title: Evidence for Paralichthys olivaceus IFITM1 antiviral effect by impeding viral entry into target cells

text: Abstract Interferon-inducible transmembrane (IFITM) protein family is novel viral restriction factors with representative transmembrane structure. These proteins also exist in fish, however, their roles in the innate immune response remain unknown. Here, we report a characterization of teleost IFITM1 from flounder Paralichthys olivaceus (PoIFITM1), which exhibits conserved structure characteristic of the IFITM family but comprises a relatively longer N-terminal region. The expression and promoter activity of PoIFITM1 are markedly induced by aquatic animal viruses: Rana grylio virus (RGV) and Scophthalmus maximus rhabdovirus (SMRV). Overexpression and siRNA-mediated knockdown demonstrate that PoIFITM1 exhibits strong antiviral effects against both DNA virus (RGV) and RNA virus (SMRV), expanding the spectrum of viruses inhibited by IFITM proteins. Further analysis shows that PoIFITM1 suppresses viral entry into host cells, confirming that the IFITM-mediated restriction is conserved from lower vertebrates to mammals. Deletion mutagenesis reveals that PoIFITM1 exerts antiviral activity by targeting to Golgi complex and the N-terminal region is required for its subcellular localization, which is not observed in other known IFITM family members. Our current data provide the first evidence that IFITM1 functions as a key effector of the innate immune to restrict virus replication in lower vertebrates, through the action of impeding viral entry.


title: Corticosteroids for pain relief in sore throat: systematic review and meta-analysis

text: Objective To evaluate whether systemic corticosteroids improve symptoms of sore throat in adults and children. Design Systematic review and meta-analysis. Data sources Cochrane Central, Medline, Embase, Database of Reviews of Effectiveness (DARE), NHS Health Economics Database, and bibliographies. Outcome measures Percentage of patients with complete resolution at 24 and 48 hours, mean time to onset of pain relief, mean time to complete resolution of symptoms, days missed from work or school, recurrence, and adverse events. Results We included eight trials, consisting of 743 patients in total (369 children, 374 adults). 348 (47%) had exudative sore throat, and 330 (44%) were positive for group A β-haemolytic streptococcus. In addition to antibiotics and analgesia, corticosteroids significantly increased the likelihood of complete resolution of pain at 24 hours (four trials) by more than three times (relative risk 3.2, 95% confidence interval 2.0 to 5.1), and at 48 hours (three trials) to a lesser extent (1.7, 1.3 to 2.1). Corticosteroids (six trials) reduced mean time to onset of pain relief by more than 6 hours (95% confidence interval 3.4 to 9.3, P<0.001), although significant heterogeneity was present. The mean time to complete resolution was inconsistent across trials and a pooled analysis was not undertaken. Reporting of other outcomes was limited. Conclusions Corticosteroids provide symptomatic relief of pain in sore throat, in addition to antibiotic therapy, mainly in participants with severe or exudative sore throat.


title: Kinetic Analysis of Bacteriophage Sf6 Binding to Outer Membrane Protein A Using Whole Virions

text: For successful infection, viruses must recognize their respective host cells. A common mechanism of host recognition by viruses is to utilize a portion of the host cell as a receptor. Bacteriophage Sf6, which infects Shigella flexneri, uses lipopolysaccharide as a primary receptor and then requires interaction with a secondary receptor, a role that can be fulfilled by either outer membrane proteins (Omp) A or C. Our previous work showed that specific residues in the loops of OmpA mediate Sf6 infection. To better understand Sf6 interactions with OmpA loop variants, we determined the kinetics of these interactions through the use of biolayer interferometry, an optical biosensing technique that yields data similar to surface plasmon resonance. Here, we successfully tethered whole Sf6 virions, determined the binding constant of Sf6 to OmpA to be 36 nM. Additionally, we showed that Sf6 bound to five variant OmpAs and the resulting kinetic parameters varied only slightly. Based on these data, we propose a model in which Sf6: Omp receptor recognition is not solely based on kinetics, but likely also on the ability of an Omp to induce a conformational change that results in productive infection.


Rethinking the respiratory paradigm of COVID-19: a ‘hole’ in the argument


title: Posttranscriptional modification of messenger RNAs in eukaryotes

text: Transcriptome-wide mapping of posttranscriptional modifications in eukaryotic RNA revealed tens of thousands of modification sites. Modified nucleotides include 6-methyladenosine, 5-methylcytidine, pseudouridine, inosine, etc. Many modification sites are conserved, and many are regulated. The function is known for a minor subset of modified nucleotides, while the role of their majority is still obscure. In view of the global character of mRNA modification, RNA epigenetics arose as a new field of molecular biology. The review considers posttranscriptional modification of eukaryotic mRNA, focusing on the major modified nucleotides, the role they play in the cell, the methods to detect them, and the enzymes responsible for modification.


title: Implications of the One Health Paradigm for Clinical Microbiology

text: Clinical microbiologists have a new and unique opportunity to increase our value to health care by broadening how we think about disease processes and asking ourselves what we can do to help resolve a disease, assist in tracking a cause, or even predict an outbreak before it occurs. Human health, animal health (both wildlife and domestic animals), and environmental health are forever bound together. The convergence of people, animals, and the environment defines the parameters of One Health and directs attention to the impact this overlap has on public health, disease detection, and control. One Health (sometimes referred to as One Medicine) is a concept that promotes, improves, and defends the health and well-being of all species through the integration of the sciences of human medicine, veterinary medicine, and environmental studies. As microbiologists, we need to be aware of this One Health concept and how it can positively impact our profession by allowing us to be more productive members of the health care team. There are several things we can do to get started. We can review organism pathogenicity and evaluate and question test results that may signal an unusual event or process that led to a disease. We can be alert to the epidemiologic potential of organism isolates from patients as they may apply to infection control or community epidemiology. We can become familiar with the zoonotic diseases and recognize the etiologic agents associated with wild and domestic animals and apply that knowledge to our diagnostic skills. As we further understand the “big picture” of One Health, we can ask strategic questions that can lead us to provide further technical assistance to facilitate earlier interventions that lead to positive patient outcomes and ultimately healthier populations. In human medicine, we generally work with one species of animal. Veterinarians work with all the rest. It is time to communicate with and learn from our veterinary clinical microbiology colleagues and begin to understand the critical nature of the human, animal, and environment interface. This is our opportunity to be at the front of this line and not stand on the sidelines watching.


title: Development of An Android Application for Viewing Covid-19 Containment Zones and Monitoring Violators Who are Trespassing into It Using Firebase and Geofencing

text: The World Health Organization has declared the outbreak of the novel coronavirus, Covid-19 as pandemic across the world. With its alarming surge of affected cases throughout the world, lockdown, and awareness (social distancing, use of masks etc.) among people are found to be the only means for restricting the community transmission. In a densely populated country like India, it is very difficult to prevent the community transmission even during lockdown without social awareness and precautionary measures taken by the people. Recently, several containment zones had been identified throughout the country and divided into red, orange and green zones, respectively. The red zones indicate the infection hotspots, orange zones denote some infection and green zones indicate an area with no infection. This paper mainly focuses on development of an Android application which can inform people of the Covid-19 containment zones and prevent trespassing into these zones. This Android application updates the locations of the areas in a Google map which are identified to be the containment zones. The application also notifies the users if they have entered a containment zone and uploads the user’s IMEI number to the online database. To achieve all these functionalities, many tools, and APIs from Google like Firebase and Geofencing API are used in this application. Therefore, this application can be used as a tool for creating further social awareness about the arising need of precautionary measures to be taken by the people of India.


title: An Open Receptor-Binding Cavity of Hemagglutinin-Esterase-Fusion Glycoprotein from Newly-Identified Influenza D Virus: Basis for Its Broad Cell Tropism

text: Influenza viruses cause seasonal flu each year and pandemics or epidemic sporadically, posing a major threat to public health. Recently, a new influenza D virus (IDV) was isolated from pigs and cattle. Here, we reveal that the IDV utilizes 9-O-acetylated sialic acids as its receptor for virus entry. Then, we determined the crystal structures of hemagglutinin-esterase-fusion glycoprotein (HEF) of IDV both in its free form and in complex with the receptor and enzymatic substrate analogs. The IDV HEF shows an extremely similar structural fold as the human-infecting influenza C virus (ICV) HEF. However, IDV HEF has an open receptor-binding cavity to accommodate diverse extended glycan moieties. This structural difference provides an explanation for the phenomenon that the IDV has a broad cell tropism. As IDV HEF is structurally and functionally similar to ICV HEF, our findings highlight the potential threat of the virus to public health.


title: Schutz vor SARS-CoV-2: Wie viel Maske sollte es sein?: COVID-19-Pandemie

text: Gesunde junge Leute mit FFP-Masken im Supermarkt, reaktivierte Nähmaschinen im Dienst der Pandemiebekämpfung, dubiose Händler, die Masken meistbietend verhökern: Das Thema Masken bewegt die Gemüter. Die Unsicherheit ist groß. Wen harte Evidenz interessiert, der bleibt am Ende etwas ratlos zurück. Trotzdem gibt es gut begründete Empfehlungen — vor allem für medizinisches Personal. In der Bevölkerung gilt: Wenn Maske, dann richtig.


title: Tracking the Volume of Neurosurgical Care during the COVID-19 Pandemic

text: Abstract Objective This study quantifies the impact of COVID-19 on the volume of adult and pediatric neurosurgical procedures, inpatient consults, and clinic visits at an academic medical center. Methods Neurosurgical procedures, inpatient consults, and outpatient appointments at Vanderbilt University Medical Center were identified in the time periods of March 23, 2020 through May 8, 2020 ("During COVID-19") and March 25, 2019 through May 10, 2019 ("Before COVID-19"). Neurosurgical volume was compared between these periods. Results A 40% reduction in weekly procedural volume was demonstrated during COVID-19 (median 75 [IQR 72-80] to 45 [43-47], p<0.001). There was a 42% reduction for weekly adult procedures (62 [54-70] to 36 [34-39], p<0.001), and 31% reduction for weekly pediatric procedures (13 [12-14] to 9 [8-10], p=0.004). Among adult procedures, the most significant decreases were seen for spine (p<0.001), endovascular (p<0.001), and cranioplasty (p<0.001). There was not a significant change for adult open vascular (p=0.291), functional (p=0.263), cranial tumor (p=0.143), or hydrocephalus (p=0.173) procedural volume. Weekly inpatient consults to neurosurgery decreased by 24% (99 [94-114] to 75 [68-84], p=0.008) for adults. Weekly in-person adult and pediatric outpatient clinic visits witnessed a 91% decrease (329 [326-374] to 29 [26-39], p<0.001). Weekly telehealth encounters increased from 0 [0-0] to 151 [126-156] (p<0.001). Conclusion There were significant reductions in neurosurgical operations, clinic visits, and inpatient consults during COVID-19. Telehealth was increasingly used for assessment. The long-term impacts of reduced neurosurgical volume and increased telehealth utilization on patient outcomes should be explored.


title: The trinity of COVID-19: immunity, inflammation and intervention

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract — severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation.


title: A 4 year prospective study to determine risk factors for severe community acquired pneumonia in children in southern China

text: BACKGROUND: Pneumonia is the major cause of death under 5 years. With high CAP numbers in China and growing access to PICUs, factors associated with severe CAP need to be determined to optimize care. OBJECTIVE: To prospectively determine PICU CAP admission features and outcomes. METHODS: A 4 year prospective study of CAP aged 1 month to <14 years admitted to PICU, Children's Hospital Affiliated to Soochow University, China. All were managed in a standard manner. Clinical, laboratory, and imaging findings were collected systematically. All received antibiotics. RESULTS: Eight hundred ten (7%) of 10,836 CAP hospital admissions needed PICU. Seven hundred seven (87%) were enrolled. PICU CAP children were young (76% ≤ 12 months) and 33% had co‐morbid conditions; 21% congenital heart disease.21% required mechanical ventilation. The average length of PICU stay was 5 days (range, 3–27). The case fatality rate was 5.8%. Viruses were detected in 38%, RSV 24%; bacteria in 23%, Streptococcus pneumoniae 7%, Haemophilus influenza b 4%, Mycoplasma 11%. On single factor analysis, PICU admission respiratory rate >70/min, grunting/groaning, head nodding, cyanosis, and anemia were associated with respiratory failure and with fatality. On multivariate analysis only presence of congenital heart disease, Trisomy 21 and immunodeficiency correlated with fatality; not microbe nor PICU findings. CONCLUSIONS: Young age and underlying congenital heart disease were associated factors for PICU support in CAP in China. Early referral if altered sensorium, high respiratory rate, head nodding, grunting and anemia, and universal access to conjugated vaccines may decrease morbidity and mortality. Pediatr Pulmonol. 2013; 48:390–397. © 2012 Wiley Periodicals, Inc.


title: Experimental verification of tracking algorithm for dynamically-releasing single indoor contaminant

text: Identifying contaminant sources in a precise and rapid manner is critical to indoor air quality (IAQ) management as disclosed source information can facilitate proper and effective IAQ controls in environments with airborne infection, fire smoke and chemical pollutant release etc. Probability-based inverse modeling method was shown feasible for locating single instantaneous source in IAQ events. To tackle more realistic sources of continuous release, this paper advances the method to identify continuously releasing single contaminant source. The study formulates a suite of inverse modeling algorithms that can promptly locate dynamic source with known release time for IAQ events. Two field experiments are employed to verify the prediction: one in a multi-room apartment and the other in a hospital ward which was involved in a SARS outbreak in Hong Kong in 2003. The developed algorithms promptly and accurately identify the source locations in both cases.


title: The global scientific research response to the public health emergency of Zika virus infection

text: BACKGROUND: Science studies have been a field of research for different knowledge areas, and they have been successfully used to analyse the construction of scientific knowledge, practice and dissemination. In this study, we aimed to verify how the Zika epidemic has moulded the scientific articles published worldwide by analysing international collaborations and the knowledge landscape through time, as well as research topics and country involvement. METHODOLOGY: We searched the Web of Science (WoS), Scopus and PubMed for studies published up to 31st December 2018 on Zika using the search terms “zika”, “zkv” or “zikv”. We analysed the scientific production regarding which countries have published the most, on which topics, as well as country level collaboration. We performed a scientometric analysis of research on Zika focusing on knowledge mapping and the scientific research path over time and space. FINDINGS: We found two well defined research areas divided into three subtopics accounting for six clusters. With regard to country analysis, the USA and Brazil were the countries with the highest numbers of publications on Zika. China entered as a new player focusing on specific research areas. When we took into consideration the epidemics and reported cases, Brazil and France were the leading research countries on related topics. As for international collaboration, the USA followed by England and France stand out as the main hubs. The research areas most published included public health-related topics from 2015 until the very beginning of 2016, followed by an increase in topics related to the clinical aspects of the disease in 2016 and the emergence of laboratory research in 2017/2018. CONCLUSIONS: Mapping the response to Zika, a public health emergency, demonstrated a clear pattern of the participation of countries in the scientific advances. The pattern of knowledge production found in this study represented varying country perspectives, research capacity and interests based first on their level of exposure to the epidemic and second on their financial positions regarding science.


title: The 3D8 single chain variable fragment protein suppress infectious bronchitis virus transmission in the transgenic chickens

text: Abstract Infectious bronchitis (IB) generated by the infectious bronchitis virus (IBV) causes economic difficulties for livestock farmers. The 3D8 single chain variable fragment (scFv) protein is a recombinant antibody with nuclease activity that shows antiviral effects against various DNA and RNA viruses in mice and chickens. In this experiment, 3D8 scFv G2 transgenic chickens produced by crossing 3D8 scFv G1 transgenic rooster and wild type hens were screened by genomic PCR and immunohistochemistry analysis. 3D8 scFv transgenic chickens, wild type sibling chickens, and SPF chickens were directly infected with IBV (5 chickens per group) and indirectly infected by airborne propagation (15 chickens per group). The relative IBV shedding titers were measured by quantitative real-time PCR using oropharyngeal and cloacal swabs on days 3 and 5 after intraocular infection. The viral load was significantly decreased in the 3D8 scFv transgenic chickens from the contact transmission group. Additionally, blood was collected from each group on day 17 post-infection. The ELISA results showed a marked reduction of the antibody titer against IBV in the 3D8 scFv transgenic chickens from the contact transmission group. These results suggest that the 3D8 scFv protein potentially inhibits infectious bronchitis virus transmission in chickens.


title: Microwave assisted nanofibrous air filtration for disinfection of bioaerosols

text: Abstract Airborne biological agents, albeit intentionally released or naturally occurring, pose one of the biggest threats to public health and security. In this study, a microwave assisted nanofibrous air filtration system was developed to disinfect air containing airborne pathogens. Aerosolized E. coli vegetative cells and B. subtilis endospores, as benign surrogates of pathogens, were collected on nanofibrous filters and treated by microwave irradiation. Both static on-filter and dynamic in-flight tests were carried out. Results showed that E. coli cells were efficiently disinfected in both static and in-flight tests, whereas B. subtilis endospores were more resistant to this treatment. Microwave power level was found to be the major factor determining the effectiveness of disinfection. Both thermal and non-thermal effects of microwave irradiation contributed to the disinfection. Reducing flow velocity to decrease heat loss yielded higher disinfection efficiency.


title: A Novel Strategy for the Preparation of Codon-Optimized Truncated Ulp1 and its Simplified Application to Cleavage the SUMO Fusion Protein

text: Ubiquitin-like protease 1 (Ulp1) of Saccharomyces cerevisiae emerges as a fundamental tool to obtain the natural N-terminal target protein by cleavage of the small ubiquitin-related modifier (SUMO) fusion protein. However, the costly commercial Ulp1 and its complicated procedures limit its application in the preparation of the target protein with natural N-terminal sequence. Here, we describe the preparation of bioactive codon-optimized recombinant truncated Ulp1 (Leu403-Lys621) (rtUlp1) of S. cerevisiae in Escherichia coli using only one-step with Ni–NTA affinity chromatograph, and the application of rtUlp1 to cleave the SUMO fusion protein by simply mixing the purified rtUlp1, SUMO fusion protein and DL-Dithiothreitol in Tris–HCl buffer. The optimal expression level of non-fusion protein rtUlp1 accounts for approximately 50 % of the total cellular protein and 36 % of the soluble form by addition of isopropyl β-D-l-thiogalactopyranoside at a final concentration of 0.4 mM at 18 °C for 20 h. The purification of target protein rtUlp1 was conducted by Ni–NTA affinity chromatography. The final yield of rtUlp1 was 45 mg/l in flask fermentation with a purity up to 95 %. Furthermore, the high purity of rtUlp1 could effectively cleave the SUMO-tTβRII fusion protein (SUMO gene fused to truncated transforming growth factor-beta receptor type II gene) with the above simplified approach, and the specific activity of the rtUlp1 reached up to 2.8 × 10(4) U/mg, which is comparable to the commercial Ulp1. The preparation and application strategy of the rtUlp1 with commonly available laboratory resources in this study will be convenient to the cleavage of the SUMO fusion protein to obtain the natural N-terminal target protein, which can be implemented in difficult-to-express protein functional analysis.


The Father-Daughter Dinner Dance: A Waltz With Ethics and COVID-19


title: Estimating the Early Outbreak Cumulative Incidence of COVID-19 in the United States: Three Complementary Approaches

text: Effectively designing and evaluating public health responses to the ongoing COVID-19 pandemic requires accurate estimation of the weekly incidence of COVID-19. Unfortunately, a lack of systematic testing across the United States (US) due to equipment shortages and varying testing strategies has hindered the usefulness of the reported positive COVID-19 case counts. We introduce three complementary approaches to estimate the cumulative incidence of symptomatic COVID-19 during the early outbreak in each state in the US as well as in New York City, using a combination of excess influenza-like illness reports, COVID-19 test statistics, and COVID-19 mortality reports. Instead of relying on an estimate from a single data source or method that may be biased, we provide multiple estimates, each relying on different assumptions and data sources. Across our three approaches, there is a consistent conclusion that estimated state-level COVID-19 symptomatic case counts from March 1 to April 4, 2020 varied from 5 to 50 times greater than the official positive test counts. Nationally, our estimates of COVID-19 symptomatic cases in the US as of April 4 have a likely range of 2.2 to 5.1 million cases, with possibly as high as 8.1 million cases, up to 26 times greater than the cumulative confirmed cases of about 311,000. Extending our method to May 16, 2020, we estimate that cumulative symptomatic incidence ranges from 6.0 to 12.2 million, which compares with 1.5 million positive test counts. Our approaches demonstrate the value of leveraging existing influenza-like-illness surveillance systems during the flu season for measuring the burden of new diseases that share symptoms with influenza-like-illnesses. Our methods may prove useful in assessing the burden of COVID-19 during upcoming flu seasons in the US and other countries with comparable influenza surveillance systems.


title: Sample preparation: the weak link in microfluidics-based biodetection

text: As a broad generalization, clinicians and laboratory personnel who use microfluidics-based automated or semi-automated instrumentation to perform biomedical assays on real-world samples are more pleased with the state of the assays than they are with the state of the front-end sample preparation. The end-to-end procedure requires one to collect, manipulate, prepare, and analyze the sample. The appeal of microfluidics for this procedure is partly based on its combination of small size and its ability to process very small liquid volumes, thus minimizing the use of possibly expensive reagents. However, real-world samples are often large and incompatible with the input port and the μm-scale channels of a microfluidic device, and very small liquid volumes can be inappropriate in analyzing low concentrations of target analytes. It can be a worthy challenge to take a raw sample, introduce it into a microfluidics-based system, and perform the sample preparation, which may include separation and concentration of the target analytes, so that one can benefit from the reagent-conserving small volumes and obtain the correct answer when finally implementing the assay of interest.


title: Assessment of the viral safety of antivenoms fractionated from equine plasma

text: Abstract Antivenoms are preparations of intact or fragmented (F(ab′)2 or Fab) immunoglobulin G (IgG) used in human medicine to treat the severe envenomings resulting from the bites and stings of various animals, such as snakes, spiders, scorpions, or marine animals, or from the contact with poisonous plants. They are obtained by fractionating plasma collected from immunized horses or, less frequently, sheep. Manufacturing processes usually include pepsin digestion at acid pH, papain digestion, ammonium sulphate precipitation, caprylic acid precipitation, heat coagulation and/or chromatography. Most production processes do not have deliberately introduced viral inactivation or removal treatments, but antivenoms have never been found to transmit viruses to humans. Nevertheless, the recent examples of zoonotic diseases highlight the need to perform a careful assessment of the viral safety of antivenoms. This paper reviews the characteristics of equine viruses of antivenoms and discusses the potential of some manufacturing steps to avoid risks of viral contamination. Analysis of production parameters indicate that acid pH treatments and caprylic acid precipitations, which have been validated for the manufacture of some human IgG products, appear to provide the best potential for viral inactivation of antivenoms. As many manufacturers of antivenoms located in developing countries lack the resources to conduct formal viral validation studies, it is hoped that this review will help in the scientific understanding of the viral safety factors of antivenoms, in the controlled implementation of the manufacturing steps with expected impact on viral safety, and in the overall reinforcement of good manufacturing practices of these essential therapeutic products.


title: Impact of health challenges on pig growth performance, carcass characteristics, and net returns under commercial conditions

text: Understanding how disease affects commercial production is imperative for pig producers to quantify its full impact on pig performance, carcass quality, and net returns. The objective of this experiment was to assess the productivity and economic importance of naturally occurring health challenges (HC) under commercial conditions. Three 1,000 pig grow-finish facilities received 936 pigs each. The experimental period started approximately 34 d post placement at an average start BW of 13.1 ± 0.2 kg. Barns were characterized based on the relative HC, determined by diagnostic assessments as the main characterization tool, along with other health indicators. Barns were characterized as low challenge health (LCh), moderate challenge health (MCh), and high challenge health (HCh). All barns tested positive for porcine reproductive and respiratory syndrome virus infection prior to the start of the experiment. Additionally, the MCh and HCh barns experienced influenza type A virus of swine. Similar to commercial production conditions, the disease challenge was not imposed but rather occurred naturally. Reduced ADG, ADFI, and G:F were observed with an increased HC (P < 0.001). Similarly, mortality was increased when the HC increased (P < 0.001). Decreased ADG increased days to achieve harvest BW, by 10 and 15 d in the MCh and HCh treatments compared with LCh, respectively (P < 0.001). No differences were observed for percent lean, loin depth, or fat depth (P > 0.10). The economic impact of the HC was assessed by applying these growth performance data to two economic models encompassing the two main marketing methods used by U.S. pig producers: fixed-weight and fixed-time. Financial losses attributed to the variation in disease severity that occurred in the present study ranged from $8.49 and $26.10 U.S. dollars (USD)/pig marketed using a fixed-market weight model, or between $11.02 and $29.82 USD/pig using a fixed-time model, depending on feed costs and market hog prices. In conclusion, increasing severity of HC under commercial conditions reduced ADG by 8% and 14% and resulted in mortality as high as 19.9%. Losses of $8.49 to $29.82/pig marketed underscore the potential magnitude of the economic impact of mixed etiology concurrent diseases in pork production.


title: Diagnostics of rare disorders: whole-exome sequencing deciphering locus heterogeneity in telomere biology disorders

text: BACKGROUND: The telomere biology disorders (TBDs) include a range of multisystem diseases characterized by mucocutaneous symptoms and bone marrow failure. In dyskeratosis congenita (DKC), the clinical features of TBDs stem from the depletion of crucial stem cell populations in highly proliferative tissues, resulting from abnormal telomerase function. Due to the wide spectrum of clinical presentations and lack of a conclusive laboratory test it may be challenging to reach a clinical diagnosis, especially if patients lack the pathognomonic clinical features of TBDs. METHODS: Clinical sequencing was performed on a cohort of patients presenting with variable immune phenotypes lacking molecular diagnoses. Hypothesis-free whole-exome sequencing (WES) was selected in the absence of compelling diagnostic hints in patients with variable immunological and haematological conditions. RESULTS: In four patients belonging to three families, we have detected five novel variants in known TBD-causing genes (DKC1, TERT and RTEL1). In addition to the molecular findings, they all presented shortened blood cell telomeres. These findings are consistent with the displayed TBD phenotypes, addressing towards the molecular diagnosis and subsequent clinical follow-up of the patients. CONCLUSIONS: Our results strongly support the utility of WES-based approaches for routine genetic diagnostics of TBD patients with heterogeneous or atypical clinical presentation who otherwise might remain undiagnosed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13023-018-0864-9) contains supplementary material, which is available to authorized users.


title: Recomendaciones prácticas en la paciente obstétrica con infección por COVID-19

text: Resumen La infección por COVID 19 afecta también a las pacientes obstétricas. La atención obstétrica habitual ha continuado a pesar de la pandemia. Existen series de casos de pacientes obstétricas. Parece que las técnicas neuroaxiales son seguras y es importante asegurarse que los bloqueos funcionen correctamente antes de una cesárea. Es por esto, que se recomienda que los bloqueos sean realizados por anestesiólogos expertos. La protección y seguridad de los profesionales es un punto fundamental y en caso de anestesia general, también se recomienda acudir al anestesiólogo más experto. Las pacientes gravemente enfermas, deben reconocerse rápida y precozmente, para poder suministrarles el tratamiento adecuado lo antes posible. La susceptibilidad a las trombosis hace que la anticoagulación profiláctica sea prioritaria. Abstract COVID 19 infection also affects obstetric patients. Regular obstetric care has continued despite the pandemic. Case series of obstetric patients have been published. Neuroaxial techniques appear to be safe and it is important to obtain the highest possible rate of success of the blocks before a cesarean section. For this reason, it is recommended that the blocks be carried out by senior anesthesiologists. The protection and safety of professionals is a key point and in case of general anesthesia, so it is also recommended to call to the most expert anesthesiologist. Seriously ill patients should be recognized quickly and early, in order to provide them with the appropriate treatment as soon as possible. Susceptibility to thrombosis makes prophylactic anticoagulation a priority.


title: Diagnóstico microbiológico de las infecciones gastrointestinales

text: Acute gastrointestinal tract infections are among the most common infectious diseases. In the present review, the different methods of diagnosing gastrointestinal infections caused by bacteria, viruses, and parasites are examined. Stool culture is the method of choice for diagnosing bacterial intestinal infections; however, infections caused by Clostridium difficile can be diagnosed by detection of toxins A and B in stools, and infections caused by diarrheagenic Escherichia coli by PCR detection of specific virulence factor genes harbored by several E. coli pathotypes. The techniques used to diagnose viral gastrointestinal infections include detection of viral antigens and nucleic acids. Finally, gastrointestinal infections caused by parasites can be diagnosed by testing for trophozoites and cysts of protozoa, or larvae and eggs of helminths in stools by direct microscopic examination, with concentration techniques, or by specific stains.


title: Why we went for full elimination

text: The doctor who devised New Zealand's early and extensive coronavirus response tells Alice Klein what inspired his successful strategy


title: Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial

text: BACKGROUND: A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. METHODS: We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5 × 10(10), 1 × 10(11), and 1·5 × 10(11) viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127. FINDINGS: Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination. INTERPRETATION: The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation. FUNDING: National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.


title: Responding to the accumulation of adverse childhood experiences in the wake of the COVID-19 pandemic: implications for practice

text: In early 2020, the world as we knew it began to change dramatically and rapidly with the COVID-19 outbreak. Social distancing restrictions and lockdown measures have been the most effective course of action and an inarguably imperative approach at this time. However, in trying to keep the global population safe, social distancing measures unwittingly placed children already experiencing maltreatment and disadvantage in harm’s way. This paper will consider the evidence base which attests to the importance of considering the accumulation of adversity when seeking to understand risk and impact of child maltreatment and disadvantage. Given the unique and unprecedented circumstances which have accompanied the COVID-19 outbreak, and the dearth of research pertaining to the impact of pandemics on child welfare, the paper draws on an emerging body of literature about the effect of natural disasters, conflict and significant global events on child maltreatment. The paper synthesises the research to date in order to call attention to the cumulative impact of the COVID-19 pandemic on children already experiencing abuse and neglect. The paper concludes with an outline of the implications for practice in the helping professions.


title: Cardiac surgery in the time of the coronavirus

text: The current Covid‐19 pandemic is a significant global health threat. The outbreak has profoundly affected all healthcare professionals, including heart surgeons. To adapt to these exceptional circumstances, cardiac surgeons had to change their practice significantly. We herein discuss the challenges and broad implications of the Covid‐19 pandemic from the perspective of the heart surgeons.


title: Molecular immune pathogenesis and diagnosis of COVID-19

text: Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The emergence of SARS-CoV-2 has been marked as the third introduction of a highly pathogenic coronavirus into the human population after the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) in the twenty-first century. In this minireview, we provide a brief introduction of the general features of SARS-CoV-2 and discuss current knowledge of molecular immune pathogenesis, diagnosis and treatment of COVID-19 on the base of the present understanding of SARS-CoV and MERS-CoV infections, which may be helpful in offering novel insights and potential therapeutic targets for combating the SARS-CoV-2 infection.


title: Factors Influencing Health Behaviours during the COVID-19 Outbreak in China: an Extended IMB Model

text: Abstract Objectives This study explored the factors influencing health behaviours during the coronavirus disease 2019 (COVID-19) outbreak in China. The impact of perceived stress and positive perception of interventions on health behaviours in China were assessed using the extended information-motivation-behaviour skills (IMB) model. Study design Cross-sectional survey. Methods The Questionstar online survey tool was used to construct a structured questionnaire based on the IMB model. Between 14 and 22 February 2020, during the peak of COVID-19 epidemic in China, 2449 participants were recruited by snowball sampling on WeChat and Tencent QQ social media platforms in China. Data were collected through an online questionnaire and structural equation modelling was performed to evaluate the extended IMB model. Results Health behaviours were assessed using a scoring system (total score range 8–40); the average health behaviour score in this study was 34.62 ± 4.44. The term ‘health risk stress’ refers to the impact that perceived stress has on health and this was experienced by 39.9% of participants. Only 35.9% of participants answered all 7 questions on COVID-19 information correctly. The final model showed that information, motivation, behavioural skills, heath risk stress and positive perception of interventions had significant direct effects on health behaviours. Health behaviours were positively associated with the positive perception of interventions, but negatively associated with health risk stress. Behavioural skills had the greatest impact on health behaviours. Conclusions In the face of public health emergencies, the extended IMB model has been used as a theoretical framework to construct more effective interventions. The government should pay attention to publicity and guidance, strengthen positive interactions with the public and disclose relevant information in a timely manner to gain trust and to maintain the positive public perception of the interventions. In terms of health education, the government should focus on behavioural skills, promptly rectify ineffective prevention information and raise awareness about the disease in order to relieve stress and anxiety in the population.


title: Prediction of Number of Cases of 2019 Novel Coronavirus (COVID-19) Using Social Media Search Index

text: Predicting the number of new suspected or confirmed cases of novel coronavirus disease 2019 (COVID-19) is crucial in the prevention and control of the COVID-19 outbreak. Social media search indexes (SMSI) for dry cough, fever, chest distress, coronavirus, and pneumonia were collected from 31 December 2019 to 9 February 2020. The new suspected cases of COVID-19 data were collected from 20 January 2020 to 9 February 2020. We used the lagged series of SMSI to predict new suspected COVID-19 case numbers during this period. To avoid overfitting, five methods, namely subset selection, forward selection, lasso regression, ridge regression, and elastic net, were used to estimate coefficients. We selected the optimal method to predict new suspected COVID-19 case numbers from 20 January 2020 to 9 February 2020. We further validated the optimal method for new confirmed cases of COVID-19 from 31 December 2019 to 17 February 2020. The new suspected COVID-19 case numbers correlated significantly with the lagged series of SMSI. SMSI could be detected 6–9 days earlier than new suspected cases of COVID-19. The optimal method was the subset selection method, which had the lowest estimation error and a moderate number of predictors. The subset selection method also significantly correlated with the new confirmed COVID-19 cases after validation. SMSI findings on lag day 10 were significantly correlated with new confirmed COVID-19 cases. SMSI could be a significant predictor of the number of COVID-19 infections. SMSI could be an effective early predictor, which would enable governments’ health departments to locate potential and high-risk outbreak areas.


title: Husbandry of Dairy Animals | Goat: Replacement Management

text: Raising replacement dairy kids begins with prenatal care of the doe. The doe needs to be properly vaccinated before kidding, be in proper body condition, and have good nutrition, including vitamins and minerals. A program to prevent caprine arthritis encephalitis must be instituted, which involves removal of the kid from the doe at birth, feeding heat treated colostrum the first day of life, and feeding with milk replacer, heat treated milk, or a mixture thereafter. Milk should be fed generously (3 times a day) to 2 weeks of life. Milk consumption can become limited by feeding 0.5l per feeding, twice a day. More milk can be fed, by feeding 3 times a day or using acidified or cold milk procedures. A high-quality starter feed should be fed beginning the second week of life. A kid must be a minimum of 6 weeks of age to be weaned, weigh at least 10kg, and have a starter intake of at least 250gday-1. Kids can be transitioned to weaning by reducing milk feeding to one time a day. After weaning, the kid should be fed 360g of starter feed per day and all of the high-quality hay they can eat. The kid should gain 150gday-1 from birth and weigh 35kg by 7 months of age when they can be bred. Kid health problems can be prevented by consumption of adequate colostrum, well-ventilated environment, avoiding crowding, and good sanitation. Attention needs to be given to making gradual changes in feeding.


The covid‐19 outbreak in Italy: preventive and protective measures adopted by the dermatology unit of bologna university hospital


Post-mortem routine practice in the era of the COVID-19 pandemic


title: COVID-19 Modifications for Remote Teleassessment and Teletraining of a Complementary Alternative Medicine Intervention for People With Multiple Sclerosis: Protocol for a Randomized Controlled Trial

text: BACKGROUND: Access to comprehensive exercise and rehabilitation services for people with multiple sclerosis (MS) remains a major challenge, especially in rural, low-income areas. Hence, the Tele-Exercise and Multiple Sclerosis (TEAMS) study aims to provide patient-centered, coordinated care by implementing a 12-week complementary and alternative medicine (CAM) intervention for adults with MS. However, due to the societal impact of coronavirus disease (COVID-19) in mid-March 2020, the University of Alabama at Birmingham announced a limited business model halting all nonessential research requiring on-site visits, which includes the TEAMS study. OBJECTIVE: In compliance with the shelter-in-place policy and quarantine guidance, a modified testing and training protocol was developed to allow participants to continue the study. METHODS: The modified protocol, which replaces on-site data collection and training procedures, includes a teleassessment package (computer tablet, blood pressure cuff, hand dynamometer, mini disc cone, measuring tape, an 8” step, and a large-print 8” × 11” paper with ruler metrics and wall-safe tape) and a virtual meeting platform for synchronous interactive training between the therapist and the participant. The teleassessment measures include resting blood pressure and heart rate, grip strength, Five Times Sit to Stand, Timed Up & Go, and the Berg Balance Scale. The teletraining component includes 20 sessions of synchronous training sessions of dual tasking, yoga, and Pilates exercises designed and customized for a range of functional levels. Teletraining lasts 12 weeks and participants are instructed to continue exercising for a posttraining period of 9 months. RESULTS: The protocol modifications were supported with supplemental funding (from the Patient-Centered Outcomes Research Institute) and approved by the University Institutional Review Board for Human Use. At the time nonessential research visits were halted by the university, there were 759 people enrolled and baseline tested, accounting for 92.5% of our baseline testing completion target (N=820). Specifically, 325 participants completed the 12-week intervention and follow-up testing visits, and 289 participants needed to complete either the intervention or follow-up assessments. A modified analysis plan will include sensitivity analyses to ensure the robustness of the study results in the presence of uncertainty and protocol deviations. Study results are projected to be published in 2021. CONCLUSIONS: This modified remote teleassessment/teletraining protocol will impact a large number of participants with MS who would otherwise have been discontinued from the study. TRIAL REGISTRATION: ClinicalTrials.gov NCT03117881; https://clinicaltrials.gov/ct2/show/NCT03117881 INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18415


title: Chapter 3.1 Structural Biology of Noroviruses

text: Abstract Noroviruses constitute a major genus in the family Caliciviridae, which contains icosahedral viruses with positive-sense single-stranded RNA genome. In humans, these constantly evolving viruses are the cause of sporadic and epidemic gastroenteritis. Despite a lack of a reproducible cell culture system or a small animal model, remarkable progress has been made in our understanding of the molecular biology, immunology, structural biology, and evolution of human noroviruses. This understanding is further enhanced by studies of nonhuman noroviruses and animal caliciviruses that are cultivatable. The main focus of this chapter is to review our current understanding of the structural biology of noroviruses in particular and of caliciviruses in general, with an emphasis on the unique modular organization of the capsid that allows for strain-dependent variations in glycan recognition and antigenicity to facilitate sustained virus evolution. Finally, structures of the proteins are reviewed that are critical for virus replication and that can be targeted in the design of small molecule drugs for use as effective antivirals.


title: Streptococcus pneumoniae Coinfection Is Correlated with the Severity of H1N1 Pandemic Influenza

text: BACKGROUND: Initial reports in May 2009 of the novel influenza strain H1N1pdm estimated a case fatality rate (CFR) of 0.6%, similar to that of seasonal influenza. In July 2009, however, Argentina reported 3056 cases with 137 deaths, representing a CFR of 4.5%. Potential explanations for increased CFR included virus reassortment or genetic drift, or infection of a more vulnerable population. Virus genomic sequencing of 26 Argentinian samples representing both severe and mild disease indicated no evidence of reassortment, mutations associated with resistance to antiviral drugs, or genetic drift that might contribute to virulence. Furthermore, no evidence was found for increased frequency of risk factors for H1N1pdm disease. METHODS/PRINCIPAL FINDINGS: We examined nasopharyngeal swab samples (NPS) from 199 cases of H1N1pdm infection from Argentina with MassTag PCR, testing for 33 additional microbial agents. The study population consisted of 199 H1N1pdm-infected subjects sampled between 23 June and 4 July 2009. Thirty-nine had severe disease defined as death (n = 20) or hospitalization (n = 19); 160 had mild disease. At least one additional agent of potential pathogenic importance was identified in 152 samples (76%), including Streptococcus pneumoniae (n = 62); Haemophilus influenzae (n = 104); human respiratory syncytial virus A (n = 11) and B (n = 1); human rhinovirus A (n = 1) and B (n = 4); human coronaviruses 229E (n = 1) and OC43 (n = 2); Klebsiella pneumoniae (n = 2); Acinetobacter baumannii (n = 2); Serratia marcescens (n = 1); and Staphylococcus aureus (n = 35) and methicillin-resistant S. aureus (MRSA, n = 6). The presence of S. pneumoniae was strongly correlated with severe disease. S. pneumoniae was present in 56.4% of severe cases versus 25% of mild cases; more than one-third of H1N1pdm NPS with S. pneumoniae were from subjects with severe disease (22 of 62 S. pneumoniae-positive NPS, p = 0.0004). In subjects 6 to 55 years of age, the adjusted odds ratio (OR) of severe disease in the presence of S. pneumoniae was 125.5 (95% confidence interval [CI], 16.95, 928.72; p<0.0001). CONCLUSIONS/SIGNIFICANCE: The association of S. pneumoniae with morbidity and mortality is established in the current and previous influenza pandemics. However, this study is the first to demonstrate the prognostic significance of non-invasive antemortem diagnosis of S. pneumoniae infection and may provide insights into clinical management.


COVID-19 and Obesity—the Management of Pre- and Post-bariatric Patients Amidst the COVID-19 Pandemic


title: Population genetics, community of parasites, and resistance to rodenticides in an urban brown rat (Rattus norvegicus) population

text: Brown rats are one of the most widespread urban species worldwide. Despite the nuisances they induce and their potential role as a zoonotic reservoir, knowledge on urban rat populations remains scarce. The main purpose of this study was to characterize an urban brown rat population from Chanteraines park (Hauts-de-Seine, France), with regards to haematology, population genetics, immunogenic diversity, resistance to anticoagulant rodenticides, and community of parasites. Haematological parameters were measured. Population genetics was investigated using 13 unlinked microsatellite loci. Immunogenic diversity was assessed for Mhc-Drb. Frequency of the Y139F mutation (conferring resistance to rodenticides) and two linked microsatellites were studied, concurrently with the presence of anticoagulant residues in the liver. Combination of microscopy and molecular methods were used to investigate the occurrence of 25 parasites. Statistical approaches were used to explore multiple parasite relationships and model parasite occurrence. Eighty-six rats were caught. The first haematological data for a wild urban R. norvegicus population was reported. Genetic results suggested high genetic diversity and connectivity between Chanteraines rats and surrounding population(s). We found a high prevalence (55.8%) of the mutation Y139F and presence of rodenticide residues in 47.7% of the sampled individuals. The parasite species richness was high (16). Seven potential zoonotic pathogens were identified, together with a surprisingly high diversity of Leptospira species (4). Chanteraines rat population is not closed, allowing gene flow and making eradication programs challenging, particularly because rodenticide resistance is highly prevalent. Parasitological results showed that co-infection is more a rule than an exception. Furthermore, the presence of several potential zoonotic pathogens, of which four Leptospira species, in this urban rat population raised its role in the maintenance and spread of these pathogens. Our findings should stimulate future discussions about the development of a long-term rat-control management program in Chanteraines urban park.


Implementation of a Novel Bluetooth Technology for Remote Deep Brain Stimulation Programming: The Pre– and Post–COVID‐19 Beijing Experience


title: Aminopeptidase N-null neonatal piglets are protected from transmissible gastroenteritis virus but not porcine epidemic diarrhea virus

text: Swine enteric diseases have caused significant economic loss and have been considered as the major threat to the global swine industry. Several coronaviruses, including transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV), have been identified as the causative agents of these diseases. Effective measures to control these diseases are lacking. The major host cells of transmissible gastroenteritis virus and porcine epidemic diarrhea virus have thought to be epithelial cells on small intestine villi. Aminopeptidase-N (APN) has been described as the putative receptor for entry of transmissible gastroenteritis virus and porcine epidemic diarrhea virus into cells in vitro. Recently, Whitworth et al. have reported that APN knockout pigs are resistant to TGEV but not PEDV after weaning. However, it remains unclear if APN-null neonatal pigs are protected from TGEV. Here we report the generation of APN-null pigs by using CRISPR/Cas9 technology followed by somatic cell nuclear transfer. APN-null pigs are produced with normal pregnancy rate and viability, indicating lack of APN is not embryonic lethal. After viral challenge, APN-null neonatal piglets are resistant to highly virulent transmissible gastroenteritis virus. Histopathological analyses indicate APN-null pigs exhibit normal small intestine villi, while wildtype pigs show typical lesions in small intestines. Immunochemistry analyses confirm that no transmissible gastroenteritis virus antigen is detected in target tissues in APN-null piglets. However, upon porcine epidemic diarrhea virus challenge, APN-null pigs are still susceptible with 100% mortality. Collectively, this report provides a viable tool for producing animals with enhanced resistance to TGEV and clarifies that APN is dispensable for the PEDV infection in pigs.


title: Griffithsin Inhibits Nipah Virus Entry and Fusion and Can Protect Syrian Golden Hamsters From Lethal Nipah Virus Challenge

text: Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus that causes fatal encephalitis and respiratory disease in humans. There is currently no approved therapeutic for human use against NiV infection. Griffithsin (GRFT) is high-mannose oligosaccharide binding lectin that has shown in vivo broad-spectrum activity against viruses including severe acute respiratory syndrome coronavirus, human immunodeficiency virus 1, hepatitis C virus, and Japanese encephalitis virus. In this study, we evaluated the in vitro antiviral activities of GRFT and its synthetic trimeric tandemer (3mG) against NiV and other viruses from across 4 virus families. The 3mG had comparatively greater potency than GRFT against NiV due to its enhanced ability to block NiV glycoprotein-induced syncytia formation. Our initial in vivo prophylactic evaluation of an oxidation-resistant GRFT (Q-GRFT) showed significant protection against lethal NiV challenge in Syrian golden hamsters. Our results warrant further development of Q-GRFT and 3mG as potential NiV therapeutics.


title: Olfactory and gustatory abnormalities in COVID-19 cases

text: PURPOSE: At the time of writing, there is a pandemic affecting virtually every country on Earth. There is considerable discussion amongst clinicians as well as lay people about anosmia and ageusia in COVID-19 sufferers. We aimed to report the results from comprehensive olfactory and gustatory testing in a series of hospital in-patients. METHODS: The prospective study evaluated 81 individuals with a COVID-19 infection, as confirmed by 2019 n-cov Real-Time PCR laboratory testing. The control group consisted of forty individuals with COVID-19 negative. Olfactory and gustatory testings were carried out by an examiner utilizing stringent safety standards and wearing full personal protective equipment. The results obtained in the case group were then compared with those obtained for the controls. RESULTS: In the case group, 41(50.6%) of patients were male and 40 (49.4%) were female, mean age of 54.16 ± 16.98 years (18–95). In the control group, 21 (52.5%) of subjects were male and 19 (47.5%) were female, and mean age was 55 ± 15.39 years (18–90). Fifty (61.7%) COVID-19-positive patients had complaints related to olfaction. The distribution of olfactory symptoms in the case group differed at the level of statistical significance from the control group (p < 0.001). Turning to gustatory abnormalities, within the case group, 22 individuals (27.2%) had taste malfunction. A statistically significant difference was found in the distribution of gustatory abnormalities between cases and controls (p < 0.001). CONCLUSIONS: Olfactory and gustatory dysfunctions are strongly associated with SARS-CoV-2 infection. Hyposmia with or without hypogeusia is potentially a reliable indicator of latent COVID-19.


title: Purification, crystallization and preliminary crystallographic analysis of avian infectious bronchitis virus nsp3 ADRP domain

text: Avian infectious bronchitis virus (IBV) encodes 15 nonstructural proteins (nsps) which play crucial roles in RNA transcription and genome replication. One of them, nsp3, contains an ADRP (adenosine diphosphate-ribose-1′-phosphatase) domain which was revealed in recent studies to have ADP-ribose-1′-monophosphatase (Appr-1′-pase) activity. Appr-1′-pase catalyzes the conversion of ADP-ribose-1′-monophosphate (Appr-1′-p) to ADP-ribose in the tRNA-splicing pathway. The gene segment encoding the IBV nsp3 ADRP domain has been cloned and expressed in Escherichia coli. The protein has been crystallized and the crystals diffracted to 1.8 Å resolution. They belonged to space group P1, with unit-cell parameters a = 41.1, b = 43.2, c = 48.9 Å, α = 78.0, β = 80.0, γ = 73.6°. Each asymmetric unit contains two molecules.


title: Development of broad‐spectrum human monoclonal antibodies for rabies post‐exposure prophylaxis

text: Currently available rabies post‐exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad‐spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non‐RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20–RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post‐vaccination antibody response.


title: Clinical presentations and outcome of severe community-acquired pneumonia

text: Abstract Background Severe community-acquired pneumonia (SCAP) represents a frequent and potentially life-threatening condition. About 10% of all hospitalized patients with CAP require admission to the intensive care unit (ICU), and the mortality of these patients reaches 20–50%. Objective To evaluate the clinical presentation, bacteriological profile and outcome of severe community-acquired pneumonia (SCAP). Patients and methods 54 patients presented by symptoms and sign of severe community acquired pneumonia who were admitted to respiratory care unit of Alhussein, Al-Azhar University Hospital from August 2015 to March 2016 were subjected to full clinical examination, chest X ray, complete blood picture, sputum and blood culture, PCR for suspected cases of Influenza H1N1 and MERS-COV, treatment, follow up, data collections and statistical analysis. Results The present study included 54 patients 26 males and 28 females with SCAP who were admitted to respiratory care unit of Alhussein, Al-Azhar University Hospital. The most common comorbidities were diabetes mellitus and hypertension. The most common presentations were fever, cough, dyspnea and hypoxemia. Two patients developed renal failure and 4 patients developed septic shock. The most common isolated organism was Streptococcus pneumoniae, Influenza H1N1, and Staphylococcus aureus. Mortality was 24% and it was common in patients with comorbidity than in patients without comorbidities. Conclusion SCAP occurs more frequently in those with comorbidities. The most frequent isolated causative organism of SCAP is S. pneumoniae, Influenza H1N1 and S. aureus. SCAP is associated with significant mortality, early recognition and prompt treatment may improve outcome.


title: Complementary and alternative medicine use among outpatients during the 2015 MERS outbreak in South Korea: a cross-sectional study

text: BACKGROUND: The 2015 MERS outbreak in South Korea was the largest event outside of the Middle East. Under such circumstances, individuals tend to resort to non-conventional solutions such as complementary and alternative medicine (CAM) to manage health. Thus, this study aims to examine characteristics of CAM use among outpatients in a community hospital setting during the 2015 MERS outbreak and to assess potential predictors of CAM use during the epidemic. METHODS: A cross-sectional study was conducted among 331 patients (response rate: 82.75%) at a community hospital located in Seoul, South Korea. The survey instrument included 36 questions on the use of CAM, demographic characteristics, health status, and respondents’ perceptions and concerns about MERS infection. Chi-square test and logistic regression were conducted for data analysis using SPSS ver. 21.0., and a p-value of less than 0.05 was considered statistically significant for all analyses. RESULTS: 76.1% of respondents used one or more types of CAM modalities during the MERS outbreak. Consumption of easily accessible modalities such as multivitamin (51.2%) and food products (32.1%) was most popular, and the majority of CAM users relied on mass media (52.4%) and the internet (27.4%) to obtain information on CAM. The use of CAM was associated with age between 40 and 49, age over 50, prior CAM use, and dissatisfaction with the government response to the MERS outbreak. CONCLUSIONS: CAM was commonly used by outpatients during the 2015 MERS outbreak in Korea, and mass media was the main source of information. Establishing a media platform is of paramount importance to provide reliable information and ensure the safety of its use.


title: Nasopharyngeal Shedding of Severe Acute Respiratory Syndrome—Associated Coronavirus Is Associated with Genetic Polymorphisms

text: Background. A high initial or peak severe acute respiratory syndrome (SARS)—associated coronavirus (SARS-CoV) load in nasopharyngeal specimens was shown to be associated with a high mortality rate. Because all infected individuals were devoid of preeexisting protective immunity against SARS-CoV, the biological basis for the variable virus burdens in different patients remains elusive. Methods. The nationwide SARS database in Taiwan was analyzed, and genotyping of 281 single-nucleotide polymorphisms (SNPs) of 65 genes was performed for 94 patients with SARS, to identify SNPs for which distribution between patients with or without detectable nasopharyngeal shedding of SARS-CoV was biased. Results. Titers of SARS-CoV shed in nasopharyngeal specimens varied widely, ranging from nondetectable to 10(8) SARS-CoV RNA copies/mL, and they were correlated positively with a high mortality rate (P < .0001, by trend test) and with early death (i.e., death occurring within 2 weeks of the onset of illness) (P = .0015, by trend test). Virus shedding was found to be higher among male patients (P = .0014, by multivariate logistic regression) and among older patients (P = .015, by multivariate logistic regression). Detectable nasopharyngeal shedding of SARS-CoV was associated with polymorphic alleles of interleukins 18 (P = .014) and 1A (P = .031) and a member of NFκB complex (reticuloendotheliosis viral oncogene homolog B [RelB]) (P = .034), all of which are proinflammatory in nature, as well as the procoagulation molecule fibrinogen-like protein 2 (P = .008). Conclusion. The SARS-CoV load is a determinant of clinical outcomes of SARS, and it is associated with polymorphisms of genes involved in innate immunity, which might be regulated in an age- and sex-dependent manner. The findings of the present study provided leads to genes involved in the host response to SARS-CoV infection; if substantiated with functional studies, these findings may be applicable to other newly emerged respiratory viruses (e.g., the influenza pandemic strain).


title: CSF1R antagonism limits local restimulation of antiviral CD8(+) T cells during viral encephalitis

text: BACKGROUND: Microglia are resident macrophages of the central nervous system (CNS) locally maintained through colony-stimulating factor 1 receptor (CSF1R) signaling. Microglial depletion via CSF1R inactivation improves cognition in mouse models of neuroinflammation, but limits virologic control in the CNS of mouse models of neurotropic infections by unknown mechanisms. We hypothesize that CSF1R plays a critical role in myeloid cell responses that restrict viral replication and locally restimulate recruited antiviral T cells within the CNS. METHODS: The impact of CSF1R signaling during West Nile virus infection was assessed in vivo using a mouse model of neurotropic infection. Pharmacological inactivation of CSF1R was achieved using PLX5622 prior to infection with virulent or attenuated strains of West Nile virus (WNV), an emerging neuropathogen. The subsequent effect of CSF1R antagonism on virologic control was assessed by measuring mortality and viral titers in the CNS and peripheral organs. Immune responses were assessed by flow cytometric-based phenotypic analyses of both peripheral and CNS immune cells. RESULTS: Mice treated with CSF1R antagonist prior to infection exhibited higher susceptibility to lethal WNV infection and lack of virologic control in both the CNS and periphery. CSFR1 antagonism reduced B7 co-stimulatory signals on peripheral and CNS antigen-presenting cells (APCs) by depleting CNS cellular sources, which limited local reactivation of CNS-infiltrating virus-specific T cells and reduced viral clearance. CONCLUSIONS: Our results demonstrate the impact of CSF1R antagonism on APC activation in the CNS and periphery and the importance of microglia in orchestrating the CNS immune response following neurotropic viral infection. These data will be an important consideration when assessing the benefit of CSF1R antagonism, which has been investigated as a therapeutic for neurodegenerative conditions, in which neuroinflammation is a contributing factor. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-019-1397-4) contains supplementary material, which is available to authorized users.


title: If COVID‐19 Becomes Endemic will the Current Dental Guidelines Still Remain Valid?

text: In a recent paper, the authors Jamal et al reviewed various guidelines published by dental societies of the world for the prevention of transmission of COVID‐19 virus in the dental care setting during the current pandemic(Jamal et al., 2020). While this review is very interesting, I have a genuine apprehension that these guidelines may not be valid for a long time and very soon new guidelines will be required in the unfortunate event of COVID‐19 becoming endemic.


title: Genetic characterization of a novel picornavirus in Algerian bats: co-evolution analysis of bat-related picornaviruses

text: Bats are reservoirs of numerous zoonotic viruses. The Picornaviridae family comprises important pathogens which may infect both humans and animals. In this study, a bat-related picornavirus was detected from Algerian Minioptreus schreibersii bats for the first time in the country. Molecular analyses revealed the new virus originates to the Mischivirus genus. In the operational use of the acquired sequence and all available data regarding bat picornaviruses, we performed a co-evolutionary analysis of mischiviruses and their hosts, to authentically reveal evolutionary patterns within this genus. Based on this analysis, we enlarged the dataset, and examined the co-evolutionary history of all bat-related picornaviruses including their hosts, to effectively compile all possible species jumping events during their evolution. Furthermore, we explored the phylogeny association with geographical location, host-genus and host-species in both data sets.


Critically ill COVID‐19 infected patients exhibit increased clot waveform analysis parameters consistent with hypercoagulability


title: Distinct regulation of MHC molecule expression on astrocytes and microglia during viral encephalomyelitis

text: The potential interplay of glial cells with T cells during viral induced inflammation was assessed by comparing major histocompatibility complex molecule upregulation and retention on astrocytes and microglia. Transgenic mice expressing green fluorescent protein under control of the astrocyte‐specific glial fibrillary acidic protein promoter were infected with a neurotropic coronavirus to facilitate phenotypic characterization of astrocytes and microglia using flow cytometry. Astrocytes in the adult central nervous system up‐regulated class I surface expression, albeit delayed compared with microglia. Class II was barely detectable on astrocytes, in contrast to potent up‐regulation on microglia. Maximal MHC expression in both glial cell types correlated with IFN‐γ levels and lymphocyte accumulation. Despite a decline of IFN‐γ concomitant to virus clearance, MHC molecule expression on glia was sustained. These data demonstrate distinct regulation of both class I and class II expression by microglia and astrocytes in vivo following viral induced inflammation. Furthermore, prolonged MHC expression subsequent to viral clearance implies a potential for ongoing presentation. © 2007 Wiley‐Liss, Inc.


title: Viral etiologies and epidemiology of patients with acute respiratory infections based on sentinel hospitals in Gansu Province, Northwest China, 2011‐2015

text: Understanding etiological role and epidemiological profile is needed to improve clinical management and prevention of acute respiratory infections (ARIs). A 5‐year prospective study about active surveillance for outpatients and inpatients with ARIs was conducted in Gansu province, China, from January 2011 to November 2015. Respiratory specimens were collected from patients and tested for eight respiratory viruses using polymerase chain reaction (PCR) or reverse transcription polymerase chain reaction (RT‐PCR). In this study, 2768 eligible patients with median age of 43 years were enrolled including pneumonia (1368, 49.2%), bronchitis (435, 15.7%), upper respiratory tract infection or URTI (250, 9.0%), and unclassified ARI (715, 25.8%). Overall, 29.2% (808/2768) were positive for any one of eight viruses, of whom 130 cases were identified with two or more viruses. Human rhinovirus (HRV) showed the highest detection rate (8.6%), followed by influenza virus (Flu, 7.3%), respiratory syncytial virus (RSV, 6.1%), human coronavirus (hCoV, 4.3%), human parainfluenza (PIV, 4.0%), adenovirus (ADV, 2.1%), human metapneumovirus (hMPV, 1.6%), and human bocavirus (hBoV, 0.7%). Compared with URTI, RSV was more likely identified in pneumonia (χ(2) = 12.720, P < 0.001) and hCoV was more commonly associated with bronchitis than pneumonia (χ(2) = 15.019, P < 0.001). In patients aged less than 5 years, RSV showed the highest detection rate and hCoV was the most frequent virus detected in adults and elderly. The clear epidemical seasons were observed in HRV, Flu, and hCoV infections. These findings could serve as a reference for local health authorities in drawing up further plans to prevent and control ARIs associated with viral etiologies.


title: Translation of Korean Medicine Use to ICD-Codes Using National Health Insurance Service-National Sample Cohort

text: Background. Korean medicine was incorporated into the Korean Classification of Diseases (KCD) 6 through the development of U codes (U20–U99). Studies of the burden of disease have used summary measures such as disability-adjusted life years. Although Korean medicine is included in the official health care system, studies of the burden of disease that include Korean medicine are lacking. Methods. A data-based approach was used with National Health Insurance Service-National Sample Cohort data for the year 2012. U code diagnoses for patients covered by National Health Insurance were collected. Using the main disease and subdisease codes, the proportion of U codes was redistributed into the related KCD 6 codes and visualized. U code and KCD code relevance was appraised prior to the analysis by consultation with medical professionals and from the beta draft version of the International Classification of Diseases-11 traditional medicine chapter. Results. This approach enabled redistribution of U codes into KCD 6 codes. Musculoskeletal diseases had the greatest increase in the burden of disease through this approach. Conclusion. This study provides a possible method of incorporating Korean medicine into burden of disease analyses through a data-based approach. Further studies should analyze potential yearly differences.


title: Chapter 15 Human Bocavirus

text: Human bocavirus 1 (HBoV1), family Parvoviridae, subfamily Parvovirinae, genus Bocavirus, is a recently described respiratory virus with a worldwide distribution. It is recognized as one of the most frequently detected respiratory viruses in hospitalized children below 5 years of age and mainly detected in children between 6 and 24 months of age. The severe clinical course of HBoV1 infection can be seen in prematurely born children or children, but rarely adults, with other underlying medical conditions. The seroepidemiological studies show that most of the children are infected with HBoV1 by the age of 6 and that the IgG antibodies remain for life. The routine laboratory diagnostics of HBoV1 infections is almost exclusively based on detection of HBoV1 DNA in respiratory samples by PCR. Due to frequent coinfections with other respiratory viruses, PCR of plasma samples and detection of specific IgM might aid in determining the etiology of infection.


title: The antiviral and the coronavirus-host protein pathways inhibiting properties of herbs and natural compounds - Additional weapons in the fight against the COVID-19 pandemic?

text: INTRODUCTION: As of March 11th, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic. Articles published after the SARS-CoV-1 (2002) epidemic suggest that the use of an herbal-drug integrative medical approach could have contributed to a lower fatality rate and a more rapid response in controlling the outbreak. METHODS: Pubmed was searched for articles that investigated the antiviral properties and mechanisms of action of herbs or natural compounds against the SARS-coronavirus (CoV). RESULTS: Forty-three (43) relevant papers were located. A general count rendered 450+ herbs and natural compounds with antiviral properties against the SARS-CoV and related viruses. From the 43 articles, thirty-one (31) uncovered the mechanisms of action of the natural substances able to oppose the coronavirus. DISCUSSION: A series of herbs and natural compounds demonstrated moderate to strong antiviral activity. Research on many herbs-natural compounds also showed potent and significant inhibition of CoV-host protein pathways responsible for different phases of viral replication specifically targeting 3CL(PRO), PL(PRO), RdRp, helicase protein, S protein, N protein, 3a protein, Cathepsin L, Nsp1, Nsp3c, and ORF7a, and the S protein-ACE-2 interaction. CONCLUSION: The herbs-natural compounds with antiviral activity and that caused inhibition/blockade of the CoV-host protein pathways are potential therapeutic candidates. The homology between the SARS-CoV-1 and SARS-CoV-2 is around 80%. Thus, effective herbs-compounds for the former would likely be beneficial for the latter also depending on target protein similarities between the viruses. Here we provide the mechanistic bases supporting an integrative approach that includes natural compounds to fight coronavirus infections.


Severe refractory Kawasaki disease in seven infants in the COVID-19 era


title: Development and Characterization of a Severe Acute Respiratory Syndrome—Associated Coronavirus—Neutralizing Human Monoclonal Antibody That Provides Effective Immunoprophylaxis in Mice

text: Background. Severe acute respiratory syndrome (SARS) remains a significant public health concern after the epidemic in 2003. Human monoclonal antibodies (MAbs) that neutralize SARS-associated coronavirus (SARSCoV) could provide protection for exposed individuals. Methods. Transgenic mice with human immunoglobulin genes were immunized with the recombinant major surface (S) glycoprotein ectodomain of SARS-CoV. Epitopes of 2 neutralizing MAbs derived from these mice were mapped and evaluated in a murine model of SARS-CoV infection. Results. Both MAbs bound to S glycoprotein expressed on transfected cells but differed in their ability to block binding of S glycoprotein to Vero E6 cells. Immunoprecipitation analysis revealed 2 antibody-binding epitopes: one MAb (201) bound within the receptor-binding domain at aa 490–510, and the other MAb (68) bound externally to the domain at aa 130–150. Mice that received 40 mg/kg of either MAb prior to challenge with SARS-CoV were completely protected from virus replication in the lungs, and doses as low as 1.6 mg/kg offered significant protection. Conclusions. Two neutralizing epitopes were defined for MAbs to SARS-CoV S glycoprotein. Antibodies to both epitopes protected mice against SARS-CoV challenge. Clinical trials are planned to test MAb 201, a fully human MAb specific for the epitope within the receptor-binding region.


title: Probing the Effects of Pyrimidine Functional Group Switches on Acyclic Fleximer Analogues for Antiviral Activity

text: Due to their ability to inhibit viral DNA or RNA replication, nucleoside analogues have been used for decades as potent antiviral therapeutics. However, one of the major limitations of nucleoside analogues is the development of antiviral resistance. In that regard, flexible nucleoside analogues known as “fleximers” have garnered attention over the years due to their ability to survey different amino acids in enzyme binding sites, thus overcoming the potential development of antiviral resistance. Acyclic fleximers have previously demonstrated antiviral activity against numerous viruses including Middle East Respiratory Syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), and, most recently, flaviviruses such as Dengue (DENV) and Yellow Fever Virus (YFV). Due to these interesting results, a Structure Activity Relationship (SAR) study was pursued in order to analyze the effect of the pyrimidine functional group and acyl protecting group on antiviral activity, cytotoxicity, and conformation. The results of those studies are presented herein.


title: Viral respiratory tract infections in the neonatal intensive care unit

text: Abstract Introduction Viral respiratory infections cause major morbidity and mortality in preterm infants. We have performed a prospective study in our neonatal intensive care unit (NICU) to determine the incidence of respiratory infections, their impact and the epidemiology and outcome in high risk neonates. Patients and methods From September 2011 to May 2013 a prospective study was conducted in all preterm infants <32 weeks gestational age and in all term newborns admitted to NICU for any pathology that was anticipated to have an admission exceeding two weeks. A nasopharyngeal aspirate (NPA) was collected the first day of life and weekly until discharge for virologic study with polymerase chain reaction. When these babies presented respiratory symptoms a new NPA was collected at this moment. A clinical form was filled by the physician. Results A total of 60 infants were analysed: 30 (50%) had a gestational age <32 weeks and 36 (60%) weighed less than 1500g. We collected a total of 256 nasopharyngeal aspirate samples, 24 of them being positive (9.3%). These 24 positive samples corresponded to 13 infants in our cohort (21.6% of the patients). Of them, 9 were symptomatic and had 11 episodes of infection (2 patients had two different episodes with negative control between them). The most frequently identified virus was rhinovirus in (19) 79% of cases. The most frequent clinical data was the presence or increase in apneas (75%) and the need for oxygenotherapy. Conclusions HRV infections are prevalent in the NICU, and preterm infants have a high risk of infections with clinical relevance.


title: Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial

text: Abstract Background Accumulating evidence proposed JAK inhibitors as therapeutic targets warranting rapid investigation. Objective This study evaluated the efficacy and safety of ruxolitinib, a Janus-associated kinase (JAK1/2) inhibitor, for COVID-19. Methods We conducted a prospective, multicenter, single-blind, randomized controlled phase II trial involving patients with severe COVID-19. Results Forty-three patients were randomly assigned (1:1) to receive ruxolitinib plus SoC treatment (22 patients) or placebo based on SoC treatment (21 patients). After exclusion of 2 patients (1 ineligible, 1 consent withdrawn) from the ruxolitinib group, 20 patients in intervention group and 21 patients in control group were included in the study. Treatment with ruxolitinib plus SoC was not associated with significantly accelerated clinical improvement in severe patients with COVID-19, although ruxolitinib recipients had a numerically faster clinical improvement. Eighteen (90%) patients from the ruxolitinib group showed CT improvement at D14 compared with 13 (61.9%) patients from the control group (P = 0.0495). Three patients in the control group died of respiratory failure, with 14.3% overall mortality at D28; no patients died in the ruxolitinib group. Ruxolitinib was well tolerated with low toxicities and no new safety signals. Levels of 7 cytokines were significantly decreased in the ruxolitinib group in comparison to the control group. Conclusions Although no statistical difference was observed, ruxolitinib recipients had a numerically faster clinical improvement. Significant chest CT improvement, a faster recovery from lymphopenia and favorable side-effect profile in ruxolitinib group were encouraging and informative to future trials to test efficacy of ruxolitinib in a larger population. This trial is registered at www.chictr.org.cn as ChiCTR-OPN-2000029580.


title: Replication of Viruses

text: In general terms, virus replication involves three broad stages which are present in all viruses: initiation of infection, replication and expression of the genome, and the release of mature virions from the infected cell. At a more detailed level, virus replication can be broken down into the stages of attachment, entry, uncoating, transcription and genome replication, assembly, maturation, and release. However, there are many subtle differences between the replication processes of different viruses, imposed by the biology of the host cell and the nature of the virus genome.


title: Loss of the abundant nuclear non-coding RNA MALAT1 is compatible with life and development

text: The metastasis-associated lung adenocarcinoma transcript 1, MALAT1, is a long non-coding RNA (lncRNA) that has been discovered as a marker for lung cancer metastasis. It is highly abundant, its expression is strongly regulated in many tumor entities including lung adenocarcinoma and hepatocellular carcinoma as well as physiological processes, and it is associated with many RNA binding proteins and highly conserved throughout evolution. The nuclear transcript MALAT-1 has been functionally associated with gene regulation and alternative splicing and its regulation has been shown to impact proliferation, apoptosis, migration and invasion. Here, we have developed a human and a mouse knockout system to study the loss-of-function phenotypes of this important ncRNA. In human tumor cells, MALAT1 expression was abrogated using Zinc Finger Nucleases. Unexpectedly, the quantitative loss of MALAT1 did neither affect proliferation nor cell cycle progression nor nuclear architecture in human lung or liver cancer cells. Moreover, genetic loss of Malat1 in a knockout mouse model did not give rise to any obvious phenotype or histological abnormalities in Malat1-null compared with wild-type animals. Thus, loss of the abundant nuclear long ncRNA MALAT1 is compatible with cell viability and normal development.


title: COVID-19-Related Web Search Behaviors and Infodemic Attitudes in Italy: Infodemiological Study

text: BACKGROUND: Since the beginning of the novel coronavirus disease (COVID-19) outbreak, fake news and misleading information have circulated worldwide, which can profoundly affect public health communication. OBJECTIVE: We investigated online search behavior related to the COVID-19 outbreak and the attitudes of “infodemic monikers” (ie, erroneous information that gives rise to interpretative mistakes, fake news, episodes of racism, etc) circulating in Italy. METHODS: By using Google Trends to explore the internet search activity related to COVID-19 from January to March 2020, article titles from the most read newspapers and government websites were mined to investigate the attitudes of infodemic monikers circulating across various regions and cities in Italy. Search volume values and average peak comparison (APC) values were used to analyze the results. RESULTS: Keywords such as “novel coronavirus,” “China coronavirus,” “COVID-19,” “2019-nCOV,” and “SARS-COV-2” were the top infodemic and scientific COVID-19 terms trending in Italy. The top five searches related to health were “face masks,” “amuchina” (disinfectant), “symptoms of the novel coronavirus,” “health bulletin,” and “vaccines for coronavirus.” The regions of Umbria and Basilicata recorded a high number of infodemic monikers (APC weighted total >140). Misinformation was widely circulated in the Campania region, and racism-related information was widespread in Umbria and Basilicata. These monikers were frequently searched (APC weighted total >100) in more than 10 major cities in Italy, including Rome. CONCLUSIONS: We identified a growing regional and population-level interest in COVID-19 in Italy. The majority of searches were related to amuchina, face masks, health bulletins, and COVID-19 symptoms. Since a large number of infodemic monikers were observed across Italy, we recommend that health agencies use Google Trends to predict human behavior as well as to manage misinformation circulation in Italy.


Managing chronic wounds during novel coronavirus pneumonia outbreak


title: La PCR multiplex : un outil diagnostic d’infection respiratoire basse chez l’adulte

text: L’identification des agents pathogènes est importante pour la mise en œuvre d’un traitement adapté des infections respiratoires basses (IRB) mais les méthodes diagnostic classiques sont souvent mises en défaut. Nous rapportons l’impact sur la pratique clinique de l’utilisation de la PCR multiplex pour la détection de 18 virus et 4 bactéries. Entre janvier 2012 et avril 2014, une PCR multiplex a été réalisée sur aspiration nasopharyngée chez tous les patients adultes hospitalisés pour une IRB dans le service de maladies infectieuses du CHU de Tours. Sur 133 patients testés, un pathogène a été identifié chez 72 patients (54 %) dont 4 cas avec un Mycoplasma pneumoniae. Les 68 autres identifications étaient des virus avec Myxovirus influenzae A (22 patients), Rhino/entérovirus (16), Coronavirus (11), Bocavirus (11), Metapneumovirus (6), virus syncitial respiratoire (4), Adénovirus (4), Myxovirus influenzae B (3) et Paramyxovirus influenzae (2). Avec les méthodes classiques, un agent pathogène a été identifié dans 6 cas : 3 Streptococcus pneumoniae et 3 Mycoplasma pneumoniae. Lorsqu’un virus a été identifié comme cause de l’IRB, la radiographie pulmonaire montrait un syndrome alvéolaire dans 21 cas. L’identification d’un agent viral par PCR multiplex a permis un arrêt anticipé de l’antibiothérapie chez 14 patients et l’absence d’initiation d’un antibiotique chez 6 autres patients. La PCR multiplex est utile pour l’identification microbiologique des infections respiratoires virales (54 %) et pour la prise en charge des patients en limitant la prescription inappropriée d’antibiotique (15 % d’arrêt ou de non prescription).


title: The Financial Impact of Controlling a Respiratory Virus Outbreak in a Teaching Hospital: Lessons Learned from SARS

text: BACKGROUND: Outbreaks of Severe Acute Respiratory Syndrome (SARS) in 2003 and renewed concerns regarding pandemic influenza have resulted in widespread planning for future respiratory disease outbreaks. Such planning should include accurate cost estimates for any proposed disease control strategies. From the acute care hospital perspective, such estimates typically take into account the cost of supplies and equipment, but rarely consider indirect costs such as lost revenue due to the scaling down of programs. METHODS: Retrospective cost analysis. Costs and savings were calculated from the hospital perspective using financial records. Costs were categorized to determine the major areas of expenditure and savings. RESULTS: We report that controlling a SARS outbreak in a teaching hospital over an 8-week period cost $12 million Canadian. Lost revenue and labour accounted for two thirds of the costs incurred while excess spending on services, materials, supplies and renovation of existing space accounted for the remaining one third. CONCLUSIONS: Cost estimates that consider only excess expenditures may considerably underestimate the true cost of infection control strategies.


title: Spherical Fuzzy Cost/Benefit Analysis of Wind Energy Investments

text: Energy investments are highly risky due to the uncertainties of the energy market. Over the past two decades, the usage of wind energy has been increased dramatically. Appropriate wind energy investment valuations are vital for both the public and private sectors. The fluctuations in the energy prices, the uncertainties in the production levels and the changes in the investment costs harden the wind energy investment decision. Using the traditional investment valuations overlooks the necessary managerial flexibility of investments, uncertainty and risk concepts. The spherical fuzzy sets enable us dealing with this uncertain structure with the hesitancy. In this study, a new Spherical fuzzy cost benefit analysis is developed and modified to the wind energy investment evaluation. In order to show the applicability of the proposed method a wind energy investment is analyzed with it. This new approach by taking into account the hesitancy may enable investments to be evaluated with more flexibility and accuracy.


title: WSV 2019: The First Committee Meeting of the World Society for Virology

text: The World Society for Virology (WSV) was founded and incorporated as a nonprofit organization in the United States in 2017. WSV seeks to strengthen and support both virological research and virologists who conduct research of viruses that affect humans, other animals, plants, and other organisms. One of the objectives of WSV is to connect virologists worldwide and support collaboration. Fulfilling this objective, virologists from fourteen countries in North America, Europe, Africa, Asia, and the Middle East met on 25–27th August 2019 in Stockholm, Sweden at the Karolinska University Hospital for the first Committee Meeting of WSV. This meeting included compelling keynote and honorary speeches and a series of 18 scientific talks were given encompassing a diverse array of subjects within virology. Followed by the scientific session, a business session was held where multiple aspects and next steps of the society were discussed and charted out.


title: Community-Acquired Pneumonia in the Conjugate Vaccine Era

text: Community-acquired pneumonia (CAP) remains one of the most common serious infections encountered among children worldwide. In this review, we highlight important literature and recent scientific discoveries that have contributed to our current understanding of pediatric CAP. We review the current epidemiology of childhood CAP in the developed world, appraise the state of diagnostic testing for etiology and prognosis, and discuss disease management and areas for future research in the context of recent national guidelines.