title: Is gold a hedge against inflation? New evidence from a nonlinear ARDL approach

text: This paper aims to study the role of gold as a hedge against inflation based on local monthly gold prices in China, India, Japan, France, the United Kingdom and the United States of America in periods ranging from 1955 to 2015. We extend the literature by using a novel approach with the nonlinear autoregressive distributed lags (NARDL) model (Shin et al., 2014). The main advantage of this model relies on its ability to simultaneously capture the short- and long-run asymmetries through positive and negative partial sum decompositions of changes in the independent variable(s). Moreover, we rely on local gold prices instead of those from London converted into local currencies like in most of previous studies. The results show that gold is not a hedge against inflation in the long run in all cases. In the short run, gold is an inflation hedge only in the UK, USA, and India. Furthermore, there is no long-run equilibrium between gold prices and the CPI in China, India and France. This difference may be due to traditional aspects of gold and custom controls for gold trade in these countries. Our robustness check suggests that the data time-frequency does not change the specification of the NARDL model but can change conclusions regarding the role of gold as a hedge against inflation in certain countries.


The impact of Coronavirus (COVID-19) on head and neck cancer patients’ care


title: 3 Viral contaminants of molluscan shellfish: detection and characterisation

text: Abstract: Environmental virology started with the detection of poliovirus in water. Since then other enteric viruses responsible for gastroenteritis and hepatitis have replaced enteroviruses as the main target for detection. Most shellfish-borne viral outbreaks are restricted to norovirus and hepatitis A virus, making them the main targets for bivalve virological analysis. The inclusion of virus analysis in regulatory standards for viruses in molluscan bivalve samples must overcome several shortcomings such as the technical difficulties and high costs of virus monitoring, the lack of harmonised and standardised assays and the challenge posed by the ever-changing nature of viruses. Nowadays methods are available to detect, quantify and characterise viral pathogens in molluscan shellfish to reduce the risks of shellfish-borne virus diseases.


title: Analysis of SARS-CoV E protein ion channel activity by tuning the protein and lipid charge

text: Abstract A partial characterization of the ion channels formed by the SARS coronavirus (CoV) envelope (E) protein was previously reported (C. Verdiá-Báguena et al., 2012 [12]). Here, we provide new significant insights on the involvement of lipids in the structure and function of the CoV E protein channel on the basis of three series of experiments. First, reversal potential measurements over a wide range of pH allow the dissection of the contributions to channel selectivity coming from ionizable residues of the protein transmembrane domain and also from the negatively charged groups of diphytanoyl phosphatidylserine (DPhPS) lipid. The corresponding effective pKas are consistent with the model pKas of the acidic residue candidates for titration. Second, the change of channel conductance with salt concentration reveals two distinct regimes (Donnan-controlled electrodiffusion and bulk-like electrodiffusion) fully compatible with the outcomes of selectivity experiments. Third, by measuring channel conductance in mixtures of neutral diphytanoyl phosphatidylcholine (DPhPC) lipids and negatively charged DPhPS lipids in low and high salt concentrations we conclude that the protein–lipid conformation in the channel is likely the same in charged and neutral lipids. Overall, the whole set of experiments supports the proteolipidic structure of SARS-CoV E channels and explains the large difference in channel conductance observed between neutral and charged membranes.


Please cite this paper as: Qian et al. (2011) Attempted early detection of influenza A (H1N1) pandemic with surveillance data of influenza‐like illness and unexplained pneumonia. Influenza and Other Respiratory Viruses 5(6), e479–e486. Background To collect disease information and provide data for early detection of epidemics, two surveillance systems were established for influenza‐like illness (ILI) and unexplained pneumonia (UP) in Wuxi, People’s Republic of China. Objectives The current study aims to describe the performance of these surveillance systems during 2004–2009 and to evaluate the value of surveillance data in detection of influenza epidemics. Methods Two national ILI sentinel hospitals and three UP sentinel hospitals provided data to the surveillance systems. The surveillance data from hospital‐based outpatient clinics and emergency rooms were compared by year. The ILI data of 2009 were further modeled based on previous data using both a control chart method and a moving average regression method. Alarms of potential epidemics would be raised when the input surveillance data surpassed a threshold. Results In 2009, the proportions of ILI and respiratory illness with fever (one surveillance syndrome of the UP system) to total patient visits (3·40% and 11·76%, respectively) were higher than the previous years. The surveillance data of both systems also showed developing trends similar to the influenza A (H1N1) pandemic in 2009. When the surveillance data of 2009 were fitted in the two detection models, alarms were produced on the occurrence of the first local case of influenza A (H1N1), outbreaks in schools and in general populations. Conclusions The results indicated the potential for using ILI and UP surveillance data as syndromic indicators to detect and provide an early warning for influenza epidemics.


title: Immunosensor Based on Antibody-Functionalized MoS(2) for Rapid Detection of Avian Coronavirus on Cotton Thread

text: Infectious bronchitis virus (IBV), an avian coronavirus, significantly affects the performance of both the egg-laying and meat-type birds causing the foremost of economic loss in poultry industry. This paper aims to develop a rapid, low-cost, and sensitive biosensor for IBV detection by using molybdenum disulfide (MoS(2)). MoS(2) is a 2-D nanosheet which has strong high fluorescence-quenching ability when applied to a dye-labeled antibody (Ab). In this paper, we developed an Ab-functionalized MoS(2)-based fluorescent immunosensor, which utilized the fluorescence resonance energy transfer (FRET) between the MoS(2) and fluorescence dye during the Ab–antigen interaction. The assay was performed on a low-cost cotton thread-based microfluidic platform due to the good wicking property and flexibility. Upon the optimization of assay conditions, the immunosensor demonstrated remarkable sensitivity of [Formula: see text] EID(50) per mL and specificity with a dynamic linear response range of 10(2)–10(6) EID(50) per mL for IBV standard solutions. The developed immunoassay successfully detected the IBV spiked chicken serum with satisfactory results. The foregoing presents its potential application for on-farm detection.


title: Endosomal acidification and cathepsin L activity is required for calicivirus replication

text: Abstract The role of cellular proteases and endosome maturation in the entry of caliciviruses including porcine enteric calicivirus (PEC), murine norovirus (MNV)-1 and feline calicivirus (FCV) were investigated. Treatment with chloroquine or cathepsin L inhibitors, but not cathepsin B inhibitors, significantly reduced the replication of PEC, MNV and FCV. When concentrated PEC, MNV or FCV were incubated with recombinant cathepsin L, the minor capsid protein VP2 of PEC and the major capsid protein VP1 of MNV and FCV were cleaved by the protease based on the Western blot analysis. Confocal microscopy analysis of PEC and MNV-1 showed that viral capsid proteins were retained in the endosomes in the presence of a cathepsin L inhibitor or chloroquine during virus entry. The results of this study suggest the important role of endosome maturation and cathepsin L in the entry of caliciviruses, and cathepsin L as a potential therapeutic target for calicivirus infection.


COVID-19 Prevention and Control Strategies for Psychiatric Hospitals


title: Is Adipose Tissue a Reservoir for Viral Spread, Immune Activation, and Cytokine Amplification in Coronavirus Disease 2019?

text: Coronavirus disease 2019 (COVID‐19), the worst pandemic in more than a century, has claimed >125,000 lives worldwide to date. Emerging predictors for poor outcomes include advanced age, male sex, preexisting cardiovascular disease, and risk factors including hypertension, diabetes, and, more recently, obesity. This article posits new obesity‐driven predictors of poor COVID‐19 outcomes, over and above the more obvious extant risks associated with obesity, including cardiometabolic disease and hypoventilation syndrome in intensive care patients. This article also outlines a theoretical mechanistic framework whereby adipose tissue in individuals with obesity may act as a reservoir for more extensive viral spread, with increased shedding, immune activation, and cytokine amplification. This paper proposes studies to test this reservoir concept with a focus on specific cytokine pathways that might be amplified in individuals with obesity and COVID‐19. Finally, this paper underscores emerging therapeutic strategies that might benefit subsets of patients in which cytokine amplification is excessive and potentially fatal.


title: Methods for Preparation of MS2 Phage-Like Particles and Their Utilization as Process Control Viruses in RT-PCR and qRT-PCR Detection of RNA Viruses From Food Matrices and Clinical Specimens

text: RNA viruses are pathogenic agents of many serious infectious diseases affecting humans and animals. The detection of pathogenic RNA viruses is based on modern molecular methods, of which the most widely used methods are the reverse transcription polymerase chain reaction (RT-PCR) and the real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). All steps of RT-PCR and qRT-PCR should be strictly controlled to ensure the validity of obtained results. False-negative results may be caused not only by inhibition of RT or/and PCR steps but also by failure of the nucleic acid extraction step, particularly in the case of viral RNA extraction. The control of nucleic acid extraction generally involves the utilization of a non-pathogenic virus (process control virus) of similar structural properties to those of the target virus. Although in clinical samples the use of such process control virus is only recommended, in other kinds of settings such as food matrices its use is necessary. Currently, several different process control viruses are used for these purposes. Process control viruses can also be constructed artificially using technology for production of MS2 phage-like particles, which have many advantages in comparison with other used controls and are especially suited for controlling the detection and quantification of certain types of RNA viruses. The technology for production of MS2 phage-like particles is theoretically well established, uses the knowledge gained from the study of the familiar bacteriophage MS2 and utilizes many different approaches for the construction of the various process control viruses. Nevertheless, the practical use of MS2 phage-like particles in routine diagnostics is relatively uncommon. The current situation with regard to the use of MS2 phage-like particles as process control viruses in detection of RNA viruses and different methods of their construction, purification and use are summarized and discussed in this review.


title: Coupling infectious diseases, human preventive behavior, and networks – A conceptual framework for epidemic modeling

text: Human-disease interactions involve the transmission of infectious diseases among individuals and the practice of preventive behavior by individuals. Both infectious diseases and preventive behavior diffuse simultaneously through human networks and interact with one another, but few existing models have coupled them together. This article proposes a conceptual framework to fill this knowledge gap and illustrates the model establishment. The conceptual model consists of two networks and two diffusion processes. The two networks include: an infection network that transmits diseases and a communication network that channels inter-personal influence regarding preventive behavior. Both networks are composed of same individuals but different types of interactions. This article further introduces modeling approaches to formulize such a framework, including the individual-based modeling approach, network theory, disease transmission models and behavioral models. An illustrative model was implemented to simulate a coupled-diffusion process during an influenza epidemic. The simulation outcomes suggest that the transmission probability of a disease and the structure of infection network have profound effects on the dynamics of coupled-diffusion. The results imply that current models may underestimate disease transmissibility parameters, because human preventive behavior has not been considered. This issue calls for a new interdisciplinary study that incorporates theories from epidemiology, social science, behavioral science, and health psychology.


title: Acute peripheral immune activation alters cytokine expression and glial activation in the early postnatal rat brain

text: BACKGROUND: Neuroinflammation can modulate brain development; however, the influence of an acute peripheral immune challenge on neuroinflammatory responses in the early postnatal brain is not well characterized. To address this gap in knowledge, we evaluated the peripheral and central nervous system (CNS) immune responses to a mixed immune challenge in early postnatal rats of varying strains and sex. METHODS: On postnatal day 10 (P10), male and female Lewis and Brown Norway rats were injected intramuscularly with either a mix of bacterial and viral components in adjuvant, adjuvant-only, or saline. Immune responses were evaluated at 2 and 5 days post-challenge. Cytokine and chemokine levels were evaluated in serum and in multiple brain regions using a Luminex multiplex assay. Multi-factor ANOVAs were used to compare analyte levels across treatment groups within strain, sex, and day of sample collection. Numbers and activation status of astrocytes and microglia were also analyzed in the cortex and hippocampus by quantifying immunoreactivity for GFAP, IBA-1, and CD68 in fixed brain slices. Immunohistochemical data were analyzed using a mixed-model regression analysis. RESULTS: Acute peripheral immune challenge differentially altered cytokine and chemokine levels in the serum versus the brain. Within the brain, the cytokine and chemokine response varied between strains, sexes, and days post-challenge. Main findings included differences in T helper (Th) type cytokine responses in various brain regions, particularly the cortex, with respect to IL-4, IL-10, and IL-17 levels. Additionally, peripheral immune challenge altered GFAP and IBA-1 immunoreactivity in the brain in a strain- and sex-dependent manner. CONCLUSIONS: These findings indicate that genetic background and sex influence the CNS response to an acute peripheral immune challenge during early postnatal development. Additionally, these data reinforce that the developmental time point during which the challenge occurs has a distinct effect on the activation of CNS-resident cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-019-1569-2) contains supplementary material, which is available to authorized users.


title: COVID-19 por SARS-Cov2 también ha afectado a la Educación Médica

text: Resumen El virus, además de provocar una pandemia, con centenares de miles de enfermos y con decenas de miles de fallecidos, ha tenido la capacidad (“el poder”) de romper las prácticas educativas estándar. Esto ha tenido, o puede tener, un beneficio: reconsiderar lo que es realmente importante y lo que no lo es tanto. Y eso tiene un gran valor para el docente y para el discente. Y también ha servido para reconocer y encontrar formas alternativas con las que se puede transmitir el saber. En definitiva, el profesor ha tenido la oportunidad de contribuir a crear un modelo educativo capaz de impulsar el desarrollo de nuevas formas y métodos de aprendizaje. Ciertas técnicas y recursos educativos han podido ser reconocidos como “presentes” o “ausentes” de nuestro sistema educativo. Esto implica que ciertos recursos han de estar presentes, o que es preciso optimizar los que ya están disponibles para enseñar, para aprender, o para evaluar. La tecnología permite facilitar el contacto “directo” entre profesor y alumno, entre profesores, y entre alumnos. Pero sobra decir que la tecnología ha de estar disponible. Abstract The virus, besides causing a pandemic, with hundreds of thousands ill, and with tens of thousands dead, has had the ability (“the power”) to break standard education practices. This has had, or may have, one benefit: to reconsider that which is really important and that which is not so important. And this is of great value for the teacher and for the student. And it has also served to recognise and find alternative ways to transmit the knowledge. All things considered, the teacher has had the opportunity to contribute in creating an education model capable of boosting the development of new ways and methods of learning. Certain educational techniques and resources have been able to be recognised as “present” or “absent” in our education system. This implies that certain recourses have to be present, or that is required to optimise those that are available in order to teach, to learn, or to evaluate. Technology helps to provide “direct” contact between teacher and student, between teachers and between students. But it goes without saying that the technology has to be available.


title: Characterization of an Avian Infectious Bronchitis Virus Isolated in China from Chickens with Nephritis

text: One IBV isolate, SC021202, was isolated from the kidneys of the infected young chickens by inoculating embryonated eggs, and its morphology, physiochemical and haemagglutonating properties were detected. Virulence of the isolate SC021202 was determined with specific pathogen‐free (SPF) chicken inoculation. Nucleotide acid sequence of S1 gene of the isolate SC021202 was further sequenced and analysed. The physiochemical and morphological properties of the isolate SC021202 were in accordance to that of typical infectious bronchitis virus (IBV). In a pathogenicity experiment, the clinical signs and related gross lesions resembling those of field outbreak were reproduced and the virus isolate SC021202 was re‐isolated from the kidneys of the infected chicken. Sequence data demonstrated that the full length of the amplified S1 gene of the isolate SC021202 was composed of 1931 nucleotides, coding a polypeptide of 543 amino acid residues. Compared with IBV strains from GenBank, the nucleotide and deduced amino acid sequence of S1 gene of the isolate SC021202 shared 60.0–91.4% and 49.1–88.9% identities, respectively. A nucleotide fragment of ′CTTTTTAATTATACTAACGGA′ was inserted at nucleotide site 208 in the S1 gene of the isolate. These results indicated that IBV isolate SC021202 was a new variant IBV isolate and responsible for field outbreak of nephritis.


title: Use of the Human Coronavirus 2012 (MERS) GeneSig kit for MERS-CoV detection

text: Abstract Introduction Mortality due to MERS-CoV infection is common especially among immunocompromised patients. The pathogenesis and the transmission mode of this virus are still not well understood. The name of the virus is derived from the area of its appearance and the genomic sequence that was used in the development of qRT-PCR assays for MERS-CoV detection was retrieved from the first detected case isolate. The employed assays target various regions including the area upstream of the envelope gene (upE) that is used for screening and the open reading frames (ORF) 1a and 1b used for confirmation. Aim This study assesses the use of a MERS-CoV specific assay for screening of respiratory samples in anticipation of the possible spread of the virus in the region. Methods 46 respiratory specimens were tested using the qualitative one-step qRT-PCR GeneSig Human Coronavirus 2012 (MERS) kit (PrimerDesign™). Results Out of the 46 tested samples, 45 were negative for MERS-CoV and one sample was found MERS-CoV positive. Conclusion The GeneSig Human Coronavirus 2012 (MERS) kit is very useful for the screening of suspected respiratory cases in the Middle East area as well as other regions.


title: H1N1 infection and acute respiratory failure: Can we give non-invasive ventilation a chance?

text: Abstract In 2009, a novel H1N1 Influenza virus has emerged and on June 11 the World Health Organization declared it as pandemic. It may cause acute respiratory failure ranging from severe Acute Respiratory Distress Syndrome to exacerbations of airflow limitation. Non-invasive ventilation is now considered first-line intervention for different causes of acute respiratory failure and may be considered in the context of H1N1 pandemic. Although infection control issues have been arisen, non-invasive ventilation was effective and safe during the Severe Acute Respiratory Syndrome in Asia. It is reasonable to recommend non-invasive ventilation in H1N1-related exacerbations of chronic respiratory diseases, especially in negative-pressure wards. Treatment of early Acute Respiratory Distress Syndrome associated with H1N1 using non-invasive ventilation could be tried rapidly identifying those who fail without delaying endotracheal intubation. Considering the high demand for critical care beds during the pandemic, non-invasive ventilation may have a role in reducing the estimated load.


title: In the Name of COVID-19: Is the ECB Fuelling the Climate Crisis?

text: We offer preliminary evidence drawing on a novel dataset of corporate bonds issued in the European energy sector since January 2020 in combination with the European Central Bank’s (ECB) purchases under the Pandemic Emergency Purchase Programme (PEPP) in response to COVID-19. We show that the likelihood of a European energy company bond to be bought as part of the ECB’s programme increases with the greenhouse gas (GHG) intensity of the bond issuing firm. We also find weaker evidence that the ECB’s PEPP portfolio during the pandemic is likely to become tilted towards companies with anti-climate lobbying activities and companies with less transparent GHG emissions disclosure. Our findings imply that, at later stages of the COVID-19 recovery, an in-depth analysis may be necessary to understand if, and if yes why, the ECB fuelled the climate crisis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10640-020-00450-z) contains supplementary material, which is available to authorized users.


title: Ruling out trouble: Unacceptable behaviour and its control in Hong Kong’s public housing

text: Resident satisfaction is contingent not only on housing design and construction, but also on neighbourhood quality. However, many neighbourhoods around the world are distressed by neighbourhood nuisances or unacceptable behaviour of the residents. While interventionist approaches and incentives have been adopted in many countries to curb these problems, a punitive measure is used in Hong Kong instead. The Housing Department launched the Marking Scheme for Tenancy Enforcement in Public Housing Estates immediately after the SARS epidemic. The scheme operates as a penalty-point system where sitting tenants will be expelled from public housing if they receive sixteen points for the misdeeds they have committed. Yet, the marking scheme itself was put onto the stage without any prior public consultation. Besides, it has been criticised for its unfair and tenure-biased enforcement. Also, whether the scheme is widely accepted is highly doubtful. Against this background, this study aims to explore the tenants’ views regarding residents’ unacceptable behaviour and the marking scheme in Hong Kong’s public housing. The findings of this research offer valuable insights into the perceived extent and causes of the neighbourhood problems. Moreover, this research lets the public administrators know the acceptability of the marking scheme among public housing tenants.


title: Safe management of surgical smoke in the age of COVID‐19

text: BACKGROUND: The COVID‐19 global pandemic has resulted in a plethora of guidance and opinion from surgical societies. A controversial area concerns the safety of surgically created smoke and the perceived potential higher risk in laparoscopic surgery. METHODS: The limited published evidence was analysed in combination with expert opinion. A review was undertaken of the novel coronavirus with regards to its hazards within surgical smoke and the procedures that could mitigate the potential risks to healthcare staff. RESULTS: Using existing knowledge of surgical smoke, a theoretical risk of virus transmission exists. Best practice should consider the operating room set‐up, patient movement and operating theatre equipment when producing a COVID‐19 operating protocol. The choice of energy device can affect the smoke produced, and surgeons should manage the pneumoperitoneum meticulously during laparoscopic surgery. Devices to remove surgical smoke, including extractors, filters and non‐filter devices, are discussed in detail. CONCLUSION: There is not enough evidence to quantify the risks of COVID‐19 transmission in surgical smoke. However, steps can be undertaken to manage the potential hazards. The advantages of minimally invasive surgery may not need to be sacrificed in the current crisis.


title: Using Telemedicine and Infographics for Physician-Guided Home Drain Removal

text: OBJECTIVE: Measures to decrease hospital length of stay and outpatient visits are crucial during the coronavirus disease 2019 (COVID-19) pandemic. Physician-guided home drain removal presents a potential opportunity for mitigating viral spread and transmission. METHODS: A prospective case series on patients undergoing major head and neck surgery with Jackson-Pratt drain placement was conducted. Patients were shown an infographic detailing drain care and removal at preoperative assessment and prior to discharge. At a 1-week follow-up telemedicine visit, patients were instructed to remove the drain under physician guidance. Patients were assessed 7 days after to determine complication rate and satisfaction. RESULTS: Twenty-five patients were enrolled with 100% patients undergoing successful drain removal at home with caregiver support. There were no complications reported at the 7-day postdrain removal time point, and overall patient satisfaction was high. DISCUSSION: Infographics and telemedicine are 2 synergistic strategies to guide safe and effective home drain removal. IMPLICATIONS FOR PRACTICE: This study demonstrates how telemedicine and an infographic can be effectively used in physician-guided home drain removal. During a time like the COVID-19 pandemic, innovative measures are necessary to curb transmission and infection rates. We propose a unique and replicable yet safe solution to limit unnecessary exposure and encourage other surgical providers to adopt a similar strategy.


title: COVID-19 for the Cardiologist: A Current Review of the Virology, Clinical Epidemiology, Cardiac and Other Clinical Manifestations and Potential Therapeutic Strategies

text: Summary The coronavirus disease-2019 (COVID-19), a contagious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), has reached pandemic status. As it spreads across the world, it has overwhelmed healthcare systems, strangled the global economy and led to a devastating loss of life. Widespread efforts from regulators, clinicians and scientists are driving a rapid expansion of knowledge of the SARS-CoV2 virus and the COVID-19 disease. We review the most current data with a focus on our basic understanding of the mechanism(s) of disease and translation to the clinical syndrome and potential therapeutics. We discuss the basic virology, epidemiology, clinical manifestation, multi-organ consequences, and outcomes. With a focus on cardiovascular complications, we propose several mechanisms of injury. The virology and potential mechanism of injury form the basis for a discussion of potential disease-modifying therapies.


title: Successful treatment of feline leishmaniosis using a combination of allopurinol and N-methyl-glucamine antimoniate

text: CASE SUMMARY: This work describes the diagnosis and successful treatment of a 2-year-old domestic cat infected with Leishmania species and presenting fever, and ulcerative and nodular skin lesions after being treated for pyodermatitis for 1 year without clinical improvement. After anamnesis the cat was submitted to a complete clinical examination. Blood was collected for determination of haematological and biochemical parameters, detection of feline leukaemia virus (FeLV), feline immunodeficiency virus (FIV), feline coronavirus (FCoV) and Leishmania amastigotes. Fine-needle aspiration puncture from the skin nodules was also performed. After definitive diagnosis the animal was treated and followed up over a 2 year period. The animal tested negative for FIV-specific antibodies, FeLV antigen and feline coronavirus RNA. Leishmania amastigotes in the skin nodules were confirmed by cytology and molecular diagnosis. Treatment was initiated with allopurinol, resulting in a slight clinical improvement. Thus, N-methyl-glucamine antimoniate was added and administered for 30 days, with complete closure of the ulcerative lesions in the hindlimbs requiring a surgical approach. Close monitoring of the patient in the following 24 months indicated that combined therapy was safe and clinical cure was achieved without further relapses or side effects. RELEVANCE AND NOVEL INFORMATION: Considering the increasing number of feline leishmaniosis cases and the inconsistent results of most therapeutic protocols described in the literature, the use of new approaches, especially in refractory cases, is essential. Although the use of allopurinol and N-methyl-glucamine antimoniate is off-label in cats, in this case the combination treatment was followed by an extensive analytical monitoring, supporting their safety and effectiveness.


title: Practice recommendations for the neurovascular ultrasound investigations of acute stroke patients in the setting of COVID‐19 pandemic: an expert consensus from the European Society of Neurosonology and Cerebral Hemodynamics

text: Since the COVID‐19 pandemic stormed into the healthcare systems worldwide, protected stroke pathways have been suggested, in order not to spread the viral infection and ensure hyper‐acute treatment. Noteworthy, patients with acute ischemic stroke are at high‐risk for contracting SARS‐CoV‐2 virus, particularly the severe form, because COVID‐19 and cerebrovascular diseases share common risk factors. Conversely, among patients hospitalized with SARS‐CoV‐2 respiratory distress, about 5% might suffer a stroke. During the acute stages of the pandemic, thousands of healthcare professionals have already contracted COVID‐19 infection, although the actual number is likely to be higher because healthcare workers are not always tested and protection measures at hospitals are not always readily available. This is the setting in which neurovascular ultrasound providers (physicians, sonographers) should expect to be involved in the care of stroke patients.


title: Étiologies virales des infections respiratoires basses chez des patients adultes hospitalisés dans un service de pneumologie à Abidjan, Côte d’Ivoire

text: INTRODUCTION: La pneumonie est une cause majeure de morbidité et une cause importante de mortalité dans le monde [1]. Les étiologies sont dominées par les causes infectieuses, parmi lesquelles les bactéries et les virus occupent une place importante. Les virus sont responsables de la forme la plus grave de l’infection [2]. L’objectif de cette étude était d’identifier les causes virales des infections respiratoires basses chez les patients adultes. MÉTHODES: Il s’agit d’une étude prospective et descriptive menée sur la base de recrutement successif de patients âgés de 15 ans et plus, admis au service de pneumologie du CHU de Cocody du 1(er) février 2016 au 31 octobre 2017 pour pneumopathie alvéolo-interstitielle fébrile sévère confirmée à la radiographie du thorax de face ou au scanner thoracique avec des bacilloscopies négatives et qui ont bénéficié d’une fibroscopie bronchique avec lavage broncho-alvéolaire. RÉSULTATS: Nous avons inclus 33 dossiers sur 90 dossiers durant la période d’étude. Le sex-ratio était de 1,1 avec une moyenne d’âge de 39,6 ans (19–68 ans). La tranche d’âge de 30–40 ans était plus sujette aux pneumonies (48,5 %). L’inclusion des patients était plus importante pendant la saison de mars à juin (45,5 %). La détection de virus respiratoire par la réaction en chaîne de polymérase inverse multiplex en temps réel (RT-PCR) était positive dans 21,2 % des cas (7/33). Les virus retrouvés étaient : parainfluenza-3 (57,1 % 4/7), coronavirus OC43 (14,3 % 1/7), coronavirus HKUI (14,3 % 1/7) et rhinovirus humain (14,3 % 1/7). CONCLUSION: Les infections respiratoires d’étiologie virale sont peu fréquentes à Abidjan. Elles sont essentiellement dominées par le virus para influenzae de type 3.


title: Tissue tropism and transmission ecology predict virulence of human RNA viruses

text: Novel infectious diseases continue to emerge within human populations. Predictive studies have begun to identify pathogen traits associated with emergence. However, emerging pathogens vary widely in virulence, a key determinant of their ultimate risk to public health. Here, we use structured literature searches to review the virulence of each of the 214 known human-infective RNA virus species. We then use a machine learning framework to determine whether viral virulence can be predicted by ecological traits, including human-to-human transmissibility, transmission routes, tissue tropisms, and host range. Using severity of clinical disease as a measurement of virulence, we identified potential risk factors using predictive classification tree and random forest ensemble models. The random forest approach predicted literature-assigned disease severity of test data with mean accuracy of 89.4% compared to a null accuracy of 74.2%. In addition to viral taxonomy, the ability to cause systemic infection was the strongest predictor of severe disease. Further notable predictors of severe disease included having neural and/or renal tropism, direct contact or respiratory transmission, and limited (0 < R(0) ≤ 1) human-to-human transmissibility. We present a novel, to our knowledge, comparative perspective on the virulence of all currently known human RNA virus species. The risk factors identified may provide novel perspectives in understanding the evolution of virulence and elucidating molecular virulence mechanisms. These risk factors could also improve planning and preparedness in public health strategies as part of a predictive framework for novel human infections.


title: Developing Novel G-Quadruplex Ligands: From Interaction with Nucleic Acids to Interfering with Nucleic Acid–Protein Interaction

text: G-quadruplex is a special secondary structure of nucleic acids in guanine-rich sequences of genome. G-quadruplexes have been proved to be involved in the regulation of replication, DNA damage repair, and transcription and translation of oncogenes or other cancer-related genes. Therefore, targeting G-quadruplexes has become a novel promising anti-tumor strategy. Different kinds of small molecules targeting the G-quadruplexes have been designed, synthesized, and identified as potential anti-tumor agents, including molecules directly bind to the G-quadruplex and molecules interfering with the binding between the G-quadruplex structures and related binding proteins. This review will explore the feasibility of G-quadruplex ligands acting as anti-tumor drugs, from basis to application. Meanwhile, since helicase is the most well-defined G-quadruplex-related protein, the most extensive research on the relationship between helicase and G-quadruplexes, and its meaning in drug design, is emphasized.


title: Analysis of Maternal Coronavirus Infections and Neonates Born to Mothers with 2019-nCoV; a Systematic Review

text: INTRODUCTION: The emergence and fast spread of 2019 novel coronavirus (2019-nCoV) threatens the world as a new public health crisis. This study aimed to clarify the impact of novel coronavirus disease (COVID-19) on pregnant patients and maternal and neonatal outcomes. METHODS: A comprehensive literature search was conducted in databases including PubMed, Scopus, Embase, ProQuest, and Science Direct. All studies including original data; case reports, case series, descriptive and observational studies, and randomized controlled trials were searched from December 2019 until 19 March 2020. RESULTS: The search identified 1472 results and 939 abstracts were screened. 928 articles were excluded because studies did not include pregnant women. Full texts of eleven relevant studies were reviewed and finally nine studies were included in this study. The characteristics of 89 pregnant women and their neonates were studied. Results revealed that low-grade fever and cough were the principal symptoms in all patients. The main reported laboratory findings were lymphopenia, elevated C-Reactive Protein (CRP), Amino alanine transferase (ALT), and Aspartate amino transferase (AST). In all symptomatic cases, chest Computerized Tomography (CT) scans were abnormal. Fetal distress, premature rupture of membranes and preterm labor were the main prenatal complications. Two women needed intensive care unit admission and mechanical ventilation, one of whom developed multi-organ dysfunction and was on Extracorporeal Membrane Oxygenation (ECMO). No case of maternal death was reported up to the time the studies were published. 79 mothers delivered their babies by cesarean section and five women had a vaginal delivery. No fetal infection through intrauterine vertical transmission was reported. CONCLUSIONS: Available data showed that pregnant patients in late pregnancy had clinical manifestations similar to non-pregnant adults. It appears that the risk of fetal distress, preterm delivery and prelabor rupture of membranes (PROM) rises with the onset of COVID-19 in the third trimester of pregnancy. There is also no evidence of intrauterine and transplacental transmission of COVID-19 to the fetus in the third trimester of pregnancies.


title: Extremely Severe Case of COVID-19 Pneumonia Recovered Despite Bad Prognostic Indicators: a Didactic Report

text: COVID-19 is a highly infectious respiratory disease caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Starting from Wuhan (China) where it was firstly reported, it rapidly spread to the rest of the world, causing a pandemic with more than 300,000 deaths to date. We report an extremely severe case of coronavirus pneumonia in an over 80-year-old patient with hypertension, coronary heart disease, chronic heart failure, and chronic obstructive pulmonary disease. Despite a clearly poor anamnestic and clinical prognostic forecast, she was successfully discharged thanks to a careful evaluation of the case and of the complications that have arisen. Although a higher vulnerability of geriatric patients has been observed, the literature on elderly COVID-19 patients has remained very scarce, especially in those over 80. The article aims to explore factors that may allow the successful outcome and provides important elements to better understand this disease.


title: A novel full-length isoform of murine pregnancy-specific glycoprotein 16 (psg16) is expressed in the brain but does not mediate murine coronavirus (MHV) entry

text: The mouse pregnancy-specific glycoprotein 16 (PSG16) has been reported to be an alternative receptor for mouse hepatitis virus (MHV), some strains of which cause encephalitis in mice lacking the canonical receptor CEACAM1a. The known isoforms of PSG16 are N-terminally truncated relative to other PSG family proteins and are expressed in neurons as well as in the placenta. We have cloned a novel full-length isoform of psg16 that is also expressed in the brain, placenta, and retina but, like the truncated form, lacks MHV receptor activity when expressed on 293T cells, suggesting that PSG16 does not mediate CEACAM1a-independent spread of MHV.


title: Cancer, COVID-19 and the precautionary principle: prioritizing treatment during a global pandemic

text: During the COVID-19 global pandemic, the cancer community faces many difficult questions. We will first discuss safety considerations for patients with cancer requiring treatment in SARS-CoV-2 endemic areas. We will then discuss a general framework for prioritizing cancer care, emphasizing the precautionary principle in decision making.


title: Changes in blood coagulation in patients with severe coronavirus disease 2019 (COVID‐19): a meta‐analysis

text: Coronavirus disease 2019 (COVID-19) is widely spread and poses a critical threat to global health (Zhang et al). Prominent changes in coagulation function in severe patients of COVID-19 have been reported in a recent study (Han, et al 2020). Therefore, we conducted this quantitative meta-analysis to explore the difference in blood coagulation parameters between severe and mild cases of COVID-19.


title: Microbiota in viral infection and disease in humans and farm animals

text: Abstract The influence of the microbiota on viral infection susceptibility and disease outcome is undisputable although varies among viruses. The purpose of understanding the interactions between microbiota, virus, and host is to identify practical, effective, and safe approaches that target microbiota for the prevention and treatment of viral diseases in humans and animals, as currently there are few effective and reliable antiviral therapies available. The initial step for achieving this goal is to gather clinical evidences, focusing on the viral pathogens—from human and animal studies—that have already been shown to interact with microbiota. The subsequent step is to identify mechanisms, through experimental evidences, to support the development of translational applications that target microbiota. In this chapter, we review evidences of virus infections altering microbiota and of microbiota enhancing or suppressing infectivity, altering host susceptibility to certain viral diseases, and influencing vaccine immunogenicity in humans and farm animals.


title: Not all cows are epidemiologically equal: quantifying the risks of bovine viral diarrhoea virus (BVDV) transmission through cattle movements

text: Many economically important cattle diseases spread between herds through livestock movements. Traditionally, most transmission models have assumed that all purchased cattle carry the same risk of generating outbreaks in the destination herd. Using data on bovine viral diarrhoea virus (BVDV) in Scotland as a case example, this study provides empirical and theoretical evidence that the risk of disease transmission varies substantially based on the animal and herd demographic characteristics at the time of purchase. Multivariable logistic regression analysis revealed that purchasing pregnant heifers and open cows sold with a calf at foot were associated with an increased risk of beef herds being seropositive for BVDV. Based on the results from a dynamic within-herd simulation model, these findings may be partly explained by the age-related probability of animals being persistently infected with BVDV as well as the herd demographic structure at the time of animal introductions. There was also evidence that an epidemiologically important network statistic, “betweenness centrality” (a measure frequently associated with the potential for herds to acquire and transmit disease), was significantly higher for herds that supplied these particular types of replacement beef cattle. The trends for dairy herds were not as clear, although there was some evidence that open heifers and open lactating cows were associated with an increased risk of BVDV. Overall, these findings have important implications for developing simulation models that more accurately reflect the industry-level transmission dynamics of infectious cattle diseases.


Persistence of Physical Symptoms in and Abnormal Laboratory Findings for Survivors of Severe Acute Respiratory Syndrome


title: Reasoning within expressive fuzzy rough description logics

text: Abstract It is generally accepted that the management of imprecision and vagueness will yield more intelligent and realistic knowledge-based applications. Description Logics (DLs) are suitable, well-known logics for managing structured knowledge that have gained considerable attention the last decade. The current research progress and the existing problems of uncertain or imprecise knowledge representation and reasoning in DLs are analyzed in this paper. An integration between the theories of fuzzy DLs and rough DLs has been attempted by providing fuzzy rough DLs based on fuzzy rough set theory. The syntax, semantics and properties of fuzzy rough DLs are given. It is proved that the satisfiability, subsumption, entailment and ABox consistency reasoning in fuzzy rough DLs may be reduced to the ABox consistency reasoning in the corresponding fuzzy DLs.


A unique role in global nephrology The International Society of Nephrology 2011-2020


title: Transforming laparoendoscopic surgical protocols during COVID-19 pandemic; big data analytics, resource allocation and operational considerations; a review article

text: The current dreadful pandemic of coronavirus disease (COVID-19) is playing havoc with humanity, socio-communal systems and economic reservoirs worldwide. Certain countries have managed to curtail COVID-19 crisis to some extent, however, a great majority still remains helpless in containing this outbreak. Rapidly evolving disease patterns and complex epidemiology of COVID-19 necessitate a tailored approach by medical experts in dealing with this devastating outbreak. Similar to other medical disciplines, surgical associations and societies have developed a tailored approach of patients’ selection and planning with improvised endolaparoscopic practice during the COVID-19 pandemic. Non-essential and non-urgent surgical procedures are deferred till this outbreak is abated. Benefits of delaying elective and non-urgent surgery outweighs the risk of performing surgical procedures on patients with asymptomatic or active COVID-19 disease. Laparoendoscopic procedures increase the risk of aerosol exposure, disease transmission and contamination. Limiting the number of operating room personnel, use of disposable instruments, small trocar incisions, negative pressure environment, and setting energy devices at low modes can help reduce disease transmission during laparoendocsopic procedures. This write up provides a brief account of the impact of the COVID-19, big data analytics of response of medical personnel in curtailing and understanding the disease process and the consensus guidelines for carrying out laparoscopic and endoscopic procedures.


Data resource profile: Household Influenza Vaccine Evaluation (HIVE) Study


title: Cytoplasmic domains of cellular and viral integral membrane proteins substitute for the cytoplasmic domain of the vesicular stomatitis virus glycoprotein in transport to the plasma membrane

text: Oligonucleotide-directed mutagenesis was used to construct chimeric cDNAs that encode the extracellular and transmembrane domains of the vesicular stomatitis virus glycoprotein (G) linked to the cytoplasmic domain of either the immunoglobulin mu membrane heavy chain, the hemagglutinin glycoprotein of influenza virus, or the small glycoprotein (p23) of infectious bronchitis virus. Biochemical analyses and immunofluorescence microscopy demonstrated that these hybrid genes were correctly expressed in eukaryotic cells and that the hybrid proteins were transported to the plasma membrane. The rate of transport to the Golgi complex of G protein with an immunoglobulin mu membrane cytoplasmic domain was approximately sixfold slower than G protein with its normal cytoplasmic domain. However, this rate was virtually identical to the rate of transport of micron heavy chain molecules measured in the B cell line WEHI 231. The rate of transport of G protein with a hemagglutinin cytoplasmic domain was threefold slower than wild type G protein and G protein with a p23 cytoplasmic domain, which were transported at similar rates. The combined results underscore the importance of the amino acid sequence in the cytoplasmic domain for efficient transport of G protein to the cell surface. Also, normal cytoplasmic domains from other transmembrane glycoproteins can substitute for the G protein cytoplasmic domain in transport of G protein to the plasma membrane. The method of constructing precise hybrid proteins described here will be useful in defining functions of specific domains of viral and cellular integral membrane proteins.


title: Infectious Diseases and Agriculture

text: Synopsis • Agriculture has huge impacts on human health, both positive and negative • Agriculture has not been oriented to achieving health outcomes • The livestock sector creates a disproportionate share of risks and benefits • Health problems related to farming and food require solutions that include these sectors


title: Ideas for how informaticians can get involved with COVID-19 research

text: The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on population health and wellbeing. Biomedical informatics is central to COVID-19 research efforts and for the delivery of healthcare for COVID-19 patients. Critical to this effort is the participation of informaticians who typically work on other basic science or clinical problems. The goal of this editorial is to highlight some examples of COVID-19 research areas that could benefit from informatics expertise. Each research idea summarizes the COVID-19 application area, followed by an informatics methodology, approach, or technology that could make a contribution. It is our hope that this piece will motivate and make it easy for some informaticians to adopt COVID-19 research projects.


title: An investigation into the identification of potential inhibitors of SARS-CoV-2 main protease using molecular docking study

text: A new strain of a novel infectious disease affecting millions of people, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently been declared as a pandemic by the World Health Organization (WHO). Currently, several clinical trials are underway to identify specific drugs for the treatment of this novel virus. The inhibition of the SARS-CoV-2 main protease is necessary for the blockage of the viral replication. Here, in this study, we have utilized a blind molecular docking approach to identify the possible inhibitors of the SARS-CoV-2 main protease, by screening a total of 33 molecules which includes natural products, anti-virals, anti-fungals, anti-nematodes and anti-protozoals. All the studied molecules could bind to the active site of the SARS-CoV-2 protease (PDB: 6Y84), out of which rutin (a natural compound) has the highest inhibitor efficiency among the 33 molecules studied, followed by ritonavir (control drug), emetine (anti-protozoal), hesperidin (a natural compound), lopinavir (control drug) and indinavir (anti-viral drug). All the molecules, studied out here could bind near the crucial catalytic residues, HIS41 and CYS145 of the main protease, and the molecules were surrounded by other active site residues like MET49, GLY143, HIS163, HIS164, GLU166, PRO168, and GLN189. As this study is based on molecular docking, hence being particular about the results obtained, requires extensive wet-lab experimentation and clinical trials under in vitro as well as in vivo conditions. Communicated by Ramaswamy H. Sarma


title: Luteolin suppresses inflammation-associated gene expression by blocking NF-κB and AP-1 activation pathway in mouse alveolar macrophages

text: Abstract Luteolin, a plant flavonoid, has potent anti-inflammatory properties both in vitro and in vivo. However, the molecular mechanism of luteolin-mediated immune modulation has not been fully understood. In this study, we examined the effects of luteolin on the production of nitric oxide (NO) and prostaglandin E2 (PGE2), as well as the expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in mouse alveolar macrophage MH-S and peripheral macrophage RAW 264.7 cells. Luteolin dose-dependently inhibited the expression and production of these inflammatory genes and mediators in macrophages stimulated with lipopolysaccharide (LPS). Semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay further confirmed the suppression of LPS-induced TNF- α, IL-6, iNOS and COX-2 gene expression by luteolin at a transcriptional level. Luteolin also reduced the DNA binding activity of nuclear factor-kappa B (NF-κB) in LPS-activated macrophages. Moreover, luteolin blocked the degradation of IκB-α and nuclear translocation of NF-κB p65 subunit. In addition, luteolin significantly inhibited the LPS-induced DNA binding activity of activating protein-1 (AP-1). We also found that luteolin attenuated the LPS-mediated protein kinase B (Akt) and IKK phosphorylation, as well as reactive oxygen species (ROS) production. In sum, these data suggest that, by blocking NF-κB and AP-1 activation, luteolin acts to suppress the LPS-elicited inflammatory events in mouse alveolar macrophages, and this effect was mediated, at least in part, by inhibiting the generation of reactive oxygen species. Our observations suggest a possible therapeutic application of this agent for treating inflammatory disorders in lung.


title: Preparation and characterization of a single-domain antibody specific for the porcine epidemic diarrhea virus spike protein

text: Porcine epidemic diarrhea (PED) is a diarrheal disease of swine caused by porcine epidemic diarrhea virus (PEDV). It is characterized by acute watery diarrhea, dehydration and vomiting in swine of all ages and is especially fatal for neonatal and postweaning piglets. The spike protein of PEDV plays an important role in mediating virus attachment and fusion to target cells, and recent studies also reported that the neutralizing epitopes of the spike protein were mainly located in the S1 subunit, which makes it a candidate for vaccine development and clinical diagnosis. In this study, we successfully constructed an immune phage display single-domain antibody library with a library size of 3.4 × 10(6). A single-domain antibody, named S7, specific for the spike protein of PEDV was identified from the phage display single-domain antibody library. S7 could be expressed in a soluble form in E. coli, bound to the spike protein of PEDV in ELISA and stained the PEDV virus in Vero cells, but it showed no neutralization activity on PEDV. These results indicated the potent application of the S7 antibody as an imaging probe or as a candidate for the development of a diagnostic assay. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13568-019-0834-1) contains supplementary material, which is available to authorized users.


title: Evaluation of local and systemic immune responses in pigs experimentally challenged with porcine reproductive and respiratory syndrome virus

text: The host-associated defence system responsible for the clearance of porcine reproductive and respiratory syndrome virus (PRRSV) from infected pigs is currently poorly understood. To better understand the dynamics of host–pathogen interactions, seventy-five of 100 pigs infected with PRRSV-JA142 and 25 control pigs were euthanized at 3, 10, 21, 28 and 35 days post-challenge (dpc). Blood, lung, bronchoalveolar lavage (BAL) and bronchial lymph node (BLN) samples were collected to evaluate the cellular immune responses. The humoral responses were evaluated by measuring the levels of anti-PRRSV IgG and serum virus-neutralizing (SVN) antibodies. Consequently, the highest viral loads in the sera and lungs of the infected pigs were detected between 3 and 10 dpc, and these resulted in moderate to mild interstitial pneumonia, which resolved accompanied by the clearance of most of the virus by 28 dpc. At peak viremia, the frequencies of alveolar macrophages in infected pigs were significantly decreased, whereas the monocyte-derived DC/macrophage and conventional DC frequencies were increased, and these effects coincided with the early induction of local T-cell responses and the presence of proinflammatory cytokines/chemokines in the lungs, BAL, and BLN as early as 10 dpc. Conversely, the systemic T-cell responses measured in the peripheral blood mononuclear cells were delayed and significantly induced only after the peak viremic stage between 3 and 10 dpc. Taken together, our results suggest that activation of immune responses in the lung could be the key elements for restraining PRRSV through the early induction of T-cell responses at the sites of virus replication.


Neurological Issues in COVID-19, Summarized in Verse


title: Viral Diversity of Microbats within the South West Botanical Province of Western Australia

text: Bats are known reservoirs of a wide variety of viruses that rarely result in overt clinical disease in the bat host. However, anthropogenic influences on the landscape and climate can change species assemblages and interactions, as well as undermine host-resilience. The cumulative result is a disturbance of bat–pathogen dynamics, which facilitate spillover events to sympatric species, and may threaten bat communities already facing synergistic stressors through ecological change. Therefore, characterisation of viral pathogens in bat communities provides important basal information to monitor and predict the emergence of diseases relevant to conservation and public health. This study used targeted molecular techniques, serological assays and next generation sequencing to characterise adenoviruses, coronaviruses and paramyxoviruses from 11 species of insectivorous bats within the South West Botanical Province of Western Australia. Phylogenetic analysis indicated complex ecological interactions including virus–host associations, cross-species infections, and multiple viral strains circulating concurrently within selected bat populations. Additionally, we describe the entire coding sequences for five alphacoronaviruses (representing four putative new species), and one novel adenovirus. Results indicate that viral burden (both prevalence and richness) is not homogeneous among species, with Chalinolobus gouldii identified as a key epidemiological element within the studied communities.


title: Clinical characteristics and outcomes of patients with severe acute respiratory infections (SARI): results from the Egyptian surveillance study 2010–2014

text: BACKGROUND: Respiratory viral and atypical bacterial infections data in Egyptian patients are sparse. This study describes the clinical features and outcomes of patients with severe acute respiratory infections (SARI) in hospitalized patients in Egypt. METHODS: SARI surveillance was implemented at Cairo University Hospital (CUH) during the period 2010–2014. All hospitalized patients meeting the WHO case definition for SARI were enrolled. Nasopharyngeal/oropharyngeal (NP/OP) swabs were collected and samples were tested using RT-PCR for influenza A, B, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), parainfluenza virus (PIV 1,2,3,4), adenovirus, bocavirus, coronavirus, enterovirus, rhinovirus, and atypical bacteria. Data were analyzed to calculate positivity rates for viral pathogens and determine which pathogens related to severe outcomes or resulted in death. RESULTS: Overall, 1,075/3,207 (33.5%) cases had a viral etiology, with a mean age of 5.74 (±13.87) years. The highest rates were reported for RSV (485 cases, 45.2%), PIV (125, 11.6%), and adenovirus (105, 9.8%). Children had a higher viral rate (981, 91.2%) compared to 94 (8.8%) cases in adults. Patients with identified viruses had significantly lower rates for ICU admission, hospital stay, mechanical ventilation, and overall mortality than those without identified viruses. No infections were independently associated with severe outcomes. CONCLUSIONS: Viral pathogens were encountered in one-third of hospitalized adult and pediatric Egyptian patients with SARI, while atypical bacteria had a minor role. Highest rates of viral infections were reported for RSV, PIV, and adenovirus. Viral infections had neither negative impacts on clinical features nor outcomes of patients with SARI in our locality.


title: Function of the RNA Coliphage Qβ Proteins in Medical In Vitro Evolution

text: Qβ is a positive (+) single-stranded RNA bacteriophage covered by a 25 nm icosahedral shell. Qβ belongs to the family of Leviviridae and is found throughout the world (bacterial isolates and sewage). The genome of Qβ is about 4.2 kb, coding for four proteins. This genome is surrounded by 180 copies of coat proteins (capsomers) each comprised of 132 residues of amino acids. The other proteins, the subunit II (β) of a replicase, the maturation protein (A(2)) and the read-through or minor coat protein (A(1)), play a key role in phage infection. With the replicase protein, which lacks proofreading activity, as well as its short replication time, and high population size, Qβ phage has attractive features for in vitro evolution. The A(1) protein gene shares the same initiation codon with the coat protein gene and is produced during translation when the coat protein’s UGA stop codon triplet (about 400 nucleotides from the initiation) is suppressed by a low level of ribosome misincorporation of tryptophan. Thus, A(1) is termed the read-through protein. This RNA phage platform technology not only serves to display foreign peptides but is also exceptionally suited to address questions about in vitro evolution. The C-terminus of A(1) protein confers to this RNA phage platform an exceptional feature of not only a linker for foreign peptide to be displayed also a model for evolution. This platform was used to present a peptide library of the G-H loop of the capsid region P1 of the foot-and-mouth disease virus (FMDV) called VP1 protein. The library was exposed on the exterior surface of Qβ phages, evolved and selected with the monoclonal antibodies (mAbs) SD6 of the FMDV. These hybrid phages could principally be good candidates for FMDV vaccine development. Separately, the membrane proximal external region (MPER) of human immunodeficiency virus type 1 (HIV-1) epitopes was fused with the A(1) proteins and exposed on the Qβ phage exterior surface. The engineered phages with MPER epitopes were recognized by anti-MPER specific antibodies. This system could be used to overcome the challenge of effective presentation of MPER to the immune system. A key portion of this linear epitope could be randomized and evolved with the Qβ system. Overall, antigens and epitopes of RNA viruses relevant to public health can be randomized, evolved and selected in pools using the proposed Qβ model to overcome their plasticity and the challenge of vaccine development. Major epitopes of a particular virus can be engineered or displayed on the Qβ phage surface and used for vaccine efficacy evaluation, thus avoiding the use of live viruses.


title: Analysis of an improved workflow of endoscope reprocessing for bedside endoscopic diagnosis and treatment on COVID-19 patients

text: Severe cases infected with the coronavirus disease 2019 (COVID-19), named by the World Health Organization (WHO) on Feb. 11, 2020, tend to present a hypercatabolic state because of severe systemic consumption, and are susceptible to stress ulcers and even life-threatening gastrointestinal bleeding. Endoscopic diagnosis and treatment constitute an irreplaceable part in the handling of severe COVID-19 cases. Endoscopes, as reusable precision instruments with complicated structures, require more techniques than other medical devices in cleaning, disinfection, sterilization, and other reprocessing procedures. From 2016 to 2019, health care-acquired infection caused by improper endoscope reprocessing has always been among the top 5 on the list of top 10 health technology hazards issued by the Emergency Care Research Institute. Considering the highly infective nature of COVID-19 and the potential aerosol contamination therefrom, it is of pivotal significance to ensure that endoscopes are strictly reprocessed between uses. In accordance with the national standard “Regulation for Cleaning and Disinfection Technique of Flexible Endoscope (WS507-2016),” we improved the workflow of endoscope reprocessing including the selection of chemicals in an effort to ensure quality control throughout the clinical management towards COVID-19 patients. Based on the experience we attained from the 12 severe COVID-19 cases in our hospital who underwent endoscopy 23 times in total, the article provides an improved version of endoscopic reprocessing guidelines for bedside endoscopic diagnosis and treatment on COVID-19 patients for reference. ELECTRONIC SUPPLEMENTARY MATERIALS: The online version of this article (10.1631/jzus.B2000109) contains supplementary materials, which are available to authorized users


title: An enhanced isothermal amplification assay for viral detection

text: Rapid, inexpensive, robust diagnostics are essential to control the spread of infectious diseases. Current state of the art diagnostics are highly sensitive and specific, but slow, and require expensive equipment. We developed a molecular diagnostic test for SARS-CoV-2, FIND (Fast Isothermal Nucleic acid Detection), based on an enhanced isothermal recombinase polymerase amplification reaction. FIND has a detection limit on patient samples close to that of RT-qPCR, requires minimal instrumentation, and is highly scalable and cheap. It can be performed in high throughput, does not cross-react with other common coronaviruses, avoids bottlenecks caused by the current worldwide shortage of RNA isolation kits, and takes ~45 minutes from sample collection to results. FIND can be adapted to future novel viruses in days once sequence is available. One sentence summary Sensitive, specific, rapid, scalable, enhanced isothermal amplification method for detecting SARS-CoV-2 from patient samples.


title: Antiviral activity and possible mode of action of ellagic acid identified in Lagerstroemia speciosa leaves toward human rhinoviruses

text: BACKGROUND: Human rhinoviruses (HRVs) are responsible for more than half of all cases of the common cold and cause billions of USD annually in medical visits and school and work absenteeism. An assessment was made of the cytotoxic and antiviral activities and possible mode of action of the tannin ellagic acid from the leaves of Lagerstroemia speciosa toward HeLa cells and three rhinoviruses, HRV-2, -3, and -4. METHODS: The antiviral property and mechanism of action of ellagic acid were evaluated using a sulforhodamine B assay and real-time reverse transcription-PCR (RT-PCR) with SYBR Green dye. Results were compared with those of the currently used broad-spectrum antiviral agent, ribavirin. RESULTS: As judged by 50% inhibitory concentration values, natural ellagic acid was 1.8, 2.3, and 2.2 times more toxic toward HRV-2 (38 μg/mL), HRV-3 (31 μg/mL), and HRV-4 (29 μg/mL) than ribavirin, respectively. The inhibition rate of preincubation with 50 μg/mL ellagic acid was 17%, whereas continuous presence of ellagic acid during infection led to a significant increase in the inhibition (70%). Treatment with 50 μg/mL ellagic acid considerably suppressed HRV-4 infection only when added just after the virus inoculation (0 h) (87% inhibition), but not before -1 h or after 1 h or later (<20% inhibition). These findings suggest that ellagic acid does not interact with the HRV-4 particles and may directly interact with the human cells in the early stage of HRV infections to protect the cells from the virus destruction. Furthermore, RT-PCR analysis revealed that 50 μg/mL ellagic acid strongly inhibited the RNA replication of HRV-4 in HeLa cells, suggesting that ellagic acid inhibits virus replication by targeting on cellular molecules, rather than virus molecules. CONCLUSIONS: Global efforts to reduce the level of antibiotics justify further studies on L. speciosa leaf-derived materials containing ellagic acid as potential anti-HRV products or a lead molecule for the prevention or treatment of HRV infection.


title: Covid‐19 in Bone Marrow Transplant Recipients: Reflecting on a Single Centre Experience

text: Covid‐19 disease is caused by a novel SARS‐CoV‐2 virus and has been declared a pandemic on the 9(th) of March by WHO. Hallmark of COVID‐19 management is supportive care and there is still no convincing evidence on a treatment which will reduce mortality. Severe COVID‐19 associated sepsis characterized by acute respiratory distress syndrome (ARDS), secondary bacterial pneumonias thrombotic complications, myocarditis, and gastrointestinal involvement are more prevalent in those with comorbidities such as hypertension, diabetes, cardiac disease, cancer and age>70 years (Liang et al; 2020, Guan et al; 2019).


title: Identification of SARS-like coronaviruses in horseshoe bats (Rhinolophus hipposideros) in Slovenia

text: Bats have been identified as a natural reservoir for an increasing number of emerging zoonotic viruses, such as Hendra virus, Nipah virus, Ebola virus, Marburg virus, rabies and other lyssaviruses. Recently, a large number of viruses closely related to members of the genus Coronavirus have been associated with severe acute respiratory syndrome (SARS) and detected in bat species. In this study, samples were collected from 106 live bats of seven different bat species from 27 different locations in Slovenia. Coronaviruses were detected by RT-PCR in 14 out of 36 horseshoe bat (Rhinolophus hipposideros) fecal samples, with 38.8% virus prevalence. Sequence analysis of a 405-nucleotide region of the highly conserved RNA polymerase gene (pol) showed that all coronaviruses detected in this study are genetically closely related, with 99.5–100% nucleotide identity, and belong to group 2 of the coronaviruses. The most closely related virus sequence in GenBank was SARS bat isolate Rp3/2004 (DQ071615) within the SARS-like CoV cluster, sharing 85% nucleotide identity and 95.6% amino acid identity. The potential risk of a new group of bat coronaviruses as a reservoir for human infections is highly suspected, and further molecular epidemiologic studies of these bat coronaviruses are needed.


Reply to “COVID-19 in persons with haematological cancers”: a focus on myeloid neoplasms and risk factors for mortality


title: Old drugs as lead compounds for a new disease? Binding analysis of SARS coronavirus main proteinase with HIV, psychotic and parasite drugs

text: Abstract The SARS-associated coronavirus (SARS-CoV) main proteinase is a key enzyme in viral polyprotein processing. To allow structure-based design of drugs directed at SARS-CoV main proteinase, we predicted its binding pockets and affinities with existing HIV, psychotic and parasite drugs (lopinavir, ritonavir, niclosamide and promazine), which show signs of inhibiting the replication of SARS-CoV. Our results suggest that these drugs and another two HIV inhibitors (PNU and UC2) could be used as templates for designing SARS-CoV proteinase inhibitors.


title: Chapter 4 Diagnosis and Methods

text: Abstract A number of methodologies are currently available for viral diagnosis and basic research, ranging from immunological methods, such as ELISA, to molecular methods, such as PCR-based diagnosis. Other immunological methods include immunofluorescence assay and immunoblot. In addition, some classical methods, such as plaque assay and hemagglutination, are still utilized in laboratories. Tissue culture is conveniently used for virus cultivation and propagation. Experimental animals are used for studies involving viral pathogenesis. Density gradient centrifugation is used for the purification of virus particles. Finally, molecular methods are used for the genetic analysis (ie, mutation) of viral gene function by using the replicon.


title: Challenge infection model for MERS-CoV based on naturally infected camels

text: BACKGROUND: Middle East Respiratory Syndrome coronavirus (MERS-CoV) is an emerging virus that infects humans and camels with no approved antiviral therapy or vaccine. Some vaccines are in development for camels as a one-health intervention where vaccinating camels is proposed to reduce human viral exposure. This intervention will require an understanding of the prior exposure of camels to the virus and appropriate vaccine efficacy studies in camels. METHODS: We conducted a cross sectional seroprevalence study in young dromedary camels to determine the rate of MERS-CoV seropositivity in young camels. Next, we utilised naturally infected camels as a natural challenge model that can be used by co-housing these camels with healthy naive camels in a ratio of 1 to 2. This model is aimed to support studies on natural virus transmission as well as evaluating drug and vaccine efficacy. RESULTS: We found that 90% of the screened camels have pre-existing antibodies for MERS-CoV. In addition, the challenge model resulted in MERS-CoV transmission within 48 h with infections that continued for 14 days post challenge. CONCLUSIONS: Our finding suggests that the majority of young dromedary camels in Saudi Arabia are seropositive and that naturally infected camels can serve as a challenge model to assess transmission, therapeutics, and vaccine efficacy.


title: Prevalence of Respiratory Viral Infections in Korean Adult Asthmatics With Acute Exacerbations: Comparison With Those With Stable State

text: PURPOSE: Viral infections are involved in ~50% of exacerbations among Caucasian adult asthmatics. However, there have been few reports on the causative virus of exacerbations in Korean adult asthmatics. Thus, we compared frequencies and types of viruses between lower respiratory tract illnesses (LRTIs) with exacerbations (exacerbated LRTIs) and those without exacerbations (stable LRTIs) to evaluate contribution of respiratory viruses to exacerbations. METHODS: Viral RNA was extracted from sputum using the Viral Gene-spin™ Kit. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect adenovirus (ADV), metapneumovirus (MPV), parainfluenza virus (PIV) 1/2/3, influenza virus (IFV) A, IFV B, respiratory syncytial virus (RSV) A/B, and rhinovirus (RV) A. RESULTS: Among the 259 patients, 210 underwent a single sputum examination, and the remaining 49 underwent 2 to 4 sputum examinations. Virus was detected in 68 of the 259 exacerbated episodes and in 11 of the 64 stable episodes. Among the exacerbated episodes, RV was the most frequently detected virus, followed by influenza A, parainfluenza, RSV A/B, and ADV. Among the 11 stable episodes, RV was most frequently detected. Detection rates of these viruses did not differ between the 2 groups (P>0.05). Thirty-five patients underwent the virus examination at 2 episodes of exacerbation, while 14 patients underwent at each time of exacerbated and stable episodes. Virus detection rate at the second examination was significantly higher in cases with 2 exacerbation episodes than in those with initial exacerbation and sequential stable episodes (P=0.003). A seasonal pattern was noted in the detection rates of RV (September to December), IFV (January to April), PIV (May to September), and RSV A/B (September to April). CONCLUSIONS: Respiratory viruses were identified in approximately 20% of LRTI irrespective of the presence of asthma exacerbation. RV and IFV A/B were most frequently detected. A group of patients experienced frequent viral infections followed by asthma exacerbations.


Which Threats to Global Health Pose a Problem for Turkey’s Health?


title: Efficient hepatic delivery and protein expression enabled by optimized mRNA and ionizable lipid nanoparticle

text: mRNA is a novel class of therapeutic modality that holds great promise in vaccination, protein replacement therapy, cancer immunotherapy, immune cell engineering etc. However, optimization of mRNA molecules and efficient in vivo delivery are quite important but challenging for its broad application. Here we present an ionizable lipid nanoparticle (iLNP) based on iBL0713 lipid for in vitro and in vivo expression of desired proteins using codon-optimized mRNAs. mRNAs encoding luciferase or erythropoietin (EPO) were prepared by in vitro transcription and formulated with proposed iLNP, to form iLP171/mRNA formulations. It was revealed that both luciferase and EPO proteins were successfully expressed by human hepatocellular carcinoma cells and hepatocytes. The maximum amount of protein expression was found at 6 h post-administration. The expression efficiency of EPO with codon-optimized mRNA was significantly higher than that of unoptimized mRNA. Moreover, no toxicity or immunogenicity was observed for these mRNA formulations. Therefore, our study provides a useful and promising platform for mRNA therapeutic development.


title: Thoracic Surgical Oncology –Maintaining a High-Volume Surgical Program during the Covid-19 Pandemic

text: Abstract Thoracic surgical oncology is a time sensitive, high resource, complex surgical speciality to which Coronavirus has posed a unique challenge. In response to the evolving situation in mainland Europe, our department rapidly established a Covid-free site to maintain elective cancer surgery. This necessitated a strict admission pathway and perioperative patient management. It resulted in the maintenance of a high-volume, high-quality thoracic surgical oncology program with no Covid-19 positive cases to date. Maintaining satisfactory training levels amongst surgical and anaesthetic trainees has also been achieved. We suggest that this model could be adapted to local resource capabilities.


Host range of SARS-CoV-2 and implications for public health


title: Advising the traveller

text: Abstract Global travel continues to increase, particularly to tropical destinations that have different health risks from those encountered closer to home. Currently, over a billion people travel annually, with over 65 million visits made from the UK. Seeking pre-travel advice should be an essential part of any trip for a traveller. The key elements of pre-travel advice are health risk assessment, health promotion and risk management; this involves advice on prevention of malaria, travellers' diarrhoea, sexually transmitted infections and accidents, as well as appropriate vaccinations. Higher risk groups of travellers, such as those visiting friends and relatives, those with co-morbidities, pregnant women and very young or elderly individuals, particularly need to be targeted.


title: Dengue Virus and Autophagy

text: Several independent groups have published that autophagy is required for optimal RNA replication of dengue virus (DENV). Initially, it was postulated that autophagosomes might play a structural role in replication complex formation. However, cryo-EM tomography of DENV replication complexes showed that DENV replicates on endoplasmic reticulum (ER) cisternae invaginations and not on classical autophagosomes. Recently, it was reported that autophagy plays an indirect role in DENV replication by modulating cellular lipid metabolism. DENV-induced autophagosomes deplete cellular triglycerides that are stored in lipid droplets, leading to increased β-oxidation and energy production. This is the first example of a virus triggering autophagy to modulate cellular physiology. In this review, we summarize these data and discuss new questions and implications for autophagy during DENV replication.


A Keynesian antitrust response to the COVID-19 crisis


title: Design of multi epitope-based peptide vaccine against E protein of human COVID-19: An immunoinformatics approach

text: Background New endemic disease has been spread across Wuhan City, China on December 2019. Within few weeks, the World Health Organization (WHO) announced a novel coronavirus designated as coronavirus disease 2019 (COVID-19). In late January 2020, WHO declared the outbreak of a “public-health emergency of international concern” due to the rapid and increasing spread of the disease worldwide. Currently, there is no vaccine or approved treatment for this emerging infection; thus the objective of this study is to design a multi epitope peptide vaccine against COVID-19 using immunoinformatics approach. Method Several techniques facilitating the combination of immunoinformatics approach and comparative genomic approach were used in order to determine the potential peptides for designing the T cell epitopes-based peptide vaccine using the envelope protein of 2019-nCoV as a target. Results Extensive mutations, insertion and deletion were discovered with comparative sequencing in COVID-19 strain. Additionally, ten peptides binding to MHC class I and MHC class II were found to be promising candidates for vaccine design with adequate world population coverage of 88.5% and 99.99%, respectively. Conclusion T cell epitopes-based peptide vaccine was designed for COVID-19 using envelope protein as an immunogenic target. Nevertheless, the proposed vaccine is rapidly needed to be validated clinically in order to ensure its safety, immunogenic profile and to help on stopping this epidemic before it leads to devastating global outbreaks.


title: Viral Vaccines and Antiviral Therapy

text: Abstract In this article the authors review the important viral infections affecting humans, and how they are prevented by vaccines and controlled by antiviral drugs. The different types of drugs and vaccines are listed and their mechanisms of action are discussed. For drugs, these include toxicity and viral resistance, whereas for vaccines, these include generation of autoimmune reactions, contamination by other previously unknown pathogens, reversion of an attenuated to virulent strain, and reactogenicity. The authors discuss how these were understood and the preventative methods instituted to prevent them.


title: Lineage specific antigenic differences in porcine torovirus hemagglutinin-esterase (PToV-HE) protein

text: Hemagglutinin-esterases (HE) are viral envelope proteins present in some members from the toro-, corona- and orthomyxovirus families, all related with enteric and/or respiratory tract infections. HE proteins mediate reversible binding to sialic acid receptor determinants, very abundant glycan residues in the enteric and respiratory tracts. The role of the HE protein during the torovirus infection cycle remains unknown, although it is believed to be important in the natural infection process. The phylogenetic analysis of HE coding sequences from porcine torovirus (PToV) field strains revealed the existence of two distinct HE lineages. In a previous study, PToV virus strains with HE proteins from the two lineages were found coexisting in a pig herd, and they were even obtained from the same animal at two consecutive sampling time points. In this work, we report antigenic differences between the two HE lineages, and discuss the possible implications that the coexistence of viruses belonging to both lineages might have on the spread and sustainment of PToV infection in the farms.


title: Part II Value and Influencing Factors of the Cooperation, Convergence, and Harmonization in the Pharmaceutical Sector

text: Abstract Cooperation and harmonisation of standards in the pharmaceutical domain is already a reality and, in fact, has been increasingly important in recent decades. This harmonisation seems natural and logical in the current environment of increased globalisation imposed by the current geo-economic-political situation. However, even though this is a reality, it is important to analyse whether or not all stakeholders benefit from this increased cooperation and harmonisation, in order to recommend future actions or potential improvements. Cooperation, convergence and harmonisation is indeed not an end in itself. Elimination of differences, agreement on common standards and the increase of cooperation are needed to protect and promote global public health. It is therefore very important to thoroughly analyse the value and impact of the harmonisation and cooperation process, and to determine whether or not all the efforts made throughout the years have indeed met expectations. After many years of experience, it seems important to have a thorough evaluation to answer several important questions: ▸ What has been the benefit of the multiple harmonisation and cooperation initiatives so far? ▸ Should such processes continue? Are there any other alternatives to resolve current challenges? ▸ Should current initiatives and projects be improved? If so, how and what are the priorities? ▸ Would greater harmonisation and closer cooperation be beneficial? Is it possible? Is it necessary? What are the limits of this process? ▸ What are the important lessons from the past and the on-going harmonisation initiatives that should be considered for planning the next steps? This book section’s goal is to answer these important questions by thoroughly evaluating the added value of cooperation, convergence and harmonisation. This book section also reviews the critical parameters and influencing factors for cooperation, convergence and harmonisation. This review/analysis of critical parameters and influencing factors is essential to understand the complexity of the situation and effectively discuss how to organise the next steps of global cooperation.


title: Pandemic COVID-19: current status and challenges of antiviral therapies

text: Abstract The pandemic COVID-19, caused by a new coronavirus SARS-CoV-2 infection, has infected over 6 million individuals and caused more than 364,000 death worldwide. Currently, there is no specific drug to treating this disease. Here we summarized the mechanisms of antiviral therapies and the clinic findings from different countries. Antiviral chemotherapies have been conducted by in multiple cohorts in different counties. Although FDA has fast approved remdesivir for treating COVID-19, it only speeds up recovery from COVID-19 with mildly reduced mortality. The chloroquine was suggested a potential drug against SARS-CoV-2 infection due to its in vitro antiviral effects, it is imperative high-quality data from worldwide clinical trials are necessitated for an approved therapy. In terms of hydroxychloroquine (HCQ) therapy, although WHO has stopped all the clinic trials due to its strong side-effects in COVID patients, large scale clinical trials with a long-term outcome follow-up may warrant HCQ and azithromycin combination in combating the virus. Convalescent plasma (CP) therapy suggested its safety use in SARS-CoV-2 infection; but both CP immunotherapy and NK cellular therapy must be manufactured and utilized according to scrupulous ethical and controlled conditions to guarantee a possible role of these products of human origin. Further research should be conducted to define the exact mechanism of SARS-CoV-2 pathogenesis, suitable animal models or ex vivo human lung tissues aid in studying replication, transmission and spread of the novel viruses, thereby facilitating highly effective therapies.


title: Lithium as a candidate treatment for COVID‐19: Promises and pitfalls

text: The pandemic of respiratory illness caused by a novel coronavirus (SARS‐nCoV‐2) is a global health crisis. Despite numerous preliminary results, there is as yet no treatment of proven efficacy for this condition. In this context, the pharmacological properties of lithium, better known as a treatment for mood disorders, merit closer examination. Lithium has shown in vitro efficacy at inhibiting the replication of coronaviruses responsible for gastrointestinal and respiratory diseases in animals. It has immunomodulatory properties that may be of additional benefit in moderating the host inflammatory response to the novel coronavirus (SARS‐CoV‐2). Furthermore, there is evidence that lithium may exert a protective action against upper respiratory infections and influenza‐like illnesses in patients taking it for other indications. These promising reports must be balanced against the narrow therapeutic index and high risk of toxicity associated with lithium therapy, its documented interactions with several commonly used drugs, and the absence of evidence of its efficacy against coronaviruses responsible for human disease. Nevertheless, naturalistic studies of the risk of COVID‐19 in patients already receiving lithium could provide indirect evidence of its efficacy, and understanding the putative antiviral and immune‐regulatory mechanisms of lithium in models of SARS‐CoV‐2 infection may provide leads for the development of safer and more effective treatments with a specific action against COVID‐19.


ISUOG Interim Guidance on coronavirus disease 2019 (COVID‐19) during pregnancy and puerperium: information for healthcare professionals – an update


The Psychiatry Milestones 2.0: How Did We Get from 1.0 to 2.0 and What Can Users Expect?


title: How severe will the flu outbreak be?

text: Epidemiologists race to pin numbers on the global H1N1 spread.


Modulation of metabolic functions through Cas13d-mediated gene knockdown in liver


title: Prosocial polio vaccination in Israel

text: Regions with insufficient vaccination have hindered worldwide poliomyelitis eradication, as they are vulnerable to sporadic outbreaks through reintroduction of the disease. Despite Israel’s having been declared polio-free in 1988, a routine sewage surveillance program detected polio in 2013. To curtail transmission, the Israel Ministry of Health launched a vaccine campaign to vaccinate children—who had only received the inactivated polio vaccine—with the oral polio vaccine (OPV). Determining the degree of prosocial motivation in vaccination behavior is challenging because vaccination typically provides direct benefits to the individual as well as indirect benefits to the community by curtailing transmission. However, the Israel OPV campaign provides a unique and excellent opportunity to quantify and model prosocial vaccination as its primary objective was to avert transmission. Using primary survey data and a game-theoretical model, we examine and quantify prosocial behavior during the OPV campaign. We found that the observed vaccination behavior in the Israeli OPV campaign is attributable to prosocial behavior and heterogeneous perceived risk of paralysis based on the individual’s comprehension of the prosocial nature of the campaign. We also found that the benefit of increasing comprehension of the prosocial nature of the campaign would be limited if even 24% of the population acts primarily from self-interest, as greater vaccination coverage provides no personal utility to them. Our results suggest that to improve coverage, communication efforts should also focus on alleviating perceived fears surrounding the vaccine.


COVID-19 & PPE: Treatment and Prevention of Skin Conditions Related to the Occupational Use of Personal Protective Equipment


title: Quantifying the Risk and Cost of Active Monitoring for Infectious Diseases

text: During outbreaks of deadly emerging pathogens (e.g., Ebola, MERS-CoV) and bioterror threats (e.g., smallpox), actively monitoring potentially infected individuals aims to limit disease transmission and morbidity. Guidance issued by CDC on active monitoring was a cornerstone of its response to the West Africa Ebola outbreak. There are limited data on how to balance the costs and performance of this important public health activity. We present a framework that estimates the risks and costs of specific durations of active monitoring for pathogens of significant public health concern. We analyze data from New York City’s Ebola active monitoring program over a 16-month period in 2014-2016. For monitored individuals, we identified unique durations of active monitoring that minimize expected costs for those at “low (but not zero) risk” and “some or high risk”: 21 and 31 days, respectively. Extending our analysis to smallpox and MERS-CoV, we found that the optimal length of active monitoring relative to the median incubation period was reduced compared to Ebola due to less variable incubation periods. Active monitoring can save lives but is expensive. Resources can be most effectively allocated by using exposure-risk categories to modify the duration or intensity of active monitoring.


title: Decline of transmissible gastroenteritis virus and its complex evolutionary relationship with porcine respiratory coronavirus in the United States

text: The epidemiology and genetic diversity of transmissible gastroenteritis virus (TGEV) in the United States (US) was investigated by testing clinical cases for TGEV by real time RT-PCR between January 2008 and November 2016. Prevalence of TGEV ranged between 3.8–6.8% and peaked during cold months until March 2013, in which prevalence decreased to < 0.1%. Nineteen complete TGEV genomes and a single strain of porcine respiratory coronavirus (PRCV) from the US were generated and compared to historical strains to investigate the evolution of these endemic coronaviruses. Sixteen of our TGEV strains share 8 unique deletions and 119 distinct amino acid changes, which might greatly affect the biological characteristics of the variant TGEV, and resulted in a “variant” genotype of TGEV. The “variant” genotype shared similar unique deletions and amino acid changes with the recent PRCV strain identified in this study, suggesting a recombination event occurred between the ‘‘variant’’ TGEV and PRCV. Moreover, the results indicate the “variant” genotype is the dominant genotype circulating in the US. Therefore, this study provides insight into the occurrence, origin, genetic characteristics, and evolution of TGEV and PRCV circulating in the US.


title: A Comprehensive Review on Tocilizumab in COVID‐19 Acute Respiratory Distress Syndrome

text: Currently, the world is facing the pandemic of a novel strain of beta‐coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Acute respiratory distress syndrome (ARDS) is the most devastating complication of SARS‐CoV‐2. It was indicated that cytokine release syndrome (CRS) and dominantly IL‐6 play a central role in the pathophysiology of ARDS related to the novel 2019 coronavirus disease (COVID‐19). Despite the global emergency of the disease, at this time, there are no proven therapies for the management of the disease. Tocilizumab is a potential recombinant monoclonal antibody against IL‐6 and currently is under investigation for the management of ARDS in patients with COVID‐19. Given these points, we reviewed the current evidence regarding the potential therapeutic role of tocilizumab and its important clinical issues in the treatment of ARDS related to COVID‐19. This article is protected by copyright. All rights reserved


Stresses and anxieties in the time of the COVID-19 pandemic — what we can learn


title: A hybrid model for investigating transient particle transport in enclosed environments

text: Abstract It is important to accurately model person-to-person particle transport in mechanical ventilation spaces to create and maintain a healthy indoor environment. The present study introduces a hybrid DES-Lagrangian and RANS-Eulerian model for simulating transient particle transport in enclosed environments; this hybrid model can ensure the accuracy and reduce the computing cost. Our study estimated two key time constants for the model that are important parameters for reducing the computing costs. The two time constants estimated were verified by airflow data from both an office and an aircraft cabin case. This study also conducted experiments in the first-class cabin of an MD-82 commercial airliner with heated manikins to validate the hybrid model. A pulse particle source was applied at the mouth of an index manikin to simulate a cough. The particle concentrations versus time were measured at the breathing zone of the other manikins. The trend of particle concentrations versus time predicted by the hybrid model agrees with the experimental data. Therefore, the proposed hybrid model can be used for investigating transient particle transport in enclosed environments.


title: Effects of colchicine on platelet aggregation in patients on dual antiplatelet therapy with aspirin and clopidogrel

text: Platelets aggregation leading to thrombosis plays a pivotal role in the pathophysiology of acute coronary syndrome (ACS) and of stent thrombosis. Antiplatelet therapy with aspirin plus an ADP-receptor inhibitor (ticagrerol, prasugrel or clopidogrel) is recommended to reduce the risk of other platelet-mediated events. Clopidogrel is recommended in patients with Chronic Coronary Syndromes (CCS) or in ACS patients at high bleeding risk. Unfortunately, up to 30% of patients are non-responders to clopidogrel and show residual high platelet reactivity (HPR). Colchicine (COLC) is a drug with cardiovascular effects. We have demonstrated that COLC might exert protective cardiovascular effects by interfering with cytoskeleton rearrangement, a phenomenon involved in platelet aggregation. Here, we investigate in vitro the effects of colchicine on platelet aggregation of patients on DAPT with clopidogrel. Platelets obtained from 35 CCS patients on therapy with clopidogrel were pre-incubated with COLC 10 µM before being stimulated with ADP (20 µM), or TRAP (25 µM) at 0, 30, 60 and 90 min to measure max aggregation by LTA. Platelets not COLC-preincubated served as controls. Seven patients were pre-selected as clopidogrel non-responders. COLC significantly reduced TRAP-induced platelet aggregation in clopidogrel responders and non-responders. Interestingly, COLC inhibited ADP-induced platelet aggregation in clopidogrel non-responders in which ADP still caused activation despite DAPT. We demonstrate that COLC inhibits platelet aggregation in clopidogrel non-responders with HPR despite DAPT with this ADP receptor-inhibitor. Further in vivo studies should be designed to evaluate the opportunity to prescribe colchicine after ACS/CCS to overcome the clopidogrel limitations in the DAPT therapy.