title: Hepatitis C Virus RNA Replication

text: Genome replication is a crucial step in the life cycle of any virus. HCV is a positive strand RNA virus and requires a set of nonstructural proteins (NS3, 4A, 4B, 5A, and 5B) as well as cis-acting replication elements at the genome termini for amplification of the viral RNA. All nonstructural proteins are tightly associated with membranes derived from the endoplasmic reticulum and induce vesicular membrane alterations designated the membranous web, harboring the viral replication sites. The viral RNA-dependent RNA polymerase NS5B is the key enzyme of RNA synthesis. Structural, biochemical, and reverse genetic studies have revealed important insights into the mode of action of NS5B and the mechanism governing RNA replication. Although a comprehensive understanding of the regulation of RNA synthesis is still missing, a number of important viral and host determinants have been defined. This chapter summarizes our current knowledge on the role of viral and host cell proteins as well as cis-acting replication elements involved in the biogenesis of the membranous web and in viral RNA synthesis.


title: Sinonasal pathophysiology of SARS‐CoV‐2 and COVID‐19: A systematic review of the current evidence

text: OBJECTIVE: The ongoing pandemic of coronavirus disease (2019 coronavirus disease [COVID‐19]), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) virus, is highly contagious with high morbidity and mortality. The role of the nasal and paranasal sinus cavities is increasingly recognized for COVID‐19 symptomatology and transmission. We therefore conducted a systematic review, synthesizing existing scientific evidence about sinonasal pathophysiology in COVID‐19. STUDY DESIGN: Systematic review. METHODS: Systematic searches were performed of all indexed studies in PubMed/Medline and Cochrane databases through 28 March 2020 and studies searchable on http://preprints.com (including ArXiv and Scilit repositories) through 30 March 2020. Data extraction focused on sinonasal pathophysiology in COVID‐19. RESULTS: A total of 19 studies were identified. The sinonasal cavity may be a major site of infection by SARS‐CoV‐2, where susceptibility genes required for infection are expressed at high levels and may be modulated by environmental and host factors. Viral shedding appears to be highest from the nose, therefore reflecting a major source for transmission. This has been highlighted by multiple reports of health care‐associated infection (HAI) during rhinologic procedures, which are now consequently considered to be high risk for SARS‐CoV‐2 transmission to health care workers. While sinonasal symptomatology, such as rhinorrhea or congestion, appears to be a rarer symptom of COVID‐19, anosmia without nasal obstruction is reported as highly specific predictor of COVID‐19+ patients. CONCLUSION: Sinonasal pathophysiology is increasingly important in our understanding of COVID‐19. The sinonasal tract may be an important site of infection while sinonasal viral shedding may be an important transmission mechanism—including HAI. Anosmia without nasal obstruction may be a highly specific indicator of COVID‐19. LEVEL OF EVIDENCE: 2a.


A comprehensive assessment of the coagulation profile in critically ill COVID-19 patients


title: Success of tumorsphere isolation from WHO grade IV gliomas does not correlate with the weight of fresh tumor specimens: an immunohistochemical characterization of tumorsphere differentiation

text: BACKGROUND: A trend of stage-by-stage increase in tumorsphere (TS) formation from glioma samples has been reported. Despite this trend, not all surgical specimens give rise to TSs, even World Health Organization (WHO) grade IV gliomas. Furthermore, it has been reported that differences in overall survival of primary glioblastoma patients depends on the propensity of their tumors to form TSs. However, the weights of fresh specimens vary from one surgical isolate to the next. METHODS: Accordingly, we evaluated the relationship between the weights of surgical specimens in WHO grade IV gliomas with the capacity to isolate TSs. Thirty-five fresh WHO grade IV glioma specimens were separated into two groups, based on whether they were positive or negative for TS isolation, and the relationship between TS isolation and weight of surgical specimens was assessed. RESULTS: We observed no significant difference in the weights of surgical samples in the two groups, and found that the optimal weight of specimens for TSs isolation was 500 mg. CONCLUSION: Thus, contrary to our expectations, the ability to isolate TSs from WHO grade IV glioma specimens was not related to the weight of fresh specimens.


Animal-to-Human SARS-associated Coronavirus Transmission?


title: CHARACTERIZATION OF ANTIBODIES INDUCED BY VACCINATION WITH HEPATITIS C VIRUS ENVELOPE GLYCOPROTEINS

text: Hepatitis C virus (HCV) envelope glycoproteins, E1 and E2, were used with MF59 adjuvant as a candidate vaccine for a phase I safety and immunogenicity trial. Ten of the 41 vaccinee sera tested displayed a VSV/HCV surrogate pseudotype neutralization titer of ≥1/20, 15 of the 36 sera tested had a neutralization titer of ≥ 1/400 against HIV/HCV pseudotype, and 10 of the 36 sera tested had a neutralization titer of ≥1/20 of cell culture grown HCVgenotype 1a. Neutralizing sera had increased affinity, and displayed >2 fold higher specific activity to well characterized epitopes on E1/E2, especially to the hypervariable region 1 (HVR1) of E2.


title: Evaluation of a new community-based curriculum in disaster medicine for undergraduates

text: BACKGROUND: Nowadays, many medical schools include training in disaster medicine in undergraduate studies. This study evaluated the efficacy of a disaster medicine curriculum recently designed for Saudi Arabian medical students. METHODS: Participants were 15 male and 14 female students in their fourth, fifth or sixth year at Jazan University Medical School, Saudi Arabia. The course was held at the Research Center in Emergency and Disaster Medicine and Computer Sciences Applied to the Medical Practice in Novara, Italy. RESULTS: The overall mean score on a test given before the course was 41.0 % and it increased to 67.7 % on the post-test (Wilcoxon test for paired samples: z = 4.71, p < 0.0001). There were no significant differences between the mean scores of males and females, or between students in their fourth, fifth or sixth year of medical school. CONCLUSIONS: These results show that this curriculum is effective for teaching disaster medicine to undergraduate medical students. Adoption of this course would help to increase the human resources available for dealing with disaster situations.


title: Geroprotective and senoremediative strategies to reduce the comorbidity, infection rates, severity, and lethality in gerophilic and gerolavic infections

text: The recently identified SARS-CoV-2 betacoronavirus responsible for the COVID-19 pandemic has uncovered the age-associated vulnerability in the burden of disease and put aging research in the spotlight. The limited data available indicates that COVID-19 should be referred to as a gerolavic (from Greek, géros “old man” and epilavís, “harmful”) infection because the infection rates, severity, and lethality are substantially higher in the population aged 60 and older. This is primarily due to comorbidity but may be partially due to immunosenescence, decreased immune function in the elderly, and general loss of function, fitness, and increased frailty associated with aging. Immunosenescence is a major factor affecting vaccination response, as well as the severity and lethality of infectious diseases. While vaccination reduces infection rates, and therapeutic interventions reduce the severity and lethality of infections, these interventions have limitations. Previous studies showed that postulated geroprotectors, such as sirolimus (rapamycin) and its close derivative rapalog everolimus (RAD001), decreased infection rates in a small sample of elderly patients. This article presents a review of the limited literature available on geroprotective and senoremediative interventions that may be investigated to decrease the disease burden of gerolavic infections. This article also highlights a need for rigorous clinical validation of deep aging clocks as surrogate markers of biological age. These could be used to assess the need for, and efficacy of, geroprotective and senoremediative interventions and provide better protection for elderly populations from gerolavic infections. This article does not represent medical advice and the medications described are not yet licensed or recommended as immune system boosters, as they have not undergone clinical evaluation for this purpose.


title: Antibodies against MERS Coronavirus in Dromedary Camels, Kenya, 1992–2013

text: Dromedary camels are a putative source for human infections with Middle East respiratory syndrome coronavirus. We showed that camels sampled in different regions in Kenya during 1992–2013 have antibodies against this virus. High densities of camel populations correlated with increased seropositivity and might be a factor in predicting long-term virus maintenance.


title: Engineering of Live Chimeric Vaccines against Human Metapneumovirus

text: Human metapneumovirus (HMPV) is an important human pathogen that, along with respiratory syncytial virus (RSV), is a major cause of respiratory tract infections in young infants. Development of an effective vaccine against Pneumoviruses has proven to be particularly difficult; despite over 50 years of research in this field, no vaccine against HMPV or RSV is currently available. Recombinant chimeric viruses expressing antigens of other viruses can be generated by reverse genetics and used for simultaneous immunization against more than one pathogen. This approach can result in the development of promising vaccine candidates against HMPV, and several studies have indeed validated viral vectors expressing HMPV antigens. In this review, we summarize current efforts in generating recombinant chimeric vaccines against HMPV, and we discuss their potential optimization based on the correspondence with RSV studies.


title: Coronavirus-Pandemie und ihre Auswirkungen auf Orthopädie und Unfallchirurgie: Operationen, Risiken und Prävention?

text: In order to assess the effects of COVID-19, all health care workers must be aware of the symptoms and course of the disease. Experience and studies from the regions most affected in China and Italy give preliminary information on issues such as the course of infection and the risk to hospital staff. This suggests that surgically treated COVID-19 patients have a higher risk compared to noninfected patients. The surgical staff also appear to be at increased risk of infection. Furthermore, to prevent the health care system from collapse, resources must be saved elsewhere. Elective operations must be reduced. In order to develop criteria for which operations can be performed, the pandemic is divided into different phases. These are based on the development of the pandemic curve. Various aspects should be taken into account when deciding whether an operation is feasible (stage of pandemic, dysfunction in case of omission, conflict with resources for COVID-19 treatment, alternative: outpatient surgery). Thus, the recommendations for carrying out operations should always be adapted to the current, regional and epidemiological situation of the hospital. For this purpose, it is necessary to form a local committee in the hospital to carry out this assessment on a daily basis. General surgical bans do not seem to make medical sense.


title: A conserved region of nonstructural protein 1 from alphacoronaviruses inhibits host gene expression and is critical for viral virulence

text: Coronaviruses are enveloped, single-stranded RNA viruses that are distributed worldwide. They include transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), and the human coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), many of which seriously endanger human health and well-being. Only alphacoronaviruses and betacoronaviruses harbor nonstructural protein 1 (nsp1), which performs multiple functions in inhibiting antiviral host responses. The role of the C terminus of betacoronavirus nsp1 in virulence has been characterized, but the location of the alphacoronavirus nsp1 region that is important for virulence remains unclear. Here, using TGEV nsp1 as a model to explore the function of this protein in alphacoronaviruses, we demonstrate that alphacoronavirus nsp1 inhibits host gene expression. Solving the crystal structure of full-length TGEV at 1.85-Å resolution and conducting several biochemical analyses, we observed that a specific motif (amino acids 91–95) of alphacoronavirus nsp1 is a conserved region that inhibits host protein synthesis. Using a reverse-genetics system based on CRISPR/Cas9 technology to construct a recombinant TGEV in which this specific nsp1 motif was altered, we found that this mutation does not affect virus replication in cell culture but significantly reduces TGEV pathogenicity in pigs. Taken together, our findings suggest that alphacoronavirus nsp1 is an essential virulence determinant, providing a potential paradigm for the development of a new attenuated vaccine based on modified nsp1.


Victoria's perioperative response to the COVID‐19 pandemic


title: Pandemic influenza in Australia: Using telephone surveys to measure perceptions of threat and willingness to comply

text: BACKGROUND: Baseline data is necessary for monitoring how a population perceives the threat of pandemic influenza, and perceives how it would behave in the event of pandemic influenza. Our aim was to develop a module of questions for use in telephone health surveys on perceptions of threat of pandemic influenza, and on preparedness to comply with specific public health behaviours in the event of pandemic influenza. METHODS: A module of questions was developed and field tested on 192 adults using the New South Wales Department of Health's in-house Computer Assisted Telephone Interviewing (CATI) facility. The questions were then modified and re field tested on 202 adults. The module was then incorporated into the New South Wales Population Health Survey in the first quarter of 2007. A representative sample of 2,081 adults completed the module. Their responses were weighted against the state population. RESULTS: The reliability of the questions was acceptable with kappa ranging between 0.25 and 0.51. Overall 14.9% of the state population thought pandemic influenza was very or extremely likely to occur; 45.5% were very or extremely concerned that they or their family would be affected by pandemic influenza if it occurred; and 23.8% had made some level of change to the way they live their life because of the possibility of pandemic influenza. In the event of pandemic influenza, the majority of the population were willing to: be vaccinated (75.4%), be isolated (70.2%), and wear a face mask (59.9%). People with higher levels of threat perception are significantly more likely to be willing to comply with specific public health behaviours. CONCLUSION: While only 14.9% of the state population thought pandemic influenza was very or extremely likely to occur, a significantly higher proportion were concerned for self and family should a pandemic actually occur. The baseline data collected in this survey will be useful for monitoring changes over time in the population's perceptions of threat, and preparedness to comply with specific public health behaviours.


title: Rapid Optical Cavity PCR

text: Recent outbreaks of deadly infectious diseases, such as Ebola and Middle East respiratory syndrome coronavirus, have motivated the research for accurate, rapid diagnostics that can be administered at the point of care. Nucleic acid biomarkers for these diseases can be amplified and quantified via polymerase chain reaction (PCR). In order to solve the problems of conventional PCR—speed, uniform heating and cooling, and massive metal heating blocks—an innovative optofluidic cavity PCR method using light‐emitting diodes (LEDs) is accomplished. Using this device, 30 thermal cycles between 94 °C and 68 °C can be accomplished in 4 min for 1.3 μL (10 min for 10 μL). Simulation results show that temperature differences across the 750 μm thick cavity are less than 2 °C and 0.2 °C, respectively, at 94 °C and 68 °C. Nucleic acid concentrations as low as 10(–8) ng μL(–1) (2 DNA copies per μL) can be amplified with 40 PCR thermal cycles. This simple, ultrafast, precise, robust, and low‐cost optofluidic cavity PCR is favorable for advanced molecular diagnostics and precision medicine. It is especially important for the development of lightweight, point‐of‐care devices for use in both developing and developed countries.


Clinical performance of a rapid test compared to a microplate test to detect total anti SARS-CoV-2 antibodies directed to the spike protein


title: A diagnostic tool to determine a strategic improvisation Readiness Index Score (IRIS) to survive, adapt, and thrive in a crisis

text: Abstract Crises for business-to-business (B2B) firms are characterized by unexpected or unanticipated severe threats that are highly uncertain where strategic response times are low in which executives are victim of overwhelming time pressures to action fast strategic responses to these events—as the threats bring to question the viability and survivability of the firm. Consequently, crises provoke a profound impact on executives' sensemaking, as they attempt strategically navigate these events. We bridge thinking around crisis management with theories of strategic decision-making and conclude that strategic improvisation is a vital mechanism that enables effective management interventions to be executed as a means of surviving, adapting, or potentially thriving under challenging circumstances. We derive a theoretically grounded framework of five strategic imperatives underlying our 10C Strategic Imperative Framework for improvisation readiness. First, we develop the Improvisation Readiness Index Score (IRIS) as a means for executives to diagnose their organization's improvisation readiness according to the requisite strategic imperatives. Second, we present a three-step guide for executives to consider for managing through crisis with improvisation and the strategic imperatives at its heart. Third, we illustrate the strategy improvisation challenges. This allows executives to close the strategic improvisation gaps between their ‘actual’ and ‘preferred’ readiness.


title: Assessment of Specimen Pooling to Conserve SARS CoV-2 Testing Resources

text: Objectives To establish the optimal parameters for group testing of pooled specimens for the detection of SARS-CoV-2. Methods The most efficient pool size was determined to be 5 specimens using a web-based application. From this analysis, 25 experimental pools were created using 50 microliter from one SARS-CoV-2 positive nasopharyngeal specimen mixed with 4 negative patient specimens (50 microliter each) for a total volume of 250 microliter l. Viral RNA was subsequently extracted from each pool and tested using the CDC SARS-CoV-2 RT-PCR assay. Positive pools were consequently split into individual specimens and tested by extraction and PCR. This method was also tested on an unselected group of 60 nasopharyngeal specimens grouped into 12-pools. Results All 25 pools were positive with Cycle threshold (Ct) values within 0 and 5.03 Ct of the original individual specimens. The analysis of 60 specimens determined that two pools were positive followed by identification of two individual specimens among the 60 tested. This testing was accomplished while using 22 extractions/PCR tests, a savings of 38 reactions. Conclusions When the incidence rate of SARS-CoV-2 infection is 10% or less, group testing will result in the saving of reagents and personnel time with an overall increase in testing capability of at least 69%.


title: Measles Control and the Prospect of Eradication

text: Remarkable progress has been made in reducing measles incidence and mortality as a consequence of implementing the measles mortality reduction strategy of the World Health Organization (WHO) and United Nations Children's Fund (UNICEF). The revised global measles mortality reduction goal set forth in the WHO-UNICEF Global Immunization Vision and Strategy for 2006–2015 is to reduce measles deaths by 90% by 2010 compared to the estimated 757,000 deaths in 2000. The possibility of measles eradication has been discussed for almost 40 years, and measles meets many of the criteria for eradication. Global measles eradication will face a number of challenges to achieving and sustaining high levels of vaccine coverage and population immunity, including population growth and demographic changes, conflict and political instability, and public perceptions of vaccine safety. To achieve the measles mortality reduction goal, continued progress needs to be made in delivering measles vaccines to the world's children.


title: Egyptian rousette bats maintain long-term protective immunity against Marburg virus infection despite diminished antibody levels

text: Although bats are natural reservoir hosts for numerous zoonotic viruses, little is known about the long-term dynamics of the host immune response following infection and how these viruses are maintained in nature. The Egyptian rousette bat (ERB) is a known reservoir host for Marburg virus (MARV). Following infection of ERBs with MARV, virus-specific IgG antibodies are induced but rapidly wane and by 3 months post-infection the bats are seronegative. To determine whether reinfection of ERBs plays a role in MARV maintenance, we challenge groups of ERBs that were “naturally” or experimentally infected with MARV 17–24 months prior. No bats in either group exhibit evidence of MARV replication or shedding and all bats develop virus-specific secondary immune responses. This study demonstrates that infection of ERBs with MARV induces long-term protective immunity against reinfection and indicates that other factors, such as host population dynamics, drive MARV maintenance in nature.


title: CD4(+) T-cell counts and interleukin-8 and CCL-5 plasma concentrations discriminate disease severity in children with RSV infection

text: BACKGROUND: Current tools to predict the severity of respiratory syncytial virus (RSV) infection might be improved by including immunological parameters. We hypothesized that a combination of inflammatory markers would differentiate between severe and mild disease in RSV-infected children. METHODS: Blood and nasopharyngeal samples from 52 RSV-infected children were collected during acute infection and after recovery. Retrospectively, patients were categorized into three groups based on disease severity: mild (no supportive treatment), moderate (supplemental oxygen and/or nasogastric feeding), and severe (mechanical ventilation). Clinical data, number of flow-defined leukocyte subsets, and cytokine concentrations were compared. RESULTS: Children with severe RSV infection were characterized by young age; lymphocytopenia; increased interleukin (IL)-8, granulocyte colony-stimulating factor (G-CSF), and IL-6 concentrations; and decreased chemokine (C-C motif) ligand (CCL-5) concentrations in plasma. The combination of plasma levels of IL-8 and CCL-5, and CD4(+) T-cell counts, with cutoff values of 67 pg/ml, 13 ng/ml, and 2.3 × 10(6)/ml, respectively, discriminated severe from mild RSV infection with 82% sensitivity and 96% specificity. CONCLUSION: This study demonstrates that the combination of CD4(+) T-cell counts and IL-8 and CCL-5 plasma concentrations correlates with disease severity in RSV-infected children. In addition to clinical features, these immunological markers may be used to assess severity of RSV infection and guide clinical management. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/pr.2012.163) contains supplementary material, which is available to authorized users.


Middle East respiratory syndrome (MERS) in Asia: lessons gleaned from the South Korean outbreak


title: Multi-level regulation of cellular recognition of viral dsRNA

text: Effective antiviral immunity depends on accurate recognition of viral RNAs by the innate immune system. Double-stranded RNA (dsRNA) often accumulates in virally infected cells and was initially considered a unique viral signature that was sufficient to initiate antiviral response through dsRNA receptors and dsRNA-dependent effectors such as Toll-like receptor 3, retinoic acid inducible gene-1, protein kinase RNA-activated and oligoadenylate synthetase. However, dsRNA is also present in many cellular RNAs, raising a question of how these receptors and effectors discriminate between viral and cellular dsRNAs. Accumulating evidence suggests that innate immune sensors detect not only dsRNA structure but also other and often multiple features of RNA such as length, sequence, cellular location, post-transcriptional processing and modification, which are divergent between viral and cellular RNAs. This review summarizes recent findings on the substrate specificities of a few selected dsRNA-dependent effectors and receptors, which have revealed more complex mechanisms involved in cellular discrimination between self and non-self RNA.


title: Demographic and attitudinal determinants of protective behaviours during a pandemic: A review

text: Purpose. A new strain of H1N1 influenza, also known as swine flu was confirmed in the UK in May 2009 and has spread to over 100 countries around the world causing the World Health Organization to declare a global flu pandemic. The primary objectives of this review are to identify the key demographic and attitudinal determinants of three types of protective behaviour during a pandemic: preventive, avoidant, and management of illness behaviours, in order to describe conceptual frameworks in which to better understand these behaviours and to inform future communications and interventions in the current outbreak of swine flu and subsequent influenza pandemics. Methods. Web of Science and PubMed databases were searched for references to papers on severe acute respiratory syndrome, avian influenza/flu, H5N1, swine influenza/flu, H1N1, and pandemics. Forward searching of the identified references was also carried out. In addition, references were gleaned from an expert panel of the Behaviour and Communications sub‐group of the UK Scientific Pandemic Influenza Advisory Group. Papers were included if they reported associations between demographic factors, attitudes, and a behavioural measure (reported, intended, or actual behaviour). Results. Twenty‐six papers were identified that met the study inclusion criteria. The studies were of variable quality and most lacked an explicit theoretical framework. Most were cross‐sectional in design and therefore not predictive over time. The research shows that there are demographic differences in behaviour: being older, female and more educated, or non‐White, is associated with a higher chance of adopting the behaviours. There is evidence that greater levels of perceived susceptibility to and perceived severity of the diseases and greater belief in the effectiveness of recommended behaviours to protect against the disease are important predictors of behaviour. There is also evidence that greater levels of state anxiety and greater trust in authorities are associated with behaviour. Conclusions. The findings from this review can be broadly explained by theories of health behaviour. However, theoretically driven prospective studies are required to further clarify the relationship between demographic factors, attitudes, and behaviour. The findings suggest that intervention studies and communication strategies should focus on particular demographic groups and on raising levels of perceived threat of the pandemic disease and belief in the effectiveness of measures designed to protect against it.


title: Potential neurological effects of severe COVID-19 infection

text: Coronaviruses (CoVs) are large positive stranded enveloped RNA viruses that generally cause enteric and respiratory diseases in humans and in animals. Most human CoVs have recently attracted global attention to their lethal potential and great infectious capacity. A highly pathogenic CoV, called COVID-19 or SARS‐CoV2, dramatically emerged in December 2019 in Wuhan, China. This new CoV has caused severe pneumonia in China and rapidly spreads around the world, the COVID-19 pandemic. Growing evidence pieces show that viruses, such as CoVs, can enter the central nervous system from different pathways and inducing neurotoxicity. Therefore, it is urgent to make clear whether SARS-CoV-2 has access to the central nervous system and can cause direct neuronal effects. Moreover, a brain–lung–brain axis is been proposed from the scientific community where severe neurological dysfunction and injury are associated with lung injury, and vice versa. In this axis, virus-induced inflammation and oxidative stress could be the common mechanisms responsible for CoV neurological symptoms. Therefore, is important to make clear whether SARS-CoV-2 lung damage can cause indirect or indirect neuronal effects.


title: Optimal design and validation of antiviral siRNA for targeting HIV-1

text: We propose rational designing of antiviral short-interfering RNA (siRNA) targeting highly divergent HIV-1. In this study, conserved regions within HIV-1 genomes were identified through an exhaustive computational analysis, and the functionality of siRNAs targeting the highest possible conserved regions was validated. We present several promising antiviral siRNA candidates that effectively inhibited multiple subtypes of HIV-1 by targeting the best conserved regions in pandemic HIV-1 group M strains.


title: Equine coronavirus induces apoptosis in cultured cells

text: Abstract Equine coronavirus (ECoV) was first isolated from a diarrheic foal and was found genetically similar to group II coronaviruses. However, its pathological characteristics were not adequately investigated. In our preliminary in vitro investigation, ECoV-induced cell death was observed in bovine kidney-derived MDBK cells. Based on this finding, we investigated whether the ECoV-induced CPE was apoptosis. Following ECoV infection, MDBK cells showed morphological changes such as cell rounding and detachment from the culture surface. Moreover, syncytium formation was observed as the other type of cytopathic effect in ECoV infection. Morphologic and biochemical features of apoptosis, such as nuclear fragmentation and DNA ladder formation, were also detected in ECoV-infected cells. Moreover, as is commonly observed in coronavirus infection in other animals, the activities of effecter caspases – caspase-3/7 – and initiator caspases – caspase-8 and caspase-9 – that are representative factors in the death receptor-mediated apoptotic pathway and mitochondrial apoptotic pathway, respectively, were increased in ECoV-infected MDBK cells. Therefore, it was suggested that ECoV can induce apoptosis in MDBK cells via a caspase-dependent pathway. Apoptotic death of infected cells is detrimental because it causes cell and tissue destruction and inflammatory responses. Although the pathological characteristics of ECoV are largely unknown, apoptosis may be the pathological basis of lesions of the digestive system in ECoV infection.


title: Selenylated-oxadiazoles as promising DNA intercalators: Synthesis, electronic structure, DNA interaction and cleavage

text: Abstract A series of selenylated-oxadiazoles were prepared and their interaction with DNA was investigated. The photophysical studies showed that all the selenylated compounds presented absorption between 270 and 329 nm, assigned to combined n→π* and π→π* transitions, and an intense blue emission (325–380 nm) with quantum yield in the range of Φ F = 0.1–0.4. DFT and TD-DFT calculations were also performed to study the likely geometry and the excited state of these compounds. Electrochemical studies revealed the ionization potential energies (−5.13 to −6.01 eV) and electron affinity energies (−2.25 to −2.83 eV), depending directly on the electronic effect (electron-donating or electron-withdrawing) of the substituent attached to the product. Finally, the UV–Vis DNA interaction experiments indicated that the compounds can interact with the DNA molecule due to intercalation, except for 3g (which interacted via electrostatic interaction). Plasmid cleavage assay presented positive results only for 3f that presented the strongest interaction results. These results made the tested selenylated-oxadiazoles as suitable structures for the development of drugs and the design of structurally-related therapeutics.


title: Serologically diagnosed acute human bocavirus 1 infection in childhood community‐acquired pneumonia

text: AIM: To assess the role of human bocavirus 1 (HBoV1) as a causative agent of non‐severe community‐acquired pneumonia (CAP) in children. METHODS: Patients aged 2‐59 months with non‐severe CAP (respiratory complaints and radiographic pulmonary infiltrate/consolidation) attending a University Hospital in Salvador, Brazil were enrolled in a prospective cohort. From 820 recruited children in a clinical trial (http://ClinicalTrials.gov NCT01200706), nasopharyngeal aspirate (NPA), and acute and convalescent serum samples were obtained from 759 (92.6%) patients. NPAs were tested for 16 respiratory viruses by PCR. Acute HBoV1 infection was confirmed by measuring specific IgM and IgG responses in paired serum samples. RESULTS: Respiratory viruses were detected in 693 (91.3%; 95%CI: 89.1‐93.2) CAP cases by PCR. HBoV1‐DNA was detected in 159 (20.9%; 95%CI: 18.2‐24.0) cases. Of these 159 PCR positive cases, acute HBoV1 infection was confirmed serologically in 38 cases (23.9%; 95%CI: 17.8‐31.0). Overall, acute HBoV1 infection was confirmed in 5.0% (38/759) of non‐severe CAP patients. HBoV1 was detected in 151 cases with at least one other virus making 31.7% of all multiple virus (n = 477) detections. Among all 759 cases, 216 had one respiratory virus detected, and sole HBoV1 was detected in only 8 (3.7%). Acute HBoV1 infection was serologically diagnosed in 34 (22.5%) HBoV1‐DNA‐positive cases with another virus, compared to 4 (50.0%) cases with sole virus detection (p = 0.09). CONCLUSION: HBoV1 was detected by PCR in one fifth of the children with non‐severe CAP and acute HBoV1 infection was serologically confirmed in one quarter of these cases.


title: 2015 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) nosocomial outbreak in South Korea: insights from modeling

text: Background. Since the emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in 2012, more than 1,300 laboratory confirmed cases of MERS-CoV infections have been reported in Asia, North Africa, and Europe by July 2015. The recent MERS-CoV nosocomial outbreak in South Korea quickly became the second largest such outbreak with 186 total cases and 36 deaths in a little more than one month, second only to Saudi Arabia in country-specific number of reported cases. Methods. We use a simple mathematical model, the Richards model, to trace the temporal course of the South Korea MERS-CoV outbreak. We pinpoint its outbreak turning point and its transmissibility via basic reproduction number R(0) in order to ascertain the occurrence of this nosocomial outbreak and how it was quickly brought under control. Results. The estimated outbreak turning point of t(i) = 23.3 days (95% CI [22.6–24.0]), or 23–24 days after the onset date of the index case on May 11, pinpoints June 3–4 as the time of the turning point or the peak incidence for this outbreak by onset date. R(0) is estimated to range between 7.0 and 19.3. Discussion and Conclusion. The turning point of the South Korea MERS-CoV outbreak occurred around May 27–29, when control measures were quickly implemented after laboratory confirmation of the first cluster of nosocomial infections by the index patient. Furthermore, transmissibility of MERS-CoV in the South Korea outbreak was significantly higher than those reported from past MERS-CoV outbreaks in the Middle East, which is attributable to the nosocomial nature of this outbreak. Our estimate of R(0) for the South Korea MERS-CoV nosocomial outbreak further highlights the importance and the risk involved in cluster infections and superspreading events in crowded settings such as hospitals. Similar to the 2003 SARS epidemic, outbreaks of infectious diseases with low community transmissibility like MERS-CoV could still occur initially with large clusters of nosocomial infections, but can be quickly and effectively controlled with timely intervention measures.


title: Suspected sphenoid bone osteomyelitis causing visual impairment in two dogs and one cat

text: Objective To present the clinical and magnetic resonance imaging (MRI) characteristics of sphenoid bone osteomyelitis. Procedures Two dogs (English Springer Spaniel – ESS, Golden Retriever – GR) and one cat (Domestic Long Haired) were presented with a 2–14‐day history of visual deficits and reduced pupillary light reflexes. Investigations included physical, ophthalmologic and neurological examination as well as hematology, serum biochemistry, MRI of the head and cerebrospinal fluid (CSF) analysis. Results MRI changes included thickening of the sphenoid bone and a loss of normal bone marrow signal on T1W MRI. Enhancement of the sphenoid bones, ventral meninges and ventral surface of the brain was present using paramagnetic contrast medium. CSF analysis was abnormal in the two dogs with increased cellularity, neutrophilic pleocytosis, intracellular bacteria and increased total protein in one, and with lymphocytic pleocytosis in another. CSF analysis was normal in the cat. An underlying cause for the osteomyelitis could not be identified. The use of broad‐spectrum antibiotics for 3–6 weeks combined with anti‐inflammatory medications proved effective. Full clinical recovery occurred with no relapse during the follow up time of 7 (ESS) and 4 (Domestic Long Haired) years. The GR relapsed 10 months after treatment and recovered following a second 3‐week course of broad‐spectrum antibiotics with no relapse during the following 3 years. Conclusion Visual pathway deficits in dogs and cats may be due to sphenoid bone osteomyelitis. MRI and CSF analysis can assist diagnosing this potentially treatable condition. To the authors’ knowledge this is the first report of sphenoid bone osteomyelitis in these species.


title: Geographical tracking and mapping of coronavirus disease COVID-19/severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic and associated events around the world: how 21st century GIS technologies are supporting the global fight against outbreaks and epidemics

text: In December 2019, a new virus (initially called ‘Novel Coronavirus 2019-nCoV’ and later renamed to SARS-CoV-2) causing severe acute respiratory syndrome (coronavirus disease COVID-19) emerged in Wuhan, Hubei Province, China, and rapidly spread to other parts of China and other countries around the world, despite China’s massive efforts to contain the disease within Hubei. As with the original SARS-CoV epidemic of 2002/2003 and with seasonal influenza, geographic information systems and methods, including, among other application possibilities, online real-or near-real-time mapping of disease cases and of social media reactions to disease spread, predictive risk mapping using population travel data, and tracing and mapping super-spreader trajectories and contacts across space and time, are proving indispensable for timely and effective epidemic monitoring and response. This paper offers pointers to, and describes, a range of practical online/mobile GIS and mapping dashboards and applications for tracking the 2019/2020 coronavirus epidemic and associated events as they unfold around the world. Some of these dashboards and applications are receiving data updates in near-real-time (at the time of writing), and one of them is meant for individual users (in China) to check if the app user has had any close contact with a person confirmed or suspected to have been infected with SARS-CoV-2 in the recent past. We also discuss additional ways GIS can support the fight against infectious disease outbreaks and epidemics.


title: TRIM52 inhibits Japanese Encephalitis Virus replication by degrading the viral NS2A

text: The members of tripartite-motif containing (TRIM) protein participate in various cellular processes and play an important role in host antiviral function. TRIM proteins exert their antiviral activity either directly by degrading viral proteins through their E3 ligase activity, or indirectly by promoting host innate immunity. This study demonstrated for the first time that TRIM52 is a novel antiviral TRIM protein against Japanese encephalitis virus (JEV) infection. Overexpression of TRIM52 restricted JEV replication in BHK-21 and 293T cells. In addition, JEV nonstructural protein 2A (NS2A) is a protein that interacts with TRIM52. Their interaction degraded NS2A in a proteasome-dependent manner via the E3 ligase activity of TRIM52. Thus, TRIM52 is a novel antiviral TRIM protein, and it exerted antiviral activity against JEV infection by targeting and degrading viral NS2A.


title: Expression Pattern Analysis of Antiviral Genes and Inflammatory Cytokines in PEDV-Infected Porcine Intestinal Epithelial Cells

text: Porcine diarrhea disease in newborn and suckling piglets due to infection with porcine epidemic diarrhea virus (PEDV) is a leading cause of economic loss in the pig industry globally. In this study, we investigated the molecular mechanism of the host innate immune response to PEDV infection. The expression dynamics of antiviral genes (e.g., RIG-1, PKR, OAS1, Mx1, and Mx2) and inflammatory cytokines (e.g., IFN-α, IFN-β, TNF-α, IL-6, IL-8, and IL-12) in porcine small intestinal epithelial (IPEC-J2) cells were analyzed following PEDV stimulation. The results showed that the expression of antiviral genes (e.g., PKR, OAS1, and Mx2) and inflammatory cytokines (e.g., IFN-α and TNF-α) were significantly reduced within 0–4 h post-infection (P < 0.05). However, all antiviral genes and inflammatory cytokines were up-regulated from 12 to 24 h (P < 0.05), and cytopathic changes were observed during this time. The expression of RIG-1, PKR, OAS1, Mx1, and Mx2 were significantly and positively correlated to each other during the entire infection (P < 0.01). The results suggested that the RIG-1, PKR, OAS1, Mx1, and Mx2 genes may play an important role in PEDV infection in piglets. Initially, PEDV displayed cellular invasion by inhibiting IFN-α transcription and interfering with the antiviral function of PKR, OAS1, and Mx2, ultimately induced an intense inflammatory response. The relationship between antiviral genes and inflammatory cytokines with PEDV infection at the cellular level provides a reference for studying the mechanism of resistance to PEDV infection in piglets.


title: Paediatric Inflammatory Multisystem Syndrome: Temporally Associated with SARS-CoV-2 (PIMS-TS): Cardiac Features, Management and Short-Term Outcomes at a UK Tertiary Paediatric Hospital

text: Children were relatively spared during COVID-19 pandemic. However, the recently reported hyperinflammatory syndrome with overlapping features of Kawasaki disease and toxic shock syndrome—“Paediatric Inflammatory Multisystem Syndrome-temporally associated with SARS-CoV-2” (PIMS-TS) has caused concern. We describe cardiac findings and short-term outcomes in children with PIMS-TS at a tertiary children’s hospital. Single-center observational study of children with PIMS-TS from 10th April to 9th May 2020. Data on ECG and echocardiogram were retrospectively analyzed along with demographics, clinical features and blood parameters. Fifteen children with median age of 8.8 (IQR 6.4–11.2) years were included, all were from African/Afro-Caribbean, South Asian, Mixed or other minority ethnic groups. All showed raised inflammatory/cardiac markers (CRP, ferritin, Troponin I, CK and pro-BNP). Transient valve regurgitation was present in 10 patients (67%). Left Ventricular ejection fraction was reduced in 12 (80%), fractional shortening in 8 (53%) with resolution in all but 2. Fourteen (93%) had coronary artery abnormalities, with normalization in 6. ECG abnormalities were present in 9 (60%) which normalized in 6 by discharge. Ten (67%) needed inotropes and/or vasopressors. None needed extracorporeal life support. Improvement in cardiac biochemical markers was closely followed by improvement in ECG/echocardiogram. All patients were discharged alive and twelve (80%) have been reviewed since. Our entire cohort with PIMS-TS had cardiac involvement and this degree of involvement is significantly more than other published series and emphasizes the need for specialist cardiac review. We believe that our multi-disciplinary team approach was crucial for the good short-term outcomes.


title: High prevalence of common respiratory viruses and no evidence of Middle East Respiratory Syndrome Coronavirus in Hajj pilgrims returning to Ghana, 2013

text: OBJECTIVE: The Middle East respiratory syndrome coronavirus (MERS‐CoV) emerged in 2012 on the Arabian Peninsula and has caused severe respiratory disease with more than 800 laboratory‐confirmed cases. The return of infected pilgrims to their home countries with a putative spread of MERS‐CoV necessitates further surveillance. METHODS: A cross sectional study of 839 adult African Hajj pilgrims returning to Accra in Ghana, West Africa, was conducted in 2013 to assess the prevalence of respiratory symptoms as well as of MERS‐CoV, human rhinovirus (HRV), respiratory syncytial virus (RSV) and influenza A virus (FLU A) infection. RESULTS: Six hundred and fifty‐one (77.6%) pilgrims had respiratory symptoms. Tests were positive for at least one of the viruses other than MERS‐CoV in 179 (21.3%) of all pilgrims, with 22.4% detection in symptomatic vs. 17.6% detection in asymptomatic pilgrims. No MERS‐CoV was detected, although common respiratory viruses were prevalent, with positive findings for HRV in 141 individuals (16.8%), RSV in 43 individuals (5.1%) and FLU A in 11 individuals (1.3%). Results were positive for more than one virus in 16 (1.9%) individuals, including 14 (1.7%) RSV/HRV co‐infections and 2 (0.2%) FLU A/HRV co‐infections. A total 146 (22.4%) of the symptomatic returnees tested positive for at least one respiratory virus compared with 33 (17.6%) of the asymptomatic pilgrims who had at least one detectable virus in their sample. CONCLUSIONS: The prevalence of viral respiratory infections among Hajj pilgrims in both symptomatic and asymptomatic subjects was high. Although it is reassuring that MERS‐CoV was not detected in the tested population, there is a need for active surveillance of Hajj pilgrims.


WHO is SARS?


title: SARS and New York's Chinatown: The politics of risk and blame during an epidemic of fear

text: Abstract This paper examines the production of risk and blame discourses during the 2003 SARS epidemic and responses to those messages in New York City's Chinatown, a community stigmatized during the SARS epidemic despite having no SARS cases. The study consisted of 6 weeks participant observation and 37 semi-structured, open-ended interviews with community members. Stigmatizing discourses from the late 19th century resurfaced to blame Chinese culture and people for disease, and were recontextualized to fit contemporary local and global political-economic concerns. Many informants discursively distanced themselves from risk but simultaneously reaffirmed the association of Chinese culture with disease by redirecting such discourses onto recent Chinese immigrants. Legitimizing cultural blame obfuscates the structural and biological causes of epidemics and naturalizes health disparities in marginalized populations. This research demonstrates that myriad historical, political, and economic factors shape responses and risk perceptions during an unfamiliar epidemic, even in places without infection.


title: The impact of viral dynamics on the clinical severity of infants with respiratory syncytial virus bronchiolitis

text: The impact of dynamic respiratory syncytial virus (RSV) load on the clinical severity of hospitalized infants with bronchiolitis has not been clarified. Nasopharyngeal aspirates were obtained from 60 infants who were diagnosed with bronchiolitis within 96 hr of wheezing onset upon admission and on days 3, 5, and 7 in the hospital, and 17 respiratory viruses were detected. The RSV load was quantified by real‐time qPCR for RSV subtypes A and B at different time points. Scoring criteria were used to evaluate the degree of severity. A total of 40 infants were determined to be RSV‐positive, nine were identified as RSV subtype A (RSVA), and 31 were RSV subtype B (RSVB). The peak RSV load was observed upon admission, and the RSV load decreased significantly over time; in addition, this decrease began to have significant differences on day 5. There was a positive correlation between the RSV load and the clinical score (r(2) = 0.121 and P < 0.001). According to the clinical scores, the infants in the severe group tended to have higher RSV loads than those in the moderate and mild groups. Multivariate logistic regression models revealed that the viral load on day 3 was independently associated with the degree of severity. This study elucidated that a higher mean RSV load was associated with a more severe disease and a longer duration of hospitalization and symptoms. This study also clarified RSV replication in infants and provides a theoretical basis for specifying an anti‐RSV therapy strategy. J. Med. Virol. 87:1276–1284, 2015. © 2015 Wiley Periodicals, Inc.


title: Problematic Internet Use and Perceived Quality of Life: Findings from a Cross-Sectional Study Investigating Work-Time and Leisure-Time Internet Use

text: Avoiding the potential negative impact brought by problematic internet use is becoming more important. To better understand public health and addiction, this study investigated to what extent work-time and leisure-time internet use relate to problematic internet use and perceived quality of life among college students and highly educated adults. An online cross-sectional survey with 446 individuals was assessed in Germany. Linear regression analyses were used to predict problematic internet use. Ordinal regression analyses were applied to predict perceived quality of life. Results showed that leisure-time internet use, but not work-time internet use, was positively associated with problematic internet use. Participants whose work-time internet use could be considered balanced (5–28 h/week in this study) indicated a higher perceived quality of life compared to individuals with little or large amount of internet use for work. The findings still emerged when taking negative feelings, perceived stress, smoking status and alcohol consumption into account. As both work-time and leisure-time internet use can be risk factors for mental health in terms of problematic internet use and perceived quality of life, well-controlled internet use rather than excessive use is recommended. This should be kept in mind when dealing with the Coronavirus pandemic and its aftermath.


Clinical Distancing of Hospitalized Patients with Advanced Heart Failure and Cardiac Transplantation During COVID-19


Use of Face Masks in Dermatology Department During the COVID‐19 Outbreak


title: Asymptomatic and presymptomatic transmission of SARS-CoV-2: A systematic review

text: BACKGROUND AND PURPOSE: Many of the statutes comprising the shelter-in-place and phased-reopening orders are centered around minimizing asymptomatic and presymptomatic transmission. Assumptions about the presence and relative importance of asymptomatic and presymptomatic transmission are based on case reports, the failing of quarantine measures aimed at sequestering ill patients, viral dynamic studies suggesting SARS-CoV-2 production peaks before symptoms appear, and modeling evidence that calculates serial interval between successive generations of infection. In aggregate, these data offer compelling evidence of asymptomatic and presymptomatic transmission, but individually these studies have notable shortcomings that undermine their conclusions. The purpose of this review is to discuss the literature of asymptomatic and presymptomatic transmission, highlight limitations of recent studies, and propose experiments that, if conducted, would provide a more definitive analysis of the relative role of asymptomatic and presymptomatic transmission in the ongoing SARS-CoV-2 pandemic. METHODS: We conducted a systematic review of literature on PubMed using search filters that relate to asymptomatic and presymptomatic transmission as well as serial interval and viral dynamics. We focused on studies that provided primary clinical data. RESULTS: 34 studies were eligible for inclusion in this systematic review: 11 case reports pertaining to asymptomatic transmission, 9 viral kinetic studies, 13 serial interval studies, and 1 study with viral kinetics and serial interval. CONCLUSION: Different approaches to determining the presence and prevalence of asymptomatic and presymptomatic SARS-CoV-2 transmission have notable shortcomings, which were highlighted in this review and limit our ability to draw definitive conclusions. Conducting high quality studies with the aim of understanding the relative role of asymptomatic and presymptomatic transmission is instrumental to developing the most informed policies on reopening our cities, states, and countries.


title: Intellectual and Developmental Disability and COVID-19 Case-Fatality Trends: TriNetX Analysis

text: BACKGROUND: Despite possibly higher risk of severe outcomes from COVID-19 among people with intellectual and developmental disabilities (IDD), there has been limited reporting of COVID-19 trends for this population. OBJECTIVE: To compare COVID-19 trends among people with and without IDD, overall and stratified by age. METHODS: Data from the TriNetX COVID-19 Research Network platform was used to identify COVID-19 patients. Analysis focused on trends in comorbidities, number of cases, number of deaths, and case-fatality rate among patients with and without IDD who had a positive diagnosis for COVID-19 through May 14, 2020. RESULTS: People with IDD had higher prevalence of specific comorbidities associated with poorer COVID-19 outcomes. Distinct age-related differences in COVID-19 trends were present among those with IDD, with a higher concentration of COVID-19 cases at younger ages. In addition, while the overall case-fatality rate was similar for those with IDD (5.1%) and without IDD (5.4%), these rates differed by age: ages <17 – IDD 1.6%, without IDD <.01%; ages 18-74 – IDD 4.5%, without IDD 2.7%; ages >75– IDD 21.1%, without IDD, 20.7%. CONCLUSIONS: Though of concern for all individuals, COVID-19 appears to present a greater risk to people with IDD, especially at younger ages. Future research should seek to document COVID-19 trends among people with IDD, with particular attention to age related trends.


title: Comment on “Organ‐protective effect of angiotensin‐converting enzyme 2 and its effect on the prognosis of COVID‐19”

text: I read with this informative review article by Cheng et al. “ Organ‐protective effect of angiotensin‐converting enzyme 2 and its effect on the prognosis of COVID‐19”. I would like to talk about the role of ACE2 in endothelial cell function. Besides, I would like to mention that COVID‐19 patients might benefit from ACEI/ARBs concerning improving endothelial dysfunction in COVID‐19. This article is protected by copyright. All rights reserved.


title: Recent advances in “universal” influenza virus antibodies: the rise of a hidden trimeric interface in hemagglutinin globular head

text: Influenza causes seasonal outbreaks yearly and unpredictable pandemics with high morbidity and mortality rates. Despite significant efforts to address influenza, it remains a major threat to human public health. This issue is partially due to the lack of antiviral drugs with potent antiviral activity and broad reactivity against all influenza virus strains and the rapid emergence of drug-resistant variants. Moreover, designing a universal influenza vaccine that is sufficiently immunogenic to induce universal antibodies is difficult. Some novel epitopes hidden in the hemagglutinin (HA) trimeric interface have been discovered recently, and a number of antibodies targeting these epitopes have been found to be capable of neutralizing a broad range of influenza isolates. These findings may have important implications for the development of universal influenza vaccines and antiviral drugs. In this review, we focused on the antibodies targeting these newly discovered epitopes in the HA domain of the influenza virus to promote the development of universal anti-influenza antibodies or vaccines and extend the discovery to other viruses with similar conformational changes in envelope proteins.


COVID‐19 and obesity


title: Molecular approaches in the diagnosis of primary immunodeficiency diseases

text: Over 120 inherited primary immunodeficiency diseases (PIDs) are known to exist. The genes responsible for many of these diseases have also been identified. Recent advances in diagnostic procedures have enabled these to be identified earlier and appropriately treated. While a number of approaches are available to identify mutations, direct sequencing remains the gold standard. This approach identifies the exact genetic change with substantial precision. We suggest that a sensitive and economical approach to mutation detection could be the direct sequencing of cDNA followed by the confirmatory sequencing of the corresponding exon. While screening techniques such as single‐stranded conformation polymorphism (SSCP), heteroduplex analysis (HA), denaturing gradient gel electrophoresis (DGGE), and denaturing high‐performance liquid chromatography (dHPLC) have proven useful, each has inherent advantages and disadvantages. We discuss these advantages and disadvantages and also discuss the potential of future sequencing technologies such as pyrosequencing, combinatorial sequencing‐by‐hybridization, multiplex polymerase colony (polony), and resequencing arrays as tools for future mutation detection. In addition we briefly discuss several high‐throughput SNP detection technologies. Hum Mutat 27(12), 1163–1173, 2006. © 2006 Wiley‐Liss, Inc.


title: Effect of Chloroquine, Hydroxychloroquine, and Azithromycin on the Corrected QT Interval in Patients With SARS-CoV-2 Infection

text: The novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is responsible for the global coronavirus disease 2019 pandemic. Small studies have shown a potential benefit of chloroquine/hydroxychloroquine±azithromycin for the treatment of coronavirus disease 2019. Use of these medications alone, or in combination, can lead to a prolongation of the QT interval, possibly increasing the risk of Torsade de pointes and sudden cardiac death. METHODS: Hospitalized patients treated with chloroquine/hydroxychloroquine±azithromycin from March 1 to the 23 at 3 hospitals within the Northwell Health system were included in this prospective, observational study. Serial assessments of the QT interval were performed. The primary outcome was QT prolongation resulting in Torsade de pointes. Secondary outcomes included QT prolongation, the need to prematurely discontinue any of the medications due to QT prolongation, and arrhythmogenic death. RESULTS: Two hundred one patients were treated for coronavirus disease 2019 with chloroquine/hydroxychloroquine. Ten patients (5.0%) received chloroquine, 191 (95.0%) received hydroxychloroquine, and 119 (59.2%) also received azithromycin. The primary outcome of torsade de pointes was not observed in the entire population. Baseline corrected QT interval intervals did not differ between patients treated with chloroquine/hydroxychloroquine (monotherapy group) versus those treated with combination group (chloroquine/hydroxychloroquine and azithromycin; 440.6±24.9 versus 439.9±24.7 ms, P=0.834). The maximum corrected QT interval during treatment was significantly longer in the combination group versus the monotherapy group (470.4±45.0 ms versus 453.3±37.0 ms, P=0.004). Seven patients (3.5%) required discontinuation of these medications due to corrected QT interval prolongation. No arrhythmogenic deaths were reported. CONCLUSIONS: In the largest reported cohort of coronavirus disease 2019 patients to date treated with chloroquine/hydroxychloroquine±azithromycin, no instances of Torsade de pointes, or arrhythmogenic death were reported. Although use of these medications resulted in QT prolongation, clinicians seldomly needed to discontinue therapy. Further study of the need for QT interval monitoring is needed before final recommendations can be made. VISUAL OVERVIEW: A visual overview is available for this article.


title: Replacement Management in Cattle | Breeding Standards and Pregnancy Management

text: Rearing replacement heifers is part of herd survivability and represents 15–20% of total farm costs. Proper attention to the growth of heifers is paramount to producing heifers that achieve adequate stature and body weight before first breeding and calving. Timely entry of heifers into the milking herd by 2 years of age, or their first eligible calving season in seasonal pasture-based dairy enterprises, can be facilitated by applying synchronization of estrus and ovulation in addition to traditional detection of estrus by visual or other means. Because fertility is better in heifers than in lactating cows, artificial insemination of heifers with semen from the best available progeny-tested bulls is a wise investment to ensure genetic gain of economically important traits. Annual culling rates of 25–33% necessitate a supply of herd replacement heifers. Application of gender-biased semen to produce more female offspring is also warranted for increasing the replacement population. The main goal of a heifer replacement program is to develop heifers at minimal cost and in a timely manner to obtain heifers of desired size and body weight so that they attain puberty, establish pregnancy, calve easily, and achieve their maximum genetic lifetime milk production as cows.


Rapid and severe Covid‐19 pneumonia with severe acute chest syndrome in a sickle cell patient successfully treated with tocilizumab


title: Analysis of the complete genomic sequences of two virus subpopulations of the Australian infectious bronchitis virus vaccine VicS

text: Although sequencing of the 3′ end of the genome of Australian infectious bronchitis viruses (IBVs) has shown that their structural genes are distinct from those of IBVs found in other countries, their replicase genes have not been analysed. To examine this, the complete genomic sequences of the two subpopulations of the VicS vaccine, VicS-v and VicS-del, were determined. Compared with VicS-v, the more attenuated VicS-del strain had two non-synonymous changes in the non-structural protein 6 (nsp6), a transmembrane (TM) domain that may participate in autocatalytic release of the 3-chymotrypsin-like protease, a polymorphic difference at the end of the S2 gene, which coincided with the body transcription-regulating sequence (B-TRS) of mRNA 3 and a truncated open reading frame for a peptide encoded by gene 4 (4b). These genetic differences could be responsible for the differences between these variants in pathogenicity in vivo, and replication in vitro. Phylogenetic analysis of the whole genome showed that VicS-v and VicS-del did not cluster with strains from other countries, supporting the hypothesis that Australian IBV strains have been evolving independently for some time, and analyses of individual polymerase peptide and S glycoprotein genes suggested a distant common ancestor with no recent recombination. This study suggests the potential role of the TM domain in nsp6, the integrity of the S2 protein and the B-TRS 3, and the putative accessory protein 4b, as well as the 3′ untranslated region, in the virulence and replication of IBV and has provided a better understanding of relationships between the Australian vaccine strain of IBV and those used elsewhere.


Collateral effects of COVID‐19 pandemic in pediatric hematooncology: Fatalities caused by diagnostic delay


title: Incidence, significance, and persistence of human coronavirus infection in hematopoietic stem cell transplant recipients

text: Hematopoietic stem cell transplant (HSCT) recipients are at increased risk of respiratory viral infections and their associated complications. Unlike other respiratory viruses, little is known about the clinical significance of human coronavirus infection (HCoV) in this population. We retrospectively identified all HSCT recipients who were transplanted between May 2013 and June 2017 at our institution and characterized the cumulative incidence of post-transplant HCoV infection. Of 678 patients who underwent HSCT during the study period, 112 (17%) developed HCoV infection, making HCoV the fourth most common respiratory viral infection. Thirty-four (30%) HCoV-infected patients progressed to proven or probable lower respiratory tract infection (LRTI). Age ≥50, graft-versus-host disease, corticosteroids, hypoalbuminemia, and inpatient status at the time of infection were independently associated with progression to LRTI. Twenty-seven (59%) patients who underwent repeat NP swab had persistent viral shedding for ≥21 days, with a median duration of 4 weeks of viral shedding. We conclude that HCoV is common and clinically significant in HSCT recipients, with nearly one-third of patients progressing to proven or probable LRTI. Evaluating for LRTI risk factors found in this study may identify patients who require closer surveillance and aggressive supportive care when infected with HCoV.


title: Elevated N-terminal pro-brain natriuretic peptide is associated with increased mortality in patients with COVID-19: systematic review and meta-analysis

text: OBJECTIVES: This systematic review and meta-analysis aimed to assess the association between N-terminal pro-brain natriuretic peptide (NT-proBNP) and mortality in patients with COVID-19. METHODS: Systematic literature search from several electronic databases were performed. The outcome was mortality (non-survivor) in patients with COVID-19 pneumonia. NT-proBNP data were in continuous variable (pg/mL), dichotomous data (elevated/non-elevated) and effect estimate adjusted to cardiac injury/elevated biomarkers of cardiac injury. RESULTS: A total of 967 patients from six studies were included in this analysis. NT-proBNP was higher in non-survivor group (standardised mean difference 0.75 (0.44, 1.07), p<0.001; I(2): 61%). Elevated NT-proBNP was associated with increased mortality (RR 3.63 (92.21, 5.95), p<0.001; I(2): 60%). Sensitivity analysis by removing a study reduces heterogeneity (risk ratio 3.47 (2.36, 5.11), p<0.001; I(2): 49%). Pooled adjusted HR (adjusted to cardiac injury/elevated biomarkers of cardiac injury) showed that elevated NT-proBNP was independently associated with mortality (HR 1.37 (1.19, 1.57), p<0.001; I(2): 0%, p=0.77). Pooled analysis of multiple cut-off point resulted in a sensitivity of 76% (46%–92%) and specificity of 88% (71%–96%). Summary receiver operating characteristic curve analysis demonstrates an area under curve of 0.90 (0.87–0.93). Elevated NT-proBNP has a likelihood ratio (LR) +6.4 and LR -0.3. CONCLUSION: Elevated NT-proBNP level was associated with increased mortality in COVID-19 pneumonia.


title: Genomic Dissection of an Icelandic Epidemic of Respiratory Disease in Horses and Associated Zoonotic Cases

text: Iceland is free of the major infectious diseases of horses. However, in 2010 an epidemic of respiratory disease of unknown cause spread through the country’s native horse population of 77,000. Microbiological investigations ruled out known viral agents but identified the opportunistic pathogen Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) in diseased animals. We sequenced the genomes of 257 isolates of S. zooepidemicus to differentiate epidemic from endemic strains. We found that although multiple endemic clones of S. zooepidemicus were present, one particular clone, sequence type 209 (ST209), was likely to have been responsible for the epidemic. Concurrent with the epidemic, ST209 was also recovered from a human case of septicemia, highlighting the pathogenic potential of this strain. Epidemiological investigation revealed that the incursion of this strain into one training yard during February 2010 provided a nidus for the infection of multiple horses that then transmitted the strain to farms throughout Iceland. This study represents the first time that whole-genome sequencing has been used to investigate an epidemic on a national scale to identify the likely causative agent and the link to an associated zoonotic infection. Our data highlight the importance of national biosecurity to protect vulnerable populations of animals and also demonstrate the potential impact of S. zooepidemicus transmission to other animals, including humans.


title: Genetic dissection of host immune response in pneumonia development and progression

text: The role of host genetic variation in pneumonia development and outcome is poorly understood. We studied common polymorphisms in the genes of proinflammatory cytokines (IL6 rs1800795, IL8 rs4073, IL1B rs16944), anti-inflammatory cytokines (IL10 rs1800896, IL4 rs2243250, IL13 rs20541) and toll-like receptors (TLR2 rs5743708 and rs4696480, TLR4 rs4986791, TLR9 rs352139, rs5743836 and rs187084) in patients with community-acquired pneumonia (CAP) (390 cases, 203 controls) and nosocomial pneumonia (355 cases, 216 controls). Experimental data were included in a series of 11 meta-analyses and eight subset analyses related to pneumonia susceptibility and outcome. TLR2 rs5743708 minor genotype appeared to be associated with CAP/Legionnaires’ disease/pneumococcal disease. In CAP patients, the IL6 rs1800795-C allele was associated with severe sepsis/septic shock/severe systemic inflammatory response, while the IL10 rs1800896-A allele protected against the development of these critical conditions. To contribute to deciphering of the above results, we performed an in silico analysis and a qualitative synthesis of literature data addressing basal and stimulated genotype-specific expression level. This data together with database information on transcription factors’ affinity changes caused by SNPs in putative promoter regions, the results of linkage disequilibrium analysis along with SNPs functional annotations supported assumptions about the complexity underlying the revealed associations.


title: Phylogeny of SARS-CoV as inferred from complete genome comparison

text: SARS-CoV, as the pathogeny of severe acute respiratory syndrome (SARS), is a mystery that the origin of the virus is still unknown even a few isolates of the virus were completely sequenced. To explore the genesis of SARS-CoV, the FDOD method previously developed by us was applied to comparing complete genomes from 12 SARS-CoV isolates to those from 12 previously identified coronaviruses and an unrooted phylogenetic tree was constructed. Our results show that all SARS-CoV isolates were clustered into a clique and previously identified coronaviruses formed the other clique. Meanwhile, the three groups of coronaviruses depart from each other clearly in our tree that is consistent with the results of prevenient papers. Differently, from the topology of the phylogenetic tree we found that SARS-CoV is more close to group 1 within genus coronavirus. The topology map also shows that the 12 SARS-CoV isolates may be divided into two groups determined by the association with the SARS-CoV from the Hotel M in Hong Kong that may give some information about the infectious relationship of the SARS.


title: The persistence of multiple strains of avian influenza in live bird markets

text: Multiple subtypes of avian influenza (AI) and novel reassortants are frequently isolated from live bird markets (LBMs). However, our understanding of the drivers of persistence of multiple AI subtypes is limited. We propose a stochastic model of AI transmission within an LBM that incorporates market size, turnover rate and the balance of direct versus environmental transmissibility. We investigate the relationship between these factors and the critical community size (CCS) for the persistence of single and multiple AI strains within an LBM. We fit different models of seeding from farms to two-strain surveillance data collected from Shantou, China. For a single strain and plausible estimates for continuous turnover rates and transmissibility, the CCS was approximately 11 800 birds, only a 4.2% increase in this estimate was needed to ensure persistence of the co-infecting strains (two strains in a single host). Precise values of CCS estimates were sensitive to changes in market turnover rate and duration of the latent period. Assuming a gradual daily sell rate of birds the estimated CCS was higher than when an instantaneous selling rate was assumed. We were able to reproduce prevalence dynamics similar to observations from a single market in China with infection seeded every 5–15 days, and a maximum non-seeding duration of 80 days. Our findings suggest that persistence of co-infections is more likely to be owing to sequential infection of single strains rather than ongoing transmission of both strains concurrently. In any given system for a fixed set of ecological and epidemiological conditions, there is an LBM size below which the risk of sustained co-circulation is low and which may suggest a clear policy opportunity to reduce the frequency of influenza co-infection in poultry.


title: Identification of Novel Rosavirus Species That Infects Diverse Rodent Species and Causes Multisystemic Dissemination in Mouse Model

text: While novel picornaviruses are being discovered in rodents, their host range and pathogenicity are largely unknown. We identified two novel picornaviruses, rosavirus B from the street rat, Norway rat, and rosavirus C from five different wild rat species (chestnut spiny rat, greater bandicoot rat, Indochinese forest rat, roof rat and Coxing's white-bellied rat) in China. Analysis of 13 complete genome sequences showed that “Rosavirus B” and “Rosavirus C” represent two potentially novel picornavirus species infecting different rodents. Though being most closely related to rosavirus A, rosavirus B and C possessed distinct protease cleavage sites and variations in Yn-Xm-AUG sequence in 5’UTR and myristylation site in VP4. Anti-rosavirus B VP1 antibodies were detected in Norway rats, whereas anti-rosavirus C VP1 and neutralizing antibodies were detected in Indochinese forest rats and Coxing's white-bellied rats. While the highest prevalence was observed in Coxing's white-bellied rats by RT-PCR, the detection of rosavirus C from different rat species suggests potential interspecies transmission. Rosavirus C isolated from 3T3 cells causes multisystemic diseases in a mouse model, with high viral loads and positive viral antigen expression in organs of infected mice after oral or intracerebral inoculation. Histological examination revealed alveolar fluid exudation, interstitial infiltration, alveolar fluid exudate and wall thickening in lungs, and hepatocyte degeneration and lymphocytic/monocytic inflammatory infiltrates with giant cell formation in liver sections of sacrificed mice. Since rosavirus A2 has been detected in fecal samples of children, further studies should elucidate the pathogenicity and emergence potential of different rosaviruses.


title: Hospitality unionism and labour market adjustment: Toward Schumpeterian unionism?

text: Abstract This paper proposes a conceptual model for understanding emerging changes in a North American labour union. UNITE-HERE, largely representing textile and hospitality workers, has been at the forefront of debates on union revitalization in the US and Canada. UNITE-HERE is often characterized as a successful example of North American union renewal, but I argue that this often oversimplifies many complex and contradictory labour strategies. Much of the labour union renewal literature remains prescriptive and is only beginning to escape false binaries such as business versus social unionism, the servicing versus organizing model, or ‘top-down’ versus ‘bottom-up’ administration. In this paper, I attempt to conceptualize the strategies adopted by the union as they exist in relation to the changing political economic landscape. I characterize the current labour practices as ‘Schumpeterian unionism’, a model which captures the shifting, contradictory, and multi-scalar relationships labour has with the broader community, capital and the state. The model is illustrated with a case study of UNITE-HERE Local 75’s response to the 2003 SARS outbreak through their establishment of a Hospitality Workers Resource Centre to service unemployed workers.


title: Go slow to go fast: A plea for sustained scientific rigor in air pollution research during the COVID-19 pandemic

text: Present studies on the role of air pollution and COVID-19 spread and prognosis in patients do not fulfill quality criteria and are at present not sufficiently informative.


title: Molecular and serological surveillance of canine enteric viruses in stray dogs from Vila do Maio, Cape Verde

text: BACKGROUND: Infections caused by canine parvovirus, canine distemper virus and canine coronavirus are an important cause of mortality and morbidity in dogs worldwide. Prior to this study, no information was available concerning the incidence and prevalence of these viruses in Cape Verde archipelago. RESULTS: To provide information regarding the health status of the canine population in Vila do Maio, Maio Island, Cape Verde, 53 rectal swabs were collected from 53 stray dogs during 2010 and 93 rectal swabs and 88 blood samples were collected from 125 stray dogs in 2011. All rectal swabs (2010 n = 53; 2011 n = 93) were analysed for the presence of canine parvovirus, canine distemper virus and canine coronavirus nucleic acids by quantitative PCR methods. Specific antibodies against canine distemper virus and canine parvovirus were also assessed (2011 n = 88). From the 2010 sampling, 43.3% (23/53) were positive for canine parvovirus DNA, 11.3% (6/53) for canine distemper virus RNA and 1.9% (1/53) for canine coronavirus RNA. In 2011, the prevalence values for canine parvovirus and canine coronavirus were quite similar to those from the previous year, respectively 44.1% (41/93), and 1.1% (1/93), but canine distemper virus was not detected in any of the samples analysed (0%, 0/93). Antibodies against canine parvovirus were detected in 71.6% (63/88) blood samples and the seroprevalence found for canine distemper virus was 51.1% (45/88). CONCLUSIONS: This study discloses the data obtained in a molecular and serological epidemiological surveillance carried out in urban populations of stray and domestic animals. Virus transmission and spreading occurs easily in large dog populations leading to high mortality rates particularly in unvaccinated susceptible animals. In addition, these animals can act as disease reservoirs for wild animal populations by occasional contact. Identification of susceptible wildlife of Maio Island is of upmost importance to evaluate the risk of pathogen spill over from domestic to wild animals in Cape Verde and to evaluate the associated threat to the wild susceptible species.


The impact of COVID‐19 pandemic on ophthalmological emergency department visits


title: Ibuprofen and thromboembolism in SARS‐COV2

text: Recent and developing literature has begun reporting on the incidence of thromboembolic events associated with COVID‐19. Klok et al. analysed 184 SARS‐CoV2‐positive ICU patients in two Dutch University Hospitals, reporting an incidence of thrombotic complications to be 31%, with Pulmonary Embolism (PE) comprising 81% of these complications. [1] Moreover, Cui et al. reports on a population of 81 ICU patients at the Union Hospital, Wuhan, an incidence of 25% in VTE, also possibly related to worse prognosis.[2] Wang et al. collected data from 1026 COVID‐19 positive patients in 31 provincial administrative regions in China and found 40% of the patients as high risk for VTE according to the Padua Prediction Score, with 11% being predicted to go on developing VTE. [3] Other reports and studies have also discussed the role of acute PE in COVID‐19. Recent studies have also reported and advised on the use of prophylactic Low Molecular Weight Heparin (LMWH) in COVID‐19 patients, to prevent the severe outcomes associated with thromboembolic complications.


Covid-19 and community development


title: Virus‐like particules in the poison glant of the parasitic wasp Opius concolor

text: Virus‐like particles (VLP's) have been found in the poison glands of adult females of the parasitic wasp Opius concolor Szèpl. (Hymenoptera, Braconidae). These VLP's are found in the secretory cells either free in the cytoplasm or within cytoplasmic vesicles, sometimes associated to a secretory apparatus. Negative staining of these VLP's has revealed the occurrence of two different particles. The first type exhibits icosahedral symmetry (diameter around 70nm) and hollow surface spikes, this morphology being typical of the genus Cypovirus (Reoviridae). The other type is pleomorphic and presents an envelope with clubshaped projections (diameter ranging from 30 to 60nm), as classical textbook examples of Coronaviruses, but smaller. Function and full characterisation of these particles are not yet known.


title: Rapid implementation of virtual clinics due to COVID-19: report and early evaluation of a quality improvement initiative

text: BACKGROUND: The COVID-19 outbreak has placed the National Health Service under significant strain. Social distancing measures were introduced in the UK in March 2020 and virtual consultations (via telephone or video call) were identified as a potential alternative to face-to-face consultations at this time. LOCAL PROBLEM: The Royal National Orthopaedic Hospital (RNOH) sees on average 11 200 face-to-face consultations a month. On average 7% of these are delivered virtually via telephone. In response to the COVID-19 crisis, the RNOH set a target of reducing face-to-face consultations to 20% of all outpatient attendances. This report outlines a quality improvement initiative to rapidly implement virtual consultations at the RNOH. METHODS: The COVID-19 Action Team, a multidisciplinary group of healthcare professionals, was assembled to support the implementation of virtual clinics. The Institute for Healthcare Improvement approach to quality improvement was followed using the Plan-Do-Study-Act (PDSA) cycle. A process of enablement, process redesign, delivery support and evaluation were carried out, underpinned by Improvement principles. RESULTS: Following the target of 80% virtual consultations being set, 87% of consultations were delivered virtually during the first 6 weeks. Satisfaction scores were high for virtual consultations (90/100 for patients and 78/100 for clinicians); however, outside of the COVID-19 pandemic, video consultations would be preferred less than 50% of the time. Information to support the future redesign of outpatient services was collected. CONCLUSIONS: This report demonstrates that virtual consultations can be rapidly implemented in response to COVID-19 and that they are largely acceptable. Further initiatives are required to support clinically appropriate and acceptable virtual consultations beyond COVID-19. REGISTRATION: This project was submitted to the RNOH’s Project Evaluation Panel and was classified as a service evaluation on 12 March 2020 (ref: SE20.09).


title: Livestock Drugs and Disease: The Fatal Combination behind Breeding Failure in Endangered Bearded Vultures

text: There is increasing concern about the impact of veterinary drugs and livestock pathogens as factors damaging wildlife health, especially of threatened avian scavengers feeding upon medicated livestock carcasses. We conducted a comprehensive study of failed eggs and dead nestlings in bearded vultures (Gypaetus barbatus) to attempt to elucidate the proximate causes of breeding failure behind the recent decline in productivity in the Spanish Pyrenees. We found high concentrations of multiple veterinary drugs, primarily fluoroquinolones, in most failed eggs and nestlings, associated with multiple internal organ damage and livestock pathogens causing disease, especially septicaemia by swine pathogens and infectious bursal disease. The combined impact of drugs and disease as stochastic factors may result in potentially devastating effects exacerbating an already high risk of extinction and should be considered in current conservation programs for bearded vultures and other scavenger species, especially in regards to dangerous veterinary drugs and highly pathogenic poultry viruses.


Who should perform the rhinopharyngeal swab in COVID‐19 positive patients?


title: Origin, Adaptation and Evolutionary Pathways of Fungal Viruses

text: Fungal viruses or mycoviruses are widespread in fungi and are believed to be of ancient origin. They have evolved in concert with their hosts and are usually associated with symptomless infections. Mycoviruses are transmitted intracellularly during cell division, sporogenesis and cell fusion, and they lack an extracellular phase to their life cycles. Their natural host ranges are limited to individuals within the same or closely related vegetative compatibility groups. Typically, fungal viruses are isometric particles 25–50 nm in diameter, and possess dsRNA genomes. The best characterized of these belong to the family Totiviridae whose members have simple undivided dsRNA genomes comprised of a coat protein (CP) gene and an RNA dependent RNA polymerase (RDRP) gene. A recently characterized totivirus infecting a filamentous fungus was found to be more closely related to protozoan totiviruses than to yeast totiviruses suggesting these viruses existed prior to the divergence of fungi and protozoa. Although the dsRNA viruses at large are polyphyletic, based on RDRP sequence comparisons, the totiviruses are monophyletic. The theory of a cellular self-replicating mRNA as the origin of totiviruses is attractive because of their apparent ancient origin, the close relationships among their RDRPs, genome simplicity and the ability to use host proteins efficiently. Mycoviruses with bipartite genomes (partitiviruses), like the totiviruses, have simple genomes, but the CP and RDRP genes are on separate dsRNA segments. Because of RDRP sequence similarity, the partitiviruses are probably derived from a totivirus ancestor. The mycoviruses with unencapsidated dsRNA-like genomes (hypoviruses) and those with bacilliform (+) strand RNA genomes (barnaviruses) have more complex genomes and appear to have common ancestry with plant (+) strand RNA viruses in supergroup 1 with potyvirus and sobemovirus lineages, respectively. The La France isometric virus (LIV), an unclassified virus with multipartite dsRNA genome, is associated with a severe die-back disease of the cultivated mushroom. LIV appears to be of recent origin since it differs from its host in codon usage.


title: Postoperative online follow-up improves the quality of life of patients who undergo extraction of impacted madibular third molars: a randomized controlled trial

text: OBJECTIVE: To evaluate the effect of online follow-up on the quality of life of patients who undergo extraction of impacted mandibular third molars. MATERIALS AND METHODS: This study enrolled patients with impacted mandibular third molars who were treated at the Department of Oral and Maxillofacial Surgery of the Stomatological Hospital at Southern Medical University and divided them into test and control groups. The test group received an online follow-up on the first, third, and fifth days after tooth extraction, while the control group was not followed up with. Patients in both groups were reexamined on the postoperative seventh day, completing the postoperative symptom severity (PoSSe) scale to comprehensively and quantitatively evaluate their quality of life after tooth extraction. A visual analogue scale (VAS) was used to evaluate the degree of approval for an online follow-up after tooth extraction by 20 senior doctors (≥ 40 years old) and 20 young doctors (<4 0 years old). RESULTS: The PoSSe scale scores of the remaining options in the test group were significantly lower than those in the control group. The VAS score of senior doctors for online follow-up was significantly lower than that of young doctors. CONCLUSIONS: A postoperative online follow-up effectively improved the quality of life of patients who underwent extraction of impacted mandibular third molars. Compared with senior doctors, young doctors were more likely to approve an online follow-up after tooth extraction. CLINICAL RELEVANCE: Online medical care can be considered as an auxiliary tool to improve the effect of oral treatment.


title: Recombination in Avian Gamma-Coronavirus Infectious Bronchitis Virus

text: Recombination in the family Coronaviridae has been well documented and is thought to be a contributing factor in the emergence and evolution of different coronaviral genotypes as well as different species of coronavirus. However, there are limited data available on the frequency and extent of recombination in coronaviruses in nature and particularly for the avian gamma-coronaviruses where only recently the emergence of a turkey coronavirus has been attributed solely to recombination. In this study, the full-length genomes of eight avian gamma-coronavirus infectious bronchitis virus (IBV) isolates were sequenced and along with other full-length IBV genomes available from GenBank were analyzed for recombination. Evidence of recombination was found in every sequence analyzed and was distributed throughout the entire genome. Areas that have the highest occurrence of recombination are located in regions of the genome that code for nonstructural proteins 2, 3 and 16, and the structural spike glycoprotein. The extent of the recombination observed, suggests that this may be one of the principal mechanisms for generating genetic and antigenic diversity within IBV. These data indicate that reticulate evolutionary change due to recombination in IBV, likely plays a major role in the origin and adaptation of the virus leading to new genetic types and strains of the virus.


title: Temporal Variation in Physiological Biomarkers in Black Flying-Foxes (Pteropus alecto), Australia

text: Bats of the genus Pteropus (Pteropodidae) are recognised as the natural host of multiple emerging pathogenic viruses of animal and human health significance, including henipaviruses, lyssaviruses and ebolaviruses. Some studies have suggested that physiological and ecological factors may be associated with Hendra virus infection in flying-foxes in Australia; however, it is essential to understand the normal range and seasonal variability of physiological biomarkers before seeking physiological associations with infection status. We aimed to measure a suite of physiological biomarkers in P. alecto over time to identify any seasonal fluctuations and to examine possible associations with life-cycle and environmental stressors. We sampled 839 adult P. alecto in the Australian state of Queensland over a 12-month period. The adjusted population means of every assessed hematologic and biochemical parameter were within the reported reference range on every sampling occasion. However, within this range, we identified significant temporal variation in these parameters, in urinary parameters and body condition, which primarily reflected the normal annual life cycle. We found no evident effect of remarkable physiological demands or nutritional stress, and no indication of clinical disease driving any parameter values outside the normal species reference range. Our findings identify underlying temporal physiological changes at the population level that inform epidemiological studies and assessment of putative physiological risk factors driving Hendra virus infection in P. alecto. More broadly, the findings add to the knowledge of Pteropus populations in terms of their relative resistance and resilience to emerging infectious disease.


title: Emergence of Enteric Viruses in Production Chickens Is a Concern for Avian Health

text: Several viruses have been identified in recent years in the intestinal contents of chickens and turkeys with enteric problems, which have been observed in commercial farms worldwide, including Brazil. Molecular detection of these viruses in Brazil can transform to a big threat for poultry production due to risk for intestinal integrity. This disease is characterized by severely delayed growth, low uniformity, lethargy, watery diarrhea, delayed feed consumption, and a decreased conversion rate. Chicken astrovirus (CAstV), rotavirus, reovirus, chicken parvovirus (ChPV), fowl adenovirus of subgroup I (FAdV-1), and avian nephritis virus (ANV) were investigated using the conventional polymerase chain reaction (PCR) and the reverse transcription polymerase chain reaction (RT-PCR). In addition, the infectious bronchitis virus (IBV), which may play a role in enteric disease, was included. The viruses most frequently detected, either alone or in concomitance with other viruses, were IBV, ANV, rotavirus, and CAstV followed by parvovirus, reovirus, and adenovirus. This study demonstrates the diversity of viruses in Brazilian chicken flocks presenting enteric problems characterized by diarrhea, growth retard, loss weight, and mortality, which reflects the multicausal etiology of this disease.


title: Pulling a DNA molecule through a nanopore embedded in an anionic membrane: tension propagation coupled to electrostatics

text: We consider the influence of electrostatic forces on driven translocation dynamics of a flexible polyelectrolyte being pulled through a nanopore by an external force on the head monomer. To this end, we augment the iso-flux tension propagation (IFTP) theory with electrostatics for a negatively charged biopolymer pulled through a nanopore embedded in a similarly charged anionic membrane. We show that for the realistic case such as a single-stranded DNA, the translocation dynamics at low salt where screening is weak and at finite negative membrane charge is unexpectedly accelerated despite the large repulsive electrostatic interactions between the polymer coil on the {\it cis} side and the charged membrane. This is due to the rapid release of the electrostatic potential energy of the coil during translocation, leading to an effectively attractive force that assists end-driven translocation. The speedup results in non-monotonic polymer length and membrane charge dependence of the exponent $\alpha$ characterizing the translocation time $\tau \propto N_0^\alpha$ of the polymer with length $N_0$. In the regime of long polymers $N_0\gtrsim500$, the translocation exponent exceeds its upper limit $\alpha=2$ previously observed for the same system without electrostatic interactions.


title: An advanced numerical model for the assessment of airborne transmission of influenza in bus microenvironments

text: Abstract A CFD-based numerical model was integrated with the Wells–Riley equation to numerically assess the risk of airborne influenza infection in a popular means of public transportation, e.g. the bus microenvironment. Three mixing ventilation methods, which are widely used in current bus configurations, and an alternative displacement ventilation method were numerically assessed in terms of their ability to limit the risk of airborne influenza infection. Furthermore, both the non air-recirculation and air-recirculation with filtration ventilation modes were investigated in terms of the influenza infection probability. According to the simulation results, air-recirculation mode with high efficiency filtration was found to cause almost the same infection risk as non air-recirculation mode (100% outdoor air supply), which indicated a potential benefit of filtration in reducing the infection risk. Additionally, for the commonly used mixing ventilation methods, air distribution method, location of return/exhaust opening and seat arrangement affected the airborne transmission of influenza between passengers. The displacement ventilation method was found to be more effective in limiting the risk of airborne infection. Overall, the developed numerical model can provide insights into how the micro-environmental conditions affect airborne infection transmission in buses. This numerical model can assist in developing effective control strategies related to airborne transmitted diseases for other frequently used public transportation systems, such as trains and airplanes.


title: Candidate drugs against SARS-CoV-2 and COVID-19

text: Abstract Outbreak and pandemic of coronavirus SARS-CoV-2 in 2019/2020 will challenge global health for the future. Because a vaccine against the virus will not be available in the near future, we herein try to offer a pharmacological strategy to combat the virus. There exists a number of candidate drugs that may inhibit infection with and replication of SARS-CoV-2. Such drugs comprise inhibitors of TMPRSS2 serine protease and inhibitors of angiotensin-converting enzyme 2 (ACE2). Blockade of ACE2, the host cell receptor for the S protein of SARS-CoV-2 and inhibition of TMPRSS2, which is required for S protein priming may prevent cell entry of SARS-CoV-2. Further, chloroquine and hydroxychloroquine, and off-label antiviral drugs, such as the nucleotide analogue remdesivir, HIV protease inhibitors lopinavir and ritonavir, broad-spectrum antiviral drugs arbidol and favipiravir as well as antiviral phytochemicals available to date may prevent spread of SARS-CoV-2 and morbidity and mortality of COVID-19 pandemic.


First Middle East respiratory syndrome coronavirus (MERS-CoV) case in Southeast Asia (outside Middle East)