title: Novel viral vectors utilizing intron splice-switching to activate genome rescue, expression and replication in targeted cells

text: BACKGROUND: The outcome of virus infection depends from the precise coordination of viral gene expression and genome replication. The ability to control and regulate these processes is therefore important for analysis of infection process. Viruses are also useful tools in bio- and gene technology; they can efficiently kill cancer cells and trigger immune responses to tumors. However, the methods for constructing tissue- or cell-type specific viruses typically suffer from low target-cell specificity and a high risk of reversion. Therefore novel and universal methods of regulation of viral infection are also important for therapeutic application of virus-based systems. METHODS: Aberrantly spliced introns were introduced into crucial gene-expression units of adenovirus vector and alphavirus DNA/RNA layered vectors and their effects on the viral gene expression, replication and/or the release of infectious genomes were studied in cell culture. Transfection of the cells with splice-switching oligonucleotides was used to correct the introduced functional defect(s). RESULTS: It was demonstrated that viral gene expression, replication and/or the release of infectious genomes can be blocked by the introduction of aberrantly spliced introns. The insertion of such an intron into an adenovirus vector reduced the expression of the targeted gene more than fifty-fold. A similar insertion into an alphavirus DNA/RNA layered vector had a less dramatic effect; here, only the release of the infectious transcript was suppressed but not the subsequent replication and spread of the virus. However the insertion of two aberrantly spliced introns resulted in an over one hundred-fold reduction in the infectivity of the DNA/RNA layered vector. Furthermore, in both systems the observed effects could be reverted by the delivery of splice-switching oligonucleotide(s), which corrected the splicing defects. CONCLUSIONS: Splice-switch technology, originally developed for genetic disease therapy, can also be used to control gene expression of viral vectors. This approach represents a novel, universal and powerful method for controlling gene expression, replication, viral spread and, by extension, virus-induced cytotoxic effects and can be used both for basic studies of virus infection and in virus-based gene- and anti-cancer therapy.


title: Epidemiology of Human Adenoviruses: A 20-Year Retrospective Observational Study in Hospitalized Patients in Bern, Switzerland

text: BACKGROUND: Human adenovirus (HAdV) is an important pathogen seen in clinical practice. Long-term studies may help better understand epidemiological trends and changes in circulating genotypes over time. PURPOSE: Using a large biobank of samples from hospitalized, adenovirus-positive patients over a 20-year period, we aimed to analyze long-term epidemiological trends and genotypic relatedness among circulating HAdV strains. METHODS: Based on samples from hospitalized patients confirmed to be HAdV positive in Bern, Switzerland, from 1998 to 2017, and on their associated demographic and clinical data, we identified epidemiological trends and risk factors associated with HAdV infection. HAdV genotyping was performed by PCR amplification and sequencing of the hypervariable hexon gene. The obtained sequences were phylogenetically compared with sequences from international HAdV strains. RESULTS: HAdV was identified in 1302 samples tested. Cases of HAdV infection were reported throughout the years with no clear seasonality. Upper respiratory tract samples, conjunctivitis swabs, and stool had the highest positivity rate (56.2%, 18.7%, and 14.2% of the cases, respectively). HAdV infection was highest among children ≤4 years old. Increased number of HAdV cases were observed in years 2009 (n = 110) and 2010 (n =112). HAdV8 was the predominant genotype among patients older than 20 years, and was mostly associated with ophthalmic infection. Predominant genotypes among children ≤4 years old were HAdV1, HAdV2, and HAdV3, which were mostly associated with respiratory tract infections. Recurring peaks of increased HAdV cases were evidenced every 4 years among children ≤4 years old. CONCLUSION: Our study gives novel insights on long-term epidemiological trends and phylogenetic relatedness among circulating HAdV strains in Switzerland, country in which little data on HAdV prevalence and diversity was so far available.


title: Respiratory virus infection after allogeneic hematopoietic stem cell transplant in a tropical center: Predictive value of the immunodeficiency scoring index

text: BACKGROUND: Respiratory virus infection (RVI) is a prevalent infection in patients after allogeneic hematopoietic stem cell transplant (allo‐HSCT) and can result in significant morbidity and mortality. Ability to assess the potential severity of RVI is important in the management of such patients. METHODS: We reviewed the cases of RVI in allo‐HSCT recipients and explored the predictive value of the immunodeficiency scoring index (ISI) established for respiratory syncytial virus (RSV) and its applicability for RVI caused by other respiratory viruses. RESULTS: RVI occurred year‐round in our tropical transplant center, with peaks in the middle and end of the year. Ninety‐five of the 195 recipients developed a total of 191 episodes of RVI, giving a cumulative incidence of 28% by 6 months and 52% by 24 months for the first episode of RVI. RSV, influenza, rhinovirus, and parainfluenza were the most common viruses. Pneumonia occurred in 63.64%, 42.31%, and 32.42% of adenovirus, influenza, and RSV RVI episodes, respectively, but was also non‐negligible in the more benign viruses, such as coronavirus (31.58%) and rhinovirus (23.68%). Nineteen of the 63 episodes of viral pneumonia required mechanical ventilation and 14 deaths occurred within 6 weeks of the RVI. Receiver operating characteristic analysis showed that an ISI of ≥8 predicted pneumonia with a positive predictive value of >80% for RVI caused by RSV, influenza, adenovirus, and parainfluenza, while it was not predictive for coronavirus and rhinovirus. CONCLUSIONS: The ISI is a useful aid for decision‐making during clinic consultation for patients presenting with symptoms suggestive of an RVI.


title: Human Respiratory Coronaviruses Detected In Patients with Influenza-Like Illness in Arkansas, USA

text: Acute respiratory viruses often result in significant morbidity and mortality. The potential impact of human respiratory coronavirus (CoV) infections was underestimated until the severe acute respiratory syndrome (SARS-CoV) outbreak in 2003, which showed that new, highly pathogenic coronaviruses could be introduced to humans, highlighting the importance of monitoring the circulating coronaviruses. The use of sensitive molecular methods has contributed to the differential diagnosis of viruses circulating in humans. Our study aim was to investigate the molecular epidemiology of human CoV strains circulating in Arkansas, their genetic variability and their association with reported influenza-like symptoms. We analyzed 200 nasal swab samples, collected by the Arkansas Department of Health in 2010, for influenza diagnosis. All samples were from patients showing acute respiratory symptoms while testing negative for influenza. Samples were pre-screened, using a quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) multiprobe for coronavirus, and subjected to confirmatory pancoronavirus and/or strain-specific reverse transcriptase (RT)-PCR followed by sequence analysis. Seventy-nine samples (39.5%) were positive by qRT-PCR and 35 samples (17.5%) were confirmed by conventional RT-PCR. Twenty-three of the confirmed samples (59%) were sequenced. The most frequent strain detected was HCoV-OC43-like followed by NL63-like; only one sample was positive for HCoV-229E and one for HCoV-HKU1. Feline-like CoV strains were detected in three samples, representing possible evidence of interspecies transmission or a new human strain. Seventeen percent of the coronavirus positive samples were also positive for other respiratory viruses, such as Respiratory Syncytial Virus (RSV), Parainfluenza 2 and 3, and Rhinovirus. Thus, HCoV-OC43, NL63, HKU1 and new feline-like strains were circulating in Arkansas in 2010. HCoV was the sole respiratory virus detected in 16% of the patients who showed acute respiratory symptoms with negative diagnoses for influenza virus.


title: Strategies for Human Tumor Virus Discoveries: From Microscopic Observation to Digital Transcriptome Subtraction

text: Over 20% of human cancers worldwide are associated with infectious agents, including viruses, bacteria, and parasites. Various methods have been used to identify human tumor viruses, including electron microscopic observations of viral particles, immunologic screening, cDNA library screening, nucleic acid hybridization, consensus PCR, viral DNA array chip, and representational difference analysis. With the Human Genome Project, a large amount of genetic information from humans and other organisms has accumulated over the last decade. Utilizing the available genetic databases, Feng et al. (2007) developed digital transcriptome subtraction (DTS), an in silico method to sequentially subtract human sequences from tissue or cellular transcriptome, and discovered Merkel cell polyomavirus (MCV) from Merkel cell carcinoma. Here, we review the background and methods underlying the human tumor virus discoveries and explain how DTS was developed and used for the discovery of MCV.


title: Building predictive models for MERS-CoV infections using data mining techniques

text: Summary Background Recently, the outbreak of MERS-CoV infections caused worldwide attention to Saudi Arabia. The novel virus belongs to the coronaviruses family, which is responsible for causing mild to moderate colds. The control and command center of Saudi Ministry of Health issues a daily report on MERS-CoV infection cases. The infection with MERS-CoV can lead to fatal complications, however little information is known about this novel virus. In this paper, we apply two data mining techniques in order to better understand the stability and the possibility of recovery from MERS-CoV infections. Method The Naive Bayes classifier and J48 decision tree algorithm were used to build our models. The dataset used consists of 1082 records of cases reported between 2013 and 2015. In order to build our prediction models, we split the dataset into two groups. The first group combined recovery and death records. A new attribute was created to indicate the record type, such that the dataset can be used to predict the recovery from MERS-CoV. The second group contained the new case records to be used to predict the stability of the infection based on the current status attribute. Results The resulting recovery models indicate that healthcare workers are more likely to survive. This could be due to the vaccinations that healthcare workers are required to get on regular basis. As for the stability models using J48, two attributes were found to be important for predicting stability: symptomatic and age. Old patients are at high risk of developing MERS-CoV complications. Finally, the performance of all the models was evaluated using three measures: accuracy, precision, and recall. In general, the accuracy of the models is between 53.6% and 71.58%. Conclusion We believe that the performance of the prediction models can be enhanced with the use of more patient data. As future work, we plan to directly contact hospitals in Riyadh in order to collect more information related to patients with MERS-CoV infections.


title: Degenerate PCR primer design for the specific identification of rhinovirus C

text: Abstract Human rhinovirus (HRV)-A and -B is a common cause of upper respiratory tract infections. Recently, a third species, HRV-C, was categorized based on molecular typing studies. The results showed that the HRV-C genome had diverged from that of HRV-A and -B. Despite its late identification, increasing evidence suggests that HRV-C causes more severe pathogenic infections than HRV-A or -B; however, a large amount of epidemiological data is required to confirm this association in different clinical settings. Consequently, a simple and rapid method for identifying HRV-C is required to expedite such epidemiological studies. Here, two degenerate primer sets (HEV and HRVC) were designed based on bioinformatic analyses. The HEV set targeting the fifth IRES domain sequence within the 5′-UTR, which is highly conserved among enteroviruses, was designed to detect all enteroviruses, whereas the HRVC set, which targeted the VP2 coding region, was designed to detect HRV-C alone. Both primer sets were tested against a panel of standard enteroviruses and clinical lavage samples. HEV detected all enteroviruses tested whereas HRVC was specific for HRV-C. Although the primer design strategy was confirmed with a limited number of samples, extensive tests are required to be applied in clinical settings.


docid: qrzmwqye

title: Response to Carletti et al, “About the origin of the first two SARS‐CoV‐2 infections in Italy: Inference not supported by appropriate sequence analysis”

text: The first one, as the authors should know, that in order to estimate phylogenies on a natural timescale a 'molecular clock' analysis has to be applied. A molecular clock is a theory attributed to Emile Zuckerkandl and Linus Pauling (1962), describing the relationship between observed genetic distances and time. This article is protected by copyright. All rights reserved.


title: Lifestyle as Risk Factor for Infectious Causes of Death in Young Dogs: A Retrospective Study in Southern Italy (2015–2017)

text: Infectious diseases are a common cause of death in young dogs. Several factors are thought to predispose young dogs to microbiological infections. Identifying the cause of death is often a challenge, and broad diagnostic analysis is often needed. Here, we aimed to determine the infectious causes of death in young dogs aged up to 1 year, examining how it relates to age (under and over 6 months), lifestyle (owned versus ownerless), breed (purebred and crossbreed), and gender. A retrospective study was conducted in a 3-year period (2015–2017) on 138 dead dogs that had undergone necropsy and microbiological diagnostics. Enteritis and pneumonia were the most commonly observed lesions. Polymicrobism was more prevalent (62.3%) than single-agent infections and associated with a higher rate of generalised lesions. Ownerless dogs showed over a three-fold higher predisposition to viral coinfections than owned dogs. Above all, canine parvovirus was the most prevalent agent (77.5%), followed by canine coronavirus (31.1%) and canine adenovirus (23.9%); ownerless pups had a higher predisposition to these viruses. Escherichia coli (23.9%), Clostridium perfringens type A (18.1%), and Enterococcus spp. (8.7%) were the most commonly identified bacteria, which mostly involved in coinfections. A lower prevalence of CDV and Clostridium perfringens type A was observed in puppies under 6 months of age. In conclusion, this study is the first comprehensive survey on a wide panel of microbiological agents related to necropsy lesions. It lays the groundwork for future studies attempting to understand the circulation of infectious agents in a determined area.


The third coronavirus epidemic in the third millennium: what’s next?


title: Chapter 1 A History of Public Health

text: Abstract Concepts of preventing infection, malnutrition, and sanitation have existed since ancient times. Ideals of “sanctity of human life” and “improve the world” in Mosaic Law, linked with Greek traditions of healthful nutrition and lifestyle, are relevant in modern public health. Roman sanitary engineering and military medicine made pivotal contributions. Hospital organization and university training for physicians developed during Islamic and Christian periods. The rise of cities, the Renaissance, and rapid changes in agriculture, trade, and industry all contributed to public health. New social, political, and economic reforms in the eighteenth and nineteenth centuries, contributing to sanitation, social reform, and improved nutrition and medical care, led to improved longevity and quality of life in the twentieth century. Immunology, social security, health insurance, and health promotion expanded the scope and effectiveness of global health. Biomedical and social sciences, technology, and public health organization are critical as public health faces old and new health challenges.


title: The Use of Decision Modelling to Inform Timely Policy Decisions on Cardiac Resource Capacity during the COVID-19 Pandemic.

text: In Ontario, on March 16(th), 2020, a directive was issued to all acute care hospitals to halt non-essential procedures in anticipation for a potential surge in COVID-19 patients. This included scheduled outpatient cardiac surgical and interventional procedures that required the use of intensive care units, ventilators, and skilled critical care personnel, given that these procedures would draw from the same pool of resources required for critically ill COVID-19 patients. We adapted the COVID-19 Resource Estimator (CORE) decision analytic model by adding a cardiac component to determine the impact of various policy decisions on the incremental waitlist growth and estimated waitlist mortality for three key groups of cardiovascular disease patients; coronary artery disease, valvular heart disease, and arrhythmias. We provided predictions based on COVID-19 epidemiology available in real-time, in 3 phases. First, in the initial crisis phase, in a worst case scenario, we showed that the potential number of waitlist related cardiac deaths would be orders of magnitude less than those who would die of COVID-19 if critical cardiac care resources were diverted to the care of COVID-19 patients. Second, with better local epidemiology data, we predicted that across five regions of Ontario, there may be insufficient resources to resume all elective outpatient cardiac procedures. Finally in the recovery phase, we showed that the estimated incremental growth in waitlist for all cardiac procedures is likely substantial. These outputs informed timely, data-driven decisions during the COVID-19 pandemic regarding the provision of cardiovascular care.


docid: cqcfstst

title: Growth kinetics of SARS-coronavirus in Vero E6 cells

text: Abstract Vero E6 cells are commonly used for in vitro studies of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and for antiviral evaluation purposes. A better understanding of the SARS-CoV growth kinetics in Vero E6 cells is crucial to help elucidate the mechanism of antiviral activity of selective antiviral agents. In this study, the growth kinetics of SARS-CoV in Vero E6 cells were studied by quantitation of intra- and extracellular viral RNA load as well as extracellular virus yield at different time points post-infection. At 12h post-infection, the intracellular viral RNA load was 3×102-fold higher than at the time of infection, and the extracellular viral RNA load was increased with a factor of 2×103. Intracellular viral RNA levels started to rise at 6h post-infection. One hour later (at 7h post-infection), the levels of extracellular SARS-CoV RNA also began to rise. This was corroborated by the fact that infectious progeny SARS-CoV also first appeared in the supernatant between 6 and 7h post-infection. At 12h post-infection, SARS-CoV reached titers in the supernatant of 5.2×103 CCID50/ml.


title: Experiencing the Surge: Report from a Large New York Radiation Oncology Department During the COVID-19 Pandemic

text: Purpose/Objective(s): The COVID-19 pandemic is impacting all aspects of life and changing the practice of medicine. Multiple recommendations exist on how radiation oncology practices should deal with this crisis, but little information is available on what actually happens when the COVID-19 surge arrives. New York City experienced the first surge of COVID-19 in the United States and is now the epicenter of the global pandemic. This study reviews the impact of COVID-19 on a hospital system in New York on aspects of medicine, nursing, radiation therapy, and administration. Materials/Methods: A retrospective review was conducted of the department of radiation oncology in a single health system in New York from 3/1/20 to 4/1/20. Collaboration was obtained from physicians, nursing, radiation therapy, and administration to recall their policies and impact on specific duties. A timeline was reconstructed to chronicle significant events. Numbers were obtained for patients on treatment, treatments breaks, and COVID-19 infections amongst staff and patients. Results The COVID-19 surge had a tremendous impact on the health system including cessation of all of surgeries, including oncologic surgery, as well as transfer of all inpatient oncology services to makeshift outpatient facilities. Radiation Oncology made aggressive efforts to reduce patients on treatment to protect patients and staff as well reallocate staff and space for more acute clinical needs. Patients on-beam were reduced by 27% from 172 to 125 by 4/1/20. Almost all visits were changed to telemedicine within 2 weeks. Infection rates and quarantine were quite low amongst staff and patients. The majority of residents were deployed into COVID-19 clinical settings. Conclusion While “planning for the worst”, our health system was able to make necessary changes to still function at a reduced capacity. Our experience will give other departments a concrete experience to help them make their own policies and manage expectations.


title: Rationale and significance of patient selection in awake prone positioning for COVID-19 pneumonia

text: We read with interest a research letter by Ng et al., which described their experience in prone positioning (PP) for awake patients with COVID-19 pneumonia, and concluded that this maneuver could delay or reduce the need for intensive care [1]. We agree that the authors demonstrated safety and feasibility of PP in COVID-19 pneumonia patients. However, we humbly suggest a few crucial points be addressed before drawing conclusions on the efficacy of PP.


COVID reverse transcriptase PCR in private laboratories: from theory to reality


title: Quantification of SARS-CoV-2 antibodies with eight commercially available immunoassays

text: Since the emergence of SARS-CoV-2 numerous antibody assays have become available, demonstrating different performance characteristics. This study focused on a quantitative correlation between different commercial assays and a neutralization test (NT). Comparative data is needed as a basis for the production of convalescent plasma and potential interpretations COVID-19 immunity. Sera of 100 SARS-CoV-2 convalescent plasma donors were collected and SARS-CoV-2 antibodies were characterized using three different IgG-ELISAs EUROIMMUN IgG and NCP-IgG ELISA, Wantai ELISA), two CLIA (Elecsys, LIAISON) and two lateral flow tests (MEDsan IgM/IgG-Rapid-Test, Wantai Rapid Test) and subsequently correlated to neutralization titers. The Wantai ELISA and the Elecsys provide the highest sensitivities in this sample (98 and 95 percent respectively). Titers with the best overall quantitative correlation to the NT titer were obtained with the Euroimmun IgG ELISA assay (Rho=0.759) and the Wantai ELISA assay (Rho=0.729). An infection without fever and negative or weakly positive reactions in the Wantai Rapid test were negative predictive factors for NT titers >1:200 (negative predictive value of 92% and 92% respectively, combination of both 100%). The Wantai ELISA titer could be a suitable substitute for NT. An adequate pooling strategy of plasma units additionally could compensate deviations of individual antibody titers.


title: Visual detection of turkey coronavirus RNA in tissues and feces by reverse-transcription loop-mediated isothermal amplification (RT-LAMP) with hydroxynaphthol blue dye

text: Abstract A sensitive reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for the rapid visual detection of turkey coronavirus (TCoV) infection. The reaction is performed in one step in a single tube at 65 °C for 45 min, with hydroxynaphthol blue (HNB) dye added prior to amplification. The detection limit of the RT-LAMP assay was approximately 102 EID50/50 μl TCoV genome, and no cross-reaction with other avian viruses was observed. The assay was evaluated further in tissue suspensions prepared from the ileum and ileum–caecal junctions of infected turkey embryos; 100% of these samples were positive in the RT-LAMP assay. All individual feces samples collected in the field were considered positive by both conventional RT-PCR and RT-LAMP. In conclusion, RT-LAMP with HNB dye was shown to be a sensitive, simple assay for the rapid diagnosis of TCoV infection, either directly from feces or in association with virus isolation methods.


docid: iwkbmday

title: Regional technology gap and innovation efficiency trap in Chinese pharmaceutical manufacturing industry

text: OBJECTIVE: There is a huge technology gap between regions in Chinese pharmaceutical manufacturing industry, which is the reality that must be faced. However, most of the available researches on innovation efficiency are based on the logic of a given technology level, ignoring the regional technological gap. This paper will stand from the perspective of technology gap and re-examine the innovation efficiency of pharmaceutical manufacturing industry in different regions of China and its impact on regional industrial competitiveness. METHODS: We use the DEA-BCC input-oriented model to measure innovation efficiency of 28 provinces from the data of China's pharmaceutical manufacturing industry. The threshold model is constructed, with technology level as the threshold variable, innovation efficiency as the main explanatory variable, and industrial competitiveness as the dependent variable. In the threshold model, 28 regions are divided into three technical groups, and further, the impact of innovation efficiency on industrial competitiveness in different groups is analyzed and compared. RESULTS: According to the empirical research results, an U-shaped efficiency trap has been found in Chinese pharmaceutical manufacturing industry, and the areas with medium technical level are at the bottom of the trap. The improvement of innovation efficiency does not necessarily promote the improvement of regional industrial competitiveness. Only in high-level and low-level technology groups, innovation efficiency has effectively promoted the improvement of industrial competitiveness. In addition, the intensity of R&D investment has a similar impact on industrial competitiveness. CONCLUSIONS: The findings suggest that, regions in the efficiency trap should strive to seek opportunities for industrial transformation and focus on the industrial transformation of new technology, new industry and new opportunities, instead of blindly pursuing R&D investment intensity and superstitious innovation efficiency. So as to free up innovation resources for high-quality technological innovation in other regions. In addition, the Chinese government should make use of its public hospital system to normalize and expand the centralized drug procurement and eliminate the low-quality innovation.


title: Use of Anakinra to Prevent Mechanical Ventilation in Severe COVID‐19: A Case Series

text: OBJECTIVE: To report the clinical experience with anakinra for preventing mechanical ventilation (MV) in patients with COVID‐19, features of cytokine storm syndrome (CSS), and acute hypoxic respiratory failure (AHRF). METHODS: In this retrospective case series, patients must have had SARS‐CoV‐2, fever, ferritin >1,000 ng/mL with one additional laboratory marker of hyperinflammation, and AHRF. AHRF was defined as requiring 15L of supplemental oxygen via non‐rebreather mask combined with 6L nasal cannula or use of ≥95% oxygen by high flow nasal cannula. We excluded patients with suspicion for bacterial infection or on immunosuppressants. Subcutaneous anakinra was initiated at 100 mg q6 hours and gradually tapered off completely. Primary outcome was prevention of MV. RESULTS: Eleven of 14 patients meeting criteria received anakinra for a maximum of 19 days. Seven of those who initiated anakinra ≤36 hours after onset of AHRF did not require MV, and all were discharged home. Four patients who started anakinra ≥4 days after onset of AHRF required MV. Of those, 3 patients were extubated (2 discharged home, 1 remains hospitalized) and 1 died. All 3 patients who met criteria but did not receive anakinra required MV. Two were extubated (1 discharged and 1 remains hospitalized) and 1 remains on MV. CONCLUSIONS: Our data suggest that anakinra could be beneficial in COVID‐19 patients with evidence of CSS when initiated early after onset of AHRF. Our patient selection and treatment approach should be considered for investigation in a clinical trial to determine the safety and efficacy of anakinra in patients with COVID‐19 and features of CSS.


COVID-19: A Perspective of a Frontline Worker


title: Role of phosphorylation clusters in the biology of the coronavirus infectious bronchitis virus nucleocapsid protein

text: Abstract The coronavirus infectious bronchitis virus (IBV) nucleocapsid (N) protein is an RNA binding protein which is phosphorylated at two conserved clusters. Kinetic analysis of RNA binding indicated that the C-terminal phosphorylation cluster was involved in the recognition of viral RNA from non-viral RNA. The IBV N protein has been found to be essential for the successful recovery of IBV using reverse genetics systems. Rescue experiments indicated that phosphorylated N protein recovered infectious IBV more efficiently when compared to modified N proteins either partially or non-phosphorylated. Our data indicate that the phosphorylated form of the IBV N protein plays a role in virus biology.


title: Phytotherapic compounds against coronaviruses: Possible streams for future research

text: Recently, an epidemic disease outbreak caused by a novel human coronavirus has surged worldwide. Our aim is to briefly describe the potential help of phytotherapy research in finding new integrative therapeutic options against human coronaviruses, and to provide researchers with some essential hints to be used for planning future studies. Existing evidence mostly derives from laboratory studies, whereas clinical data have been only collected for multi-component formulations used in Traditional Chinese Medicine in addition to standard care. Herbs with anti-viral properties like Glycyrrhiza glabra, Scutellaria baicalensis, Sambucus nigra, Pelargonium sidoides, or Cistus incanus, as well as herbal remedies with immune boosting effects like Astragalus membranaceus or Echinacea purpurea may all appear interesting options to study. This article is protected by copyright. All rights reserved.


COVID‐19: 2020 a year in turmoil


Retraction—Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis


docid: oryreahw

title: Penile rehabilitation and cancer spread


title: Manage COVID‐19 stress, anxiety by reframing your outlook

text: Mike Taigman, Improvement Guide at FirstWatch, helps law enforcement and other agencies improve situational awareness, clinical performance, and patient outcomes by providing strategies to change mindsets and reframe challenging circumstances to help decrease anxiety or stress. He shared his expertise for stress and anxiety management in the face of COVID‐19 for law enforcement officials and other first responders in a webinar hosted by Lexipol.


title: Stereoselective pharmacokinetic study of epiprogoitrin and progoitrin in rats with UHPLC–MS/MS method

text: Abstract An accurate and precise liquid chromatography–electrospray ionization–tandem mass spectrometry (LC–ESI–MS/MS) method was developed and validated for the pharmacokinetic study of epiprogoitrin and progoitrin, a pair of epimers that can be deglycosylated to epigoitrin and goitrin, respectively. These analytes were administered intravenously or intragastrically to male Sprague–Dawley rats, and the influence of 3(R/S)-configuration on the pharmacokinetics of both epimers in rat plasma was elucidated. The analytes and an internal standard (i.e., sinigrin) were resolved by LC–MS/MS on a reverse-phase ACQUITY UPLCTM HSS T3 column equilibrated and eluted with acetonitrile and water (0.1% formic acid) at a ﬂow rate of 0.3 mL/min. Quantitation was achieved by applying the multiple reaction monitoring mode, in the negative ion mode, at transitions of m/z 388 → 97 and m/z 358 → 97 for the epimers and sinigrin, respectively. The method demonstrated good linearity over the concentration range of 2–5000 ng/mL (r > 0.996). The lower limit of quantification for epiprogoitrin and progoitrin was 2 ng/mL. The interday and intraday accuracy and precision were within ±15%. The extraction recovery, stability, and matrix effect were demonstrated to be within acceptable limits. The validated method was thus successfully applied for the pharmacokinetic study of both the epimers. After the rats received the same oral dose of the epimers, the pharmacokinetic profiles were similar. The maximum plasma concentration (Cmax) and AUC values of epiprogoitrin were a bit higher than those of progoitrin, whereas the pharmacokinetic behaviours of the epimers were obviously different upon intravenous administration. The Cmax and AUC values of epiprogoitrin were approximately three-fold higher than those of progoitrin, and the half-life of progoitrin was much shorter than that of epiprogoitrin. The oral bioavailability of progoitrin was 20.1%–34.1%, which is three times higher than that of epiprogoitrin.


docid: mweeepam

title: Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor

text: The 2002–3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history(1). An ongoing outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV)(2) suggests that this group of viruses remains a major threat and that their distribution is wider than previously recognized. Although bats have been suggested as the natural reservoirs of both viruses(3–5), attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa(5–8), but none are considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins (S) to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2)(9,10). Here, we report whole genome sequences of two novel bat CoVs from Chinese horseshoe bats (Family: Rhinolophidae) in Yunnan, China; RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat CoVs, particularly in the receptor binding domain (RDB) of the S protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat fecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses the ACE2s from human, civet and Chinese horseshoe bat for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.


title: Isolation and Morphology of the Internal Component of Human Coronavirus, Strain 229E

text: Biochemical studies on human coronavirus, strain 229E, indicate that the RNA is present in the virion in association with protein as a ribonucleoprotein (RNP) complex. Morphological studies have revealed that this nucleocapsid is probably a continuous helical RNP.


title: Phi29 polymerase based random amplification of viral RNA as an alternative to random RT-PCR

text: BACKGROUND: Phi29 polymerase based amplification methods provides amplified DNA with minimal changes in sequence and relative abundance for many biomedical applications. RNA virus detection using microarrays, however, can present a challenge because phi29 DNA polymerase cannot amplify RNA nor small cDNA fragments (<2000 bases) obtained by reverse transcription of certain viral RNA genomes. Therefore, ligation of cDNA fragments is necessary prior phi29 polymerase based amplification. We adapted the QuantiTect Whole Transcriptome Kit (Qiagen) to our purposes and designated the method as Whole Transcriptome Amplification (WTA). RESULTS: WTA successfully amplified cDNA from a panel of RNA viruses representing the diversity of ribovirus genome sizes. We amplified a range of genome copy numbers from 15 to 4 × 10(7 )using WTA, which yielded quantities of amplified DNA as high as 1.2 μg/μl or 10(10 )target copies. The amplification factor varied between 10(9 )and 10(6). We also demonstrated that co-amplification occurred when viral RNA was mixed with bacterial DNA. CONCLUSION: This is the first report in the scientific literature showing that a modified WGA (WTA) approach can be successfully applied to viral genomic RNA of all sizes. Amplifying viral RNA by WTA provides considerably better sensitivity and accuracy of detection compared to random RT-PCR.


title: Surgical decision-making and prioritization for cancer patients at the onset of the COVID-19 pandemic: A multidisciplinary approach

text: Abstract In the midst of the coronavirus disease 2019 (COVID-19) pandemic, governmental agencies, state medical boards, and healthcare organizations have called for restricting “elective” operations to mitigate the risk of transmission of the virus amongst patients and healthcare providers and to preserve essential resources for potential regional surges of COVID patients. While the fear of delaying surgical care for many of our patients is deeply challenging for us as cancer care providers, we must balance our personal commitment to providing timely and appropriate oncologic care to our cancer patients with our societal responsibility to protect our patients (including those on whom we are operating), co-workers, trainees, families, and community, from undue risks of contracting and propagating COVID-19. Herein, we present guidelines for surgical decision-making and case prioritization developed among all adult disease specialties in the MD Anderson Cancer Center Departments of Surgical Oncology and Breast Surgical Oncology in Houston, Texas.


title: Evaluation of Serologic and Antigenic Relationships Between Middle Eastern Respiratory Syndrome Coronavirus and Other Coronaviruses to Develop Vaccine Platforms for the Rapid Response to Emerging Coronaviruses

text: Background. Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012, causing severe acute respiratory disease and pneumonia, with 44% mortality among 136 cases to date. Design of vaccines to limit the virus spread or diagnostic tests to track newly emerging strains requires knowledge of antigenic and serologic relationships between MERS-CoV and other CoVs. Methods. Using synthetic genomics and Venezuelan equine encephalitis virus replicons (VRPs) expressing spike and nucleocapsid proteins from MERS-CoV and other human and bat CoVs, we characterize the antigenic responses (using Western blot and enzyme-linked immunosorbent assay) and serologic responses (using neutralization assays) against 2 MERS-CoV isolates in comparison with those of other human and bat CoVs. Results. Serologic and neutralization responses against the spike glycoprotein were primarily strain specific, with a very low level of cross-reactivity within or across subgroups. CoV N proteins within but not across subgroups share cross-reactive epitopes with MERS-CoV isolates. Our findings were validated using a convalescent-phase serum specimen from a patient infected with MERS-CoV (NA 01) and human antiserum against SARS-CoV, human CoV NL63, and human CoV OC43. Conclusions. Vaccine design for emerging CoVs should involve chimeric spike protein containing neutralizing epitopes from multiple virus strains across subgroups to reduce immune pathology, and a diagnostic platform should include a panel of nucleocapsid and spike proteins from phylogenetically distinct CoVs.


Health and social justice


title: Reverse genetic characterization of the natural genomic deletion in SARS-Coronavirus strain Frankfurt-1 open reading frame 7b reveals an attenuating function of the 7b protein in-vitro and in-vivo

text: During the outbreak of SARS in 2002/3, a prototype virus was isolated from a patient in Frankfurt/Germany (strain Frankfurt-1). As opposed to all other SARS-Coronavirus strains, Frankfurt-1 has a 45-nucleotide deletion in the transmembrane domain of its ORF 7b protein. When over-expressed in HEK 293 cells, the full-length protein but not the variant with the deletion caused interferon beta induction and cleavage of procaspase 3. To study the role of ORF 7b in the context of virus replication, we cloned a full genome cDNA copy of Frankfurt-1 in a bacterial artificial chromosome downstream of a T7 RNA polymerase promoter. Transfection of capped RNA transcribed from this construct yielded infectious virus that was indistinguishable from the original virus isolate. The presumed Frankfurt-1 ancestor with an intact ORF 7b was reconstructed. In CaCo-2 and HUH7 cells, but not in Vero cells, the variant carrying the ORF 7b deletion had a replicative advantage against the parental virus (4- and 6-fold increase of virus RNA in supernatant, respectively). This effect was neither associated with changes in the induction or secretion of type I interferon, nor with altered induction of apoptosis in cell culture. However, pretreatment of cells with interferon beta caused the deleted virus to replicate to higher titers than the parental strain (3.4-fold in Vero cells, 7.9-fold in CaCo-2 cells). In Syrian Golden Hamsters inoculated intranasally with 10e4 plaque forming units of either virus, mean titers of infectious virus and viral RNA in the lungs after 24 h were increased 23- and 94.8-fold, respectively, with the deleted virus. This difference could explain earlier observations of enhanced virulence of Frankfurt-1 in Hamsters as compared to other SARS-Coronavirus reference strains and identifies the SARS-CoV 7b protein as an attenuating factor with the SARS-Coronavirus genome. Because attenuation was focused on the early phase of infection in-vivo, ORF 7b might have contributed to the delayed accumulation of virus in patients that was suggested to have limited the spread of the SARS epidemic.


title: Small molecules targeting viral RNA

text: Highly conserved noncoding RNA (ncRNA) elements in viral genomes and transcripts offer new opportunities to expand the repertoire of drug targets for the development of antiinfective therapy. Ligands binding to ncRNA architectures are able to affect interactions, structural stability or conformational changes and thereby block processes essential for viral replication. Proof of concept for targeting functional RNA by small molecule inhibitors has been demonstrated for multiple viruses with RNA genomes. Strategies to identify antiviral compounds as inhibitors of ncRNA are increasingly emphasizing consideration of drug‐like properties of candidate molecules emerging from screening and ligand design. Recent efforts of antiviral lead discovery for RNA targets have provided drug‐like small molecules that inhibit viral replication and include inhibitors of human immunodeficiency virus (HIV), hepatitis C virus (HCV), severe respiratory syndrome coronavirus (SARS CoV), and influenza A virus. While target selectivity remains a challenge for the discovery of useful RNA‐binding compounds, a better understanding is emerging of properties that define RNA targets amenable for inhibition by small molecule ligands. Insight from successful approaches of targeting viral ncRNA in HIV, HCV, SARS CoV, and influenza A will provide a basis for the future exploration of RNA targets for therapeutic intervention in other viral pathogens which create urgent, unmet medical needs. Viruses for which targeting ncRNA components in the genome or transcripts may be promising include insect‐borne flaviviruses (Dengue, Zika, and West Nile) and filoviruses (Ebola and Marburg). WIREs RNA 2016, 7:726–743. doi: 10.1002/wrna.1373 1.. RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems; 2.. RNA Interactions with Proteins and Other Molecules > Small Molecule–RNA Interactions; 3.. Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.


SARS Vaccine Protective in Mice


title: A Correlation between the Severity of Lung Lesions on Radiographs and Clinical Findings in Patients with Severe Acute Respiratory Syndrome

text: OBJECTIVE: The purpose of this study was to quantify lesions on chest radiographs in patients with severe acute respiratory syndrome (SARS) and analyze the severity of the lesions with clinical parameters. MATERIALS AND METHODS: Two experienced radiologists reviewed chest radiographs of 28 patients with SARS. Each lung was divided into upper, middle, and lower zones. A SARS-related lesion in each zone was scored using a four-point scale: zero to three. The mean and maximal radiographic scores were analyzed statistically to determine if the scorings were related to the laboratory data and clinical course. RESULTS: Forward stepwise multiple linear regression showed that the mean radiographic score correlated most significantly with the number of hospitalized days (p < 0.001). The second most significant factor was the absolute lymphocyte count (p < 0.001) and the third most significant factor was the number of days of intubation (p = 0.025). The maximal radiographic score correlated best with the percentage of lymphocytes in a leukocyte count (p < 0.001), while the second most significant factor was the number of hospitalized days (p < 0.001) and the third most significant factor was the absolute lymphocyte count (p = 0.013). The mean radiographic scores of the patients who died, with comorbidities and without a comorbidity were 11.1, 6.3 and 2.9, respectively (p = 0.032). The corresponding value for maximal radiographic scores were 17.7, 9.7 and 6.0, respectively (p = 0.033). CONCLUSION: The severity of abnormalities quantified on chest radiographs in patients with SARS correlates with the clinical parameters.


title: AI governance in the public sector: Three tales from the frontiers of automated decision-making in democratic settings

text: Abstract The rush to understand new socio-economic contexts created by the wide adoption of AI is justified by its far-ranging consequences, spanning almost every walk of life. Yet, the public sector's predicament is a tragic double bind: its obligations to protect citizens from potential algorithmic harms are at odds with the temptation to increase its own efficiency - or in other words - to govern algorithms, while governing by algorithms. Whether such dual role is even possible, has been a matter of debate, the challenge stemming from algorithms' intrinsic properties, that make them distinct from other digital solutions, long embraced by the governments, create externalities that rule-based programming lacks. As the pressures to deploy automated decision making systems in the public sector become prevalent, this paper aims to examine how the use of AI in the public sector in relation to existing data governance regimes and national regulatory practices can be intensifying existing power asymmetries. To this end, investigating the legal and policy instruments associated with the use of AI for strenghtening the immigration process control system in Canada; “optimising” the employment services” in Poland, and personalising the digital service experience in Finland, the paper advocates for the need of a common framework to evaluate the potential impact of the use of AI in the public sector. In this regard, it discusses the specific effects of automated decision support systems on public services and the growing expectations for governments to play a more prevalent role in the digital society and to ensure that the potential of technology is harnessed, while negative effects are controlled and possibly avoided. This is of particular importance in light of the current COVID-19 emergency crisis where AI and the underpinning regulatory framework of data ecosystems, have become crucial policy issues as more and more innovations are based on large scale data collections from digital devices, and the real-time accessibility of information and services, contact and relationships between institutions and citizens could strengthen – or undermine - trust in governance systems and democracy.


title: Vimentin modulates infectious porcine circovirus type 2 in PK-15 cells

text: Abstract Porcine circovirus type 2 (PCV2) is the pathogen that causes postweaning multisystemic wasting syndrome, which leads to significant economic losses for swine farms worldwide. However, the infection mechanism of PCV2 is not completely understood yet. Vimentin is a part of the cytoskeleton network and plays an important role in several virus infections. It is not clear whether vimentin has a role in PCV2 infection nor how it affects PCV2 infection. In this study, the function of vimentin in PK-15 cells infected with PCV2 has been elucidated. We found that vimentin had a restrictive effect on the replication of PCV2 in PK-15 cells. Overexpression of vimentin by transferred pCAGGS-vimentin and down-regulation by the respective scrambled small interfering RNA showed that vimentin restricted the replication and virion production of PCV2. A special interaction between vimentin and PCV2 Cap protein was observed using laser confocal microscopy and immunoprecipitation assay. Moreover, overexpression of vimentin could decrease NF-κB activity and increase PCV2-induced caspase-3 activity in PK-15 cells. These data suggest that vimentin is involved in the replication of PCV2 and has a restrictive effect on it, which is helpful in the study of the replication mechanism of PCV2.


title: Phenotypic and functional characterization of the major lymphocyte populations in the fruit-eating bat Pteropus alecto

text: The unique ability of bats to act as reservoir for viruses that are highly pathogenic to humans suggests unique properties and functional characteristics of their immune system. However, the lack of bat specific reagents, in particular antibodies, has limited our knowledge of bat’s immunity. Using cross-reactive antibodies, we report the phenotypic and functional characterization of T cell subsets, B and NK cells in the fruit-eating bat Pteropus alecto. Our findings indicate the predominance of CD8(+) T cells in the spleen from wild-caught bats that may reflect either the presence of viruses in this organ or predominance of this cell subset at steady state. Instead majority of T cells in circulation, lymph nodes and bone marrow (BM) were CD4(+) subsets. Interestingly, 40% of spleen T cells expressed constitutively IL-17, IL-22 and TGF-β mRNA, which may indicate a strong bias towards the Th17 and regulatory T cell subsets. Furthermore, the unexpected high number of T cells in bats BM could suggest an important role in T cell development. Finally, mitogenic stimulation induced proliferation and production of effector molecules by bats immune cells. This work contributes to a better understanding of bat’s immunity, opening up new perspectives of therapeutic interventions for humans.


Reducing child mortality in China: successes and challenges


title: Current efforts and challenges facing responses to 2019-nCoV in Africa

text: The novel coronavirus is a pandemic that has started to creep into Africa thus making the virus a truly global, health security threat. The number of new 2019-nCoV cases has been rising in Africa, though currently lower than the cases reported outside the region. African countries have activated their Emergency Operations Centres to coordinate responses and preparedness activities to the pandemic. A series of measures such as restricting travel, case detection and contact tracing, mandatory quarantine, guidance and information to the public among other efforts are being implemented across Africa. However, the presence of porous borders, the double burden of communicable and non-communicable diseases, poverty, poor health literacy, infodemic and family clustering, and most of all, weak health systems, may make containment challenging. It is important for African countries to continue to intensify efforts and address the challenges to effectively respond to the uncertainty the pandemic poses.


title: Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses

text: Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine-induced antibodies and therapeutic antibodies will enable a better understanding of their capacity to prevent and/or control HIV-1 infection in vivo.


title: Field-deployable, rapid diagnostic testing of saliva samples for SARS-CoV-2.

text: Abstract Rapid, scalable, point-of-need, COVID-19 diagnostic testing is necessary to safely re-open economies and prevent future outbreaks. We developed an assay that detects single copies of SARS-CoV-2 virus directly from saliva and swab samples in 30 min using a simple, one-step protocol that utilizes only a heat block and microcentrifuge tube prefilled with a mixture containing the necessary reagents and has a sensitivity and specificity of 97% and 100%, respectively.


title: Transmission of SARS to healthcare workers. The experience of a Hong Kong ICU

text: OBJECTIVE: To describe the extent and temporal pattern of transmission of severe acute respiratory syndrome (SARS) to intensive care unit staff. DESIGN: Retrospective observational cohort study. SETTING: University hospital intensive care unit, caring solely for patients with SARS or suspected to have SARS. PARTICIPANTS: Thirty-five doctors and 152 nurses and healthcare assistants who worked in the ICU during the SARS epidemic. Interventions: Infection control measures designed to prevent transmission of disease to staff were implemented. MEASUREMENTS AND RESULTS: Sixty-seven patients with SARS were admitted to the intensive care unit. Four nurses and one healthcare assistant contracted SARS, with three of these developing symptoms within 10 days of admission of the first patient with SARS. Doctors were exposed to patients with SARS for a median (IQR) of 284 (97–376) h, while nurses and healthcare assistants were exposed for a median (IQR) of 119 (57–166) h. The ICU did not meet international standards for physical space or ventilation. CONCLUSIONS: In an ICU in which infection control procedures are rigorously applied, the risk to staff of contracting SARS from patients is low, despite long staff exposure times and a sub-standard physical environment. ELECTRONIC SUPPLEMENTARY MATERIAL: The electronic reference of this article is http://dx.doi.org/10.1007/s00134-006-0081-1 The online full-text version of this article includes electronic supplementary material. This material is available to authorised users and can be accessed by means of the ESM button beneath the abstract or in the structured full-text article. To cite or link to this article you can use the above reference.


title: Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic Mechanisms

text: [Image: see text] The recent outbreak of coronavirus infectious disease 2019 (COVID-19) has gripped the world with apprehension and has evoked a scare of epic proportion regarding its potential to spread and infect humans worldwide. As we are in the midst of an ongoing pandemic of COVID-19, scientists are struggling to understand how it resembles and differs from the severe acute respiratory syndrome coronavirus (SARS-CoV) at the genomic and transcriptomic level. In a short time following the outbreak, it has been shown that, similar to SARS-CoV, COVID-19 virus exploits the angiotensin-converting enzyme 2 (ACE2) receptor to gain entry inside the cells. This finding raises the curiosity of investigating the expression of ACE2 in neurological tissue and determining the possible contribution of neurological tissue damage to the morbidity and mortality caused by COIVD-19. Here, we investigate the density of the expression levels of ACE2 in the CNS, the host–virus interaction and relate it to the pathogenesis and complications seen in the recent cases resulting from the COVID-19 outbreak. Also, we debate the need for a model for staging COVID-19 based on neurological tissue involvement.


title: The One Health Concept: 10 Years Old and a Long Road Ahead

text: Over the past decade, a significant increase in the circulation of infectious agents was observed. With the spread and emergence of epizootics, zoonoses, and epidemics, the risks of pandemics became more and more critical. Human and animal health has also been threatened by antimicrobial resistance, environmental pollution, and the development of multifactorial and chronic diseases. This highlighted the increasing globalization of health risks and the importance of the human–animal–ecosystem interface in the evolution and emergence of pathogens. A better knowledge of causes and consequences of certain human activities, lifestyles, and behaviors in ecosystems is crucial for a rigorous interpretation of disease dynamics and to drive public policies. As a global good, health security must be understood on a global scale and from a global and crosscutting perspective, integrating human health, animal health, plant health, ecosystems health, and biodiversity. In this study, we discuss how crucial it is to consider ecological, evolutionary, and environmental sciences in understanding the emergence and re-emergence of infectious diseases and in facing the challenges of antimicrobial resistance. We also discuss the application of the “One Health” concept to non-communicable chronic diseases linked to exposure to multiple stresses, including toxic stress, and new lifestyles. Finally, we draw up a list of barriers that need removing and the ambitions that we must nurture for the effective application of the “One Health” concept. We conclude that the success of this One Health concept now requires breaking down the interdisciplinary barriers that still separate human and veterinary medicine from ecological, evolutionary, and environmental sciences. The development of integrative approaches should be promoted by linking the study of factors underlying stress responses to their consequences on ecosystem functioning and evolution. This knowledge is required for the development of novel control strategies inspired by environmental mechanisms leading to desired equilibrium and dynamics in healthy ecosystems and must provide in the near future a framework for more integrated operational initiatives.


title: Changing epidemiological patterns of HIV and AIDS in China in the post-SARS era identified by the nationwide surveillance system

text: BACKGROUND: China has made substantial progress in tackling its HIV and AIDS epidemic. But the changing patterns of HIV and AIDS incidence based on the longitudinal observation data were rarely studied. METHODS: The reporting incidence (RI) and mortality data on HIV and AIDS in China covering 31 provinces from 2004 to 2014 were collected from the Chinese Public Health Science Data Center. To decompose the time-series data, Empirical Mode Decomposition (EMD) was applied to properly describe the trends of HIV and AIDS incidence. A mathematical model was used to estimate the relative change of incidence among provinces and age groups. RESULTS: A total of 483,010 newly HIV infections and 214,205 AIDS cases were reported between 2004 and 2014 nationwide. HIV infection increased from 13,258 in 2004 (RI 1.02 per 100,000 person years) to 74,048 in 2014 (RI 5.46 per 100,000). The number of AIDS cases increased from 3054 in 2004 (RI 0.23 per 100,000) to 45,145 in 2014 (RI 3.33 per 100,000). The overall relative changes for HIV infection and AIDS incidence were 1.11 (95% confidence interval [CI] 1.10–1.13) and 1.28 (95% CI 1.23–1.33), respectively. The relative increase for HIV and AIDS RI was higher in northwest provinces while lower in Henan, Xinjiang, Guangxi and Yunnan. The overall relative changes for HIV infection were 1.12 (95% CI 1.11–1.14) in males and 1.10 (95% CI 1.06–1.13) in females. For AIDS RI, the relative increases were 1.31 (95% CI 1.26–1.36) in males and 1.22 (95% CI 1.17–1.28) in females. The lowest relative increase was detected among young adults, while the largest relative increase (odds ratio [OR] > 1.30) was detected in people aged 55 years or above. CONCLUSIONS: HIV and AIDS showed an increasing trend in China from 2004 to 2014, respectively, but the epidemic tended to be under control among provinces and young people that used to have a high HIV and AIDS incidence. Northwest China and older people could be new “hop-spots” for HIV and AIDS risk.


title: Viral Shedding Prolongation in a Kidney Transplant Patient with COVID‐19 Pneumonia

text: Coronavirus disease 2019 (COVID‐19) pandemic sweeps the globe. The information regarding the kinetic changes of SARS‐CoV‐2 in immunosuppressed patients is unclear. Herein, we present a case of prolonged viral shedding in a transplant patient with COVID‐19 pneumonia. A 49‐year‐old male kidney recipient was admitted to the hospital on February 7, 2020, for fever and fatigue. He was a permanent resident in Wuhan, China, and began having symptoms on January 29 (day 1 of illness). His maintenance immunosuppressive regime was consisted of tacrolimus (TAC, 1mg twice a day, orally), mycophenolate mofetil (MMF, 0.5g twice a day, orally) and prednisone (Pred, 5mg daily, orally) triple combination.


title: A reach-out system for video microscopy analysis of ciliary motions aiding PCD diagnosis

text: BACKGROUNDS: High-speed Video-Microscopy Analysis (HVMA) is now being used to aid diagnosis of Primary Ciliary Dyskinesia (PCD). Only a few centers however, are equipped with the available resources and equipment to perform these tests. We describe our experience in HVMA reaching-out to many more peripheral and relatively remote areas. A portable computer with HVMA software, video camera and a microscope were used. Fourteen disperse pediatric centers were reached and a total of 203 subjects were tested within a relatively short time (Clinical Trial Registration: NCT 01070914 (registered February 6, 2010). RESULTS: With an average time of 20 minutes per patient, the system enabled us to test approximately 10–15 subjects per day. A valid HVMA result was made in 148 subjects and helped in the diagnosis of PCD in many of the patients who were subsequently confirmed to have PCD by electron microscopy and/or immunofluoresence and/or genetics and/or nasal Nitric Oxide testing. The sensitivity of abnormal HVMA to accurately predict PCD was 90.2%. DISCUSSION AND CONCLUSION: This is the first report of an out-reach system to record HVMA for improved diagnosis of PCD in remote regions that are not within reach of PCD centers and experts. It provides immediate preliminary results and instantaneous feedback to the physician, patient and his/her family members in these areas. Future studies to compare this system to conventional desk top systems are warranted. TRIAL REGISTRATION: NCT 01070914 (registered February 6, 2010).


title: Epidemiologic and Clinical Characteristics of 91 Hospitalized Patients with COVID-19 in Zhejiang, China: A retrospective, multi-centre case series

text: BACKGROUND: Recent studies have focused initial clinical and Epidemiologic characteristics on the COVID-19, mainly revealing situation in Wuhan, Hubei. AIM: To reveal more data on the epidemiologic and clinical characteristics of COVID-19 patients outside of Wuhan, in Zhejiang, China. DESIGN: Retrospective case series. METHODS: 88 cases of laboratory-confirmed and 3 cases of clinical-confirmed COVID-19 were admitted to five hospitals in Zhejiang province, China. Data were collected from 20 January 2020 to 11 February 2020. RESULTS: Of all 91 patients, 88 (96.70%) were laboratory-confirmed COVID-19 with throat swab samples that tested positive for SARS-Cov-2 while 3 (3.30%) were clinical-diagnosed COVID-19 cases. The median age of the patients was 50 (36.5-57) years, and female accounted for 59.34%. In this sample 40 (43.96%) patients had contracted the diseases from local cases, 31 (34.07%) patients had been to Wuhan/Hubei, 8 (8.79%) cases had contacted with people from Wuhan, 11 (12.09%) cases were confirmed aircraft transmission. In particular within the city of Ningbo, 60.52% cases can be traced back to an event held in a temple. The most common symptoms were fever (71.43%), cough (60.44%) and fatigue (43.96%). The median of incubation period was 6 (IQR, 3-8) days and the median time from first visit to a doctor to confirmed diagnosis was 1 (1-2) days. According to the Chest computed tomography scans, 67.03% cases had bilateral pneumonia. CONCLUSIONS: Social activity cluster, family cluster and travel by airplane were how COVID-19 patients get transmitted and could be rapidly diagnosed COVID-19 in Zhejiang.


title: Direct molecular detection of a broad range of bacterial and viral organisms and Streptococcus pneumoniae vaccine serotypes in children with otitis media with effusion

text: BACKGROUND: Otitis media with effusion (OME) causes significant morbidity in children, but the causes of OME and methods for prevention are unclear. To look for potential infectious etiologies, we performed a pilot study using multiple-target real-time polymerase chain reaction (qPCR) for 27 infectious agents, including nine bacterial organisms and 18 respiratory viruses in middle ear fluids (MEFs) from children with OME. QPCR was also performed for the 13 Streptococcus pneumoniae serotypes contained in the current vaccine. RESULTS: Forty-eight MEF samples were obtained and qPCR detected bacterial nucleic acid (NA) in 39/48 (81 %) and viral NA in 7/48 (15 %). Alloiococcus otitidis and S. pneumoniae were both detected in 15/48 (31 %) MEFs, followed by M. catarrhalis in 14/48 (29 %), H. influenzae in 5/48 (10 %) and M. pneumoniae in 4/48 (8 %). Rhinoviruses were most common virus type detected, found in 4/48 (8 %) MEFs. Serotypes included in the current 13-serotype vaccine were detected in only 3/15 (20 %) S. pneumoniae qPCR-positive MEFs. CONCLUSIONS: Bacteria may play an important role in OME, since over 80 % of MEFs contained bacterial NA. Further research into the role of A. otitidis in OME will be helpful. Serotypes of S. pneumoniae not included in the current 13-serotype vaccine may be involved in OME. Larger studies of OME S. pneumoniae serotypes are needed to help determine which additional serotypes should be included in future vaccine formulations in order to try to prevent OME.


title: Mitigating Psychological Impact: The Experience of Korean Disaster Management

text: The psychological impact of disasters has not been adequately addressed in Korea. This research aims to evaluate how Korea should improve its management of the psychological impact of disasters toward the ultimate goal of effective disaster management. Qualitative content analysis is the main method applied. Nonprofessional management is compared with professional management by considering governments, psychology specialists, disaster victims, and local communities. The main finding is that Korea must change its current management style from nonprofessional to professional. Neighboring nations need to implement supplementary measures toward adopting a systematic approach that considers all phases of the disaster management cycle, emergency planning, and a long-term approach. The value of this study lies in its comprehensive examination of the issue of psychological impact from the perspective of disaster management in Korea.


title: Protecting an island nation from extreme pandemic threats: Proof-of-concept around border closure as an intervention

text: BACKGROUND: Countries are well advised to prepare for future pandemic risks (e.g., pandemic influenza, novel emerging agents or synthetic bioweapons). These preparations do not typically include planning for complete border closure. Even though border closure may not be instituted in time, and can fail, there might still plausible chances of success for well organized island nations. OBJECTIVE: To estimate costs and benefits of complete border closure in response to new pandemic threats, at an initial proof-of-concept level. New Zealand was used as a case-study for an island country. METHODS: An Excel spreadsheet model was developed to estimate costs and benefits. Case-study specific epidemiological data was sourced from past influenza pandemics. Country-specific healthcare cost data, valuation of life, and lost tourism revenue were imputed (with lost trade also in scenario analyses). RESULTS: For a new pandemic equivalent to the 1918 influenza pandemic (albeit with half the mortality rate, “Scenario A”), it was estimated that successful border closure for 26 weeks provided a net societal benefit (e.g., of NZ$11.0 billion, USD$7.3 billion). Even in the face of a complete end to trade, a net benefit was estimated for scenarios where the mortality rate was high (e.g., at 10 times the mortality impact of “Scenario A”, or 2.75% of the country’s population dying) giving a net benefit of NZ$54 billion (USD$36 billion). But for some other pandemic scenarios where trade ceased, border closure resulted in a net negative societal value (e.g., for “Scenario A” times three for 26 weeks of border closure–but not for only 12 weeks of closure when it would still be beneficial). CONCLUSIONS: This “proof-of-concept” work indicates that more detailed cost-benefit analysis of border closure in very severe pandemic situations for some island nations is probably warranted, as this course of action might sometimes be worthwhile from a societal perspective.


title: Tackling the overdose crisis: The role of safe supply

text: North America is experiencing an unprecedented overdose crisis driven by the proliferation of fentanyl and its analogues in the illicit drug supply. In 2018 there were 67,367 drug overdose deaths in the United States, and since 2016, there have been more than 14,700 overdose deaths in Canada, with most related to fentanyl. Despite concerted efforts and some positive progress, current public health, substance use treatment, and harm reduction interventions (such as widespread naloxone distribution and implementation of supervised consumption sites) have not been able to rapidly decrease overdose fatalities. In view of the persistent gaps in services and the limitations of available options, immediate scale-up of low-barrier opioid distribution programs are urgently needed. This includes “off-label” prescription of pharmaceutical grade opioids (e.g., hydromorphone) to disrupt the toxic drug supply and make safer opioids widely available to people at high risk of fatal overdose.


docid: eyejnexx

title: Assembly and immunogenicity of coronavirus-like particles carrying infectious bronchitis virus M and S proteins

text: Infectious bronchitis virus (IBV) as an avian coronavirus is still posing a persistent and imminent threat to the poultry industry worldwide. Here we report that transfection of Sf9 cells with a single recombinant baculovirus encoding M and S proteins resulted in the assembly of IBV VLPs; this is the first report that S protein plus M protein alone were able to be assembled into VLPs for coronaviruses. We further showed that the generated IBV VLPs could induce humoral immune responses in a level comparable to that of inactivated IBV vaccine, and more importantly the IBV VLPs could elicit significantly higher cellular immune responses than the inactivated IBV vaccine. In summary, the assembly of IBV VLPs with M and S proteins provided a simple strategy for generating VLPs for coronaviruses, and the generated IBV VLPs laid a feasible foundation for the development of an effective vaccine against infection of IBV in the future.


title: The impact of virus infections on pneumonia mortality is complex in adults: a prospective multicentre observational study

text: BACKGROUND: Various viruses are known to be associated with pneumonia. However, the impact of viral infections on adult pneumonia mortality remains unclear. This study aimed to clarify the effect of virus infection on pneumonia mortality among adults stratified by virus type and patient comorbidities. METHODS: This multicentre prospective study enrolled pneumonia patients aged ≥15 years from September 2011 to August 2014. Sputum samples were tested by in-house multiplex polymerase chain reaction assays to identify 13 respiratory viruses. Viral infection status and its effect on in-hospital mortality were examined by age group and comorbidity status. RESULTS: A total of 2617 patients were enrolled in the study and 77.8% was aged ≥65 years. 574 (21.9%) did not have comorbidities, 790 (30.2%) had chronic respiratory disease, and 1253 (47.9%) had other comorbidities. Viruses were detected in 605 (23.1%) patients. Human rhinovirus (9.8%) was the most frequently identified virus, followed by influenza A (3.9%) and respiratory syncytial virus (3.9%). Respiratory syncytial virus was more frequently identified in patients with chronic respiratory disease (4.7%) than those with other comorbidities (4.2%) and without comorbidities (2.1%) (p = 0.037). The frequencies of other viruses were almost identical between the three groups. Virus detection overall was not associated with increased mortality (adjusted risk ratio (ARR) 0.76, 95% CI 0.53–1.09). However, influenza virus A and B were associated with three-fold higher mortality in patients with chronic respiratory disease but not with other comorbidities (ARR 3.38, 95% CI 1.54–7.42). Intriguingly, paramyxoviruses were associated with dramatically lower mortality in patients with other comorbidities (ARR 0.10, 95% CI 0.01–0.70) but not with chronic respiratory disease. These effects were not affected by age group. CONCLUSIONS: The impact of virus infections on pneumonia mortality varies by virus type and comorbidity status in adults. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-017-2858-y) contains supplementary material, which is available to authorized users.


title: Chapter 1 Protein-Rich By-Products: Production Statistics, Legislative Restrictions, and Management Options

text: Abstract Congruent to a rapidly growing population is the generation of horticultural and agricultural by-products and waste. The modern-day food cycle includes agricultural production, postharvest handling and storage, food processing and packaging, and distribution and retail, ending with consumption and waste disposal. Of these, agricultural production and postharvest handling and storage result in unintended losses and by-products whereas the other steps generally result in food waste. Approximately one-third of the worldwide food production is wasted each year. Although it is most desirable to prevent waste and by-product formation, followed by reuse or recycling, the formation of by-products and waste is inevitable, and management options must be innovative and also meet legislative requirements. However, management options are mostly a compromise between what is viewed acceptable based on legal requirements and local perceptions, and what is deemed technologically and financially feasible.


title: The prevalence of childhood adversity among healthcare workers and its relationship to adult life events, distress and impairment

text: Abstract Objective We investigated the prevalence of childhood adversity among healthcare workers and if such experiences affect responses to adult life stress. Methods A secondary analysis was conducted of a 2003 study of 176 hospital-based healthcare workers, which surveyed lifetime traumatic events, recent life events, psychological distress, coping, social support, and days off work due to stress or illness. Results Sixty eight percent (95% CI 61.1–74.9) of healthcare workers had one or more experience of violence, abuse or neglect, 33% (95% CI 26.1–40.0) before the age of 13. Compared to healthcare workers who did not experience childhood adversity, those who did reported more recent life events (median 11 vs. 5 over the previous 6 months, p <.001) and greater psychological distress (median score 17 vs. 13, p <.001). The relationship between life events and psychological distress was not linear. Most healthcare workers without childhood adversity (73%) reported a low number of life events which were not associated with psychological distress. Most healthcare workers with childhood adversity (81%) reported a higher number of life events, for which the correlation between events and distress was moderately strong (Spearman's rho=.50, p <.001). Childhood adversity was also associated with more missed work days. Each of these outcomes was higher in 22 healthcare workers (13%) who had experienced more than one type of childhood adversity. Conclusions Childhood adversity is common among healthcare workers and is associated with a greater number of life events, more psychological distress and impairment.


title: High detection rate of dog circovirus in diarrheal dogs

text: BACKGROUND: Diarrhea is one of the most common clinical symptoms reported in companion animal clinics. Dog circovirus (DogCV) is a new mammalian circovirus that is considered to be a cause of alimentary syndromes such as diarrhea, vomiting and hemorrhagic enteritis. DogCV has previously only been identified in the United States, Italy, Germany (GeneBank accession number: KF887949) and China (GeneBank accession number: KT946839). Therefore, the aims of this study were to determine the prevalence of DogCV in Taiwan and to explore the correlation between diarrhea and DogCV infection. Clinical specimens were collected between 2012 and 2014 from 207 dogs suffering from diarrhea and 160 healthy dogs. RESULTS: In this study, we developed a sensitive and specific SYBR Green-based real-time PCR assays to detected DogCV in naturally infected animals. Of the analyzed fecal samples from diarrheal dogs and health dogs, 58 (28.0 %) and 19 (11.9 %), respectively, were DogCV positive. The difference in DogCV prevalence was highly significant (P = 0.0002755) in diarrheal dogs. CONCLUSIONS: This is the first study to reveal that DogCV is currently circulating in domestic dogs in Taiwan and to demonstrate its high detection rate in dogs with diarrhea. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-016-0722-8) contains supplementary material, which is available to authorized users.


docid: nyevhwqz

title: Telemedicine in Neurosurgery: Lessons Learned and Transformation of Care during the COVID-19 Pandemic

text: ABSTRACT Background Prior to the COVID-19 pandemic, telemedicine utilization was mostly used for postoperative visits only in neurosurgery. The shelter-in-place measures led the rapid expansion of telemedicine to address the needs of the neurosurgical patient population. Our goal is to determine the extent of adoption of telemedicine across tumor, vascular, spine and function neurosurgery and utilization for new patient visits. Methods Single-center retrospective cohort study of patients who received neurosurgical care at a tertiary academic center from February to April 2020 was conducted. Patients evaluated from March to April 2019 were included for comparison. A total of 10,746 patients were included: 1247 patients underwent surgery, 8,742 were seen in clinic via an in-person outpatient visit and 757 were assessed via telemedicine during the study period. Results A 40-fold increase in the use of telemedicine was noted after the shelter-in-place measures were initiated with a significant increase in the mean number of patients evaluated via telemedicine per week across all divisions of neurosurgery (4.5±0.9 to 180.4±13.9, p<0.001). The majority of telemedicine appointments were established patient visits (61.2%), but the proportion of new patient visits also significantly increased to an average of 8.2±5.3 per week across all divisions. Conclusion Use of telemedicine drastically increased across all four divisions within neurosurgery with a significant increase in online-first encounters in order to meet the needs of our patients once the shelter-in-place measures were implemented. We provide a detailed account of the lessons learned and discuss the anticipated role of telemedicine in surgical practices once the shelter-in-place measures are lifted.


title: Reprint of: Core protein-mediated 5′–3′ annealing of the West Nile virus genomic RNA in vitro

text: Abstract Genome cyclization through conserved RNA sequences located in the 5′ and 3′ terminal regions of flavivirus genomic RNA is essential for virus replication. Although the role of various cis-acting RNA elements in panhandle formation is well characterized, almost nothing is known about the potential contribution of protein cofactors to viral RNA cyclization. Proteins with nucleic acid chaperone activities are encoded by many viruses (e.g., retroviruses, coronaviruses) to facilitate RNA structural rearrangements and RNA–RNA interactions during the viral replicative cycle. Since the core protein of flaviviruses is also endowed with potent RNA chaperone activities, we decided to examine the effect of West Nile virus (WNV) core on 5′–3′ genomic RNA annealing in vitro. Core protein binding resulted in a dramatic, dose-dependent increase in 5′–3′ complex formation. Mutations introduced in either the UAR (upstream AUG region) or CS (conserved sequence) elements of the viral RNA diminished core protein-dependent annealing, while compensatory mutations restored the 5′–3′ RNA interaction. The activity responsible for stimulating RNA annealing was mapped to the C-terminal RNA-binding region of WNV core protein. These results indicate that core protein – besides its function in viral particle formation – might be involved in the regulation of flavivirus genomic RNA cyclization, and thus virus replication.


title: Chapter Twenty-Eight Nature killer cells in the central nervous system

text: Publisher Summary Natural killer (NK) cells, a prominent component of the innate immune system, are large granular lymphocytes that respond rapidly to a variety of insults via cytokine secretion and cytolytic activity. Recently, there has been growing insight into the biological functions of NK cells, in particular into their roles in infection, tumorurveillance and autoimmunity. Under these pathophysiological circumstances, NK cells readily home to the central nervous system (CNS) tissues to combat infection and presumably to curb progression of tumor. Bystander neuronal and/or glial cell damage can occur in this setting. Paradoxically, NK cells appear to have an inhibitory role for autoimmune responses within the CNS. As in the periphery, NK cells act in concert with T cells and other lymphocytes responsible for CNS pathology and immune regulation. Insights into the molecular signals and pathways governing the diverse biological effects of NK cells are keys for designing NK cell-based therapy for CNS infections, tumor and autoimmune diseases.NK cells readily accumulate in homing to CNS tissues under the pathophysiological situations. This process is tightly controlled by a number of chemokines and chemokine receptors. There is ample of evidence that NK cells within the CNS contribute to the control of infections and might limit progression of certain tumor. Bystander neuronal and/or glial cell damage can occur. In certain autoimmune conditions of the CNS, NK cells appear to have an inhibitory role. Disassociation of disease-inhibiting versus disease-promoting effects of NK cells is a key to harnessing NK cells for therapeutic purposes. To achieve this goal, a generation of genetic models with selective NK cell deficiency, and development of reagents (antibodies) for visualizing subsets of NK cells in situ will be necessary.


docid: nxhdxejh

title: Cytokine response in pediatric patients with pandemic influenza H1N1 2009 virus infection and pneumonia: Comparison with pediatric pneumonia without H1N1 2009 infection

text: OBJECTIVES: We investigated serum cytokine levels in pediatric patients with pandemic influenza H1N1 2009 virus (H1N1) infection‐pneumonia and in pediatric patients with pneumonia but without H1N1 infection, and examined correlations between cytokine levels and clinical/laboratory findings. METHODS: Fifty‐seven cases of infection by H1N1 were confirmed by RT‐PCR and enrolled. Of these 57 cases, 26 had a severe H1N1 infection (group 1), and 31 had a mild H1N1 infection (group 2). Sera from 18 cases with pneumonia without H1N1 infection (group 3) were used as controls. The serum levels of 10 cytokines were determined by multiplex assay. RESULTS: The serum levels of IFN‐α, IL‐6, and IP‐10 were significantly higher in H1N1 infected cases than in group 3, and levels of IL‐6 and IP‐10 were significantly higher in group 1 than in group 2. The level of IL‐10 was significantly higher in groups 1 and 3 than in group 2. However, levels of IFN‐γ and IL‐17 were not significantly different between the three groups. IL‐1β, IL‐4, and MIP‐1α were not detectable in most patients. IP‐10 and IL‐6 levels were found to show negative correlations with lymphocyte count and oxygen saturation. CONCLUSIONS: We found higher levels of cytokines (IFN‐α, IL‐6, IP‐10) of innate immunity than those of acquired immunity in pediatric H1N1 infection. Of the cytokines found to be increased in cases with H1N1 infection, IP‐10 and IL‐6 were found to be correlated with disease severity (lymphopenia and hypoxia). IP‐10 and IL‐6 may be important markers in pediatric H1N1 infection. Pediatr Pulmonol. 2011; 46: 1233–1239. © 2011 Wiley Periodicals, Inc.


docid: louivjim

title: Mechanisms and Regulation of RNA Condensation in RNP Granule Formation

text: Abstract Ribonucleoprotein (RNP) granules are RNA-protein assemblies involved in multiple aspects of RNA metabolism and are linked with memory, development and disease. Some RNP granules form, in part, through formation of intermolecular RNA–RNA interactions. In vitro, such trans RNA condensation occurs readily, suggesting that cells require mechanisms to modulate RNA-based condensation. Herein, we assess mechanisms of RNA condensation and how cells modulate this phenomenon. We propose that cells control RNA condensation through ATP-dependent processes, static RNA buffering, and dynamic post-translational mechanisms. Moreover, perturbations in these mechanisms can be involved in disease. This reveals multiple cellular mechanisms of kinetic and thermodynamic control to maintain the proper distribution of RNA molecules between dispersed and condensed forms.


title: The nucleocapsid protein of SARS-associated coronavirus inhibits B23 phosphorylation

text: Abstract Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is responsible for SARS infection. Nucleocapsid (N) protein of SARS-CoV encapsidates the viral RNA and plays an important role in virus particle assembly and release. In this study, the N protein of SARS-CoV was found to associate with B23, a phosphoprotein in nucleolus, in vitro and in vivo. Mapping studies localized the critical N sequences for this interaction to amino acid residues 175–210, which included a serine/arginine (SR)-rich domain. In vitro phosphorylation assay showed that the N protein inhibited the B23 phosphorylation at Thr199.


title: Influenza A virus transmission via respiratory aerosols or droplets as it relates to pandemic potential

text: Many respiratory viruses of humans originate from animals. For instance, there are now eight paramyxoviruses, four coronaviruses and four orthomxoviruses that cause recurrent epidemics in humans but were once confined to other hosts. In the last decade, several members of the same virus families have jumped the species barrier from animals to humans. Fortunately, these viruses have not become established in humans, because they lacked the ability of sustained transmission between humans. However, these outbreaks highlighted the lack of understanding of what makes a virus transmissible. In part triggered by the relatively high frequency of occurrence of influenza A virus zoonoses and pandemics, the influenza research community has started to investigate the viral genetic and biological traits that drive virus transmission via aerosols or respiratory droplets between mammals. Here we summarize recent discoveries on the genetic and phenotypic traits required for airborne transmission of zoonotic influenza viruses of subtypes H5, H7 and H9 and pandemic viruses of subtypes H1, H2 and H3. Increased understanding of the determinants and mechanisms of respiratory virus transmission is not only key from a basic scientific perspective, but may also aid in assessing the risks posed by zoonotic viruses to human health, and preparedness for such risks.


title: Progress and challenges in maternal health in western China: a Countdown to 2015 national case study

text: BACKGROUND: China is one of the few Countdown countries to have achieved Millennium Development Goal 5 (75% reduction in maternal mortality ratio between 1990 and 2015). We aimed to examine the health systems and contextual factors that might have contributed to the substantial decline in maternal mortality between 1997 and 2014. We chose to focus on western China because poverty, ethnic diversity, and geographical access represent particular challenges to ensuring universal access to maternal care in the region. METHODS: In this systematic assessment, we used data from national census reports, National Statistical Yearbooks, the National Maternal and Child Health Routine Reporting System, the China National Health Accounts report, and National Health Statistical Yearbooks to describe changes in policies, health financing, health workforce, health infrastructure, coverage of maternal care, and maternal mortality by region between 1997 and 2014. We used a multivariate linear regression model to examine which contextual and health systems factors contributed to the regional variation in maternal mortality ratio in the same period. Using data from a cross-sectional survey in 2011, we also examined equity in access to maternity care in 42 poor counties in western China. FINDINGS: Maternal mortality declined by 8·9% per year between 1997 and 2014 (geometric mean ratio for each year 0·91, 95% CI 0·91–0·92). After adjusting for GDP per capita, length of highways, female illiteracy, the number of licensed doctors per 1000 population, and the proportion of ethnic minorities, the maternal mortality ratio was 118% higher in the western region (2·18, 1·44–3·28) and 41% higher in the central region (1·41, 0·99–2·01) than in the eastern region. In the rural western region, the proportion of births in health facilities rose from 41·9% in 1997 to 98·4% in 2014. Underpinning such progress was the Government's strong commitment to long-term strategies to ensure access to delivery care in health facilities—eg, professionalisation of maternity care in large hospitals, effective referral systems for women medically or socially at high risk, and financial subsidies for antenatal and delivery care. However, in the poor western counties, substantial disparity by education level of the mother existed in access to health facility births (44% of illiterate women vs 100% of those with college or higher education), antenatal care (17% vs 69%) had at least four visits), and caesarean section (8% vs 44%). INTERPRETATION: Despite remarkable progress in maternal survival in China, substantial disparities remain, especially for the poor, less educated, and ethnic minority groups in remote areas in western China. Whether China's highly medicalised model of maternity care will be an answer for these populations is uncertain. A strategy modelled after China's immunisation programme, whereby care is provided close to the women's homes, might need to be explored, with township hospitals taking a more prominent role. FUNDING: Government of Canada, UNICEF, and the Bill & Melinda Gates Foundation.


title: Molecular characterization of a virulent canine coronavirus BGF strain

text: Abstract Molecular characterisation of a canine coronavirus (CCoV) isolate (BGF), associated with an outbreak of diarrhoea in puppies, showed 92.7% identity with attenuated Insavc-1 strain. Canine coronavirus BGF revealed a full length non-structural protein 3b (nsp 3b), associated with virulence in other coronaviruses, and a highly divergent region at the amino terminal domain of the membrane protein that may be implicated in avoiding the host immune reaction. This new canine coronavirus strain could help to identify virulence factors in coronavirus.


SARS-associated Coronavirus Infection in Teenagers


title: Perspectives: Coping with the Coronavirus fallout

text: As dentistry continues to settle into a new pattern following guidance relating to the Coronavirus, practitioners remain in a state of flux Dr Gina Vega and Dr Kunal Patel talk to BDJ In Practice about how they and their businesses are coping with the pandemic crisis


title: Shielded from harm

text: For some, covid-19 is fatal, but others have no symptoms at all. How can we predict who will get seriously sick – and how best to protect them? Carrie Arnold reports


docid: lsgyubdj

title: An applied mathematician's perspective on Rosennean Complexity

text: Abstract The theoretical biologist Robert Rosen developed a highly original approach for investigating the question “What is life?”, the most fundamental problem of biology. Considering that Rosen made extensive use of mathematics it might seem surprising that his ideas have only rarely been implemented in mathematical models. On the one hand, Rosen propagates relational models that neglect underlying structural details of the components and focus on relationships between the elements of a biological system, according to the motto “throw away the physics, keep the organisation”. Rosen's strong rejection of mechanistic models that he implicitly associates with a strong form of reductionism might have deterred mathematical modellers from adopting his ideas for their own work. On the other hand Rosen's presentation of his modelling framework, (M, R) systems, is highly abstract which makes it hard to appreciate how this approach could be applied to concrete biological problems. In this article, both the mathematics as well as those aspects of Rosen's work are analysed that relate to his philosophical ideas. It is shown that Rosen's relational models are a particular type of mechanistic model with specific underlying assumptions rather than a fundamentally different approach that excludes mechanistic models. The strengths and weaknesses of relational models are investigated by comparison with current network biology literature. Finally, it is argued that Rosen's definition of life, “organisms are closed to efficient causation”, should be considered as a hypothesis to be tested and ideas how this postulate could be implemented in mathematical models are presented.


title: The N-Terminal Domain of the Arenavirus L Protein Is an RNA Endonuclease Essential in mRNA Transcription

text: Arenaviridae synthesize viral mRNAs using short capped primers presumably acquired from cellular transcripts by a ‘cap-snatching’ mechanism. Here, we report the crystal structure and functional characterization of the N-terminal 196 residues (NL1) of the L protein from the prototypic arenavirus: lymphocytic choriomeningitis virus. The NL1 domain is able to bind and cleave RNA. The 2.13 Å resolution crystal structure of NL1 reveals a type II endonuclease α/β architecture similar to the N-terminal end of the influenza virus PA protein. Superimposition of both structures, mutagenesis and reverse genetics studies reveal a unique spatial arrangement of key active site residues related to the PD…(D/E)XK type II endonuclease signature sequence. We show that this endonuclease domain is conserved and active across the virus families Arenaviridae, Bunyaviridae and Orthomyxoviridae and propose that the arenavirus NL1 domain is the Arenaviridae cap-snatching endonuclease.