title: Acute Myopericarditis caused by Human Metapneumovirus

text: Human metapneumovirus is known to be similar to respiratory syncytial virus. Because of an incomplete protective immune response to new genotypes, re-infection occurs frequently, especially in the elderly. However, the clinical manifestations of human metapneumovirus need to be further characterized in adults. A 73-year-old woman presented to the emergency room with acute dyspnea, chest discomfort and influenza-like illness. The patient was diagnosed with human metapneumovirus infection, complicated by pneumonia and myopericarditis. With supportive care including oxygen supplementation, the patient recovered completely without any serious sequelae. Human metapneumovirus infection may contribute to the development of cardiovascular manifestations, particularly in the elderly population.


title: First comes the A, then the B: what we learned from the COVID-19 outbreak()

text: The SARS-CoV-2 epidemic, which has spread to many countries around the world, has hit Europe particularly hard. From our point of view, in a rural emergency department (with an annual patient census of around 25,000) in northeastern Italy, it is necessary to preserve the hospital and prevent it from becoming an outbreak of infection. In our experience, we reevaluated the negative predictive value of lung ultrasound to rule out lung involvement. Since severe acute respiratory failure appears to be the leading cause of death for COVID-19 patients, it is essential to focus on this clinical feature. We currently believe that a patient suspected of COVID-19, if he has a normal ultrasound examination (a so-called "A-profile"), can be discharged home to continue isolation and be treated without being hospitalized.


title: This could be the start of something big—20 years since the identification of bats as the natural host of Hendra virus

text: Hendra virus was first described in 1994 in Australia, causally associated with a cluster of fatal equine and human cases at a thoroughbred racing stable in the Brisbane suburb of Hendra. This year marks the twentieth anniversary of the identification of pteropid bats (flying-foxes) as the natural host of the virus, and it is timely to reflect on a pivotal meeting of an eclectic group of scientists in that process. They included animal and public health experts, environmental scientists, veterinary and horse industry representatives, and wildlife experts. The task was to review and prioritise wildlife surveillance seeking the origin of the previously unknown virus. The group determined that the likely reservoir must occur in disparate locations, and be capable of moving between locations, or exist in continuous, overlapping populations spanning multiple locations. Flying-foxes were considered to be a more probable source of the novel virus than birds. Within weeks, antibodies were detected in several species of flying-fox, and the virus was subsequently isolated. While the identification of the natural host of Hendra virus within 18 months of its description was remarkable in itself, a broader legacy followed. In the subsequent years, a suite of zoonotic viruses including Australian bat lyssavirus, Nipah virus, SARS coronavirus, and Ebola and Marburg viruses have been detected in bats. Bats are now the “go to” taxa for novel viruses. History has repeatedly demonstrated that knowledge begets knowledge. This simple notion of bringing a diverse group of people together in an environment of mutual respect reinforced this principle and proves that the sum is often so much more powerful than the parts.


title: Time Course of MERS-CoV Infection and Immunity in Dromedary Camels

text: Knowledge about immunity to Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels is essential for infection control and vaccination. A longitudinal study of 11 dam–calf pairs showed that calves lose maternal MERS-CoV antibodies 5–6 months postparturition and are left susceptible to infection, indicating a short window of opportunity for vaccination.


title: The Inhibition of HIV-1 Entry Imposed by Interferon Inducible Transmembrane Proteins Is Independent of Co-Receptor Usage

text: Interferon inducible transmembrane proteins (IFITMs) are one of several IFN-stimulated genes (ISGs) that restrict entry of enveloped viruses, including flaviviruses, filoviruses and retroviruses. It has been recently reported that in U87 glioblastoma cells IFITM proteins inhibit HIV-1 entry in a co-receptor-dependent manner, that is, IFITM1 is more inhibitory on CCR5 tropic HIV-1 whereas IFITM2/3 confers a greater suppression of CXCR4 counterparts. However, how entry of HIV-1 with distinct co-receptor usage is modulated by different IFITM orthologs in physiologically relevant CD4(+) T cells and monocytes/macrophages has not been investigated in detail. Here, we report that overexpression of IFITM1, 2 and 3 in human CD4(+) HuT78 cells, SupT1 cells, monocytic THP-1 cells and U87 cells expressing CD4 and co-receptor CCR5 or CXCR4, suppressed entry of CXCR4 tropic viruses NL4.3 and HXB2, CCR5 tropic viruses AD8 and JRFL, dual tropic 89.6 virus, as well as a panel of 32 transmitted founder (T/F) viruses, with a consistent order of potency, that is, IFITM3 > IFITM2 > IFITM1. Consistent with previous reports, we found that some CCR5-using HIV-1 isolates, such as AD8 and JRFL, were relatively resistant to inhibition by IFITM2 and IFITM3, although the effect can be cell-type dependent. However, in no case have we observed that IFITM1 had a stronger inhibition on entry of any HIV-1 strains tested, including those of CCR5-using T/Fs. We knocked down the endogenous IFITMs in peripheral blood mononuclear cells (PBMCs) and purified CD4(+) T cells and observed that, while this treatment did greatly enhance the multiple-round of HIV-1 replication but had modest effect to rescue the single-round HIV-1 infection, reinforcing our previous conclusion that the predominant effect of IFITMs on HIV-1 infection is in viral producer cells, rather than in target cells to block viral entry. Overall, our results argue against the idea that IFITM proteins distinguish co-receptors CCR5 and CXCR4 to inhibit entry but emphasize that the predominant role of IFITMs on HIV-1 is in producer cells that intrinsically impair the viral infectivity.


Medicine in the time of corona: Fundamental molecular research is “essential”


title: Respiratory viruses in individuals with a high frequency of animal exposure in southern and highland Vietnam

text: Active surveillance for zoonotic respiratory viruses is essential to inform the development of appropriate interventions and outbreak responses. Here we target individuals with a high frequency of animal exposure in Vietnam. Three‐year community‐based surveillance was conducted in Vietnam during 2013‐2016. We enrolled a total of 581 individuals (animal‐raising farmers, slaughterers, animal‐health workers, and rat traders), and utilized reverse transcription‐polymerase chain reaction to detect 15 common respiratory viruses in pooled nasal‐throat swabs collected at baseline or acute respiratory disease episodes. A respiratory virus was detected in 7.9% (58 of 732) of baseline samples, and 17.7% (136 of 770) of disease episode samples (P < .001), with enteroviruses (EVs), rhinoviruses and influenza A virus being the predominant viruses detected. There were temporal and spatial fluctuations in the frequencies of the detected viruses over the study period, for example, EVs and influenza A viruses were more often detected during rainy seasons. We reported the detection of common respiratory viruses in individuals with a high frequency of animal exposure in Vietnam, an emerging infectious disease hotspot. The results show the value of baseline/control sampling in delineating the causative relationships and have revealed important insights into the ecological aspects of EVs, rhinoviruses and influenza A and their contributions to the burden posed by respiratory infections in Vietnam.


“Water, water, everywhere”: a challenge to ventilators in the COVID-19 pandemic


docid: dcihyqhs

title: Transitioning undergraduate research from wet lab to the virtual in the wake of a pandemic

text: The COVID‐19 outbreak has shut down universities, and teaching faculty have moved to online classrooms to address students. This change has been supported by numerous online teaching tools and development of virtual classrooms. Undergraduate research programs in the sciences and biochemistry/molecular biology teaching labs, however, are affected by this change due to inaccessibility to laboratories. This communication outlines three concepts to engage undergraduate students who are involved in research: (a) remote data analysis, (b) literature review and science writing, and (c) science journal clubs.


title: Infectious vaccine-derived rubella viruses emerge, persist, and evolve in cutaneous granulomas of children with primary immunodeficiencies

text: Rubella viruses (RV) have been found in an association with granulomas in children with primary immune deficiencies (PID). Here, we report the recovery and characterization of infectious immunodeficiency-related vaccine-derived rubella viruses (iVDRV) from diagnostic skin biopsies of four patients. Sequence evolution within PID hosts was studied by comparison of the complete genomic sequences of the iVDRVs with the genome of the vaccine virus RA27/3. The degree of divergence of each iVDRV correlated with the duration of persistence indicating continuous intrahost evolution. The evolution rates for synonymous and nonsynonymous substitutions were estimated to be 5.7 x 10(−3) subs/site/year and 8.9 x 10(−4) subs/site/year, respectively. Mutational spectra and signatures indicated a major role for APOBEC cytidine deaminases and a secondary role for ADAR adenosine deaminases in generating diversity of iVDRVs. The distributions of mutations across the genes and 3D hotspots for amino acid substitutions in the E1 glycoprotein identified regions that may be under positive selective pressure. Quasispecies diversity was higher in granulomas than in recovered infectious iVDRVs. Growth properties of iVDRVs were assessed in WI-38 fibroblast cultures. None of the iVDRV isolates showed complete reversion to wild type phenotype but the replicative and persistence characteristics of iVDRVs were different from those of the RA27/3 vaccine strain, making predictions of iVDRV transmissibility and teratogenicity difficult. However, detection of iVDRV RNA in nasopharyngeal specimen and poor neutralization of some iVDRV strains by sera from vaccinated persons suggests possible public health risks associated with iVDRV carriers. Detection of IgM antibody to RV in sera of two out of three patients may be a marker of virus persistence, potentially useful for identifying patients with iVDRV before development of lesions. Studies of the evolutionary dynamics of iVDRV during persistence will contribute to development of infection control strategies and antiviral therapies.


title: Contemporary management of severe influenza disease in the intensive care unit

text: Abstract Despite continued efforts to optimize vaccination composition, severe influenza disease requiring intensive care unit (ICU) admission remains a clinical issue. Influenza epidemics and pandemics worldwide continue to challenge clinicians with managing infected patients requiring ICU care. While routine use of antiviral therapy is deployed in ambulatory outpatients, their use in the ICU in patients with hypoxemic respiratory failure is less well established. Additionally, these therapies primarily target the neuraminidase protein, while contemporary research is increasingly demonstrating potential therapeutic benefits of targeting the hemagglutinin protein. These data have given rise to a growing interest in the use of immune modulating therapies for treatment of severe influenza. Additionally, pandemic outbreaks have revealed the growing need for salvage management, wherein lies the potential role for venovenous extracorporeal membrane oxygenation therapy in refractory respiratory failure. In this report, we review the contemporary ICU care of the severe influenza patient.


title: Comparison of electron microscopy, ELISA, real time RT-PCR and insulated isothermal RT-PCR for the detection of Rotavirus group A (RVA) in feces of different animal species

text: Abstract There is no gold standard for detection of Rotavirus Group A (RVA), one of the main causes of diarrhea in neonatal animals. Sensitive and specific real-time RT-PCR (rtRT-PCR) assays are available for RVA but require submission of the clinical samples to diagnostic laboratories. Patient-side immunoassays for RVA protein detection have shown variable results, particularly with samples from unintended species. A sensitive and specific test for detection of RVA on the farm would facilitate rapid management decisions. The insulated isothermal RT-PCR (RT-iiPCR) assay works in a portable machine to allow sensitive and specific on-site testing. The aim of this investigation was to evaluate a commercially available RT-iiPCR assay for RVA detection in feces from different animal species. This assay was compared to an in-house rtRT-PCR assay and a commercially available rtRT-PCR kit, as well as an ELISA and EM for RVA detection. All three PCR assays targeted the well-conserved NSP5 gene. Clinical fecal samples from 108 diarrheic animals (mainly cattle and horses) were tested. The percentage of positive samples by ELISA, EM, in-house rtRT-PCR, commercial rtRT-PCR, and RT-iiPCR was 29.4%, 31%, 36.7%, 51.4%, 56.9%, respectively. The agreement between different assays was high (81.3–100%) in samples containing high viral loads. The sensitivity of the RT-iiPCR assay appeared to be higher than the commercially available rtRT-PCR assay, with a limit of detection (95% confidence index) of 3–4 copies of in vitro transcribed dsRNA. In conclusion, the user-friendly, field-deployable RT-iiPCR system holds substantial promise for on-site detection of RVA.


title: Evaluation of farm-level parameters derived from animal movements for use in risk-based surveillance programmes of cattle in Switzerland

text: BACKGROUND: This study focused on the descriptive analysis of cattle movements and farm-level parameters derived from cattle movements, which are considered to be generically suitable for risk-based surveillance systems in Switzerland for diseases where animal movements constitute an important risk pathway. METHODS: A framework was developed to select farms for surveillance based on a risk score summarizing 5 parameters. The proposed framework was validated using data from the bovine viral diarrhoea (BVD) surveillance programme in 2013. RESULTS: A cumulative score was calculated per farm, including the following parameters; the maximum monthly ingoing contact chain (in 2012), the average number of animals per incoming movement, use of mixed alpine pastures and the number of weeks in 2012 a farm had movements registered. The final score for the farm depended on the distribution of the parameters. Different cut offs; 50, 90, 95 and 99 %, were explored. The final scores ranged between 0 and 5. Validation of the scores against results from the BVD surveillance programme 2013 gave promising results for setting the cut off for each of the five selected farm level criteria at the 50th percentile. Restricting testing to farms with a score ≥ 2 would have resulted in the same number of detected BVD positive farms as testing all farms, i.e., the outcome of the 2013 surveillance programme could have been reached with a smaller survey. CONCLUSIONS: The seasonality and time dependency of the activity of single farms in the networks requires a careful assessment of the actual time period included to determine farm level criteria. However, selecting farms in the sample for risk-based surveillance can be optimized with the proposed scoring system. The system was validated using data from the BVD eradication program. The proposed method is a promising framework for the selection of farms according to the risk of infection based on animal movements.


title: Long Non-Coding RNAs Regulating Immunity in Insects

text: Recent advances in modern technology have led to the understanding that not all genetic information is coded into protein and that the genomes of each and every organism including insects produce non-coding RNAs that can control different biological processes. Among RNAs identified in the last decade, long non-coding RNAs (lncRNAs) represent a repertoire of a hidden layer of internal signals that can regulate gene expression in physiological, pathological, and immunological processes. Evidence shows the importance of lncRNAs in the regulation of host–pathogen interactions. In this review, an attempt has been made to view the role of lncRNAs regulating immune responses in insects.


title: Development of a highly sensitive, field operable biosensor for serological studies of Ebola virus in central Africa

text: Abstract We describe herein a newly developed optical immunosensor for detection of antibodies directed against antigens of the Ebola virus strains Zaire and Sudan. We employed a photo immobilization methodology based on a photoactivatable electrogenerated poly(pyrrole-benzophenone) film deposited upon an indium tin oxide (ITO) modified conductive surface fiber-optic. It was then linked to a biological receptor, Ebola virus antigen in this case, on the fiber tip through a light driven reaction. The photochemically modified optical fibers were tested as an immunosensor for detection of antibodies against Ebola virus, in animal and human sera, by use of a coupled chemiluminescent reaction. The immunosensor was tested for sensitivity, specificity, and compared to standard chemiluminescent ELISA under the same conditions. The analyte, anti-Ebola IgG, was detected at a low titer of 1:960,000 and 1:1,000,000 for subtypes Zaire and Sudan, respectively. While the same serum tested by ELISA was one order (24 times) less sensitive.


title: Welche Phytos gegen Husten?

text: Zur pflanzlichen Therapie von Kindern und Jugendlichen mit akuten Atemwegsinfekten liegen bisher nur wenige Studien vor. Beim Pädiatriekongress haben Experten ein Update gegeben.


title: Multiple Myeloma in the Time of COVID-19

text: We provide our recommendations (not evidence based) for managing multiple myeloma patients during the pandemic of COVID-19. We do not recommend therapy for smoldering myeloma patients (standard or high risk). Screening for COVID-19 should be done in all patients before therapy. For standard-risk patients, we recommend the following: ixazomib, lenalidomide, and dexamethasone (IRd) (preferred), cyclophosphamide lenalidomide and dexamethasone (CRd), daratumumab lenalidomide and dexamethasone (DRd), lenalidomide, bortezomib, and dexamethasone (RVd), or cyclophosphamide, bortezomib, and dexamethasone (CyBorD). For high-risk patients we recommend carfilzomib, lenalidomide, and dexamethasone (KRd) (preferred) or RVd. Decreasing the dose of dexamethasone to 20 mg and giving bortezomib subcutaneously once a week is recommended. We recommend delaying autologous stem cell transplant (ASCT), unless the patient has high-risk disease that is not responding well, or if the patient has plasma cell leukemia (PCL). Testing for COVID-19 should be done before ASCT. If a patient achieves a very good partial response or better, doses and frequency of drug administration can be modified. After 10–12 cycles, lenalidomide maintenance is recommended for standard-risk patients and bortezomib or ixazomib are recommended for high-risk patients. Daratumumab-based regimens are recommended for relapsed patients. Routine ASCT is not recommended for relapse during the epidemic unless the patient has an aggressive relapse or secondary PCL. Patients on current maintenance should continue their therapy.


title: Estimating the risk of COVID-19 death during the course of the outbreak in Korea, february–may 2020

text: Background: In Korea, a total of 10,840 confirmed cases of COVID-19 including 256 deaths have been recorded as of May 9, 2020. The time-delay adjusted case fatality risk (CFR) of COVID-19 in Korea is yet to be estimated. Methods: We obtained the daily series of confirmed cases and deaths in Korea reported prior to May 9, 2020. Using statistical methods, we estimated the time-delay adjusted risk for death from COVID-19 in Daegu, Gyeongsangbuk-do, other regions in Korea, as well as the entire country. Results: Our model-based crude CFR fitted the observed data well throughout the course of the epidemic except for the very early stage in Gyeongsangbuk-do; this was partially due to the reporting delay. Our estimates of the risk of death in Gyeongsangbuk-do reached 25.9% (95% Credible Interval (CrI): 19.6%–33.6%), 20.8% (95% CrI: 18.1%–24.0%) in Daegu, and 1.7% (95% CrI: 1.1%–2.5%) in other regions, whereas the national estimate was 10.2% (95% CrI: 9.0%–11.5%). Conclusions: The latest estimates of CFR of COVID-19 in Korea are considerably high, even with the early implementation of public health interventions including widespread testing, social distancing, and delayed school openings. Geographic differences in the CFR are likely influenced by clusters tied to hospitals and nursing homes.


title: Grief During the COVID-19 Pandemic: Considerations for Palliative Care Providers

text: Abstract The COVID-19 pandemic is anticipated to continue spreading widely across the globe throughout 2020. To mitigate the devastating impact of COVID-19, social distancing and visitor restrictions in healthcare facilities have been widely implemented. Such policies and practices, along with the direct impact of the spread of COVID-19, complicate issues of grief that are relevant to medical providers. We describe the relationship of the COVID-19 pandemic to anticipatory grief, disenfranchised grief, and complicated grief for individuals, families, and their providers. Further, we provide discussion regarding countering this grief through communication, advance care planning, and self-care practices. We provide resources for healthcare providers, in addition to calling on palliative care providers to consider their own role as a resource to other specialties during this public health emergency.


title: A Review of Functional Motifs Utilized by Viruses

text: Short linear motifs (SLiM) are short peptides that facilitate protein function and protein-protein interactions. Viruses utilize these motifs to enter into the host, interact with cellular proteins, or egress from host cells. Studying functional motifs may help to predict protein characteristics, interactions, or the putative cellular role of a protein. In virology, it may reveal aspects of the virus tropism and help find antiviral therapeutics. This review highlights the recent understanding of functional motifs utilized by viruses. Special attention was paid to the function of proteins harboring these motifs, and viruses encoding these proteins. The review highlights motifs involved in (i) immune response and post-translational modifications (e.g., ubiquitylation, SUMOylation or ISGylation); (ii) virus-host cell interactions, including virus attachment, entry, fusion, egress and nuclear trafficking; (iii) virulence and antiviral activities; (iv) virion structure; and (v) low-complexity regions (LCRs) or motifs enriched with residues (Xaa-rich motifs).


title: Complexation of thorium with pyridine monocarboxylate-N-oxides: Thermodynamic and computational studies

text: Abstract The feed wastes and waste water treatment plants are the major sources for the entry of N-oxides into the soils then to aquatic life. The complexation of actinides with potentially stable anthropogenic ligands facilitate the transportation and migration of the actinides from the source confinement. The present study describes the determination of thermodynamic parameters for the complexation of Th(IV) with the three isomeric pyridine monocarboxylates (PCNO) namely picolinic acid-N-oxide (PANO), nicotinic acid-N-oxide (NANO) and isonicotinic acid-N-oxide (IANO). The potentiometric and isothermal calorimetric titrations were carried out to determine the stability and enthalpy of the formations for all the Th(IV)-PCNO complexes. Th-PANO complexes are more stable than Th-NANO and Th-IANO complexes which can be attributed to chelate formation in the former complexes. Formation of all the Th-PCNO complexes are endothermic and are entropy driven. The geometries for all the predicted complexes are optimized the energies, bond distances and charges on individual atoms are obtained using TURBOMOLE software. The theoretical calculation corroborated the experimental determinations.


title: 13 Essentials of Pulmonology

text: Abstract Pulmonary complications are a major cause of perioperative morbidity in the pediatric population. Although preexisting pulmonary pathologic processes in children can present significant challenges to anesthetic delivery, a thorough assessment of the problem combined with meticulous anesthetic management allows most children to undergo surgical interventions without long-term adverse sequelae. Asthma, cystic fibrosis and sickle cell disease continue to pose challenges during anesthesiology. Consultation with a pediatric pulmonologist is indicated when appropriate for specific problems as outlined in this chapter; a team approach may markedly improve operative and postoperative outcomes.


title: The etiology, pathophysiology, and management of otitis media with effusion

text: Otitis media with effusion (OME) is a common and important condition that may result in developmental delay in children, and significant health care resources are devoted to its management. Newer techniques including polymerase chain reaction are implicating organisms not previously considered important in etiology. The role of gastroesophageal reflux as a cause of OME is likely to receive greater research attention. Regarding prevention, more is being learned about potentially modifiable risk factors such as environmental smoke, care outside the home, and breast feeding. Although immunization may to play a role in the future, existing evidence suggests that the general population of children should not be immunized in order to prevent OME. Several major studies have recently added to the understanding of epidemiology and management. Large trials in the United States, the Netherlands, and the UK suggest that OME is not an appropriate condition to include in a screening program. In addition, the advantages of early treatment with ventilation tubes over watchful waiting in terms of language development tend be modest and diminish by about 18 months. Treatment with hearing aids should be further evaluated. The search for effective medical management continues, and better ways are being identified of targeting interventions to those children with OME who are most likely to benefit.


title: Identified Transmission Dynamics of Middle East Respiratory Syndrome Coronavirus Infection During an Outbreak: Implications of an Overcrowded Emergency Department

text: A total 130 cases of Middle East respiratory syndrome coronavirus were identified during a large hospital outbreak in Saudi Arabia; 87 patients and 43 healthcare workers. The majority (80%) of transmission was healthcare-acquired (HAI) infection, with 4 generations of HAI transmission. The emergency department was the main location of exposure.


title: Test sensitivity is secondary to frequency and turnaround time for COVID-19 surveillance

text: The COVID-19 pandemic has created a public health crisis. Because SARS-CoV-2 can spread from individuals with pre-symptomatic, symptomatic, and asymptomatic infections, the re-opening of societies and the control of virus spread will be facilitated by robust surveillance, for which virus testing will often be central. After infection, individuals undergo a period of incubation during which viral titers are usually too low to detect, followed by an exponential growth of virus, leading to a peak viral load and infectiousness, and ending with declining viral levels and clearance. Given the pattern of viral load kinetics, we model surveillance effectiveness considering test sensitivities, frequency, and sample-to-answer reporting time. These results demonstrate that effective surveillance, including time to first detection and outbreak control, depends largely on frequency of testing and the speed of reporting, and is only marginally improved by high test sensitivity. We therefore conclude that surveillance should prioritize accessibility, frequency, and sample-to-answer time; analytical limits of detection should be secondary.


title: Communicating uncertainty - how Australian television reported H1N1 risk in 2009: a content analysis

text: BACKGROUND: Health officials face particular challenges in communicating with the public about emerging infectious diseases of unknown severity such as the 2009 H1N1(swine 'flu) pandemic (pH1N1). Statements intended to create awareness and convey the seriousness of infectious disease threats can draw accusations of scare-mongering, while officials can be accused of complacency if such statements are not made. In these communication contexts, news journalists, often reliant on official sources to understand issues are pivotal in selecting and emphasising aspects of official discourse deemed sufficiently newsworthy to present to the public. This paper presents a case-study of news communication regarding the emergence of pH1N1. METHODS: We conducted a content analysis of all television news items about pH1N1. We examined news and current affairs items broadcast on 5 free-to-air Sydney television channels between April 25 2009 (the first report) and October 9 (prior to the vaccine release) for statements about [1] the seriousness of the disease [2] how the public could minimise contagion [3] government responses to emerging information. RESULTS: pH1N1 was the leading health story for eight of 24 weeks and was in the top 5 for 20 weeks. 353 news items were identified, yielding 3086 statements for analysis, with 63.4% related to the seriousness of the situation, 12.9% providing advice for viewers and 23.6% involving assurances from government. Coverage focused on infection/mortality rates, the spread of the virus, the need for public calm, the vulnerability of particular groups, direct and indirect advice for viewers, and government reassurances about effective management. CONCLUSIONS: Overall, the reporting of 2009 pH1N1 in Sydney, Australia was generally non-alarmist, while conveying that pH1N1 was potentially serious. Daily infection rate tallies and commentary on changes in the pandemic alert level were seldom contextualised to assist viewers in understanding personal relevance. Suggestions are made about how future reporting of emerging infectious diseases could be enhanced.


title: Chapter 7 HHV-6 and Multiple Sclerosis

text: Multiple sclerosis (MS) is an inflammatory demyelinating disease affecting the central nervous system, thought to be an autoimmune disease mediated by autoreactive lymphocytes. The pathogenesis of MS is multifactorial and is thought to be triggered by multiple environmental factors in genetically susceptible individuals. Viruses have long been postulated as potential environmental triggers in MS, and there is increasing evidence of a link between viruses and MS. Some of the most compelling data have been found in human herpesvirus 6 (HHV-6) research. HHV-6 is a ubiquitous, neurotropic herpesvirus; HHV-6 DNA has been found in MS plaques compared to healthy brain tissue. Studies have also shown that MS patients have higher viral titers and higher DNA detection in serum and CSF compared to controls, and that the virus seems to be more actively replicating in MS patients. Potential mechanisms for HHV-6 leading to autoimmunity include molecular mimicry, bystander activation, and epitope spreading, among others.


title: Evaluation of Three Automated Nucleic Acid Extraction Systems for Identification of Respiratory Viruses in Clinical Specimens by Multiplex Real-Time PCR

text: A total of 84 nasopharyngeal swab specimens were collected from 84 patients. Viral nucleic acid was extracted by three automated extraction systems: QIAcube (Qiagen, Germany), EZ1 Advanced XL (Qiagen), and MICROLAB Nimbus IVD (Hamilton, USA). Fourteen RNA viruses and two DNA viruses were detected using the Anyplex II RV16 Detection kit (Seegene, Republic of Korea). The EZ1 Advanced XL system demonstrated the best analytical sensitivity for all the three viral strains. The nucleic acids extracted by EZ1 Advanced XL showed higher positive rates for virus detection than the others. Meanwhile, the MICROLAB Nimbus IVD system was comprised of fully automated steps from nucleic extraction to PCR setup function that could reduce human errors. For the nucleic acids recovered from nasopharyngeal swab specimens, the QIAcube system showed the fewest false negative results and the best concordance rate, and it may be more suitable for detecting various viruses including RNA and DNA virus strains. Each system showed different sensitivity and specificity for detection of certain viral pathogens and demonstrated different characteristics such as turnaround time and sample capacity. Therefore, these factors should be considered when new nucleic acid extraction systems are introduced to the laboratory.


title: Cumulative effect of aging and SARS-CoV2 infection on poor prognosis in the elderly: Insights from transcriptomic analysis of lung and blood

text: Introduction The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) has affected millions of people worldwide and with notable heterogeneity in its clinical presentation. Probability of contracting this highly contagious infection is similar across age groups but disease severity and fatality among aged patients with or without comorbidities are higher. We hypothesized that SARS-CoV-2 infection may augment aging-related gene expression alterations resulting in severe outcomes in elderly patients. Methodology We performed a comparative analysis of publicly available transcriptome data from Broncho Alveolar Lavage Fluid (BALF)/lung/blood of healthy aging group with i) COVID-19 patients; and ii) data of host genes interacting with SARS-CoV-2 proteins. Results We observed i) a significant overlap of gene expression profiles of patients’ BALF and blood with lung and blood of the healthy group respectively; ii) a more pronounced overlap in blood compared to lung; and iii) a similar overlap between host genes interacting with SARS-CoV-2 and aging blood transcriptome. Conclusions Pathway enrichment analysis of overlapping gene sets suggests that infection alters expression of genes already dysregulated in the elderly, which together may lead to poor prognosis. eQTLs in these genes may also confer poor outcome in young patients worsening with age and co-morbidities. Furthermore, the pronounced overlap observed in blood may explain clinical symptoms including blood clots, strokes, heart attack, multi-organ failure etc. in severe cases. This model based on a limited patient dataset seems robust and holds promise for testing larger tissue specific datasets from patients with varied severity and across populations.


title: The potential chemical structure of anti‐SARS‐CoV‐2 RNA‐dependent RNA polymerase

text: An outbreak of coronavirus disease 2019 (COVID‐19) occurred in Wuhan and it has rapidly spread to almost all parts of the world. For coronaviruses, RNA‐dependent RNA polymerase (RdRp) is an important protease that catalyzes the replication of RNA from RNA template and is an attractive therapeutic target. In this study, we screened these chemical structures from traditional Chinese medicinal compounds proven to show antiviral activity in severe acute respiratory syndrome coronavirus (SARS‐CoV) and the similar chemical structures through a molecular docking study to target RdRp of SARS‐CoV‐2, SARS‐CoV, and Middle East respiratory syndrome coronavirus (MERS‐CoV). We found that theaflavin has a lower idock score in the catalytic pocket of RdRp in SARS‐CoV‐2 (−9.11 kcal/mol), SARS‐CoV (−8.03 kcal/mol), and MERS‐CoV (−8.26 kcal/mol) from idock. To confirm the result, we discovered that theaflavin has lower binding energy of −8.8 kcal/mol when it docks in the catalytic pocket of SARS‐CoV‐2 RdRp by using the Blind Docking server. Regarding contact modes, hydrophobic interactions contribute significantly in binding and additional hydrogen bonds were found between theaflavin and RdRp. Moreover, one π‐cation interaction was formed between theaflavin and Arg553 from the Blind Docking server. Our results suggest that theaflavin could be a potential SARS‐CoV‐2 RdRp inhibitor for further study.


title: Comparative Study of Microbiological Monitoring Results from Three Types of Sampling Methods after Gastrointestinal Endoscope Reprocessing

text: OBJECTIVE: Compare the effects of three sampling methods on the microbiological monitoring results after reprocessing of gastrointestinal endoscopes, providing scientific basis for improving the monitoring quality of gastrointestinal endoscope cleaning and disinfection. METHOD: Gastrointestinal endoscopes after reprocessing were selected randomly at the gastrointestinal endoscopy center of a tertiary hospital in Shanghai from October 2018 to February 2019. The endoscopes selected were all sampled in three different methods under continuous sampling and intermittent sampling respectively. Methods used includes, the biopsy channel group (Group A), the entire channel group (Group B), and the disc brush group (Group C). Then the colony forming units (CFU/piece) were counted in the laboratory. RESULTS: A total of 12 endoscopes were sampled by using continuous sampling approach, in which the detection rate of bacteria in disc brush group (33.3%) and entire channel group (33.3%) was higher than biopsy channel group (8.3%). Among the 12 endoscopes sampled with intermittent approach, the detection rate of bacteria from high to low was the disc brush group (50%), the entire channel group (41.7%), and the biopsy channel group (8.3%). CONCLUSION: Different sampling methods will lead to the difference of microbiological culture results after reprocessing of gastrointestinal endoscope, indicating that the improved sampling method is beneficial to objectively reflect the endoscope cleaning and disinfection effect, and improve the monitoring quality of endoscope disinfection.


title: Many cuts to ruin: a comprehensive update of caspase substrates

text: Apoptotic cell death is executed by the caspase-mediated cleavage of various vital proteins. Elucidating the consequences of this endoproteolytic cleavage is crucial for our understanding of cell death and other biological processes. Many caspase substrates are just cleaved as bystanders, because they happen to contain a caspase cleavage site in their sequence. Several targets, however, have a discrete function in propagation of the cell death process. Many structural and regulatory proteins are inactivated by caspases, while other substrates can be activated. In most cases, the consequences of this gain-of-function are poorly understood. Caspase substrates can regulate the key morphological changes in apoptosis. Several caspase substrates also act as transducers and amplifiers that determine the apoptotic threshold and cell fate. This review summarizes the known caspase substrates comprising a bewildering list of more than 280 different proteins. We highlight some recent aspects inferred by the cleavage of certain proteins in apoptosis. We also discuss emerging themes of caspase cleavage in other forms of cell death and, in particular, in apparently unrelated processes, such as cell cycle regulation and cellular differentiation.


title: Classification system and case definition for SARS‐CoV‐2 infection in pregnant women, fetuses, and neonates

text: The possibility of mother-to-fetus transmission of SARS-CoV-2, the cause of coronavirus disease 2019 (COVID-19), is currently a highly debated concept in perinatal medicine. It has implications for the mother, fetus, and neonate, as well as for healthcare providers present at the time of birth and caring for the child during the neonatal period, including obstetricians, midwives, family doctors, anesthetists, pediatricians, neonatologists, nurses, and respiratory therapists. At present the evidence for intrauterine transmission from mother to fetus or intrapartum transmission from mother to the neonate is sparse. There are limitations associated with sensitivity and specificity of diagnostic tests used and classification of patients based on test results has also been questioned.


title: Chapter 18 Use of artificial intelligence in infectious diseases

text: Abstract Infectious diseases are caused by microorganisms belonging to the class of bacteria, viruses, fungi, or parasites. These pathogens are transmitted, directly or indirectly, and can lead to epidemics or even pandemics. The resulting infection may lead to mild-to-severe symptoms such as life-threatening fever or diarrhea. Infectious diseases may be asymptomatic in some individuals but may lead to disastrous effects in others. Despite the advances in medicine, infectious diseases are a leading cause of death worldwide, especially in low-income countries. With the advent of mathematical tools, scientists are now able to better predict epidemics, understand the specificity of each pathogen, and identify potential targets for drug development. Artificial intelligence and its components have been widely publicized for their ability to better diagnose certain types of cancer from imaging data. This chapter aims at identifying potential applications of machine learning in the field of infectious diseases. We are deliberately focusing on key aspects of infection: diagnosis, transmission, response to treatment, and resistance. We are proposing the use of extreme values as an avenue of interest for future developments in the field of infectious diseases. This chapter covers a series of applications selectively chosen to showcase how artificial intelligence is moving the field of infectious disease further and how it helps institutions to better tackles them, especially in low-income countries.


title: Transgene Biocontainment Strategies for Molecular Farming

text: Advances in plant synthetic biology promise to introduce novel agricultural products in the near future. ‘Molecular farms’ will include crops engineered to produce medications, vaccines, biofuels, industrial enzymes, and other high value compounds. These crops have the potential to reduce costs while dramatically increasing scales of synthesis and provide new economic opportunities to farmers. Current transgenic crops may be considered safe given their long-standing use, however, some applications of molecular farming may pose risks to human health and the environment. Unwanted gene flow from engineered crops could potentially contaminate the food supply, and affect wildlife. There is also potential for unwanted gene flow into engineered crops which may alter their ability to produce compounds of interest. Here, we briefly discuss the applications of molecular farming and explore the various genetic and physical methods that can be used for transgene biocontainment. As yet, no technology can be applied to all crop species, such that a combination of approaches may be necessary. Effective biocontainment is needed to enable large scale molecular farming.


title: Prophylactic and therapeutic activity of fully human monoclonal antibodies directed against Influenza A M2 protein

text: Influenza virus infection is a prevalent disease in humans. Antibodies against hemagglutinin have been shown to prevent infection and hence hemagglutinin is the major constituent of current vaccines. Antibodies directed against the highly conserved extracellular domain of M2 have also been shown to mediate protection against Influenza A infection in various animal models. Active vaccination is generally considered the best approach to combat viral diseases. However, passive immunization is an attractive alternative, particularly in acutely exposed or immune compromized individuals, young children and the elderly. We recently described a novel method for the rapid isolation of natural human antibodies by mammalian cell display. Here we used this approach to isolate human monoclonal antibodies directed against the highly conserved extracellular domain of the Influenza A M2 protein. The identified antibodies bound M2 peptide with high affinities, recognized native cell-surface expressed M2 and protected mice from a lethal influenza virus challenge. Moreover, therapeutic treatment up to 2 days after infection was effective, suggesting that M2-specific monoclonals have a great potential as immunotherapeutic agents against Influenza infection.


title: Identification of Diverse Bat Alphacoronaviruses and Betacoronaviruses in China Provides New Insights Into the Evolution and Origin of Coronavirus-Related Diseases

text: Outbreaks of severe acute respiratory syndrome (SARS) in 2002, Middle East respiratory syndrome in 2012 and fatal swine acute diarrhea syndrome in 2017 caused serious infectious diseases in humans and in livestock, resulting in serious public health threats and huge economic losses. All such coronaviruses (CoVs) were confirmed to originate from bats. To continuously monitor the epidemic-related CoVs in bats, virome analysis was used to classify CoVs from 831 bats of 15 species in Yunnan, Guangxi, and Sichuan Provinces between August 2016 and May 2017. We identified 11 CoV strains from 22 individual samples of four bat species. Identification of four alpha-CoVs from Scotophilus kuhlii in Guangxi, which was closely related to a previously reported bat CoV and porcine epidemic diarrhea virus (PEDV), revealed a bat-swine lineage under the genus Alphacoronavirus. A recombinant CoV showed that the PEDV probably originated from the CoV of S. kuhlii. Another alpha-CoV, α-YN2018, from Rhinolophus affinis in Yunnan, suggested that this alpha-CoV lineage had multiple host origins, and α-YN2018 had recombined with CoVs of other bat species over time. We identified five SARS-related CoVs (SARSr-CoVs) in Rhinolophus bats from Sichuan and Yunnan and confirmed that angiotensin-converting enzyme 2 usable SARSr-CoVs were continuously circulating in Rhinolophus spp. in Yunnan. The other beta-CoV, strain β-GX2018, found in Cynopterus sphinx of Guangxi, represented an independently evolved lineage different from known CoVs of Rousettus and Eonycteris bats. The identification of diverse CoVs here provides new genetic data for understanding the distribution and source of pathogenic CoVs in China.


docid: iygxrlxg

title: Mapping public health responses with attitude networks: the emergence of opinion‐based groups in the UK’s early COVID‐19 response phase

text: Partisan patterns of compliance with public health measures are a feature of early COVID‐19 responses. In many cases, these differences in behaviour relate to pre‐existing group identities. However, in times of rapid societal change, novel opinion‐based groups can emerge and provide a new basis for partisan identification and divergent collective behaviour. Here, we use network methods to map the emergence of opposing opinion‐based groups and assess their implications for public health behaviour. In a longitudinal study, we tracked public health attitudes and self‐reported behaviour in a sample of UK participants over four time points. Network visualisation reveal a rift in attitudinal alignment over time and the genesis of two distinct groups characterised by trust, or distrust, in science (Study 1a; N = 253). These groups also diverge in public health behaviour. In a brief follow‐up study (N = 206), we find that this opinion polarization partially reflects underlying societal divides. We discuss implications for opinion‐based group research and public health campaigns.


title: Increased serum aminotransferase activity and clinical outcomes in Coronavirus disease 2019

text: OBJECTIVE: Elevation of hepatic aminotransferases (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]) is commonly noted among COVID-19 patients. It is unclear if they can predict the clinical outcomes among hospitalized COVID-19 patients. We aim to assess if elevations in AST/ALT were associated with poor outcomes in hospitalized COVID-19 patients. METHODS: We retrospectively evaluated hospitalized COVID-19 patients with clinically significant elevated aminotransferases (defined as >2 times upper limit of normal) and compared them with COVID-19 patients without an elevation in aminotransferases. RESULTS: The prevalence of elevation in AST/ALT was found to be 13.7% (20/145). The two groups were similar in baseline demographics, comorbidities, and the majority of laboratory tests. There was no difference in the mortality (50% vs. 36.8%, P=0.32) and median hospital stay (7 days vs. 7 days, P=0.78). However, there was a statistically significant increase in the rates of mechanical ventilation among elevated aminotransferases group compared to individuals without elevation (50% vs. 24%, P= 0.028). However, this difference was not observed after adjusting for inflammatory markers such as ferritin, lactate dehydrogenase (LDH), and lactic acid levels. CONCLUSION: Elevated aminotransferases among hospitalized COVID-19 patients is associated with higher rates of mechanical ventilation, but did not achieve statistical significance after controlling for inflammatory markers. Also, patients with elevated aminotransferases did not have higher rates of mortality or prolonged length of stay.


title: Prevalence and predictive value of hypocalcemia in severe COVID-19 patients

text: Abstract Background The aim of this study was to investigate the performance and predictive value of hypocalcemia in severe COVID-19 patients. Methods We retrospectively investigated the clinical and laboratory characteristics of severe COVID-19 patients. 107 patients were divided into hypocalcemia group and normal serum calcium group. The clinical and laboratory data were compared between two groups. The discriminative power of hypocalcemia regarding poor outcome were evaluated by receiver operating curves (ROC) analyze. Results 67 patients (62.6%) had hypocalcemia. In hypocalcemia group, leukocytes, c-reactive protein(CRP), procalcitonin(PCT), Interleukin 6(IL-6), and D-dimer levels was higher, while lymphocytes and albumin(ALB) levels was lower. No significant difference was identified in gender, age, signs and symptoms, comorbidities and other laboratory indicators. Serum calcium levels were negatively correlated with leukocytes, CRP, PCT, IL-6 and D-dimer, while positively correlated with lymphocytes and ALB. Patients with hypocalcemia more commonly presented poor outcome (47.8% (32/67) vs 25% (10/40), p =0.02). Median serum calcium levels were significantly lower in the patients with poor outcome (2.01(1.97-2.05) vs 2.10(2.03-2.20), p<0.001), and it could predict the prognosis with an area under the ROC curve (AUC) of 0.73(95% confidence interval (CI) 0.63-0.83, p<0.001). Conclusions Hypocalcemia commonly occurred in severe COVID-19 patients and it was associated with poor outcome.


title: Rhinovirus and the lower respiratory tract

text: Human rhinoviruses (HRVs) are well‐recognised causes of common colds and associated upper respiratory tract complications such as sinusitis and otitis media. This article reviews information linking HRV infection to illness in the lower respiratory tract. HRVs are capable of efficient replication in vitro at temperatures present in the tracheobronchial tree and have been shown to cause productive infection, elaboration of cytokines and chemokines, and up‐regulation of cell surface markers in human bronchial epithelial cells. In situ hybridisation studies have proven that HRV infection occurs in the tracheobronchial tree following experimental infection. Clinical studies report that HRV infection is the second most frequently recognised agent associated with pneumonia and bronchiolitis in infants and young children and commonly causes exacerbations of pre‐existing airways disease in those with asthma, chronic obstructive pulmonary disease or cystic fibrosis. HRV infection is associated with one‐third to one‐half of asthma exacerbations depending on age and is linked to asthma hospitalisations in both adults and children. Limited information implicates HRV infection as a cause of severe lower respiratory tract illness in older adults and in highly immunocompromised hosts, particularly bone marrow transplant recipients. More information is needed about the pathogenesis of HRV infection with regard to lower respiratory tract complications in these diverse patient groups. Given the large unmet medical need associated with HRV infections, safe and effective antiviral agents are needed for both prevention and treatment of these infections. Copyright © 2004 John Wiley & Sons, Ltd.


title: Emergence of whooping cough: notes from three early epidemics in Persia

text: Summary Whooping cough is a relatively new infectious disease afflicting human beings, compared with other infectious diseases, and is undergoing a resurgence despite decades of vaccination. The oldest known epidemic is thought to be the Paris outbreak of 1578. In this Historical Review, we describe three epidemics of whooping cough in Persia, which although arising roughly one century before the Paris outbreak, have not been examined in detail. A great amount of epidemiological detail was reported that not only distinguishes the various stages and complications of whooping cough, but also reveals unique immunological aspects of this disease. The first of these epidemics is the oldest recorded whooping cough epidemic. On the basis of epidemiological features, we propose that this whooping cough epidemic was the first to have taken place in Persia and might have been part of the first pandemic. This theory pushes back the date of first documented emergence of whooping cough by almost a century, which matches molecular data about its spread. Here, we discuss features of these early epidemics in relation to their initial emergence, potential origins, and spread to Europe.


title: Rhinovirus inhibits IL-17A and the downstream immune responses in allergic asthma

text: The proinflammatory cytokine interleukin-17A (IL-17A) is known to mediate antimicrobial activity, but its role during rhinovirus (RV) infections and in asthma needs further investigation. Therefore, we addressed the role of IL-17A during allergic asthma and antiviral immune response in human and murine immunocompetent cells. In this study we found that asthmatic children with a RV infection in their upper airways have upregulated mRNA levels of the antiviral cytokine interferon type I (IFN)-β and the transcription factor T-box 21 (TBX21) and reduced levels of IL-17A protein in their peripheral blood mononuclear cells (PBMCs). We also found that IL-17A inhibited RV1b replication in infected human lung epithelial cells A549. Furthermore, by using gene array analysis we discovered that targeted deletion of Il17a in murine lung CD4(+) T cells impaired Oas1g mRNA downstream of Ifnβ, independently from RV infection. Additionally, in PBMCs of children with a RV infection in their nasalpharyngeal fluid OAS1 gene expression was found downregulated. Finally RV1b inhibited IL-17A production in lung CD4(+) T cells in a setting of experimental asthma. These results indicate that the RV1b inhibits IL-17A in T helper type 17 cells and IL-17A clears RV1b infection in epithelial cells. In both cases IL-17A contributes to fend off RV1b infection by inducing genes downstream of interferon type I pathway. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/mi.2015.130) contains supplementary material, which is available to authorized users.


title: CCL28 chemokine: An anchoring point bridging innate and adaptive immunity

text: Abstract Chemokines are an extensive family of small proteins which, in conjunction with their receptors, guide the chemotactic activity of various immune cells throughout the body. CCL28, β- or CC chemokine, is involved in the host immunity at various epithelial and mucosal linings. The unique roles of CCL28 in several facets of immune responses have attracted considerable attention and may represent a promising approach to combat various infections. CCL28 displays a broad spectrum of antimicrobial activity against gram-negative and gram-positive bacteria, as well as fungi. Here, we will summarize various research findings regarding the antimicrobial activity of CCL28 and the relevant mechanisms behind it. We will explore how the structure of CCL28 is involved with this activity and how this function may have evolved. CCL28 displays strong homing capabilities for B and T cells at several mucosal and epithelial sites, and orchestrates the trafficking and functioning of lymphocytes. The chemotactic and immunomodulatory features of CCL28 through the interactions with its chemokine receptors, CCR10 and CCR3, will also be discussed in detail. Thus, in this review, we emphasize the dual properties of CCL28 and suggest its role as an anchoring point bridging the innate and adaptive immunity.


title: Continuous Intravenous Anakinra Infusion to Calm the Cytokine Storm in Macrophage Activation Syndrome

text: OBJECTIVE: The objective of this study was to report the benefit of a therapeutic approach consisting of intravenous (IV) continuous anakinra (recombinant human interleukin‐1 receptor antagonist) infusions in treating severely ill adult patients with secondary hemophagocytic lymphohistiocytosis or macrophage activation syndrome (MAS). METHODS: A retrospective chart review of five patients treated at Regions Hospital from 2016 to 2019 was conducted. Demographic, clinical, and laboratory characteristics and outcomes were recorded. RESULTS: Continuous IV anakinra infusions up to 2400 mg/d resulted in rapid serologic, then clinical response in 4 of 5 severely ill patients who were refractory to all other therapies, including subcutaneous anakinra. Subsequently, 3 of 5 patients have been maintained on anakinra or canakinumab, with no recurrence of MAS. CONCLUSION: Continuous infusion of IV anakinra may result in rapid serologic and subsequent clinical improvement in adult patients with MAS. This method for treating cytokine storm should be considered in the current COVID‐19 pandemic in the subgroup of patients with severe disease who have a cytokine storm presentation.


title: Using Social Media for Rapid Information Dissemination in a Pandemic: #PedsICU and Coronavirus Disease 2019

text: To describe the impact of a strategy for international collaboration and rapid information dissemination on Twitter among the pediatric critical care community during a global pandemic. DESIGN: Analysis of #PedsICU and coronavirus disease 2019 Twitter data in the Symplur Signals Database between February 1, 2020, and May 1, 2020. SETTING: Social media platform Twitter. PATIENTS: None. INTERVENTIONS: Promotion of the joint usage of #PedsICU and #COVID19 throughout the international pediatric critical care community in tweets relevant to the coronavirus disease 2019 pandemic and pediatric critical care. MEASUREMENTS AND MAIN RESULTS: We collected data on all tweets containing the hashtag #PedsICU in addition to those containing both #PedsICU and coronavirus disease 2019 hashtags. Tweets including #PedsICU were shared 49,865 times on six continents between February 1, 2020, and May 1, 2020; between February 1 and March 13, only 8% of #PedsICU tweets included a coronavirus disease 2019 hashtag. After a sharp rise during the week of March 14, 2020, coronavirus disease 2019 content has dominated the #PedsICU conversation on Twitter, comprising 69% of both #PedsICU tweets and impressions (p < 0.001). The most commonly used coronavirus disease 2019 hashtag over the study period was #COVID19 (69%). Proportionately, a greater percentage of #PedsICU tweets including the coronavirus disease 2019 hashtag (vs not) had images or videos (45% vs 41%; p < 0.001). In addition, non–physician healthcare providers were the largest group of users (46%) of the combination of #PedsICU and coronavirus disease 2019 hashtags. The most popular tweets shared on Twitter were open-access resources, including links for updated literature, narrative reviews, and educational videos relevant to coronavirus disease 2019 clinical care. Concurrent hashtags and words in tweets containing #PedsICU and coronavirus disease 2019 hashtags spanned several different disciplines and topics in pediatric critical care. CONCLUSION: Twitter has been used widely for real-time information sharing and collaboration among the international pediatric critical care community during the coronavirus disease 2019 pandemic. Targeted use of #PedsICU and #COVID19 for engagement on Twitter is a conduit to combat misinformation and optimize reach to pediatric critical care stakeholders across the globe when rapid dissemination is needed.


Letter to the editor: Headline stress disorder caused by Netnews during the outbreak of COVID‐19


title: Massively parallel pathogen identification using high‐density microarrays

text: Identification of microbial pathogens in clinical specimens is still performed by phenotypic methods that are often slow and cumbersome, despite the availability of more comprehensive genotyping technologies. We present an approach based on whole‐genome amplification and resequencing microarrays for unbiased pathogen detection. This 10 h process identifies a broad spectrum of bacterial and viral species and predicts antibiotic resistance and pathogenicity and virulence profiles. We successfully identify a variety of bacteria and viruses, both in isolation and in complex mixtures, and the high specificity of the microarray distinguishes between different pathogens that cause diseases with overlapping symptoms. The resequencing approach also allows identification of organisms whose sequences are not tiled on the array, greatly expanding the repertoire of identifiable organisms and their variants. We identify organisms by hybridization of their DNA in as little as 1–4 h. Using this method, we identified Monkeypox virus and drug‐resistant Staphylococcus aureus in a skin lesion taken from a child suspected of an orthopoxvirus infection, despite poor transport conditions of the sample, and a vast excess of human DNA. Our results suggest this technology could be applied in a clinical setting to test for numerous pathogens in a rapid, sensitive and unbiased manner.


title: Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes

text: Abstract Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in southern China in late 2002 and caused a global outbreak with a fatality rate around 10% in 2003. Ten years later, a second highly pathogenic human CoV, MERS-CoV, emerged in the Middle East and has spread to other countries in Europe, North Africa, North America and Asia. As of November 2017, MERS-CoV had infected at least 2102 people with a fatality rate of about 35% globally, and hence there is an urgent need to identify antiviral drugs that are active against MERS-CoV. Here we show that a clinically available alcohol-aversive drug, disulfiram, can inhibit the papain-like proteases (PLpros) of MERS-CoV and SARS-CoV. Our findings suggest that disulfiram acts as an allosteric inhibitor of MERS-CoV PLpro but as a competitive (or mixed) inhibitor of SARS-CoV PLpro. The phenomenon of slow-binding inhibition and the irrecoverability of enzyme activity after removing unbound disulfiram indicate covalent inactivation of SARS-CoV PLpro by disulfiram, while synergistic inhibition of MERS-CoV PLpro by disulfiram and 6-thioguanine or mycophenolic acid implies the potential for combination treatments using these three clinically available drugs.


title: Mutations in the IGF-II pathway that confer resistance to lytic reovirus infection

text: BACKGROUND: Viruses are obligate intracellular parasites and rely upon the host cell for different steps in their life cycles. The characterization of cellular genes required for virus infection and/or cell killing will be essential for understanding viral life cycles, and may provide cellular targets for new antiviral therapies. RESULTS: A gene entrapment approach was used to identify candidate cellular genes that affect reovirus infection or virus induced cell lysis. Four of the 111 genes disrupted in clones selected for resistance to infection by reovirus type 1 involved the insulin growth factor-2 (IGF-II) pathway, including: the mannose-6-phosphate/IGF2 receptor (Igf2r), a protease associated with insulin growth factor binding protein 5 (Prss11), and the CTCF transcriptional regulator (Ctcf). The disruption of Ctcf, which encodes a repressor of Igf2, was associated with enhanced Igf2 gene expression. Plasmids expressing either the IGF-II pro-hormone or IGF-II without the carboxy terminal extension (E)-peptide sequence independently conferred high levels of cellular resistance to reovirus infection. Forced IGF-II expression results in a block in virus disassembly. In addition, Ctcf disruption and forced Igf2 expression both enabled cells to proliferate in soft agar, a phenotype associated with malignant growth in vivo. CONCLUSION: These results indicate that IGF-II, and by inference other components of the IGF-II signalling pathway, can confer resistance to lytic reovirus infection. This report represents the first use of gene entrapment to identify host factors affecting virus infection. Concomitant transformation observed in some virus resistant cells illustrates a potential mechanism of carcinogenesis associated with chronic virus infection.


Orphan viruses, orphan diseases: still the raw material for virus discovery


title: Potential inhibitors for 2019-nCoV coronavirus M protease from clinically approved medicines

text: Starting from December 2019, a novel coronavirus, named 2019-nCoV, was found to cause Severe Acute Respiratory (SARI) symptoms and rapid pandemic in China. With the hope to identify candidate drugs for 2019-nCoV, we adopted a computational approach to screen for available commercial medicines which may function as inhibitors for the Mpro of 2019-nCoV. Up to 10 commercial medicines that may form hydrogen bounds to key residues within the binding pocket of 2019-nCoV Mpro were identified, which may have higher mutation tolerance than lopinavir/ritonavir and may also function as inhibitors for other coronaviruses with similar Mpro binding sites and pocket structures.


title: Surveillance of COVID-19 in the General Population Using an Online Questionnaire: Report From 18,161 Respondents in China

text: BACKGROUND: The recent outbreak of the coronavirus disease (COVID-19) has become an international pandemic. So far, little is known about the role of an internet approach in COVID-19 participatory surveillance. OBJECTIVE: The aim of this study is to investigate whether an online survey can provide population-level information for observing prevalence trends during the early phase of an outbreak and identifying potential risk factors of COVID-19 infection. METHODS: A 10-item online questionnaire was developed according to medical guidelines and relevant publications. It was distributed between January 24 and February 17, 2020. The characteristics of respondents and temporal changes of various questionnaire-derived indicators were analyzed. RESULTS: A total of 18,161 questionnaires were returned, including 6.45% (n=1171) from Wuhan City. Geographical distributions of the respondents were consistent with the population per province (R(2)=0.61, P<.001). History of contact significantly decreased with time, both outside Wuhan City (R(2)=0.35, P=.002) and outside Hubei Province (R(2)=0.42, P<.001). The percentage of respondents reporting a fever peaked around February 8 (R(2)=0.57, P<.001) and increased with a history of contact in the areas outside Wuhan City (risk ratio 1.31, 95% CI 1.13-1.52, P<.001). Male sex, advanced age, and lung diseases were associated with a higher risk of fever in the general population with a history of contact. CONCLUSIONS: This study shows the usefulness of an online questionnaire for the surveillance of outbreaks like COVID-19 by providing information about trends of the disease and aiding the identification of potential risk factors.


title: Recent advancements for the evaluation of anti-viral activities of natural products

text: Significant progress has been achieved for the development of novel anti-viral drugs in the recent years. Large numbers of these newly developed drugs belong to three groups of compounds, nucleoside analogues, thymidine kinase-dependent nucleotide analogues and specific viral enzyme inhibitors. It has been found that the natural products, like plant extract, plant-derived compounds (phytochemicals) and so on, as well as traditional medicines, like Ayurvedic, traditional Chinese medicine (TCM), Chakma medicines and so on, are the potential sources for potential and novel anti-viral drugs based on different in vitro and in vivo approaches. In this chapter some of these important approaches utilised in the drug discovery process of potential candidate(s) for anti-viral agents are being discussed. The key conclusion is that natural products are one of the most important sources of novel anti-viral agents.


docid: vpbdtnyl

title: Immune stimulating properties of a novel polysaccharide from the medicinal plant Tinospora cordifolia

text: Abstract An α-d-glucan (RR1) composed of (1→4) linked back bone and (1→6) linked branches with a molecular mass of >550 kDa and exhibiting unique immune stimulating properties is isolated and characterized from the medicinal plant Tinospora cordifolia. This novel polysaccharide is noncytotoxic and nonproliferating to normal lymphocytes as well as tumor cell lines at 0–1000 μg/ml. It activated different subsets of the lymphocytes such as natural killer (NK) cells (331%), T cells (102%), and B cells (39%) at 100 μg/ml concentration. The significant activation of NK cells is associated with the dose-dependent killing of tumor cells by activated normal lymphocytes in a functional assay. Immune activation by RR1 in normal lymphocytes elicited the synthesis of interleukin (IL)-1β (1080 pg/ml), IL-6 (21,833 pg/ml), IL-12 p70 (50.19 pg/ml), IL-12 p40 (918.23 pg/ml), IL-18 (27.47 pg/ml), IFN- γ (90.16 pg/ml), tumor necrosis factor (TNF)-α (2225 pg/ml) and monocyte chemoattractant protein (MCP)-1 (2307 pg/ml) at 100 μg/ml concentration, while it did not induce the production of IL-2, IL-4, IL-10, interferon (IFN)-α and TNF-β. The cytokine profile clearly demonstrates the Th1 pathway of T helper cell differentiation essential for cell mediated immunity, with a self-regulatory mechanism for the control of its overproduction. RR1 also activated the complements in the alternate pathway, demonstrated by a stepwise increase in C3a des Arg components. Incidentally, RR1 stimulation did not produce any oxidative stress or inducible nitric oxide synthase (iNOS) in the lymphocytes or any significant increase in nitric oxide production. The water solubility, high molecular mass, activation of lymphocytes especially NK cells, complement activation, Th1 pathway-associated cytokine profile, together with a low level of nitric oxide synthesis and absence of oxidative stress confer important immunoprotective potential to this novel α-d-glucan.


title: Reducing medical error during a pandemic

text: On 30 January 2020, the WHO declared the coronavirus disease 2019 (COVID-19) a public health emergency of international concern. By 11 March 2020, it was designated a pandemic owing to its rapid worldwide spread. In this short article we provide some information that might be useful and help equip colleagues to reduce medical error during a pandemic. We advocate a systems-based approach, rather than an individual’s sole responsibility, and, look at ways to provide safer healthcare.


Decrease in surgical activity in the COVID‐19 pandemic: an economic crisis


Covid-19, dignité humaine et traumatisme psychologique pour les soignants : une lettre ouverte aux autorités sanitaires


docid: tgpaidhp

title: Interaction of the prototypical α-ketoamide inhibitor with the SARS-CoV-2 main protease active site in silico: Molecular dynamic simulations highlight the stability of the ligand-protein complex

text: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes an illness known as COVID-19, which has been declared a global pandemic with over 2 million confirmed cases and 137,000 deaths in 185 countries and regions at the time of writing (16 April 2020), over a quarter of these cases being in the United States. In the absence of a vaccine, or an approved effective therapeutic, there is an intense interest in repositioning available drugs or designing small molecule antivirals. In this context, in silico modelling has proven to be an invaluable tool. An important target is the SARS-CoV-2 main protease (M(pro)), involved in processing translated viral proteins. Peptidomimetic α-ketoamides represent prototypical inhibitors of M(pro). A recent attempt at designing a compound with enhanced pharmacokinetic properties has resulted in the synthesis and evaluation of the α-ketoamide 13b analogue. Here, we performed molecular docking and molecular dynamics simulations to further characterize the interaction of α-ketoamide 13b with the active site of the SARS-CoV-2 M(pro). We included the widely used antibiotic, amoxicillin, for comparison. Our findings indicate that α-ketoamide 13b binds more tightly (predicted GlideScore = -8.7 and -9.2 kcal/mol for protomers A and B, respectively), to the protease active site compared to amoxicillin (-5.0 and -4.8 kcal/mol). Further, molecular dynamics simulations highlight the stability of the interaction of the α-ketoamide 13b ligand with the SARS-CoV-2 M(pro) (ΔG = -25.2 and -22.3 kcal/mol for protomers A and B). In contrast, amoxicillin interacts unfavourably with the protease (ΔG = +32.8 kcal/mol for protomer A), with unbinding events observed in several independent simulations. Overall, our findings are consistent with those previously observed, and highlight the need to further explore the α-ketoamides as potential antivirals for this ongoing COVID-19 pandemic.


title: Determining the source of transmission of SARS-CoV-2 infection in a healthcare worker

text: Healthcare workers (HCWs) are at the frontlines of the COVID-19 pandemic and are at risk of exposure to SARS-CoV-2 infection from their interactions with patients and in the community. Limited availability of recommended personal protective equipment (PPE), in particular N95 respirators, has fueled concerns about whether HCWs are adequately protected from exposure while caring for patients. Understanding the source of SARS-CoV-2 infection in a HCW - the community or the healthcare system - is critical for understanding the effectiveness of hospital infection control and PPE practices. In Dane County, Wisconsin, community prevalence of SARS-CoV-2 is relatively low (cumulative prevalence of ~0.06% - positive cases / total population in Dane county as of April 17). Although SARS-CoV-2 infections in HCWs are often presumed to be acquired during the course of patient care, there are few reports unambiguously identifying the source of acquisition. The objective of this brief report was to determine the source of transmission of SARS-CoV-2 in a healthcare worker.


title: During the summer 2009 outbreak of "swine flu" in Scotland what respiratory pathogens were diagnosed as H1N1/2009?

text: BACKGROUND: During the April-July 2009 outbreak of H1N1/2009 in scotland the West of Scotland Specialist Virology Centre (WoSSVC) in Glasgow tested > 16 000 clinical samples for H1N1/2009. Most were from patients clinically diagnosed with H1N1/2009. Out of these, 9% were positive. This study sought to determine what respiratory pathogens were misdiagnosed as cases of H1N1/2009 during this time. METHODS: We examined the results from 3247 samples which were sent to the laboratory during April-July 2009. All were from patients clinically diagnosed as having H1N1/2009 (based on accepted criteria) and all were given a full respiratory screen using real time reverse transcriptase polymerase chain reaction (rtRT-PCR) assays. RESULTS: In total, respiratory pathogens were detected in 27.9% (95% confidence interval, 26.3-29.5%) of the samples submitted. Numerous pathogens were detected, the most common of which were rhinovirus (8.9% (95% confidence interval, 7.9-9.9%)), parainfluenza 1 (1.9% (95% confidence interval, 1.4-2.4%)) and 3 (4.1% (95% confidence interval, 3.3-4.9%)), and adenovirus ((3.5% (95% confidence interval, 2.9-4.2%)). CONCLUSIONS: This study highlights the problems of using a clinical algorithm to detect H1N1/2009. Clinicians frequently misdiagnosed common respiratory pathogens as H1N1/2009 during the spring/summer outbreak in Scotland. Many undesirable consequences would have resulted, relating to treatment, infection control, and public health surveillance.


The 2020 COVID-19 Pandemic


Implications pour la santé publique du déplacement des enfants almajiri dans certains États du nord du Nigeria dans le cadre de la pandémie de COVID-19


title: Distribution and genetic diversity of adeno-associated viruses in bats from coastal areas of Southeast China

text: Bats are associated with several important zoonotic viruses from different families. One example includes adeno-associated viruses (AAVs), that are extensively detected in several animals, especially primates. To understand AAVs distribution and genetic diversity in the coastal areas of Southeast China, a total of 415 intestine samples were mostly collected from two provinces of southeast China, i.e., Zhejiang and Fujian province. Intestine samples from five bat species were collected for AAVs detection. The average prevalence rate for AAV detection among these samples was 18.6% (77 positives out of 415 samples) and ranged from 11.8 to 28.9% between the five bat species. This suggests that AAVs are widely distributed in diverse bat populations in southeast coastal areas of China. Based on the genome sequence of bat adeno-associated virus-CXC1(BtAAV-CXC1) from one AAV-positive sample, the genetic diversity of the detected AAVs were assessed and analyzed. Phylogenetic analysis revealed that BtAAV-CXC1 was comparatively distant to other major AAVs from mammals and non-mammals, with only a 52.9~64.7% nucleotide identity. However, they were phylogenetically closer to Rhinolophus sinicus bat adeno-associated virus (Rs-BtAAV1), with a 74.5% nt similarity. Partial analysis of the rep and cap overlapping open reading frame (ORF) sequences from bat AAV samples revealed 48 partial rep sequences and 23 partial cap sequences from positive samples shared 86.9 to 100% and 72.3 to 98.8% nucleotide identities among themselves, respectively. This suggests that the detected AAVs had a distinctly high genetic diversity. These findings led us to conclude that diverse AAVs may be widely distributed in bat populations from the southeast regions of China.


title: Expression and Cleavage of Middle East Respiratory Syndrome Coronavirus nsp3-4 Polyprotein Induce the Formation of Double-Membrane Vesicles That Mimic Those Associated with Coronaviral RNA Replication

text: Betacoronaviruses, such as Middle East respiratory syndrome coronavirus (MERS-CoV), are important pathogens causing potentially lethal infections in humans and animals. Coronavirus RNA synthesis is thought to be associated with replication organelles (ROs) consisting of modified endoplasmic reticulum (ER) membranes. These are transformed into double-membrane vesicles (DMVs) containing viral double-stranded RNA and into other membranous elements such as convoluted membranes, together forming a reticulovesicular network. Previous evidence suggested that the nonstructural proteins (nsp’s) 3, 4, and 6 of the severe acute respiratory syndrome coronavirus (SARS-CoV), which contain transmembrane domains, would all be required for DMV formation. We have now expressed MERS-CoV replicase self-cleaving polyprotein fragments encompassing nsp3-4 or nsp3-6, as well as coexpressed nsp3 and nsp4 of either MERS-CoV or SARS-CoV, to characterize the membrane structures induced. Using electron tomography, we demonstrate that for both MERS-CoV and SARS-CoV coexpression of nsp3 and nsp4 is required and sufficient to induce DMVs. Coexpression of MERS-CoV nsp3 and nsp4 either as individual proteins or as a self-cleaving nsp3-4 precursor resulted in very similar DMVs, and in both setups we observed proliferation of zippered ER that appeared to wrap into nascent DMVs. Moreover, when inactivating nsp3-4 polyprotein cleavage by mutagenesis, we established that cleavage of the nsp3/nsp4 junction is essential for MERS-CoV DMV formation. Addition of the third MERS-CoV transmembrane protein, nsp6, did not noticeably affect DMV formation. These findings provide important insight into the biogenesis of coronavirus DMVs, establish strong similarities with other nidoviruses (specifically, the arteriviruses), and highlight possible general principles in viral DMV formation.


title: Chile’s role in global health diplomacy: a narrative literature review

text: BACKGROUND: Global health diplomacy (GHD) has become an important field of investigation due to health concerns increasingly entering the foreign policy domain. Much of the existing academic writing focuses on North-South cooperation in global health, and emphasizes the role of security and economic interests by Northern countries as drivers of GHD. Chile presents a favourable environment for an expanded involvement in future GHD activities. However, there is little knowledge about what has been driving Chile’s integration of health into foreign policy, and little effort to appropriate knowledge from international relations theories to better theoretically grasp the emergence of GHD. METHODS: To fill this knowledge gap, we conducted a narrative literature review of the driving forces behind Chile’s integration of health into foreign policy. Drawing on a popular analytical framework used in international relations scholarship, we identified driving forces of the integration of health into Chile foreign policy at three levels of analysis. RESULTS: At the international/global level of analysis, the main driving forces were related to national security concerns and compliance with regulations of international organizations. At the regional level, GHD was driven by a commitment to regional solidarity through mutually beneficial cooperation in response to neoliberal reforms; health coordination in emergencies; and protection of indigenous peoples. Finally, at the domestic level, drivers identified include economic interests of various productive sectors and how health regulations might impact those; the high degree of social inequity which impacts on access to healthcare; and management of natural disasters. CONCLUSION: Health actions in the context of international relations in Chile are still mainly motivated by more traditional foreign policy interests rather than by a desire to satisfy health needs per se. This seems to conform with findings of existing GHD scholarship that emphasize the importance of security and economic interests as driving forces of GHD, and how health is often appropriated instrumentally within foreign policy settings to achieve other goals. But the review also reveals that in the context of South-South cooperation (and regional health diplomacy), solidarity and normative considerations can be important driving forces as well. Finally, the review demonstrates that there has been an evolution from chiefly domestically focused health policies (e.g. maternal and child nutrition treatment) towards internationally inspired integrated policies (e.g. maternal and child nutrition promotion aligned with international guidelines). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12992-018-0428-8) contains supplementary material, which is available to authorized users.


title: Not sick enough to worry? "Influenza-like" symptoms and work-related behavior among healthcare workers and other professionals: Results of a global survey

text: BACKGROUND: Healthcare workers (HCWs) and non-HCWs may contribute to the transmission of influenza-like illness (ILI) to colleagues and susceptible patients by working while sick (presenteeism). The present study aimed to explore the views and behavior of HCWs and non-HCWs towards the phenomenon of working while experiencing ILI. METHODS: The study was a cross-sectional online survey conducted between October 2018 and January 2019 to explore sickness presenteeism and the behaviour of HCWs and non-HCWs when experiencing ILI. The survey questionnaire was distributed to the members and international networks of the International Society of Antimicrobial Chemotherapy (ISAC) Infection Prevention and Control (IPC) Working Group, as well as via social media platforms, including LinkedIn, Twitter and IPC Blog. RESULTS: In total, 533 respondents from 49 countries participated (Europe 69.2%, Asia-Pacific 19.1%, the Americas 10.9%, and Africa 0.8%) representing 249 HCWs (46.7%) and 284 non-HCWs (53.2%). Overall, 312 (58.5%; 95% confidence interval [CI], 56.2–64.6) would continue to work when sick with ILI, with no variation between the two categories. Sixty-seven (26.9%) HCWs and forty-six (16.2%) non-HCWs would work with fever alone (p<0 .01) Most HCWs (89.2–99.2%) and non-HCWs (80%-96.5%) would work with “minor” ILI symptoms, such as sore throat, sinus cold, fatigue, sneezing, runny nose, mild cough and reduced appetite. CONCLUSION: A future strategy to successfully prevent the transmission of ILI in healthcare settings should address sick-leave policy management, in addition to encouraging the uptake of influenza vaccine.


title: Baiting studies on oral vaccination of the greater kudu (Tragelaphus strepsiceros) against rabies

text: Rabies in the greater kudu (Tragelaphus strepsiceros), one of the largest African antelopes, is a phenomenon unique to Namibia. Since the mid-1970s, the country has been plagued by two epizootics that claimed thousands of casualties among the indigenous kudu population. Reasons as to why kudus appear to be exceptionally susceptible to the disease still remain speculative at best. Because the Namibian economy relies heavily on trophy hunting, game meat hunting, and ecotourism, the current severe spread of rabies among kudus calls for effective measures to protect these antelopes. Oral vaccination of kudus may offer a possibility provided efficacious oral rabies vaccines are available. In this screening study, we explored options for attractive baits that facilitate optimal vaccine uptake by the target species and a bait distribution system that maximizes bait availability to the target species meanwhile minimizing bait depletion by non-target species. The results show that gelatin-based baits mixed with local (pods of the camel thorn tree) but also imported (apple-flavored corn meal) attractants are highly attractive for kudus providing a basis for future oral rabies vaccine baits. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10344-018-1220-z) contains supplementary material, which is available to authorized users.


title: Viruses as key modulators of the TGF‐β pathway; a double‐edged sword involved in cancer

text: Transforming growth factor‐β (TGF‐β) signaling pathway is a key network in cell signaling that controls vital processes such as proliferation, differentiation, apoptosis, epithelial‐mesenchymal transition, and migration, thus acting as a double‐edged sword in normal development and diseases, in particular organ fibrosis, vascular disorders, and cancer. Early in tumorigenesis, the pathway exerts anti‐tumor effects through suppressing cell cycle and inducing apoptosis, while during late stages, it functions as a tumor promoter by enhancing tumor invasiveness and metastasis. This signaling pathway can be perturbed by environmental and genetic factors such as microbial interference and mutation, respectively. In this way, the present review describes the modulation of the TGF‐β pathway by oncogenic human viral pathogens and other viruses. The main mechanisms by which viruses interferes with TGF‐β signaling seems to be through (1) the alteration of either TGF‐β protein expression or activation, (2) the modulation of the TGF‐β receptors or SMADs factors (by interfering with their levels and functions), (3) the alteration of none‐SMAD pathways, and (4) indirect interaction with the pathway by the modulation of transcriptional co‐activator/repressor and regulators of the pathway. Given the axial role of this pathway in tumorigenesis, it can be regarded as an attractive target for cancer therapy. Hence, further investigations on this subject may represent molecular targets among either TGF‐β signaling molecules or viral factors for the treatment and management of viral infection consequences such as cancer.


title: Tocilizumab's efficacy in patients with Coronavirus Disease 2019 (COVID‐19) is determined by the presence of cytokine storm

text: We read with great interest the research article written by Borku Uysal B et al which is in accordance with the so far accumulating knowledge that tocilizumab is an effective treatment for COVID-19 cytokine storm syndrome (CSS). This article is protected by copyright. All rights reserved.


title: The clinical pathology of severe acute respiratory syndrome (SARS): a report from China

text: In order to investigate the clinical pathology of severe acute respiratory syndrome (SARS), the autopsies of three patients who died from SARS in Nan Fang Hospital Guangdong, China were studied retrospectively. Routine haematoxylin and eosin (H&E) staining was used to study all of the tissues from the three cases. The lung tissue specimens were studied further with Macchiavello staining, viral inclusion body staining, reticulin staining, PAS staining, immunohistochemistry, ultrathin sectioning and staining, light microscopy, and transmission electron microscopy. The first symptom was hyperpyrexia in all three cases, followed by progressive dyspnoea and lung field shadowing. The pulmonary lesions included bilateral extensive consolidation, localized haemorrhage and necrosis, desquamative pulmonary alveolitis and bronchitis, proliferation and desquamation of alveolar epithelial cells, exudation of protein and monocytes, lymphocytes and plasma cells in alveoli, hyaline membrane formation, and viral inclusion bodies in alveolar epithelial cells. There was also massive necrosis of splenic lymphoid tissue and localized necrosis in lymph nodes. Systemic vasculitis included oedema, localized fibrinoid necrosis, and infiltration of monocytes, lymphocytes, and plasma cells into vessel walls in the heart, lung, liver, kidney, adrenal gland, and the stroma of striated muscles. Thrombosis was present in small veins. Systemic toxic changes included degeneration and necrosis of the parenchyma cells in the lung, liver, kidney, heart, and adrenal gland. Electron microscopy demonstrated clusters of viral particles, consistent with coronavirus, in lung tissue. SARS is a systemic disease that injures many organs. The lungs, immune organs, and systemic small vessels are the main targets of virus attack, so that extensive consolidation of the lung, diffuse alveolar damage with hyaline membrane formation, respiratory distress, and decreased immune function are the main causes of death. Copyright © 2003 John Wiley & Sons, Ltd.


title: SARS‐CoV‐2 and Multiple Sclerosis: Not All Immune Depleting DMTs are Equal or Bad

text: A major concern during the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic1 is the use of immunosuppressive therapies for the treatment of multiple sclerosis (MS) due to an increased risk of contracting SARS-CoV-2 and more severe disease. The Society of Italian Neurologists (SIN) and the Association of British Neurologists (ABN) MS and Neuroimmunology Advisory Group published guidance for the use of current disease modifying treatments (DMTs) in MS (Table 1)2 . However, taking into account, less conservative viewpoints3 , the emerging knowledge of the biology of SARS-CoV-2, and in particular the role of the immune mechanisms contributing to the disease, we propose modification of these guidelines since it is not clear that immunosuppression is indeed detrimental in people with MS infected with SARS-CoV-2. We are thus proposing a more nuanced approach and that the categories of DMTs should be modified based on scientific principles and the biology of severe COVID-19 (Table 2). This article is protected by copyright. All rights reserved.


title: Prioritisation of Anti‐SARS‐Cov‐2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics

text: There is a rapidly expanding literature on the in vitro antiviral activity of drugs that may be repurposed for therapy or chemoprophylaxis against SARS‐CoV‐2. However, this has not been accompanied by a comprehensive evaluation of the target plasma and lung concentrations of these drugs following approved dosing in humans. Accordingly, EC(90) values recalculated from in vitro anti‐SARS‐CoV‐2 activity data was expressed as a ratio to the achievable maximum plasma concentrations (Cmax) at an approved dose in humans (Cmax/EC(90) ratio). Only 14 of the 56 analysed drugs achieved a Cmax/EC(90) ratio above 1. A more in‐depth assessment demonstrated that only nitazoxanide, nelfinavir, tipranavir (ritonavir‐boosted) and sulfadoxine achieved plasma concentrations above their reported anti‐SARS‐CoV‐2 activity across their entire approved dosing interval. An unbound lung to plasma tissue partition coefficient (K(p)U(lung)) was also simulated to derive a lung Cmax/EC(50) as a better indicator of potential human efficacy. Hydroxychloroquine, chloroquine, mefloquine, atazanavir (ritonavir‐boosted), tipranavir (ritonavir‐boosted), ivermectin, azithromycin and lopinavir (ritonavir‐boosted) were all predicted to achieve lung concentrations over 10‐fold higher than their reported EC(50). Nitazoxanide and sulfadoxine also exceeded their reported EC(50) by 7.8‐ and 1.5‐fold in lung, respectively. This analysis may be used to select potential candidates for further clinical testing, while deprioritising compounds unlikely to attain target concentrations for antiviral activity. Future studies should focus on EC(90) values and discuss findings in the context of achievable exposures in humans, especially within target compartments such as the lung, in order to maximise the potential for success of proposed human clinical trials.


title: Do antimicrobial mass medications work? A systematic review and meta-analysis of randomised clinical trials investigating antimicrobial prophylaxis or metaphylaxis against naturally occurring bovine respiratory disease

text: A distinct difference between veterinary and human medicine is the routine use of antimicrobial mass medications (prophylaxis, metaphylaxis) to healthy individuals. The need for antimicrobial mass medications is based on beliefs that group/s of animals will contract a bacterial disease (i.e. morbidity) and/or die (i.e. mortality). Bovine respiratory disease (BRD) represents the major indication for cattle antimicrobials worldwide. The objectives were to perform a systematic review and meta-analysis of randomised controlled clinical trials (RCTs) for naturally occurring BRD investigating antimicrobial prophylaxis/metaphylaxis to prevent morbidity/mortality. In total, 58 publications met the inclusion criteria summarizing 169 individual RCTs, spanning 50 years (1966–2016). Antimicrobial prophylaxis and metaphylaxis demonstrated moderate, yet highly variable relative risk reductions in BRD morbidity. These were dependent on the antimicrobial classes used, dependent on metaphylaxis definition, BRD attack rates and duration of the RCTs. Best relative risk reductions were from broad-spectrum critically important antimicrobials, or combinations. BRD prophylaxis/metaphylaxis represents major antimicrobial consumption for highly variable short-term gains in absolute risk reduction of morbidity/mortality. Despite widespread use of prevention products, the need for antimicrobial mass medications should be re-evaluated since the underlying problem is more likely the segmented infrastructure of the feedlot and veal calf industries compared to the disease itself.


title: Purification of infectious rubella virus by gel filtration on sepharose 2B compared to gradient centrifugation in sucrose, sodium metrizoate and metrizamide

text: Abstract Rubella virus was purified by chromatography on Sepharose 2B after concentration by ultrafiltration on hollow fibers and hydroextraction with PEG 20,000. Yields of 40% infectivity and 70% hemagglutinating activity were routinely obtained. Chromatographie purification was compared to ultracentrifugation in sucrose, metrizamide and sodium metrizoate. Yields were lower in sucrose and metrizamide, while sodium metrizoate reduced the infectivity of the virus below detectable levels. These results demonstrate the advantage of Sepharose 2B for the purification of infectious rubella virus.