title: Treatment of COVID-19 Patients with Convalescent Plasma

text: COVID-19 disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally, and no proven treatments are available. Convalescent plasma therapy has been used with varying degrees of success to treat severe microbial infections for more than 100 years. Patients (n = 25) with severe and/or life-threatening COVID-19 disease were enrolled at the Houston Methodist hospitals from March 28 – April 14, 2020. Patients were transfused with convalescent plasma obtained from donors with confirmed SARS-CoV-2 infection and had recovered. The primary study outcome was safety, and the secondary outcome was clinical status at day 14 post-transfusion. Clinical improvement was assessed based on a modified World Health Organization 6-point ordinal scale and laboratory parameters. Viral genome sequencing was performed on donor and recipient strains. At day 7 post-transfusion with convalescent plasma, nine patients had at least a 1-point improvement in clinical scale, and seven of those were discharged. By day 14 post-transfusion, 19 (76%) patients had at least a 1-point improvement in clinical status and 11 were discharged. No adverse events as a result of plasma transfusion were observed. Whole genome sequencing data did not identify a strain genotype-disease severity correlation. The data indicate that administration of convalescent plasma is a safe treatment option for those with severe COVID-19 disease.


title: Comparison of a Laboratory-Developed Test Targeting the Envelope gene with three Nucleic Acid Amplification Tests for Detection of SARS-CoV-2

text: ABSTRACT Background Numerous nucleic acid amplification tests, including real-time, reverse transcription PCR (rRT-PCR) and isothermal amplification methods, have been developed to detect SARS-CoV-2 RNA, including many that have received emergency use authorization (EUA). There is a need to assess their test performance relative to one another. Objectives The aim of this study was to compare the test performance of a high complexity laboratory-developed rRT-PCR EUA from Stanford Health Care (SHC) targeting the SARS-CoV-2 envelope (E) gene with other tests: the Atila isothermal amplification assay targeting the nucleocapsid (N) gene and open reading frame 1ab (ORF1ab), the Altona E and spike (S) multiplex, real-time RT-PCR, and the US Centers for Disease Control and Prevention (CDC) N1 and N2 rRT-PCRs. Study Design A diagnostic comparison study was performed by testing nasopharyngeal samples from persons under investigation for coronavirus disease 2019 (COVID-19). Assay performance was assessed by percent agreement and Cohen’s kappa coefficient. Results Positive percent agreement with the SHC EUA reference assay was 82.8% (95% confidence interval (CI) 65.0 to 92.9) for Atila, 86.7% (95% CI 69.7 to 95.3) for the Altona E and S targets, and 86.7% (95% CI 69.7 to 95.3) and 90.0% (95% CI 73.6 to 97.3), for the CDC N1 and N2 targets, respectively. All assays demonstrated 100% negative percent agreement. Kappa coefficients ranged from 0.86 to 0.92, indicating excellent agreement. Conclusions Performance was comparable among the SARS-CoV-2 nucleic acid amplification methods tested, with a limited number of discrepancies observed in specimens with low viral loads.


docid: xuhxqkyj

title: Hyperglycaemia on admission to hospital and COVID-19


title: Impact of Coronavirus Disease 2019 outbreak on acute coronary syndrome admissions: four weeks to reverse the trend

text: Data whether the COVID-19 outbreak impacts the acute coronary syndromes (ACS) admissions and the time required to reverse the downward curve are scarce. We included all consecutive patients referred for an ACS who underwent PCI from February 17, 2020 to April 26, 2020 in a high-volume PCI coronary care unit. We compared the number of ACS patients in 2020 to the same period in 2018 and 2019. Predictors of adverse outcome in ST-elevation myocardial infarction (STEMI) patients were recorded: symptom-onset-to-first medical contact (FMC), and FMC-to-sheath insertion times. During the studied period (calendar weeks 8–17, 2018–2020), 144 ACS patients were included. In 2020, we observed two distinct phases in the ACS admissions: a first significant fall, with a relative reduction of 73%, from the week of lockdown (week 12) to 3 weeks later and then an increase of ACS. Median symptom-onset-to-FMC time was significantly higher in 2020 than in the two previous years (600 min [298–632] versus 121 min [55–291], p < 0.001). Median FMC-to-sheath insertion did not differ significantly (93 min [81–131] in 2020 versus 90 min [67–137] in 2018–2019, p = 0.57). The main findings are (1) a pattern of a U-curve in ACS admissions, with a first decrease in ACS admissions and a return to “normality” 4 weeks after; (2) a significant increase in the total ischemic time exclusively due to an increase in the symptom-onset-to-first-medical-contact time.


title: Successful treatment of severe COVID-19 pneumonia with clazakizumab in a heart transplant recipient: case report

text: Abstract Background Severe Acute Respiratory Syndrome caused by coronavirus 2 (SARS-CoV-2) is characterized by an overwhelming cytokine response. Various treatment strategies have been attempted. Methods and Results A 61-year-old male with heart transplantation in 2017 presented with fever, cough, and dyspnea, and confirmed positive for the SARS-CoV-2 disease (COVID-19). Laboratory tests showed significant elevations in C-reactive protein and interleukin-6 (IL-6). Echocardiogram showed LVEF 58% (with EF 57% 6 months prior). Given the lack of clear management guidelines, the patient was initially managed symptomatically. However, the patient subsequently had a rapid respiratory deterioration with worsening inflammatory markers on day 5 of admission. Tocilizumab (anti-IL-6R) was in low supply in the hospital. The patient was offered clazakizumab (anti-IL-6) for compassionate use. Patient received 25 mg intravenously x1 dose. Within 24 hours, he noted significant improvement in symptoms, oxygen requirements, radiological findings and inflammatory markers. There was a transient leukopenia which improved in 4 days. He was discharged home on day 11, with negative nasopharyngeal SARS-CoV-2 PCR as an outpatient on day 35, development of positive serum COVID-19 IgG antibody, and he continued to do well on day 60, with no heart-related symptoms. Conclusion Clazakizumab is a monoclonal antibody against human IL-6, which may be helpful in inhibiting the cytokine response to SARS-CoV-2 in COVID-19. Although not yet FDA approved, it is being investigated for treatment of renal antibody-mediated rejection. Clinical trials of clazakizumab for treatment of COVID-19 are underway worldwide.


title: Virus-induced neurobehavioral disorders: mechanisms and implications

text: Abstract One hypothesis for the etiology of neuropsychiatric disorders proposes that viral infection contributes to the induction of neuronal system dysfunction, resulting in a wide range of behavioral abnormalities. Recent research in molecular biology supports this hypothesis and refocuses on the role of viral infection in the development of psychiatric disorders. Viral infection can induce deleterious effects in the central nervous system by direct and/or indirect pathways. Understanding the mechanisms of glial cell dysfunction caused by persistent viral infection should lead to novel insights into the development of neurobehavioral disorders, including human mental illnesses, and to the possible development of treatments.


title: Clinical and computed tomography characteristics of COVID-19 associated acute pulmonary embolism: A different phenotype of thrombotic disease?

text: INTRODUCTION: COVID-19 infections are associated with a high prevalence of venous thromboembolism, particularly pulmonary embolism (PE). It is suggested that COVID-19 associated PE represents in situ immunothrombosis rather than venous thromboembolism, although the origin of thrombotic lesions in COVID-19 patients remains largely unknown. METHODS: In this study, we assessed the clinical and computed tomography (CT) characteristics of PE in 23 consecutive patients with COVID-19 pneumonia and compared these to those of 100 consecutive control patients diagnosed with acute PE before the COVID-19 outbreak. Specifically, RV/LV diameter ratio, pulmonary artery trunk diameter and total thrombus load (according to Qanadli) were measured and compared. RESULTS: We observed that all thrombotic lesions in COVID-19 patients were found to be in lung parenchyma affected by COVID-19. Also, the thrombus load was lower in COVID-19 patients (Qanadli score −8%, 95% confidence interval [95%CI] −16 to −0.36%) as was the prevalence of the most proximal PE in the main/lobar pulmonary artery (17% versus 47%; −30%, 95%CI −44% to −8.2). Moreover, the mean RV/LV ratio (mean difference −0.23, 95%CI −0.39 to −0.07) and the prevalence of RV/LV ratio >1.0 (prevalence difference −23%, 95%CI −41 to −0.86%) were lower in the COVID-19 patients. CONCLUSION: Our findings therefore suggest that the phenotype of COVID-19 associated PE indeed differs from PE in patients without COVID-19, fuelling the discussion on its pathophysiology.


title: Airborne transmission of severe acute respiratory syndrome coronavirus‐2 to healthcare workers: a narrative review

text: Healthcare workers are at risk of infection during the severe acute respiratory syndrome coronavirus‐2 pandemic. International guidance suggests direct droplet transmission is likely and airborne transmission occurs only with aerosol‐generating procedures. Recommendations determining infection control measures to ensure healthcare worker safety follow these presumptions. Three mechanisms have been described for the production of smaller sized respiratory particles (‘aerosols’) that, if inhaled, can deposit in the distal airways. These include: laryngeal activity such as talking and coughing; high velocity gas flow; and cyclical opening and closure of terminal airways. Sneezing and coughing are effective aerosol generators, but all forms of expiration produce particles across a range of sizes. The 5‐μm diameter threshold used to differentiate droplet from airborne is an over‐simplification of multiple complex, poorly understood biological and physical variables. The evidence defining aerosol‐generating procedures comes largely from low‐quality case and cohort studies where the exact mode of transmission is unknown as aerosol production was never quantified. We propose that transmission is associated with time in proximity to severe acute respiratory syndrome coronavirus‐1 patients with respiratory symptoms, rather than the procedures per se. There is no proven relation between any aerosol‐generating procedure with airborne viral content with the exception of bronchoscopy and suctioning. The mechanism for severe acute respiratory syndrome coronavirus‐2 transmission is unknown but the evidence suggestive of airborne spread is growing. We speculate that infected patients who cough, have high work of breathing, increased closing capacity and altered respiratory tract lining fluid will be significant producers of pathogenic aerosols. We suggest several aerosol‐generating procedures may in fact result in less pathogen aerosolisation than a dyspnoeic and coughing patient. Healthcare workers should appraise the current evidence regarding transmission and apply this to the local infection prevalence. Measures to mitigate airborne transmission should be employed at times of risk. However, the mechanisms and risk factors for transmission are largely unconfirmed. Whilst awaiting robust evidence, a precautionary approach should be considered to assure healthcare worker safety.


title: Exhaled Air Dispersion During Noninvasive Ventilation via Helmets and a Total Facemask

text: BACKGROUND Noninvasive ventilation (NIV) via helmet or total facemask is an option for managing patients with respiratory infections in respiratory failure. However, the risk of nosocomial infection is unknown. METHODS We examined exhaled air dispersion during NIV using a human patient simulator reclined at 45° in a negative pressure room with 12 air changes/h by two different helmets via a ventilator and a total facemask via a bilevel positive airway pressure device. Exhaled air was marked by intrapulmonary smoke particles, illuminated by laser light sheet, and captured by a video camera for data analysis. Significant exposure was defined as where there was ≥ 20% of normalized smoke concentration. RESULTS During NIV via a helmet with the simulator programmed in mild lung injury, exhaled air leaked through the neck-helmet interface with a radial distance of 150 to 230 mm when inspiratory positive airway pressure was increased from 12 to 20 cm H2O, respectively, while keeping the expiratory pressure at 10 cm H2O. During NIV via a helmet with air cushion around the neck, there was negligible air leakage. During NIV via a total facemask for mild lung injury, air leaked through the exhalation port to 618 and 812 mm when inspiratory pressure was increased from 10 to 18 cm H2O, respectively, with the expiratory pressure at 5 cm H2O. CONCLUSIONS A helmet with a good seal around the neck is needed to prevent nosocomial infection during NIV for patients with respiratory infections.


title: Methods to detect infectious human enteric viruses in environmental water samples

text: Abstract Currently, a wide range of analytical methods is available for virus detection in environmental water samples. Molecular methods such as polymerase chain reaction (PCR) and quantitative real time PCR (qPCR) have the highest sensitivity and specificity to investigate virus contamination in water, so they are the most commonly used in environmental virology. Despite great sensitivity of PCR, the main limitation is the lack of the correlation between the detected viral genome and viral infectivity, which limits conclusions regarding the significance for public health. To provide information about the infectivity of the detected viruses, cultivation on animal cell culture is the gold standard. However, cell culture infectivity assays are laborious, time consuming and costly. Also, not all viruses are able to produce cytopathic effect and viruses such as human noroviruses have no available cell line for propagation. In this brief review, we present a summary and critical evaluation of different approaches that have been recently proposed to overcome limitations of the traditional cell culture assay and PCR assay such as integrated cell culture-PCR, detection of genome integrity, detection of capsid integrity, and measurement of oxidative damages on viral capsid protein. Techniques for rapid detection of infectious viruses such as fluorescence microscopy and automated flow cytometry have also been suggested to assess virus infectivity in water samples.


title: Chapter 6 Involvement and Roles of Long Noncoding RNAs in the Molecular Mechanisms of Emerging and Reemerging Viral Infections

text: Abstract The studies on the mechanisms of viral–host interactions in infections have been focusing on protein-coding sequences of the genome. Although it is essential to consider the nonprotein-coding part that represents approximately 80% of the human genome. Thus advances in sequencing techniques have led to the discovery of thousands of RNAs with low or no capacity to encode proteins but are exhibiting crucial biological functions. Long noncoding RNAs (ncRNAs) (lncRNAs) are a heterogeneous class of these ncRNAs that are longer than 200nt. Accumulating evidences have demonstrated the involvement of these molecules in development and physiological processes, especially through their regulation of gene expression. LncRNAs are encoded in mammalian cells as well as in microorganisms and viruses. Several studies have found differential expressions of lncRNAs in response to viral infection of emerging viruses, which suggest important roles. In fact, they are involved in promoting viral replication, evading host immunity and regulating the host response to the infection. In addition, lncRNAs do not induce immune response compared to viral proteins; thus viruses might employ them as an effective strategy to invade their hosts. In this chapter, we discuss particularly the emerging virus–host interaction associated lncRNAs through addressing their involvement in the mechanisms underlying emerging viral infections as well as in the pathways of immune system in response to these infections. We also discuss the promising role of these noncoding transcripts as biomarkers for diagnosing viral pathologies.


title: Topographic Changes in SARS Coronavirus–infected Cells at Late Stages of Infection

text: Scanning electron and atomic force microscopy was used for the first time to view the maturation of the severe acute respiratory syndrome–associated coronavirus at the cell surface. The surface form of the cells at advanced infection displayed prolific pseudopodia that, in addition to the rest of the plasma membrane, were also active sites of virus release. High magnification of the maturing virus particles showed a rosette appearance with short knoblike spikes under both the scanning electron and atomic force microscopes. The final expulsion step of the maturing virus particles seemed to result in some disruptions to the plasma membrane. The cytoskeletal network along the edge of the infected cells was enhanced and could be involved in transporting and expelling the progeny virus particles. Thickening of the actin filaments at the cell edge provided the bending force to extrude the virus particles.


docid: raycnjbl

title: Constructing Markov matrices for real-time transient contaminant transport analysis for indoor environments

text: Abstract Predicting the movement of contaminants in the indoor environment has applications in tracking airborne infectious disease, ventilation of gaseous contaminants, and the isolation of spaces during biological attacks. Markov matrices provide a convenient way to perform contaminant transport analysis. However, no standardized method exists for calculating these matrices. A methodology based on set theory is developed for calculating contaminant transport in real-time utilizing Markov matrices from CFD flow data (or discrete flow field data). The methodology provides a rigorous yet simple strategy for determining the number and size of the Markov states, the time step associated with the Markov matrix, and calculation of individual entries of the Markov matrix. The procedure is benchmarked against scalar transport of validated airflow fields in enclosed and ventilated spaces. The approach can be applied to any general airflow field, and is shown to calculate contaminant transport over 3000 times faster than solving the corresponding scalar transport partial differential equation. This near real-time methodology allows for the development of more robust sensing and control procedures of critical care environments (clean rooms and hospital wards), small enclosed spaces (like airplane cabins) and high traffic public areas (train stations and airports).


title: 101 MPs urge Chancellor to throw dentists a lifeline

text: The British Dental Association (BDA) has applauded the call from 101 MPs - from 7 parties - who have joined forces to demand immediate action from the Chancellor to save the UK's dental services Fleur Anderson, Labour MP for Putney, Roehampton and Southfields has led efforts in parliament, delivering a stark warning to the government that unless urgent action is taken dental practices across the country will not recover from the COVID-19 crisis


title: COVID-19, MERS and SARS with Concomitant Liver Injury—Systematic Review of the Existing Literature

text: The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection has been predominantly linked to respiratory distress syndrome, but gastrointestinal symptoms and hepatic injury have also been reported. The mechanism of liver injury is poorly understood and may result as a consequence of viral hepatitis, systemic inflammatory response, gut barrier and microbiome alterations, intensive care treatment or drug toxicity. The incidence of hepatopathy among patients with coronavirus disease 2019 (COVID-19) is unclear, but studies have reported liver injury in patients with SARS and Middle East respiratory syndrome (MERS). We aimed to systematically review data on the prevalence of hepatic impairments and their clinical course in SARS and MERS Coronaviridae infections. A systematic literature search (PubMed/Embase/Cinahl/Web of Science) according to preferred reporting items for systematic review and meta-analysis protocols (PRISMA) was conducted from database inception until 17/03/2020 for studies that evaluated the incidence of hepatic abnormalities in SARS CoV-1, SARS CoV-2 and MERS infected patients with reported liver-related parameters. A total of forty-three studies were included. Liver anomalies were predominantly mild to moderately elevated transaminases, hypoalbuminemia and prolongation of prothrombin time. Histopathology varied between non-specific inflammation, mild steatosis, congestion and massive necrosis. More studies to elucidate the mechanism and importance of liver injury on the clinical course and prognosis in patients with novel SARS-CoV-2 infection are warranted.


title: Bats Are an Untapped System for Understanding Microbiome Evolution in Mammals

text: Mammals evolved in a microbial world, and consequently, microbial symbionts have played a role in their evolution. An exciting new subdiscipline of metagenomics considers the ways in which microbes, particularly those found in the gut, have facilitated the ecological and phylogenetic radiation of mammals. However, the vast majority of such studies focus on domestic animals, laboratory models, or charismatic megafauna (e.g., pandas and chimpanzees). The result is a plethora of studies covering few taxa across the mammal tree of life, leaving broad patterns of microbiome function and evolution unclear. Wildlife microbiome research urgently needs a model system in which to test hypotheses about metagenomic involvement in host ecology and evolution. We propose that bats (Order: Chiroptera) represent a model system ideal for comparative microbiome research, affording opportunities to examine host phylogeny, diet, and other natural history characteristics in relation to the evolution of the gut microbiome.


title: Characteristics, symptom management and outcomes of 101 patients with COVID-19 referred for hospital palliative care

text: Abstract Hospital palliative care is an essential part of the COVID-19 response but data are lacking. We identified symptom burden, management, response to treatment, and outcomes for a case series of 101 in-patients with confirmed COVID-19 referred to hospital palliative care. Patients (64 male, median [IQR] age 82 [72-89] years, Elixhauser Comorbidity Index 6 [2-10], Australian-modified Karnofsky Performance Status 20 [10-20]), were most frequently referred for end of life care or symptom control. Median [IQR] days from hospital admission to referral was 4 [1-12] days. Most prevalent symptoms (n) were breathlessness (67), agitation (43), drowsiness (36), pain (23) and delirium (24). Fifty-eight patients were prescribed a subcutaneous infusion. Frequently used medicines (median-maximum dose/24h) were opioids (morphine, 10-30mg; fentanyl, 100-200mcg; alfentanil 500-1000 mcg) and midazolam (10-20mg). Infusions were assessed as at least partially effective for 40/58 patients, while 13 patients died before review. Patients spent a median [IQR] of 2 [1–4] days under the palliative care team, who made 3 [2–5] contacts across patient, family and clinicians. At March 30 2020, 75 patients had died, 13 been discharged back to team, home or hospice, and 13 continued to receive inpatient palliative care. Palliative care is an essential component to the COVID-19 response, and teams must rapidly adapt with new ways of working. Breathlessness and agitation are common but respond well to opioids and benzodiazepines. Availability of subcutaneous infusion pumps is essential. An international minimum dataset for palliative care would accelerate finding answers to new questions as the COVID-19 pandemic develops.


Social Science and the Public Interest: May/June 2020


title: Fever detection from free-text clinical records for biosurveillance

text: Abstract Automatic detection of cases of febrile illness may have potential for early detection of outbreaks of infectious disease either by identification of anomalous numbers of febrile illness or in concert with other information in diagnosing specific syndromes, such as febrile respiratory syndrome. At most institutions, febrile information is contained only in free-text clinical records. We compared the sensitivity and specificity of three fever detection algorithms for detecting fever from free-text. Keyword CC and CoCo classified patients based on triage chief complaints; Keyword HP classified patients based on dictated emergency department reports. Keyword HP was the most sensitive (sensitivity 0.98, specificity 0.89), and Keyword CC was the most specific (sensitivity 0.61, specificity 1.0). Because chief complaints are available sooner than emergency department reports, we suggest a combined application that classifies patients based on their chief complaint followed by classification based on their emergency department report, once the report becomes available.


title: The Ebola clinical trials: a precedent for research ethics in disasters

text: The West African Ebola epidemic has set in motion a collective endeavour to conduct accelerated clinical trials, testing unproven but potentially lifesaving interventions in the course of a major public health crisis. This unprecedented effort was supported by the recommendations of an ad hoc ethics panel convened in August 2014 by the WHO. By considering why and on what conditions the exceptional circumstances of the Ebola epidemic justified the use of unproven interventions, the panel's recommendations have challenged conventional thinking about therapeutic development and clinical research ethics. At the same time, unanswered ethical questions have emerged, in particular: (i) the specification of exceptional circumstances, (ii) the specification of unproven interventions, (iii) the goals of interventional research in terms of individual versus collective interests, (iv) the place of adaptive trial designs and (v) the exact meaning of compassionate use with unapproved interventions. Examination of these questions, in parallel with empirical data from research sites, will help build pragmatic foundations for disaster research ethics. Furthermore, the Ebola clinical trials signal an evolution in the current paradigms of therapeutic research, beyond the case of epidemic emergencies.


title: Detection of SARS-CoV-2 by bronchoscopy after negative nasopharyngeal testing: Stay vigilant for COVID-19

text: PURPOSE: Real-time polymerase chain reaction (RT-PCR) detection of severe acute respiratory syndrome coronavirus (SARS-CoV-2) is required for diagnosis of coronavirus disease 2019 (COVID-19). Sensitivity of RT-PCR nasopharyngeal (NP) testing is presumed to be high, but there is no gold standard against which this has been determined. The objective was to determine whether lower respiratory tract infection (LRTI), detected in bronchoalveolar lavage fluid (BALF), occurs in the absence of upper respiratory tract infection with clinical testing of both specimen types. METHODS: Between March 26, 2020 and April 17, 2020 at the University of Washington Medical Center all patients with BALF specimens clinically tested for SARS-CoV-2 were identified. We assessed the proportion of patients with positive RT-PCR for SARS-CoV-2 in BALF after negative NP testing. We describe 3 cases with positive testing in BALF. RESULTS: Among 16 patients with BALF samples, 3 cases (19%) had SARS-CoV-2 detected in BALF. In Case 1, negative NP testing occurred early in the infection and respiratory symptoms may have been missed due to neurologic injury. In Case 2, outpatient diagnosis was aspiration pneumonia, but clinical suspicion remained high for COVID-19 at hospitalization based on epidemiological and clinical features. All 3 cases involved older adults (age >65 years), one of whom was immunosuppressed in the setting of lung transplantation (Case 3). CONCLUSIONS: These data demonstrate that SARS-CoV-2 LRTI occurs in the presence of negative NP testing. NP testing may underestimate the prevalence of COVID-19 and has implications for spread of SARS-CoV2 in the community and healthcare setting.


Vaccines of the future


title: Strongyloides Hyperinfection Syndrome Combined with Cytomegalovirus Infection

text: The mortality in Strongyloides hyperinfection syndrome (SHS) is alarmingly high. This is particularly common in bone marrow, renal, and other solid organ transplant (SOT) patients, where figures may reach up to 50–85%. Immunosuppressives, principally corticosteroids, are the primary triggering factor. In general, the clinical features of Strongyloides stercoralis hyperinfection are nonspecific; therefore, a high index of suspicion is required for early diagnosis and starting appropriate therapy. Although recurrent Gram-negative sepsis and meningitis have been previously reported, the combination of both cytomegalovirus (CMV) and strongyloidiasis had rarely been associated. We here describe a patient who survived SHS with recurrent Escherichia coli (E. coli) urosepsis and CMV infection.


APIC's role in emergency management: Proceedings of the 2008 APIC Emergency Preparedness Mini-Summit


title: Chapter 5 Virus Transmission and Epidemiology

text: Abstract For transmission of a virus to occur, a virus must enter a host through a portal of entry, replicate or disseminate within the host, and be transmitted to a new host through a portal of exit. Unless delivered directly into bodily tissues through a bite or needle, most viruses interact with the epithelium at the site of entry. Localized infections replicate at the initial site of infection, while systemic infections spread to additional areas of the body. Viruses are shed into the environment most often through the same route they entered the body. The stability of virions within the environment is dependent upon virion and environmental factors. Epidemiology is the study of how diseases are transmitted through a population. Epidemiologists perform descriptive or analytic studies to characterize the chain of viral infection throughout a population and design control measures to interrupt it.


title: In Vivo Persistence of Human Rhinoviruses in Immunosuppressed Patients

text: Several species of the genus Enterovirus cause persistent infections in humans. Human rhinovirus (HRV) infections are generally self-limiting but occasionally persistent infections have been described. This study aimed to identify persistent HRV infections and investigate the clinical and virologic characteristics of patients with persistent infections. From January 2012 to March 2015, 3714 respiratory specimens from 2608 patients were tested for respiratory viruses by using a multiplex reverse transcription–polymerase chain reaction. A retrospective study was performed. Patients with at least two specimens positive for HRV/enterovirus taken 45 days or longer apart were identified and the HRV/enteroviruses were typed. Patients with persistent infection were compared to patients with reinfection and patients with cleared infection. Phylogenetic analysis of the viral protein(VP)4/VP2 region was performed. 18 patients with persistent HRV/enterovirus infection were identified. Minimum median duration of persistence was 92 days (range 50–455 days). All but one patients with persistence were immunosuppressed. Immunosuppression and hematologic disorders were more frequent in patients with persistence (n = 18) than in patients with reinfection (n = 33) and with cleared infection (n = 25) (p = 0.003 and p = 0.001, respectively). In conclusion, this retrospective study identified HRV persistence in vivo which occurred mainly in immunosuppressed patients.


Respiratorische Virusinfektionen


title: Role of laboratory variables in differentiating SARS-coronavirus from other causes of community-acquired pneumonia within the first 72 h of hospitalization

text: The Centers for Disease Control and Prevention (CDC) recommend that SARS-coronavirus (SARS-CoV) testing be considered in epidemiologically high-risk patients hospitalized with community-acquired pneumonia (CAP) if no alternative diagnosis is identified after 72 h. The aim of this study was to identify routine laboratory variables that might indicate the need for SARS-CoV testing. Routine hematological/biochemical variables in patients with laboratory-confirmed SARS (2003) were compared with those in consecutive patients hospitalized June–December 2004 with radiologically confirmed CAP. Stepwise logistic regression analyses were performed to identify discriminating variables at baseline and by day 3 of hospitalization. Nasopharyngeal aspiration and antigen detection for influenza virus and respiratory syncytial virus using an immunofluorescence assay (IFA) were routinely performed in patients with CAP. Altogether, 181 patients with CAP (who remained undiagnosed by IFA) and 303 patients with SARS were studied. The mean intervals from symptom onset to admission were 3.1 and 2.8 days, respectively (p > 0.05). The etiological agent of CAP was identified retrospectively in only 39% of cases, the majority being bacterial pathogens. At baseline, age and absolute neutrophil count (ANC) were the only independent discriminating variables (p < 0.0001). Using a value of <4.4 × 10(9)/l as the cutoff for ANC, the sensitivity and specificity of ANC for discriminating SARS were 64 and 95%, respectively (AUC 0.90). By day 3 of hospitalization, age (p < 0.0001), change in ANC (p = 0.0003), and change in bilirubin (p = 0.0065) were discriminating variables. A model combining age <65 years, a change in ANC of >−3 × 10(9)/l, and a change in bilirubin of ≥0 mmol/l had a sensitivity of 43% and a specificity of 95% for SARS (AUC 0.90). There are only a few laboratory features (including lymphopenia) that clearly discriminate SARS from other causes of CAP. Nevertheless, when evaluating epidemiologically high-risk patients with CAP and no immediate alternative diagnosis, a low ANC on presentation along with poor clinical and laboratory responses after 72 h of antibiotic treatment may raise the index of suspicion for SARS and indicate a need to perform SARS-CoV testing.


title: Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome

text: Summary Background Human infection with avian influenza A H7N9 virus emerged in eastern China in February, 2013, and has been associated with exposure to poultry. We report the clinical and microbiological features of patients infected with influenza A H7N9 virus and compare genomic features of the human virus with those of the virus in market poultry in Zhejiang, China. Methods Between March 7 and April 8, 2013, we included hospital inpatients if they had new-onset respiratory symptoms, unexplained radiographic infiltrate, and laboratory-confirmed H7N9 virus infection. We recorded histories and results of haematological, biochemical, radiological, and microbiological investigations. We took throat and sputum samples, used RT-PCR to detect M, H7, and N9 genes, and cultured samples in Madin-Darby canine kidney cells. We tested for co-infections and monitored serum concentrations of six cytokines and chemokines. We collected cloacal swabs from 86 birds from epidemiologically linked wet markets and inoculated embryonated chicken eggs with the samples. We identified and subtyped isolates by RT-PCR sequencing. RNA extraction, complementary DNA synthesis, and PCR sequencing were done for one human and one chicken isolate. We characterised and phylogenetically analysed the eight gene segments of the viruses in the patient's and the chicken's isolates, and constructed phylogenetic trees of H, N, PB2, and NS genes. Findings We identified four patients (mean age 56 years), all of whom had contact with poultry 3–8 days before disease onset. They presented with fever and rapidly progressive pneumonia that did not respond to antibiotics. Patients were leucopenic and lymphopenic, and had impaired liver or renal function, substantially increased serum cytokine or chemokine concentrations, and disseminated intravascular coagulation with disease progression. Two patients died. Sputum specimens were more likely to test positive for the H7N9 virus than were samples from throat swabs. The viral isolate from the patient was closely similar to that from an epidemiologically linked market chicken. All viral gene segments were of avian origin. The H7 of the isolated viruses was closest to that of the H7N3 virus from domestic ducks in Zhejiang, whereas the N9 was closest to that of the wild bird H7N9 virus in South Korea. We noted Gln226Leu and Gly186Val substitutions in human virus H7 (associated with increased affinity for α-2,6-linked sialic acid receptors) and the PB2 Asp701Asn mutation (associated with mammalian adaptation). Ser31Asn mutation, which is associated with adamantane resistance, was noted in viral M2. Interpretation Cross species poultry-to-person transmission of this new reassortant H7N9 virus is associated with severe pneumonia and multiorgan dysfunction in human beings. Monitoring of the viral evolution and further study of disease pathogenesis will improve disease management, epidemic control, and pandemic preparedness. Funding Larry Chi-Kin Yung, National Key Program for Infectious Diseases of China.


title: Recommandations jointes des comités de l’AFU (Neuro-Urologie, CUROPF, CTMH) pour l’urologie fonctionnelle durant la crise sanitaire liée au COVID-19

text: AIM The management of urology patient is currently disrupted by the COVID-19 epidemic. In the field of functional urology, there are clinical situations with a high risk of complication if management is delayed and a great heterogeneity of advisable reprogramming times after cancellation. A prioritization of functional urology procedures is necessary to adapt management during the COVID-19 crisis and to better organize post-epidemic recovery. MATERIAL AND METHODS The advice of AFU scientific committees in the field of functional urology (neuro-urology, female and perineology, male LUTS) was requested and supplemented by a review of the currently available recommendations on the subject of urology and COVID-19. These opinions were combined to draw up temporary recommendations to help reorganize practices during the epidemic and prepare the post-critical phase. RESULTS Most of the recommendations available on career-oriented social networks (Twitter, LinkedIn) or in literature concern cancer or general urology. Eight out of ten propose a cancellation of all functional urology procedures without distinction. But the 3 AFU committees covering the field of functional urology have identified three clinical situations in which surgical procedures that can be maintained during the COVID-19 epidemic (priority level A): conclusion of a neuromodulation test in progress (implantation or explantation), botulinum toxin A bladder injections for unbalanced neurologic bladder, cystectomy and ileal conduit for urinary fistula in perineal bedsore or refractory unbalanced neurologic bladder with acute renal failure and vesico-enteric or prostato-pubic fistulas. Management adaptation of the other pathologies are proposed, as well as the application of 3 priority levels (B, C, D) for rescheduled procedures for a better management of the post-crisis activity resumption. CONCLUSION The joint functional urology committees indicate that there are specific clinical situations in this field that demand non-delayed care during COVID crisis. They underline the need to establish a hierarchy for the cancelled surgeries, in order to reduce the arm of long reschedule delays and to optimize post-lockdown activity resumption.


title: Ultrafast physical bacterial inactivation and photocatalytic self-cleaning of ZnO nanoarrays for rapid and sustainable bactericidal applications

text: Abstract Various nanostructured surfaces have been developed recently to physically inactivate bacteria, for reducing the rapidly spreading threat of pathogenic bacteria. However, it generally takes several hours for these surfaces to inactivate most of the bacteria, which greatly limits their application in the fields favoring rapid bactericidal performance. Besides, the accumulated bacteria debris left on these surfaces is rarely discussed in the previous reports. Herein we report the nanotip-engineered ZnO nanoarrays (NAs) with ultrafast physical bactericidal rate and the ability to photocatalytically remove the bacteria debris. Neither chemical (Zn2+ or reactive oxygen species) nor photocatalytic effect leads to the ultrafast bactericidal rate, where 97.5% of E. coli and 94.9% of S. aureus are inactivated within only 1 min. The simulation analysis further supported our proposed mechanism attributing the ultrafast bactericidal activity to the great stress enabled by the uneven topography. Moreover, the re-exposure of the ZnO NAs nanotips can be achieved in only 10 min under a mild UV light source. This study not only presents an ultrafast physical bactericidal activity, but also demonstrates the potential of the recyclable and photocatalytic self-cleaning functions of theses surfaces for applications that desire rapid and sustainable bactericidal performance.


COVID‐19: Vulnerability and the power of privilege in a pandemic


docid: ygtqbqjf

title: Gestión de los cadáveres durante la pandemia por COVID-19 en España

text: Resumen El brote por el Coronavirus/COVID-19, declarado Emergencia de Salud Pública de Importancia Internacional el 30 de enero de 2020 por la Organización Mundial de la Salud, ha sobrepasado en numerosos países la capacidad de respuesta del sistema sanitario por su alta contagiosidad, y la de gestión de las personas fallecidas por su elevado riesgo de letalidad. Se revisan las principales guías y protocolos promovidos por las instituciones y las principales sociedades científicas, orientados a la contención de la pandemia mediante la adopción de medidas de protección de los profesionales y a la adecuada gestión del alto número de cadáveres. Se analizan los centros especiales de recogida de cadáveres en situación de epidemias y las clasificaciones de los cadáveres en función del riesgo infecto-contagioso. Específicamente se resumen las resoluciones dictadas por las autoridades sanitarias y se describen los protocolos de actuación ante fallecidos durante la pandemia COVID-19, incluyendo las autopsias forenses. Abstract The Coronavirus/COVID-19 outbreak, declared a Public Health Emergency of International Importance on January 30, 2020 by the World Health Organization, has in many countries exceeded the capacity of health systems to respond, due to its high contagiousness and the capacity to manage the deceased, due to its high fatality risk. A review is necessary of the principal guidelines and protocols promoted by the institutions and the main scientific societies, aimed at containing the pandemic by adopting professional protection measures and appropriately managing the high number of cadavers. The temporary mortuaries in an epidemic crisis and the classification of bodies according to infectious risk are analysed. In particular the resolutions issued by the health authorities are summarised and the protocols for dealing with deaths during the COVID-19 pandemic are described, including forensic autopsies.


title: Toll-like receptor 9 ligand D-type oligodeoxynucleotide D35 as a broad inhibitor for influenza A virus replication that is associated with suppression of neuraminidase activity

text: Abstract The most effective drugs available to treat influenza are neuraminidase (NA) inhibitors, which provide important additional measures for the control of influenza virus infections. However, since the emergence of NA inhibitor-resistant viruses may compromise the clinical utility of this class of anti-influenza agents, it is very important to develop new anti-influenza agents which target a different region in NA responsible for its sensitivity from that for NA inhibitors and could be used to treat NA inhibitors-resistant isolates. The oligodeoxynucleotide D35, multimerized and aggregated, suppressed replication of influenza A viruses except A/WSN/33 (WSN). The suppressive viral replication by D35 depended on G-terad and multimer formation. The range of the suppressive viral replication at the late stage, including virus assembly and release from infected cells, was much larger than that at the initial stage, viral attachment and entry. D35 suppressed NA activity of influenza A viruses. Furthermore, replacing the NA gene of A/Puerto Rico/8/34 (PR8), in which viral replication was inhibited by D35 at the late stage, with the NA gene from WSN, in which viral replication was not inhibited, eliminated the D35-dependent suppression. D35 showed an additive anti-influenza effect with oseltamivir. It was also effective in vivo. These results suggest that the influenza virus NA mainly contributse to the D35-suppressible virus release from infected cells at the late stage. In addition, because administration of D35 into the virus-infected mice suppressed viral replication and weight loss, clinical application of D35 could be considered.


title: Breastfeeding and Medication Use in Kidney Disease

text: Abstract Pregnancy in chronic kidney disease is a condition fraught with challenges including multiple medications, high risk pregnancy followed by maternal and fetal compromise such as preterm delivery and low birth weight infant. Breastfeeding is unique in its impact on the mother and the baby, their bonding and future health implications impacting the society. Breastmilk is produced specific for the infant by the biological mother. It changes in composition with lactation stage, and leads to optimal growth of the baby including establishing circadian rhythms, getting protective antibodies and establishing a healthy gut microbiome. Multiple hormones influence the composition of the milk. Lactation is maintained by removal of the milk. Blood-milk barrier allows for the specific composition of milk by transporting different sized molecules through different mechanisms. It is safe to assume that most medications will be found in some amount in human milk, however, the impact of that is usually not enough to justify stopping breastfeeding. When mothers milk is not available, formula or donor milk can be considered. There are resources to guide the use of medications during lactation that the providers should be aware of and use, to guide medication and breastfeeding recommendations.


title: Association of Human bocavirus with Respiratory Infections in Outpatients and in Patients Attended at a Reference Hospital

text: The role of Human bocavirus (HBoV) in human infectious disease is unclear due to the frequent detection of this virus in association with other respiratory viruses with a recognized pathogenic role in acute respiratory infection. We have analyzed the impact of HBoV in outpatients and in patients requiring hospitalisation or emergency attention for acute respiratory infections. Respiratory viruses were investigated by real-time PCR, direct antigen detection and/or viral culture by shell-vial assay. Nasopharyngeal aspirates, BAL and/or sputum samples from patients attended at a reference hospital, and nasal/throat swabs from outpatients were used. Respiratory viruses were detected in 660 samples (47%). HBoV detection rate was 12.6%, only preceded by respiratory syncytial virus (25%). Co-detections were observed in 12.9% of samples, and HBoV was present in 81% of them. Similar detection rates of HBoV were obtained in individuals with positive and negative results for other respiratory viruses (12.5% and 12.7%, respectively). The crossing point value was taken as a measure of HBoV viral load. Higher HBoV loads were observed in children, and in patients from the hospital. HBoV viral load was not associated with symptoms of upper respiratory tract infection or lower respiratory tract disease. Although HBoV is frequently detected in respiratory specimens, there is a poor association between HBoV-positive specimens and clinical parameters. A clinical impact of HBoV in respiratory infection probably occurs in few cases.


title: The Elabela-APJ axis: a promising therapeutic target for heart failure

text: Heart failure (HF) is a growing epidemic with high morbidity and mortality at an international scale. The apelin–APJ receptor pathway has been implicated in HF, making it a promising therapeutic target. APJ has been shown to be activated by a novel endogenous peptide ligand known as Elabela (ELA, also called Toddler or Apela), with a critical role in cardiac development and function. Activation of the ELA–APJ receptor axis exerts a wide range of physiological effects, including depressor response, positive inotropic action, diuresis, anti-inflammatory, anti-fibrotic, and anti-remodeling, leading to its cardiovascular protection. The ELA–APJ axis is essential for diverse biological processes and has been shown to regulate fluid homeostasis, myocardial contractility, vasodilation, angiogenesis, cellular differentiation, apoptosis, oxidative stress, cardiorenal fibrosis, and dysfunction. The beneficial effects of the ELA–APJ receptor system are well-established by treating hypertension, myocardial infarction, and HF. Additionally, administration of ELA protects human embryonic stem cells against apoptosis and stress-induced cell death and promotes survival and self-renewal in an APJ-independent manner (X receptor) via the phosphatidylinositol 3-kinase/Akt pathway, which may provide a new therapeutic approach for HF. Thus, targeting the ELA–APJ axis has emerged as a pre-warning biomarker and a novel therapeutic approach against progression of HF. An increased understanding of cardiovascular actions of ELA will help to develop effective interventions. This article gives an overview of the characteristics of the ELA–apelin–APJ axis and summarizes the current knowledge on its cardioprotective roles, potential mechanisms, and prospective application for acute and chronic HF.


title: Transmission and control of an emerging influenza pandemic in a small-world airline network

text: Abstract The avian influenza virus H5N1 and the 2009 swine flu H1N1 are potentially serious pandemic threats to human health, and air travel readily facilitates the spread of infectious diseases. However, past studies have not yet incorporated the effects of air travel on the transmission of influenza in the construction of mathematical epidemic models. Therefore, this paper focused on the human-to-human transmission of influenza, and investigated the effects of air travel activities on an influenza pandemic in a small-world network. These activities of air travel include passengers’ consolidation, conveyance and distribution in airports and flights. Dynamic transmission models were developed to assess the expected burdens of the pandemic, with and without control measures. This study also investigated how the small-world properties of an air transportation network facilitate the spread of influenza around the globe. The results show that, as soon as the influenza is spread to the top 50 global airports, the transmission is greatly accelerated. Under the constraint of limited resources, a strategy that first applies control measures to the top 50 airports after day 13 and then soon afterwards to all other airports may result in remarkable containment effectiveness. As the infectiousness of the disease increases, it will expand the scale of the pandemic, and move the start time of the pandemic ahead.


title: Epidemiological investigation of Middle East respiratory syndrome coronavirus in dromedary camel farms linked with human infection in Abu Dhabi Emirate, United Arab Emirates

text: The objective of this research was to investigate the prevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) infection primarily in dromedary camel farms and the relationship of those infections with infections in humans in the Emirate of Abu Dhabi. Nasal swabs from 1113 dromedary camels (39 farms) and 34 sheep (1 farm) and sputum samples from 2 MERS-CoV-infected camel farm owners and 1 MERS-CoV-infected sheep farm owner were collected. Samples from camels and humans underwent real-time reverse-transcription quantitative PCR screening to detect MERS-CoV. In addition, sequencing and phylogenetic analysis of partially characterized MERS-CoV genome fragments obtained from camels were performed. Among the 40 farms, 6 camel farms were positive for MERS-CoV; the virus was not detected in the single sheep farm. The maximum duration of viral shedding from infected camels was 2 weeks after the first positive test result as detected in nasal swabs and in rectal swabs obtained from infected calves. Three partial camel sequences characterized in this study (open reading frames 1a and 1ab, Spike1, Spike2, and ORF4b) together with the corresponding regions of previously reported MERS-CoV sequence obtained from one farm owner were clustering together within the larger MERS-CoV sequences cluster containing human and camel isolates reported for the Arabian Peninsula. Data provided further evidence of the zoonotic potential of MERS-CoV infection and strongly suggested that camels may have a role in the transmission of the virus to humans.


Covid-19, la Société française du cancer (SFC) et le Bulletin du Cancer


Coronavirus‐JHM‐Induced Demyelinating Encephalomyelitis in Rats: Analysis of the Intrathecal Immune Response


title: Emerging infections in transfusion medicine

text: The risk of transfusion-transmitted infectious diseases (TTIDs) has declined dramatically in high-income nations over the past 2 decades, primarily because of extraordinary success in preventing HIV and other established transfusion-transmitted viruses from entering the blood supply. Despite this achievement, TTIDs remain a public health concern, and attention is refocusing on new and emerging pathogens, such as West Nile virus, infectious proteins (the presumed cause of variant Creutzfeldt-Jakob disease), and other transmissible organisms such as bacteria and parasites. In this article the authors concentrate on this heterogeneous group of infectious agents, describe individual pathogens and the risks they pose to transfusion recipients, and comment on existing and evolving procedures that are designed to protect the blood supply from this threat.


title: A simple and rapid immunochromatographic test kit for rabies diagnosis

text: In rabies endemic countries, funds and infrastructure are often insufficient to employ the approved gold standard for the definitive diagnosis of rabies: the direct fluorescent test. In the present study, two types (type 1 and 2) of an ICT kit were evaluated for detection of rabies. These were developed using monoclonal antibodies which recognize epitope II and III of the nucleoprotein of rabies virus. Both kits specifically detected all rabies virus strains and there was no cross reactivity with Lyssaviruses (Lagos, Mokola and Duvenhage), Rhabdovirus (VSV and Oita 296/1972) and other common canine‐pathogenic viruses. In type 1, a single type of monoclonal antibody was used. It was capable of detecting recombinant nucleoprotein and showed sensitivity of 95.5% (42/44) and specificity of 88.9% (32/36) using brain samples from rabid dogs. In contrast, type 2 which was made of two different monoclonal antibodies had a lower sensitivity of 93.2% (41/44) and higher specificity of 100% (36/36). These ICT kits provide a simple and rapid method for rabies detection. They need neither cold chain for transportation nor complicated training for personnel. This diagnostic test is suitable for rabies screening, particularly in areas with a high prevalence of rabies and where the fluorescent antibody test is not available.


docid: bpuyrsza

title: Hosting the severe acute respiratory syndrome coronavirus: specific cell factors required for infection

text: As with all viruses, the severe acute respiratory syndrome coronavirus (SARS‐CoV) utilizes specific host cell factors during its infection cycle. Some of these factors have been identified and are now increasingly scrutinized as targets to intervene with infection. In this brief review, we describe the current understanding of how the SARS‐CoV is able to use the cellular machinery for its replication.


title: Clinical time course of COVID-19, its neurological manifestation and some thoughts on its management

text: Coronavirus disease-2019 (COVID‐19) has become a global pandemic. COVID-19 runs its course in two phases, the initial incubation phase and later clinical symptomatic phase. Patients in the initial incubation phase often have insidious clinical symptoms, but they are still highly contagious. At the later clinical symptomatic phase, the immune system is fully activated and the disease may enter the severe infection stage in this phase. Although many patients are known for their respiratory symptoms, they had neurological symptoms in their first 1–2 days of clinical symptomatic phase, and ischaemic stroke occurred 2 weeks after the onset of the clinical symptomatic phase. The key is to prevent a patient from progressing to this severe infection from mild infection. We are sharing our experience on prevention and management of COVID-19.


title: Coronaviruses in bats from Mexico

text: Bats are reservoirs for a wide range of human pathogens including Nipah, Hendra, rabies, Ebola, Marburg and severe acute respiratory syndrome coronavirus (CoV). The recent implication of a novel beta (β)-CoV as the cause of fatal respiratory disease in the Middle East emphasizes the importance of surveillance for CoVs that have potential to move from bats into the human population. In a screen of 606 bats from 42 different species in Campeche, Chiapas and Mexico City we identified 13 distinct CoVs. Nine were alpha (α)-CoVs; four were β-CoVs. Twelve were novel. Analyses of these viruses in the context of their hosts and ecological habitat indicated that host species is a strong selective driver in CoV evolution, even in allopatric populations separated by significant geographical distance; and that a single species/genus of bat can contain multiple CoVs. A β-CoV with 96.5 % amino acid identity to the β-CoV associated with human disease in the Middle East was found in a Nyctinomops laticaudatus bat, suggesting that efforts to identify the viral reservoir should include surveillance of the bat families Molossidae/Vespertilionidae, or the closely related Nycteridae/Emballonuridae. While it is important to investigate unknown viral diversity in bats, it is also important to remember that the majority of viruses they carry will not pose any clinical risk, and bats should not be stigmatized ubiquitously as significant threats to public health.


title: Mutations from bat ACE2 orthologs markedly enhance ACE2-Fc neutralization of SARS-CoV-2

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates infection of cells expressing angiotensin-converting enzyme 2 (ACE2). ACE2 is also the viral receptor of SARS-CoV (SARS-CoV-1), a related coronavirus that emerged in 2002–2003. Horseshoe bats (genus Rhinolophus) are presumed to be the original reservoir of both viruses, and a SARS-like coronavirus, RaTG13, closely related SARS-CoV-2, has been isolated from one horseshoe-bat species. Here we characterize the ability of S-protein receptor-binding domains (RBDs) of SARS-CoV-1, SARS-CoV-2, and RaTG13 to bind a range of ACE2 orthologs. We observed that the SARS-CoV-2 RBD bound human, pangolin, and horseshoe bat (R. macrotis) ACE2 more efficiently than the SARS-CoV-1 or RaTG13 RBD. Only the RaTG13 RBD bound rodent ACE2 orthologs efficiently. Five mutations drawn from ACE2 orthologs of nine Rhinolophus species enhanced human ACE2 binding to the SARS-CoV-2 RBD and neutralization of SARS-CoV-2 by an immunoadhesin form of human ACE2 (ACE2-Fc). Two of these mutations impaired neutralization of SARS-CoV-1. An ACE2-Fc variant bearing all five mutations neutralized SARS-CoV-2 five-fold more efficiently than human ACE2-Fc. These data narrow the potential SARS-CoV-2 reservoir, suggest that SARS-CoV-1 and −2 originate from distinct bat species, and identify a more potently neutralizing form of ACE2-Fc.


title: Successful yellow head virus infection of Penaeus monodon requires clathrin heavy chain

text: Abstract Viral disease caused by the Yellow head virus (YHV) had great impact on economic loss in the aquaculture industry. Prevention or curing YHV disease is still not possible due to the lack of understanding of the basic mechanisms of YHV infection. In this report, the endocytosis inhibitors (chlorpromazine (CPZ), amiloride and methyl-β-cyclodextrin (MβCD)) were used to identify the cellular entry pathway of YHV. Pretreating shrimp with CPZ but not amiloride or MβCD followed by YHV challenge resulted in a significant reduction of YHV levels, suggesting that YHV entered the shrimp cells via clathrin-mediated endocytosis. Next, the major component of the clathrin-coated vesicle, Penaeus monodon clathrin heavy chain (PmCHC) was cloned and characterized. The complete coding sequence of PmCHC is 5055bp encoding a putative protein of 1684 amino acids. Specific silencing of PmCHC mRNA by dsRNA-PmCHC showed an inhibition of YHV replication for 48h post YHV injection as well as exhibiting a delay in shrimp mortality. These results indicated that PmCHC was an essential component for YHV infection of shrimp cells.


title: 50 States or 50 Countries: What Did We Miss and What Do We Do Now?

text: There have been multiple inconsistencies in the manner the COVID-19 pandemic has been investigated and managed by countries. Population-based management (PBM) has been inconsistent, yet serves as a necessary first step in managing public health crises. Unfortunately, these have dominated the landscape within the United States and continue as of this writing. Political and economic influences have greatly influenced major public health management and control decisions. Responsibility for global public health crises and modeling for management are the responsibility of the World Health Organization (WHO) and the International Health Regulations Treaty (IHR). This review calls upon both to reassess their roles and responsibilities that must be markedly improved and better replicated world-wide in order to optimize the global public health protections and its PBM. “Ask a big enough question, and you need more than one discipline to answer it.” Liz Lerman, MacArthur “Genius” Fellow, Choreographer, Modern Dance legend, and 2011 Artist-in Residence, Harvard Music Department


title: Co-infections among patients with COVID-19: the need for combination therapy with non-anti-SARS-CoV-2 agents?

text: Abstract Co-infection has been reported in patients with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, but there is limited knowledge on co-infection among patients with coronavirus disease 2019 (COVID-19). The prevalence of co-infection was variable among COVID-19 patients in different studies, however, it could be up to 50% among non-survivors. Co-pathogens included bacteria, such as Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumonia, Legionella pneumophila and Acinetobacter baumannii; Candida species and Aspergillus flavus; and viruses such as influenza, coronavirus, rhinovirus/enterovirus, parainfluenza, metapneumovirus, influenza B virus, and human immunodeficiency virus. Influenza A was one of the most common co-infective viruses, which may have caused initial false-negative results of real-time reverse-transcriptase polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory and imaging findings alone cannot help distinguish co-infection from SARS-CoV-2 infection. Newly developed syndromic multiplex panels that incorporate SARS-CoV-2 may facilitate the early detection of co-infection among COVID-19 patients. By contrast, clinicians cannot rule out SARS-CoV-2 infection by ruling in other respiratory pathogens through old syndromic multiplex panels at this stage of the COVID-19 pandemic. Therefore, clinicians must have a high index of suspicion for coinfection among COVID-19 patients. Clinicians can neither rule out other co-infections caused by respiratory pathogens by diagnosing SARS-CoV-2 infection nor rule out COVID-19 by detection of non-SARS-CoV-2 respiratory pathogens. After recognizing the possible pathogens causing co-infection among COVID-19 patients, appropriate antimicrobial agents can be recommended.


title: Newcastle disease in pheasants (Phasianus colchicus): A review

text: Abstract Newcastle disease (ND) is regarded throughout the world as one of the most important diseases of poultry, not only due to the serious disease and high flock mortality that may result from some ND virus (NDV) infections, but also through the economic impact that may ensue due to trading restrictions and embargoes placed on areas and countries where outbreaks have occurred. All ages of pheasants are purported to be highly susceptible to infection with NDV, but clinical signs and mortality levels in infected birds vary considerably. This article reviews the available literature relating to infections in pheasants, describing the clinical presentation of the disease and the epidemiological role these hosts may have in the spread of ND.


title: 15 Respiratory medicine

text: ●. Upper respiratory infections are commonplace, especially in young people, and are often contagious; ●. Lower respiratory infections are often contagious and some are potentially fatal; ●. Asthma is common and may be life-threatening; ●. Chronic obstructive pulmonary disease is common and disabling; ●. Tuberculosis worldwide is an important infection, affecting people with HIV/AIDS or malnutrition particularly; ●. Lung cancer is common and usually has a poor prognosis.


title: ISG15 Is Critical in the Control of Chikungunya Virus Infection Independent of UbE1L Mediated Conjugation

text: Chikungunya virus (CHIKV) is a re-emerging alphavirus that has caused significant disease in the Indian Ocean region since 2005. During this outbreak, in addition to fever, rash and arthritis, severe cases of CHIKV infection have been observed in infants. Challenging the notion that the innate immune response in infants is immature or defective, we demonstrate that both human infants and neonatal mice generate a robust type I interferon (IFN) response during CHIKV infection that contributes to, but is insufficient for, the complete control of infection. To characterize the mechanism by which type I IFNs control CHIKV infection, we evaluated the role of ISG15 and defined it as a central player in the host response, as neonatal mice lacking ISG15 were profoundly susceptible to CHIKV infection. Surprisingly, UbE1L(−/−) mice, which lack the ISG15 E1 enzyme and therefore are unable to form ISG15 conjugates, displayed no increase in lethality following CHIKV infection, thus pointing to a non-classical role for ISG15. No differences in viral loads were observed between wild-type (WT) and ISG15(−/−) mice, however, a dramatic increase in proinflammatory cytokines and chemokines was observed in ISG15(−/−) mice, suggesting that the innate immune response to CHIKV contributes to their lethality. This study provides new insight into the control of CHIKV infection, and establishes a new model for how ISG15 functions as an immunomodulatory molecule in the blunting of potentially pathologic levels of innate effector molecules during the host response to viral infection.


title: Impact of Online Information on Self-Isolation Intention During the COVID-19 Pandemic: Cross-Sectional Study

text: BACKGROUND: During the coronavirus disease (COVID-19) pandemic, governments issued movement restrictions and placed areas into quarantine to combat the spread of the disease. In addition, individuals were encouraged to adopt personal health measures such as social isolation. Information regarding the disease and recommended avoidance measures were distributed through a variety of channels including social media, news websites, and emails. Previous research suggests that the vast amount of available information can be confusing, potentially resulting in overconcern and information overload. OBJECTIVE: This study investigates the impact of online information on the individual-level intention to voluntarily self-isolate during the pandemic. Using the protection-motivation theory as a framework, we propose a model outlining the effects of cyberchondria and information overload on individuals’ perceptions and motivations. METHODS: To test the proposed model, we collected data with an online survey (N=225) and analyzed it using partial least square-structural equation modeling. The effects of social media and living situation were tested through multigroup analysis. RESULTS: Cyberchondria and information overload had a significant impact on individuals’ threat and coping perceptions, and through them on self-isolation intention. Among the appraisal constructs, perceived severity (P=.002) and self-efficacy (P=.003) positively impacted self-isolation intention, while response cost (P<.001) affected the intention negatively. Cyberchondria (P=.003) and information overload (P=.003) indirectly affected self-isolation intention through the aforementioned perceptions. Using social media as an information source increased both cyberchondria and information overload. No differences in perceptions were found between people living alone and those living with their families. CONCLUSIONS: During COVID-19, frequent use of social media contributed to information overload and overconcern among individuals. To boost individuals’ motivation to adopt preventive measures such as self-isolation, actions should focus on lowering individuals’ perceived response costs in addition to informing them about the severity of the situation.


docid: lfjxjgmg

title: How effective response to COVID‐19 relies on nursing research


title: Chapter 4 Interaction of Virus Populations with Their Hosts

text: Abstract Viral population numbers are extremely large compared with those of their host species. Population bottlenecks are frequent during the life cycle of viruses and can reduce viral populations transiently to very few individuals. Viruses have to confront several types of constraints that can be divided in basal, cell-dependent, and organism-dependent constraints. Viruses overcome them exploiting a number of molecular mechanisms, with an important contribution of population numbers and genome variation. The adaptive potential of viruses is reflected in modifications of cell tropism and host range, escape to components of the host immune response, and capacity to alternate among different host species, among other phenotypic changes. Despite a fitness cost of most mutations required to overcome a selective constraint, viruses can find evolutionary pathways that ensure their survival in equilibrium with their hosts.


title: Addressing Collegiate Mental Health Amid COVID-19 Pandemic

text: Abstract College students encounter unique challenges leading to poor mental health in the wake of the COVID-19 outbreak. Before the pandemic started, one in five college students experienced one or more diagnosable mental disorders worldwide. The fact that the COVID-19 pandemic affects collegiate mental health underscores the urgent need to understand these challenges and concerns in order to inform the development of courses of action and public health messaging that can better support college students in this crisis. This article provides recommendations that prepare higher education institutions and health professionals for addressing collegiate mental health needs and challenges posed by COVID-19.


title: Letter to the Editor: Acute hypertriglyceridemia in patients with COVID‐19 receiving tocilizumab

text: Tocilizumab is an interleukin‐6 (IL‐6) receptor antibody and is progressing as a viable and promising treatment option in patients with severe coronavirus disease 2019 (COVID‐19). IL‐6 is known to have both immunomodulatory and metabolic actions. In this letter we outline two cases of acute hypertriglyceridemia in patients with COVID‐19 treated with tocilizumab: one with elevated biomarkers consistent with acute pancreatitis the other without. Given the paucity of robust clinical trial data for most COVID‐19 pharmacotherapies at this time, clinicians should continue to remain steadfast in recognition of interventions that improve clinical outcomes and vigilant in monitoring for acute adverse effects that are difficult to detect in clinical trials with small sample sizes. The observations from our two cases highlight the complex, not fully elucidated interrelationship between elevated IL‐6 and pharmacologic interventions impacting this pathway. Clinicians should consider monitoring for hypertriglyceridemia and acute pancreatitis as described with chronic tocilizumab use for rheumatoid arthritis in those receiving it for COVID‐19. This article is protected by copyright. All rights reserved.


title: Structure-function and application of plant lectins in disease biology and immunity

text: Abstract Lectins are proteins with a high degree of stereospecificity to recognize various sugar structures and form reversible linkages upon interaction with glyco-conjugate complexes. These are abundantly found in plants, animals and many other species and are known to agglutinate various blood groups of erythrocytes. Further, due to the unique carbohydrate recognition property, lectins have been extensively used in many biological functions that make use of protein-carbohydrate recognition like detection, isolation and characterization of glycoconjugates, histochemistry of cells and tissues, tumor cell recognition and many more. In this review, we have summarized the immunomodulatory effects of plant lectins and their effects against diseases, including antimicrobial action. We found that many plant lectins mediate its microbicidal activity by triggering host immune responses that result in the release of several cytokines followed by activation of effector mechanism. Moreover, certain lectins also enhance the phagocytic activity of macrophages during microbial infections. Lectins along with heat killed microbes can act as vaccine to provide long term protection from deadly microbes. Hence, lectin based therapy can be used as a better substitute to fight microbial diseases efficiently in future.


title: Current perspectives on the diagnosis and epidemiology of Mycoplasma hyopneumoniae infection

text: Abstract Mycoplasma hyopneumoniae is the principal aetiological agent of enzootic pneumonia (EP), a chronic respiratory disease that affects mainly finishing pigs. Although major efforts to control M. hyopneumoniae infection and its detrimental effects have been made, significant economic losses in pig production worldwide due to EP continue. M. hyopneumoniae is typically introduced into pig herds by the purchase of subclinically infected animals or, less frequently, through airborne transmission over short distances. Once in the herd, M. hyopneumoniae may be transmitted by direct contact from infected sows to their offspring or between pen mates. The ‘gold standard’ technique used to diagnose M. hyopneumoniae infection, bacteriological culture, is laborious and is seldom used routinely. Enzyme-linked immunosorbent assay and polymerase chain reaction detection methods, in addition to post-mortem inspection in the form of abattoir surveillance or field necropsy, are the techniques most frequently used to investigate the potential involvement of M. hyopneumoniae in porcine respiratory disease. Such techniques have been used to monitor the incidence of M. hyopneumoniae infection in herds both clinically and subclinically affected by EP, in vaccinated and non-vaccinated herds and under different production and management conditions. Differences in the clinical course of EP at farm level and in the efficacy of M. hyopneumoniae vaccination suggest that the transmission and virulence characteristics of different field isolates of M. hyopneumoniae may vary. This paper reviews the current state of knowledge of the epidemiology of M. hyopneumoniae infection including its transmission, infection and seroconversion dynamics and also compares the various epidemiological tools used to monitor EP.


title: Glycogen synthase kinase (GSK)-3 and the double-strand RNA-dependent kinase, PKR: When two kinases for the common good turn bad()

text: Glycogen synthase kinase (GSK)-3α/β and the double-stranded RNA-dependent kinase PKR are two sentinel kinases that carry-out multiple similar yet distinct functions in both the cytosol and the nucleus. While these kinases belong to separate signal transduction cascades, they demonstrate an uncanny propensity to regulate many of the same proteins either through direct phosphorylation or by altering transcription/translation, including: c-MYC, NF-κB, p53 and TAU, as well as each another. A significant number of studies centered on the GSK3 kinases have led to the identification of the GSK3 interactome and a number of substrates, which link GSK3 activity to metabolic control, translation, RNA splicing, ribosome biogenesis, cellular division, DNA repair and stress/inflammatory signaling. Interestingly, many of these same pathways and processes are controlled by PKR, but unlike the GSK3 kinases, a clear picture of proteins interacting with PKR and a complete listing of its substrates is still missing. In this review, we take a detailed look at what is known about the PKR and GSK3 kinases, how these kinases interact to influence common cellular processes (innate immunity, alternative splicing, translation, glucose metabolism) and how aberrant activation of these kinases leads to diseases such as Alzheimer's disease (AD), diabetes mellitus (DM) and cancer.


title: Biosynthesis of anti-HCV compounds using thermophilic microorganisms

text: Abstract This work describes the application of thermophilic microorganisms for obtaining 6-halogenated purine nucleosides. Biosynthesis of 6-chloropurine-2′-deoxyriboside and 6-chloropurine riboside was achieved by Geobacillus stearothermophilus CECT 43 with a conversion of 90% and 68%, respectively. Furthermore, the selected microorganism was satisfactorily stabilized by immobilization in an agarose matrix. This biocatalyst can be reused at least 70 times without significant loss of activity, obtaining 379mg/L of 6-chloropurine-2′-deoxyriboside. The obtained compounds can be used as antiviral agents.


title: Molecular characterization of variant infectious bronchitis virus in China, 2019: Implications for control programmes

text: Infectious bronchitis virus (IBV), an ongoing emergence enveloped virus with a single‐stranded positive‐sense RNA genome, belongs to the Gammacoronavirus genus in the Coronaviridae family. IBV‐associated tracheitis, nephritis, salpingitis, proventriculitis and egg drop have caused devastating economic losses to poultry industry worldwide. Since the end of 2018, a remarkably increasing number of commercial broilers and layers, vaccinated or not, were infected with IBV in China. Here, we described two IB outbreaks with severe respiratory system or kidney injury in IBV‐vaccinated commercial poultry farms in central China. Other possible causative viral pathogens, including avian influenza virus (AIV), Newcastle disease virus (NDV) and Kedah fatal kidney syndrome virus (KFKSV), were excluded by reverse transcription‐polymerase chain reaction (RT‐PCR), and three virulent IBV strains, HeN‐1/China/2019, HeN‐2/China/2019 and HeN‐101/China/2019, were identified. Although the gross pathologic appearance of these two IB outbreaks was different, the newly identified IBV strains were all closely related to the ck/China/I0529/17 strain and grouped into GI‐19 genotype clade based on the sequencing and phylogenetic analysis of the complete S1 genes. Moreover, there are still some evolutionary distance between the newly identified IBV strains, HeN‐101/China/2019 in particular, and other GI‐19 strains, suggesting that Chinese IBV strains constantly emerge and evolve towards different directions. In conclusion, this study provided an insight of the recently emerging IBV outbreaks in IBV‐vaccinated commercial poultry farms and identified the genetic characteristics of three virulent GI‐19 IBV strains, which shows the need to carry out proper preventive measures and control strategies.


title: Synthesis and antitumor activity against HepG-2, PC-3, and HCT-116 cells of some naphthyridine and pyranopyridinecarbonitrile derivatives

text: A series of substituted and fused heterocyclic derivatives 2–17 were synthesized using 3,5-bis(4-methoxybenzylidene)-1-propylpiperidin-4-one (1) as starting material. Treatment of 1 with malononitrile or semicarbazide afforded compounds 2 and 3, respectively. Condensation of 1 with ethyl cyanoacetate afforded naphthyridine-3-carbonitrile derivative 4, which reacted with phosphorus pentachloride and phosphoryl chloride to give chloro derivative 5. Treatment of 5 with thiosemicarbazide afforded compound 6. The reaction of 1 with malononitrile gave cyano aminopyrane derivative 7 which was condensed with pyromellitic dianhydride, phthalic anhydride, succinic anhydride, or morpholine in glacial acetic acid to obtain imide derivatives 8–11. Additionally, the reaction of 7 with aromatic aldehydes gave derivatives 12a–12c. Acetylation of 7 with acetic anhydride in boiling acetic acid gave N-acetyl derivative 13 which was cyclized to pyridine derivative 14 by refluxing in dioxane in the presence of triethylamine. Treatment of 7 with hydrazine hydrate gave pyrazolo derivative 15. Finally, the reaction of 7 with triethyl orthoformate in the presence of acetic anhydride gave formimidate 16 which was treated with hydrazine hydrate to form N-amino derivative 17. Some of the synthesized compounds were examined in vitro for their antitumor activity against HepG-2, PC-3, and HCT-116 human carcinoma cell lines using MTT assay.


Droplet evacuating strategy for simulated coughing during aerosol generating procedures in COVID-19 patients


title: Resurgence of scarlet fever in China: a 13-year population-based surveillance study

text: Summary Background A re-emergence of scarlet fever has been noted in Hong Kong, South Korea, and England, UK, since 2008. China also had a sudden increase in the incidence of the disease in 2011. In this study, we aimed to assess the epidemiological changes before and after the upsurge. We also aimed to explore the reasons for the upsurge in disease in 2011, the epidemiological factors that contributed to it, and assess how these could be managed to prevent future epidemics. Methods In this observational study, we extracted the epidemiological data for all cases of scarlet fever between 2004 and 2016 in China from the Chinese Public Health Science Data Center, the official website of National Health Commission of the People's Republic of China, and the National Notifiable Infectious Disease Surveillance System. These data had been collected from 31 provinces and regions in China and included geographical, seasonal, and patient demographic information. We used descriptive statistical methods and joinpoint regression to examine the spatiotemporal patterns and annual percentage change in incidence of the upsurge of disease across China. Findings Between Jan 1, 2004, and Dec 31, 2016, 502 723 cases of scarlet fever, with ten fatalities, were reported in China, resulting in an annualised average incidence of 2·8807 per 100 000 people. The annual average incidence increased from 1·457 per 100 000 people in 2004 to 4·7638 per 100 000 people in 2011 (incidence rate ratio [IRR] 3·27, 95% CI 3·22–3·32; p<0·0001), peaking in 2015 (5·0092 per 100 000 people). The annual incidence after the 2011 upsurge of scarlet fever, between 2011 and 2016, was twice the average annual incidence reported between 2004 and 2010 (4·0125 vs 1·9105 per 100 000 people; IRR 2·07, 95% CI 2·06–2·09; p<0·0001). Most cases were distributed in the north, northeast, and northwest of the country. Semi-annual patterns were observed in May–June and November–December. The median age at onset of disease was 6 years, with the annual highest incidence observed in children aged 6 years (49·4675 per 100 000 people). The incidence among boys and men was 1·54 greater than that among girls and women before the upsurge, and 1·51 times greater after the upsurge (p<0·0001 for both). The median time from disease onset to reporting of the disease was shorter after the upsurge in disease than before (3 days vs 4 days; p=0·001). Interpretation To our knowledge, this is the largest epidemiological study of scarlet fever worldwide. The patterns of infection across the country were similar before and after the 2011 upsurge, but the incidence of disease was substantially higher after 2011. Prevention and control strategies being implemented in response to this threat include improving disease surveillance and emergency response systems. In particular, the school absenteeism and symptom monitoring and early-warning system will contribute to the early diagnosis and report of the scarlet fever. This approach will help combat scarlet fever and other childhood infectious diseases in China. Funding National Key R&D Plan of China Science and key epidemiological disciplines of Zhejiang Provincial Health of China.


Image and structure quantitative analysis


title: Reducing agents affect inhibitory activities of compounds: Results from Multiple Drug Targets

text: High-throughput screening (HTS) of large compound libraries has become a commonly used method for the identification of drug leads, and non-physiological reducing agents have been widely used for HTS. However, a comparison of the difference in the HTS results based on the choice of reducing agent used and potency comparisons of selected inhibitors has not been done with the physiological reducing agent, reduced glutathione (GSH). Here, we compared the effects of three reducing agents: dithiothreitol (DTT), β-mercaptoethanol (β-MCE), and tris-(2-carboxyethyl)-phosphine (TCEP), in addition to GSH, against three drug target proteins. Approximately 100,000 compounds were computationally screened for each target protein, and experimental testing of high scoring compounds (~560 compounds) with the four reducing agents surprisingly produced many non-overlapping hits. More importantly, we find that various reducing agents alter inhibitor potency (IC(50)) from ~10 µM with one reducing agent to complete loss (IC(50) > 200 µM) of inhibitory activity with another reducing agent. Therefore, the choice of reducing agent in a HTS is critical as this may lead to the pursuit of falsely identified active compounds or failure to identify the true active compounds. We demonstrate the feasibility of using GSH for in vitro HTS assays with these three target enzymes.


Comment on “Practice Recommendations for Risk-Adapted Head and Neck Cancer Radiotherapy During the COVID-19 Pandemic: An ASTRO-ESTRO Consensus Statement”


title: The SARS-CoV-2 receptor, Angiotensin converting enzyme 2 (ACE2) is required for human endometrial stromal cell decidualization

text: STUDY QUESTION Is SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE 2) expressed in the human endometrium during the menstrual cycle, and does it participate in endometrial decidualization? SUMMARY ANSWER ACE2 protein is highly expressed in human endometrial stromal cells during the secretory phase and is essential for human endometrial stromal cell decidualization. WHAT IS KNOWN ALREADY ACE2 is expressed in numerous human tissues including the lungs, heart, intestine, kidneys and placenta. ACE2 is also the receptor by which SARS-CoV-2 enters human cells. STUDY DESIGN, SIZE, DURATION Proliferative (n = 9) and secretory (n = 6) phase endometrium biopsies from healthy reproductive-age women and primary human endometrial stromal cells from proliferative phase endometrium were used in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS ACE2 expression and localization were examined by qRT-PCR, Western blot, and immunofluorescence in both human endometrial samples and mouse uterine tissue. The effect of ACE2 knockdown on morphological and molecular changes of human endometrial stromal cell decidualization were assessed. Ovariectomized mice were treated with estrogen or progesterone to determine the effects of these hormones on ACE2 expression. MAIN RESULTS AND THE ROLE OF CHANCE In human tissue, ACE2 protein is expressed in both endometrial epithelial and stromal cells in the proliferative phase of the menstrual cycle, and expression increases in stromal cells in the secretory phase. The ACE2 mRNA (P < 0.0001) and protein abundance increased during primary human endometrial stromal cell (HESC) decidualization. HESCs transfected with ACE2-targeting siRNA were less able to decidualize than controls, as evidenced by a lack of morphology change and lower expression of the decidualization markers PRL and IGFBP1 (P < 0.05). In mice during pregnancy, ACE2 protein was expressed in uterine epithelial and stromal cells increased through day six of pregnancy. Finally, progesterone induced expression of Ace2 mRNA in mouse uteri more than vehicle or estrogen (P < 0.05). LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Experiments assessing the function of ACE2 in human endometrial stromal cell decidualization were in vitro. Whether SARS-CoV-2 can enter human endometrial stromal cells and affect decidualization have not been assessed. WIDER IMPLICATIONS OF THE FINDINGS Expression of ACE2 in the endometrium allow SARS-CoV-2 to enter endometrial epithelial and stromal cells, which could impair in vivo decidualization, embryo implantation, and placentation. If so, women with COVID-19 may be at increased risk of early pregnancy loss. STUDY FUNDINGS/COMPETING INTEREST(S) This study was supported by National Institutes of Health / National Institute of Child Health and Human Development grants R01HD065435 and R00HD080742 to RK and Washington University School of Medicine start-up funds to RK. The authors declare that they have no conflicts of interest.


title: Biosynthesis of acetylacetone inspired by its biodegradation

text: BACKGROUND: Acetylacetone is a commercially bulk chemical with diverse applications. However, the traditional manufacturing methods suffer from many drawbacks such as multiple steps, harsh conditions, low yield, and environmental problems, which hamper further applications of petrochemical-based acetylacetone. Compared to conventional chemical methods, biosynthetic methods possess advantages such as being eco-friendly, and having mild conditions, high selectivity and low potential costs. It is urgent to develop biosynthetic route for acetylacetone to avoid the present problems. RESULTS: The biosynthetic pathway of acetylacetone was constructed by reversing its biodegradation route, and the acetylacetone was successfully produced by engineered Escherichia coli (E. coli) by overexpression of acetylacetone-cleaving enzyme (Dke1) from Acinetobacter johnsonii. Several promising amino acid residues were selected for enzyme improvement based on sequence alignment and structure analysis, and the acetylacetone production was improved by site-directed mutagenesis of Dke1. The double-mutant (K15Q/A60D) strain presented the highest acetylacetone-producing capacity which is 3.6-fold higher than that of the wild-type protein. Finally, the strain accumulated 556.3 ± 15.2 mg/L acetylacetone in fed-batch fermentation under anaerobic conditions. CONCLUSIONS: This study presents the first intuitive biosynthetic pathway for acetylacetone inspired by its biodegradation, and shows the potential for large-scale production.


title: Immune responses elicited by bacterial minicells capable of simultaneous DNA and protein antigen delivery

text: Recent events surrounding emerging infectious diseases, bioterrorism and increasing multidrug antibiotic resistance in bacteria have drastically increased current needs for effective vaccines. Many years of study have shown that live, attenuated pathogens are often more effective at delivering heterologous protein or DNA to induce protective immune responses. However, these vaccine carriers have inherent safety concerns that have limited their development and their use in many patient populations. Studies using nonliving delivery mechanisms have shown that providing both protein antigen and DNA encoding the antigen to an individual induces an improved, more protective immune response but rarely, if ever, are both delivered simultaneously. Here, non-replicating bacterial minicells derived from a commensal E. coli strain are shown to effectively induce antigen-specific immune responses after simultaneous protein and DNA delivery. These data demonstrate the potential use of achromosomal bacterial minicells as a vaccine carrier.


title: COVID‐19 and Finance: Market Developments So Far and Potential Impacts on the Financial Sector and Centres

text: This paper offers an informed commentary on the actual and potential impacts of the pandemic on financial markets, sector and centres, grounded in literature on financial centres, the state‐finance nexus, and trends affecting the landscape of finance since the global financial crisis. We expect a slowdown in new financial regulation, continued firm‐level consolidation, and a continued rise of business services related to finance. The application of new financial technologies is likely to accelerate, affecting retail banking in particular, but will not necessarily be led by FinTech firms. Local and regional financial centres are likely to face larger challenges than leading international centres. As the panic and partial recovery in financial markets in March and April 2020 highlighted the significance of the international monetary hierarchy, with the US$ in the lead, a radical shift of financial power to Asia seems unlikely.


title: Comparative Analysis of PCR–Electrospray Ionization/Mass Spectrometry (MS) and MALDI-TOF/MS for the Identification of Bacteria and Yeast from Positive Blood Culture Bottles

text: BACKGROUND: Emerging technologies for rapid identification of microbes demonstrate a shift from traditional biochemical and molecular testing algorithms toward methods using mass spectrometry (MS) for the semiquantitative analysis of microbial proteins and genetic elements. This study was performed to assess the diagnostic accuracy of 2 such technologies, PCR–electrospray ionization (ESI)/MS and MALDI-TOF/MS, with respect to phenotypic and biochemical profiling as a reference standard method. A positive challenge set of blood culture bottles was used to compare PCR-ESI/MS and MALDI-TOF/MS performance on a matched set of samples. METHODS: We performed characterization of bloodstream infections from blood cultures using the Ibis T5000 PCR-ESI/MS and the Bruker MALDI Biotyper 2.0 (MALDI-TOF/MS) platforms for microbial identification. Diagnostic accuracy was determined by independent comparison of each method to phenotypic and biochemical characterization with Vitek2 analysis as the reference standard identification. RESULTS: The diagnostic accuracy, represented as positive agreement, at the genus level was 0.965 (0.930–0.984) for PCR-ESI/MS and 0.969 (0.935–0.987) for MALDI-TOF/MS, and at the species level was 0.952 (0.912–0.974) with PCR-ESI/MS and 0.943 (0.902–0.968) for MALDI-TOF/MS. No statistically significant difference was found between PCR-ESI/MS and MALDI-TOF/MS in the ability to rapidly identify microorganisms isolated from blood culture. CONCLUSIONS: Our results demonstrate that PCR-ESI/MS and MALDI-TOF/MS are equivalent in their ability to characterize bloodstream infections with respect to the reference standard, and highlight key differences in the methods that allow for each method to have a unique niche as a tool for rapid identification of microbes in blood cultures.


Letter to the Editor: Two Perspectives on the COVID-19 Pandemic Nobody Is Talking About—and It's Costing Lives


title: The Toxic Effects of Subjective Wellbeing and Potential Tonics

text: The paper offers a provocation to the geographies of health in relation to one of our governing concepts, that of wellbeing. The paper brings together government survey data from the United Kingdom with other published research into a critical argument that the dominant ways of conceptualising and practising subjective wellbeing have become toxic and harmful to wellbeing outcomes. The paper argues that a ‘hyper-individualised and thwarted self’ and ‘supermarket model’ of social resources for individual wellbeing underpins the contemporary dominant understanding of subjective wellbeing. This approach neglects wider spatial and temporal considerations such as inequality, inter-generationality and sustainability, and the rise of wellbeing as a technology of soft capitalism. The paper discusses the potential for relational approaches from the social sciences to provide a more ‘wholesome tonic’ to current understandings of subjective wellbeing that might rehabilitate its capability to do helpful rather than harmful work and argues for an ethical obligation to sustain critical engagement.


title: Emergence of SARS-CoV-2 through Recombination and Strong Purifying Selection

text: COVID-19 has become a global pandemic caused by a novel coronavirus SARS-CoV-2. Understanding the origins of SARS-CoV-2 is critical for deterring future zoonosis and for drug discovery and vaccine development. We show evidence of strong purifying selection around the receptor binding motif (RBM) in the spike gene and in other genes among bat, pangolin and human coronaviruses, indicating similar strong evolutionary constraints in different host species. We also demonstrate that SARS-CoV-2’s entire RBM was introduced through recombination with coronaviruses from pangolins, possibly a critical step in the evolution of SARS-CoV-2’s ability to infect humans. Similar purifying selection in different host species and frequent recombination among coronaviruses suggest a common evolutionary mechanism that could lead to new emerging human coronaviruses. One Sentence Summary Extensive Recombination and Strong Purifying Selection among coronaviruses from different hosts facilitate the emergence of SARS-CoV-2