title: Epimedium-derived phytoestrogen exert beneficial effect on preventing steroid-associated osteonecrosis in rabbits with inhibition of both thrombosis and lipid-deposition

text: Abstract Objectives This study tested the effect of Epimedium-derived phytoestrogen (PE) on preventing steroid-associated osteonecrosis (ON) in rabbit model. Methods Thirty 28-week-old male New-Zealand white rabbits were divided into control group (CON; n =14) and PE group (PE; n =16; 5 mg/kg body weight/day) after receiving an established inductive protocol for inducing steroid-associated ON. Before and after inductive protocol, Dynamic-MRI was employed on bilateral femora for local intra-osseous perfusion, blood samples were examined for coagulation, fibrinolysis and lipid-transportation, and marrow samples were quantified for adipogenesis-gene mRNA expression. Six weeks later, bilateral femora were dissected for Micro-CT-based micro-angiography, and then ON lesion, intravascular thrombosis and extravascular fat-cell-size were examined histopathologically. Results The incidence of ON in the PE group (31%) was significantly lower than that in the CON group (93%). Compared to the CON group, local intra-osseous perfusion was maintained in the PE group. Blocked trunk vessels were seldom found in micro-angiography of the PE-treated rabbits. Thrombosis incidence and fat-cell-size were both significantly lower in the PE group than those in the CON group. During the early period after induction, indicator of coagulation, fibrinolysis, lipid-transportation and adipogenesis-gene expression were found with significantly changing pattern in the PE group compared to the CON group. Conclusion PE was able to exert beneficial effect on preventing steroid-associated ON in rabbits with inhibition of both thrombosis and lipid deposition.


title: HoBi-like pestivirus experimental infection in pregnant ewes: Reproductive disorders and generation of persistently infected lambs

text: Abstract In order to evaluate sheep as experimental model to test the efficacy of HoBi-like pestivirus vaccines for cattle, 10 sheep at different stages of pregnancy (30 or 50 days) were experimentally infected with the Italian prototype isolate Italy-1/10-1. Irrespective of the stage of pregnancy, virus inoculation resulted in reproductive failures, consisting of abortion, stillbirths or birth of weak or persistently infected (PI) lambs. Aborted fetuses, stillborn and dead lambs displayed extensive histopathological changes, consisting of hemorrhages, congestion and mononuclear infiltration in major organs. Pestiviral antigens were detected by immunohistochemistry in most tissues with remarkable signals in lungs and kidneys. PI lambs were constantly viremic, shed the virus through the nasal secretions and feces and, in all cases but one, did not have detectable HoBi-like pestivirus antibodies before the assumption of colostrum. The single seropositive infected lamb showed low-titer viremia and viral shedding that ceased only several weeks after the 3-month observation period. The study proves that sheep are susceptible to the reproduction failures caused by HoBi-like pestivirus infection and can serve as a suitable model for the evaluation of the fetal protection induced by homologous experimental vaccines.


title: Virus growth and antibody responses following respiratory tract infection of ferrets and mice with WT and P/V mutants of the paramyxovirus Simian Virus 5

text: P/V gene substitutions convert the non-cytopathic paramyxovirus Simian Virus 5 (SV5), which is a poor inducer of host cell responses in human tissue culture cells, into a mutant (P/V-CPI–) that induces high levels of apoptosis, interferon (IFN)-beta, and proinflammatory cytokines. However, the effect of SV5-P/V gene mutations on virus growth and adaptive immune responses in animals has not been determined. Here, we used two distinct animal model systems to test the hypothesis that SV5-P/V mutants which are more potent activators of innate responses in tissue culture will also elicit higher antiviral antibody responses. In mouse cells, in vitro studies identified a panel of SV5-P/V mutants that ranged in their ability to limit IFN responses. Intranasal infection of mice with these WT and P/V mutant viruses elicited equivalent anti-SV5 IgG responses at all doses tested, and viral titers recovered from the respiratory tract were indistinguishable. In primary cultures of ferret lung fibroblasts, WT rSV5 and P/V-CPI– viruses had phenotypes similar to those established in human cell lines, including differential induction of IFN secretion, IFN signaling and apoptosis. Intranasal infection of ferrets with a low dose of WT rSV5 elicited ~500 fold higher anti-SV5 serum IgG responses compared to the P/V-CPI– mutant, and this correlated with overall higher viral titers for the WT virus in tracheal tissues. There was a dose-dependent increase in antibody response to infection of ferrets with P/V-CPI–, but not with WT rSV5. Together our data indicate that WT rSV5 and P/V mutants can elicit distinct innate and adaptive immunity phenotypes in the ferret animal model system, but not in the mouse system. We present a model for the effect of P/V gene substitutions on SV5 growth and immune responses in vivo.


title: Characterization of a pathogenic full-length cDNA clone of a virulent porcine epidemic diarrhea virus strain AH2012/12 in China

text: Abstract Since 2010, outbreaks of variant porcine epidemic diarrhea virus (PEDV) have swept across the world causing substantial economic losses. The development of new, more effective vaccines has been hampered by difficulties in isolating strains and viral genome manipulation. In the present study, we successfully isolated a highly pathogenic field strain AH2012/12, from a pig farm reporting severe diarrhea in China. Phylogenetic analysis revealed that the new isolate belongs to group G2, which represents epidemic and pandemic field strains. Furthermore, we constructed an infectious cDNA clone of the newly isolated strain, rAH2012/12, and the rescued virus displayed phenotypic properties identical to the parental virus in vitro. In vivo experiments demonstrated that the rescued virus displayed similar pathogenicity to the parental isolate, causing high mortality rates in suckling pigs. This study provided a strong basis for the development of live attenuated vaccines and for research into the pathogenic mechanisms of this virus.


title: Identification of two auto-cleavage products of nonstructural protein 1 (nsp1) in porcine reproductive and respiratory syndrome virus infected cells: nsp1 function as interferon antagonist

text: Abstract The porcine reproductive and respiratory syndrome virus nsp1 is predicted to be auto-cleaved from the replicase polyprotein into nsp1α and nsp1β subunits. In infected cells, we detected the actual existence of nsp1α and nsp1β. Cleavage sites between nsp1α/nsp1β and nsp1β/nsp2 were identified by protein microsequencing analysis. Time course study showed that nsp1α and nsp1β mainly localize into the cell nucleus after 10 h post infection. Further analysis revealed that both proteins dramatically inhibited IFN-β expression. The nsp1β was observed to significantly inhibit expression from an interferon-stimulated response element promoter after Sendai virus infection or interferon treatment. It was further determined to inhibit nuclear translocation of STAT1 in the JAK–STAT signaling pathway. These results demonstrated that nsp1β has ability to inhibit both interferon synthesis and signaling, while nsp1α alone strongly inhibits interferon synthesis. These findings provide important insights into mechanisms of nsp1 in PRRSV pathogenesis and its impact in vaccine development.


Three Emerging Coronaviruses in Two Decades: The Story of SARS, MERS, and Now COVID-19


title: Combating physical inactivity during the COVID-19 pandemic

text: Physical inactivity is common during periods of self-isolation, but for patients with rheumatic diseases, there are crucial benefits to be gained from maintaining an active lifestyle throughout the COVID-19 pandemic. Patients should be provided with support to maintain physical activity and avoid prolonged periods of time spent sitting.


title: Comparison of mortality associated with respiratory viral infections between December 2019 and March 2020 with that of the previous year, Southeastern France

text: Abstract Respiratory viruses are a major global cause of mortality worldwide and in France where they cause several thousands of deaths yearly. University Hospital Institute-Méditerranée Infection performs real-time surveillance of all diagnoses of infections and associated deaths in public hospitals of Marseille, Southeastern France. Here, mortality associated with diagnoses of respiratory viruses was compared during colder months of 2018-2019 and 2019-2020 (week 47-week 14). In 2018-2019, 73 patients (0.17% of 42,851 hospitalized patients) died after being diagnosed with a respiratory virus; 40 and 13 deaths occurred in patients diagnosed with influenza A virus and respiratory syncytial virus (RSV), respectively. In 2019-2020, 50 patients (0.10% of 49,043 patients hospitalized) died after being diagnosed with a common respiratory virus; 7 and 7 deaths occurred in patients diagnosed with influenza A virus and RSV, respectively. Additionally, 55 patients died after being diagnosed with SARS-CoV-2. The proportion of respiratory virus-associated deaths among hospitalized patients was thus significantly lower for common respiratory viruses in 2019-2020 than in 2018-2019 (102 versus 170 per 100,000 hospitalized patients; p=0.003), majoritarily as a consequence of a decrease in influenza A virus (-83%) and RSV (-46%)-associated deaths. Overall, the proportion of respiratory virus-associated deaths among hospitalized patients was higher but not significantly in 2019-2020 than in 2018-2019 (214 versus 170 per 100,000 hospitalized patients; p=0.08, Yates-corrected chi-square test). These findings allow putting into perspective the death burden of SARS-CoV-2 infections in our geographical area.


title: Porcine epidemic diarrhea virus: Viral RNA detection and quantification using a validated one-step real time RT-PCR

text: Since 2014, porcine epidemic diarrhea virus (PEDV) has reemerged in Europe. RT-PCR methods have been described for the detection of PEDV, but none have been validated according to a norm. In this study we described the development and validation of a SYBR™ Green one-step RT-qPCR according to the French norm NF U47-600, for the detection and quantification of PEDV viral RNA. The method was validated from sample preparation (feces or jejunum) through to nucleic acid extraction and RT-qPCR detection. Specificity and sensitivity, limit of detection (LoD), limit of quantification (LQ), linearity, intra and inter assay variability were evaluated using transcribed RNA and fecal and jejunum matrices spiked with virus. The analytical and diagnostic specificities and sensitivities of this RT-qPCR were 100% in this study. A LoD of 50 genome copies/5 µl of extract from fecal matrices spiked with virus or RNA transcript and 100 genome copies/5 µl of extract from jejunum matrices spiked with virus were obtained. The Lower LQ (LLQ) was 100 genome copies/5 µl and the Upper LQ (ULQ) 10(8) copies/5 µl. This method is the first, validated according a norm for PEDV and may serve as a global reference method to harmonize detection and quantification of PEDV viral RNA in both field and experimental settings.


title: The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types

text: A novel isolate of the SARS-CoV-2 virus carrying a point mutation in the Spike protein (D614G) has recently emerged and rapidly surpassed others in prevalence. This mutation is in linkage disequilibrium with an ORF1b protein variant (P314L), making it difficult to discern the functional significance of the Spike D614G mutation from population genetics alone. Here, we perform site-directed mutagenesis to introduce the D614G variant and show that in multiple cell lines, including human lung epithelial cells, that the D614G mutation is up to 8-fold more effective at transducing cells than wild-type. We demonstrate increased infection using both Spike-pseudotyped lentivirus and intact SARS-CoV-2 virus. Although there is minimal difference in ACE2 receptor binding between the Spike variants, we show that the G614 variant is more resistant to proteolytic cleavage in vitro and in human cells, suggesting a possible mechanism for the increased transduction. This result has important implications for the efficacy of Spike-based vaccines currently under development in protecting against this recent and highly-prevalent SARS-CoV-2 isolate.


title: The impact of 2019 novel coronavirus on heart injury: A systemic review and Meta-analysis

text: Abstract Background Evidence about COVID-19 on cardiac injury is inconsistent. Objectives We aimed to summarize available data on severity differences in acute cardiac injury and acute cardiac injury with mortality during the COVID-19 outbreak. Methods We performed a systematic literature search across Pubmed, Embase and pre-print from December 1, 2019 to March 27, 2020, to identify all observational studies that reported cardiac specific biomarkers (troponin, creatine kinase–MB fraction, myoglobin, or NT-proBNP) during COVID-19 infection. We extracted data on patient demographics, infection severity, comorbidity history, and biomarkers during COVID-19 infection. Where possible, data were pooled for meta-analysis with standard (SMD) or weighted (WMD) mean difference and corresponding 95% confidence intervals (CI). Results We included 4189 confirmed COVID-19 infected patients from 28 studies. More severe COVID-19 infection is associated with higher mean troponin (SMD 0.53, 95% CI 0.30 to 0.75, p < 0.001), with a similar trend for creatine kinase–MB, myoglobin, and NT-proBNP. Acute cardiac injury was more frequent in those with severe, compared to milder, disease (risk ratio 5.99, 3.04 to 11.80; p < 0.001). Meta regression suggested that cardiac injury biomarker differences of severity are related to history of hypertension (p = 0.030). Also COVID19-related cardiac injury is associated with higher mortality (summary risk ratio 3.85, 2.13 to 6.96; p < 0.001). hsTnI and NT-proBNP levels increased during the course of hospitalization only in non-survivors. Conclusion The severity of COVID-19 is associated with acute cardiac injury, and acute cardiac injury is associated with death. Cardiac injury biomarkers mainly increase in non-survivors. This highlights the need to effectively monitor heart health to prevent myocarditis in patients infected with COVID-19.


The Doctor Will Call You Now! Telemedicine in the midst of a pandemic


title: Plagues, pandemics and epidemics in Irish history prior to COVID-19 (coronavirus): what can we learn?

text: OBJECTIVES: This paper seeks to provide a brief overview of epidemics and pandemics in Irish history and to identify any lessons that might be useful in relation to psychiatry in the context of COVID-19. METHODS: A review of selected key reports, papers and publications related to epidemics and pandemics in Irish history was conducted. RESULTS: Viruses, epidemics and pandemics are recurring features of human history. Early Irish sources record a broad array of plagues, pandemics and epidemics including bubonic plague, typhus, cholera, dysentery and smallpox, as well as an alleged epidemic of insanity in the 19th century (that never truly occurred). Like the Spanish flu pandemic (1918–20), COVID-19 (a new coronavirus) presents both the challenge of the illness itself and the problems caused by the anxiety that the virus triggers. Managing this anxiety has always been a challenge, especially with the Spanish flu. People with mental illness had particularly poor outcomes with the Spanish flu, often related to the large, unhygienic mental hospitals in which so many were housed. CONCLUSIONS: Even today, a full century after the Spanish flu pandemic, people with mental illness remain at increased risk of poor physical health, so it is imperative that multi-disciplinary care continues during the current outbreak of COVID-19, despite the manifest difficulties involved. The histories of previous epidemics and pandemics clearly demonstrate that good communication and solidarity matter, now more than ever, especially for people with mental illness.


title: Identification of heat-dissociable RNA complexes in two porcine coronaviruses

text: THE coronavirus genome has been shown to comprise single-stranded RNA(1,2). Examination of the viral nucleic acid synthesised by pig kidney cells infected with transmissible gastroenteritis virus (TGEV) suggested that several molecular species, ranging in size between 18 and 28S, were involved in the viral replicative cycle(3); similarly Tannock found a wide variation in the size of RNA molecules extracted from avian infectious bronchitis virus (IBV) by a phenol–sodium dodecyl sulphate (SDS) method(2). Extraction of IBV RNA by 1% SDS at 60 °C has, however, revealed a single component of molecular weight 9×10(6) corresponding to 60S by electrophoresis through 2.2% polyacrylamide gels(4).


title: Is molecular mimicry the culprit in the autoimmune haemolytic anaemia affecting patients with COVID‐19?

text: This Journal recently published two papers describing autoimmune hemolytic anemia (AIHA) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (1, 2). AIHA is characterized by the destruction of red cells by autoantibodies, but the mechanism underpinning autoimmunity in COVID-19 patients has yet to be elucidated.


title: Mice with different susceptibility to tick-borne encephalitis virus infection show selective neutralizing antibody response and inflammatory reaction in the central nervous system

text: BACKGROUND: The clinical course of tick-borne encephalitis (TBE), a disease caused by TBE virus, ranges from asymptomatic or mild influenza-like infection to severe debilitating encephalitis or encephalomyelitis. Despite the medical importance of this disease, some crucial steps in the development of encephalitis remain poorly understood. In particular, the basis of the disease severity is largely unknown. METHODS: TBE virus growth, neutralizing antibody response, key cytokine and chemokine mRNA production and changes in mRNA levels of cell surface markers of immunocompetent cells in brain were measured in mice with different susceptibilities to TBE virus infection. RESULTS: An animal model of TBE based on BALB/c-c-STS/A (CcS/Dem) recombinant congenic mouse strains showing different severities of the infection in relation to the host genetic background was developed. After subcutaneous inoculation of TBE virus, BALB/c mice showed medium susceptibility to the infection, STS mice were resistant, and CcS-11 mice were highly susceptible. The resistant STS mice showed lower and delayed viremia, lower virus production in the brain and low cytokine/chemokine mRNA production, but had a strong neutralizing antibody response. The most sensitive strain (CcS-11) failed in production of neutralizing antibodies, but exhibited strong cytokine/chemokine mRNA production in the brain. After intracerebral inoculation, all mouse strains were sensitive to the infection and had similar virus production in the brain, but STS mice survived significantly longer than CcS-11 mice. These two strains also differed in the expression of key cytokines/chemokines, particularly interferon gamma-induced protein 10 (IP-10/CXCL10) and monocyte chemotactic protein-1 (MCP-1/CCL2) in the brain. CONCLUSIONS: Our data indicate that the genetic control is an important factor influencing the clinical course of TBE. High neutralizing antibody response might be crucial for preventing host fatality, but high expression of various cytokines/chemokines during TBE can mediate immunopathology and be associated with more severe course of the infection and increased fatality.


title: Middle East respiratory syndrome coronavirus (MERS-CoV): evidence and speculations

text: In 2012, a novel human coronavirus emerged and was tentatively named “Middle East respiratory syndrome coronavirus” (MERS-CoV). The high mortality rate of MERS-CoV focused attention on the ecology of the virus. It has been found that MERS-CoV belongs to the group C lineage of the genus Betacoronavirus. Coronavirus surveillance studies in different populations of bats have suggested that they are probable reservoirs for this novel virus, and phylogenetic analysis of both the spike (S1) and RNA-dependent RNA polymerase proteins of MERS-CoV have revealed that it is related to bat viruses. Recently, the MERS-CoV and its neutralizing antibodies were detected in dromedary camels. Despite the limited number of reported cases of person-to-person transmission, the rapid evolution of the virus poses a continuous threat to humans worldwide. This paper reviews the current state of knowledge regarding the virology, clinical spectrum, evolution, diagnosis and treatment of MERS-CoV infections.


title: Detection and genetic analysis of porcine hemagglutinating encephalomyelitis virus in South Korea

text: Porcine hemagglutinating encephalomyelitis virus (PHEV) causes vomiting and wasting disease (VWD) or encephalomyelitis, and primarily affects pigs under 3 weeks of age. In this study, we detected PHEV from clinically ill pigs in conventional pig farms in South Korea. From November 2009 to March 2010, a total of 239 pig tissue samples from 91 farms were tested by nested RT-PCR. Among 239 samples, 22 samples from 17 farms were positive for PHEV. The detection rate of suckling pigs, weaning pigs, growers and finishers were 14.3% (12/84), 6.5% (7/107), 7% (3/43), and 0% (0/5), respectively. Symptoms were neurological, respiratory, enteric sign (diarrhea), or nasal bleeding. All pigs were co-infected with other viruses and bacteria and this might have resulted in age variation and clinical signs in the affected pigs. Phylogenetic analysis showed that the PHEV-positive samples and PHEV reference strains were clustered in the same group. These findings imply the presence of only one genogroup of PHEV, regardless of porcine age, clinical signs, and geographical location.


title: Perspektiven für das Coaching nach der Corona-Krise

text: Considering the actual corona crisis, coaches should be concerned about the question what will come up to us in all areas of life and especially in the working environments: Which problems, conflicts or requirements for change and new ambivalences we can anticipate? Which special questions we have to emphasize in the context of coaching? There are trends which are identifiable long ago and which nowadays undergo an intensification or acceleration, and on the other hand largely new developments. In this discourse, the author presents some assumptions for understanding the psycho-social situation provoked by the corona crisis and with regard to the central issues in coaching and counselling.


title: Targeted antigen delivery to dendritic cells elicits robust antiviral T cell-mediated immunity in the liver

text: Hepatotropic viruses such as hepatitis C virus cause life-threatening chronic liver infections in millions of people worldwide. Targeted in vivo antigen-delivery to cross-presenting dendritic cells (DCs) has proven to be extraordinarily efficient in stimulating antigen-specific T cell responses. To determine whether this approach would as well be suitable to induce local antiviral effector T cells in the liver we compared different vaccine formulations based on either the targeting of DEC-205 or TLR2/6 on cross-presenting DCs or formulations not involving in vivo DC targeting. As read-outs we used in vivo hepatotropic adenovirus challenge, histology and automated multidimensional fluorescence microscopy (MELC). We show that targeted in vivo antigen delivery to cross-presenting DCs is highly effective in inducing antiviral CTLs capable of eliminating virus-infected hepatocytes, while control vaccine formulation not involving DC targeting failed to induce immunity against hepatotropic virus. Moreover, we observed distinct patterns of CD8(+) T cell interaction with virus-infected and apoptotic hepatocytes in the two DC-targeting groups suggesting that the different vaccine formulations may stimulate distinct types of effector functions. Our findings represent an important step toward the future development of vaccines against hepatotropic viruses and the treatment of patients with hepatic virus infection after liver transplantation to avoid reinfection.


title: Ultraviolet germicidal irradiation of influenza-contaminated N95 filtering facepiece respirators

text: BACKGROUND: Safe and effective decontamination and reuse of N95 filtering facepiece respirators (FFRs) has the potential to significantly extend FFR holdings, mitigating a potential shortage due to an influenza pandemic or other pandemic events. Ultraviolet germicidal irradiation (UVGI) has been shown to be effective for decontaminating influenza-contaminated FFRs. This study aims to build on past research by evaluating the UVGI decontamination efficiency of influenza-contaminated FFRs in the presence of soiling agents using an optimized UVGI dose. METHODS: Twelve samples each of 15 N95 FFR models were contaminated with H1N1 influenza (facepiece and strap), then covered with a soiling agent—artificial saliva or artificial skin oil. For each soiling agent, 3 contaminated FFRs were treated with 1 J/cm(2) UVGI for approximately 1 minute, whereas 3 other contaminated FFRs remained untreated. All contaminated surfaces were cut out and virus extracted. Viable influenza was quantified using a median tissue culture infectious dose assay. RESULTS: Significant reductions (≥3 log) in influenza viability for both soiling conditions were observed on facepieces from 12 of 15 FFR models and straps from 7 of 15 FFR models. CONCLUSIONS: These data suggest that FFR decontamination and reuse using UVGI can be effective. Implementation of a UVGI method will require careful consideration of FFR model, material type, and design.


title: The effect of loss of regulation of minus-strand RNA synthesis on sindbis virus replication

text: Abstract During the replication cycle of Sindbis virus minus-strand synthesis stops normally at the time that plus-strand synthesis reaches a maximum rate. We have isolated and characterized revertants of ts24, a member of the A complementation group of Sindbis HR mutants, that we had demonstrated previously to have a temperature-sensitive defect in the regulation of minus-strand synthesis. These revertants of ts24 replicated efficiently at 40° but nevertheless retained the temperature sensitive defect in the regulation of minus-strand synthesis: they continued to synthesize minus strands late in the replication cycle at 40° but not at 30° and in the presence or absence of protein synthesis. Although failure to regulate the synthesis of minus strands resulted in continuous minus-strand synthesis and in the accumulation of minus strands, the rate of plus-strand synthesis was not increased concertedly. Minus strands synthesized after the rate of plus-strand synthesis had become constant were demonstrated to be utilized as templates for 26 S mRNA synthesis. Thus, the change from an increasing to a constant rate of plus-strand synthesis during the alphavirus replication cycle cannot be governed solely by the number of minus strands that accumulate in infected cells. We present a model for the preferential utilization of minus strands as a mechanism for the cessation of minus-strand synthesis that occurs normally during alphavirus replication.


title: Seroprävalenz und SARS-CoV-2-Testung in Gesundheitsberufen

text: The SARS-CoV‑2 causes a disease spectrum that includes asymptomatic and mildly symptomatic infections with subclinical manifestations but which can nevertheless still be potentially contagious. Evidence from SARS-CoV‑2 infected macaque monkeys and from studies with seasonal coronaviruses suggests that the infection is likely to produce an immunity that is protective for a certain period of time. Available test methods enable a high degree of reliability, e.g. if high-quality serological methods are combined. Although individual test results have to be interpreted with caution, serosurveillance in a tertiary eye care center and large eye research institute can reduce anxiety and provide clarity regarding the actual number of (unreported) SARS-CoV‑2 infections.


title: Acute respiratory distress syndrome

text: Acute respiratory distress syndrome (ARDS) can be associated with various disorders. Among these, coronavirus infection may cause life-threatening severe acute respiratory syndrome (SARS). In this review, we present animal models and techniques for the study of ARDS, and discuss the roles and possible mechanisms of various chemical factors, including nitric oxide (NO). Our early work revealed that cerebral compression elicits severe hemorrhagic pulmonary edema (PE), leading to central sympathetic activation that results in systemic vasoconstriction. The consequence of systemic vasoconstriction is volume and pressure loading in the pulmonary circulation. Vasodilators, but not oxidant radical scavengers, are effective in the prevention of centrogenic PE. In isolated perfused lung, exogenous and endogenous NO enhances lung injury following air embolism and ischemia/reperfusion. In contrast, NO synthase (NOS) inhibitors reverse such lung injury. Although NO is important in maintaining vasodilator tone, hypoxia-induced pulmonary vasoconstriction is accompanied by an increase instead of a decrease in NO release. In animal and isolated lung studies, endotoxin produces acute lung injury that is associated with increases in cytokines and inducible NOS mRNA expression, suggesting that NO is toxic to the lung in endotoxin shock. Recently, we reported several rare cases that indicate that ARDS in patients with Japanese B encephalitis, lymphangitis with breast cancer and fat embolism is caused by different mechanisms. Our early and recent studies on ARDS and PE may provide information for clinical practice and the understanding of the pathogenesis of SARS.


title: One Aspect of Coronavirus disease (COVID-19) Outbreak in Iran: High Anxiety among MS Patients

text: • The incidence rate of COVID-19 is increasing in Iran on each successive day. • This increasing incidence causes anxiety in Iranian population. • This study revealed a significant level of anxiety among the MS patients.


title: Pathogenicity and transmissibility of 2019-nCoV—A quick overview and comparison with other emerging viruses

text: Abstract A zoonotic coronavirus, tentatively labeled as 2019-nCoV by the World Health Organization (WHO), has been identified as the causative agent of the viral pneumonia outbreak in Wuhan, China, at the end of 2019. Although 2019-nCoV can cause a severe respiratory illness like SARS and MERS, evidence from clinics suggested that 2019-nCoV is generally less pathogenic than SARS-CoV, and much less than MERS-CoV. The transmissibility of 2019-nCoV is still debated and needs to be further assessed. To avoid the 2019-nCoV outbreak turning into an epidemic or even a pandemic and to minimize the mortality rate, China activated emergency response procedures, but much remains to be learned about the features of the virus to refine the risk assessment and response. Here, the current knowledge in 2019-nCoV pathogenicity and transmissibility is summarized in comparison with several commonly known emerging viruses, and information urgently needed for a better control of the disease is highlighted.


title: Synthesis and antiviral evaluation of 7-O-arylmethylquercetin derivatives against SARS-associated coronavirus (SCV) and hepatitis C virus (HCV)

text: Aryl diketoacid (ADK) is well known for antiviral activity which can be enhanced by introduction of an aromatic arylmethyl substituent. A natural flavonoid quercetin has a 3,5-dihydroxychromone pharmacophore which is in bioisosteric relationship with the 1,3-diketoacid moiety of the ADK. Thus, it was of our interest to test the antiviral activity of the quercetin derivatives with an arylmethyl group attached. In this study, we prepared a series of the 7-O-arylmethylquercetin derivatives with various aromatic substituents and evaluated their antiviral activity against the SARS-associated coronavirus (SARS-CoV, SCV) as well as hepatitis C virus (HCV). Single difference in the aromatic substituent fine-tuned the biological activity of the 7-O-arylmethylquercetin derivatives to result in two different classes of derivatives selectively active against SCV and HCV.


title: Cutaneous small vessel vasculitis secondary to COVID‐19 infection: A case report

text: We present a case of an 83‐year‐old woman with a history of hypertension, transient ischemic attack (TIA), atrial fibrillation, chronic renal impairment presented to our dermatology emergency room on April 9, 2020, for evaluation of purple palpable papules and serohaematic blisters on both her lower legs, feet and toes that had appeared 5 days earlier (Figure 1).


Turning a surgical unit into a COVID-19 facility: governance counts. Correspondence


title: Public Health Communication in Time of Crisis: Readability of On-Line COVID-19 Information

text: OBJECTIVE: The purpose of this study was to assess the readability of information on the Internet posted about coronavirus disease 2019 (COVID-19) to determine how closely these materials are written to the recommended reading levels. METHODS: Using the search term “coronavirus,” information posted on the first 100 English language websites was identified. Using an online readability calculator, multiple readability tests were conducted to ensure a comprehensive representation would result. RESULTS: The mean readability scores ranged between grade levels 6.2 and 17.8 (graduate school level). Four of the 5 measures (GFI, CLI, SMOG, FRE) found that readability exceeded the 10th grade reading level indicating that the text of these websites would be difficult for the average American to read. The mean reading level for nearly all noncommercial and commercial websites was at or above the 10th grade reading level. CONCLUSIONS: Messages about COVID-19 must be readable at an “easy” level, and must contain clear guidelines for behavior. The degree to which individuals seek information in response to risk messages is positively related to the expectation that the information will resolve uncertainty. However, if the information is too complex to interpret and it fails to lead to disambiguation, this can contribute to feelings of panic.


Author’s correction for Euro Surveill. 2020;25(10)


title: DC-SIGN Interacts with Mycobacterium leprae but Sequence Variation in This Lectin Is Not Associated with Leprosy in the Pakistani Population

text: The C-type lectin DC-SIGN is involved in early interactions between human innate immune cells and a variety of pathogens. Here we sought to evaluate whether DC-SIGN interacts with the leprosy bacillus, Mycobacterium leprae, and whether DC-SIGN genetic variation influences the susceptibility and/or pathogenesis of the disease. A case–control study conducted in a cohort of 272 individuals revealed no association between DC-SIGN variation and leprosy. However, our results clearly show that DC-SIGN recognizes M. leprae, indicating that mycobacteria recognition by this lectin is not as narrowly restricted to the Mycobacterium tuberculosis complex as previously thought. Altogether, our results provide further elucidation of M. leprae interactions with the host innate immune cells and emphasize the importance of DC-SIGN in the early interactions between the human host and the infectious agents.


title: Liver injury during highly pathogenic human coronavirus infections

text: The severe acute respiratory syndrome coronavirus 2 (SARS‐Cov‐2), the pathogen of 2019 novel coronavirus disease (COVID‐19), has posed a serious threat to global public health. The WHO has declared the outbreak of SARS‐CoV‐2 infection an international public health emergency. Lung lesions have been considered as the major damage caused by SARS‐CoV‐2 infection. However, liver injury has also been reported to occur during the course of the disease in severe cases. Similarly, previous studies have shown that liver damage was common in the patients infected by the other two highly pathogenic coronavirus – severe acute respiratory syndrome coronavirus (SARS‐CoV) and the Middle East respiratory syndrome coronavirus (MERS‐CoV), and associated with the severity of diseases. In this review, the characteristics and mechanism of liver injury caused by SARS‐CoV, MERS‐CoV as well as SARS‐CoV‐2 infection were summarized, which may provide help for further studies on the liver injury of COVID‐19.


title: A moonshot approach toward the management of cancer patients in the COVID-19 time: what have we learned and what could the Italian network of cancer centers (Alliance Against Cancer, ACC) do after the pandemic wave?

text: If we focus our attention on seven main features of COVID-19 infection (heterogeneity, fragility, lack of effective treatments and vaccines, “miraculous cures”, psychological suffering, deprivation, and globalization), we may establish parallelism with the challenges faced in the steep road to the understanding and treatment of neoplastic diseases. How the similarities between these two conditions can help us cope with the emergency effort represented by the management of cancer patients in the COVID-19 era, today and in the future? In a manner similar to the Cancer Moonshot initiative in the United States, we can hypothesize a multinational moonshot project towards the management of cancer patients during COVID-19 pandemic. In particular, we believe that the main road to elaborate meaningful scientific evidence is represented by the collection of all the data on COVID-19 and cancer comorbidity that are and will become available in cancer centers, coupled with the design of large clinical studies. To address this goal, it is essential to identify the entity that can produce this scientific evidences and the potentially most successful research strategy to undertake. The largest Italian organization for cancer research, Alliance Against Cancer (Alleanza Contro il Cancro, ACC), is called to play a scientific leadership in addressing these challenges, which requires the coordination of oncology teams at regional, national, and international levels. To fulfill this commitment, ACC will create a liaison with health government agencies in order to develop “dynamic” indications able to fight such an unpredictable pandemic.


title: Molecular confirmation of an adenovirus in brushtail possums (Trichosurus vulpecula)

text: Abstract Partial genome characterisation of a non-cultivable marsupial adenovirus is described. Adenovirus-like particles were found by electron microscopy (EM) in the intestinal contents of brushtail possums (Trichosurus vulpecula) in New Zealand. Using degenerate PCR primers complementary to the most conserved genome regions of adenoviruses, the complete nucleotide sequence of the penton base gene, and partial nucleotide sequences of the DNA polymerase, hexon, and pVII genes were obtained. Phylogenetic analysis of the penton base gene strongly suggested that the brushtail possum adenovirus (candidate PoAdV-1) belongs to the recently proposed genus Atadenovirus. Sequence analysis of the PCR products amplified from the intestinal contents of brushtail possums originating from different geographical regions of New Zealand identified a single genotype. This is the first report of molecular confirmation of an adenovirus in a marsupial.


title: Chapter One Parasites of seabirds: A survey of effects and ecological implications

text: Abstract Parasites are ubiquitous in the environment, and can cause negative effects in their host species. Importantly, seabirds can be long-lived and cross multiple continents within a single annual cycle, thus their exposure to parasites may be greater than other taxa. With changing climatic conditions expected to influence parasite distribution and abundance, understanding current level of infection, transmission pathways and population-level impacts are integral aspects for predicting ecosystem changes, and how climate change will affect seabird species. In particular, a range of micro- and macro-parasites can affect seabird species, including ticks, mites, helminths, viruses and bacteria in gulls, terns, skimmers, skuas, auks and selected phalaropes (Charadriiformes), tropicbirds (Phaethontiformes), penguins (Sphenisciformes), tubenoses (Procellariiformes), cormorants, frigatebirds, boobies, gannets (Suliformes), and pelicans (Pelecaniformes) and marine seaducks and loons (Anseriformes and Gaviiformes). We found that the seabird orders of Charadriiformes and Procellariiformes were most represented in the parasite-seabird literature. While negative effects were reported in seabirds associated with all the parasite groups, most effects have been studied in adults with less information known about how parasites may affect chicks and fledglings. We found studies most often reported on negative effects in seabird hosts during the breeding season, although this is also the time when most seabird research occurs. Many studies report that external factors such as condition of the host, pollution, and environmental conditions can influence the effects of parasites, thus cumulative effects likely play a large role in how parasites influence seabirds at both the individual and population level. With an increased understanding of parasite-host dynamics it is clear that major environmental changes, often those associated with human activities, can directly or indirectly affect the distribution, abundance, or virulence of parasites and pathogens.


title: Emerging and reemerging diseases: a historical perspective

text: Summary: Between mid‐century and 1992, there was a consensus that the battle against infectious diseases had been won, and the Surgeon General announced that it was time to close the book. Experience with human immunodeficiency virus/acquired immunodeficiency syndrome, the return of cholera to the Americas in 1991, the plague outbreak in India in 1994, and the emergence of Ebola in Zaire in 1995 created awareness of a new vulnerability to epidemics due to population growth, unplanned urbanization, antimicrobial resistance, poverty, societal change, and rapid mass movement of people. The increasing virulence of dengue fever with dengue hemorrhagic fever and dengue shock syndrome disproved the theory of the evolution toward commensalism, and the discovery of the microbial origins of peptic ulcer demonstrated the reach of infectious diseases. The Institute of Medicine coined the term ‘emerging and reemerging diseases’ to explain that the world had entered an era in which the vulnerability to epidemics in the United States and globally was greater than ever. The United States and the World Health Organization took devised rapid response systems to monitor and contain disease outbreaks and to develop new weapons against microbes. These mechanisms were tested by severe acute respiratory syndrome in 2003, and a series of practical and conceptual blind spots in preparedness were revealed.


COVID-19: Le jour d’après


title: Towards reduction in bias in epidemic curves due to outcome misclassification through Bayesian analysis of time-series of laboratory test results: case study of COVID-19 in Alberta, Canada and Philadelphia, USA

text: BACKGROUND: Despite widespread use, the accuracy of the diagnostic test for SARS-CoV-2 infection is poorly understood. The aim of our work was to better quantify misclassification errors in identification of true cases of COVID-19 and to study the impact of these errors in epidemic curves using publicly available surveillance data from Alberta, Canada and Philadelphia, USA. METHODS: We examined time-series data of laboratory tests for SARS-CoV-2 viral infection, the causal agent for COVID-19, to try to explore, using a Bayesian approach, the sensitivity and specificity of the diagnostic test. RESULTS: Our analysis revealed that the data were compatible with near-perfect specificity, but it was challenging to gain information about sensitivity. We applied these insights to uncertainty/bias analysis of epidemic curves under the assumptions of both improving and degrading sensitivity. If the sensitivity improved from 60 to 95%, the adjusted epidemic curves likely falls within the 95% confidence intervals of the observed counts. However, bias in the shape and peak of the epidemic curves can be pronounced, if sensitivity either degrades or remains poor in the 60–70% range. In the extreme scenario, hundreds of undiagnosed cases, even among the tested, are possible, potentially leading to further unchecked contagion should these cases not self-isolate. CONCLUSION: The best way to better understand bias in the epidemic curves of COVID-19 due to errors in testing is to empirically evaluate misclassification of diagnosis in clinical settings and apply this knowledge to adjustment of epidemic curves.


title: Bacterial and fungal coinfection among hospitalised patients with COVID-19: A retrospective cohort study in a UK secondary care setting

text: OBJECTIVES: We investigate the incidence of bacterial and fungal co-infection of hospitalised patients with confirmed SARS-CoV-2 in this retrospective observational study across two London hospitals during the first UK wave of COVID-19. METHODS: A retrospective case-series of hospitalised patients with confirmed SARS-CoV-2 by PCR was analysed across two acute NHS hospitals (February 20–April 20; each isolate reviewed independently in parallel). This was contrasted to a control group of influenza positive patients admitted during 2019/20 flu season. Patient demographics, microbiology, and clinical outcomes were analysed. RESULTS: 836 patients with confirmed SARS-CoV-2 were included; 27/836(3.2%) had early confirmed bacterial isolates identified (0-5 days post-admission) rising to 51/836(6.1%) throughout admission. Blood cultures, respiratory samples, pneumococcal or legionella urinary antigens, and respiratory viral PCR panels were obtained from 643(77%), 112(13%), 249(30%), 246(29%) and 250(30%) COVID-19 patients, respectively. A positive blood culture was identified in 60(7.1%) patients, of which 39/60 were classified as contaminants. Bacteraemia secondary to respiratory infection was confirmed in two cases (1 community-acquired K. pneumoniae and 1 ventilator-associated E. cloacae). Line-related bacteraemia was identified in six patients (3 candida, 2 Enterococcus spp. and 1 Pseudomonas aeruginosa). All other community acquired bacteraemias(16) were attributed to non-respiratory infection. Zero concomitant pneumococcal, legionella or influenza infection was detected. A low yield of positive respiratory cultures was identified; S. aureus the most common respiratory pathogen isolated in community-acquired coinfection (4/24;16.7%) with pseudomonas and yeast identified in late-onset infection. Invasive fungal infections (n=3) were attributed to line related infections. Comparable rates of positive co-infection were identified in the control group of confirmed influenza infection; clinically relevant bacteraemias (2/141;1.4%), respiratory cultures (10/38;26.1%) and pneumococcal-positive antigens (1/19;5.2%) were low. CONCLUSION: We find a low frequency of bacterial co-infection in early COVID hospital presentation, and no evidence of concomitant fungal infection, at least in the early phase of COVID-19.


title: Chapter 37 Infections

text: Publisher Summary This chapter reviews the epidemiological evidence implicating infectious pathogens as triggers and will discuss the mechanisms of interaction between the host–pathogen response and preexisting airway pathology that result in an exacerbation. Asthma is a multifaceted syndrome involving atopy, bronchial hyperreactivity, and IgE and non-IgE-mediated acute and chronic immune responses. The asthmatic airway is characterized by an infiltrate of eosinophils and of T-lymphocytes expressing the type 2 cytokines IL-4, IL-5, and IL-13. Trigger factors associated with acute exacerbations of asthma include exposure to environmental allergens, especially animals, molds, pollens and mites, cold, exercise, and drugs. The frequency of exacerbations is a major factor in the quality of life of patients with COPD. The typical clinical features of an exacerbation include increased dyspnea, wheezing, cough, sputum production, and worsened gas exchange. Although noninfectious causes of exacerbations such as allergy, air pollution, or inhaled irritants including cigarette smoke may be important, acute airway infections are the major precipitants. The infection and consequent host inflammatory response result in increased airway obstruction. The success of vaccination to prevent respiratory virus infections has been limited by significant variation within the major virus types causing disease. Currently much of the treatment of infective exacerbations of asthma and COPD is symptomatic, consisting of increased bronchodilators, either short-acting β 2—agonists in inhaled or intravenous form or anticholinergics or theophyllines, or supportive in the form of oxygen and in severe cases noninvasive or invasive ventilatory measures.


title: Annexin A2 Binds RNA and Reduces the Frameshifting Efficiency of Infectious Bronchitis Virus

text: Annexin A2 (ANXA2) is a protein implicated in diverse cellular functions, including exocytosis, DNA synthesis and cell proliferation. It was recently proposed to be involved in RNA metabolism because it was shown to associate with some cellular mRNA. Here, we identified ANXA2 as a RNA binding protein (RBP) that binds IBV (Infectious Bronchitis Virus) pseudoknot RNA. We first confirmed the binding of ANXA2 to IBV pseudoknot RNA by ultraviolet crosslinking and showed its binding to RNA pseudoknot with ANXA2 protein in vitro and in the cells. Since the RNA pseudoknot located in the frameshifting region of IBV was used as bait for cellular RBPs, we tested whether ANXA2 could regulate the frameshfting of IBV pseudoknot RNA by dual luciferase assay. Overexpression of ANXA2 significantly reduced the frameshifting efficiency from IBV pseudoknot RNA and knockdown of the protein strikingly increased the frameshifting efficiency. The results suggest that ANXA2 is a cellular RBP that can modulate the frameshifting efficiency of viral RNA, enabling it to act as an anti-viral cellular protein, and hinting at roles in RNA metabolism for other cellular mRNAs.


title: Severe cerebral involvement in adult-onset hemophagocytic lymphohistiocytosis

text: Abstract The diagnosis of hemophagocytic lymphohistiocytosis (HLH) with cerebral involvement is challenging given the rarity of HLH and its resemblance to the much more common severe sepsis. Timely diagnosis and treatment may be lifesaving. We report two cases demonstrating different and rare forms of severe brain involvement in adult patients with HLH: acute necrotizing encephalopathy, and diffuse hemorrhagic disease due to disseminated intravascular coagulation. Severe HLH with brain involvement in adults is rare. HLH with cerebral involvement should be considered in patients presenting with severe systemic inflammatory response syndrome (SIRS) but negative cultures and unusual or unexpectedly severe clinical and/or radiologic signs of cerebral dysfunction. Similar brain injury may occur in patients with cytokine storm syndrome due to COVID-19. Background Hemophagocytic lymphohistiocytosis (HLH) presents with fevers, rash, organomegaly, cytopenia, and increased triglycerides and ferritin (Ramos-Casals et al., 2014) [1]. Neurologic abnormalities are reported in about one-third of patients (Cai et al., 2017), including a few cases of acute necrotizing encephalopathy (ANE) (Xiujuan et al., 2015). Coagulation abnormalities are frequent in HLH patients (Valade et al., 2015). Objective To raise awareness about the importance of early diagnosis and treatment of HLH with neurological involvement to prevent serious complications and demise.


title: A secretary bi-cistronic baculovirus expression system with improved production of the HA1 protein of H6 influenza virus in insect cells and Spodoptera litura larvae

text: Abstract A bi-cistronic baculovirus expression vector was constructed to facilitate the expression, detection, and isolation of the hemagglutinin (HA) fragment HA1 of H6N1 avian influenza virus (AIV) in an insect and a culture of its cells. In this construct, the GP67sp signal peptide promoted the secretion of the recombinant protein into the culture medium, and improved protein expression and purification. Enhanced green fluorescent protein, co-expressed through an internal ribosome entry site, served as a visible reporter for protein expression detection. The hemolymph of Spodoptera litura larvae infected with the bi-cistronic baculovirus was collected for the purification of the recombinant HA1, which was found to be glycosylated, and monomeric and trimeric forms of the recombinant HA1 were identified. Proteins expressed in both the cell culture and larvae served as effective subunit vaccines for the production of antiserum against HA. The antiserum recognized the H6 subtype of AIV but not the H5 subtype.


title: Stabilizing HIV-1 envelope glycoprotein trimers to induce neutralizing antibodies

text: An effective HIV-1 vaccine probably will need to be able to induce broadly neutralizing HIV-1 antibodies (bNAbs) in order to be efficacious. The many bNAbs that have been isolated from HIV-1 infected patients illustrate that the human immune system is able to elicit this type of antibodies. The elucidation of the structure of the HIV-1 envelope glycoprotein (Env) trimer has further fueled the search for Env immunogens that induce bNAbs, but while native Env trimer mimetics are often capable of inducing strain-specific neutralizing antibodies (NAbs) against the parental virus, they have not yet induced potent bNAb responses. To improve the performance of Env trimer immunogens, researchers have studied the immune responses that Env trimers have induced in animals; they have evaluated how to best use Env trimers in various immunization regimens; and they have engineered increasingly stabilized Env trimer variants. Here, we review the different approaches that have been used to increase the stability of HIV-1 Env trimer immunogens with the aim of improving the induction of NAbs. In particular, we draw parallels between the various approaches to stabilize Env trimers and ones that have been used by nature in extremophile microorganisms in order to survive in extreme environmental conditions.


title: Combination effects of ribavirin and interferons on severe fever with thrombocytopenia syndrome virus infection

text: BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an acute infectious disease caused by SFTS virus and characterized by a high case fatality rate. Currently, there is no effective therapy for the disease. While the administration of ribavirin does not improve the case fatality rate or viral load in patient blood, it can inhibit viral infection in vitro. METHODS: Vero cells were pre-treated with interferons (IFNs) α, β, and γ alone and in combination with ribavirin drugs and inoculated with SFTS virus. Three days later, supernatants were harvested and subjected to virus titration. An unpaired t-test was used for statistical analysis of the drugs’ effects. RESULTS: While the effects of IFNγ at high concentrations were slightly weaker than those of the other IFNs, all IFNs showed dose-dependent inhibitory effects. The combined usage of IFNs with ribavirin at 90 % effective concentrations showed large inhibitory effects, with over a 3 log(10) reduction in viral titers. CONCLUSIONS: The combined usage of one of type-I/II IFNs with ribavirin drastically reduced SFTS virus infection and therefore may be useful in the treatment of SFTS.


MERS


title: Canada’s role in strengthening global health security during the COVID-19 pandemic

text: The world is confronted by the current pandemic of Corona Virus Disease (COVID-19), which is a wake-up call for all nations irrespective of their development status or geographical location. Since the start of the century we have seen five big infectious outbreaks which proved that epidemics are no more regarded as historic and geographically confined threats. The Canadian government underlined that these infectious disease outbreaks are threats to global health security and disrupt societal wellbeing and development. In this context, the Public Health Agency of Canada is proactive and has shown its preparedness for outbreaks of emerging and epidemic-prone diseases, and in dealing with these pathogens. Even before the declaration of pandemic, Canada has proved its global health leadership by ensuring collective action and multisectoral coordination which still remains a serious challenge especially for low and middle- income countries with existing poor health systems. In this article we discuss how Canada is addressing the global challenges posed by the COVID-19 pandemic through its leadership and practice of global health diplomacy.


title: Forecasting the cumulative number of confirmed cases of COVID-19 in Italy, UK and USA using fractional nonlinear grey Bernoulli model

text: Since the new coronavirus (COVID-19) outbreak spread from China to other countries, it has been a curiosity for how and how long the number of cases will increase. This study aims to forecast the number of confirmed cases of COVID-19 in Italy, the United Kingdom (UK) and the United States of America (USA). In this study, grey model (GM(1,1)), nonlinear grey Bernoulli model (NGBM(1,1)) and fractional nonlinear grey Bernoulli model (FANGBM(1,1)) are compared for the prediction. Therefore, grey prediction models, especially the fractional accumulated grey model, are used for the first time in this topic and it is believed that this study fills the gap in the literature. This model is applied to predict the data for the period 19/03-22/04/2020 (35 days) and forecast the data for the period 23/04-22/05/2020. The number of cases of COVID-19 in these countries are handled cumulatively. The prediction performance of the models is measured by the calculation of root mean square error (RMSE), mean absolute percentage error (MAPE) and R(2) values. It is obtained that FANGBM(1,1) gives the highest prediction performance with having the lowest RMSE and MAPE values and the highest R(2) values for these countries. Results show that the cumulative number of cases for Italy, UK and USA is forecasted to be about 233000, 184000 and 1090000, respectively, on May 22, 2020 which corresponds to the average daily rate is 0.80%, 1.19% and 1.13%, respectively, from 22/04/2020 to 22/05/2020. The FANGBM(1,1) presents that the cumulative number of cases of COVID-19 increases at a diminishing rate from 23/04/2020 to 22/05/2020 for these countries.


title: Expression and purification of turkey coronavirus nucleocapsid protein in Escherichia coli

text: Abstract Purification of turkey coronavirus (TCoV) nucleocapsid (N) protein, expressed in a prokaryotic expression system as histidine-tagged fusion protein is demonstrated in the present study. Turkey coronavirus was partially purified from infected intestine of turkey embryo by sucrose gradient ultracentrifugation and RNA was extracted. The N protein gene was amplified from the extracted RNA by reverse transcription-polymerase chain reaction and cloned. The recombinant expression construct (pTri-N) was identified by polymerase chain reaction and sequencing analysis. Expression of histidine-tagged fusion N protein with a molecular mass of 57kd was determined by Western blotting analysis. By chromatography on nickel-agarose column, the expressed N protein was purified to near homogeneity as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. The protein recovery could be 2.5mg from 100ml of bacterial culture. The purified N protein was recognized by antibody to TCoV in Western blotting assay. The capability of the recombinant N protein to differentiate positive serum of turkey infected with TCoV from normal turkey serum was evident in enzyme-linked immunosorbent assays (ELISA). These results indicated that the expressed N protein is a superior source of TCoV antigen for development of antibody-capture ELISA for detection of antibodies to TCoV.


title: Global Health Capacity and Workforce Development: Turning the World Upside Down

text: This article explores global health and the way in which the whole world is increasingly interdependent in terms of health. High-income countries need to help redress the balance of power and resources around the world, for self interest and self preservation if for no other reason. These countries have a particular responsibility to help support the training of more health workers and to strengthen health systems in low-income and middle-income countries. In this interdependent world, high-income countries can learn a great deal from poorer ones as well as vice versa, and concepts of mutuality and codevelopment will become increasingly important.


Sars-Cov-2 hurricane impacting proctology outpatient clinics and proctologic emergencies. On the verge of phase 2, learning from phase 1. Correspondence


title: Expression of the C-type lectins DC-SIGN or L-SIGN alters host cell susceptibility for the avian coronavirus, infectious bronchitis virus

text: Infectious bronchitis virus (IBV), an avian coronavirus, is a cause of great economic loss in the poultry industry. The virus mainly infects respiratory epithelium, but can be also detected in other organs. The functional receptor for the virus has not been found and field strains of IBV do not infect conventional cell lines. Recently, it has been shown that the C-type lectins DC-SIGN/L-SIGN can promote entry of several coronaviruses. Here we examine whether DC-SIGN/L-SIGN are entry determinants for IBV. We show that by introducing human DC-SIGN/L-SIGN into non-permissive cells, infection by the IBV is dramatically increased. DC-SIGN mediated infection was inhibited by mannan and anti-lectin antibodies, and was independent of sialic acid levels on the cell. Enhancement of IBV infection also occurred for different serotypes of IBV. Our findings demonstrated that even in the absence of avian-specific receptor, DC-SIGN-like lectins are capable of mediating efficient IBV infection.


title: Expression and purification of SARS coronavirus proteins using SUMO-fusions

text: Abstract Severe acute respiratory syndrome coronavirus (SARS-CoV) proteins belong to a large group of proteins that is difficult to express in traditional expression systems. The ability to express and purify SARS-CoV proteins in large quantities is critical for basic research and for development of pharmaceutical agents. The work reported here demonstrates: (1) fusion of SUMO (small ubiquitin-related modifier), a 100 amino acid polypeptide, to the N-termini of SARS-CoV proteins dramatically enhances expression in Escherichia coli cells and (2) 6× His-tagged SUMO-fusions facilitate rapid purification of the viral proteins on a large scale. We have exploited the natural chaperoning properties of SUMO to develop an expression system suitable for proteins that cannot be expressed by traditional methodologies. A unique feature of the system is the SUMO tag, which enhances expression, facilitates purification, and can be efficiently cleaved by a SUMO-specific protease to generate native protein with a desired N-terminus. We have purified various SARS-CoV proteins under either native or denaturing conditions. These purified proteins have been used to generate highly specific polyclonal antibodies. Our study suggests that the SUMO-fusion technology will be useful for enhancing expression and purification of the viral proteins for structural and functional studies as well as for therapeutic uses.


title: Pneumonia in Adults: the Practical Emergency Department Perspective

text: In those patients who are hospitalized with pneumonia, mortality is 15%. Close to 90% of deaths attributed to pneumonia are in patients older than 65 years. This article provides the emergency physician with an understanding of how to make the diagnosis, initiate early and appropriate antibiotic therapy, risk stratify patients with respect to the severity of illness, and recognize indications for admission. The discussion is balanced with an emphasis on cost-effective management, an understanding of the changing spectrum of pathogenesis, and a cognizance toward variable and less common presentations.


title: Comparison of cytokine expression profiles in infants with a rhinovirus induced lower respiratory tract infection with or without wheezing: a comparison with respiratory syncytial virus

text: PURPOSE: The aim of this study was to evaluate whether infants with rhinovirus (RV) infection-induced wheezing and those with respiratory syncytial virus (RSV) infection-induced wheezing have different cytokine profiles in the acute stage. METHODS: Of the infants with lower respiratory tract infection (LRTI) between September 2011 and May 2012, 88 were confirmed using reverse transcription polymerase chain reaction and hospitalized. Systemic interferon-gamma (IFN-γ), interleukin (IL)-2, IL-12, IL-4, IL-5, IL-13, and Treg-type cytokine (IL-10) responses were examined with multiplex assay using acute phase serum samples. RESULTS: Of the 88 patients, 38 had an RV infection (RV group) and 50 had an RSV infection (RSV group). In the RV group, the IFN-γ and IL-10 concentrations were higher in the patients with than in the patients without wheezing (P=0.022 and P=0.007, respectively). In the RSV group, the differences in IFN-γ and IL-10 concentrations did not reach statistical significance between the patients with and the patients without wheezing (P=0.105 and P=0.965, respectively). The IFN-γ and IL-10 concentrations were not significantly different between the RV group with wheezing and the RSV group with wheezing (P=0.155 and P=0.801, respectively), in contrast to the significant difference between the RV group without wheezing and the RSV group without wheezing (P=0.019 and P=0.035, respectively). CONCLUSION: In comparison with RSV-induced LRTI, RV-induced LRTI combined with wheezing showed similar IFN-γ and IL-10 levels, which may have an important regulatory function.


title: COVID-19-Related Factors Associated with Sleep Disturbance and Suicidal Thoughts among the Taiwanese Public: A Facebook Survey

text: Coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of people’s lives all over the world. This Facebook survey study aimed to investigate the COVID-19-related factors that were associated with sleep disturbance and suicidal thoughts among members of the public during the COVID-19 pandemic in Taiwan. The online survey recruited 1970 participants through a Facebook advertisement. Their self-reported experience of sleep disturbance and suicidal thoughts in the previous week were collected along with a number of COVID-19-related factors, including level of worry, change in social interaction and daily lives, any academic/occupational interference, levels of social and specific support, and self-reported physical health. In total, 55.8% of the participants reported sleep disturbance, and 10.8% reported having suicidal thoughts in the previous week. Multiple COVID-19-related factors were associated with sleep disturbance and suicidal thoughts in the COVID-19 pandemic. Increased worry about COVID-19, more severe impact of COVID-19 on social interaction, lower perceived social support, more severe academic/occupational interference due to COVID-19, lower COVID-19-specified support, and poorer self-reported physical health were significantly associated with sleep disturbance. Less handwashing, lower perceived social support, lower COVID-19-specified support, poorer self-reported physical health, and younger age were significantly associated with suicidal thoughts. Further investigation is needed to understand the changes in mental health among the public since the mitigation of the COVID-19 pandemic.


title: Viral suppression of the interferon system

text: Type I interferons (IFN-α/β) were originally discovered by their strong and direct antiviral activity [A. Isaacs, J. Lindenmann, Virus interference. I. The interferon, Proc. R. Soc. Lond. B Biol. Sci. 147 (1957) 258–267]. (see review by J. Lindenmann on p. 719, in this issue). Nevertheless, only very recently it was entirely realized that viruses would not succeed without efficient tools to undermine this potent host defense system. Current investigations are revealing an astonishing variety of viral IFN antagonistic strategies targeting virtually all parts of the IFN system, often in a highly specific manner. Viruses were found to interfere with induction of IFN synthesis, IFN-induced signaling events, the antiviral effector proteins, or simply shut off the host cell macromolecule synthesis machinery to avoid booting of the antiviral host defense. Here, we will describe a few well-characterized examples to illustrate the sophisticated and often multi-layered anti-IFN mechanisms employed by viruses.


Managing a radiotherapy center safely and efficiently using risk-adaptive strategies during coronavirus disease pandemic: Experience from national cancer center of china


Introduction to the Special Issue on viral channel forming proteins


title: Nucleotide-Resolution Profiling of RNA Recombination in the Encapsidated Genome of a Eukaryotic RNAVirus by Next-Generation Sequencing

text: Next-Generation Sequencing has been used in numerous investigations to characterize andquantifythe genetic diversity of a virus samplethrough the mapping of polymorphisms and measurement of mutation frequencies.Next-Generation Sequencing has also been employed to identifyrecombinationevents occurring within the genomes of higher organisms, for example, detecting alternative RNA splicing events and oncogenic chromosomal rearrangements. Here, we combine these two approaches toprofile RNA recombination within the encapsidated genome of a eukaryotic RNA virus, Flock House Virus. We detect hundreds of thousands of recombination events, with single-nucleotide resolution, which result indiversity in the encapsidated genome rivaling that due to mismatch mutation. We detect previously identified Defective-RNAs as well as many other abundant and novel Defective-RNAs. Our approach is exceptionally sensitive, unbiased, and requires no prior knowledge beyond the virus genome sequence. RNA recombination is a powerful driving force behind the evolution and adaptation of RNA viruses. The strategy implemented here is widely applicable and provides a highly detailed description of the complex mutational landscape of the transmissible viral genome.


title: Impact of treating Staphylococcus aureus nasal carriers on wound infections in cardiac surgery

text: Summary Staphylococcus aureus is a common cause of postoperative wound infections, and nasal colonization by this organism is an important factor in the development of infections. Treatment with mupirocin can eradicate the organism in the short term, and prophylactic treatment of colonized patients may prevent postoperative S. aureus infections. A double-blind, randomized, placebo-controlled trial was performed to determine whether nasal mupirocin administered pre-operatively to S. aureus carriers reduces the rates of sternal and leg wound infections after cardiac surgery. The study enrolled 263 patients with nasal S. aureus undergoing elective cardiac surgery at St. Michael's Hospital, Toronto, Canada. Patients were assessed for infections in the immediate postoperative period and two months later. Two hundred and fifty-seven patients were included in the intention-to-treat analysis and re-analysed according to the actual treatment applied. Wound infections occurred in 17 (13.5%) mupirocin recipients and 11 (9.1%) placebo recipients (P =0.319), with seven (5.4%) and six (4.7%) sternal infections, respectively. Two (1.6%) wound infections were acquired postoperatively in the mupirocin group, neither of which were caused by S. aureus. The placebo group had three (2.4%) nosocomial wound infections, with two (1.6%) S. aureus bacteraemias (P =0.243). Among patients receiving mupirocin, 106 (81.5%) cleared S. aureus compared with 59 (46.5%) patients receiving placebo (P <0.0001). There was no significant difference between intention-to-treat and actual treatment groups. Prophylactic intranasal mupirocin administered to S. aureus carriers did not reduce the rates of overall surgical site infections by S. aureus, and only showed a trend towards decreased incidence of nosocomial S. aureus infections.


title: Understanding bat SARS-like coronaviruses for the preparation of future coronavirus outbreaks — Implications for coronavirus vaccine development

text: The severe acute respiratory syndrome coronavirus (SARS-CoV) first emerged in 2003, causing the SARS epidemic which resulted in a 10% fatality rate. The advancements in metagenomic techniques have allowed the identification of SARS-like coronaviruses (SL-CoVs) sequences that share high homology to the human SARS-CoV epidemic strains from wildlife bats, presenting concrete evidence that bats are the origin and natural reservoir of SARS-CoV. The application of reverse genetics further enabled that characterization of these bat CoVs and the prediction of their potential to cause disease in humans. The knowledge gained from such studies is valuable in the surveillance and preparation of a possible future outbreak caused by a spill-over of these bat SL-CoVs.


title: Structural basis of nectin-1 recognition by pseudorabies virus glycoprotein D

text: An early and yet indispensable step in the alphaherpesvirus infection is the engagement of host receptors by the viral envelope glycoprotein D (gD). Of the thus-far identified gD receptors, nectin-1 is likely the most effective in terms of its wide usage by multiple alphaherpesviruses for cell entry. The molecular basis of nectin-1 recognition by the gD protein is therefore an interesting scientific question in the alphaherpesvirus field. Previous studies focused on the herpes simplex virus (HSV) of the Simplexvirus genus, for which both the free gD structure and the gD/nectin-1 complex structure were reported at high resolutions. The structural and functional features of other alphaherpesviral gDs, however, remain poorly characterized. In the current study, we systematically studied the characteristics of nectin-1 binding by the gD of a Varicellovirus genus member, the pseudorabies virus (PRV). We first showed that PRV infects host cells via both human and swine nectin-1, and that its gD exhibits similar binding affinities for nectin-1 of the two species. Furthermore, we demonstrated that removal of the PRV gD membrane-proximal residues could significantly increase its affinity for the receptor binding. The structures of PRV gD in the free and the nectin-1-bound states were then solved, revealing a similar overall 3D fold as well as a homologous nectin-1 binding mode to its HSV counterpart. However, several unique features were observed at the binding interface of PRV gD, enabling the viral ligand to utilize different gD residues (from those of HSV) for nectin-1 engagement. These observed binding characteristics were further verified by the mutagenesis study using the key-residue mutants of nectin-1. The structural and functional data obtained in this study, therefore, provide the basis of receptor recognition by PRV gD.


title: Gonadal pathogenicity of an infectious bronchitis virus strain from the Massachusetts genotype

text: An outbreak of infectious bronchitis caused by the IBVPR03 strain of the Massachusetts genotype affected H-120 vaccinated laying hens in South Brazil. We investigated the cross protection of the vaccine by assessing the traqueal ciliostasis, virus recovery, and histopathological changes typically observed in the respiratory tract. Although the IBVPR03 strain is S1-genotyped as Massachusetts with a high genomic similarity to the H-120 vaccine strains, surprisingly, we found no tropism or pathogenicity to the trachea in birds infected with this strain. On the other hand, we observed ovarian and testicle lesions. Here, we show that, despite belonging in the Massachusetts genotype, the IBVPR03 pathotype differs from the expected respiratory pattern, causing instead marked histopathological changes in the gonads, so far not associated with this group.


title: Analysis and Optimal Control of Fractional-Order Transmission of a Respiratory Epidemic Model

text: The World Health Organization is yet to realise the global aim of achieving future-free and eliminating the transmission of respiratory diseases such as H1N1, SARS and Ebola since the recent reemergence of Ebola in the Democratic Republic of Congo. In this paper, a Caputo fractional-order derivative is applied to a system of non-integer order differential equation to model the transmission dynamics of respiratory diseases. The nonnegative solutions of the system are obtained by using the Generalized Mean Value Theorem. The next generation matrix approach is used to obtain the basic reproduction number [Formula: see text] . We discuss the stability of the disease-free equilibrium when [Formula: see text] , and the necessary conditions for the stability of the endemic equilibrium when [Formula: see text] . A sensitivity analysis shows that [Formula: see text] is most sensitive to the probability of the disease transmission rate. The results from the numerical simulations of optimal control strategies disclose that the utmost way of controlling or probably eradicating the transmission of respiratory diseases should be quarantining the exposed individuals, monitoring and treating infected people for a substantial period.


title: Mechanisms of Virus-Induced Airway Immunity Dysfunction in the Pathogenesis of COPD Disease, Progression, and Exacerbation

text: Chronic obstructive pulmonary disease (COPD) is the integrated form of chronic obstructive bronchitis and pulmonary emphysema, characterized by persistent small airway inflammation and progressive irreversible airflow limitation. COPD is characterized by acute pulmonary exacerbations and associated accelerated lung function decline, hospitalization, readmission and an increased risk of mortality, leading to huge social-economic burdens. Recent evidence suggests ~50% of COPD acute exacerbations are connected with a range of respiratory viral infections. Nevertheless, respiratory viral infections have been linked to the severity and frequency of exacerbations and virus-induced secondary bacterial infections often result in a synergistic decline of lung function and longer hospitalization. Here, we review current advances in understanding the cellular and molecular mechanisms underlying the pathogenesis of COPD and the increased susceptibility to virus-induced exacerbations and associated immune dysfunction in patients with COPD. The multiple immune regulators and inflammatory signaling pathways known to be involved in host-virus responses are discussed. As respiratory viruses primarily target airway epithelial cells, virus-induced inflammatory responses in airway epithelium are of particular focus. Targeting virus-induced inflammatory pathways in airway epithelial cells such as Toll like receptors (TLRs), interferons, inflammasomes, or direct blockade of virus entry and replication may represent attractive future therapeutic targets with improved efficacy. Elucidation of the cellular and molecular mechanisms of virus infections in COPD pathogenesis will undoubtedly facilitate the development of these potential novel therapies that may attenuate the relentless progression of this heterogeneous and complex disease and reduce morbidity and mortality.


title: Initiation of human astrovirus type 1 infection was blocked by inhibitors of phosphoinositide 3-kinase

text: BACKGROUND: Upon initial contact with a virus, host cells activate a series of cellular signaling cascades that facilitate viral entry and viral propagation within the cell. Little is known about how the human astrovirus (HAstV) exploits signaling cascades to establish an infection in host cells. Recent studies showed that activation of extracellular signal-regulated kinase 1/2 (ERK1/2) is important for HAstV infection, though the involvement of other signaling cascades remains unclear. METHODS: A panel of kinase blockers was used to search for cellular signaling pathways important for HAstV1 infection. To determine their impact on the infectious process, we examined viral gene expression, RNA replication, and viral RNA and capsid protein release from host cells. RESULTS: Inhibitors of phosphoinositide 3-kinase (PI3K) activation interfered with the infection, independent of their effect on ERK 1/2 activation. Activation of the PI3K signaling cascade occurred at an early phase of the infection, judging from the timeframe of Akt phosphorylation. PI3K inhibition at early times, but not at later times, blocked viral gene expression. However, inhibiting the downstream targets of PI3K activation, Akt and Rac1, did not block infection. Inhibition of protein kinase A (PKA) activation was found to block a later phase of HAstV1 production. CONCLUSIONS: Our results reveal a previously unknown, essential role of PI3K in the life cycle of HAstV1. PI3K participates in the early stage of infection, possibly during the viral entry process. Our results also reveal the role of PKA in viral production.


title: S1 domain of the porcine epidemic diarrhea virus spike protein as a vaccine antigen

text: BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is a highly contagious virus infecting pigs of all ages with high morbidity and mortality among newborn piglets. Currently, there is no effective vaccine available to protect the pigs from PEDV. The N-terminal subunit of spike protein (S1) is responsible for virus binding to the cellular receptor and contains a number of neutralizing antibody epitopes. Thus, we expressed and produced recombinant S1 protein to protect newborn piglets by immunization of sows. METHODS: Affinity tagged PEDV S1 protein was expressed in a secretory form in yeast, insect and mammalian cells to identify the most suitable production system. Purified recombinant protein was analysed by SDS-PAGE, Western blot and deglycosylation assay. A pregnant sow was intramuscularly immunized three times with adjuvanted recombinant protein prior to farrowing. PEDV-specific immune responses in sera and colostrum of the sow and piglets were assayed by ELISA and virus neutralization assays. Piglets were challenged orally with PEDV, and clinical parameters were monitored for 6 days post-challenge. RESULTS AND CONCLUSION: Of three eukaryotic expression systems tested (yeast, insect-cell, and mammalian), expression by HEK-293 T cells gave the highest yield of protein that was N-glycosylated and was the most appropriate candidate for vaccination. Administration of the subunit vaccine in a sow resulted in induction of S1-specific IgG and IgA that were passively transferred to the suckling piglets. Also, high virus neutralization titres were observed in the serum of the vaccinated sow and its piglets. After PEDV challenge, piglets born to the vaccinated sow exhibited less severe signs of disease and significantly lower mortality compared to the piglets of a control sow. However, there were no significant differences in diarrhea, body weight and virus shedding. Thus, vaccination with S1 subunit vaccine failed to provide complete protection to suckling piglets after challenge exposure, and further improvements are needed for the development of a subunit vaccine that fully protects against PEDV infection.


title: Are Community Acquired Respiratory Viral Infections an Underestimated Burden in Hematology Patients?

text: Despite a plethora of studies demonstrating significant morbidity and mortality due to community-acquired respiratory viral (CRV) infections in intensively treated hematology patients, and despite the availability of evidence-based guidelines for the diagnosis and management of respiratory viral infections in this setting, there is no uniform inclusion of respiratory viral infection management in the clinical hematology routine. Nevertheless, timely diagnosis and systematic management of CRV infections in intensively treated hematology patients has a demonstrated potential to significantly improve outcome. We have briefly summarized the recently published data on CRV infection epidemiology, as well as guidelines on the diagnosis and management of CRV infections in patients intensively treated for hematological malignancies. We have also assessed available treatment options, as well as mentioned novel agents currently in development.


title: Documento de posicionamiento AEG-SEED para el reinicio de la actividad endoscópica tras la fase pico de la pandemia de COVID-19

text: Resumen Introducción: La pandemia por COVID-19 ha conllevado la suspensión de la actividad programada en la mayoría de las Unidades de Endoscopia de nuestro medio. El objetivo del presente documento es facilitar el reinicio de la actividad endoscópica electiva de forma eficiente y segura. Material y métodos: Se formularon una serie de preguntas consideradas de relevancia clínica y logística. Para la elaboración de las respuestas, se realizó una búsqueda bibliográfica estructurada en las principales bases de datos y se revisaron las recomendaciones de las principales instituciones de Salud Pública y de endoscopia digestiva. Las recomendaciones finales se consensuaron por vía telemática. Resultados: Se han elaborado un total de 33 recomendaciones. Los principales aspectos que se discuten son: 1) La reevaluación y priorización de la indicación, 2) La restructuración de espacios, agendas y del personal sanitario, 3) El cribado de la infección, 4) Las medidas de higiene y los equipos de protección individual. Conclusión: La AEG y la SEED recomiendan reiniciar la actividad endoscópica de forma escalonada, segura, adaptada a los recursos locales y a la situación epidemiológica de la infección por SARS-CoV-2. Abstract Introduction: The COVID-19 pandemic has led to the suspension of programmed activity in most of the Endoscopy Units in our environment. The aim of this document is to facilitate the resumption of elective endoscopic activity in an efficient and safe manner. Material and methods: A series of questions considered to be of clinical and logistical relevance were formulated. In order to elaborate the answers, a structured bibliographic search was carried out in the main databases and the recommendations of the main Public Health and Digestive Endoscopy institutions were reviewed. The final recommendations were agreed upon through telematic means. Results: A total of 33 recommendations were made. The main aspects discussed are: 1) Reassessment and prioritization of the indication, 2) Restructuring of spaces, schedules and health personnel, 3) Screening for infection, 4) Hygiene measures and personal protective equipment. Conclusion: The AEG and SEED recommend restarting endoscopic activity in a phased, safe manner, adapted to local resources and the epidemiological situation of SARS-CoV-2 infection.


title: Bioaerosol Sampling for Respiratory Viruses in Singapore’s Mass Rapid Transit Network

text: As a leading global city with a high population density, Singapore is at risk for the introduction of novel biological threats. This risk has been recently reinforced by human epidemics in Singapore of SARS coronavirus, 2009 pandemic H1N1 influenza A virus, and enterovirus 71. Other major threats to Singapore include MERS-coronavirus and various avian and swine influenza viruses. The ability to quickly identify and robustly track such threats to initiate an early emergency response remains a significant challenge. In an effort to enhance respiratory virus surveillance in Singapore, our team conducted a pilot study employing a noninvasive bioaerosol sampling method to detect respiratory viruses in Singapore’s Mass Rapid Transit (MRT) network. Over a period of 52 weeks, 89 aerosol samples were collected during peak MRT ridership hours. Nine (10%) tested positive for adenovirus, four (4.5%) tested positive for respiratory syncytial virus type A, and one (1%) tested positive for influenza A virus using real-time RT-PCR/PCR. To our knowledge, this is the first time molecular evidence for any infectious respiratory agent has been collected from Singapore’s MRT. Our pilot study data support the possibility of employing bioaerosol samplers in crowded public spaces to noninvasively monitor for respiratory viruses circulating in communities.


title: Oral Cancer Surgery and COVID pandemic – Metronomic Therapy shows a promising role while awaiting surgery

text: • Metronomic therapy is a good option for locally advanced oral cancers in COVID-19 pandemic time. • In the present situation there is a need for a therapy that ensure patients remain operable while awaiting surgery. • Metronomic therapy is easily deliverable, minimally toxic, home based and cost effective.


title: Stationäre Psychosomatik in Zeiten des Coronavirus

text: The current coronavirus 2019 (COVID-19) pandemic presents psychosomatic clinics with new challenges. In order that psychotherapists in private practice can also obtain a picture for their patients, this article deals with the core aspects of hygiene. There are three fundamental patterns of care and provisions by the institutions that can be differentiated: rededication, stepwise evacuation and stand-by for rededication and continuation of the service under medical epidemic conditions. The following topics are the relevant contents: need for consultation in the matter of anxiety for coronavirus and interpersonal mental and psychosomatic problems due to the necessary social distancing, care especially in precarious living situations, altered communication structures (telephone, video consultation) and care of those occupied with the topic of “coronavirus disease 2019” (COVID-19). All patients undergo a clinical and virologic diagnostic process before admittance and receive psychosomatic psychotherapeutic inpatient care, possibly beginning under quarantine conditions. Furthermore, appropriate general hygiene regulations are explained. Finally, what the patients are told is illustrated using a simple schematic aid: distance (minimum 2 m), rubbing (wash hands with soap often and for at least 20 s), avoidance (pass by in a friendly manner), alternative communication, forsaking (shopping is not always necessary), wiping (regularly wipeing of all surfaces by the cleaning personnel as well as tablet and mobile telephone by the patients themselves) and outside activity as much as possible, alone or sitting together (with safety distance). The psychosomatic services were appropriately converted.


title: The impact of COVID‐19 on the provision of cardiac surgical services

text: The global pandemic caused by COVID‐19 has had a significant global impact on healthcare systems. One implication of this pandemic is the cancellation of elective cardiac surgeries and the centralization of services. As a result, hospitals in Europe, North America, and the United Kingdom have had to alter the services offered to patients to be able to cope with service provision for COVID infected patients. Data should be collected during this period to provide a good insight following the lockdown period to understand the implication of such service alteration. Future research should also focus on the effects on long‐term mortality and morbidity as well as financial implications on hospitals as a result of these changes.


title: Detection of Influenza and Other Respiratory Viruses in Air Sampled From a University Campus: A Longitudinal Study

text: BACKGROUND: Respiratory virus–laden particles are commonly detected in the exhaled breath of symptomatic patients or in air sampled from healthcare settings. However, the temporal relationship of detecting virus-laden particles at nonhealthcare locations vs surveillance data obtained by conventional means has not been fully assessed. METHODS: From October 2016 to June 2018, air was sampled weekly from a university campus in Hong Kong. Viral genomes were detected and quantified by real-time reverse-transcription polymerase chain reaction. Logistic regression models were fitted to examine the adjusted odds ratios (aORs) of ecological and environmental factors associated with the detection of virus-laden airborne particles. RESULTS: Influenza A (16.9% [117/694]) and influenza B (4.5% [31/694]) viruses were detected at higher frequencies in air than rhinovirus (2.2% [6/270]), respiratory syncytial virus (0.4% [1/270]), or human coronaviruses (0% [0/270]). Multivariate analyses showed that increased crowdedness (aOR, 2.3 [95% confidence interval {CI}, 1.5–3.8]; P < .001) and higher indoor temperature (aOR, 1.2 [95% CI, 1.1–1.3]; P < .001) were associated with detection of influenza airborne particles, but absolute humidity was not (aOR, 0.9 [95% CI, .7–1.1]; P = .213). Higher copies of influenza viral genome were detected from airborne particles >4 μm in spring and <1 μm in autumn. Influenza A(H3N2) and influenza B viruses that caused epidemics during the study period were detected in air prior to observing increased influenza activities in the community. CONCLUSIONS: Air sampling as a surveillance tool for monitoring influenza activity at public locations may provide early detection signals on influenza viruses that circulate in the community.


title: The Patient with Sore Throat

text: Sore throat is a common medical complaint seen by the emergency practitioner, internist, pediatrician, and otolaryngologist. The differential for sore throat is vast. However, with a directed history this can often be narrowed down to 2 to 3 possible diagnoses. By paying particular attention to the associated symptoms and duration of symptoms, common self-limited etiologies like viral pharyngitis and nonstreptococcal tonsillitis can be distinguished from those that require more investigation, such as supraglottitis and tonsillar cancer. A sore throat is most commonly caused by an infectious, inflammatory, or neoplastic etiologic factor.


title: The Wider Impacts of the Coronavirus Pandemic on the NHS

text: The coronavirus pandemic has had huge impacts on the National Health Service (NHS). Patients suffering from the illness have placed unprecedented demands on acute care, particularly on Intensive Care Units (ICUs). This has led to an effort to dramatically increase the resources available to NHS hospitals in treating these patients, involving re‐organisation of hospital facilities, redeployment of existing staff and a drive to bring in recently retired and newly graduated staff to fight the pandemic. These increases in demand and changes to supply have had large knock‐on effects on the care provided to the wider population. This paper discusses likely implications for healthcare delivery in the short and medium term of the responses to the coronavirus pandemic, focusing primarily on the implications for non‐coronavirus patients. Patterns of past care suggest those most likely to be affected by these disruptions will be older individuals and those living in more deprived areas, potentially exacerbating pre‐existing health inequalities. Effects are likely to persist into the longer‐run, with particular challenges around recruitment and ongoing staff shortages. This article is protected by copyright. All rights reserved


COVID-19 and diabetes: is metformin a friend or foe?


title: The coronavirus (COVID‐19) fatality risk perception of US adult residents in March and April 2020

text: The study compares empirical results on the coronavirus SARS‐CoV‐2 (causing COVID‐19) fatality risk perception of US adult residents stratified for age, gender, and race in mid‐March 2020 (N(1) = 1,182) and mid‐April 2020 (N(2) = 953). While the fatality risk perception has increased from March 2020 to April 2020, our findings suggest that many US adult residents severely underestimated their absolute and relative fatality risk (i.e., differentiated for subgroups defined by pre‐existing medical conditions and age) at both time points compared to current epidemiological figures. These results are worrying because risk perception, as our study indicates, relates to actual or intended health‐protective behaviour that can reduce SARS‐CoV‐2 transmission rates.


title: Viral enanthema in oral mucosa: a possible diagnostic challenge in the COVID‐19 pandemic

text: Recalcati (2020), for example, reported that 20.4% of 88 COVID‐19 patients presented cutaneous manifestations such as erythematous rash, generalized urticaria and vesicles. They suggested that the skin lesions were similar to ones found in common viral diseases but emphasized that additional studies are necessary to confirm its association with COVID‐19.