption and urine output levels decreased to almost normal levels and USG increased from 1.006 to 1.022. These findings provide strong evidence that primary polydipsia was the underlying etiology of the cat’s condition. RELEVANCE AND NOVEL INFORMATION: This case report exemplifies the challenges faced when a cat presents for polyuria and polydipsia without an obvious cause identified on routine diagnostics. To our knowledge, this is the first report of primary polydipsia in a cat.


title: Infertility remains a top stressor despite the COVID-19 pandemic

text: Research Question: What is the psychological impact of the COVID-19 pandemic on infertility patients? Design: An anonymous cross-sectional online survey was sent to patients who attended a large university-affiliated infertility practice, in the United States, between January 1(st) 2019 and April 1(st) 2020. Respondents were asked to note their top three stressors, from a list of ten commonly reported life stressors at three different time points. Results: The questionnaire was sent to 10,481 patients with 3,604 responses (response rate 34%) received. We included 2,202 non-pregnant, female respondents in the final analysis. One third of respondents had a prior diagnosis of an anxiety disorder and 11% reported taking anxiolytic medications; over one quarter had a prior diagnosis of a depressive disorder and 11% reported taking anti-depressant medications. At all three time points, infertility was noted to be the most frequent top stressor. Coronavirus was noted to be the third most common stressor amongst the respondents in early March but, currently, is similar to that of infertility (63% and 66% respectively). 6% of patients stated that infertility treatment, including IVF, should not be offered during the COVID-19 pandemic. Conclusion: Despite the unprecedented global pandemic of COVID-19, causing economic and societal uncertainty, the stress of infertility remains significant and is comparable a stressor to the pandemic itself.


title: EML webinar overview: Simulation-assisted discovery of membrane targeting nanomedicine

text: The COVID-19 pandemic has brought infectious diseases again to the forefront of global public health concerns. In this EML webinar (Gao, 2020), we discuss some recent work on simulation-assisted discovery of membrane targeting nanomedicine to counter increasing antimicrobial resistance and potential application of similar ideas to the current pandemic. A recent report led by the world health organization (WHO) warned that 10 million people worldwide could die of bacterial infections each year by 2050. To avert the crisis, membrane targeting antibiotics are drawing increasing attention due to their intrinsic advantage of low resistance development. In collaboration with a number of experimental groups, we show examples of simulation-assisted discovery of molecular agents capable of selectively penetrating and aggregating in bacterial lipid membranes, causing membrane permeability/rupture. Through systematic all-atom molecular dynamics simulations and free energy analysis, we demonstrate that the membrane activity of the molecular agents correlates with their ability to enter, perturb and permeabilize the lipid bilayers. Further study on different cell membranes demonstrates that the selectivity results from the presence of cholesterol in mammalian but not in bacterial membranes, as the cholesterol can condense the hydrophobic region of membrane, preventing the penetration of the molecular agents. Following the molecular penetration, we establish a continuum theory and derive the energetic driving force for the domain aggregation and pore growth on lipid membrane. We show that the energy barrier to membrane pore formation can be significantly lowered through molecular aggregation on a large domain with intrinsic curvature and a sharp interface. The theory is consistent with experimental observations and validated with coarse-grained molecular dynamics simulations of molecular domain aggregation leading to pore formation in a lipid membrane. The mechanistic modelling and simulation provide some fundamental principles on how molecular antimicrobials interact with bacterial membranes and damage them through domain aggregation and pore formation. For treating viral infections and cancer therapy, we discuss potential size- and lipid-type-based selectivity principles for developing membrane active nanomedicine. These studies suggest a general simulation-assisted platform to accelerate discovery and innovation in nanomedicine against infectious diseases. EML Webinar speakers are updated at https://imechanica.org/node/24132


title: Uitgelicht

text: In de geschiedschrijving over pandemieën is altijd veel aandacht voor artsen. Maar verpleegkundigen spelen ook hun rol. Het Florence Nightingale Instituut verzamelt ervaringen van verpleegkundigen in de Covid-19 Verhalenbank op www.fni.nl. Om latere generaties te laten zien wat verpleegkundigen betekenen tijdens een virale crisis, en wat hen bezighoudt. Ervaringen met morele stress mogen niet ontbreken - wanneer kon je niet de zorg geven zoals je wilde? En daarnaast melige groepsfoto’s en filmpjes die ik zag op social media, want in tijden van crisis is samen lachen belangrijk dan ooit.


title: Nosocomial transmission of SARS

text: Severe acute respiratory syndrome is a newly emerged infectious disease with moderately high transmissibility. Nosocomial outbreaks were responsible for the propagation of the epidemic worldwide. Health care workers (HCW) are at particular high risk because of their close contact with patients, involvement in medical procedures, and handling of excreta/fomites. Good hospital organization and appropriate infection control strategies are essential to prevent/interrupt disease transmission from patients to HCWs (and vice versa) and among inpatients and HCWs themselves. Education and training should target broadly to all HCWs.


title: Parallel molecular evolution and adaptation in viruses

text: Parallel molecular evolution is the independent evolution of the same genotype or phenotype from distinct ancestors. The simple genomes and rapid evolution of many viruses mean they are useful model systems for studying parallel evolution by natural selection. Parallel adaptation occurs in the context of several viral behaviours, including cross-species transmission, drug resistance, and host immune escape, and its existence suggests that at least some aspects of virus evolution and emergence are repeatable and predictable. We introduce examples of virus parallel evolution and summarise key concepts. We outline the difficulties in detecting parallel adaptation using virus genomes, with a particular focus on phylogenetic and structural approaches, and we discuss future approaches that may improve our understanding of the phenomenon.


title: Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong

text: Summary Background Health authorities worldwide, especially in the Asia Pacific region, are seeking effective public-health interventions in the continuing epidemic of severe acute respiratory syndrome (SARS). We assessed the epidemiology of SARS in Hong Kong. Methods We included 1425 cases reported up to April 28, 2003. An integrated database was constructed from several sources containing information on epidemiological, demographic, and clinical variables. We estimated the key epidemiological distributions: infection to onset, onset to admission, admission to death, and admission to discharge. We measured associations between the estimated case fatality rate and patients’age and the time from onset to admission. Findings After the initial phase of exponential growth, the rate of confirmed cases fell to less than 20 per day by April 28. Public-health interventions included encouragement to report to hospital rapidly after the onset of clinical symptoms, contact tracing for confirmed and suspected cases, and quarantining, monitoring, and restricting the travel of contacts. The mean incubation period of the disease is estimated to be 6.4 days (95% Cl 5.2–7.7). The mean time from onset of clinical symptoms to admission to hospital varied between 3 and 5 days, with longer times earlier in the epidemic. The estimated case fatality rate was 13.2% (9.8–16.8) for patients younger than 60 years and 43.3% (35.2–52.4) for patients aged 60 years or older assuming a parametric γ distribution. A non-parametric method yielded estimates of 6.8% (4.0–9.6) and 55.0% (45.3–64.7), respectively. Case clusters have played an important part in the course of the epidemic. Interpretation Patients’age was strongly associated with outcome. The time between onset of symptoms and admission to hospital did not alter outcome, but shorter intervals will be important to the wider population by restricting the infectious period before patients are placed in quarantine. Published online May 7, 2003 http://image.thelancet.com/extras/03art4453web.pdf


title: A review of feline infectious peritonitis virus: molecular biology, immunopathogenesis, clinical aspects, and vaccination

text: Abstract Feline infectious peritontis (FIP) has been an elusive and frustrating problem for veterinary practitioners and cat breeders for many years. Over the last several years, reports have begun to elucidate aspects of the molecular biology of the causal virus (FIPV). These papers complement a rapidly growing base of knowledge concerning the molecular organization and replication of coronaviruses in general. The fascinating immunopathogenesis of FIPV infection and the virus' interaction with macrophages has also been the subject of several recent papers. It is now clear that FIPV may be of interest to scientists other than veterinary virologists since its pathogenesis may provide a useful model system for other viruses whose infectivity is enhanced in the presence of virus-specific antibody. With these advances and the recent release of the first commercially-available FIPV vaccine, it is appropriate to review what is known about the organization and replication of coronaviruses and the pathogenesis of FIPV infection.


title: Identification of amino acids in highly pathogenic avian influenza H5N1 virus hemagglutinin that determine avian influenza species specificity

text: To test the role of neutralizing antibodies (nAbs) and receptor adaptation in interspecies transmission of influenza virus, two H5N1 strains, isolated from human and avian hosts, with four amino acid differences in hemagglutinin (HA) and seven HA mutations were studied. We found that a mutation at amino acid position 90 in the H5N1 HA, outside the receptor-binding domain (RBD), could simultaneously induce changes in the RBD conformation to escape from nAb binding and alter the receptor preference through long-range regulation. This mutation was deemed a “key event” for interspecies transmission. It is likely a result of positive selection caused by antibodies, allowing the original invasion by new species-specific variants. A mutation at amino acid position 160 in the RBD only induced a change in receptor preference. This mutation was deemed a “maintaining adaptation”, which ensured that influenza virus variants would be able to infect new organisms of a different species successfully. The mutation is the result of adaptation caused by the receptor. Our results suggest that continuing occurrence of these two types of mutations made the variants persist in the new host species. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-011-1056-2) contains supplementary material, which is available to authorized users.


title: Viruses causing gastroenteritis

text: Acute gastroenteritis is one of the most common diseases in humans worldwide. Viruses are recognized as important causes of this disease, particularly in children. Since the Norwalk virus was identified as a cause of gastroenteritis, the number of viral agents associated with diarrheal disease in humans has steadily increased. Rotavirus is the most common cause of severe diarrhea in children under 5 years of age. Astrovirus, calicivirus and enteric adenovirus are also important etiologic agents of acute gastroenteritis. Other viruses, such as toroviruses, coronaviruses, picobirnaviruses and pestiviruses, are increasingly being identified as causative agents of diarrhea. In recent years, the availability of diagnostic tests, mainly immunoassays or molecular biology techniques, has increased our understanding of this group of viruses. The future development of a safe and highly effective vaccine against rotavirus could prevent, at least, cases of severe diarrhea and reduce mortality from this disease.


title: Prime-O-glucosylcimifugin attenuates lipopolysaccharide-induced acute lung injury in mice

text: Abstract Prime-O-glucosylcimifugin is an active chromone isolated from Saposhnikovia root which has been reported to have various activities, such as anti-convulsant, anticancer, anti-inflammatory properties. The purpose of this study was to evaluate the effect of prime-O-glucosylcimifugin on acute lung injury (ALI) induced by lipopolysaccharide in mice. BALB/c mice received intraperitoneal injection of Prime-O-glucosylcimifugin 1h before intranasal instillation (i.n.) of lipopolysaccharide (LPS). Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and interleukin (IL)-6 in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Pulmonary histological changes were evaluated by hematoxylin–eosin, myeloperoxidase (MPO) activity in the lung tissue and lung wet/dry weight ratios were observed. Furthermore, the mitogen-activated protein kinases (MAPK) signaling pathway activation and the phosphorylation of IκBα protein were determined by Western blot analysis. Prime-O-glucosylcimifugin showed promising anti-inflammatory effect by inhibiting the activation of MAPK and NF-κB signaling pathway.


title: Brief review of the chicken Major Histocompatibility Complex: the genes, their distribution on chromosome 16, and their contributions to disease resistance

text: Nearly all genes presently mapped to chicken chromosome 16 (GGA 16) have either a demonstrated role in immune responses or are considered to serve in immunity by reason of sequence homology with immune system genes defined in other species. The genes are best described in regional units. Among these, the best known is the polymorphic major histocompatibility complex-B (MHC-B) region containing genes for classical peptide antigen presentation. Nearby MHC-B is a small region containing two CD1 genes, which encode molecules known to bind lipid antigens and which will likely be found in chickens to present lipids to specialized T cells, as occurs with CD1 molecules in other species. Another region is the MHC-Y region, separated from MHC-B by an intervening region of tandem repeats. Like MHC-B, MHC-Y is polymorphic. It contains specialized class I and class II genes and c-type lectin-like genes. Yet another region, separated from MHC-Y by the single nucleolar organizing region (NOR) in the chicken genome, contains olfactory receptor genes and scavenger receptor genes, which are also thought to contribute to immunity. The structure, distribution, linkages and patterns of polymorphism in these regions, suggest GGA 16 evolves as a microchromosome devoted to immune defense. Many GGA 16 genes are polymorphic and polygenic. At the moment most disease associations are at the haplotype level. Roles of individual MHC genes in disease resistance are documented in only a very few instances. Provided suitable experimental stocks persist, the availability of increasingly detailed maps of GGA 16 genes combined with new means for detecting genetic variability will lead to investigations defining the contributions of individual loci and more applications for immunogenetics in breeding healthy poultry.


How to prepare the operating room for COVID-19 patients


title: Influenza is more common than Middle East Respiratory Syndrome Coronavirus (MERS-CoV) among hospitalized adult Saudi patients

text: Abstract Background Since the initial description of Middle East Respiratory Syndrome Coronavirus (MERS-CoV), we adopted a systematic process of screening patients admitted with community acquired pneumonia. Here, we report the result of the surveillance activity in a general hospital in Saudi Arabia over a four year period. Materials and methods All admitted patients with community acquired pneumonia from 2012 to 2016 were tested for MERS-CoV. In addition, testing for influenza viruses was carried out starting April 2015. Results During the study period, a total of 2657 patients were screened for MERS-CoV and only 20 (0.74%) tested positive. From January 2015 to December 2016, a total of 1644 patients were tested for both MERS-CoV and influenza. None of the patients tested positive for MERS-CoV and 271 (16.4%) were positive for influenza. The detected influenza viruses were Influenza A (107, 6.5%), pandemic 2009 H1N1 (n = 120, 7.3%), and Influenza B (n = 44, 2.7%). Pandemic H1N1 was the most common influenza in 2015 with a peak in peaked October to December and influenza A other than H1N1 was more common in 2016 with a peak in August and then October to December. Conclusions MERS-CoV was a rare cause of community acquired pneumonia and other viral causes including influenza were much more common. Thus, admitted patients are potentially manageable with Oseltamivir or Zanamivir therapy.


title: Clinical course of coronavirus disease 2019 in 11 patients after thoracic surgery and challenges in diagnosis

text: OBJECTIVES: To illustrate the clinical course and difficulties in early diagnosis of coronavirus disease 2019 (COVID-19) in patients after thoracic surgery. METHODS: We retrospectively analyzed the clinical course of the first 11 patients diagnosed with COVID-19 after thoracic surgery in early January 2020. Postoperative clinical, laboratory, and radiologic records and the time line of clinical course were summarized. Potential prognostic factors were evaluated. RESULTS: In the 11 confirmed cases (3 female, 8 male), median days from symptom onset to case detection was 8. Insidious symptom onset and misinterpreted postoperative changes on chest computed tomography (CT) resulted in delay in diagnosis. There were 3 fatalities due to respiratory failure, whereas 4 severe and 4 mild cases recovered and were discharged. All patients had once experienced leukocytosis and eosinopenia. Remittent fever and resected lung segments ≥5 were associated with fatality. CONCLUSIONS: The case fatality rate of postsurgical patients subsequently diagnosed with COVID-19 was 27.3%. Insidious symptom onset, postoperative leukocytosis with lymphopenia, and postsurgical CT changes overshadowed the early signs of viral pneumonia. Dynamic symptom monitoring, serial chest CTs, and tests for viral RNA and serum antibody improve the chance for prompt detection of COVID-19. Consideration should be given to preadmission and preoperative screening and strict contact isolation during the postoperative period.


title: How the Hong Kong government lost the public trust in SARS: Insights for government communication in a health crisis

text: Abstract This paper analyzes the crisis mismanagement of the Hong Kong government during the SARS outbreak. It addresses eight factors that characterize a government crisis and uses them as guidelines to assess how the Hong Kong government performed in SARS.


COVID-19: Launching neurosurgery into the era of telehealth in the United States


title: Moving interdisciplinary science forward: integrating participatory modelling with mathematical modelling of zoonotic disease in Africa

text: This review outlines the benefits of using multiple approaches to improve model design and facilitate multidisciplinary research into infectious diseases, as well as showing and proposing practical examples of effective integration. It looks particularly at the benefits of using participatory research in conjunction with traditional modelling methods to potentially improve disease research, control and management. Integrated approaches can lead to more realistic mathematical models which in turn can assist with making policy decisions that reduce disease and benefit local people. The emergence, risk, spread and control of diseases are affected by many complex bio-physical, environmental and socio-economic factors. These include climate and environmental change, land-use variation, changes in population and people’s behaviour. The evidence base for this scoping review comes from the work of a consortium, with the aim of integrating modelling approaches traditionally used in epidemiological, ecological and development research. A total of five examples of the impacts of participatory research on the choice of model structure are presented. Example 1 focused on using participatory research as a tool to structure a model. Example 2 looks at identifying the most relevant parameters of the system. Example 3 concentrates on identifying the most relevant regime of the system (e.g., temporal stability or otherwise), Example 4 examines the feedbacks from mathematical models to guide participatory research and Example 5 goes beyond the so-far described two-way interplay between participatory and mathematical approaches to look at the integration of multiple methods and frameworks. This scoping review describes examples of best practice in the use of participatory methods, illustrating their potential to overcome disciplinary hurdles and promote multidisciplinary collaboration, with the aim of making models and their predictions more useful for decision-making and policy formulation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0110-4) contains supplementary material, which is available to authorized users.


title: Variant influenza A (H1N1) virus infection in Canada

text: Abstract There has been an increase in influenza A variant detections in the US in recent years. In September 2012, an Ontario resident was diagnosed with influenza A (H1N1) variant infection. The demonstrated cross reactivity with the A(H1N1)pdm09 H1 gene CDC realtime PCR suggests that laboratories that only use the pdm09 H1 gene PCR to confirm this subtype would incorrectly report this variant as a A(H1N1)pdm09 subtype unless they were doing further molecular investigations.


title: Medicina, Epidemiología y Humanismo antes y después de la COVID-19

text: Abstract The rapid propagation of SARS-CoV-2 requires the generation of evidence to help mitigate its global damage. The precise measurement with the appropriate clinical and epidemiological indicators associated with COVID-19 is a necessary step in reducing the individual and population burden of the current pandemic. These unprecedented times have raised a challenge for epidemiologists of chronic diseases and have required a practical approach “to do something to help during this disaster". The options include returning to clinical care or resorting to online textbooks and resources for accelerated courses on the research of outbreaks. However, being aware of the magnitude of individual suffering endured by so many, including many esteemed and close colleagues, becomes a personal challenge of enormous proportions. The arts and other forms of humanities can help re-establish equilibrium, both during the pandemic and especially after it.


title: Human Metapneumovirus: An Emerging Respiratory Pathogen

text: Abstract Human metapneumovirus (hMPV) is an important emerging respiratory pathogen, previously unreported in the Emergency Medicine literature. It is primarily associated with the clinical syndromes of bronchiolitis and pneumonia. hMPV may predispose to bacterial pneumonia; coinfection with respiratory syncytial virus may lead to increased severity of clinical disease, and complications include asthma and chronic obstructive pulmonary disease exacerbations. Given its high prevalence and potential clinical implications as these patients present to the Emergency Department with initial infection or subsequent complications, a better understanding of hMPV will aid in their care. We report the case of a 13-month old who developed lobar pneumonia 3 weeks after being diagnosed with hMPV. The epidemiology, clinical presentation, complications, and treatment of hMPV are then discussed.


title: A quasi-experimental study to determine the effects of a multifaceted educational intervention on hand hygiene compliance in a radiography unit

text: BACKGROUND: Whilst numerous studies have investigated nurses’ compliance with hand hygiene and use of alcohol-based hand rub (ABHR), limited attention has been paid to these issues in allied health staff. Reports have linked infections to breaches in infection control in the radiography unit (RU). With advances in medical imaging, a higher proportion of patients come into contact with RU staff increasing the need for good hand hygiene compliance. This study aimed to evaluate effectiveness on compliance of an intervention to improve awareness of hand hygiene in the RU of a district hospital. METHODS: A quasi-experimental study design including questionnaires assessing knowledge and attitudes of hand hygiene and direct observation of participants was used to evaluate an educational programme on hand hygiene of the RU of a large district hospital. All healthcare workers (HCW), comprising 76 radiographers, 17 nurses, and nine healthcare assistants (HCA), agreed to participate in the study. Of these, 85 completed the initial and 76 the post-test anonymous questionnaire. The hand hygiene compliance of all 102 HCW was observed over a 3-week period prior to and after the intervention. The 2-month intervention consisted of talks on hand hygiene and benefits of ABHR, provision of visual aids, wall-mounted ABHR dispensers, and personal bottles of ABHR. RESULTS: Before the intervention, overall hand hygiene compliance was low (28.9 %). Post-intervention, compliance with hand hygiene increased to 51.4 %. This improvement was significant for radiographers and HCA. Additionally, knowledge and attitudes improved in particular, understanding that ABHR can largely replace handwashing and there is a need to perform hand hygiene after environmental contact. The increased use of ABHR allowed HCW to feel they had enough time to perform hand hygiene. CONCLUSIONS: The educational intervention led to increased awareness of hand hygiene opportunities and better acceptance of ABHR use. The reduced time needed to perform hand rubbing and improved access to dispensers resulted in fewer missed opportunities. Although radiographers and other allied HCW make frequent contact with patients, these may be mistakenly construed as irrelevant with respect to healthcare associated infections. Stronger emphasis on hand hygiene compliance of these staff may help reduce infection risk.


Abstract This article provides a brief overview of the state of discourse, politics and provision of abortion in the Anglophone West, including developments in the wake of the COVID-19 pandemic. It then surveys three promising directions for feminist abortion scholarship. The first is work inspired by the Reproductive Justice Movement, that points to the intersectional axes of inequality that shape abortion discourse and position us in relation to reproductive choice and access issues. The second is work that examines the particularity of the constitution of the aborting body, reflecting the particularity of the pregnant body. This is a specific body, with a specific history; abortion discourse draws from and makes a significant contribution to the meaning and lived experience of this body. The third area of scholarship we highlight is that which seeks to amplify the meaning of abortion as a social good. Much abortion scholarship is attuned to a critique of negative aspects of abortion—from its representation in popular culture to restrictive law and access issues. This is critical work but/and the performative nature of abortion scholarship, like all discourse, means that it can amplify the association of negativity with abortion. The article concludes by introducing the articles contained in the special section of Women's Studies International Forum, ‘Abortion at the edges: Politics, practices, performances’.


Providing health care to patients with hearing loss during COVID‐19 and physical distancing


title: Association of chemosensory dysfunction and Covid‐19 in patients presenting with influenza‐like symptoms

text: BACKGROUND: Rapid spread of the SARS‐CoV‐2 virus and concern for viral transmission by ambulatory patients with minimal to no symptoms underline the importance of identifying early or subclinical symptoms of Covid‐19 infection. Two such candidate symptoms include anecdotally reported loss of smell and taste. Understanding the timing and association of smell/taste loss in Covid‐19 may help facilitate screening and early isolation of cases. METHODS: A single‐institution, cross‐sectional study evaluating patient‐reported symptoms with a focus on smell and taste was conducted using an internet‐based platform on adult subjects who underwent testing for Covid‐19. Logistic regression was employed to identify symptoms associated with Covid‐19 positivity. RESULTS: A total of 1480 patients with influenza‐like symptoms underwent Covid‐19 testing between March 3 through 29, 2020. Our study captured 59 of 102 (58%) Covid‐19‐positive patients and 203 of 1378 (15%) Covid‐19‐negative patients. Smell and taste loss were reported in 68% (40/59) and 71% (42/59) of Covid‐19‐positive subjects, respectively, compared to 16% (33/203) and 17% (35/203) of Covid‐19‐negative patients (p<0.001). Smell and taste impairment were independently and strongly associated with Covid‐19‐positivity (anosmia: adjusted odds ratio [aOR] 10.9, 95%CI:5.08‐23.5; ageusia: aOR 10.2 95%CI:4.74‐22.1); whereas, sore throat was associated with Covid‐19‐negativity (aOR 0.23, 95%CI:0.11‐0.50). Of patients who reported Covid‐19‐associated loss of smell, 74% (28/38) reported resolution of anosmia with clinical resolution of illness. CONCLUSIONS: In ambulatory individuals with influenza‐like symptoms, chemosensory dysfunction was strongly associated with Covid‐19 infection and should be considered when screening symptoms. Most will recover chemosensory function within weeks paralleling resolution of other disease‐related symptoms. This article is protected by copyright. All rights reserved


title: Ethics-sensitivity of the Ghana national integrated strategic response plan for pandemic influenza

text: BACKGROUND: Many commentators call for a more ethical approach to planning for influenza pandemics. In the developed world, some pandemic preparedness plans have already been examined from an ethical viewpoint. This paper assesses the attention given to ethics issues by the Ghana National Integrated Strategic Plan for Pandemic Influenza (NISPPI). METHODS: We critically analyzed the Ghana NISPPI’s sensitivity to ethics issues to determine how well it reflects ethical commitments and principles identified in our review of global pandemic preparedness literature, existing pandemic plans, and relevant ethics frameworks. RESULTS: This paper reveals that important ethical issues have not been addressed in the Ghana NISPPI. Several important ethical issues are unanticipated, unacknowledged, and unplanned for. These include guidelines on allocation of scarce resources, the duties of healthcare workers, ethics-sensitive operational guidelines/protocols, and compensation programs. The NISPPI also pays scant attention to use of vaccines and antivirals, border issues and cooperation with neighboring countries, justification for delineated actions, and outbreak simulations. Feedback and communication plans are nebulous, while leadership, coordination, and budgeting are quite detailed. With respect to presentation, the NISPPI’s text is organized around five thematic areas. While each area implicates ethical issues, NISPPI treatment of these areas consistently fails to address them. CONCLUSIONS: Our analysis reveals a lack of consideration of ethics by the NISPPI. We contend that, while the plan’s content and fundamental assumptions provide support for implementation of the delineated public health actions, its consideration of ethical issues is poor. Deficiencies include a failure to incorporate guidelines that ensure fair distribution of scarce resources and a lack of justification for delineated procedures. Until these deficiencies are recognized and addressed, Ghana runs the risk of rolling out unjust and ethically indefensible actions with real negative effects in the event of a pandemic. Soliciting inputs from the public and consultation with ethicists during the next revision of the NISPPI will be useful in addressing these issues.


title: Developments in Tissue Culture Detection of Respiratory Viruses

text: Viral culture is the historical gold standard for detection of most viruses that cause respiratory tract infections. Viral culture remains valuable because it is reasonably sensitive for most respiratory viruses, and it is cheaper and less technically demanding than nucleic acid amplified tests. The disadvantages of conventional viral culture using multiple tubes of cell lines are that it is labor intensive, moderately expensive, and slow. Advances in viral culture include the introduction of new cell lines, which can be more sensitive or convenient than previously used cell lines, and the use of shell-vial culture for respiratory viruses. Shell-vial culture is as sensitive as conventional culture for most respiratory viruses and it has a much shorter turn-around time. The shorter turn-around time increases the clinical utility of these cultures.


title: The importance of microbiological testing for establishing cause of death in 42 forensic autopsies

text: Abstract Microorganisms have always been one of the great challenges of humankind, being responsible for both high morbidity and mortality throughout history. In a forensic setting microbiological information will always be difficult to interpret due to lack of antemortem information and changes in flora postmortem. With this study we aim to review the use of microbiological procedures at our forensic institute. In a retrospective study including 42 autopsies performed at our Institute, where microbiological test had been applied, analyses were made with regard to: type of microbiological tests performed, microorganisms found, histological findings, antemortem information, C-reactive protein measurement and cause of death. Fiftyone different microorganisms were found distributed among 37 cases, bacteria being the most abundant. Nineteen of the cases were classified as having a microbiological related cause of death. C-reactive protein levels were raised in 14 cases of the 19 cases, histological findings either supported or were a decisive factor for the classification of microbiologically related cause of death in 14 cases. As a multitude of abundant microorganisms are able to cause infection under the right circumstances, all findings should be compared to anamnestic antemortem information, before conclusions are drawn. A definite list of true pathogens is nearly impossible to compile.


title: Polypyrimidine tract-binding protein influences negative strand RNA synthesis of dengue virus

text: Abstract Flavivirus non-structural protein 4A (NS4A) induces membrane rearrangements to form viral replication complex and functions as interferon antagonist. However, other non-structural roles of NS4A protein in relation to virus life-cycle are poorly defined. This study elucidated if dengue virus (DENV) NS4A protein interacts with host proteins and contributes to viral pathogenesis by screening human liver cDNA yeast-two-hybrid library. Our study identified polypyrimidine tract-binding protein (PTB) as a novel interacting partner of DENV NS4A protein. We reported for the first time that PTB influenced DENV production. Gene-silencing studies showed that PTB did not have an effect on DENV entry and DENV RNA translation. Further functional studies revealed that PTB influenced DENV production by modulating negative strand RNA synthesis. This is the first study that enlightens the interaction of DENV NS4A protein with PTB, in addition to demonstrating the novel role of PTB in relation to mosquito-borne flavivirus life-cycle.


title: Monkeypox — Enhancing public health preparedness for an emerging lethal human zoonotic epidemic threat in the wake of the smallpox post-eradication era

text: Abstract The identification of monkeypox in 3 separate patients in the United Kingdom in September raised media and political attention on an emerging public health threat. Nigeria, whose last confirmed case of monkeypox was in 1978, is currently experiencing an unusually large and outbreak of human monkeypox cases, a ‘One Human-Environmental-Animal Health’ approach is being effectively used to define and tackle the outbreak. As of 13th October 2018, there have been one hundred and sixteen confirmed cases the majority of whom are under 40 years. Over the past 20 years ten Central and West African countries have reported monkeypox cases which have risen exponentially. We review the history and evolution of monkeypox outbreaks in Africa and USA, the changing clinical presentations, and discuss possible factors underlying the increasing numbers being detected including the cessation of smallpox vaccination programs. Major knowledge gaps remain on the epidemiology, host reservoir, and emergence, transmission, pathogenesis and prevention of monkeypoz.


Steps towards COVID-19 suppression


title: Use of Revised International Health Regulations during Influenza A (H1N1) Epidemic, 2009

text: Strong international health agreements and good planning created a structure and common procedure for nations involved in detection and evaluation of the emergence of influenza A (H1N1). This report describes a timeline of events that led to the determination of the epidemic as a public health emergency of international concern, following the agreed-upon procedures of the International Health Regulations. These events illustrate the need for sound international health agreements and should be a call to action for all nations to implement these agreements to the best of their abilities.


title: Rapidly Generated Multivirus-specific Cytotoxic T Lymphocytes for the Prophylaxis and Treatment of Viral Infections

text: Severe and fatal viral infections remain common after hematopoietic stem cell transplantation. Adoptive transfer of cytotoxic T lymphocytes (CTLs) specific for Epstein–Barr virus (EBV), cytomegalovirus (CMV), and adenoviral antigens can treat infections that are impervious to conventional therapies, but broader implementation and extension to additional viruses is limited by competition between virus-derived antigens and time-consuming and laborious manufacturing procedures. We now describe a system that rapidly generates a single preparation of polyclonal (CD4(+) and CD8(+)) CTLs that is consistently specific for 15 immunodominant and subdominant antigens derived from 7 viruses (EBV, CMV, Adenovirus (Adv), BK, human herpes virus (HHV)-6, respiratory syncytial virus (RSV), and Influenza) that commonly cause post-transplant morbidity and mortality. CTLs can be rapidly produced (10 days) by a single stimulation of donor peripheral blood mononuclear cells (PBMCs) with a peptide mixture spanning the target antigens in the presence of the potent prosurvival cytokines interleukin-4 (IL4) and IL7. This approach reduces the impact of antigenic competition with a consequent increase in the antigenic repertoire and frequency of virus-specific T cells. Our approach can be readily introduced into clinical practice and should be a cost-effective alternative to common antiviral prophylactic agents for allogeneic hematopoietic stem cell transplant (HSCT) recipients.


Guillain–Barré syndrome in the COVID-19 era: another occasional cluster?


title: SAFE PRESCRIBING PRACTICES IN PREGNANCY AND LACTATION

text: Midwives and other health care providers face a dilemma when a pregnant woman develops a condition that usually is treated with a pharmacologic agent. Understanding of basic teratology associated with drugs as well as the FDA categorization of agents can assist professionals in recognizing which pharmaceuticals should be used or avoided. In addition to reviewing teratology, this article addresses the use of common drugs for the treatment of upper respiratory conditions, minor pain, gastrointestinal problems, psychiatric illnesses, and neurologic disorders. In each category, current evidence is presented pertaining to which agents should be recommended for pregnant women.


title: Systemic oxygen delivery by peritoneal perfusion of oxygen microbubbles

text: Abstract Severe hypoxemia refractory to pulmonary mechanical ventilation remains life-threatening in critically ill patients. Peritoneal ventilation has long been desired for extrapulmonary oxygenation owing to easy access of the peritoneal cavity for catheterization and the relative safety compared to an extracorporeal circuit. Unfortunately, prior attempts involving direct oxygen ventilation or aqueous perfusates of fluorocarbons or hemoglobin carriers have failed, leading many researchers to abandon the method. We attribute these prior failures to limited mass transfer of oxygen to the peritoneum and have designed an oxygen formulation that overcomes this limitation. Using phospholipid-coated oxygen microbubbles (OMBs), we demonstrate 100% survival for rats experiencing acute lung trauma to at least 2 h. In contrast, all untreated rats and rats treated with peritoneal oxygenated saline died within 30 min. For rats treated with OMBs, hemoglobin saturation and heart rate were at normal levels over the 2-h timeframe. Peritoneal oxygenation with OMBs was therefore shown to be safe and effective, and the method requires less equipment and technical expertise than initiating and maintaining an extracorporeal circuit. Further translation of peritoneal oxygenation with OMBs may provide therapy for acute respiratory distress syndrome arising from trauma, sepsis, pneumonia, aspiration, burns and other pulmonary diseases.


title: Prevalence of acute enteric viral pathogens in acquired immunodeficiency syndrome patients with diarrhea

text: Abstract Diarrhea due to enteric pathogens is an important complication of advanced human immunodeficiency virus infection. Whereas numerous bacterial and parasitic agents have been implicated, the role of pathogenic enteric viruses is less clear. Stools from 153 human immunodeficiency virus seropositive men were tested by electrophoresis, enzyme-linked immunosorbent assay, and immune electron microscopy for the presence of rotaviruses (group A and non-group A), adenoviruses, and Norwalk agent. Virus was detected in 9% of the patients with acquired immunodeficiency syndrome, 3% of the patients with acquired immunodeficiency syndromerelated complex, and none of the seropositive men without these diagnoses. Virus detection was not more likely in stool from patients with diarrhea.


title: Simultaneous Detection and Differentiation of Respiratory Syncytial Virus and Other Respiratory Viral Pathogens

text: Rapid and accurate detection of respiratory syncytial virus (RSV) provides pathogen-specific diagnosis, allows implementation of appropriate infection control measures, and improves patient management. One diagnostic challenge is that respiratory infections, which can be caused by several viral pathogens including RSV, usually present with similar signs and symptoms that are nearly indistinguishable by clinical diagnosis. We have described in the chapter a rapid, high-throughput laboratory technique that can detect a panel of common viral pathogens in one single reaction. With the combination of target-enriched multiplexing PCR amplification and Luminex suspension array identification, 12 common respiratory viruses, including RSV A and B, influenza virus A and B, parainfluenza virus 1, 2, 3, and 4, human metapneumovirus, rhinoviruses, enteroviruses, and SARS coronavirus, are detected and differentiated simultaneously within five hours.


title: Influenza-related hospitalisation and death in Australians aged 50 years and older

text: Summary Estimating the true burden of influenza is problematic because relatively few hospitalisations or deaths are specifically coded as influenza related. Statistical regression techniques using influenza and respiratory syncytial virus surveillance data were used to estimate the number of excess hospitalisations and deaths attributable to influenza. Several International Classification of Diseases 10th Revision (ICD-10) groupings were used for both hospitalisation and mortality estimates, including influenza and pneumonia, other respiratory disorders, and circulatory disorders. For Australians aged 50–64 years, the annual excess hospitalisations attributable to influenza were 33.3 (95%CI: 23.2–43.4) per 100,000 for influenza and pneumonia and 57.6 (95%CI: 32.5–82.8) per 100,000 for other respiratory disorders. For Australians aged ≥65 years, the annual excess hospitalisations attributable to influenza were 157.4 (95%CI: 108.4–206.5) per 100,000 for influenza and pneumonia and 282.0 (95%CI: 183.7–380.3) per 100,000 for other respiratory disorders. The annual excess all-cause mortality attributable to influenza was 6.4 (95%CI: 2.6–10.2) per 100,000 and 116.4 (95%CI: 71.3–161.5) per 100,000, for Australians aged 50–64 years and those aged ≥65 years, respectively. In the age-group ≥65 years, a significant association was found between influenza activity and circulatory mortality. We conclude that influenza is responsible for a substantial amount of mortality and morbidity, over and above that which is directly diagnosed as influenza in Australians aged ≥50 years.


title: A model of the ACE2 structure and function as a SARS-CoV receptor

text: Abstract The angiotensin-converting enzyme 2 (ACE2) is an important regulator of the renin–angiotensin system and was very recently identified as a functional receptor for the SARS virus. The ACE2 sequence is similar (sequence identities 43% and 35%, and similarities 61% and 55%, respectively) to those of the testis-specific form of ACE (tACE) and the Drosophila homolog of ACE (AnCE). The high level of sequence similarity allowed us to build a robust homology model of the ACE2 structure with a root-mean-square deviation from the aligned crystal structures of tACE and AnCE less than 0.5Å. A prominent feature of the model is a deep channel on the top of the molecule that contains the catalytic site. Negatively charged ridges surrounding the channel may provide a possible binding site for the positively charged receptor-binding domain (RBD) of the S-glycoprotein, which we recently identified [Biochem. Biophys. Res. Commun. 312 (2003) 1159]. Several distinct patches of hydrophobic residues at the ACE2 surface were noted at close proximity to the charged ridges that could contribute to binding. These results suggest a possible binding region for the SARS-CoV S-glycoprotein on ACE2 and could help in the design of experiments to further elucidate the structure and function of ACE2.


title: STING, DCs and the link between innate and adaptive tumor immunity

text: Cancer and the immune system are intimately related. Much of the bulk of tumors is comprised of stromal leukocytes with immune functions, which serve to both promote and inhibit tumor growth, invasion and metastasis. The T lymphocytes of the adaptive immune system are essential for tumor immunity, and these T cells are generated by cross-priming against tumor associated antigens. Dendritic cells (DCs) are essential in this process, serving as the cellular link between innate and adaptive immunity. As a prerequisite for priming of adaptive immune responses, DCs must take up tumor antigens, process them and present them in the context of the major histocompatibility complex (MHC). DCs also serve as sensors of innate activation signals from cancer that are necessary for their activation and effective priming of cancer specific T cells. Here we discuss the role of DCs in the sensing of cancer and in priming the adaptive response against tumors. Furthermore, we present the essential role of the Stimulator of Interferon Genes (STING) signaling pathway in producing type I interferons (IFNs) that are essential in this process.


Infectious Diseases in Children, Never a Dull Moment!


title: Zinc Lozenges: Cold Cure or Candy? Solution Chemistry Determinations

text: Common colds were shortened by 7 days in a 1984 clinical trial using zinc gluconate throat lozenges each 2 h. Between then and 2004, 10 other double-blind, placebo-controlled clinical trials showed widely varying results. This re-analysis of these trials presents solution chemistry methods to elucidate differences in efficacy. Statistically significant correlation was shown between total daily dosages of positively charged zinc species and reductions in median (p = 0.005) and mean duration (p < 0.02) of common colds in these trials.


title: COVID‐19 Clinical Diagnostics and Testing Technology

text: Given the global nature of the COVID‐19 pandemic, the need for disease detection and expanding testing capacity remains a critical priority. This review discusses the technological advances in testing capability and methodology that are currently employed or in development for detecting the novel coronavirus. We describe the current clinical diagnostics and technology, including molecular and serological testing approaches, for SARS‐CoV‐2 testing as well as address their advantages and limitations. Nucleic acid amplification technology for molecular diagnostics remains the gold standard for virus detection. We highlight alternative molecular detection techniques used for developing novel COVID‐19 diagnostics on the horizon. Antibody response against SARS‐CoV‐2 remains poorly understood and proper validation of serology tests is necessary to demonstrate their accuracy and clinical utility. In order to bring the pandemic under control, we must speed up the development of rapid and widespread testing through improvements in clinical diagnostics and testing technology as well as access to these tools.


title: Isolation of an equine coronavirus from adult horses with pyrogenic and enteric disease and its antigenic and genomic characterization in comparison with the NC99 strain

text: Abstract A new equine coronavirus was isolated from the feces of adult horses with pyrogenic and enteric disease. The disease outbreak was mainly observed among 2- to 4-year-old horses living in stables of a draft-horse racetrack in Japan. On comparing the isolated virus (isolate Tokachi09) with the equine coronavirus NC99 strain, no significant differences were observed in several biological properties such as hemagglutinating activity, antigenicity (in indirect immunofluorescence and neutralization tests), and one-step growth (in cell culture). The sequences of the nucleocapsid and spike genes of isolate Tokachi09 showed identical size (1341 and 4092 nucleotides, 446 and 1363 amino acids, respectively) and high similarity (98.0% and 99.0% at the nucleotides, 97.3% and 99.0% at the amino acids, respectively) to those of strain NC99. However, the isolate had a 185-nucleotide deletion from four bases after the 3′-terminal end of the spike gene, resulting in the absence of the open reading frame predicted to encode a 4.7-kDa nonstructural protein in strain NC99. These results suggest that the 4.7-kDa nonstructural protein is not essential for viral replication, at least in cell culture, and that the Japanese strain probably originated from a different lineage to the North American strain. This is the first equine coronavirus to be isolated from adult horses with pyrogenic and enteric disease.


title: Is There a Doctor Onboard? Medical Emergencies at 40,000 Feet

text: It is estimated 2.75 billion people travel aboard commercial airlines every year and 44,000 in-flight medical emergencies occur worldwide each year. Wilderness medicine requires a commonsense and improvisational approach to medical issues. A sudden call for assistance in the austere and unfamiliar surroundings of an airliner cabin may present the responding medical professional with a “wilderness medicine” experience. From resource management to equipment, this article sheds light on the unique conditions, challenges, and constraints of the flight environment.


title: Clinical-forensic autopsy findings to defeat covid-19 disease: A literature review

text: The severe acute respiratory syndrome (SARS)-CoV-2 was identified for the first time in China, in December 2019. Confirmed cases of COVID-19 have been reported around the world; indeed, this infection has been declared a pandemic. Consequently, the scientific community is working hard to gain useful information about the history of this virus, its transmission, diagnosis, clinical features, radiological findings, research and development of candidate therapeutics as well as vaccines. This review aims to analyze the diagnostic techniques used to ascertain the COVID-19 infection, critically reviewing positive points and criticism for forensic implications, obviously including autopsy. Finally, this review proposes a practical workflow to be applied in the management of corpses during this outbreak of the COVID-19 infection, which could be useful in cases of future infectious disease emergencies. Analyzing the diagnostic methods, to date, virus nucleic acid RT-PCR represents the standard method used to ascertain the COVID-19 infection in living subjects and corpses, even if this technique has several criticisms: mainly, the staff should be highly specialized, working in high-throughput settings, able to handle high workloads and aware of health risks and the importance of the results. Thus, IgG/IgM serological tests have been developed, overcoming RT-qPCR duration, costs, and management, not requiring highly trained personnel. Nevertheless, serological tests present problems; the WHO recommends the use of these new point-of-care immunodiagnostic tests only in research settings. Furthermore, nothing has yet been published regarding the possibility of applying these methods during post-mortem investigations. In light of this scenario, in this review, we suggest a flow chart for the pathologist called on to ascertain the cause of death of a subject with historical and clinical findings of COVID-19 status or without any anamnestic, diagnostic, or exposure information. Indeed, the literature data confirmed the analytical vulnerabilities of the kits used for laboratory diagnosis of COVID-19, particularly during postmortem examinations. For these reasons, autopsy remains the gold standard method to ascertain the exact cause of death (from or with COVID-19 infection, or other causes), to consequently provide real data for statistical evaluations and to take necessary measures to contain the risks of the infection. Moreover, performing autopsies could provide information on the pathogenesis of the COVID-19 infection with obvious therapeutic implications.