title: Insights on cross-species transmission of SARS-CoV-2 from structural modeling

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global pandemic that has infected more than 6 million people in more than 180 countries worldwide. Like other coronaviruses, SARS-CoV-2 is thought to have been transmitted to humans from wild animals. Given the scale and widespread geographical distribution of the current pandemic, the question emerges whether human-to-animal transmission is possible and if so, which animal species are most at risk. Here, we investigated the structural properties of several ACE2 orthologs bound to the SARS-CoV-2 spike protein. We found that species known not to be susceptible to SARS-CoV-2 infection have non-conservative mutations in several ACE2 amino acid residues that disrupt key polar and charged contacts with the viral spike protein. Our models also predict affinity-enhancing mutations that could be used to design ACE2 variants for therapeutic purposes. Finally, our study provides a blueprint for modeling viral-host protein interactions and highlights several important considerations when designing these computational studies and analyzing their results.


docid: fmozpplm

title: Clinical aspects of influenza A(H1N1)pdm09 cases reported during the pandemic in Brazil, 2009-2010

text: OBJECTIVE: To describe the clinical aspects of cases of influenza A(H1N1)pdm09 in Brazil. METHODS: A descriptive study of cases reported in Sistema de Informação de Agravos de Notificação (SINAN), 2009-2010. RESULTS: As the final classification, we obtained 53,797 (56.79%) reported cases confirmed as a new influenza virus subtype, and 40,926 (43.21%) cases discarded. Fever was the most common sign, recorded in 99.74% of the confirmed and 98.92% of the discarded cases. Among the confirmed cases, the presence of comorbidities was reported in 32.53%, and in 38.29% of the discarded cases. The case fatality rate was 4.04%; 3,267 pregnant women were confirmed positive for influenza A new viral subtype and 2,730 of them were cured. The case fatality rate of pregnant women was 6.88%. CONCLUSION: The findings suggested concern of the health system with pregnant women, and patients with comorbidities and quality of care may have favored a lower mortality. We recommend that, when caring for patients with severe respiratory symptoms, with comorbidities, or pregnant women, health professionals should consider the need for hospital care, as these factors make up a worse prognosis of infection by the pandemic influenza virus.


title: Electrolyte transport in piglets infected with transmissible gastroenteritis virus Stimulation by verapamil and clonidine

text: Abstract The effects of clonidine, an α 2-adrenergic agonist, and verapamil, a Ca2+ channel blocker, on Na2+ and Cl− absorption were studied in stripped jejunal mucosa from control and transmissible-gastroenteritis-virus-infected piglets. All infected piglets developed severe diarrhea 18–24 hours after oral inoculation. Jejunum from infected animals, as compared with control jejunum, had decreased mucosal-to-serosal, serosal-to-mucosal, and net Na+ and Cl− fluxes. Clonidine and verapamil caused a decrease in short-circuit current and stimulation of Na+ and Cl− absorption in control jejunum. In infected piglets, although the jejunum exhibited severe villus atrophy, both drugs stimulated Na+ and Cl− absorption and the magnitude of Na+ and Cl− absorption was similar in control and transmissible-gastroenteritis-infected jejunum. In contrast, d-glucose stimulated Na+ absorption, and the decrease in shortcircuit current caused by verapamil and clonidine, were decreased in transmissible-gastroenteritis-infected jejunum. Such pharmacological stimulation of Na+ and Cl− absorption might be useful in the management and treatment of certain viral diarrheal diseases.


docid: grarghun

title: Cellular Reservoirs for Coronavirus Infection of the Brain in β(2)-Microglobulin Knockout Mice

text: Mouse hepatitis virus (MHV) A59 infection which causes acute encephalitis, hepatitis, and chronic demyelination, is one of the experimental models for multiple sclerosis. Previous studies showed that lethal infection of β(2)-microglobulin ‘knockout’ (β(2)M(-/-)) mice required 500-fold less virus and viral clearance was delayed as compared to infection of immunocompetent C57Bl/6 (B6) mice. To investigate the mechanism of the increased susceptibility of β(2)M(-/-) mice to MHV-A59, we studied organ pathology and the distribution of viral antigen and RNA during acute and chronic infection. A59-infected β(2)M(-/-) mice were more susceptible to acute encephalitis and hepatitis, but did not have increased susceptibility to demyelination. Viral antigen and RNA distribution in the brain was increased in microglia, lymphocytes, and small vessel endothelial cells while the distribution in neurons and glia was similar in β(2)M(-/-) mice and B6 mice. Acute hepatitis and thymus cortical hypoplasia in β(2)M(-/-) mice were delayed in onset but pathologic changes in these organs were similar to those in B6 mice. The low rate of demyelination in β(2)M(-/-) mice was consistent with the low dose of the virus given. A less neurotropic virus MHV-2, caused increased parenchymal inflammation in β(2)M(-/-) mice, but without demyelination. Thus, CD8+ cells were important for viral clearance from endothelial cells, microglia and inflammatory cells, but not from neuronal and glial cells. In addition, CD8+ cells played a role in preventing the spread of encephalitis.


title: Wildlife Trade and Global Disease Emergence

text: The global trade in wildlife provides disease transmission mechanisms that not only cause human disease outbreaks but also threaten livestock, international trade, rural livelihoods, native wildlife populations, and the health of ecosystems. Outbreaks resulting from wildlife trade have caused hundreds of billions of dollars of economic damage globally. Rather than attempting to eradicate pathogens or the wild species that may harbor them, a practical approach would include decreasing the contact rate among species, including humans, at the interface created by the wildlife trade. Since wildlife marketing functions as a system of scale-free networks with major hubs, these points provide control opportunities to maximize the effects of regulatory efforts.


Is CoronavirusDisease 2019 (COVID-19) Seen Less in Countries More Exposed to Malaria?


title: Epidemiological aspects of antibiotic resistance in respiratory pathogens

text: Abstract Respiratory infections are the most frequent reason for primary health care consultation. The main causes of respiratory tract infections in children are viruses and the most common types are upper respiratory tract infections: common cold, pharyngitis, otitis media and sinusitis. Pneumonia is much more serious. As well as viruses, bacteria are often involved in respiratory tract infections. Three bacterial species are most commonly isolated: Streptococcus pneumoniae, non-encapsulated Haemophilus influenzae and Moraxella (Branhamella) catarrhalis. The most common bacterial cause of pharyngitis is Streptococcus pyogenes. Bacteria isolated from community-acquired infection usually are sensitive to the majority of suitable drugs, but during the past two decades, significant antibiotic resistance has emerged. Resistance to penicillins has spread among H. influenzae and S. pneumoniae. The mechanism of penicillin resistance in H. influenzae is mainly by production of β-lactamases TEM-1 and ROB-1, whereas in S. pneumoniae resistance is an effect of the changes in penicillin binding proteins. Among respiratory pathogens, resistance to tetracyclines, macrolides, trimethoprim–sulphamethoxazole and fluoroquinolones has also appeared. Several mechanisms depending on changes in target, active efflux and modifying enzymes are involved.


title: Impact of the 2015 Middle East Respiratory Syndrome Outbreak on Emergency Care Utilization and Mortality in South Korea

text: PURPOSE: In May 2015, South Korea experienced an epidemic of Middle East respiratory syndrome (MERS). This study investigated the impacts of MERS epidemic on emergency care utilization and mortality in South Korea. MATERIALS AND METHODS: A natural experimental study was conducted using healthcare utilization and mortality data of the entire Korean population. The number of monthly emergency room (ER) visits was investigated to identify changes in emergency care utilization during the MERS epidemic; these trends were also examined according to patients' demographic factors, disease severity, and region. Deaths within 7 days after visiting an ER were analyzed to evaluate the impact of the reduction in ER visits on mortality. RESULTS: The number of ER visits during the peak of the MERS epidemic (June 2015) decreased by 33.1% compared to the average figures from June 2014 and June 2016. The decrease was observed in all age, sex, and income groups, and was more pronounced for low-acuity diseases (acute otitis media: 53.0%; upper respiratory infections: 45.2%) than for high-acuity diseases (myocardial infarctions: 14.0%; ischemic stroke: 16.6%). No substantial changes were detected for the highest-acuity diseases, with increases of 3.5% for cardiac arrest and 2.4% for hemorrhagic stroke. The number of deaths within 7 days of an ER visit did not change significantly. CONCLUSION: During the MERS epidemic, the number of ER visits decreased in all age, sex, and socioeconomic groups, and decreased most sharply for low-acuity diseases. Nonetheless, there was no significant change in deaths after emergency care.


title: Antiviral activity of zinc salts against transmissible gastroenteritis virus in vitro

text: Abstract Zinc has been shown to mediate antiviral effects against certain viruses. However, the underlying mechanisms are still largely unknown. We investigated the effects of the two zinc salts, zinc chloride (ZnCl2) and zinc sulfate (ZnSO4), on infection of swine testicle (ST) cells with transmissible gastroenteritis virus (TGEV) and compared it to the effects of a control salt, magnesium sulfate (MgSO4). Virus yield reduction experiments showed that ZnCl2 and ZnSO4 did not exhibit direct virucidal effects and did not affect adsorption of TGEV to ST cells. However, ZnCl2 and ZnSO4 markedly reduced viral titers as well as TGEV RNA and viral protein synthesis when applied during virus penetration and at different time points after viral cell entry. The results of the study suggest that zinc salts do not interfere with TGEV-cell binding but that they mediate antiviral effects through inhibition of viral penetration or egress or the intracellular phase of the viral life-cycle.


Breast Reconstruction and the Covid-19 Pandemic: A Viewpoint


title: Identification of intertypic recombinant infectious bronchitis viruses from slaughtered chickens

text: Avian coronavirus infectious bronchitis virus (IBV) poses a major threat to the global poultry industry. New IBV geno- and serotypes are continually reported. However, information on IBV prevalence is not frequently addressed in these reports. This study reports on a viral surveillance program in Taiwan from 2005 to 2006 with sampling conducted in poultry slaughterhouses. The genetic features of the obtained field isolates were investigated using sequence analysis and SimPlot analysis. A 1-directional neutralization test was performed to examine the antigenic variations among the collected viruses. The selection pressures that may contribute to the evolution of Taiwan IBV during recent decades were assessed. The surveillance program revealed that 8 out of 47 flocks (17%) were IBV-infected, from which 13 IBV isolates were recovered. Based on the phylogenetic analysis of the S1 gene, 11 of 13 isolates (84.6%) clustered with Taiwan group I. One IBV isolate showed evidence of frequent recombination events with China-like IBV in the spike glycoprotein (S) gene. Another isolate demonstrated the incorporation of China-like and H120-like genome fragments within the S2 gene and the membrane protein (M) gene region, respectively. Some antigenic changes were found in the 1-directional neutralization test. However, no positive selection pressures were related to those variations in the S1 genes among Taiwan IBV. Based on our work, we suggest that sampling chickens in poultry slaughterhouses is an effective and valuable means of compiling viral prevalence data, particularly in situations where there is subclinical infection. Infectious bronchitis viruses from slaughtered chickens revealed intertypic genetic recombination and antigenic diversity.


title: Cryptosporidium outbreak in calves on a large dairy farm: Effect of treatment and the association with the inflammatory response and short-term weight gain

text: Abstract Cryptosporidium spp. infections in neonatal dairy calves can cause diarrhoea and, in rare cases, death. The infection is usually self-limiting, but halofuginone lactate (HL) can be used prophylactically. Calves (n =144) in the study were born during a 2-month period on one farm. A total of 901 serum and 767 faecal samples were collected. Based on HL treatment, the calves were divided into 3 groups: I) not treated, II) treated incorrectly (treatment started >48h after birth, or lasted <7days), and III) treated correctly (started <48h after birth, and lasted ≥7days). Over the 3-month observation period, 14.6% (n =21) of the calves died, of which most (67%) had not been treated with HL. Correctly performed treatment of cryptosporidiosis significantly delayed the onset of oocysts shedding (P <0.001) and reduced haptoglobin (HP) and serum amyloid A (SAA) concentrations in the second week of life. HP concentration and HL treatment were negatively associated with weight gain at 3months of age. Cryptosporidium positive faecal samples were significantly (P <0.001) more likely to be diarrhoeic but Giardia or Eimeria positive samples were not. Correct prophylactic treatment with HL delayed the shedding of Cryptosporidium oocysts and improved survival, but was negatively associated with weight gain. Incorrect treatment had a low impact on mortality and resembled no treatment regarding the proportion of calves shedding oocysts. Acute phase response (APR) in the second week of life seemed to be positively associated with shedding high amounts of Cryptosporidium oocysts.


title: Placental Pathology in COVID-19

text: OBJECTIVES: To describe histopathologic findings in the placentas of women with coronavirus disease 2019 (COVID-19) during pregnancy. METHODS: Pregnant women with COVID-19 delivering between March 18, 2020, and May 5, 2020, were identified. Placentas were examined and compared to historical controls and women with placental evaluation for a history of melanoma. RESULTS: Sixteen placentas from patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were examined (15 with live birth in the third trimester, 1 delivered in the second trimester after intrauterine fetal demise). Compared to controls, third trimester placentas were significantly more likely to show at least one feature of maternal vascular malperfusion (MVM), particularly abnormal or injured maternal vessels, and intervillous thrombi. Rates of acute and chronic inflammation were not increased. The placenta from the patient with intrauterine fetal demise showed villous edema and a retroplacental hematoma. CONCLUSIONS: Relative to controls, COVID-19 placentas show increased prevalence of decidual arteriopathy and other features of MVM, a pattern of placental injury reflecting abnormalities in oxygenation within the intervillous space associated with adverse perinatal outcomes. Only 1 COVID-19 patient was hypertensive despite the association of MVM with hypertensive disorders and preeclampsia. These changes may reflect a systemic inflammatory or hypercoagulable state influencing placental physiology.


title: Detection and differentiation of virulent and avirulent strains of Newcastle disease virus by real-time PCR

text: Abstract A rapid diagnostic method based on the melting curve SYBR Green I real-time PCR analysis was developed to detect and differentiate Newcastle disease virus (NDV) strains. Degenerated primers based on the cleavage site sequence of the F0 gene were designed to detect specific sequences characteristic of virulent and avirulent strains of NDV. Eighteen strains of NDV from four lineages were identified and grouped into virulent and avirulent strains. Peaks on the melting temperature graph with melting temperature values between 80.00 and 83.80°C were observed for lentogenic (avirulent) strains. T m values higher than 83.80 were observed for virulent (mesogenic and velogenic) strains. The detection limit of real-time PCR was 2×102 plasmid copies per reaction or 102 EID50 for velogenic strains and 103 EID50 for lentogenic strains. The results obtained in this study demonstrate the possible applications for melting curve real-time PCR analysis in laboratory practice for the diagnosis and differentiation of avirulent and virulent strains of Newcastle disease virus.


title: Rapid optimization of antimicrobial chemotherapy given to pediatric patients with community-acquired pneumonia using PCR techniques with serology and standard culture

text: Abstract Children (n =117; mean age 2.4 ± 2.9 years) were diagnosed as having community-acquired pneumonia (CAP) using clinical symptoms, chest X-rays, and hematological data. The causative pathogen was determined using real-time polymerase chain reaction (PCR) (6 bacteria), multiple reverse transcription-PCR (MPCR; 11 viruses), bacterial culture, and serology. The initial chemotherapy was evaluated based on the pathogens identified using PCR. We found 27 viral cases (23.1%), 25 bacterial cases (21.4%), 45 mixed infections with virus and bacteria (38.5%), 10 Mycoplasma pneumoniae (8.5%), 7 mixed infections with M. pneumoniae and another pathogen (6.0%), 1 Chlamydophila pneumoniae (0.9%), and 2 unknown pathogens (1.7%). Streptococcus pneumoniae and Haemophilus influenzae accounted for 58 (49.5%) and 27 (23.0%) of the cases, respectively. The median values (50%) of the white blood cell count (WBC) and C-reactive protein (CRP) using the box-and-whisker and plot method, respectively, were 11.7 × 103 mm−3 and 1.4mg/dl in viral infections, 15.6 × 103 mm−3 and 4.8mg/dl in mixed infections with virus and bacteria, 17.8 × 103 mm−3 and 6.3mg/dl in bacterial infections, 6.7 × 103 mm−3 and 1.4mg/dl in M. pneumoniae infections, and 21.5 × 103 mm−3 and 6.4mg/dl in mixed infections with M. pneumoniae and other bacterial infections. Sulbactam/ampicillin (n =61), carbapenems (n =12), and ceftriaxone (n =7) were selected for the patients suspected of having bacterial infections alone or mixed infections with bacterial and viruses in accordance with our criteria defined tentatively. For those with M. pneumoniae and C. pneumoniae infections, azithromycin or minocycline was initially used. Treatments averaged 3–5 days. The empirical chemotherapy was improper in 9.4% of cases in relation to the etiologic agents finally identified. We conclude that rapid and comprehensive identification using PCR can provide optimal antimicrobial chemotherapy for CAP patients.


title: Genetic aspects of macrophage involvement in natural resistance to virus infections

text: Abstract Macrophages are thought to constitute an important element in the body's natural defense against invasion and dissemination of viruses. Possible antiviral mechanisms of macrophages are defined and referred to as intrinsic, i.e. the ability of macrophages to serve as a non-permissive barrier between the virus and susceptible cells and extrinsic, i.e. the ability of macrophages to affect the virus or virus replication in surrounding cells. Most studies on the role of macrophages in natural resistance to virus infections have been performed in animal models. An interesting aspect of many viral infections in animals is the finding of a genetically determined variation in natural resistance. Because of the availability of numerous inbred and congenic strains most studies on genetically determined resistance have been performed in mice. The classical examples are resistance to flaviviruses and susceptibility to mouse hepatitis virus, both of which are inherited as dominant, monogenic traits. With these viruses macrophage intrinsic restriction of virus replication has been found to express at the cellular level the genetics of resistance/susceptibility seen in the intact animal. Other examples, where macrophages have been implicated in genetically determined resistance include herpes simplex virus and influenza virus. The involvement of macrophages in natural resistance to these viruses is discussed in relation to other putative resistance determinants like interferon production and sensitivity and natural killer cell activity.


title: Diagnostic value of respiratory virus detection in symptomatic children using real-time PCR

text: BACKGROUND: Acute respiratory tract infections are an important public health problem. Sensitive and rapid diagnostic techniques have been developed and are used in daily clinical practice. Here we evaluate the clinical relevance of detecting 20 common respiratory pathogens by molecular methods in a general pediatric clinic. METHODS: Nasopharynx samples of children < 18 years of age with respiratory symptoms referred to a general pediatric clinic were tested for the presence of 19 viruses and Mycoplasma pneumoniae, using real-time polymerase chain reaction. RESULTS: Of 177 patients included in this retrospective study, 73% were positive for at least one virus. Respiratory syncytial virus (36.6%) and human rhinovirus (24%) were most frequently detected. Patients in whom a respiratory virus or Mycoplasma pneumoniae was detected, were younger (6 versus 24 months; p < 0.001) and more often hospitalized (116 versus 34; p = 0.001) than patients in whom no respiratory pathogen was detected. Also they were more likely to present with feeding problems, dyspnea, rhinorrhea and wheezing (all p < 0.05) than patients without a respiratory pathogen. In the majority of cases, clinicians did not change their antibiotic management after detecting a viral respiratory pathogen. No difference in mean Ct value was found between patients with one respiratory pathogen and those with >1 respiratory pathogen (30.5 versus 31.2; p = 0.573). CONCLUSION: Routine testing of common respiratory pathogens could lead to a better understanding of their role in disease in children with respiratory symptoms.


title: Structural basis for dimerization and RNA binding of avian infectious bronchitis virus nsp9

text: The potential for infection by coronaviruses (CoVs) has become a serious concern with the recent emergence of Middle East respiratory syndrome and severe acute respiratory syndrome (SARS) in the human population. CoVs encode two large polyproteins, which are then processed into 15–16 nonstructural proteins (nsps) that make significant contributions to viral replication and transcription by assembling the RNA replicase complex. Among them, nsp9 plays an essential role in viral replication by forming a homodimer that binds single‐stranded RNA. Thus, disrupting nsp9 dimerization is a potential anti‐CoV therapy. However, different nsp9 dimer forms have been reported for alpha‐ and beta‐CoVs, and no structural information is available for gamma‐CoVs. Here we determined the crystal structure of nsp9 from the avian infectious bronchitis virus (IBV), a representative gamma‐CoV that affects the economy of the poultry industry because it can infect domestic fowl. IBV nsp9 forms a homodimer via interactions across a hydrophobic interface, which consists of two parallel alpha helices near the carboxy terminus of the protein. The IBV nsp9 dimer resembles that of SARS‐CoV nsp9, indicating that this type of dimerization is conserved among all CoVs. This makes disruption of the dimeric interface an excellent strategy for developing anti‐CoV therapies. To facilitate this effort, we characterized the roles of six conserved residues on this interface using site‐directed mutagenesis and a multitude of biochemical and biophysical methods. We found that three residues are critical for nsp9 dimerization and its abitlity to bind RNA.


docid: cpjkltsu

title: Tracheotomy in COVID‐19 patients: Optimizing patient selection and identifying prognostic indicators

text: BACKGROUND: Tracheotomy, through its ability to wean patients off ventilation, can shorten ICU length of stay and in doing so increase ICU bed capacity, crucial for saving lives during the COVID‐19 pandemic. To date, there is a paucity of patient selection criteria and prognosticators to facilitate decision making and enhance precious ICU capacity. METHODS: Prospective study of COVID‐19 patients undergoing tracheotomy (n = 12) over a 4‐week period (March‐April 2020). Association between preoperative and postoperative ventilation requirements and outcomes (ICU stay, time to decannulation, and death) were examined. RESULTS: Patients who sustained FiO(2) ≤ 50% and PEEP ≤ 8 cm H(2)O in the 24 hours pretracheotomy exhibited a favorable outcome. Those whose requirements remained below these thresholds post‐tracheotomy could be safely stepped down after 48 hours. CONCLUSION: Sustained FiO(2) ≤ 50% and PEEP ≤ 8 cm H(2)O in the 48 hours post‐tracheotomy are strong predictive factors for a good outcome, raising the potential for these patients to be stepped down early, thus increasing ICU capacity.


title: Porcine circovirus type 2 (PCV2) enteric disease: An independent condition or part of the systemic disease?

text: Abstract Intestinal disorders in growing and finishing pigs have been associated with several infectious agents, including Porcine circovirus type 2 (PCV2). This virus has been mainly related with PCV2-systemic disease (PCV2-SD); nevertheless, some authors have suggested a possible restricted intestinal infection of this virus associated with enteric clinical signs. This condition has been referred as PCV2-enteric disease (PCV2-ED). The present study analysed retrospectively, from a pathological point of view, the relation between intestinal disorders and PCV2 infection in nursery and growing-finishing pigs. Among the 96 selected pigs suffering from enteric disease and submitted for necropsy between 1998 and 2011, the most prevalent enteric lesions were catarrhal enteritis/colitis (77.1%), followed by fibrinous lesions (11.5%), granulomatous inflammation (4.2%) and other lesions such as haemorrhages or ulceration (4.2%). Seventy-two pigs (75%) were positive for PCV2 by in situ hybridization (ISH). Among positive pigs for PCV2 ISH, 39 animals suffered from PCV2-SD and 33 had no lymphoid lesions but low amount of viral nucleic acid in several lymphoid tissues, therefore, these animals did not qualify for PCVD-ED. In conclusion, all animals with enteric disorders that were positive to PCV2 by ISH had evidence of viral systemic infection. These results suggest that PCV2-ED is probably a negligible condition and PCV2 mainly contributes to enteric clinical disorders in relation to PCV2-SD occurrence.


title: STAT3 in Skeletal Muscle Function and Disorders

text: Signal transducer and activator of transcription 3 (STAT3) signaling plays critical roles in regulating skeletal muscle mass, repair, and diseases. In this review, we discuss the upstream activators of STAT3 in skeletal muscles, with a focus on interleukin 6 (IL6) and transforming growth factor beta 1 (TGF-β1). We will also discuss the double-edged effect of STAT3 activation in the muscles, including the role of STAT3 signaling in muscle hypertrophy induced by exercise training or muscle wasting in cachectic diseases and muscular dystrophies. STAT3 is a critical regulator of satellite cell self-renewal after muscle injury. STAT3 knock out affects satellite cell myogenic progression by impairing proliferation and inducing premature differentiation. Recent studies in STAT3 signaling demonstrated its direct role in controlling myogenic capacity of myoblasts and satellite cells, as well as the potential benefit in using STAT3 inhibitors to treat muscle diseases. However, prolonged STAT3 activation in muscles has been shown to be responsible for muscle wasting by activating protein degradation pathways. It is important to balance the extent of STAT3 activation and the duration and location (cell types) of the STAT3 signaling when developing therapeutic interventions. STAT3 signaling in other tissues and organs that can directly or indirectly affects skeletal muscle health are also discussed.


title: A structure-based rationale for sialic acid independent host-cell entry of Sosuga virus

text: The bat-borne paramyxovirus, Sosuga virus (SosV), is one of many paramyxoviruses recently identified and classified within the newly established genus Pararubulavirus, family Paramyxoviridae. The envelope surface of SosV presents a receptor-binding protein (RBP), SosV-RBP, which facilitates host-cell attachment and entry. Unlike closely related hemagglutinin neuraminidase RBPs from other genera of the Paramyxoviridae, SosV-RBP and other pararubulavirus RBPs lack many of the stringently conserved residues required for sialic acid recognition and hydrolysis. We determined the crystal structure of the globular head region of SosV-RBP, revealing that while the glycoprotein presents a classical paramyxoviral six-bladed β-propeller fold and structurally classifies in close proximity to paramyxoviral RBPs with hemagglutinin-neuraminidase (HN) functionality, it presents a receptor-binding face incongruent with sialic acid recognition. Hemadsorption and neuraminidase activity analysis confirms the limited capacity of SosV-RBP to interact with sialic acid in vitro and indicates that SosV-RBP undergoes a nonclassical route of host-cell entry. The close overall structural conservation of SosV-RBP with other classical HN RBPs supports a model by which pararubulaviruses only recently diverged from sialic acid binding functionality.


title: ACE2, a new regulator of the renin–angiotensin system

text: Abstract Angiotensin-converting enzyme (ACE) is a zinc metalloproteinase and a key regulator of the renin–angiotensin system (RAS). ACE2 is a newly described enzyme identified in rodents and humans with a more restricted distribution than ACE, and is found mainly in heart and kidney. ACE2 cleaves a single residue from angiotensin I (Ang I) to generate Ang 1–9, and degrades Ang II, the main effector of the RAS, to the vasodilator Ang 1–7. The importance of ACE2 in normal physiology and pathophysiological states is largely unknown. ACE2 might act in a counter-regulatory manner to ACE, modulating the balance between vasoconstrictors and vasodilators within the heart and kidney, and playing a significant role in regulating cardiovascular and renal function.


title: A metaanalysis of bat phylogenetics and positive selection based on genomes and transcriptomes from 18 species

text: Historically, the evolution of bats has been analyzed using a small number of genetic loci for many species or many genetic loci for a few species. Here we present a phylogeny of 18 bat species, each of which is represented in 1,107 orthologous gene alignments used to build the tree. We generated a transcriptome sequence of Hypsignathus monstrosus, the African hammer-headed bat, and additional transcriptome sequence for Rousettus aegyptiacus, the Egyptian fruit bat. We then combined these data with existing genomic and transcriptomic data from 16 other bat species. In the analysis of such datasets, there is no clear consensus on the most reliable computational methods for the curation of quality multiple sequence alignments since these public datasets represent multiple investigators and methods, including different source materials (chromosomal DNA or expressed RNA). Here we lay out a systematic analysis of parameters and produce an advanced pipeline for curating orthologous gene alignments from combined transcriptomic and genomic data, including a software package: the Mismatching Isoform eXon Remover (MIXR). Using this method, we created alignments of 11,677 bat genes, 1,107 of which contain orthologs from all 18 species. Using the orthologous gene alignments created, we assessed bat phylogeny and also performed a holistic analysis of positive selection acting in bat genomes. We found that 181 genes have been subject to positive natural selection. This list is dominated by genes involved in immune responses and genes involved in the production of collagens.


title: Viral etiology of pneumonia among severely malnourished under-five children in an urban hospital, Bangladesh

text: BACKGROUND: In Bangladesh, pneumonia has a higher mortality among malnourished children aged <5 years. Evaluating pneumonia etiology among malnourished children may help improve empiric treatment guidelines. METHODS: During April 2015—December 2017, we conducted a case-control study among severe acute malnourished (SAM) children aged <5 years admitted to the Dhaka hospital of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). We enrolled hospital admitted SAM children with clinical or radiological pneumonia as cases (during April 2015 to March 2017) and hospital admitted SAM children without any respiratory symptom in the past 10 days before admission as controls (during February 2016 to December 2017). We tested nasopharyngeal wash from both case and control for respiratory syncytial virus (RSV), human metapneumovirus (HMPV), influenza viruses, human parainfluenza viruses (HPIV), rhinovirus and adenovirus by singleplex real-time reverse transcriptase polymerase chain reaction. To identify the independent association of pneumonia with viral pathogens during February 2016 to March 2017, we used multivariable logistic regression for calculating adjusted odds ratios. RESULTS: We enrolled 360 cases and 334 controls. For case and control the median age was 8 months (IQR: 5–13) and 11 months (IQR: 6–18) (p = 0.001) respectively. Weight/age Z-score was -4.3 (SD ±0.7) for cases and -4.1 (SD ±1.1) for controls (p = 0.01). Among cases 68% had both clinical and radiological pneumonia, 1% had clinical pneumonia and 31% had only radiological pneumonia. Respiratory virus detection was high in cases compared to controls [69.9% (251) vs. 44.8% (148), p = 0.0001]. The most frequently detected viruses among cases were rhinoviruses (79, 22.0%) followed by RSV (32, 8.9%), adenovirus (23, 6.4%), HPIV (22, 6.1%), influenza virus (16, 4.5%), and HMPV (16, 4.5%). Among the controls, rhinoviruses (82, 24.8%) were most commonly detected one followed by adenovirus (26,7.9%), HMPV (5, 1.5%), HPIV (4, 1.2%), RSV (3, 0.9%), and influenza virus (2, 0.6%). RSV (OR 13.1; 95% CI: 1.6, 106.1), influenza virus (OR 8.7; 95% CI: 1.0, 78.9), HPIV (3.8; 95% CI: 1.0, 14.8), and HMPV (2.7; 95% CI: 1.3, 5.5) were independently associated with pneumonia while compared between 178 cases and 174 controls. CONCLUSION: Viral etiology of pneumonia in SAM children were mainly attributable to RSV, influenza, HPIV and HMPV. Our study findings may help in planning further studies targeting vaccines or drugs against common respiratory viruses responsible for pneumonia among SAM children.


title: The assessment of transmission efficiency and latent infection period on asymptomatic carriers of SARS-CoV-2 infection

text: ABSTRACT Few studies aimed on the transmission efficiency of asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A follow-up study was performed on 147 asymptomatic carriers in Anhui Province. Of 147 asymptomatic carriers, 50.0% were male, 50.3% cases were older than 40 years, and 43.8% were farmers, 68.7% cases were from north of Anhui Province. There were 16 asymptomatic carriers developed illness in the following 14 days isolated observation, and diagnosed as confirmed cases. The possible latent infection period was evaluated ranged from one to five days before onset, and the median time was two days. The second attack rate of 16 confirmed cases whom transferred from asymptomatic carriers was 9.7% (23/236), while 131 asymptomatic carriers caused 2.6% (24/914) close contacts infection, there was a significant difference of second attack rate among two groups (P＜0.001). Our study indicated that COVID-19 cases are contagious during the incubation period, and the close contact screening should be covered the incubation period. Furthermore, the transmission efficiency of asymptomatic carriers was lower than that of confirmed cases.


title: Guillain Barre syndrome associated with COVID-19 infection: A case report

text: Abstract Novel outbreak with coronavirus 2019 began since 31 December 2019. Coronaviruses can cause multiple systemic infections that respiratory complications are the most obvious symptoms. In this report, we describe the symptoms of Guillain Barre syndrome (GBS) in one infected patient with COVID-19, for the first time. We reported a 65-years- old male patient with complaints of acute progressive symmetric ascending quadriparesis. Two weeks prior to hospitalization, the patient suffered from cough, fever, and RT-PCR was reported positive for COVID-19 infection. The electrodiagnostic test showed that the patient is an AMSAN variant of GBS. COVID-19 stimulates inflammatory cells and produces various inflammatory cytokines and as a result, it creates immune-mediated processes. GBS is an immune-mediated disorder and molecular mimicry as a mechanism of autoimmune disorder plays an important role in creating it. It is unclear whether COVID-19 induces the production of antibodies against specific gangliosides. Further investigations should be conducted about the mechanism of GBS in patients with COVID-19, in the future.


title: Increased litter survival rates, reduced clinical illness and better lactogenic immunity against TGEV in gilts that were primed as neonates with porcine respiratory coronavirus (PRCV)

text: Abstract Establishing immunological memory in female piglets at a young age with PRCV was effective in inducing a secondary immune response to a limiting dose of virulent TGEV given orally 13–18 days prior to farrowing. Subsequently, because of passive antibody transfer, the offspring of these primed gilts were more efficient in surviving a lethal TGEV challenge. An average survival rate of 89% occurred in 6 litters of piglets from primed gilts that were boosted with 2.8×106 plaque forming units (PFU) of TGEV whereas 76% of the piglets survived in three litters that suckled primed gilts boosted with 3.0×105 PFU of TGEV. Non-primed gilts given identical pre-farrowing doses of TGEV had litter survival rates of 63 and 55%, respectively. Moreover, both groups of litters from primed gilts suffered less clinical illness (as measured by the extent of weight loss post-challenge) than control litters. Priming of the piglets as neonates and boosting the pregnant gilts produced an anamnestic systemic immune response and correspondingly higher milk titers in the primed gilts compared to control animals. Thus, priming piglets with PRCV was beneficial in providing resistance to TGEV and could be incorporated into a vaccine strategy that yields better protection against TGEV.


title: Infectious disease symptoms and microbial carriage among French medical students travelling abroad: A prospective study

text: Abstract Background In France, no previous studies have focused specifically on health problems among medical students during internships abroad including the clinical symptoms suggestive of infectious diseases and the acquisition of pathogen carriage. Methods Clinical follow up and qPCR based respiratory, gastrointestinal and vaginal pathogen carriage before and after travel were prospectively assessed in a cohort of medical students departing from Marseille, France. Results 134 students were included. 73.9%, 38.8% and 5.0% of students reported gastrointestinal, respiratory and vaginal symptoms, respectively. The acquisition rate of Enteroaggregative Escherichia coli (EAEC) and Enteropathogenic E. coli (EPEC) was 53% and 41%, respectively. The acquisition of respiratory viruses was low but associated with persisting symptoms, while bacterial acquisition ranged from 3.3% for Streptococcus pyogenes to 15.0% for Haemophilus influenzae. Gardnerella vaginalis and Atopobium vaginae acquisition rates were 7.7% and 14.3% respectively. Five students (5.1%) had molecular quantification criteria for bacterial vaginosis on return. Conclusion This preliminary study demonstrates that besides the known risk of gastrointestinal and respiratory infections and associated changes in intestinal and respiratory microbiota, medical students abroad may also experience changes in vaginal microbiota leading, in some cases, to clinical symptoms or the acquisition of bacterial vaginosis, which may be asymptomatic.


title: Impact of SARS-CoV-2 infection on neurodegenerative and neuropsychiatric diseases: A delayed pandemic?

text: Abstract Introduction SARS-CoV-2 was first detected in December 2019 in the Chinese city of Wuhan and has since spread across the world. At present, the virus has infected over 1.7 million people and caused over 100000 deaths worldwide. Research is currently focused on understanding the acute infection and developing effective treatment strategies. In view of the magnitude of the epidemic, we conducted a speculative review of possible medium- and long-term neurological consequences of SARS-CoV-2 infection, with particular emphasis on neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin, based on the available evidence on neurological symptoms of acute SARS-CoV-2 infection. Development We systematically reviewed the available evidence about the pathogenic mechanisms of SARS-CoV-2 infection, the immediate and lasting effects of the cytokine storm on the central nervous system, and the consequences of neuroinflammation for the central nervous system. Conclusions SARS-CoV-2 is a neuroinvasive virus capable of triggering a cytokine storm, with persistent effects in specific populations. Although our hypothesis is highly speculative, the impact of SARS-CoV-2 infection on the onset and progression of neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin should be regarded as the potential cause of a delayed pandemic that may have a major public health impact in the medium to long term. Cognitive and neuropsychological function should be closely monitored in COVID-19 survivors.


title: SARS‐CoV‐2 and Oral Ulcers; a Causative Agent or a Predisposing Factor?

text: Earlier reports on COVID‐19 have reported certain orofacial manifestations like taste loss and salivary gland infection (Dar‐Odeh et al, 2020). More recently, two studies from Spain and France reported oral ulcerative lesions in COVID‐19 patients ( Chaux‐Bodard et al, 2020; Carreras‐ Presas et al, 2020). The study from Spain included three patients. The first two cases (males) were suspected cases of COVID‐19 as testing was not done for them. Intraorally, they had oral ulcers affecting the hard palate unilaterally in the anatomic area innervated by greater palatine nerve.


title: Time for a Change: Personal Experiences With COVID-19 and Diabetes

text: Personal experiences during the COVID-19 pandemic.


title: The Host Restriction Factor Interferon-Inducible Transmembrane Protein 3 Inhibits Vaccinia Virus Infection

text: Interferons (IFNs) establish dynamic host defense mechanisms by inducing various IFN-stimulated genes that encodes many antiviral innate immune effectors. IFN-inducible transmembrane (IFITM) proteins have been identified as intrinsic antiviral effectors, which block the entry of a broad spectrum of enveloped RNA viruses by interrupting virus-endosomal fusion. However, antiviral activity of IFITM proteins against mammalian DNA virus has not been demonstrated till date. Here, we sought to investigate the antiviral activities and mechanisms of interferon-inducible transmembrane protein 3 (IFITM3) protein against poxvirus infection. Analysis of expression kinetics of cell endogenous IFITM3 protein indicated that vaccinia virus (VACV) infection suppressed its translation, which was independent of IRF3 phosphorylation triggered by VACV. Although silencing of endogenous IFITM proteins did not affect their baseline antiviral effects in the cell, it has reduced the IFN-α-mediated inhibition of VACV infection, and also modulated VACV-induced cell death. Moreover, we discovered that overexpression of IFITM3 significantly restricted VACV infection, replication and proliferation mainly by interfering with virus entry processes prior to the virus nucleocapsid entry into the cytoplasm. Interestingly, IFITM3 overexpression showed an impact on virus binding. Furthermore, IFITM3 interfered with the cytosolic entry of virus through low pH-dependent fashion. Taken together, our findings provide the first evidence of exogenously expressed IFITM3 protein restricting infection of an enveloped DNA virus, thus expanding their antiviral spectrum. This study further explores the complex mechanism and provides novel insights into the interaction between virus infection and host defense.


From Fear to Fortitude: Using the Power Within the Nursing Profession to Fight COVID-19


title: Investigation of an experimental infection model of equine coronavirus in adult horses

text: BACKGROUND: Equine coronavirus (ECoV) is a recently reported enteric disease of adult horses. Natural infection by ECoV has been reported in adult horses worldwide, whereas experimental infection has only been reported in juvenile horses. An experimental infection model is needed to study the clinical presentation, laboratory abnormalities, and pathophysiological changes associated with ECoV. OBJECTIVES: To investigate the clinical, hematologic, molecular, and serological features of adult horses experimentally infected with ECoV. ANIMALS: Eight adult horses. METHODS: Four horses were intragastrically infected with fecal material containing 10(9) genome equivalents of ECoV. Four additional horses were exposed daily to the feces from the experimentally‐infected horses. Monitoring included physical examinations, as well as daily nasal swab, whole blood, and fecal collection for molecular detection of ECoV. Blood was collected every other day for hematologic analysis and weekly for serologic analysis. RESULTS: All 8 horses shed ECoV in feces. Six of the 8 horses (75%) exhibited mild, clinical disease with soft, formed manure; 1 horse exhibited transient pyrexia. All horses maintained total white cell counts within normal limits, but 3 horses developed transient lymphopenia. No statistically significant differences (P = .20) were observed in quantity of fecal shedding of ECoV between the 2 groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Experimental infection of adult horses with ECoV was associated with mild and self‐limiting clinical signs, transient lymphopenia, and fecal shedding of ECoV, which mimics natural infection. No differences between experimentally‐infected horses and horses exposed to ECoV‐containing feces were identified. Results of our study support a fecal‐oral route of transmission.


title: From the Argonauts Mythological Sailors to the Argonautes RNA-Silencing Navigators: Their Emerging Roles in Human-Cell Pathologies

text: Regulation of gene expression has emerged as a fundamental element of transcript homeostasis. Key effectors in this process are the Argonautes (AGOs), highly specialized RNA-binding proteins (RBPs) that form complexes, such as the RNA-Induced Silencing Complex (RISC). AGOs dictate post-transcriptional gene-silencing by directly loading small RNAs and repressing their mRNA targets through small RNA-sequence complementarity. The four human highly-conserved family-members (AGO1, AGO2, AGO3, and AGO4) demonstrate multi-faceted and versatile roles in transcriptome’s stability, plasticity, and functionality. The post-translational modifications of AGOs in critical amino acid residues, the nucleotide polymorphisms and mutations, and the deregulation of expression and interactions are tightly associated with aberrant activities, which are observed in a wide spectrum of pathologies. Through constantly accumulating information, the AGOs’ fundamental engagement in multiple human diseases has recently emerged. The present review examines new insights into AGO-driven pathology and AGO-deregulation patterns in a variety of diseases such as in viral infections and propagations, autoimmune diseases, cancers, metabolic deficiencies, neuronal disorders, and human infertility. Altogether, AGO seems to be a crucial contributor to pathogenesis and its targeting may serve as a novel and powerful therapeutic tool for the successful management of diverse human diseases in the clinic.


title: Rapid report: Early demand, profiles and concerns of mental health users during the coronavirus (COVID-19) pandemic

text: BACKGROUND: Trends in contact with a high volume national digital mental health service (DMHS), the MindSpot Clinic, provide a unique opportunity to assess the mental health effects of the COVID-19 pandemic. METHODS: Three methods were used to assess changes in responses to COVID-19. First, website visits and call centre traffic were compared across two time periods: the “comparison period” (1 September 2020 to 28 September 2019), and during the early weeks of the “COVID-19 pandemic” (19 March 2020 to 15 April 2020). Second, demographic and symptom data were compared across all patients who started an assessment during the comparison (n = 1650) and the COVID-19 period (n = 1668). Third, responses to questions about the impact of COVID-19 introduced to the assessment from 19 March 2020, and reports from treating therapists were examined. RESULTS: There was an 89% increase in website visits and a 90% increase in telephone calls to the clinic in the early COVID-19 period compared to the comparison period. There was a higher proportion of females in the COVID-19 sample (76.9% vs. 72.9), and a lower proportion reported being in employment (52.8% vs. 60.8%). There was a small but significant increase in the severity of anxiety symptoms, and an increase in the number of people reporting recent onset of anxiety and depression. However, there were no differences between groups in severity of symptoms of distress or depression. Most people (94%) reported concern about the impact of COVID-19, and 88% reported making changes in lifestyle. Older adults had higher levels of concern about COVID-19. Therapists reported that patients were concerned about how to access testing, manage quarantine, financial security and the effect of social isolation. CONCLUSIONS: COVID-19 has resulted in a significant increase in contact with an established DMHS, but we have not yet detected increases in baseline symptom severity. With the prospect of prolonged restriction of movement, DMHS such as MindSpot could play an important role in both providing clinical services and monitoring the mental health of the population.


title: Antigenic structures stably expressed by recombinant TGEV-derived vectors

text: Abstract Coronaviruses (CoVs) are positive-stranded RNA viruses with potential as immunization vectors, expressing high levels of heterologous genes and eliciting both secretory and systemic immune responses. Nevertheless, its high recombination rate may result in the loss of the full-length foreign gene, limiting their use as vectors. Transmissible gastroenteritis virus (TGEV) was engineered to express porcine reproductive and respiratory syndrome virus (PRRSV) small protein domains, as a strategy to improve heterologous gene stability. After serial passage in tissue cultures, stable expression of small PRRSV protein antigenic domains was achieved. Therefore, size reduction of the heterologous genes inserted in CoV-derived vectors led to the stable expression of antigenic domains. Immunization of piglets with these TGEV vectors led to partial protection against a challenge with a virulent PRRSV strain, as immunized animals showed reduced clinical signs and lung damage. Further improvement of TGEV-derived vectors will require the engineering of vectors with decreased recombination rate.


50th Anniversary Editorial: Building on firm foundations


title: Applications of RNA interference: current state and prospects for siRNA-based strategies in vivo

text: Within the recent years, RNA interference (RNAi) has become an almost-standard method for in vitro knockdown of any target gene of interest. Now, one major focus is to further explore its potential in vivo, including the development of novel therapeutic strategies. From the mechanism, it becomes clear that small interfering RNAs (siRNAs) play a pivotal role in triggering RNAi. Thus, the efficient delivery of target gene-specific siRNAs is one major challenge in the establishment of therapeutic RNAi. Numerous studies, based on different modes of administration and various siRNA formulations and/or modifications, have already accumulated promising results. This applies to various animal models covering viral infections, cancer and multiple other diseases. Continuing efforts will lead to the development of efficient and “double-specific” drugs, comprising of siRNAs with high target gene specificity and of nanoparticles enhancing siRNA delivery and target organ specificity.


title: Ebola virus disease: How can African pharmacists respond to future outbreaks?

text: Abstract In its forty years history (1976–2016), the West African region has recorded the most devastating form of the Ebola virus disease. The sparse knowledge of healthcare professionals and general public combined with lesser responses from international community are major factors for the dissemination of the disease. In the context of this outbreak, there is a need to highlight the roles and responsibilities of pharmacists, especially in the African healthcare setting. Moreover, the prerequisite of diagnostic kits for the timely detection of the infection as well as pharmacists' awareness of the current therapeutic regimen are recommended.


title: Near-infrared observations of active asteroid (3200) Phaethon reveal no evidence for hydration

text: Asteroid (3200) Phaethon is an active near-Earth asteroid and the parent body of the Geminid Meteor Shower. Because of its small perihelion distance, Phaethon's surface reaches temperatures sufficient to destabilize hydrated materials. We conducted rotationally resolved spectroscopic observations of this asteroid, mostly covering the northern hemisphere and the equatorial region, beyond 2.5-micron to search for evidence of hydration on its surface. Here we show that the observed part of Phaethon does not exhibit the 3-micron hydrated mineral absorption (within 2-sigma). These observations suggest that Phaethon's modern activity is not due to volatile sublimation or devolatilization of phyllosilicates on its surface. It is possible that the observed part of Phaethon was originally hydrated and has since lost volatiles from its surface via dehydration, supporting its connection to the Pallas family, or it was formed from anhydrous material.


title: The interaction of the SARS coronavirus non-structural protein 10 with the cellular oxido-reductase system causes an extensive cytopathic effect

text: Abstract The pathological mechanism of SARS-CoV infection was investigated. The gene for the SARS-CoV non-structural protein 10, which is located in the open reading frame of pp1a/pp1ab gene, was synthesized and used to screen for the specific cellular gene coding for the protein interacting with this nsp10 protein in a human embryo lung cDNA library using a yeast trap method. The results indicated that apart from the two subunits of cellular RNA polymerase complex, BTF3 and ATF5, this nsp10 protein was also able to interact specifically with the NADH 4L subunit and cytochrome oxidase II. Further study revealed that the activity of the NADH-cytochrome was altered and the inner mitochondrial membrane was depolarized in the transfected human embryo lung fibroblast by the nsp10 protein gene. The cytopathic effect of the Coronavirus 229E strain appeared more extensive in these cells than in the control cells.


title: Synthetic virus-like particles prepared via protein corona formation enable effective vaccination in an avian model of coronavirus infection

text: Abstract The ongoing battle against current and rising viral infectious threats has prompted increasing effort in the development of vaccine technology. A major thrust in vaccine research focuses on developing formulations with virus-like features towards enhancing antigen presentation and immune processing. Herein, a facile approach to formulate synthetic virus-like particles (sVLPs) is demonstrated by exploiting the phenomenon of protein corona formation induced by the high-energy surfaces of synthetic nanoparticles. Using an avian coronavirus spike protein as a model antigen, sVLPs were prepared by incubating 100 nm gold nanoparticles in a solution containing an optimized concentration of viral proteins. Following removal of free proteins, antigen-laden particles were recovered and showed morphological semblance to natural viral particles under nanoparticle tracking analysis and transmission electron microscopy. As compared to inoculation with free proteins, vaccination with the sVLPs showed enhanced lymphatic antigen delivery, stronger antibody titers, increased splenic T-cell response, and reduced infection-associated symptoms in an avian model of coronavirus infection. Comparison to a commercial whole inactivated virus vaccine also showed evidence of superior antiviral protection by the sVLPs. The study demonstrates a simple yet robust method in bridging viral antigens with synthetic nanoparticles for improved vaccine application; it has practical implications in the management of human viral infections as well as in animal agriculture.


title: The intensive care unit work environment: Current challenges and recommendations for the future

text: Abstract The need for critical care services has grown substantially in the last decade in most of the G8 nations. This increasing demand has accentuated an already existing shortage of trained critical care professionals. Recent studies argue that difficulty in recruiting an appropriate workforce relates to a shortage of graduating professionals and unhealthy work environments in which critical care professionals must work. Objective This narrative review summarizes existing literature and experiences about the key work environment challenges reported within the critical care context and suggests best practices—implemented in hospitals or suggested by professional associations—which can be an initial step in enhancing patient care and professional recruitment and retention in our intensive care units, with particular emphasis on the recruitment and retention of an appropriately trained and satisfied workforce. The experiences are categorized for the physical, emotional, and professional environments. A case study is appended to enhance understanding of the magnitude and some of the proposed remedies of these experiences.


title: UPDATE ON ACUTE MYOCARDITIS

text: Acute myocarditis (AM), a recent-onset inflammation of the heart, has heterogeneous clinical presentations, varying from minor symptoms to high-risk cardiac conditions with severe heart failure, refractory arrhythmias, and cardiogenic shock. AM is moving from being a definitive diagnosis based on histological evidence of inflammatory infiltrates on cardiac tissue to a working diagnosis supported by high sensitivity troponin increase in association with specific cardiac magnetic resonance imaging (CMRI) findings. Though experts still diverge between those advocating for histological definition versus those supporting a mainly clinical definition of myocarditis, in the real-world practice the diagnosis of AM has undoubtedly shifted from being mainly biopsy-based to solely CMRI-based in most of clinical scenarios. It is thus important to clearly define selected settings where EMB is a must, as information derived from histology is essential for an optimal management. As in other medical conditions, a risk-based approach should be promoted in order to identify the most severe AM cases requiring appropriate bundles of care, including early recognition, transfer to tertiary centers, aggressive circulatory supports with inotropes and mechanical devices, histologic confirmation and eventual immunosuppressive therapy. Despite improvements in recognition and treatment of AM, including a broader use of promising mechanical circulatory supports, severe forms of AM are still burdened by dismal outcomes. This review is focused on recent clinical studies and registries that shed new insights on AM. Attention will be paid to contemporary outcomes and predictors of prognosis, the emerging entity of immune checkpoint inhibitors-associated myocarditis, updated CMRI diagnostic criteria, new data on the use of temporary mechanical circulatory supports in fulminant myocarditis. The role of viruses as etiologic agents will be reviewed and a brief update on pediatric AM is also provided. Finally, we summarize a risk-based approach to AM, based on available evidence and clinical experience.


title: Antioxidant Status and Immune Activity of Glycyrrhizin in Allergic Rhinitis Mice

text: Oxidative stress is considered as a major risk factor that contributes to increased lipid peroxidation and declined antioxidants in some degenerative diseases. Glycyrrhizin is widely used to cure allergic diseases due to its medicinal properties. In the present study, we evaluated the role of glycyrrhizin on lipid peroxidation and antioxidant status in the blood and nasal mucosa of allergic rhinitis (AR) mice. Mice were divided into six groups: normal control mice, model control (MC) mice, three glycyrrhizin-treated mice groups and lycopene-treated mice. Sensitization-associated increase in lipid peroxidation was observed in the blood and nasal mucosa of MC mice. Activities of antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), total antioxidant capacity (TAOC) and levels of glutathione (GSH) were found to be significantly decreased in the blood and nasal mucosa in MC mice when compared to normal control mice. However, normalized lipid peroxidation and antioxidant defenses were reported in the glycyrrhizin-treated and lycopene-treated mice. Moreover, glycyrrhizin treatment still enhanced IFN-γ and reduced IL-4 levels in glycyrrhizin-treated mice. These findings demonstrated that glycyrrhizin treatment enhanced the antioxidant status and decreased the incidence of free radical-induced lipid peroxidation and improved immunity activities in the blood and nasal mucosa of AR mice.


title: Epidemiologic Features of 135 Patients With Coronavirus Disease (COVID-19) in Tianjin, China

text: OBJECTIVE: This study describes the epidemiologic features of an outbreak of the coronavirus disease (COVID-19) in Tianjin caused by a novel coronavirus and provides the scientific basis for prevention and control measures. METHODS: Data from COVID-19 cases were collected from daily notifications given to the National Health Commission of the People’s Republic of China and Tianjin Health Committee. All of the data were analyzed with SPSS, version 24.0 software (IBM Corp, Armonk, NY). RESULTS: As of February 24, 2020, there have been 135 confirmed cases, 3 deaths, and 87 recoveries in Tianjin, China. The incidence of COVID-19 was 8.65/1 000 000 with a 2.22% case fatality rate. Regarding geographic distribution, the incidence was 8.82 per 1 000 000 in urban areas and 8.00 per 1 000 000 in suburbs. During the early stage of the epidemic, most cases came from urban areas and in patients with a history of sojourning in Hubei Province. The majority of patients were 31–70 years old (75.97%). A familial clustering was the most important characteristic of COVID-19 (accounting for 74.81%). CONCLUSIONS: Current information suggests that people are generally susceptible to COVID-19, which has shown a familial clustering in Tianjin.


Managing Endovascular Workload During COVID-19 Outbreak – the Singapore Experience


title: Clinicopathological findings and disease staging of feline infectious peritonitis: 51 cases from 2003 to 2009 in Taiwan

text: Fifty-one cats histopathologically confirmed to have been naturally infected by feline infectious peritonitis (FIP), were collected to analyse the clinical and laboratory findings and to characterise disease staging. Effusive FIP was found in 33 cats, non-effusive FIP in 12 cats, and mixed-type in six cats. Highly significant decreases in haematocrit and albumin levels and an increase in total bilirubin level were noted in both effusive and non-effusive FIP, at first presentation and before death. In serial blood examinations of the effusive group, anaemia and increases in bilirubin and aspartate aminotransferase (AST) were observed from 2 weeks to 0–3 days before death. The packed cell volume, bilirubin, AST, potassium, and sodium levels were established to predict disease staging and survival time. Cumulative points ranging from 0 to 4, 5 to 11 and excess of 12, indicate that the cat can survive for at least 2 weeks, less than 2 weeks and less than 3 days, respectively.


docid: lqroorsh

title: Emergence of human caliciviruses among diarrhea cases in southwest China

text: BACKGROUND: Acute diarrhea is one of the most serious problems in global public health that causes considerable morbidity and mortality worldwide. Human caliciviruses (HuCV) including norovirus (NoV, genogroup GI and GII) and sapovirus (SaV), is a leading cause of acute sporadic diarrhea in individuals across all age groups. However, few studies had been conducted clarifying the characteristics of HuCV in diarrhea cases across all age groups in China. Our study was aimed at assessing the HuCV-related diarrhea burden and NoV genotypes distribution in southwest China. METHODS: The study was conducted in four hospitals in Kunming city, Yunnan province, from June 2014 to July 2015. Stool specimens were collected from 1,121 diarrhea cases and 319 healthy controls in outpatient departments. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect NoV (GI, GII) and SaV. Sequencing was applied to confirm the three viral infections and phylogenetic analysis was performed to determine their genotypes. A structured questionnaire was used to record the demographic information and clinical symptoms of subjects. RESULTS: HuCV was detected at an 11.0 % infection rate in 1,121 diarrhea cases and at 3.4 % rate in 319 non-diarrhea subjects (p < 0.0001, OR = 3.5, 95 % CI 1.8–6.5). The prevalence of the NoV genogroup GII and genotype GII.4 in diarrhea cases was significantly higher than that found in healthy controls (p < 0.0001, p = 0.018, respectively). NoV GII (n = 118, 10.5 %) was the most common HuCV subtype in diarrhea cases, followed by SaV (n = 3, 0.3 %) and NoV GI (n = 2, 0.2 %). Of 118 NoV GII strains isolated from diarrhea patients. GII.4 (n = 55, 46.6 %) was the predominant strain, followed by GII.3 (n = 28, 23.7 %), GII.12 (n = 25, 21.2 %), GII.17 (n = 8, 6.8 %), and GII.5 (n = 2, 1.7 %). Of the 55 GII.4 strains, the GII.4 Sydney 2012 variant had absolutely predominant prevalence (n = 52, 94.5 %), followed by the NoV GII.4-2006b variant (n = 3, 5.5 %). The GII.4 Orleans 2009 variant was not found in diarrhea cases of the study. CONCLUSIONS: NoV GII was the major genogroup and GII.4 was the most predominant strain detected in diarrhea patients. The GII.17 is an emergent variant in sporadic diarrhea and might become the predominant strain in diarrhea cases in the near future. Rapid, accurate detection kits need to be developed to help us find and treat NoV-associated diarrhea in clinical settings in a timely manner.


title: COVID-19 Pandemic: Global Impact and Potential Implications for Cardiovascular Disease in Canada

text: BACKGROUND: Literature indicates that cardiovascular disease (CVD, including stroke), older age, and availability of healthcare resources impact COVID-19 case fatality rates (CFR). The cumulative effect of COVID-19 CFR in global CVD populations and the extrapolated impact on access to healthcare services in the CVD population in Canada are not fully known. This study explored the relationships of factors that may impact COVID-19 CFR and estimated the potential indirect impact of COVID-19 on Canadian healthcare resources. METHODS: Country-level epidemiological data were analyzed to study the correlation, main effect, and interaction between COVID-19 CFR and: a) proportion of the population with CVD, b) proportion of the population ≥ 65 years, and c) availability of essential health services as defined by the World Health Organization Universal Health Coverage (UHC) index. For indirect implications on healthcare resources, estimates of the volume of postponed coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) and valve surgeries in Ontario were calculated. RESULTS: Positive correlations were found between COVID-19 CFR and a) proportion of the population with CVD (ρ=0.40, p=0.001), b) proportion of the population ≥ 65 years (ρ=0.43, p=0.0005) and c) UHC index (ρ=0.27, p=0.03). For every 1% increase in proportion of the population ≥ 65 years or proportion of the population with CVD, COVID-19 CFR was 9% and 19% higher, respectively. Approximately 1,252 procedures would be postponed monthly in Ontario due to current public health measures. CONCLUSIONS: Countries with more prevalent CVD reported higher COVID-19 CFR. Strain on healthcare resources is likely in Canada.


title: Levels and sources of hourly PM2.5-related elements during the control period of the COVID-19 pandemic at a rural site between Beijing and Tianjin

text: Abstract To control the spread of the novel coronavirus disease 2019 (COVID-19) in China, many anthropogenic activities were reduced and even closed on the national scale. To study the impact of this reduction and closing down, hourly concentrations of PM2.5-related elements were measured at a rural site before (12–25 January 2020), during (26 January–9 February 2020) and after (22 March–2 April 2020) all people gathered in their homes and could not return to economic zones for work. Nine major sources were identified by the positive matrix factorization model, including fireworks burning, coal combustion, vehicle emissions, dust, Cr industry, oil combustion, Se industry, Zn smelter, and iron and steel industry. Before the control period, K, Fe, Ca, Zn, Ba and Cu were the main elements, and fireworks burning, Zn smelter and vehicle emissions provide the highest contributions to the total element mass with 55%, 12.1% and 10.3%, respectively. During the control period, K, Fe, Ba, Cu and Zn were the dominating elements, and fireworks burning and vehicle emissions contributed 55% and 27% of the total element mass. After the control period, Fe, K, Ca, Zn and Ba were the main elements, and dust and iron and steel industry were responsible for 56% and 21% of the total element mass. The increased contribution from vehicle emissions during the control period could be attributed to our sampling site being near a town hospital and the fact that the vehicle activities were not restricted. The source apportionment results were also related to air mass backward trajectories. The largest reductions of dust, coal combustion, and the industrial sources (Cr industry, Zn smelter, Se industry, iron and steel industry) were distinctly seen for northwest transport (Ulanqab) and were least significant for northeast transport (Tangshan and Tianjin).


title: High-neurovirulence GDVII virus induces apoptosis in murine astrocytes through tumor necrosis factor (TNF)-receptor and TNF-related apoptosis-inducing ligand

text: Abstract We carried out a study to determine if the high-neurovirulence GDVII strain of Theiler’s murine encephalomyelitis virus (TMEV) and the demyelinating, low-neurovirulence BeAn strain induced apoptosis in murine astrocytes. Astrocytes, the major glial cell population of the central nervous system, were semipermissive for GDVII virus replication. Programmed cell death, demonstrated by apoptosis-specific caspase-3 protease activity, was maximal 8 h after GDVII infection at an m.o.i. of 1. Purified TMEV capsid proteins VP1, VP2, and VP3 did not induce apoptosis but antibodies to VP1 and VP2 inhibited it. Antibody inhibition of caspase-3 activity as well as flow cytometry experiments implicated TNF-related apoptosis-inducing ligand (TRAIL) and TNF-α-receptor (TNF-R) in apoptosis signaling. Converselly, TNF-α and the TRAIL-receptor were not upregulated. Furthermore, the number of functional TNF-α receptors, but not their affinity, was increased in apoptotic GDVII virus-infected astrocytes, as confirmed in binding experiments with 125I-labeled recombinant murine TNF-α. In vivo studies showed that most of the cells loaded with the virus when injected in the brains of SJL mice were neurons but very few showed TUNEL costaining. Conversely, many of the apoptotic cells found were also positive for GFAP staining.


title: Theoretically estimated risk of severe acute respiratory syndrome transmission through blood transfusion during an epidemic in Shenzhen, Guangdong, China in 2003

text: Abstract Background Severe acute respiratory syndrome (SARS) is a newly recognized infectious disease that caused an outbreak in south China in 2003. The cause of SARS was identified as a novel coronavirus (CoV). The existence of asymptomatic seroconvertors and the detection of the SARS-CoV RNA in plasma during the course of infection all suggest that SARS could, as least theoretically, be transmitted by transfusion. An estimate of the risk of SARS transmission through blood transfusion will contribute to decisions concerning blood safety monitoring and may be useful in the design of strategies to decrease the risk of transfusion-transmitted infections. Study design and methods Case onset dates from the 2003 Shenzhen SARS epidemic and investigational results from Taiwan on viremia in humans are used to estimate the number of cases that were viremic throughout the epidemic. Estimates of the asymptomatic-to-clinically confirmed SARS-CoV infection ratio, the proportion of asymptomatic infections reported in a seroprevalence survey in Hongkong, and the population size of Shenzhen are used to infer the SARS-CoV transfusion–transmission risk. Statistical resampling methods are used. Results Based on data from Shenzhen, Hongkong and Taiwan, the maximum and mean risk (per million) of SARS-CoV transmission from donors in Shenzhen were estimated as 23.57 (95% CI: 6.83–47.69) and 14.11 (95% CI: 11.00–17.22), respectively. The estimated risk peaked on April 02, 2003. Conclusions Although there are currently no confirmed reports of the transmission of SARS-CoV from asymptomatic individuals, recent research data indicate that transfusion-transmitted SARS-CoV is at least theoretically possible. Although the risk is low, with its rapid spread of the disease, appearance of alarmingly high infectivity and high fatality rate, public health authorities need to consider strategies for blood donor recruitment and virus inactivation during an epidemic to further ensure blood safety.


title: Knowledge of inter-facility transport among emergency nurses in Hong Kong: A questionnaire survey

text: Abstract Introduction Inter-facility transport (IFT) is a dynamic process and its quality largely depends on pre-transport preparation, emergency equipment support and recognition of possible en route adverse events. This study aims to evaluate knowledge of IFT among emergency nurses of three Accident and Emergency Departments in Hong Kong. Methods Questionnaires were distributed to registered nurses of the three departments. Data was sought on participants’ characteristics, knowledge on equipment preparation and management of en route adverse events. Four clinical IFT scenarios were set for participants and answers were scored. Measured outcomes were defined as (1) relationships between clinical experience and relevant training in IFT with questionnaire results, (2) staff knowledge of the equipment carried routinely in ambulances and (3) the en route adverse events encountered according to the participants’ past experience. Results Participants’ test scores ranged from 24 to 37 (out of 40) with a mean of 30.6 (95% confidence interval 29.7–31.5). Participants with more clinical experience demonstrated significantly better test scores (p <0.05). Most participants were familiar with the monitoring devices carried in ambulances but were less familiar with the pharmacologic agents and airway devices available routinely in Hong Kong ambulances. Thirty participants (59%) had encountered en route adverse events in the past. Conclusion Nurses in emergency departments in Hong Kong have good knowledge of IFT. Extensive clinical experience is related to better IFT knowledge. IFT training for nurses should emphasize available ambulance service resources and capabilities.


title: Avian viral surveillance in Victoria, Australia, and detection of two novel avian herpesviruses

text: Viruses in avian hosts can pose threats to avian health and some have zoonotic potential. Hospitals that provide veterinary care for avian patients may serve as a site of exposure of other birds and human staff in the facility to these viruses. They can also provide a useful location to collect samples from avian patients in order to examine the viruses present in wild birds. This study aimed to investigate viruses of biosecurity and/or zoonotic significance in Australian birds by screening samples collected from 409 birds presented to the Australian Wildlife Health Centre at Zoos Victoria’s Healesville Sanctuary for veterinary care between December 2014 and December 2015. Samples were tested for avian influenza viruses, herpesviruses, paramyxoviruses and coronaviruses, using genus- or family-wide polymerase chain reaction methods coupled with sequencing and phylogenetic analyses for detection and identification of both known and novel viruses. A very low prevalence of viruses was detected. Columbid alphaherpesvirus 1 was detected from a powerful owl (Ninox strenua) with inclusion body hepatitis, and an avian paramyxovirus most similar to Avian avulavirus 5 was detected from a musk lorikeet (Glossopsitta concinna). Two distinct novel avian alphaherpesviruses were detected in samples from a sulphur-crested cockatoo (Cacatua galerita) and a tawny frogmouth (Podargus strigoides). Avian influenza viruses and avian coronaviruses were not detected. The clinical significance of the newly detected viruses remains undetermined. Further studies are needed to assess the host specificity, epidemiology, pathogenicity and host-pathogen relationships of these novel viruses. Further genome characterization is also indicated, and would be required before these viruses can be formally classified taxonomically. The detection of these viruses contributes to our knowledge on avian virodiversity. The low level of avian virus detection, and the absence of any viruses with zoonotic potential, suggests low risk to biosecurity and human health.


title: Mass spectral profiling: An effective tool for quality control of herbal medicines

text: Abstract Quality control of herbal medicines (HMs) is a big big headache because of the high complexity and unknown mechanism on disease treatment. In this work, mass spectral profiling, a new tool for data processing is proposed to help a lot in solving this problem as gas chromatography–mass spectroscopy (GC–MS) is used to detect both the active and non-active ingredients buried in HMs. The main idea of mass spectral profiling is employment of target m/z points of GC–MS data on the extraction of chromatographic profiles of pure and/or mixed compositions concerned. Further, the absolute or relative abundance at these m/z points can be utilized for results interpretation. With the help of this tool, the qualitative and quantitative information of chemical components within complicated HMs will be mined out effectively. It can then be recommended as reference indices to assess the importance of target compositions in HMs, such as efficacy evaluation on disease treatment of the active constituents. Mass spectral profiling with less data points significantly improves the possibility to get the rich information with no strong requirements of data preprocessing procedures, like alignment of shift of retention times among different chromatographic profiles. It is powerful for quality control of HMs coupled with pattern recognition techniques on high-throughput data sets. In this study, a commonly used herbal medicine, Houttuynia cordata Thunb and its finished injection products, were used to deliver the strategies. Absolutely, the working principles can be extended to the investigation of metabonomics with gas chromatography–time-of-flight–mass spectrometry (GC–MS–TOF). The good performance of mass spectral profiling shows that it can be a promising tool in the future studies of complex mixture systems.


docid: vjzfzshh

title: Effect of mismatch repair on the mutation rate of bacteriophage ϕX174

text: Viral mutation rates vary widely in nature, yet the mechanistic and evolutionary determinants of this variability remain unclear. Small DNA viruses mutate orders of magnitude faster than their hosts despite using host-encoded polymerases for replication, which suggests these viruses may avoid post-replicative repair. Supporting this, the genome of bacteriophage ϕX174 is completely devoid of GATC sequence motifs, which are required for methyl-directed mismatch repair in Escherichia coli. Here, we show that restoration of the randomly expected number of GATC sites leads to an eightfold reduction in the rate of spontaneous mutation of the phage, without severely impairing its replicative capacity over the short term. However, the efficacy of mismatch repair in the presence of GATC sites is limited by inefficient methylation of the viral DNA. Therefore, both GATC avoidance and DNA under-methylation elevate the mutation rate of the phage relative to that of the host. We also found that the effects of GATC sites on the phage mutation rate vary extensively depending on their specific location within the phage genome. Finally, the mutation rate reduction afforded by GATC sites is fully reverted under stress conditions, which up-regulate repair pathways and expression of error-prone host polymerases such as heat and treatment with the base analog 5-fluorouracil, suggesting that access to repair renders the phage sensitive to stress-induced mutagenesis.


title: Experiences with infectious cDNA clones of equine arteritis virus: Lessons learned and insights gained

text: Abstract The advent of recombinant DNA technology, development of infectious cDNA clones of RNA viruses, and reverse genetic technologies have revolutionized how viruses are studied. Genetic manipulation of full-length cDNA clones has become an especially important and widely used tool to study the biology, pathogenesis, and virulence determinants of both positive and negative stranded RNA viruses. The first full-length infectious cDNA clone of equine arteritis virus (EAV) was developed in 1996 and was also the first full-length infectious cDNA clone constructed from a member of the order Nidovirales. This clone was extensively used to characterize the molecular biology of EAV and other Nidoviruses. The objective of this review is to summarize the characterization of the virulence (or attenuation) phenotype of the recombinant viruses derived from several infectious cDNA clones of EAV in horses, as well as their application for characterization of the molecular basis of viral neutralization, persistence, and cellular tropism.


title: Ein einziger Patient befeuerte die MERS-Epidemie

text: Wie bei SARS vor 14 Jahren wurde jetzt auch bei MERS in Südkorea ein Superverbreiter identifiziert: Ein Mann hat wohl einen Großteil der Patienten angesteckt.


title: Positive natural selection in the evolution of human metapneumovirus attachment glycoprotein

text: Abstract Human metapneumovirus (hMPV), a newly discovered virus of the family Paramyxoviridae, has been associated with upper and lower respiratory tract infections in different age groups in many countries. The putative attachment (G) glycoprotein of this virus was previously reported to have shown more extensive nucleotide and deduced amino acid sequence polymorphism than any other genomic regions of this virus, leading to four sub-lineages. Using a maximum likelihood-based codon substitution model of sequence evolution, here we report that sequences of extracellular domain of 8 amino acid sites in lineage 1a, and 3 amino acid sites each in lineage 1b, 2a, and 2b have a higher rate of nonsynonymous substitutions (dN) than the synonymous substitutions (dS) with a posterior probability above 0.95, thus suggesting the evidence of adaptive evolution driven by Darwinian selection. Although it is unclear whether these amino acid adaptations are driven by differential immune pressure or some other factors, identification of these positively selected amino acid sites would help in better screening using epitope mapping technology to identify and localize the sites that can be recognized by the immune system. We also observed surprisingly higher nucleotide substitution rates per site, per year for each lineage of hMPV than the rates that were previously reported for the human respiratory syncytial virus, suggesting rapid evolutionary dynamics of hMPV.


EMERGING RESPIRATORY DISEASE - CORONAVIRUSES


title: Norovirus in Captive Lion Cub (Panthera leo)

text: African lions (Panthera leo) are susceptible to viral diseases of domestic carnivores, including feline calicivirus infection. We report the identification of a novel enteric calicivirus, genetically related to human noroviruses of genogroup IV, in a lion cub that died of severe hemorrhagic enteritis.


title: Positive mental health-related impacts of the SARS epidemic on the general public in Hong Kong and their associations with other negative impacts

text: Summary Objectives To investigate 2 positive impacts (better family/social support and lifestyle changes) and their associations with other negative impacts. Study design and participants A telephone survey using random telephone numbers and a structured questionnaire was conducted in Hong Kong general population. Eight hundred and eighteen Hong Kong residents of age 18–60 years completed the interview (response rate: 65%) at around end of June 2003, the early ending phase of the epidemic. Results Over 60% of the respondents stated that they cared more about the family members' feelings; about 30%–40% stated that they found their friends, their family members more supportive or having more sharing with others when not feeling happy; only a few percent felt the opposite. Further, about 2/3 of the respondents paid more attention to their mental health. About 35%–40% took more time to rest, for relaxation or doing exercise. These items were, in general, negatively associated with post-traumatic stress, perception of stress and other perceptions that were related to SARS. Conclusions SARS have brought some positive impacts on social/family support, mental health awareness and lifestyle changes. These positive impacts were associated with other relevant negative impacts and might be important cushions of the negative impact.


title: Multiantibody Strategies for HIV

text: Vaccination strategies depend entirely on the appropriate responsiveness of our immune system against particular antigens. For this active immunization to be truly effective, neutralizing antibodies (nAbs) need to efficiently counter the infectivity or propagation of the pathogen. Some viruses, including HIV, are able to take advantage of this immune response in order to evade nAbs. This review focuses on viral immune evasion strategies that result directly from a robust immune response to infection or vaccination. A rationale for multi-Ab therapy to circumvent this phenomenon is discussed. Progress in the formulation, production, and regulatory approval of monoclonal antibodies (mAbs) is presented.


title: Chapter Three Type I interferons and endoplasmic reticulum stress in health and disease

text: Abstract Type I interferons (IFNs) comprise of pro-inflammatory cytokines created, as well as sensed, by all nucleated cells with the main objective of blocking pathogens-driven infections. Owing to this broad range of influence, type I IFNs also exhibit critical functions in many sterile inflammatory diseases and immunopathologies, especially those associated with endoplasmic reticulum (ER) stress-driven signaling pathways. Indeed, over the years accumulating evidence has indicated that the presence of ER stress can influence the production, or sensing of, type I IFNs induced by perturbations like pattern recognition receptor (PRR) agonists, infections (bacterial, viral or parasitic) or autoimmunity. In this article we discuss the link between type I IFNs and ER stress in various diseased contexts. We describe how ER stress regulates type I IFNs production or sensing, or how type I IFNs may induce ER stress, in various circumstances like microbial infections, autoimmunity, diabetes, cancer and other ER stress-related contexts.


title: Identification of residues on human receptor DPP4 critical for MERS-CoV binding and entry

text: Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) infects host cells through binding the receptor binding domain (RBD) on its spike glycoprotein to human receptor dipeptidyl peptidase 4 (hDPP4). Here, we report identification of critical residues on hDPP4 for RBD binding and virus entry through analysis of a panel of hDPP4 mutants. Based on the RBD–hDPP4 crystal structure we reported, the mutated residues were located at the interface between RBD and hDPP4, which potentially changed the polarity, hydrophobic or hydrophilic properties of hDPP4, thereby interfering or disrupting their interaction with RBD. Using surface plasmon resonance (SPR) binding analysis and pseudovirus infection assay, we showed that several residues in hDPP4–RBD binding interface were important on hDPP4–RBD binding and viral entry. These results provide atomic insights into the features of interactions between hDPP4 and MERS-CoV RBD, and also provide potential explanation for cellular and species tropism of MERS-CoV infection.


title: IFITM proteins are incorporated onto HIV-1 virion particles and negatively imprint their infectivity

text: BACKGROUND: Interferon induced transmembrane proteins 1, 2 and 3 (IFITMs) belong to a family of highly related antiviral factors that have been shown to interfere with a large spectrum of viruses including Filoviruses, Coronaviruses, Influenza virus, Dengue virus and HIV-1. In all these cases, the reported mechanism of antiviral inhibition indicates that the pool of IFITM proteins present in target cells blocks incoming viral particles in endosomal vesicles where they are subsequently degraded. RESULTS: In this study, we describe an additional mechanism through which IFITMs block HIV-1. In virus-producing cells, IFITMs coalesce with forming virions and are incorporated into viral particles. Expression of IFITMs during virion assembly leads to the production of virion particles of decreased infectivity that are mostly affected during entry in target cells. This mechanism of inhibition is exerted against different retroviruses and does not seem to be dependent on the type of Envelope present on retroviral particles. CONCLUSIONS: The results described here identify a novel mechanism through which IFITMs affect HIV-1 infectivity during the late phases of the viral life cycle. Put in the context of data obtained by other laboratories, these results indicate that IFITMs can target HIV at two distinct moments of its life cycle, in target cells as well as in virus-producing cells. These results raise the possibility that IFITMs could similarly affect distinct steps of the life cycle of a number of other viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-014-0103-y) contains supplementary material, which is available to authorized users.


The Challenge of Laypeople Cardio-pulmonary Resuscitation Training during and after COVID-19 Pandemic


title: Immunophysiology and Pathology of Inflammation in the Testis and Epididymis

text: ABSTRACT: The ability of spermatogenic cells to evade the host immune system and the ability of systemic inflammation to inhibit male reproductive function represent two of the most intriguing conundrums of male reproduction. Clearly, an understanding of the underlying immunology of the male reproductive tract is crucial to resolving these superficially incompatible observations. One important consideration must be the very different immunological environments of the testis, where sperm develop, and the epididymis, where sperm mature and are stored. Compared with the elaborate blood‐testis barrier, the tight junctions of the epididymis are much less effective. Unlike the seminiferous epithelium, immune cells are commonly observed within the epithelium, and can even be found within the lumen, of the epididymis. Crucially, there is little evidence for extended allograft survival (immune privilege) in the epididymis, as it exists in the testis, and the epididymis is much more susceptible to loss of immune tolerance. Moreover, the incidence of epididymitis is considerably greater than that of orchitis in humans, and susceptibility to sperm antibody formation after damage to the epididymis or vas deferens increases with increasing distance of the damage from the testis. Although we still know relatively little about testicular immunity, we know less about the interactions between the epididymis and the immune system. Given that the epididymis appears to be more susceptible to inflammation and immune reactions than the testis, and thereby represents the weaker link in protecting developing sperm from the immune system, it is probably time this imbalance in knowledge was addressed.


title: What Macromolecular Crowding Can Do to a Protein

text: The intracellular environment represents an extremely crowded milieu, with a limited amount of free water and an almost complete lack of unoccupied space. Obviously, slightly salted aqueous solutions containing low concentrations of a biomolecule of interest are too simplistic to mimic the “real life” situation, where the biomolecule of interest scrambles and wades through the tightly packed crowd. In laboratory practice, such macromolecular crowding is typically mimicked by concentrated solutions of various polymers that serve as model “crowding agents”. Studies under these conditions revealed that macromolecular crowding might affect protein structure, folding, shape, conformational stability, binding of small molecules, enzymatic activity, protein-protein interactions, protein-nucleic acid interactions, and pathological aggregation. The goal of this review is to systematically analyze currently available experimental data on the variety of effects of macromolecular crowding on a protein molecule. The review covers more than 320 papers and therefore represents one of the most comprehensive compendia of the current knowledge in this exciting area.


title: Egg yolk antibodies (IgY) and their applications in human and veterinary health: A review

text: Abstract Egg yolk constitutes a relevant alternative source of antibodies. It presents some advantages over mammalian serum immunoglobulins regarding productivity, animal welfare and specificity. The main immunoglobulin present in avian blood (IgY) is transmitted to their offspring and accumulates in egg yolks, which enables the non-invasive harvesting of high amounts of antibodies. Moreover, due to structural differences and phylogenetic distance, IgY is more suitable for diagnostic purposes than mammalian antibodies, since it does not react with certain components of the human immune system and displays greater avidity for mammalian conserved proteins. IgY has been extensively used in health researches, as both therapeutic and diagnostic tool. This article aims to review its applications in both human and veterinary health.


title: Immunogenetic Variation and Differential Pathogen Exposure in Free-Ranging Cheetahs across Namibian Farmlands

text: BACKGROUND: Genes under selection provide ecologically important information useful for conservation issues. Major histocompatibility complex (MHC) class I and II genes are essential for the immune defence against pathogens from intracellular (e.g. viruses) and extracellular (e.g. helminths) origins, respectively. Serosurvey studies in Namibian cheetahs (Acinonyx juabuts) revealed higher exposure to viral pathogens in individuals from north-central than east-central regions. Here we examined whether the observed differences in exposure to viruses influence the patterns of genetic variation and differentiation at MHC loci in 88 free-ranging Namibian cheetahs. METHODOLOGY/PRINCIPAL FINDINGS: Genetic variation at MHC I and II loci was assessed through single-stranded conformation polymorphism (SSCP) analysis and sequencing. While the overall allelic diversity did not differ, we observed a high genetic differentiation at MHC class I loci between cheetahs from north-central and east-central Namibia. No such differentiation in MHC class II and neutral markers were found. CONCLUSIONS/SIGNIFICANCE: Our results suggest that MHC class I variation mirrors the variation in selection pressure imposed by viruses in free-ranging cheetahs across Namibian farmland. This is of high significance for future management and conservation programs of this species.


title: Quasispecies as a matter of fact: Viruses and beyond

text: Abstract We review the origins of the quasispecies concept and its relevance for RNA virus evolution, viral pathogenesis and antiviral treatment strategies. We emphasize a critical point of quasispecies that refers to genome collectivities as the unit of selection, and establish parallels between RNA viruses and some cellular systems such as bacteria and tumor cells. We refer also to tantalizing new observations that suggest quasispecies behavior in prions, perhaps as a result of the same quantum-mechanical indeterminations that underlie protein conformation and error-prone replication in genetic systems. If substantiated, these observations with prions could lead to new research on the structure–function relationship of non-nucleic acid biological molecules.