title: Emerging infectious disease, the household built environment characteristics, and urban planning: Evidence on avian influenza in Vietnam

text: Abstract Recent concerns with pandemic outbreaks of human disease and their origins in animal populations have ignited concerns regarding connections between Emerging Infectious Diseases (EID) and development. As disasters, health, and infectious disease become part of planning concern (Matthew & McDonald, 2007), greater focus on household infrastructure and EID disease outbreaks among poultry is warranted. Following Spencer (2013), this study examines the relationship between the mix of household-scale water supplies, sanitation systems, and construction materials, and Highly Pathogenic Avian Influenza (HPAI) among poultry in a developing country: Vietnam. Findings of our multivariate logistic regressions suggest that a non-linear, Kuznets-shaped urban transition (Spencer, 2013) has an independent effect on the outbreak of HPAI, especially as it relates to household-level sanitation infrastructure. We conclude that the Kuznets-shape development of household infrastructure characteristics in Vietnam play a significant role in explaining where poultry outbreaks occur. Using secondary data from the Census of Population and Housing, and the Agricultural Census at the District and Commune levels for the country of Vietnam, we performed logistic regression to test the relationship between outbreaks of HPAI in poultry and newly-developed “coherence indices” (Spencer, 2013) of household water supply, sanitation, and construction materials that measure nonlinear, transitional development. Results show that district-scale coherence indices are negatively and independently correlated with HPAI outbreaks, especially for sanitation. Findings also suggest that community-scale coherence of urban infrastructures is a powerful tool for predicting where HPAI poultry outbreaks are likely to occur, thereby providing health planners new tools for efficient surveillance.


title: Ability of Recombinant Human Catalase to Suppress Inflammation of the Murine Lung Induced by Influenza A

text: Influenza A virus pandemics and emerging antiviral resistance highlight the urgent need for novel generic pharmacological strategies that reduce both viral replication and inflammation of the lung. We have previously investigated the therapeutic efficacy of recombinant human catalase (rhCAT) against viral pneumonia in mice, but the protection mechanisms involved were not explored. In the present study, we have performed a more in-depth analysis covering survival, lung inflammation, immune cell responses, production of cytokines, and inflammation signaling pathways in mice. Male imprinting control region mice were infected intranasally with high pathogenicity (H1N1) influenza A virus followed by treatment with recombinant human catalase. The administration of rhCAT resulted in a significant reduction in inflammatory cell infiltration (e.g., macrophages and neutrophils), inflammatory cytokine levels (e.g., IL-2, IL-6, TNF-α, IFN-γ), the level of the intercellular adhesion molecule 1 chemokine and the mRNA levels of toll-like receptors TLR-4, TLR-7, and NF-κB, as well as partially maintaining the activity of the antioxidant enzymes system. These findings indicated that rhCAT might play a key protective role in viral pneumonia of mice via suppression of inflammatory immune responses.


title: Contact among healthcare workers in the hospital setting: developing the evidence base for innovative approaches to infection control

text: BACKGROUND: Nosocomial, or healthcare-associated infections (HAI), exact a high medical and financial toll on patients, healthcare workers, caretakers, and the health system. Interpersonal contact patterns play a large role in infectious disease spread, but little is known about the relationship between health care workers’ (HCW) movements and contact patterns within a heath care facility and HAI. Quantitatively capturing these patterns will aid in understanding the dynamics of HAI and may lead to more targeted and effective control strategies in the hospital setting. METHODS: Staff at 3 urban university-based tertiary care hospitals in Canada completed a detailed questionnaire on demographics, interpersonal contacts, in-hospital movement, and infection prevention and control practices. Staff were divided into categories of administrative/support, nurses, physicians, and “Other HCWs” - a fourth distinct category, which excludes physicians and nurses. Using quantitative network modeling tools, we constructed the resulting HCW “co-location network” to illustrate contacts among different occupations and with locations in hospital settings. RESULTS: Among 3048 respondents (response rate 38%) an average of 3.79, 3.69 and 3.88 floors were visited by each HCW each week in the 3 hospitals, with a standard deviation of 2.63, 1.74 and 2.08, respectively. Physicians reported the highest rate of direct patient contacts (> 20 patients/day) but the lowest rate of contacts with other HCWs; nurses had the most extended (> 20 min) periods of direct patient contact. “Other HCWs” had the most direct daily contact with all other HCWs. Physicians also reported significantly more locations visited per week than nurses, other HCW, or administrators; nurses visited the fewest. Public spaces such as the cafeteria had the most staff visits per week, but the least mean hours spent per visit. Inpatient settings had significantly more HCW interactions per week than outpatient settings. CONCLUSIONS: HCW contact patterns and spatial movement demonstrate significant heterogeneity by occupation. Control strategies that address this diversity among health care workers may be more effective than “one-strategy-fits-all” HAI prevention and control programs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3093-x) contains supplementary material, which is available to authorized users.


title: Middle East respiratory syndrome coronavirus not detected in children hospitalized with acute respiratory illness in Amman, Jordan, March 2010 to September 2012

text: Hospitalized children < 2 years of age in Amman, Jordan, admitted for fever and/or respiratory symptoms, were tested for Middle East respiratory syndrome coronavirus (MERS-CoV): MERS-CoV by real-time RT-PCR (rRT-PCR). This was a prospective year-round viral surveillance study in children <2 years of age admitted with acute respiratory symptoms and/or fever from March 2010 to September 2012 and enrolled from a government-run hospital, Al-Bashir in Amman, Jordan. Clinical and demographic data, including antibiotic use, were collected. Combined nasal/throat swabs were collected, aliquoted, and frozen at −80°C. Specimen aliquots were shipped to Vanderbilt University and the Centers for Disease Control and Prevention (CDC), and tested by rRT-PCR for MERS-CoV. Of the 2433 subjects enrolled from 16 March 2010 to 10 September 2012, 2427 subjects had viral testing and clinical data. Of 1898 specimens prospectively tested for other viruses between 16 March 2010 and 18 March 2012, 474 samples did not have other common respiratory viruses detected. These samples were tested at CDC for MERS-CoV and all were negative by rRT-PCR for MERS-CoV. Of the remaining 531 samples, collected from 19 March 2012 to 10 September 2012 and tested at Vanderbilt, none were positive for MERS-CoV. Our negative findings from a large sample of young Jordanian children hospitalized with fever and/or respiratory symptoms suggest that MERS-CoV was not widely circulating in Amman, Jordan, during the 30-month period of prospective, active surveillance occurring before and after the first documented MERS-CoV outbreak in the Middle East region.


title: Clinical characteristics and risk assessment of newborns born to mothers with COVID-19

text: Abstract Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is causing an outbreak of pneumonia in Wuhan, Hubei Province, China, and other international areas. Objective Here, we report the clinical characteristics of the newborns delivered by SARS-CoV-2 infected pregnant women. Methods We prospectively collected and analyzed the clinical features, laboratory data and outcomes of 7 newborns delivered by SARS-CoV-2 infected pregnant women in Zhongnan Hospital of Wuhan University during January 20 to January 29, 2020. Results 4 of the 7 newborns were late preterm with gestational age between 36 weeks and 37 weeks, and the other 3 were full-term infants. The average birth weight was 2096 ± 660 g. All newborns were born without asphyxia. 2 premature infants performed mild grunting after birth, but relieved rapidly with non-invasive continuous positive airway pressure (nCPAP) ventilation. 3 cases had chest X-ray, 1 was normal and 2 who were supported by nCPAP presented mild neonatal respiratory distress syndrome (NRDS). Samples of pharyngeal swab in 6 cases, amniotic fluid and umbilical cord blood in 4 cases were tested by qRT-PCR, and there was no positive result of SARS-CoV-2 nucleic acid in all cases. Conclusions The current data show that the infection of SARS-CoV-2 in late pregnant women does not cause adverse outcomes in their newborns, however, it is necessary to separate newborns from mothers immediately to avoid the potential threats.


title: Characterization of the inhibitory effect of an extract of Prunella vulgaris on Ebola virus glycoprotein (GP)-mediated virus entry and infection

text: Abstract Currently, no approved antiviral therapeutic is available for treatment or prevention of Ebola virus (EBOV) infection. In this study, we characterized an EBOV-glycoprotein (GP) pseudotyped HIV-1-based vector system in different cell cultures, including human umbilical vein endothelial cells (HUVECs) and human macrophages, for the screening of anti-EBOV-GP agent(s). Based on this system, we demonstrated that an aqueous extract (CHPV) from the Chinese herb Prunella vulgaris displayed a potent inhibitory effect on EBOV-GP pseudotyped virus (EBOV-GP-V)-mediated infection in various cell lines, including HUVEC and macrophage. In addition, our results indicated that CHPV was able to block an eGFP-expressing Zaire ebola virus (eGFP-ZEBOV) infection in VeroE6 cells. The anti-EBOV activity of CHPV was exhibited in a dose-dependent manner. At a 12.5 μg/ml concentration, the CHPV showed a greater than 80% inhibition of EBOV-GP-V and eGFP-EBOV infections. Likewise, our studies suggested that the inhibitory effect of CHPV occurred by binding directly to EBOV-GP-Vs and blocking the early viral events. Interestingly, our results have shown that CHPV was able to enhance the anti-EBOV activity of the monoclonal antibody MAb 2G4 against EBOV-GP. Overall, this study provides evidence that CHPV has anti-EBOV activity and may be developed as a novel antiviral approach against EBOV infection.


title: Economic impact of government interventions during the COVID-19 pandemic: International evidence from financial markets

text: The outbreak of COVID-19 pandemic came as a rare, unprecedented event and governments around the globe scrambled with emergency actions including social distancing measures, public awareness programs, testing and quarantining policies, and income support packages. In this paper, we examine the expected economic impact of government actions by analyzing the effect of such actions on stock market returns. Using daily data from January 22 to April 17, 2020 from 77 countries, we find announcements of government social distancing measures have a direct negative effect on stock market returns due to their adverse effect on economic activity, while an indirect positive effect through the reduction in COVID-19 confirmed cases. Government announcements regarding public awareness programs, testing and quarantining policies, and income support packages largely result in positive market returns. Our findings have important policy implications, primarily by showing that government social distancing measures have both positive and negative economic impact.


title: Practical considerations for performing regional anesthesia: lessons learned from the COVID-19 pandemic

text: Coronavirus disease (COVID-19) was declared a pandemic by the World Health Organization on 11 March 2020 because of its rapid worldwide spread. In the operating room, as part of hospital outbreak response measures, anesthesiologists are required to have heightened precautions and tailor anesthetic practices to individual patients. In particular, by minimizing the many aerosol-generating procedures performed during general anesthesia, anesthesiologists can reduce exposure to patients’ respiratory secretions and the risk of perioperative viral transmission to healthcare workers and other patients. To avoid any airway manipulation, regional anesthesia should be considered whenever surgery is planned for a suspect or confirmed COVID-19 patient or any patient who poses an infection risk. Regional anesthesia has benefits of preservation of respiratory function, avoidance of aerosolization and hence viral transmission. This article explores the practical considerations and recommended measures for performing regional anesthesia in this group of patients, focusing on control measures geared towards ensuring patient and staff safety, equipment protection, and infection prevention. By doing so, we hope to address an issue that may have downstream implications in the way we practice infection control in anesthesia, with particular relevance to this new era of emerging infectious diseases and novel pathogens. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not the first, and certainly will not be the last novel virus that will lead to worldwide outbreaks. Having a well thought out regional anesthesia plan to manage these patients in this new normal will ensure the best possible outcome for both the patient and the perioperative management team.


Reply to Rheumatologists’ perspective on coronavirus disease 19: is heparin the dark horse for COVID-19?


title: Urticarial vasculitis in COVID‐19 infection: a vasculopathy‐related symptom?

text: The novel Coronavirus disease (COVID‐19) outbreak has been recently declared a pandemic by the World Health Organization (WHO), being Italy and Spain the worst‐hit European countries. Although the main clinical picture consists of fever and respiratory symptoms, an increasing number of studies have reported associated skin manifestations. Herein we present two patients with urticarial vasculitis arising in the context of COVID‐19 infection.


title: Origins and Evolution of the Global RNA Virome

text: Viruses with RNA genomes dominate the eukaryotic virome, reaching enormous diversity in animals and plants. The recent advances of metaviromics prompted us to perform a detailed phylogenomic reconstruction of the evolution of the dramatically expanded global RNA virome. The only universal gene among RNA viruses is the RNA-dependent RNA polymerase (RdRp). We developed an iterative computational procedure that alternates the RdRp phylogenetic tree construction with refinement of the underlying multiple sequence alignments. The resulting tree encompasses 4,617 RNA virus RdRps and consists of 5 major branches, 2 of which include positive-sense RNA viruses, 1 is a mix of positive-sense (+) RNA and double-stranded (ds) RNA viruses, and 2 consist of dsRNA and negative-sense (−) RNA viruses, respectively. This tree topology implies that dsRNA viruses evolved from +RNA viruses on at least two independent occasions, whereas -RNA viruses evolved from dsRNA viruses. Reconstruction of RNA virus evolution using the RdRp tree as the scaffold suggests that the last common ancestors of the major branches of +RNA viruses encoded only the RdRp and a single jelly-roll capsid protein. Subsequent evolution involved independent capture of additional genes, particularly, those encoding distinct RNA helicases, enabling replication of larger RNA genomes and facilitating virus genome expression and virus-host interactions. Phylogenomic analysis reveals extensive gene module exchange among diverse viruses and horizontal virus transfer between distantly related hosts. Although the network of evolutionary relationships within the RNA virome is bound to further expand, the present results call for a thorough reevaluation of the RNA virus taxonomy. The majority of the diverse viruses infecting eukaryotes have RNA genomes, including numerous human, animal, and plant pathogens. Recent advances of metagenomics have led to the discovery of many new groups of RNA viruses in a wide range of hosts. These findings enable a far more complete reconstruction of the evolution of RNA viruses than what was attainable previously. This reconstruction reveals the relationships between different Baltimore Classes of viruses and indicates extensive transfer of viruses between distantly related hosts, such as plants and animals. These results call for a major revision of the existing taxonomy of RNA viruses.


title: Think globally, act locally: Phylodynamic reconstruction of infectious bronchitis virus (IBV) QX genotype (GI-19 lineage) reveals different population dynamics and spreading patterns when evaluated on different epidemiological scales

text: Infectious bronchitis virus (IBV) represents one of the poultry industry major threats, particularly in high density producing countries. The emergence and spread of new IBV genotypes have frustrated the various disease control efforts implemented over time. Despite that, few comprehensive and large scale studies have been performed to understand the international and local spreading dynamics of this virus. In the present work, these phenomena were evaluated by implementing a Bayesian phylodynamic approach to reconstruct the epidemiological patterns and population history of the QX genotype (currently renamed GI-19 lineage), the most relevant IBV lineage of the Old-World. Our analysis, based on 807 partial S1 sequences of strains collected from 18 countries between 1993 and 2015, demonstrates that this genotype originated in China well before its first identification. After a prolonged local circulation, it started spreading to other European, Asian and Middle East countries in successive waves, which were mirrored by concomitant fluctuations in viral population size. Interestingly, the within-Europe spread was characterized by a higher estimated migration rate compared with the inter-continental one, potentially reflecting the closer geographic and economic relationships among these countries. Nevertheless, the colonization of new states by the GI-19 lineage appeared to occur mostly by single introduction events in both intra and inter-continental spread, likely because of epidemiological factor and health policy combination which seems to prevent the frequent introduction and mixing of different strains. On the other hand, the within Italy QX circulation reconstruction showed a much more intricate connection network among different locations, evidencing the difficulty in controlling IBV spread especially in highly densely poultry populated areas. The presence of several well supported epidemiological links among distantly related Italian regions testifies that animal transportation and indirect transmission routes rather than local airborne diffusion contribute to the QX success and persistence at local scale. Globally, the spreading dynamics and evolution of the QX genotype were reconstructed from its very origin to nowadays, demonstrating the need of more effective direct control measures, particularly within each country. Unfortunately, the incompleteness of available molecular epidemiology data represents an insurmountable limit which leaves many questions currently unsolved, thus highlighting the compulsoriness of a structured monitoring and data sharing system implementation.


title: Real-time Estimates in Early Detection of SARS

text: We propose a Bayesian statistical framework for estimating the reproduction number R early in an epidemic. This method allows for the yet-unrecorded secondary cases if the estimate is obtained before the epidemic has ended. We applied our approach to the severe acute respiratory syndrome (SARS) epidemic that started in February 2003 in Hong Kong. Temporal patterns of R estimated after 5, 10, and 20 days were similar. Ninety-five percent credible intervals narrowed when more data were available but stabilized after 10 days. Using simulation studies of SARS-like outbreaks, we have shown that the method may be used for early monitoring of the effect of control measures.


title: Electron Microscopy Analysis of Viral Morphogenesis

text: This chapter reviews the use of standard transmission electron microscopy (TEM) of plastic-embedded material, as well as protocols for the immunolabeling of cryosections, in the analysis of viral interactions with cells. It focuses particularly on the assembly of two types of enveloped viruses: (1) the beta herpesvirus—human cytomegalovirus (HCMV), and (2) the primate lentiviruses—the simian and human immunodeficiency viruses (SIV and HIV). The chapter discusses the ways EM is used to identify morphological features of the various stages in the assembly of virus particles, to distinguish immature and mature particles, or to analyze steps involved in the acquisition of lipid membranes by enveloped viruses. In addition, it demonstrates the way immunolabeling allows the quantification of viral components, even in individual virus particles, and comparisons between particles at different locations in the cell or at different stages in viral assembly. Together with the newly developed methods for electron tomography and correlative immunofluorescence studies and EM, huge potential exists to unravel more details about virus assembly in the near future.


title: Inhibition of SERPINe1 reduces rhabdoviral infections in zebrafish

text: Abstract While exploring the molecular mechanisms behind the fin hemorrhages that follow zebrafish (Danio rerio) early infection with viral haemorrhagic septicemia virus (VHSV), we discovered that most serpin (serine protease inhibitor) gene transcripts were upregulated, except those of serpine1. Surprisingly, only SERPINe1-derived 14-mer peptide and low molecular weight drugs targeting SERPINe1 (i.e. tannic acid, EGCG, tiplaxtinin) inhibited in vitro infections not only of VHSV, but also of other fish rhabdoviruses such as infectious hematopoietic necrosis virus (IHNV) and spring viremia carp virus (SVCV). While the mechanisms that inhibited rhabdoviral infections remain speculative, these and other results suggested that SERPINEe1-derived peptide specifically targeted viral infectivity rather than virions. Practical applications might be developed from these studies since preliminary evidences showed that tannic acid could be used to reduce VHSV-caused mortalities. These studies are an example of how the identification of host genes targeted by viral infections using microarrays might facilitate the identification of novel prevention drugs in aquaculture and illuminate viral infection mechanisms.


Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection during pregnancy: Report of two cases & review of the literature


title: Adult Cardiac Surgery and the COVID-19 Pandemic: Aggressive Infection Mitigation Strategies are Necessary in the Operating Room and Surgical Recovery

text: Abstract The COVID-19 pandemic necessitates aggressive infection mitigation strategies to reduce the risk to patients and healthcare providers. This document is intended to provide a framework for the adult cardiac surgeon to consider in this rapidly changing environment. Pre, intra, and post-operative detailed protective measures are outlined. These are guidance recommendations during a pandemic surge to be utilized for ALL patients while local COVID-19 disease burden remains elevated.


title: Emerging concepts in gastrointestinal aspects of HIV-1 pathogenesis and management

text: Abstract GASTROENTROLOGY 2001;120:607-621


title: Glutamine antagonist-mediated immune suppression decreases pathology but delays virus clearance in mice during nonfatal alphavirus encephalomyelitis

text: Abstract Infection of weanling C57BL/6 mice with the TE strain of Sindbis virus (SINV) causes nonfatal encephalomyelitis associated with hippocampal-based memory impairment that is partially prevented by treatment with 6-diazo-5-oxo-l-norleucine (DON), a glutamine antagonist (Potter et al., J Neurovirol 21:159, 2015). To determine the mechanism(s) of protection, lymph node and central nervous system (CNS) tissues from SINV-infected mice treated daily for 1 week with low (0.3mg/kg) or high (0.6mg/kg) dose DON were examined. DON treatment suppressed lymphocyte proliferation in cervical lymph nodes resulting in reduced CNS immune cell infiltration, inflammation, and cell death compared to untreated SINV-infected mice. Production of SINV-specific antibody and interferon-gamma were also impaired by DON treatment with a delay in virus clearance. Cessation of treatment allowed activation of the antiviral immune response and viral clearance, but revived CNS pathology, demonstrating the ability of the immune response to mediate both CNS damage and virus clearance.


title: Recomendaciones de consenso respecto al soporte respiratorio no invasivo en el paciente adulto con insuficiencia respiratoria aguda secundaria a infección por SARS-CoV-2()

text: Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus, that was first recognized in Wuhan, China, in December 2019. Currently, the World Health Organization (WHO) has defined the infection as a global pandemic and there is a health and social emergency for the management of this new infection. While most people with COVID-19 develop only mild or uncomplicated illness, approximately 14% develop severe disease that requires hospitalization and oxygen support, and 5% require admission to an intensive care unit. In severe cases, COVID-19 can be complicated by the acute respiratory distress syndrome (ARDS), sepsis and septic shock, and multiorgan failure. This consensus document has been prepared on evidence-informed guidelines developed by a multidisciplinary panel of health care providers from four Spanish scientific societies (Spanish Society of Intensive Care Medicine [SEMICYUC], Spanish Society of Pulmonologists [SEPAR], Spanish Society of Emergency [SEMES], Spanish Society of Anesthesiology, Reanimation, and Pain [SEDAR]) with experience in the clinical management of patients with COVID-19 and other viral infections, including SARS, as well as sepsis and ARDS. The document provides clinical recommendations for the noninvasive respiratory support (noninvasive ventilation, high flow oxygen therapy with nasal cannula) in any patient with suspected or confirmed presentation of COVID-19 with acute respiratory failure. This consensus guidance should serve as a foundation for optimized supportive care to ensure the best possible chance for survival and to allow for reliable comparison of investigational therapeutic interventions as part of randomized controlled trials.


title: Identification of Symptoms Prognostic of COVID-19 Severity: Multivariate Data Analysis of a Case Series in Henan Province

text: BACKGROUND: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19), has been declared a global pandemic. Identifying individuals whose infection can potentially become severe is critical to control the case fatality rate of COVID-19. However, knowledge of symptoms that are prognostic of COVID-19 severity is lacking. OBJECTIVE: The objective of our study was to identify symptoms prognostic of COVID-19 infection severity. METHODS: We analyzed documented symptoms, including fever, cough, fatigue, expectoration, sore throat, chest distress, headache, diarrhea, rhinorrhea, stuffed nose, nausea, vomiting, muscle or joint ache, shortness of breath, and their associations with disease severity using a case series, including 655 confirmed cases from January 23 to February 5, 2020 in Henan Province, China. We also analyzed the influence of individual characteristics, including age, gender, and comorbidities, on symptoms with prognostic value. RESULTS: Fatigue (95% CI 0.141 to 0.334, P<.001), expectoration (95% CI 0.107 to 0.305, P<.001) and stuffed nose (95% CI –0.499 to –0.082, P=.006) were identified as the prognostic symptoms of COVID-19 patients from the multivariate analysis. Fever occurred in 603/655 (92.1%) of the patients but was not associated with disease severity. Fatigue accounted for 184/655 (28.1%) of the patients and was linearly associated with infection severity with statistical significance. Expectoration occurred in 169/655 (25.8%) patients in the cohort and was the sole prognostic factor for patients with cardiovascular complications, including hypertension. Shortness of breath, chest distress, muscle or joint ache, and dry cough, which occurred in 33 (5%), 83 (12.7%), 78 (11.9%), and 276 (42.1%) of the 655 patients, respectively, were significantly enriched among patients classified as severe. Stuffed nose and nausea were associated with favorable disease severity, especially among male patients. More female than male patients were documented as having muscle or joint ache. Headache was most enriched in patents aged 15 to 39 years, followed by those aged 40 to 64 years, with statistical significance. CONCLUSIONS: Fatigue and expectoration are signs of severe COVID-19 infection. Shortness of breath, chest distress, muscle or joint ache, and dry cough are prevalent in severe patients. Expectoration is commonly present in older individuals and patients with cardiovascular disorders, including hypertension. Shortness of breath is prognostic of severe infection in male patients. Stuffed nose and nausea are favorable prognostic factors of severe infection, especially among male patients.


title: A resequencing pathogen microarray method for high-throughput molecular diagnosis of multiple etiologies associated with central nervous system infection

text: Central nervous system infection (CNSI) results in significant health and economic burdens worldwide, but the diversity of causative pathogens makes differential diagnosis very difficult. Although PCR and real-time fluorescent quantitative PCR (q-PCR) assays are widely applied for pathogen detection, they are generally optimized for the detection of a single or limited number of targets and are not suitable for the diagnosis of numerous CNSI agents. In this study, we describe the development of a resequencing pathogen microarray (RPM-IVDC4) method for the simultaneous detection of viruses, bacteria, fungi and parasites that cause CNSI. The test panel of this assay included more than 100 microorganism species across 45 genera and 30 families. The analytical specificity and sensitivity were examined using a panel of positive reference strains, and the clinical performance was evaluated using 432 clinical samples by comparing the results with q-PCR assays. Our results demonstrated good performance of the RPM-IVDC4 assay in terms of sensitivity, specificity and detection range, suggesting that the platform can be further developed for high-throughput CNSI diagnosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-017-3550-7) contains supplementary material, which is available to authorized users.


title: Pseudo acute myocardial infarction in a young COVID-19 patient

text: Abstract: A 29 year old man tested positive for COVID-19 and developed acute respiratory distress syndrome (ARDS). While mechanically ventilated, his electrocardiogram (EKG) showed inferior ST segment elevations, with normal serial cardiac troponin I and transthoracic echocardiograms. He was treated conservatively, with complete clinical recovery and resolution of his EKG abnormalities.


title: Broiler industry strategies for control of respiratory and enteric diseases

text: Abstract The commercial broiler industry is a modern day agricultural success due to popular consumer demand, healthy flocks, and least cost production. Preventive medicine is the key for economical control of disease in integrated broiler companies, and includes quarantine-eradication, controlled-exposure, and preventive feed medication. Respiratory and enteric diseases present a continuing, potential threat for economic loss. Most exotic and egg-transmitted poultry diseases have been controlled by reduction or eradication policies. Endemic diseases are controlled by mass vaccination and preventive feed medication. Improvements in genetics, housing, equipment, and disease surveillance has allowed continued improvements in disease prevention. Attention to detail and management of risk is crucial to industry success. With fast industry growth and market maturity of the broiler industry, new challenges have risen. These challenges include increased poultry house density, increasing economic pressures, changing industry attitudes, and increased governmental regulations that will strain the continued success of today's control strategies.


title: Minimally invasive lumbar decompression and removal of symptomatic Heterotopic bone formation after spinal fusion with rhBMP-2

text: Abstract We present a case of symptomatic heterotopic bone formation following revision of posterolateral lumbar fusion/instrumentation and “off-label” use of recombinant human bone morphogenetic protein-2 (rhBMP-2), treated successfully with the use of a minimally invasive tubular approach.


title: Lung ultrasonography for early management of patients with respiratory symptoms during COVID-19 pandemic

text: COVID-19 pandemic is representing a serious challenge to worldwide public health. Lung Ultrasonography (LUS) has been signaled as a potential useful tool in this pandemic contest either to intercept viral pneumonia or to foster alternative paths. LUS could be useful in determining early lung involvement suggestive or not of COVID-19 pneumonia and potentially plays a role in managing decisions for hospitalization in isolation or admission in general ward. In order to face pandemic, in a period in which a large number of emergency room accesses with suspicious symptoms are expected, physicians need a standardized ultrasonographic approach, fast educational processes in order to be able to recognize both suggestive and not suggestive echographic signs and shared algorithms for LUS role in early management of patients.


title: Infectious gastro-enteritis: an uncommon cause of diarrhoea in adult allogeneic and autologous stem cell transplant recipients

text: The incidence and aetiology of acute diarrhoea in 60 adult allogeneic or autologous stem cell transplant (SCT) recipients was determined in a prospective study. Stool specimens were obtained prior to SCT and on days +20, +40, +60 and +100 post transplant. Microbiological evaluation was performed for pathogenic bacteria, fungi, parasites and viruses. Forty-seven patients were evaluable of whom 31 had a total of 48 acute diarrhoeal episodes. Diarrhoea occurred in 79% of allogeneic and 47% of autologous SCT recipients (P < 0.05). intestinal infections were found in three of 48 (6%) diarrhoeal episodes. Clostridium difficile with positive toxin was cultured twice and one stool specimen was positive for cryptosporidium. Intestinal pathogens were identified in 13 out of 172 stool specimens from asymptomatic patients and included: rotavirus (4), adenovirus (3), C. difficile, toxin positive (2), and others (4). Graft-versus-host disease was confirmed by biopsy in two of 36 episodes of diarrhoea in allogeneic patients, and in three patients a relationship between reactivation of cytomegalovirus and diarrhoea was suspected. In 40 of 48 (83%) episodes of diarrhoea no clear aetiology could be found. Bone Marrow Transplantation (2000) 26, 299–303.


title: Roles and contributions of pharmacists in regulatory affairs at the Centers for Disease Control and Prevention for public health emergency preparedness and response

text: Abstract Objective To provide a general description of the roles and contributions of three pharmacists from the Regulatory Affairs program (RA) at the Centers for Disease Control and Prevention (CDC) who are involved in emergency preparedness and response activities, including the 2009 pandemic influenza A (H1N1) public health emergency. Setting Atlanta, GA. Practice description RA consists of a staff of nine members, three of whom are pharmacists. The mission of RA is to support CDC's preparedness and emergency response activities and to ensure regulatory compliance for critical medical countermeasures against potential threats from natural, chemical, biological, radiological, or nuclear events. Conclusion RA was well involved in the response to the H1N1 outbreak through numerous activities, such as submitting multiple Emergency Use Authorization (EUA) requests to the Food and Drug Administration, including those for medical countermeasures to be deployed from the Strategic National Stockpile, and developing the CDC EUA website (www.cdc.gov/h1n1flu/eua). RA will continue to support current and future preparedness and emergency response activities by ensuring that the appropriate regulatory mechanisms are in place for the deployment of critical medical countermeasures from the Strategic National Stockpile against threats to public health.


title: COVID-19 Outbreak in Italy: Protecting Worker Health and the Response of the Italian Industrial Hygienists Association

text: The number of people infected with severe acute respiratory syndrome—coronavirus 2 (SARS-CoV-2), i.e. the virus causing coronavirus disease (COVID-19), is dramatically increasing worldwide to the size of a pandemic. At the time of writing Italy is ranking first among countries both in terms of number of COVID-19 confirmed cases and in terms of number of deaths. Such a wide spread of COVID-19 has led to concern among workers who are facing the risk of becoming infected during the execution of their duties. We believe it is useful to remark on the need for professional expertise in the field of Occupational Hygiene in this emergency context, in which the indications provided by national and international bodies, the available scientific literature and the legal provisions are constantly and rapidly evolving. It is of fundamental importance that there is an effective analysis of expert inputs, to provide essential guidance to Health, Safety and Environmental managers and other prevention managers in workplaces. In this regard, not only a constant update of the regulatory framework is needed, but also a development and circulation of operational guidance to all the stakeholders to translate general indications into clear operating procedures and implementation tools to be adopted in the workplaces. We believe that the scientific associations in the field of Occupational Hygiene play a crucial role in guiding and assisting prevention professionals. There is considerable expertise in the occupational hygiene and exposure science communities that can help employers and workers to contain and delay the spread of COVID-19. For this reason, the Italian Association of Industrial Hygienists (AIDII—Associazione Italiana degli Igienisti Industriali) published documents containing operational guidelines to provide correct and constantly updated information for: (i) workers employed in essential activities (with low and medium risk of contagion), (ii) health workers and other workers at high or very high risk of contagion, and (iii) for the correct use and handling of personal protective equipment for workers and for the population in general. It is worth pointing out that the documents produced are not intended to replace those produced by authoritative bodies, but to comply with and complete them by reporting an effective summary and further indications about the measures that should be taken in practice under the light of the Italian legislation. At present, the challenge is to produce scientifically sound knowledge, appropriate tools, and effective methodologies, by coordinating the initiatives of different scientific associations, with the final aim to effectively transfer them to employers and workers.


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.


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.


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.


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.


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.


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.


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.