title: Online meetings for 12‐Step and other support groups

text: The study showing that Alcoholics Anonymous as as effective, or more effective, than psychotherapy (see “Research: AA is better pathway to abstinence than psychotherapy,” ADAW March 16, https://onlinelibrary.wiley.com/doi/full/10.1002/adaw.32655) was published a few days before COVID‐19 federal and state restrictions on group gatherings (“social distancing”) took effect, making AA and other meetings untenable. This seems like cruel timing. But John Kelly, Ph.D., one of the authors of the study, provided the below infographic to ADAW on other meetings. And Keith Humphreys, Ph.D., co‐author, was quoted recently on ABC News saying that he is concerned about patients with extreme mental health issues such as addiction, for whom face‐to‐face contact is key.


COVID‐19: A chance to be our best


title: Detection and evaluation of immunofunction of patients with severe fever with thrombocytopenia syndrome

text: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS virus (SFTSV) with a high fatality rate. But the immunofunction was still unclear. The objective of our study was to assess the immunofunction in SFTS patients. Immunofunction test with flow cytometry which contains CD3+, CD4+ and CD8+ T lymphocytes, B cells and NK cells would be used for detecting serum samples collected from 34 SFTS cases and 20 healthy donors. We found that CD3+ and CD4+ T lymphocytes were significantly diminished in SFTS compared to normal control. In contrast, the percentage of NK cells was elevated. Further analysis revealed that the number of CD3+ and CD4+ T lymphocytes showed that there was a more robust pattern of depression in acute phase and severe SFTS infection compared to the patients in recovery phase and mild SFTS infection. But NK cells were significantly increased in acute phase and severe SFTS. They reverted to the near normal levels in convalescent phase. Additionally, the levels of CD3+ and CD4+ T lymphocytes progressively decreased in death group when compared with the survival group, but the level of B cells was higher. The damages of immune system were obvious, and the immune dysfunction might be partly responsible for disease progression of patients with SFTSV infection.


title: Intubation boxes for managing the airway in patients with COVID‐19

text: I would like to commend Cook et al. [1] for their excellent, thorough and timely guidelines for airway management during this time. In particular I would like to commend the principles of airway management to encourage safe, accurate and swift performance. These guidelines have already proven invaluable in training with simulation and also in performing tracheal intubations in patients. I would like to highlight the very important point, the first step of their algorithm for tracheal intubation of critically ill adults adapted for COVID-19 which states that staff must don full checked personal protective equipment (PPE).


title: PI4KB on Inclusion Bodies Formed by ER Membrane Remodeling Facilitates Replication of Human Parainfluenza Virus Type 3

text: Many positive-strand RNA viruses remodel the endomembrane to form specialized replication organelles. However, knowledge regarding whether negative-strand RNA viruses take advantage of intracellular membranes for replication is limited. Here we show that a negative-strand RNA virus, human parainfluenza virus type 3 (HPIV3), remodels the endoplasmic reticulum (ER) membrane to form inclusion bodies (IBs), whereby the phosphoprotein (P) of HPIV3 recruits phosphatidylinositol 4-kinase beta (PI4KB) to IBs to generate PI4P, creating a PI4P-enriched microenvironment to promote HPIV3 replication. In addition, we find that human respiratory syncytial virus (HRSV) also takes advantage of the ER to form IBs and that these IBs are also enriched with PI4P. The nucleoprotein of HRSV recruits PI4KB to IBs. These results suggest that paramyxoviruses also exploit the host endomembrane to form IBs and that PI4KB is recruited by viral proteins to enrich IBs with PI4P to facilitate viral replication.


Productively protecting a cohort of vulnerable plastic surgery trainees in the COVID-19 pandemic


title: An alteration of the dopamine synthetic pathway is possibly involved in the pathophysiology of COVID‐19

text: I have read with great interest the paper by Yan Chao Lee et al. entitled "The neuroinvasive potential of SARS-CoV2 may be at least partially responsible for the respiratory failure of COVID-19 patients"1. I would like here to provide arguments indicating that an alteration of the dopamine synthetic pathways is possibly involved in the pathophysiology of COVID-19. This article is protected by copyright. All rights reserved.


Molecular Basis of Disease Cumulative Contents


title: New Rapid Validated HPTLC Method for the Determination of Lycorine in Amaryllidaceae Plants Extracts

text: A rapid, accurate, specific, repeatable and robust HPTLC method for the determination of lycorine in different Amaryllidaceae plant extracts is presented in this work. No article related to the HPTLC determination of lycorine in plant extracts has been reported in literature. Lycorine, a common alkaloid of family Amaryllidaceae, moreover, there have been some recent reports which reveal the interaction of lycorine with DNA and tRNA. It has, therefore, been to the interest of phytochemists to determine the content of this alkaloid in Amaryllidaceaous plants.


High-sensitivity cardiac troponin and the early rule out of myocardial infarction: time for action


title: COVID-19 in Dialysis Patients: Adding a Few More Pieces to the Puzzle

text: Abstract The clinical presentation and mortality rate in maintenance hemodialysis (MHD) patients with COVID-19 are not well established. Recent data from Italy and Spain suggest that these patients present with wide range of symptoms, with a significant portion being asymptomatic. There is prolonged positivity of pharyngeal swabs in MHD patients. The mortality rates are very high, reaching almost 30%. These data highlight the importance of diligent oversight and care of MHD patients during COVID-19 pandemic.


title: Single virus tracking of Ebola virus entry through lipid rafts in living host cells

text: Ebola virus (EBOV) is one of the most pathogenic viruses in humans which can cause a lethal hemorrhagic fever. Understanding the cellular entry mechanisms of EBOV can promote the development of new therapeutic strategies to control virus replication and spread. It has been known that EBOV virions bind to factors expressed at the host cell surface. Subsequently, the virions are internalized by a macropinocytosis-like process, followed by being trafficked through early and late endosomes. Recent researches indicate that the entry of EBOV into cells requires integrated and functional lipid rafts. Whilst lipid rafts have been hypothesized to play a role in virus entry, there is a current lack of supporting data. One major technical hurdle is the lack of effective approaches for observing viral entry. To provide evidence on the involvement of lipid rafts in the entry process of EBOV, we generated the fluorescently labeled Ebola virus like particles (VLPs), and utilized single-particle tracking (SPT) to visualize the entry of fluorescent Ebola VLPs in live cells and the interaction of Ebola VLPs with lipid rafts. In this study, we demonstrate the compartmentalization of Ebola VLPs in lipid rafts during entry process, and inform the essential function of lipid rafts for the entry of Ebola virus. As such, our study provides evidence to show that the raft integrity is critical for Ebola virus pathogenesis and that lipid rafts can serve as potential targets for the development of novel therapeutic strategies.


Concepts of management of plastic surgery services during the coronavirus disease 2019 pandemic


title: Bacterial Pneumonia in Dogs and Cats An Update

text: Bacterial pneumonia is a common clinical diagnosis in dogs but seems to occur less often in cats. Underlying causes include viral infection, aspiration injury, foreign body inhalation, and defects in clearance of respiratory secretions. Identification of the specific organisms involved in disease, appropriate use of antibiotics and adjunct therapy, and control of risk factors for pneumonia improve management.


title: Thymosin alpha 1: Biological activities, applications and genetic engineering production

text: Thymosin alpha 1 (Tα1), a 28-amino acid peptide, was first described and characterized from calf thymuses in 1977. This peptide can enhance T-cell, dendritic cell (DC) and antibody responses, modulate cytokines and chemokines production and block steroid-induced apoptosis of thymocytes. Due to its pleiotropic biological activities, Tα1 has gained increasing interest in recent years and has been used for the treatment of various diseases in clinic. Accordingly, there is an increasing need for the production of this peptide. So far, Tα1 used in clinic is synthesized using solid phase peptide synthesis. Here, we summarize the genetic engineering methods to produce Tα1 using prokaryotic or eukaryotic expression systems. The effectiveness of these biological products in increasing the secretion of cytokines and in promoting lymphocyte proliferation were investigated in vitro studies. This opens the possibility for biotechnological production of Tα1 for the research and clinical applications.


title: Reverse spillover of avian viral vaccine strains from domesticated poultry to wild birds

text: Transmission of viruses from the commercial poultry to wild birds is an emerging paradigm of livestock–wildlife interface. Here, we report the identification and isolation of vaccine strains of avian paramyxovirus serotype 1 (APMV1) and avian coronaviruses (ACoV) from different wild bird species across eight Egyptian governorates between January 2014 and December 2015. Surveillance of avian respiratory viruses in free-ranging wild birds (n = 297) identified three species that harboured or excreted APMV1 and ACoVs. Genetic characterization and phylogenetic analysis of recovered viruses revealed a close association with the most widely utilized vaccine strains in the country. These results highlight the potential spillover of vaccine-viruses probably due to extensive use of live-attenuated vaccines in the commercial poultry, and close interaction between domesticated and wild bird populations. Further exploring the full spectrum of vaccine-derived viral vaccine strains in wild birds might help to assess the emergence of future wild-birds origin viruses.


title: Designing of a next generation multiepitope based vaccine (MEV) against SARS-COV-2: Immunoinformatics and in silico approaches

text: Coronavirus disease 2019 (COVID-19) associated pneumonia caused by severe acute respiratory coronavirus 2 (SARS-COV-2) was first reported in Wuhan, China in December 2019. Till date, no vaccine or completely effective drug is available for the cure of COVID-19. Therefore, an effective vaccine against SARS-COV-2 is needed to be design. This study was conducted to design an effective multi-epitope vaccine (MEV) against SARS-COV-2. Seven antigenic proteins were taken as a target and epitopes (B cell, IFN-γ and T cell) were predicted. Highly antigenic and overlapping epitopes were shortlisted. Selected T cell epitopes indicated significant interactions with the HLA-binding alleles and 99.29% coverage of the world’s population. Finally, 505 amino acids long MEV was designed by connecting sixteen MHC class I and twelve MHC class II epitopes with suitable linkers and adjuvant. Linkers and adjuvant were added to enhance the immunogenicity response of the vaccine. The allergenicity, physiochemical properties, antigenicity and structural details of MEV were analyzed in order to ensure safety and immunogenicity. MEV construct was non-allergenic and antigenic. Molecular docking demonstrated a stable and strong binding affinity of MEV with TLR3 and TLR8. Codon optimization and in silico cloning ensured increased expression in the Escherichia coli K-12 system. However, to ensure its safety and immunogenic profile, the proposed vaccine needs to be experimentally validated.


title: Activation of glial cells by human coronavirus OC43 infection

text: Abstract Multiple sclerosis (MS) is an immune-mediated demyelinating disease that could be triggered by a viral infection. Coronaviruses induce an MS-like disease in rodents, are neuroinvasive in humans and can infect primary cultures of human astrocytes and microglia. Infection of the human astrocytic cell line U-373MG by the OC43 strain of human coronavirus caused an upregulation of IL-6, TNF-α, and MCP-1 mRNA expression. This virus also modulated the activity of matrix metalloproteinases-2 and -9 and augmented nitric oxide production in both U-373MG cells and the human microglial cell line CHME-5. Thus, a coronaviral infection of glial cells could lead to the production of inflammatory molecules that have been associated with central nervous system pathologies such as MS.


COVID‐19 as the primary agent


title: Detection of common respiratory viruses in tonsillar tissue of children with obstructive sleep apnea

text: BACKGROUND: Early life viral infection is associated with neurogenic inflammation that is present in lymphoid tissues of the upper airway in children with obstructive sleep apnea (OSA). We hypothesized that viral genomic material is present in tonsils of children with OSA. Therefore, we examined tonsils for the presence of respiratory viruses' nucleic acids in children with OSA, and in children without OSA (undergoing surgery for recurrent throat infections (RI)). METHODS: Tonsillar tissue from patients with OSA and RI was subjected to multiplex quantitative real time reverse transcription PCR (mqRTPCR), analyzed for the presence of common respiratory viruses' genetic material. RESULTS: Fifty‐six patients were included, of whom 34 had OSA (age (years ± S.D), 4.22 ± 1.14) and 22 with RI (4.35 ± 1.36). Respiratory viruses nucleic acids (24 detections) were observed in 17 (50%) OSA samples. In contrast, no virus was detected in RI samples (relative frequency P < 0.0001). Viruses detected, based on frequency were Rhinovirus, Adenovirus, human metapneumovirus (hMPV), respiratory syncytial virus (RSV), and corona virus. CONCLUSIONS: Respiratory viruses are detected in OSA hypertrophic tonsils, suggestive of their role in the evolution of tonsillar inflammation and hypertrophy. Early life viral infections may contribute to the pathogenesis of pediatric OSA. Pediatr Pulmonol. 2015; 50:187–195. © 2014 Wiley Periodicals, Inc.


title: Coevolution spreading in complex networks

text: The propagations of diseases, behaviors and information in real systems are rarely independent of each other, but they are coevolving with strong interactions. To uncover the dynamical mechanisms, the evolving spatiotemporal patterns and critical phenomena of networked coevolution spreading are extremely important, which provide theoretical foundations for us to control epidemic spreading, predict collective behaviors in social systems, and so on. The coevolution spreading dynamics in complex networks has thus attracted much attention in many disciplines. In this review, we introduce recent progress in the study of coevolution spreading dynamics, emphasizing the contributions from the perspectives of statistical mechanics and network science. The theoretical methods, critical phenomena, phase transitions, interacting mechanisms, and effects of network topology for four representative types of coevolution spreading mechanisms, including the coevolution of biological contagions, social contagions, epidemic–awareness, and epidemic–resources, are presented in detail, and the challenges in this field as well as open issues for future studies are also discussed.


title: Botanical immunodrugs: scope and opportunities

text: Abstract Modulation of the immune system can be addressed through a variety of specific and non-specific approaches. Many agents of synthetic and natural origin have stimulatory, suppressive or regulatory activity. There is growing evidence that drugs or biological agents capable of modulating single pathways or targets are of limited value as immune-related therapies. Systems biology approaches are now gaining more interest compared with monovalent approaches, which can be of limited benefits with complications. This has stimulated interest in the use of ‘cocktails’ of immunodrugs to restore immunostasis. Botanicals are chemically complex and diverse and could therefore provide appropriate combinations of synergistic moieties useful in drug discovery. Here, the importance of traditional medicine in natural product drug discovery related to immunodrugs is reviewed.


title: Codon usage in Alphabaculovirus and Betabaculovirus hosted by the same insect species is weak, selection dominated and exhibits no more similar patterns than expected

text: Abstract Mutations shape synonymous codon usage bias in certain organism genomes, while selection shapes it in others. Lepidopteran-specific Alphabaculovirus and Betabaculovirus are two large genera in the family of Baculoviridae. In this study, we analyzed the codon usage patterns in 17 baculoviruses, including 10 alphabaculoviruses and 7 betabaculoviruses, which were isolated from seven insect species, and we characterized the codon usage patterns between Alphabaculovirus and Betabaculovirus. Our results show that all the baculoviruses possessed a general weak trend of codon bias. The differences of ENc (effective number of codons) values, nucleotide contents and the impacts of nucleotide content on ENc value within alpha-/betabaculovirus pairs were independent of whether the host species are the same or different. Furthermore, the majority of amino acid sequences adopted codons unequally in all viruses, but the numbers of common preferred codons between alpha- and betabaculoviruses hosted by the same insect species were not significantly different from the differences observed between alpha- and betabaculoviruses hosted by different insect species. In addition, the amino acids that adopt the same synonymous codon composition between alpha- and betabaculoviruses hosted by the same insect species were statistically as few as those between alpha- and betabaculoviruses hosted by different insect species. Correspondence analysis revealed that no major factors resulted in the codon bias in these baculoviruses, implying multiple minor influential factors exist. Neutrality plot analysis indicated that selection pressure dominated mutations in shaping the codon usage. However, the levels of selection pressure were not significantly different among viruses hosted by the same insect species. We expect that evolution would cause the alpha- and betabaculoviruses hosted by the same insect species to share more patterns, but this effect was not observed.


The conundrum of rising Covid19 infection among health care workers: An emerging paradigm


title: The Multifarious Role of 14-3-3 Family of Proteins in Viral Replication

text: The 14-3-3 proteins are a family of ubiquitous and exclusively eukaryotic proteins with an astoundingly significant number of binding partners. Their binding alters the activity, stability, localization, and phosphorylation state of a target protein. The association of 14-3-3 proteins with the regulation of a wide range of general and specific signaling pathways suggests their crucial role in health and disease. Recent studies have linked 14-3-3 to several RNA and DNA viruses that may contribute to the pathogenesis and progression of infections. Therefore, comprehensive knowledge of host–virus interactions is vital for understanding the viral life cycle and developing effective therapeutic strategies. Moreover, pharmaceutical research is already moving towards targeting host proteins in the control of virus pathogenesis. As such, targeting the right host protein to interrupt host–virus interactions could be an effective therapeutic strategy. In this review, we generated a 14-3-3 protein interactions roadmap in viruses, using the freely available Virusmentha network, an online virus–virus or virus–host interaction tool. Furthermore, we summarize the role of the 14-3-3 family in RNA and DNA viruses. The participation of 14-3-3 in viral infections underlines its significance as a key regulator for the expression of host and viral proteins.


title: There is nothing permanent except change. The emergence of new virus diseases

text: Abstract The sudden appearance of apparently new viruses with pathogenic potential is of fundamental importance in medical microbiology and a constant threat to humans and animals. The emergence of a “new” pathogen is not an isolated event, as for instance the frequent appearance of new influenza virus strains demonstrates. Often the new virus strains co-circulate with the older strains in a susceptible population, but a replacement of the older strains has been also observed. In rare instances the new viruses can cause dramatic epidemics or pandemics, such as those observed with the human immunodeficiency virus, canine parvovirus, or most recently, with the agent of bovine spongiform encephalopathy in the United Kingdom. The mechanisms of the emergence are not always clearly understood, but an altered host range appears to be a common event. Whether a true change in host range occurs, or whether the virus adapted to the host and replicated more efficiently, is often unknown. This review tries to summarize the facts that are known about a wide variety of “new” viruses of mammals, such as the simian, human and feline lentiviruses, the feline coronaviruses, the feline parvoviruses, the carnivore morbilliviruses, the influenza A viruses, and the transmissible spongiform encephalopathies. A particular emphasis will be put on the genetic mechanisms that might have taken place and that might have been responsible for their sudden appearance.


title: Phoenix rising: gene therapy makes a comeback

text: Despite the first application of gene therapy in 1990, gene therapy has until recently failed to meet the huge expectations set forth by researchers, clinicians, and patients, thus dampening enthusiasm for an imminent cure for many life-threatening genetic diseases. Nonetheless, in recent years we have witnessed a strong comeback for gene therapy, with clinical successes in young and adult subjects suffering from inherited forms of blindness or from X-linked severe combined immunodeficiency disease. In this review, various gene therapy vectors progressing into clinical development and pivotal advances in gene therapy trials will be discussed.


'Dental Decisions' study launches


title: Susceptibility of Chikungunya Virus to Inactivation by Heat and Commercially and World Health Organization-Recommended Biocides

text: Despite increasing clinical relevance of Chikungunya virus (CHIKV) infection, caused by a rapidly emerging pathogen, recommended guidelines for its inactivation do not exist. In this study, we investigated the susceptibility of CHIKV to inactivation by heat and commercially available hand, surface, and World Health Organization-recommended disinfectants to define CHIKV prevention protocols for healthcare systems.


title: The Future of Skull Base Surgery: A View Through Tinted Glasses

text: ABSTRACT This article broadly outlines the potential advances in the field of skull base surgery, which may occur in the next 20 years based on many areas of current research in biology and technology. Many of these advances are also broadly applicable to other areas of neurosurgery. We ground our predictions for future developments in an exploration of what patients and surgeons most desire as outcomes for care. This leads to an examination of recent developments in the field and outlines several promising areas of future improvement in skull base surgery, per se, as well as identifying new hospital support systems needed to accommodate these changes. These include, but are not limited to advances in imaging, Raman Spectroscopy and Microscopy, 3-dimensional printing and rapid prototyping, master-slave and semi-autonomous robots, artificial intelligence applications in all areas of medicine, tele-medicine, and green technologies in hospitals. In addition, we review therapeutic approaches employing nanotechnology, genetic engineering and anti-tumoral antibodies, as well as stem cell technologies to repair damage caused by traumatic injuries, tumors, and iatrogenic injuries to the brain and cranial nerves. Additionally, we discuss the training requirements for future skull- base surgeons and stress the need for adaptability and change. However, the essential requirements for skull base surgeons remain unchanged, namely: knowledge, attention to details, technical skill, innovation, judgement, and compassion. Our conclusion is that active involvement in these rapidly evolving technologies will enable us to shape some of the future of our discipline to address the needs of both patients and our profession.


title: Atypical Escherichia coli strains and their association with poult enteritis and mortality syndrome

text: Abstract To date, no definitive etiology has been described for Poult Enteritis and Mortality Syndrome (PEMS). However, two atypical Escherichia coli colony types are isolated consistently from moribund and dead poults afflicted with PEMS. To test the infectivity of these E. coli strains, poults were placed into floor pens in three isolation treatment rooms: 1) Control: no bacterial challenge, 2) E. coli colony Types 1 or 2 posthatch oral challenge: 10(8) cfu/per poult at 1 d, and 3) E. coli colony Types 1 or 2 posthatch oral challenge: 10(8) cfu/per poult at 6 d. Daily intramuscular injections of cyclophosphamide (100 micrograms per poult) from 1 to 5 d posthatch were given to half of the poults in each treatment. Atypical E. coli challenge caused BW depression, and cyclophosphamide treatment exacerbated the response. All E. coli-challenged poults developed diarrhea similar to PEMS. Mortality was increased by both atypical E. coli colony types, but at 21 d E. coli colony Type 2 caused greater mortality than colony Type 1. With cyclophosphamide treatment, mortality was exacerbated with both colony types, but colony Type 2 at 1 d caused the greatest mortality. Ultrastructural damage to ileum epithelium cell microvilli and subcellular organelles indicated that part of the BW depression could be attributed to malabsorption of nutrients. It was concluded that the atypical E. coli colony Types 1 and 2 play a significant role in the PEMS disease.


title: Effect of restricted emissions during COVID-19 on air quality in India

text: Abstract The effectiveness and cost are always top factors for policy-makers to decide control measures and most measures had no pre-test before implementation. Due to the COVID-19 pandemic, human activities are largely restricted in many regions in India since mid-March of 2020, and it is a progressing experiment to testify effectiveness of restricted emissions. In this study, concentrations of six criteria pollutants, PM10, PM2.5, CO, NO2, ozone and SO2 during March 16th to April 14th from 2017 to 2020 in 22 cities covering different regions of India were analysed. Overall, around 43, 31, 10, and 18% decreases in PM2.5, PM10, CO, and NO2 in India were observed during lockdown period compared to previous years. While, there were 17% increase in O3 and negligible changes in SO2. The air quality index (AQI) reduced by 44, 33, 29, 15 and 32% in north, south, east, central and western India, respectively. Correlation between cities especially in northern and eastern regions improved in 2020 compared to previous years, indicating more significant regional transport than previous years. The mean excessive risks of PM reduced by ~52% nationwide due to restricted activities in lockdown period. To eliminate the effects of possible favourable meteorology, the WRF-AERMOD model system was also applied in Delhi-NCR with actual meteorology during the lockdown period and an un-favourable event in early November of 2019 and results show that predicted PM2.5 could increase by only 33% in unfavourable meteorology. This study gives confidence to the regulatory bodies that even during unfavourable meteorology, a significant improvement in air quality could be expected if strict execution of air quality control plans is implemented.


title: A sensitive real-time PCR for detection and subgrouping of human respiratory syncytial virus

text: Abstract Improved diagnostic tools for rapid detection, quantitation, and subgrouping of human respiratory syncytial virus (RSV) are needed to aid the development and evaluation of novel intervention strategies. A quantitative real-time RT-PCR using specific locked nucleic acid (LNA) probes was developed to identify RSV and to distinguish RSV subgroups A and B (RSV LNA assay). RSV subgroup diversity and the relationship between viral load and disease severity in confirmed RSV infections were also explored. 264 archived respiratory specimens from pediatric patients were tested in parallel using the commercial multiplex Seeplex™ RV detection kit (Seegene) and the novel RSV LNA assay. The LNA assay demonstrated a significantly higher sensitivity than Seeplex, improving overall detection rates from 24% (64/264) to 32% (84/264). Detection limits of 9.0×101 and 6.0×102 copies/mL were observed for RSV A and B, respectively. RSV A was detected in 53/84 (63%) cases, and 31/84 (37%) were positive for RSV B. This novel method offers a rapid, quantitative, highly specific and sensitive approach to laboratory diagnosis of RSV.


docid: nypyabyj

title: BCSH/BSBMT/UK clinical virology network guideline: diagnosis and management of common respiratory viral infections in patients undergoing treatment for haematological malignancies or stem cell transplantation

text: A joint working group established by the Haemato‐oncology subgroup of the British Committee for Standards in Haematology, the British Society for Bone Marrow Transplantation and the UK Clinical Virology Network has reviewed the available literature and made recommendations for the diagnosis and management of respiratory viral infections in patients with haematological malignancies or those undergoing haematopoietic stem cell transplantation. This guideline includes recommendations for the diagnosis, prevention and treatment of respiratory viral infections in adults and children. The suggestions and recommendations are primarily intended for physicians practising in the United Kingdom.


docid: jlsfgbsg

title: Can Healthcare Workers Reasonably Question the Duty to Care Whilst Healthcare Institutions Take a Reactive (Rather than Proactive) Approach to Infectious Disease Risks?

text: Healthcare workers (HCWs) carry a substantial risk of harm from infectious disease, particularly, but not exclusively, during outbreaks. More can be done by healthcare institutions to identify risks, quantify the current burden of preventable infectious disease amongst HCWs and identify opportunities for prevention. We suggest that institutional obligations should be clarified with respect to the mitigation of infectious disease risks to staff, and question the duty of HCWs to care while healthcare institutions persist with a reactive rather than proactive attitude to infectious disease threats.


docid: kufgwhmg

title: CHAPTER 23 Chief Complaints and ICD Codes


Advocating for group interaction in the age of COVID-19


title: Studies on the relationship between coronaviruses from the intestinal and respiratory tracts of calves

text: An immunofluorescence test on smears of nasal epithelial cells was used to detect coronavirus infection in the respiratory tract of calves. Thirteen gnotobiotic calves were infected with coronavirus isolates derived from faeces or respiratory material: virus was detected in faeces and nasal swabs from all animals. In 115 calves from a field survey, there was a significant association between coronavirus excretion from both respiratory and enteric routes in calves with diarrhoea. In a further 12 calves, at necropsy, the predilection sites for coronavirus growth were the distal small intestine, large intestine and the epithelia of the nasal cavity and trachea. Antigen was not found in lung tissue by immunofluoresence or immunoperoxidase staining. Infection with enteric coronavirus induced immunity to reinfection and to heterologous challenge with two coronavirus isolates derived from the respiratory tract. Nine coronaviruses were cultivated, cloned and antisera to three were prepared in pigs. There was complete virus neutralisation in tests with homologous sera and significant cross reactions with the eight other isolates which were of intestinal and respiratory origin. Thus, these bovine coronavirus isolates belonged to the same serotype despite the source of virus.


title: Gut microbiome and the risk factors in central nervous system autoimmunity

text: Abstract Humans are colonized after birth by microbial organisms that form a heterogeneous community, collectively termed microbiota. The genomic pool of this macro-community is named microbiome. The gut microbiota is essential for the complete development of the immune system, representing a binary network in which the microbiota interact with the host providing important immune and physiologic function and conversely the bacteria protect themselves from host immune defense. Alterations in the balance of the gut microbiome due to a combination of environmental and genetic factors can now be associated with detrimental or protective effects in experimental autoimmune diseases. These gut microbiome alterations can unbalance the gastrointestinal immune responses and influence distal effector sites leading to CNS disease including both demyelination and affective disorders. The current range of risk factors for MS includes genetic makeup and environmental elements. Of interest to this review is the consistency between this range of MS risk factors and the gut microbiome. We postulate that the gut microbiome serves as the niche where different MS risk factors merge, thereby influencing the disease process.


title: Arenavirus budding resulting from viral-protein-associated cell membrane curvature

text: Viral replication occurs within cells, with release (and onward infection) primarily achieved through two alternative mechanisms: lysis, in which virions emerge as the infected cell dies and bursts open; or budding, in which virions emerge gradually from a still living cell by appropriating a small part of the cell membrane. Virus budding is a poorly understood process that challenges current models of vesicle formation. Here, a plausible mechanism for arenavirus budding is presented, building on recent evidence that viral proteins embed in the inner lipid layer of the cell membrane. Experimental results confirm that viral protein is associated with increased membrane curvature, whereas a mathematical model is used to show that localized increases in curvature alone are sufficient to generate viral buds. The magnitude of the protein-induced curvature is calculated from the size of the amphipathic region hypothetically removed from the inner membrane as a result of translation, with a change in membrane stiffness estimated from observed differences in virion deformation as a result of protein depletion. Numerical results are based on experimental data and estimates for three arenaviruses, but the mechanisms described are more broadly applicable. The hypothesized mechanism is shown to be sufficient to generate spontaneous budding that matches well both qualitatively and quantitatively with experimental observations.


title: Feline infectious peritonitis

text: The article discusses feline infectious peritonitis (FIP), an important disease frequently seen in veterinary practice. FIP causes many problems to the veterinarian as it can be difficult to definitively diagnose the disease, as there is no effective treatment, and as prophylactic interventions are not very successful. Although intense research has created a lot of new knowledge about this disease in the last years, there are still many unanswered questions. The objective of this article is to review recent knowledge and to increase understanding of the complex pathogenesis of FIP.


title: World Health Organization

text: This article is reproduced from the previous edition, volume 6, pp. 634–640, © 2008, Elsevier Inc.


title: Effects of public health policies on the health status and medical service utilization of Chinese internal migrants

text: Abstract This paper examines the effects of the “Equalization Program of Basic Public Health and Family Planning Services for Migrants” (EHFPSM), a novel internal migrant-targeted public health policy, of China implemented in 2013. By combining the individual-level data from the “China Migrants Dynamic Survey” and city-level statistical data, we find that EHFPSM contributes to a 6.9% statistically significant increase in the probability of electronic health records coverage and a 7.2% increase in the probability of reimbursement in the last inpatient visit, as well as a 1.2% decrease in the probability of one-year prevalence. The mechanism test shows that this program promotes the migrants' understanding of the policies and social insurance coverage to enhance their health status. EHFPSM brings about more significant decreases in disease prevalence for male and less-educated migrants, and higher reimbursement probability for urban hukou migrants. Our paper facilitates better understanding of the role of public health policies in promoting the internal migrants' health from the perspective of China.


title: Characteristics of fever and response to antipyretic therapy in military personnel with adenovirus-positive community-acquired pneumonia

text: BACKGROUND: In 2014, an outbreak of adenoviral pneumonia occurred in the Korean military training center. However, there are limited data on the characteristics of the fever and its response to antipyretic therapy in immunocompetent adults with adenovirus-positive community-acquired pneumonia (CAP). METHODS: The medical records of the patients who were admitted to the Armed Forces Chuncheon Hospital for the treatment of CAP between January 2014 and December 2016 were retrospectively analyzed. The patients were divided into three groups, namely, the adenovirus-positive (Adv) group, the adenovirus-negative (Non-Adv) group and the unknown pathogen group, according to the results of a polymerase chain reaction (PCR) test and sputum culture used to measure adenovirus and other bacteria or viruses in respiratory specimens. We evaluated and compared the demographics, clinicolaboratory findings and radiological findings upon admission between the two groups. RESULTS: Out of the 251 military personnel with CAP during the study periods, 67 were classified into the Adv group, while 134 were classified into the Non-Adv group and 50 were classified into the unknown pathogen group. The patients in the Adv group had a longer duration of fever after admission (3.2 ± 1.6 vs. 1.9 ± 1.2 vs. 2.2 ± 1.5 days, P = 0.018) and symptom onset (5.8 ± 2.2 vs. 3.9 ± 2.5 vs. 3.7 ± 2.0 days, P = 0.006) than patients in the Non-Adv and unknown pathogen groups, respectively. The patients in the Adv group had a higher mean temperature at admission (37.8 ± 0.3 vs. 37.3 ± 0.3 vs. 37.3 ± 0.3, P = 0.005), and more patients were observed over 40 and 39 to 40(14.9% vs. 2.2% vs. 4.0%, 35.8% vs. 3.7% vs. 6.0%, P < 0.001) than those in the Non-Adv and unknown pathogen groups, respectively. The Adv group more commonly had no response or exhibited adverse events after antipyretic treatment compared to the Non-Adv group (17.9% vs. 1.5%, 35.0% vs. 4.3%, P < 0.001, P = 0.05, respectively). In addition, the time from admission to overall clinical stabilization was significantly longer in the patients in the Adv group than in those in the Non-Adv group (4.3 ± 2.8 vs. 2.9 ± 1.8 days, P = 0.034, respectively). Furthermore, no significant difference in the length of hospital stay was observed between the two groups, and no patient died in either group. CONCLUSION: In this study, Adv-positive CAP in immunocompetent military personnel patients had distinct fever characteristics and responses to antipyretic treatment.


title: Diagnosis of Canine Viral Infections

text: Canine viral infections may be tentatively diagnosed on the basis of clinical signs, hematologic findings, and/or gross pathology; however, definitive diagnosis generally requires laboratory assistance. Laboratory diagnosis of these infections relies on one or more of the following procedures: histopathology, virus isolation, serology, and the detection of virus, or viral antigens, using electron microscopy, fluorescent antibody techniques, immunoperoxidase techniques, and enzyme immunosorbent assays.


title: The next ten stories on antiviral drug discovery (part E): advents, advances, and adventures

text: This review article presents the fifth part (part E) in the series of stories on antiviral drug discovery. The ten stories belonging to this fifth part are dealing with (i) aurintricarboxylic acid; (ii) alkenyldiarylmethanes; (iii) human immunodeficiency virus (HIV) integrase inhibitors; (iv) lens epithelium‐derived growth factor as a potential target for HIV proviral DNA integration; (v) the status presens of neuraminidase inhibitors NAIs in the control of influenza virus infections; (vi) the status presens on respiratory syncytial virus inhibitors; (vii) tricyclic (1,N‐2‐ethenoguanine)‐based acyclovir and ganciclovir derivatives; (viii) glycopeptide antibiotics as antivirals targeted at viral entry; (ix) the potential (off‐label) use of cidofovir in the treatment of polyoma (JC and BK) virus infections; and (x) finally, thymidine phosphorylase as a target for both antiviral and anticancer agents. © 2009 Wiley Periodicals, Inc. Med Res Rev, 31, No. 1, 118–160, 2010


title: Compassionate use of hzVSF‐v13 in two patients with severe COVID‐19

text: We report the compassionate use of humanized Virus Suppressing Factor-variant 13 (hzVSF-v13) in two patients with severe coronavirus disease 2019 (COVID-19) pneumonia. Both patients, including an 81-year-old man who required extracorporeal membrane oxygenation, showed clinical improvement. These results warrant placebo-controlled trials to evaluate the hzVSF-v13 efficacy against COVID-19. This article is protected by copyright. All rights reserved.


title: Antigen selection and presentation to protect against transmissible gastroenteritis coronavirus

text: Abstract The antigenic structure of the S glycoprotein of transmissible gastroenteritis virus (TGEV) and porcine respiratory coronavirus (PRCV) has been determined and correlated with the physical structure. Four antigenic sites have been defined (A, B, C, and D). The sites involved in the neutralization of TGEV are: A, D, and B, sites A and D being antigenically dominant for TGEV neutralization in vitro. These two sites have specific properties of interest: site A is highly conserved and is present in coronaviruses of three animal species, and site D can be represented by synthetic peptides. Both sites might be relevant in protection in vivo. PRCV does not have sites B and C, due to a genomic deletion. Complex antigenic sites, i.e., conformation and glycosylation dependent sites, have been represented by simple mimotopes selected from a library expressing recombinant peptides with random sequences, or by anti-idiotypic internal image monoclonal antibodies. An epidemiological tree relating the TGEVs and PRCVs has been proposed. The estimated mutation fixation rate of 7 ± 2 × 10−4 substitutions per nucleotide and year indicates that TGEV related coronaviruses show similar variability to other RNA viruses. In order to induce secretory immunity, different segments of the S gene have been expressed using avirulent forms of Salmonella typhimurium and adenovirus. These vectors, with a tropism for Peyer's patches may be ideal candidates in protection against TGEV.


title: Two Cases of Systemic Coronavirus-Associated Disease Resembling Feline Infectious Peritonitis in Domestic Ferrets in Japan

text: Abstract A systemic disease of domestic ferrets characterized by pyogranulomatous inflammation was first recognized in Europe and the United States in 2002. The disease closely resembled feline infectious peritonitis and subsequently has been shown to be associated with ferret systemic coronavirus (FRSCV). A definitive laboratory diagnosis of this disease is typically based on a combination of immunohistochemistry (IHC) and reverse-transcriptase polymerase chain reaction tests to detect FRSCV in granulomatous lesions. In 2010, this feline infectious peritonitis–like disease was first identified in a laboratory ferret in Japan, and laboratory confirmation of the clinical diagnosis was limited to IHC. This report describes 2 cases of systemic coronavirus-associated disease in ferrets presented to Japanese veterinary hospitals. Both presented with pyogranulomatous inflammation in the abdominal cavity, and both cases tested positive for coronavirus antigen by IHC. In 1 case, for which unfixed tissues were available, FRSCV RNA was detected by reverse-transcriptase polymerase chain reaction in the affected tissues.


docid: mrucqnty

title: Multiple antigenic peptide (MAP): a synthetic peptide dendrimer for diagnostic, antiviral and vaccine strategies for emerging and re-emerging viral diseases

text: The peptide dendrimer provides novel strategies for various biological applications. Assembling of peptide in macromolecular structure is expected to give rational models as drugs, their delivery and diagnostic reagents. Improved understanding of virus structure and their molecular interactions with ligands have paved the way for treatment and control of emerging and re-emerging viral diseases. This review presents a brief account of a synthetic peptide dendrimer used for diagnostic, therapeutic and prophylactic applications. The designs comprise of multiple antigenic peptides which are being used as alternate synthetic antigens for different viruses.


title: Application of proteomics technology for analyzing the interactions between host cells and intracellular infectious agents

text: Host–pathogen interactions involve protein expression changes within both the host and the pathogen. An understanding of the nature of these interactions provides insight into metabolic processes and critical regulatory events of the host cell as well as into the mechanisms of pathogenesis by infectious microorganisms. Pathogen exposure induces changes in host proteins at many functional levels including cell signaling pathways, protein degradation, cytokines and growth factor production, phagocytosis, apoptosis, and cytoskeletal rearrangement. Since proteins are responsible for the cell biological functions, pathogens have evolved to manipulate the host cell proteome to achieve optimal replication. Intracellular pathogens can also change their proteome to adapt to the host cell and escape from immune surveillance, or can incorporate cellular proteins to invade other cells. Given that the interactions of intracellular infectious agents with host cells are mainly at the protein level, proteomics is the most suitable tool for investigating these interactions. Proteomics is the systematic analysis of proteins, particularly their interactions, modifications, localization and functions, that permits the study of the association between pathogens with their host cells as well as complex interactions such as the host–vector–pathogen interplay. A review on the most relevant proteomic applications used in the study of host–pathogen interactions is presented.


docid: svryhcgy

title: Examining the Impact of COVID-19 Lockdown in Wuhan and Lombardy: A Psycholinguistic Analysis on Weibo and Twitter

text: Many countries are taking strict quarantine policies to prevent the rapid spread of COVID-19 (Corona Virus Disease 2019) around the world, such as city lockdown. Cities in China and Italy were locked down in the early stage of the pandemic. The present study aims to examine and compare the impact of COVID-19 lockdown on individuals’ psychological states in China and Italy. We achieved the aim by (1) sampling Weibo users (geo-location = Wuhan, China) and Twitter users (geo-location = Lombardy, Italy); (2) fetching all the users’ published posts two weeks before and after the lockdown in each region (e.g., the lockdown date of Wuhan was 23 January 2020); (3) extracting the psycholinguistic features of these posts using the Simplified Chinese and Italian version of Language Inquiry and Word Count (LIWC) dictionary; and (4) conducting Wilcoxon tests to examine the changes in the psycholinguistic characteristics of the posts before and after the lockdown in Wuhan and Lombardy, respectively. Results showed that individuals focused more on “home”, and expressed a higher level of cognitive process after a lockdown in both Wuhan and Lombardy. Meanwhile, the level of stress decreased, and the attention to leisure increased in Lombardy after the lockdown. The attention to group, religion, and emotions became more prevalent in Wuhan after the lockdown. Findings provide decision-makers timely evidence on public reactions and the impacts on psychological states in the COVID-19 context, and have implications for evidence-based mental health interventions in two countries.


title: COVID‐19 and liver cancer clinical trials: not everything is lost

text: Since the first cases in Wuhan, China, during the month of December 2019, coronavirus disease (COVID‐19) evolved into a worldwide emergency, becoming one of the deadliest pandemics of modern history. As we write, the outbreak has led to 3,595,662 confirmed cases and 247,652 deaths worldwide(1). SARS‐CoV‐2, the virus responsible for the disease, is a single‐stranded RNA virus which can cause a wide clinical spectrum of symptoms. According to the available knowledge, a large but still unknown percentage of the infected patients remains asymptomatic, representing an important and insidious vehicle of transmission(2). According to the largest case series to date, most of the symptomatic patients complain of a mild respiratory syndrome (81%), while approximately 14% develop a severe disease requiring hospitalization and a further 5% need intensive care(3).


title: Understanding SARS with Wolfram Approach

text: Stepping acquired immunodeficiency syndrome (AIDS), severe acute respiratory syndrome (SARS) as another type of disease has been threatening mankind since late last year. Many scientists worldwide are making great efforts to study the etiology of this disease with different approaches. 13 species of SARS virus have been sequenced. However, most people still largely rely on the traditional methods with some disadvantages. In this work, we used Wolfram approach to study the relationship among SARS viruses and between SARS viruses and other types of viruses, the effect of variations on the whole genome and the advantages in the analysis of SARS based on this novel approach. As a result, the similarities between SARS viruses and other coronaviruses are not really higher than those between SARS viruses and non-coronaviruses.


An updated meta‐analysis on the relationship between D‐dimer levels and severity of coronavirus disease 2019


title: Phylogeny of bovine norovirus in Egypt based on VP2 gene

text: Bovine norovirus (BNoV) has emerged as a viral pathogen that causes a gastrointestinal illness and diarrhea in cattle. Despite its worldwide distribution, very little information is known about BNoV in Africa. In this study, BNoV was detected in 27.6% (8/29) of tested fecal materials, collected from sporadic cases of diarrheic calves, using the reverse transcription-polymerase chain reaction (RT-PCR) and primers that target RNA dependent RNA polymerase gene. Additionally, one primer pair was designed to flank the BNoV-VP2 (small capsid protein) gene for molecular analysis. Study VP2 sequences were phylogenetically-related to BNoV-GIII.2 (Newbury2-like) genotype, which is highly prevalent all over the world. However, they were separated within the cluster and one strain (41FR) grouped with recombinant GIII.P1/GIII.2 strains. Compared to reference VP2 sequences, 14 amino acid substitution mutations were found to be unique to our strains. The study confirms that BNoV is currently circulating among diarrheic calves of Egypt and also characterizes its ORF3 (VP2) genetically. The status of BNoV should be continuously evaluated in Egypt for effective prevention and control.


title: M2-Polarized Macrophages Determine Human Cutaneous Lesions in Lacaziosis

text: Lacaziosis is a cutaneous chronic mycosis caused by Lacazia loboi. Macrophages are important cells in the host immune response in fungal infections. The macrophage population exhibits strong plasticity that varies according to the stimuli in the microenvironment of lesions M1 profile promotes a Th1 pattern of cytokines and a microbicidal function and M2 is related to Th2 cytokines and immunomodulatory response. We investigated the population of M1 and M2 polarized macrophages in human cutaneous lesions. A total of 27 biopsies from human lesions were submitted to an immunohistochemistry protocol using antibodies to detect M1 and M2 macrophages (Arginase-1, CD163, iNOS, RBP-J and cMAF). We could observe high number of cells expressing Arginase1, CD163 and c-MAF that correspond to elements of the M2 profile of macrophage, over iNOS and RBP-J (elements of the M1 profile). The results suggest a predominant phenotype of M2 macrophages, which have an immunomodulatory role and probably contributing to chronicity of Lacaziosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11046-020-00450-z) contains supplementary material, which is available to authorized users.


docid: rvrgcugn

title: The cytokine storm and COVID‐19

text: Coronavirus disease 2019 (COVID‐19), which began in Wuhan, China in December 2019 has caused a large global pandemic and poses a serious threat to public health. More than four million cases of COVID‐19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), have been confirmed as of May 11, 2020. SARS‐CoV‐2 is a highly pathogenic and transmissible coronavirus that primarily spreads through respiratory droplets and close contact. A growing body of clinical data suggests that a cytokine storm is associated with COVID‐19 severity and is also a crucial cause of death from COVID‐19. In the absence of antivirals and vaccines for COVID‐19, there is an urgent need to understand the cytokine storm in COVID‐19. Here, we have reviewed the current understanding of the features of SARS‐CoV‐2 and the pathological features, pathophysiological mechanisms, and treatments of the cytokine storm induced by COVID‐19. Additionally, we suggest that the identification and treatment of the cytokine storm are important components for rescuing patients with severe COVID‐19. This article is protected by copyright. All rights reserved.


title: Prevalence of Epstein–Barr virus in tonsils and adenoids of United Arab Emirates nationals

text: Abstract Objective Given that Epstein–Barr virus (EBV) often inhabits human tonsils and adenoids, it remains to be distinctively determined its prevalence and in which cell and microenvironment the virus is present. Methods To determine the prevalence of EBV in the tonsils and adenoids of the United Arab Emirates (UAE) nationals and to provide a basis for understanding the origin and biology of EBV-infected cells, the immunophenotype of all EBV-infected cells in 46 tonsils and 46 adenoids was determined by EBER in situ hybridization and immunohistochemistry with monoclonal antibodies to T cells (CD3), B cells (CD20), and epithelial cells (cytokeratin AE1/AE3), as well as immunostaining with antibodies to EBV latent membrane protein-1 (LMP-1). Results EBV was found in 43% of tonsillectomy specimens and 15% of adenoidectomy specimens. All EBV-infected cells were found to be B lymphocytes. About 90% of the infected B cells are found in the interfollicular regions of tonsils and adenoids and the remaining 10% are found within the follicles. There is no significant association between EBV infection, age (P =0.324) and gender (P =0.442). Conclusion EBV is associated with tonsillar hypertrophy and is prevalent in 43% of our cases. EBV is only detected in B lymphocytes and we believe that B lymphocytes are sites of primary infection and latency. In situ hybridization is the gold standard for the detection of EBV in tissue.


title: CD200R1 Supports HSV-1 Viral Replication and Licenses Pro-Inflammatory Signaling Functions of TLR2

text: The CD200R1:CD200 axis is traditionally considered to limit tissue inflammation by down-regulating pro-inflammatory signaling in myeloid cells bearing the receptor. We generated CD200R1(−/−) mice and employed them to explore both the role of CD200R1 in regulating macrophage signaling via TLR2 as well as the host response to an in vivo, TLR2-dependent model, herpes simplex virus 1 (HSV-1) infection. CD200R1(−/−) peritoneal macrophages demonstrated a 70–75% decrease in the generation of IL-6 and CCL5 (Rantes) in response to the TLR2 agonist Pam(2)CSK(4) and to HSV-1. CD200R1(−/−) macrophages could neither up-regulate the expression of TLR2, nor assemble a functional inflammasome in response to HSV-1. CD200R1(−/−) mice were protected from HSV-1 infection and exhibited dysfunctional TLR2 signaling. Finally, both CD200R1(−/−) mice and CD200R1(−/−) fibroblasts and macrophages showed a markedly reduced ability to support HSV-1 replication. In summary, our data demonstrate an unanticipated and novel requirement for CD200R1 in “licensing” pro-inflammatory functions of TLR2 and in limiting viral replication that are supported by ex vivo and in vivo evidence.


title: Dynamic profile of RT-PCR findings from 301 COVID-19 patients in Wuhan, China: a descriptive study

text: Abstract Background With the spread of Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, its effect on society is amplified. We aimed to describe the viral detection results across different timepoints throughout the disease course. Methods A retrospective study of 301 confirmed COVID-19 patients hospitalized at Tongji Hospital in Wuhan, China, were included. Demographic characteristics of the patients were collected. Upper respiratory specimens (throat and/or nasal swabs) were obtained and analyzed by real-time RT-PCR for SARS-CoV-2 infection. Period of viral infection and the contagious stage were analyzed. Results Of 301 hospitalized COVID-19 patients, the median age was 58 years and 51.2% were male. The median period between symptoms presence and positive SARS-CoV-2 RT-PCR results was 16 days (IQR, 10-23, N = 301). The median period between symptoms presence and an effective negative SARS-CoV-2 RT-PCR result was 20 days (IQR, 17-24; N = 216). Infected patient ≥65 years old stayed contagious longer (22 days vs 19 days, p = 0.015). Although two consecutive negative results were confirmed in 70 patients, 30% of them had positive viral test results for the third time. Using specimens from nasal swabs to run the RT-PCR test showed a higher positive rate than using specimens from throat swabs. Conclusions This large-scale investigation with 1113 RT-PCR test results from 301 COVID-19 patients showed that the average contagious period of SARS-CoV-2 infected patients was 20 days. Longer observation period and more than 2 series of negative viral test are necessary for patients ≥65 years.


title: Twenty-five years of type I interferon-based treatment: A critical analysis of its therapeutic use

text: Abstract The clinical exploitation of type I interferon (IFN) as an antiviral and antineoplastic agent is based on the properties originally attributed to this cytokine family, with schedules reflecting only their antiviral and antiproliferative activities. Nevertheless, type I IFN has emerged as a central activator of the innate immunity. As current schedules of treatment for chronic hepatitis C and for hematological and solid tumors, based on the continuous administration of recombinant type I IFN or pegylated formulations, disregard viral resistance, host genetic variants predicting treatment outcome and mechanisms of refractoriness, new administration schedules, the combination of type I IFN with new drugs and the increased monitoring of patients’ susceptibility to type I IFN are expected to provide a new life to this valuable cytokine.


title: Development and Implementation of Evidence-Based Practice in Cancer Care: Challenges and Opportunities

text: The cancer burden is a global problem, and oncology nurses should be accountable for delivering safe and effective cancer care and providing the best possible experience for patients. The development and application of evidence-based practice in cancer care is an effective strategy in achieving this goal; however, the journey in which such practice involves may encounter various challenges. In this article, the author discusses her own experience, successful and unsuccessful of such a journey. Both challenges and opportunities are identified, and suggestions put forward for making collaborative efforts.


title: Coping flexibility in college students with depressive symptoms

text: BACKGROUND: The current study explored the prevalence of depressed mood among Chinese undergraduate students and examined the coping patterns and degree of flexibility of flexibility of such patterns associated with such mood. METHODS: A set of questionnaire assessing coping patterns, coping flexibility, and depressive symptoms were administered to 428 students (234 men and 194 women). RESULTS: A total of 266 participants both completed the entire set of questionnaires and reported a frequency of two or more stressful life events (the criterion needed to calculate variance in perceived controllability). Findings showed that higher levels of depressive symptoms were significantly associated with higher levels of both event frequency (r = .368, p < .001) and event impact (r = .245, p < .001) and lower levels of perceived controllability (r = -.261, p < .001), coping effectiveness (r = -.375, p < .001), and ratio of strategy to situation fit (r = -.108, p < .05). Depressive symptoms were not significantly associated with cognitive flexibility (variance of perceived controllability; r = .031, p = .527), Gender was not a significant moderator of any of the reported associations. CONCLUSIONS: Findings indicate that Chinese university students with depressive symptoms reported experiencing a greater number of negative events than did non-depressed university students. In addition, undergraduates with depressive symptoms were more likely than other undergraduates to utilize maladaptive coping methods. Such findings highlight the potential importance of interventions aimed at helping undergraduate students with a lower coping flexibility develop skills to cope with stressful life events.


20/20 foresight for 2020?


title: Recent Insight into SARS-CoV2 Immunopathology and Rationale for Potential Treatment and Preventive Strategies in COVID-19

text: As the outbreak of the new coronavirus (SARS-CoV-2) infection is spreading globally, great effort is being made to understand the disease pathogenesis and host factors that predispose to disease progression in an attempt to find a window of opportunity for intervention. In addition to the direct cytopathic effect of the virus, the host hyper-inflammatory response has emerged as a key factor in determining disease severity and mortality. Accumulating clinical observations raised hypotheses to explain why some patients develop more severe disease while others only manifest mild or no symptoms. So far, Covid-19 management remains mainly supportive. However, many researches are underway to clarify the role of antiviral and immunomodulating drugs in changing morbidity and mortality in patients who become severely ill. This review summarizes the current state of knowledge on the interaction between SARS-CoV-2 and the host immune system and discusses recent findings on proposed pharmacologic treatments.


title: Viral mechanisms of immune evasion

text: Abstract During the millions of years they have coexisted with their hosts, viruses have learned how to manipulate host immune control mechanisms. Viral gene functions provide an overview of many relevant principles in cell biology and immunology. Our knowledge of viral gene functions must be integrated into virus–host interaction networks to understand viral pathogenesis, and could lead to new anti-viral strategies and the ability to exploit viral functions as tools in medicine.


title: Bronchiolitis needs a revisit: Distinguishing between virus entities and their treatments

text: Current data indicate that the “bronchiolitis” diagnosis comprises more than one condition. Clinically, pathophysiologically, and even genetically three main clusters of patients can be identified among children suffering from severe bronchiolitis (or first wheezing episode): (a) respiratory syncytial virus (RSV)‐induced bronchiolitis, characterized by young age of the patient, mechanical obstruction of the airways due to mucus and cell debris, and increased risk of recurrent wheezing. For this illness, an effective prophylactic RSV‐specific monoclonal antibody is available; (b) rhinovirus‐induced wheezing, associated with atopic predisposition of the patient and high risk of subsequent asthma development, which may, however, be reversed with systemic corticosteroids in those with severe illness; and (c) wheeze due to other viruses, characteristically likely to be less frequent and severe. Clinically, it is important to distinguish between these partially overlapping patient groups as they are likely to respond to different treatments. It appears that the first episode of severe bronchiolitis in under 2‐year‐old children is a critical event and an important opportunity for designing secondary prevention strategies for asthma. As data have shown bronchiolitis cannot simply be diagnosed using a certain cutoff age, but instead, as we suggest, using the viral etiology as the differentiating factor.


docid: rhphldyp

title: SARS-CoV replicates in primary human alveolar type II cell cultures but not in type I-like cells

text: Abstract Severe acute respiratory syndrome (SARS) is a disease characterized by diffuse alveolar damage. We isolated human alveolar type II cells and maintained them in a highly differentiated state. Type II cell cultures supported SARS-CoV replication as evidenced by RT-PCR detection of viral subgenomic RNA and an increase in virus titer. Virus titers were maximal by 24 h and peaked at approximately 105 pfu/mL. Two cell types within the cultures were infected. One cell type was type II cells, which were positive for SP-A, SP-C, cytokeratin, a type II cell-specific monoclonal antibody, and Ep-CAM. The other cell type was composed of spindle-shaped cells that were positive for vimentin and collagen III and likely fibroblasts. Viral replication was not detected in type I-like cells or macrophages. Hence, differentiated adult human alveolar type II cells were infectible but alveolar type I-like cells and alveolar macrophages did not support productive infection.


Middle East respiratory syndrome: new disease, old lessons


title: Lessons from SARS: control of acute lung failure by the SARS receptor ACE2

text: Angiotensin-converting enzyme 2 (ACE2), a second angiotensin-converting enzyme (ACE), regulates the renin–angiotensin system by counterbalancing ACE activity. Accumulating evidence in recent years has demonstrated a physiological and pathological role of ACE2 in the cardiovascular systems. Recently, it has been shown that severe acute respiratory syndrome (SARS) coronavirus, the cause of SARS, utilizes ACE2 as an essential receptor for cell fusion and in vivo infections in mice. Intriguingly, ACE2 acts as a protective factor in various experimental models of acute lung failure and, therefore, acts not only as a key determinant for SARS virus entry into cells but also contributes to SARS pathogenesis. Here we review the role of ACE2 in disease pathogenesis, including lung diseases and cardiovascular diseases.


title: Feline orofacial pain syndrome (FOPS): a retrospective study of 113 cases

text: Feline orofacial pain syndrome (FOPS) is a pain disorder of cats with behavioural signs of oral discomfort and tongue mutilation. This report describes the findings from a case series of 113 cats including 100 Burmese. FOPS is suspected to be a neuropathic pain disorder and the predominance within the Burmese cat breed suggests an inherited disorder, possibly involving central and/or ganglion processing of sensory trigeminal information. The disease is characterised by an episodic, typically unilateral, discomfort with pain-free intervals. The discomfort is triggered, in many cases, by mouth movements. The disease is often recurrent and with time may become unremitting – 12% of cases in this series were euthanased as a consequence of the condition. Sensitisation of trigeminal nerve endings as a consequence of oral disease or tooth eruption appears to be an important factor in the aetiology – 63% of cases had a history of oral lesions and at least 16% experienced their first sign of discomfort during eruption of permanent teeth. External factors can also influence the disease as FOPS events could be directly linked to a situation causing anxiety in 20% of cats. FOPS can be resistant to traditional analgesics and in some cases successful management required anti-convulsants with an analgesic effect.


title: Cathepsin B & L Are Not Required for Ebola Virus Replication

text: Ebola virus (EBOV), family Filoviridae, emerged in 1976 on the African continent. Since then it caused several outbreaks of viral hemorrhagic fever in humans with case fatality rates up to 90% and remains a serious Public Health concern and biothreat pathogen. The most pathogenic and best-studied species is Zaire ebolavirus (ZEBOV). EBOV encodes one viral surface glycoprotein (GP), which is essential for replication, a determinant of pathogenicity and an important immunogen. GP mediates viral entry through interaction with cellular surface molecules, which results in the uptake of virus particles via macropinocytosis. Later in this pathway endosomal acidification activates the cysteine proteases Cathepsin B and L (CatB, CatL), which have been shown to cleave ZEBOV-GP leading to subsequent exposure of the putative receptor-binding and fusion domain and productive infection. We studied the effect of CatB and CatL on in vitro and in vivo replication of EBOV. Similar to previous findings, our results show an effect of CatB, but not CatL, on ZEBOV entry into cultured cells. Interestingly, cell entry by other EBOV species (Bundibugyo, Côte d'Ivoire, Reston and Sudan ebolavirus) was independent of CatB or CatL as was EBOV replication in general. To investigate whether CatB and CatL have a role in vivo during infection, we utilized the mouse model for ZEBOV. Wild-type (control), catB(−/−) and catL(−/−) mice were equally susceptible to lethal challenge with mouse-adapted ZEBOV with no difference in virus replication and time to death. In conclusion, our results show that CatB and CatL activity is not required for EBOV replication. Furthermore, EBOV glycoprotein cleavage seems to be mediated by an array of proteases making targeted therapeutic approaches difficult.


Imported Wuhan Coronavirus Infection: Is there any Correlation with Number of Immigrants from Endemic Area and Period after the First Outbreak?


title: Chlamydia trachomatis Co-opts GBF1 and CERT to Acquire Host Sphingomyelin for Distinct Roles during Intracellular Development

text: The obligate intracellular pathogen Chlamydia trachomatis replicates within a membrane-bound inclusion that acquires host sphingomyelin (SM), a process that is essential for replication as well as inclusion biogenesis. Previous studies demonstrate that SM is acquired by a Brefeldin A (BFA)-sensitive vesicular trafficking pathway, although paradoxically, this pathway is dispensable for bacterial replication. This finding suggests that other lipid transport mechanisms are involved in the acquisition of host SM. In this work, we interrogated the role of specific components of BFA-sensitive and BFA-insensitive lipid trafficking pathways to define their contribution in SM acquisition during infection. We found that C. trachomatis hijacks components of both vesicular and non-vesicular lipid trafficking pathways for SM acquisition but that the SM obtained from these separate pathways is being utilized by the pathogen in different ways. We show that C. trachomatis selectively co-opts only one of the three known BFA targets, GBF1, a regulator of Arf1-dependent vesicular trafficking within the early secretory pathway for vesicle-mediated SM acquisition. The Arf1/GBF1-dependent pathway of SM acquisition is essential for inclusion membrane growth and stability but is not required for bacterial replication. In contrast, we show that C. trachomatis co-opts CERT, a lipid transfer protein that is a key component in non-vesicular ER to trans-Golgi trafficking of ceramide (the precursor for SM), for C. trachomatis replication. We demonstrate that C. trachomatis recruits CERT, its ER binding partner, VAP-A, and SM synthases, SMS1 and SMS2, to the inclusion and propose that these proteins establish an on-site SM biosynthetic factory at or near the inclusion. We hypothesize that SM acquired by CERT-dependent transport of ceramide and subsequent conversion to SM is necessary for C. trachomatis replication whereas SM acquired by the GBF1-dependent pathway is essential for inclusion growth and stability. Our results reveal a novel mechanism by which an intracellular pathogen redirects SM biosynthesis to its replicative niche.


title: Improving air quality in high-density cities by understanding the relationship between air pollutant dispersion and urban morphologies

text: Abstract In high-density megacities, air pollution has a higher impact on public health than cities of lower population density. Apart from higher pollution emissions due to human activities in densely populated street canyons, stagnated air flow due to closely packed tall buildings means lower dispersion potential. The coupled result leads to frequent reports of high air pollution indexes at street-side stations in Hong Kong. High-density urban morphologies need to be carefully designed to lessen the ill effects of high density urban living. This study addresses the knowledge-gap between planning and design principles and air pollution dispersion potentials in high density cities. The air ventilation assessment for projects in high-density Hong Kong is advanced to include air pollutant dispersion issues. The methods in this study are CFD simulation and parametric study. The SST κ–ω model is adopted after balancing the accuracy and computational cost in the comparative study. Urban-scale parametric studies are conducted to clarify the effects of urban permeability and building geometries on air pollution dispersion, for both the outdoor pedestrian environment and the indoor environment in the roadside buildings. Given the finite land resources in high-density cities and the numerous planning and design restrictions for development projects, the effectiveness of mitigation strategies is evaluated to optimize the benefits. A real urban case study is finally conducted to demonstrate that the suggested design principles from the parametric study are feasible in the practical high density urban design.


Co-infection of Influenza B Virus and SARS-CoV-2: A Case Report from Taiwan


COVID-19 : n’oublions pas l’Afrique !


title: Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past

text: Abstract Coronavirus disease 2019 (COVID-19) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus strain disease, has recently emerged in China and rapidly spread worldwide. This novel strain is highly transmittable and severe disease has been reported in up to 16% of hospitalized cases. More than 600,000 cases have been confirmed and the number of deaths is constantly increasing. COVID-19 hospitalized patients, especially those suffering from severe respiratory or systemic manifestations, fall under the spectrum of the acutely ill medical population, which is at increased venous thromboembolism risk. Thrombotic complications seem to emerge as an important issue in patients infected with COVID-19. Preliminary reports on COVID-19 patients’ clinical and laboratory findings include thrombocytopenia, elevated D-dimer, prolonged prothrombin time, and disseminated intravascular coagulation. As the pandemic is spreading and the whole picture is yet unknown, we highlight the importance of coagulation disorders in COVID-19 infected patients and review relevant data of previous coronavirus epidemics caused by the severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and the Middle East Respiratory Syndrome coronavirus (MERS-CoV).


docid: nskewteb

title: Optimal policies for control of the novel coronavirus disease (COVID-19) outbreak

text: Understanding the early transmission dynamics of diseases and estimating the effectiveness of control policies play inevitable roles in the prevention of epidemic diseases. To this end, this paper is concerned with the design of optimal control strategies for the novel coronavirus disease (COVID-19). A mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission based on Wuhan's data is considered. To solve the problem effectively and efficiently, a multi-objective genetic algorithm is proposed to achieve high-quality schedules for various factors including contact rate and transition rate of symptomatic infected individuals to the quarantined infected class. By changing these factors, two optimal policies are successfully designed. This study has two main scientific contributions that are: (1) This is pioneer research that proposes policies regarding COVID-19, (2) This is also the first research that addresses COVID-19 and considers its economic consequences through a multi-objective evolutionary algorithm. Numerical simulations conspicuously demonstrate that by applying the proposed optimal policies, governments could find useful and practical ways for control of the disease.


Tuberculous sarcoidosis: Is it a separate entity?


title: The occurrence of Chlamydia spp. in pigs with and without clinical disease

text: BACKGROUND: Within the genera Chlamydia, the development of refined diagnostic techniques has allowed the identification of four species that are capable of infecting pigs. The epidemiology, clinical, and zoonotic impacts of these species are however largely unknown. The study aimed to investigate the presence of Chlamydia spp. in the intestines of growing pigs and in conjunctival swabs from finisher pigs, and relate the findings to clinical signs. RESULTS: By histology, 20 of 48 pigs had intestinal lesions that may be consistent with chlamydial infection. By PCR, forty-six of the pigs were positive whereas two samples were inhibited. Sequencing of 19 DNA extracts identified these as Chlamydia suis. By immunohistochemistry, 32 of 44 samples were positive and a significant relationship was detected between macroscopically visible intestinal lesions and a high degree of infection. By real-time PCR, a significant difference was detected between pigs with and without conjunctivitis when a Ct value of 36 was employed but not when a Ct value of 38 was employed. CONCLUSIONS: Chlamydia suis was demonstrated in most samples and overall, no correlation to clinical signs was detected. However, a correlation was noted between samples with a high degree of infection and the presence of clinical signs. It is possible, that the intensive pig production systems studied might predispose for the transmission and maintenance of the infection thus increasing the infectious load and the risk for disease in the pig.


title: Global Uncertainties and Portfolio Flow Dynamics of the BRICS Countries

text: Abstract This paper investigates the dynamics of bond and stock market capital flows to BRICS countries under uncertainties such as global economic policy uncertainty and the US trade policy uncertainty. We use a time-varying Granger causality framework over the January 2008-November 2019 period to analyze the predictive power of uncertainties on capital flows in the form of bond and equity. The results show that the effects are heterogeneous across countries and stronger during the Global Financial Crisis period and post-2018 period while it lost its significance in the subsequent period. The negative influence of uncertainties on capital flows directed to BRICS countries is also evident in the results of non-parametric time-varying panel models. Overall, it is thought that the heterogeneous structure of the causality between uncertainty and portfolio flows into BRICS may present portfolio diversification benefits for global investors.


docid: izexdggd

title: Covid-19 infection and mortality: a physiologist’s perspective enlightening clinical features and plausible interventional strategies


title: Innate Immune Priming by cGAS as a Preparatory Countermeasure Against RNA Virus Infection

text: The detection of nucleic acids by pattern recognition receptors is an ancient and conserved component of the innate immune system. Notably, RNA virus genomes are sensed by mammalian cytosolic RIG-I–like receptors, thereby activating interferon-stimulated gene (ISG) expression to restrict viral replication. However, recent evidence indicates that the cGAS-STING DNA sensing pathway also protects against RNA viruses. So far, the mechanisms responsible for DNA sensing of RNA viruses, which replicate without known DNA intermediates, remain unclear. By using cGAS gene knockout and reconstitution in human and mouse cell cultures, we discovered that DNA sensing and cGAMP synthase activities are required for cGAS-mediated restriction of vesicular stomatitis virus and Sindbis virus. The level of cGAMP produced in response to RNA virus infection was below the threshold of detection, suggesting that only transient and/or low levels of cGAMP are produced during RNA virus infections. To clarify the DNA ligands that activate cGAS activity, we confirmed that cGAS binds mitochondrial DNA in the cytosol of both uninfected and infected cells; however, the amount of cGAS-associated mitochondrial DNA did not change in response to virus infection. Rather, a variety of pre-existing cytosolic DNAs, including mitochondrial DNA and endogenous cDNAs, may serve as stimuli for basal cGAS activation. Importantly, cGAS knockout and reconstitution experiments demonstrated that cGAS drives low-level ISG expression at steady state. We propose that cGAS-STING restricts RNA viruses by promoting a preparatory immune activation state within cells, likely primed by endogenous cellular DNA ligands. Many medically important RNA viruses are restricted by the cGAS-STING DNA-sensing pathway of innate immune activation. Since these viruses replicate without DNA intermediates, it is unclear what DNA ligand(s) are responsible for triggering this pathway. We show here that cGAS’s DNA binding and signaling activities are required for RNA virus restriction, similar to the mechanisms by which it restricts DNA viruses. Furthermore, we confirmed that cGAS continuously binds host DNA, which was unaffected by RNA virus infection. Finally, cGAS expression correlated with the low-level expression of interferon-stimulated genes in uninfected cells, both in vitro and in vivo. We propose that cGAS-mediated sensing of endogenous DNA ligands contributes to RNA virus restriction by establishing a baseline of innate immune activation.


Effects of education on harm-reduction programmes


docid: yawwtyxg

title: Addition of poly (propylene glycol) to multiblock copolymer to optimize siRNA delivery

text: Previous studies have examined different strategies for siRNA delivery with varying degrees of success. These include use of viral vectors, cationic liposomes, and polymers. Several copolymers were designed and synthesized based on blocks of poly(ethylene glycol) PEG, poly(propylene glycol) PPG, and poly(l-lysine). These were designated as P1, P2, and P3. We studied the copolymer self-assembly, siRNA binding, particle size, surface potential, architecture of the complexes, and siRNA delivery. Silencing of GFP using copolymer P3 to deliver GFP-specific siRNA to Neuro-2a cells expressing GFP was almost as effective as using Lipofectamine 2000, with minimal cytotoxicity. Thus, we have provided a new copolymer platform for siRNA delivery that we can continue to modify for improved delivery of siRNA in vitro and eventually in vivo.


title: Prenatal Versus Postnatal Tobacco Smoke Exposure and Intensive Care Use in Children Hospitalized With Bronchiolitis

text: Abstract Objective Among children hospitalized with bronchiolitis, we examined the associations between in utero exposure to maternal cigarette smoking, postnatal tobacco smoke exposure, and risk of admission to the intensive care unit (ICU). Methods We performed a 16-center, prospective cohort study of hospitalized children aged <2 years with a physician admitting diagnosis of bronchiolitis. For 3 consecutive years, from November 1, 2007 until March 31, 2010, site teams collected data from participating families, including information about prenatal maternal smoking and postnatal tobacco exposure. Analyses used chi-square, Fisher's exact, and Kruskal-Wallis tests and multivariable logistic regression. Results Among 2207 enrolled children, 216 (10%) had isolated in utero exposure to maternal smoking, 168 (8%) had isolated postnatal tobacco exposure, and 115 (5%) experienced both. Adjusting for age, sex, race, birth weight, viral etiology, apnea, initial severity of retractions, initial oxygen saturation, oral intake, and postnatal tobacco exposure, children with in utero exposure to maternal smoking had greater odds of being admitted to the ICU (adjusted odds ratio [aOR] 1.51, 95% confidence interval [CI] 1.14–2.00). Among children with in utero exposure to maternal smoking, those with additional postnatal tobacco exposure had a greater likelihood of ICU admission (aOR 1.95, 95% CI 1.13–3.37) compared to children without postnatal tobacco smoke exposure (aOR 1.47, 95% CI 1.05–2.04). Conclusions Maternal cigarette smoking during pregnancy puts children hospitalized with bronchiolitis at significantly higher risk of intensive care use. Postnatal tobacco smoke exposure may exacerbate this risk. Health care providers should incorporate this information into counseling messages.


title: Towards a small animal model for hepatitis C

text: Hepatitis C virus (HCV) causes chronic liver disease and affects an estimated 3% of the world's population. Options for the prevention or therapy of HCV infection are limited; there is no vaccine and the nonspecific, interferon-based treatments now in use are frequently ineffective and have significant side effects. A small-animal model for HCV infection would significantly expedite antiviral compound development and preclinical testing, as well as open new avenues to decipher the mechanisms that underlie viral pathogenesis. The natural species tropism of HCV is, however, limited to humans and chimpanzees. Here, we discuss the prospects of developing a mouse model for HCV infection, taking into consideration recent results on HCV entry and replication, and new prospects in xenotransplantation biology. We highlight three independent, but possibly complementary, approaches towards overcoming current species barriers and generating a small-animal model for HCV pathogenesis.


title: Dynamic relationship between air transport demand and economic growth in the United States: A new look

text: Abstract This paper examines the short- and long-run effects of economic growth and market shocks (e.g., 9/11 terrorist attacks, Iraq war, SARS epidemic, and 2008 financial crisis) on air passenger and freight services using an autoregressive distributed lag (ARDL) approach to cointegration. Results show that, in the long-run, both air passenger and freight services tend to increase with economic growth. In the short-run, however, only air passenger service is responsive to economic growth. Finally, only the 9/11 terrorist attacks and the SARS have detrimental effects on air passenger demand both in the short- and long-run, and in the long-run, respectively. However, these market shocks are found to have little impact on air freight demand.


title: Systems vaccinology and big data in the vaccine development chain

text: Systems vaccinology has proven a fascinating development in the last decade. Where traditionally vaccine development has been dominated by trial and error, systems vaccinology is a tool that provides novel and comprehensive understanding if properly used. Data sets retrieved from systems‐based studies endorse rational design and effective development of safe and efficacious vaccines. In this review we first describe different omics‐techniques that form the pillars of systems vaccinology. In the second part, the application of systems vaccinology in the different stages of vaccine development is described. Overall, this review shows that systems vaccinology has become an important tool anywhere in the vaccine development chain.


title: Role of lipid rafts in porcine reproductive and respiratory syndrome virus infection in MARC-145 cells

text: Abstract Lipid rafts play an important role in the life cycle of many viruses. Cholesterol is a critical structural component of lipid rafts. Although the porcine reproductive and respiratory syndrome virus (PRRSV) has restricted cell tropism for cells of the monocyte/macrophage lineage, a non-macrophage cell MARC-145 was susceptible to PRRSV because of the expression of virus receptor CD163 on the cell surface, therefore MARC-145 cells is used as model cell for PRRSV studies. In order to determine if cholesterol is involved in PRRSV infection in MARC-145 cells, we used three pharmacological agents: methyl-β cyclodextrin (MβCD), mevinolin, and filipin complex to deplete cholesterol in MARC-145. Although these agents act by different mechanisms, they all significantly inhibited PRRSV infection. The inhibition could be prevented by addition of exogenous cholesterol. Cell membrane cholesterol depletion after virus infection had no effect on PRRSV production and cholesterol depletion pre-infection did not reduce the virus attachment, suggesting cholesterol is involved in virus entry. Further results showed that cholesterol depletion did not change expression levels of the PRRSV receptor CD163 in MARC-145, had no effect on clathrin-mediated endocytosis, but disturbed lipid-raft-dependent endocytosis. Collectively, these studies suggest that cholesterol is critical for PRRSV entry, which is likely to be mediated by a lipid-raft-dependent pathway.


title: Successful therapeutic management of canine Isosporosis in puppies

text: Four labrador male puppies were confirmed for the Isospora spp infection by direct smear and flotation method following complains of anorexia, haematemesis and haematochezia. The puppies were treated with trimethoprime and sulphamethoxazole @ 40 mg/kg body weight in combination with metronidazole @ 10 mg/kg body weight twice daily for 5 days which was supported with fluid therapy, aniemetics and plasma expanders. All the animals showed completed clinical recovery along with clearing of faecal oocyst.


title: Recent trends in click chemistry as a promising technology for virus-related research

text: Abstract Click chemistry involves reactions that were originally introduced and used in organic chemistry to generate substances by joining small units together with heteroatom linkages (C-X-C). Over the last few decades, click chemistry has been widely used in virus-related research. Using click chemistry, the virus particle as well as viral protein and nucleic acids can be labeled. Subsequently, the labeled virions or molecules can be tracked in real time. Here, we reviewed the recent applications of click reactions in virus-related research, including viral tracking, the design of antiviral agents, the diagnosis of viral infection, and virus-based delivery systems. This review provides an overview of the general principles and applications of click chemistry in virus-related research.


title: Successful recovery from severe COVID‐19 pneumonia after kidney transplantation: The interplay between immunosuppression and novel therapy including tocilizumab

text: Although immunosuppressed patients may be more prone to SARS‐CoV‐2 infection with atypical presentation, long‐term immunosuppression therapy may provide some sort of protection for severe clinical complications of COVID‐19. The interaction between immunosuppression and new antiviral drugs in the treatment of transplanted patients contracting COVID‐19 has not yet been fully investigated. Moreover, data regarding the optimal management of these patients are still very limited. We report a case of the successful recovery from severe COVID‐19 of a kidney‐transplanted patient treated with hydroxychloroquine, lopinavir/ritonavir, steroid, and tocilizumab.


title: Beyond Mfold: Recent advances in RNA bioinformatics

text: Abstract Computational analysis of RNA secondary structure is a classical field of biosequence analysis, which has recently gained momentum due to the manyfold regulatory functions of RNA that have become apparent. We present five recent computational approaches that address the problems of synoptic folding space analysis, pseudoknot prediction, structure alignment, comparative structure prediction, and miRNA target prediction. All these programs are in current use and are available via the Bielefeld Bioinformatics Server at http://bibiserv.techfak.uni-bielefeld.de.


title: Video for Active and Remote Learning

text: The outbreak of COVID-19 has caused the canceling of in-person lectures on a massive scale. Rapid movement of education to online platforms will eventually lead to innovations in remote education. At the moment, however, instructors lack guidance. This short article describes approaches for producing video for remote and active learning.


title: Emerging Influenza D Virus Threat: What We Know so Far!

text: Influenza viruses, since time immemorial, have been the major respiratory pathogen known to infect a wide variety of animals, birds and reptiles with established lineages. They belong to the family Orthomyxoviridae and cause acute respiratory illness often during local outbreaks or seasonal epidemics and occasionally during pandemics. Recent studies have identified a new genus within the Orthomyxoviridae family. This newly identified pathogen, D/swine/Oklahoma/1334/2011 (D/OK), first identified in pigs with influenza-like illness was classified as the influenza D virus (IDV) which is distantly related to the previously characterized human influenza C virus. Several other back-to-back studies soon suggested cattle as the natural reservoir and possible involvement of IDV in the bovine respiratory disease complex was established. Not much is known about its likelihood to cause disease in humans, but it definitely poses a potential threat as an emerging pathogen in cattle-workers. Here, we review the evolution, epidemiology, virology and pathobiology of influenza D virus and the possibility of transmission among various hosts and potential to cause human disease.


title: Clinical ocular toxoplasmosis in neonatal kittens

text: ABSTRACT: OBJECTIVE: To describe ocular findings in kittens with congenital or early neonatal infection by Toxoplasma gondii and to determine if there are detectable differences in disease caused by three strains. ANIMALS STUDIED: Six adult female cats and the offspring from seven litters. METHODS: Four kittens from uninfected specific pathogen‐free (SPF) queens and 21 kittens from SPF queens inoculated at various times late in gestation with Mozart, Maggie, or ME‐49 strain of T. gondii were used. Ocular examinations were performed on queens prior to and after delivery, and on kittens weekly to bi‐weekly for up to 27 weeks. Whole blood for serology was collected from all kittens at 5½ to 8 weeks of age and again at 12 weeks of age or later. RESULTS: No kittens from noninfected queens developed ocular lesions or antibody to T. gondii. Three of the 24 kittens from infected queens died or were euthanized early in the study. Chorioretinitis was detected in 15 of 21 living kittens from infected queens. Two developed concurrent anterior uveitis that resolved within 1 week. Posterior segment lesions varied ophthalmoscopically between strains. Of 21 kittens from T. gondii‐infected queens, six developed positive antibody titers to T. gondii during the study. All seropositive kittens were born to queens infected with Mozart strain of T. gondii. CONCLUSION: Results of this study suggest that ocular toxoplasmosis can occur without other evidence of clinical illness in kittens infected in utero or in the neonatal period, and that T. gondii strains may have varying degrees of ocular pathogenicity in cats.