title: Diagnostic performance of immunochromatography assay for rapid detection of IgM and IgG in coronavirus disease 2019

text: Serologic assays have been developed to detect infection with coronavirus disease 2019 (COVID‐19). This study was conducted to evaluate the diagnostic performance of an immunochromatography‐based assay of human serum for COVID‐19. The present study enrolled 149 subjects who had been tested by real‐time reverse transcription‐polymerase chain reaction (RT‐PCR) for COVID‐19 and were classified into two groups: 70 who were positive for COVID‐19 and 79 who were negative for COVID‐19 based on RT‐PCR. An immunochromatography‐based COVID‐19 immunoglobulin G (IgG)/immunoglobulin M (IgM) rapid test on the sera of the study population was applied to measure the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic (ROC) curve compared to RT‐PCR, with a 95% confidence interval (CI). IgM or IgG antibodies were detected in 65 subjects (92.9%) classified as positive for COVID‐19 and in three subjects (3.8%) classified as negative for COVID‐19. The sensitivity and specificity percentages for IgM or IgG antibodies were 92.9% (95% CI: 84.1‐97.6) and 96.2% (95% CI: 89.3‐99.2), respectively, with 95.6% PPV and 93.8% NPV. The PPV rapidly improved with increasing disease prevalence from 19.8% to 96.1% in the presence of either IgM or IgG, while the NPV remained high with a change from 99.9% to 93.1%. The area under the ROC curve was 0.945 (95% CI: 0.903‐0.988) for subjects with either IgM or IgG positivity. In conclusion, the immunochromatography‐based COVID‐19 IgG/IgM rapid test is a useful and practical diagnostic assay for detection of COVID‐19, especially in the presence of IgM or IgG antibodies.


title: Diagnosis and Treatment of Infectious Enteritis in Neonatal and Juvenile Ruminants

text: Common causes of infectious enteritis in neonate and juvenile ruminants include viral, bacterial, and protozoal pathogens. The most common presenting sign in ruminants with infectious enteritis is diarrhea. Diagnosis of the cause of enteritis has important zoonotic and herd health implications. Severity of clinical signs with similar pathogens may differ between calves and small ruminants. Treatment of enteritis involves supportive care to correct fluid and electrolyte imbalances, provision of nutritional support for neonates, prevention and treatment of endotoxemia or sepsis, and pathogen-specific treatments when relevant and available.


title: The regulatory landscape of precision oncology laboratory medicine in the United States – Perspective on the past 5 years and considerations for future regulation

text: The regulatory landscape for precision oncology in the United States is complicated, with multiple governmental regulatory agencies with different scopes of jurisdiction. Several regulatory proposals have been introduced since the Food and Drug Administration released a draft guidance to regulate laboratory-developed tests in 2014. Key aspects of the most recent proposals and discussion of central arguments related to the regulation of precision oncology laboratory tests provides insight to stakeholders for future discussions related to regulation of laboratory tests.


title: Conducting Psychoeducational Assessments During the COVID-19 Crisis: the Danger of Good Intentions

text: Decision-makers in school psychology are presently engaged in the process of determining how to, if possible, move forward with conducting mandated psychoeducational evaluations of students in schools during the pandemic. Whereas prominent organizations within the profession (e.g., American Psychological Association, National Association of School Psychologists) have issued guidance and encouraged practitioners to delay testing, it is not clear whether that is a viable option in every jurisdiction. Accordingly, professionals are now considering the potential use of telehealth platforms to conduct assessments, in some form, as we move forward and deal with this crisis. The goal of this brief commentary is to raise some provisional limitations associated with the use of telehealth to conduct psychological assessments that we believe will have to be considered as use of these platforms is debated. Recommendations for professional practice are also provided.


Public health saves lives: sad lessons from COVID-19


title: Remdesivir investigational trials in COVID-19: a critical reappraisal

text: Abstract During outbreak of emerging disease, the most important aim is to discover an effective drug to save life. Consequently, a lot of effort are generally made by the industry to promote clinical trials with new drugs. Here we review evidence of the 8 most recent reports including 3 randomized controlled trials on the clinical efficacy of remdesivir in treating COVID-19 patient. We conclude that it is far too premature to identify remdesivir as a curative or life-saving intervention.


title: Development and evaluation of a leadership training program for public health emergency response: results from a Chinese study

text: BACKGROUND: Since the 9/11 attack and severe acute respiratory syndrome (SARS), the development of qualified and able public health leaders has become a new urgency in building the infrastructure needed to address public health emergencies. Although previous studies have reported that the training of individual leaders is an important approach, the systemic and scientific training model need further improvement and development. The purpose of this study was to develop, deliver, and evaluate a participatory leadership training program for emergency response. METHODS: Forty-one public health leaders (N = 41) from five provinces completed the entire emergency preparedness training program in China. The program was evaluated by anonymous questionnaires and semi-structured interviews held prior to training, immediately post-training and 12-month after training (Follow-up). RESULTS: The emergency preparedness training resulted in positive shifts in knowledge, self-assessment of skills for public health leaders. More than ninety-five percent of participants reported that the training model was scientific and feasible. Moreover, the response of participants in the program to the avian influenza outbreak, as well as the planned evaluations for this leadership training program, further demonstrated both the successful approaches and methods and the positive impact of this integrated leadership training initiative. CONCLUSION: The emergency preparedness training program met its aims and objectives satisfactorily, and improved the emergency capability of public health leaders. This suggests that the leadership training model was effective and feasible in improving the emergency preparedness capability.


title: Assessment of returning travellers with fever

text: Abstract Millions of people travel to the tropics each year and a significant minority of them become ill, either during their stay, or shortly after their return. Most have mild, self-limiting illnesses, but a few will have a life-threatening condition. This article outlines how to evaluate fever in the returning traveller and discusses important infection control and public health measures. A detailed travel history, which takes into account travel destinations, specific activities and risk factors in relation to the onset of symptoms, is essential for constructing a comprehensive list of differential diagnoses and guiding appropriate investigations. Importantly, all travellers returning from the tropics with a fever should be investigated for malaria, even if their return was 3 months ago or longer.


title: The Efficacy of Lockdown Against COVID-19: A Cross-Country Panel Analysis

text: BACKGROUND: There has been much debate about the effectiveness of lockdown measures in containing COVID-19, and their appropriateness given the economic and social cost they entail. To the best of our knowledge, no existing contribution to the literature has attempted to gauge the effectiveness of lockdown measures over time in a longitudinal cross-country perspective. OBJECTIVES: This paper aims to fill the gap in the literature by assessing, at an international level, the effect of lockdown measures (or the lack of such measures) on the numbers of new infections. Given this policy’s expected change in effectiveness over time, we also measure the effect of having a lockdown implemented over a given number of days (from 7 to 20 days). METHODS: We pursue our objectives by means of a quantitative panel analysis, building a longitudinal dataset with observations from countries all over the world, and estimating the impact of lockdown via feasible generalized least squares fixed effect, random effects, generalized estimating equation, and hierarchical linear models. RESULTS: Our results show that lockdown is effective in reducing the number of new cases in the countries that implement it, compared with those countries that do not. This is especially true around 10 days after the implementation of the policy. Its efficacy continues to grow up to 20 days after implementation. CONCLUSION: Results suggest that lockdown is effective in reducing the R0, i.e. the number of people infected by each infected person, and that, unlike what has been suggested in previous analyses, its efficacy continues to hold 20 days after the introduction of the policy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40258-020-00596-3) contains supplementary material, which is available to authorized users.


title: COVID-19 vaccines: breaking record times to first-in-human trials

text: The twenty-first century has come with a new era in vaccinology, in which recombinant genetic technology has contributed to setting an unprecedented fast pace in vaccine development, clearly demonstrated during the recent COVID-19 pandemic.


title: The Cholera Epidemics in Hamburg and What to Learn for COVID‐19 (SARS‐CoV‐2)

text: © 2020 International Society for Advancement of Cytometry


title: Proteomic analysis for Type I interferon antagonism of Japanese encephalitis virus NS5 protein

text: Japanese encephalitis virus (JEV) nonstructural protein 5 (NS5) exhibits a Type I interferon (IFN) antagonistic function. This study characterizes Type I IFN antagonism mechanism of NS5 protein, using proteomic approach. In human neuroblastoma cells, NS5 expression would suppress IFNβ‐induced responses, for example, expression of IFN‐stimulated genes PKR and OAS as well as STAT1 nuclear translocation and phosphorylation. Proteomic analysis showed JEV NS5 downregulating calreticulin, while upregulating cyclophilin A, HSP 60 and stress‐induced‐phosphoprotein 1. Gene silence of calreticulin raised intracellular Ca(2+) levels while inhibiting nuclear translocalization of STAT1 and NFAT‐1 in response to IFNβ, thus, indicating calreticulin downregulation linked with Type I IFN antagonism of JEV NS5 via activation of Ca(2+)/calicineurin. Calcineurin inhibitor cyclosporin A attenuated NS5‐mediated inhibition of IFNβ‐induced responses, for example, IFN‐sensitive response element driven luciferase, STAT1‐dependent PKR mRNA expression, as well as phosphorylation and nuclear translocation of STAT1. Transfection with calcineurin (vs. control) siRNA enhanced nuclear translocalization of STAT1 and upregulated PKR expression in NS5‐expressing cells in response to IFNβ. Results prove Ca(2+), calreticulin, and calcineurin involvement in STAT1‐mediated signaling as well as a key role of JEV NS5 in Type I IFN antagonism. This study offers insights into the molecular mechanism of Type I interferon antagonism by JEV NS5.


title: Prevalence of COVID-19 among patients with chronic inflammatory rheumatic diseases treated with biologic agents or small molecules: a population-based study in the first two months of COVID-19 outbreak in Italy

text: Abstract Objective: The aim of this study is to determine the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) among adult patients treated with biologic agents or small molecules for chronic inflammatory rheumatic diseases, in particular chronic inflammatory arthritides. Methods: To this end, a population-based study, in the province of Udine (466,700 inhabitants, with age > 15 years old, Friuli Venezia Giulia region, Italy) was planned. The primary outcome was the prevalence of COVID-19 in the first two months of the outbreak. All the rheumatic patients treated with biologic agents or small molecules in the last 6 months in our province were included (N=1051). Results: From February 29 to April 25, 2020, 4 adult patients (4/1051, i.e. 3.8/1000, 95% Confidence Interval 1.5-9.7/1000) were registered as swab test positive by PCR for COVID-19. Overall, a total of 47/1051 (4,5%) cases were tested for COVID-19 by PCR in the same period, and 15 of them due to symptoms compatible with COVID-19. In the general population, the prevalence was 937 cases/466700 (2/1000, 95% Confidence Interval 1.9-2.1/1000, p value=0.33, chi square test), and 20,179/466,700 (4.3%) swab tests for COVID-19 were performed.. Conclusion: The risk of COVID-19 in rheumatic patients under biologic agents or small molecules does not appear different from that observed in the general population. Patients should be informed to safely proceed with their treatment and follow the rules for self-protection to COVID-19.


title: Atlas of coronavirus replicase structure

text: Abstract The international response to SARS-CoV has produced an outstanding number of protein structures in a very short time. This review summarizes the findings of functional and structural studies including those derived from cryoelectron microscopy, small angle X-ray scattering, NMR spectroscopy, and X-ray crystallography, and incorporates bioinformatics predictions where no structural data is available. Structures that shed light on the function and biological roles of the proteins in viral replication and pathogenesis are highlighted. The high percentage of novel protein folds identified among SARS-CoV proteins is discussed.


title: Enterovirus 71 modulates a COX‐2/PGE(2)/cAMP‐dependent viral replication in human neuroblastoma cells: Role of the c‐Src/EGFR/p42/p44 MAPK/CREB signaling pathway

text: Enterovirus 71 (EV71) has been shown to induce cyclooxygenase‐2 (COX‐2) expression in human neuroblastoma SK‐N‐SH cells through the action of MAPKs, NF‐κB, and AP‐1. On the other hand, the transcription factor CREB has also been implicated in the expression of COX‐2 in other cell lines. Here, we report that EV71‐induced COX‐2 expression and PGE(2) production were both inhibited by pretreatment with the PKA inhibitor H89 or by transfection with CREB siRNA. In addition, EV71‐induced COX‐2 expression and c‐Src/EGFR phosphorylation were both attenuated by transfection with c‐Src siRNA or pretreatment with the inhibitors of c‐Src (PP1) or EGF receptor (EGFR) (AG1478 and EGFR‐neutralizing antibody). We also observed that EV71‐induced p42/p44 MAPK phosphorylation was decreased following pretreatment with AG1478. Moreover, EV71‐induced COX‐2 expression was blocked by pretreatment with the p300 inhibitor GR343 or by transfection with p300 siRNA. Using immunoprecipitation and chromatin immunoprecipitation assays, we observed that EV71 stimulated the association of CREB and p300 with the COX‐2 promoter region. Notably, we also demonstrated that EV71‐induced COX‐2 expression and PGE(2) production promoted viral replication via cAMP signaling. In summary, this study demonstrates that EV71 activates the c‐Src/EGFR/p42/p44 MAPK pathway in human SK‐N‐SH cell, which leads to the activation of CREB/p300, and stimulates COX‐2 expression and PGE(2) release. J. Cell. Biochem. 112: 559–570, 2011. © 2010 Wiley‐Liss, Inc.


title: Performance of the TB-LAMP diagnostic assay in reference laboratories: Results from a multicentre study

text: OBJECTIVE: To evaluate the diagnostic performance of TB-LAMP, a manual molecular tuberculosis (TB) detection method, and provide comparison to the Xpert MTB/RIF assay. METHODS: In a large multicentre study, two sputum samples were collected from participants with TB symptoms in reference laboratories in Peru, South Africa, Brazil, and Vietnam. Each sample was tested with TB-LAMP. The reference standard consisted of four direct smears, four cultures, and clinical and radiological findings. Individuals negative on conventional tests were followed up after 8 weeks. The Xpert MTB/RIF assay was performed on fresh or frozen samples as a molecular test comparison. RESULTS: A total of 1036 adults with suspected TB were enrolled. Among 375 culture-confirmed TB cases with 750 sputum samples, TB-LAMP detected 75.6% (95% confidence interval (CI) 71.8–79.4%), including 97.9% (95% CI 96.4–99.4%) of smear-positive TB samples and 46.6% (95% CI 40.6–52.7%) of smear-negative TB samples. Specificity in 477 culture-negative participants not treated for TB (954 sputum samples) was 98.7% (95% CI 97.9–99.6%). TB-LAMP test results were indeterminate in 0.3% of cases. CONCLUSIONS: TB-LAMP detects nearly all smear-positive and half of smear-negative TB cases and has a high specificity when performed in reference laboratories. Performance was similar to the Xpert MTB/RIF assay.


title: Increasing Temperature and Relative Humidity Accelerates Inactivation of SARS-CoV-2 on Surfaces

text: Coronavirus disease 2019 (COVID-19) was first identified in China in late 2019 and is caused by newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Previous studies had reported the stability of SARS-CoV-2 in cell culture media and deposited onto surfaces under a limited set of environmental conditions. Here, we broadly investigated the effects of relative humidity, temperature, and droplet size on the stability of SARS-CoV-2 in a simulated clinically relevant matrix dried on nonporous surfaces. The results show that SARS-CoV-2 decayed more rapidly when either humidity or temperature was increased but that droplet volume (1 to 50 μl) and surface type (stainless steel, plastic, or nitrile glove) did not significantly impact decay rate. At room temperature (24°C), virus half-life ranged from 6.3 to 18.6 h depending on the relative humidity but was reduced to 1.0 to 8.9 h when the temperature was increased to 35°C. These findings suggest that a potential for fomite transmission may persist for hours to days in indoor environments and have implications for assessment of the risk posed by surface contamination in indoor environments. IMPORTANCE Mitigating the transmission of SARS-CoV-2 in clinical settings and public spaces is critically important to reduce the number of COVID-19 cases while effective vaccines and therapeutics are under development. SARS-CoV-2 transmission is thought to primarily occur through direct person-to-person transfer of infectious respiratory droplets or through aerosol-generating medical procedures. However, contact with contaminated surfaces may also play a significant role. In this context, understanding the factors contributing to SARS-CoV-2 persistence on surfaces will enable a more accurate estimation of the risk of contact transmission and inform mitigation strategies. To this end, we have developed a simple mathematical model that can be used to estimate virus decay on nonporous surfaces under a range of conditions and which may be utilized operationally to identify indoor environments in which the virus is most persistent.


title: Recombinant live attenuated avian coronavirus vaccines with deletions in the accessory genes 3ab and/or 5ab protect against infectious bronchitis in chickens

text: Avian coronavirus infectious bronchitis virus (IBV) is a respiratory pathogen of chickens, causing severe economic losses in poultry industry worldwide. Live attenuated viruses are widely used in both the broiler and layer industry because of their efficacy and ability to be mass applied. Recently, we established a novel reverse genetics system based on targeted RNA recombination to manipulate the genome of IBV strain H52. Here we explore the possibilities to attenuate IBV in a rational way in order to generate safe and effective vaccines against virulent IBV (van Beurden et al., 2017). To this end, we deleted the nonessential group-specific accessory genes 3 and/or 5 in the IBV genome by targeted RNA recombination and selected the recombinant viruses in embryonated eggs. The resulting recombinant (r) rIBV-Δ3ab, rIBV-Δ5ab, and rIBV-Δ3ab5ab could be rescued and grew to the same virus titer as recombinant and wild type IBV strain H52. Thus, genes 3ab and 5ab are not essential for replication in ovo. When administered to one-day-old chickens, rIBV-Δ3ab, rIBV-Δ5ab, and rIBV-Δ3ab5ab showed reduced ciliostasis as compared to rIBV H52 and wild type H52, indicating that the accessory genes contribute to the pathogenicity of IBV. After homologous challenge with the virulent IBV strain M41, all vaccinated chickens were protected against disease based on reduced loss of ciliary movement in the trachea compared to the non-vaccinated but challenged controls. Taken together, deletion of accessory genes 3ab and/or 5ab in IBV resulted in mutant viruses with an attenuated phenotype and the ability to induce protection in chickens. Hence, targeted RNA recombination based on virulent IBV provides opportunities for the development of a next generation of rationally designed live attenuated IBV vaccines.


title: Chitosan-modified poly(d,l-lactide-co-glycolide) nanospheres for improving siRNA delivery and gene-silencing effects

text: Abstract Chitosan (CS) surface-modified poly(d,l-lactide-co-glycolide) (PLGA) nanospheres (NS) for a siRNA delivery system were evaluated in vitro. siRNA-loaded PLGA NS were prepared by an emulsion solvent diffusion (ESD) method, and the physicochemical properties of NS were investigated. The level of targeted protein expression and siRNA uptake were examined in A549 cells. CS-modified PLGA NS exhibited much higher encapsulation efficiency than unmodified PLGA NS (plain-PLGA NS). CS-modified PLGA NS showed a positive zeta potential, while plain-PLGA NS were negatively charged. siRNA uptake studies by observation with confocal leaser scanning microscopy (CLSM) indicated that siRNA-loaded CS-modified PLGA NS were more effectively taken up by the cells than plain-PLGA NS. The efficiencies of different siRNA preparations were compared at the level of targeted protein expression. The gene-silencing efficiency of CS-modified PLGA NS was higher and more prolonged than those of plain-PLGA NS and naked siRNA. This result correlated with the CLSM studies, which may have been due to higher cellular uptake of CS-modified PLGA NS due to electrostatic interactions. It was concluded that CS-modified PLGA NS containing siRNA could provide an effective siRNA delivery system.


title: Establishment of a stable CHO cell line with high level expression of recombinant porcine IFN-β

text: Abstract A CHO cell clone (CHO-PoIFN-β) with stable porcine IFN-β expression under control of CMV promoter was selected under G418 pressure. In a 25cm2 cell culture flask (5ml culture medium), the cumulative protein yield of recombinant PoIFN-β reached 2.3×106 IU/ml. This cells clone maintained stable expression for at least 20 generations even in the absence of G418 selection pressure. The expressed recombinant PoIFN-β could induce the expression of porcine Mx protein in PK15 cells, and activate the chicken Mx promoter-controlled luciferase reporter gene expression, confirming that the recombinant PoIFN-β has the biological activity of natural porcine type-I interferon. In addition, the recombinant PoIFN-β fully protected PK15 cells against 1000 TCID50 of porcine transmissible gastroenteritis virus and pseudo-rabies virus infection, demonstrating its high potential in therapeutic applications. This is the first report of establishing a mammalian cell line with stable expression of porcine IFN-β.


title: Lessons Learned from 9/11: Mental Health Perspectives on the COVID-19 Pandemic

text: Abstract The COVID-19 pandemic will likely lead to high rates of PTSD, depression, and substance misuse among survivors, victims’ families, medical workers, and other essential personnel. The mental health response to the 9/11/01 terrorist attacks, culminating in a federally-funded health program, provides a template for how providers may serve affected individuals. Drawing on the 9/11 experience, we highlight effective prevention measures, likely short and long-term treatment needs, vulnerable subgroups, and important points of divergence between 9/11 and the COVID-19 pandemic. Mental health monitoring, early identification of at-risk individuals, and treatment irrespective of financial barriers is essential for minimizing chronic distress.


title: Deubiquitination in virus infection

text: Abstract Post-translational modification of proteins and peptides by ubiquitin, a highly evolutionarily conserved 76 residue protein, and ubiquitin-like modifiers has emerged as a major regulatory mechanism in various cellular activities. Eukaryotic viruses are known to modulate protein ubiquitination to their advantage in various ways. At the same time, the evidence for the importance of deubiquitination as a viral target also is growing. This review centers on known viral interactions with protein deubiquitination, on viral enzymes for which deubiquitinating activities were recently demonstrated, and on the roles of viral ubiquitin-like sequences.


title: Effect of cleaning and disinfection of toys on infectious diseases and micro-organisms in daycare nurseries

text: Summary Background The rising number of children in daycare nurseries increases opportunities for the transmission of infectious diseases. Pathogens may be transmitted directly from child to child via sneezing, coughing and touching, or indirectly via the environment. Toys are among the fomites with the highest pathogen load, but their role in disease transmission is unknown. Aim To determine if washing and disinfection of toys can reduce sickness absence and microbial pathogen load in the nursery environment. Methods Twelve nurseries (caring for 587 children) were randomized to intervention and control groups. The intervention consisted of washing and disinfection of toys and linen every two weeks for three months by a commercial cleaning company. The extent and causes of sickness absence among the children were recorded in both groups before and after introduction of the intervention. Ten sampling points in each nursery were examined for bacteria and respiratory viruses. Results The presence of respiratory virus DNA/RNA was widespread, but very few pathogenic bacteria were found in the environment. The intervention reduced the presence of adenovirus [odds ratio (OR) 2.4, 95% confidence interval (CI) 1.1–5.0], rhinovirus (OR 5.3, 95% CI 2.3–12.4) and respiratory syncytial virus (OR 4.1, 95% CI 1.5–11.2) compared with the control group, but the intervention had no effect on sickness absence or disease patterns in the nurseries. Conclusion Although cleaning and disinfection of toys every two weeks can decrease the microbial load in nurseries, it does not appear to reduce sickness absence among nursery children.


title: Acute Respiratory Distress Syndrome as an Organ Phenotype of Vascular Microthrombotic Disease: Based on Hemostatic Theory and Endothelial Molecular Pathogenesis

text: Acute respiratory distress syndrome (ARDS) is a life-threatening noncardiogenic circulatory disorder of the lungs associated with critical illnesses such as sepsis, trauma, and immune and collagen vascular disease. Its mortality rate is marginally improved with the best supportive care. The demise occurs due to progressive pulmonary hypoxia and multi-organ dysfunction syndrome (MODS) with severe inflammation. Complement activation is a part of immune response against pathogen or insult in which membrane attack complex (MAC) is formed and eliminates microbes. If complement regulatory protein such as endothelial CD59 is underexpressed, MAC may also cause pulmonary vascular injury to the innocent bystander endothelial cell of host and provokes endotheliopathy that causes inflammation and pulmonary vascular microthrombosis, leading to ARDS. Its pathogenesis is based on a novel “two-path unifying theory” of hemostasis and “two-activation theory of the endothelium” promoting molecular pathogenesis. Endotheliopathy activates two independent molecular pathways: inflammatory and microthrombotic. The former triggers the release inflammatory cytokines and the latter promotes exocytosis of unusually large von Willebrand factor multimers (ULVWF) and platelet activation. Inflammatory pathway initiates inflammation, but microthrombotic pathway more seriously produces “microthrombi strings” composed of platelet-ULVWF complexes, which become anchored on the injured endothelial cells, and causes disseminated intravascular microthrombosis (DIT). DIT is a hemostatic disease due to lone activation of ULVWF path without activated tissue factor path. It leads to endotheliopathy-associated vascular microthrombotic disease (EA-VMTD), which orchestrates consumptive thrombocytopenia, microangiopathic hemolytic anemia, and MODS. Thrombotic thrombocytopenic purpura (TTP)-like syndrome is the hematologic phenotype of EA-VMTD. ARDS is one of organ phenotypes among MODS associated with TTP-like syndrome. The most effective treatment of ARDS can be achieved by counteracting the activated microthrombotic pathway based on two novel hemostatic theories.


title: Regulatory Role of Small Nucleolar RNAs in Human Diseases

text: Small nucleolar RNAs (snoRNAs) are appreciable players in gene expression regulation in human cells. The canonical function of box C/D and box H/ACA snoRNAs is posttranscriptional modification of ribosomal RNAs (rRNAs), namely, 2′-O-methylation and pseudouridylation, respectively. A series of independent studies demonstrated that snoRNAs, as well as other noncoding RNAs, serve as the source of various short regulatory RNAs. Some snoRNAs and their fragments can also participate in the regulation of alternative splicing and posttranscriptional modification of mRNA. Alterations in snoRNA expression in human cells can affect numerous vital cellular processes. SnoRNA level in human cells, blood serum, and plasma presents a promising target for diagnostics and treatment of human pathologies. Here we discuss the relation between snoRNAs and oncological, neurodegenerative, and viral diseases and also describe changes in snoRNA level in response to artificial stress and some drugs.


title: Immunization via the anal mucosa and adjacent skin to protect against respiratory virus infections and allergic rhinitis: A hypothesis

text: Summary Exposure of the immune system to environmental antigens and infectious agents by way of the anal mucosa and perianal skin could play an important role in protecting the respiratory tract against allergic conditions and virus infections. Hygienic practices that have reduced exposure of the immune system to such agents include the use of modern toiletry, disposable diapers and clothes dryers. Historically, the anal region was cleansed following defecation with natural materials that would have brought antigens and infectious agents from the environment into frequent contact with the perianal skin and anal mucosa. This practice was a crude form of transcutaneous and mucosal vaccination, whereby antigenic agents that are topically applied to skin or mucosal surfaces, penetrate into the tissues and stimulate immune responses that can extend to the respiratory tract. Furthermore, until the 1960s, diapers and other cloth items were often dried outdoors where they would have collected environmental antigens that, when applied to the body, could have made contact with the immune system in the skin. Herein, it is hypothesized that prevention of allergic rhinitis and possibly other disorders involving the immune system could be achieved by the daily application of preparations composed of environmental antigens and infectious agents to the anal mucosa and adjacent skin. In support of the proposal, immunotherapy for allergic rhinitis currently involves administration of specific allergens to subcutaneous tissue or to the sublingual mucosa. It is considered that superior protection could be achieved by applying the allergens to the anal region where they would target the immune system in both mucosal tissue and adjacent skin. It is also hypothesized that respiratory viruses applied to the anal region would infect tissues at that site and induce immune responses that would protect the respiratory tract against the common cold and influenza. This approach is supported by evidence that orally administered adenovirus vaccine can induce an infection in the intestinal mucosa that stimulates immunity to protect the respiratory tract. Although other respiratory viruses are unlikely to survive passage through the intestinal tract, rhinovirus has on rare occasion been detected in stool specimens, suggesting the possibility of an infection at the terminal end of the digestive tract. Respiratory syncytial viruses and influenza viruses are amenable to modification by reverse genetics and other techniques and it is expected that natural or modified viruses applied to the anal region could serve to immunize the respiratory tract.


title: Strategies to Optimize ICU Liberation (A to F) Bundle Performance in Critically Ill Adults With Coronavirus Disease 2019

text: OBJECTIVES: The severe acute respiratory syndrome coronavirus 2 pandemic has stretched ICU resources in an unprecedented fashion and outstripped personal protective equipment supplies. The combination of a novel disease, resource limitations, and risks to medical personnel health have created new barriers to implementing the ICU Liberation (“A” for Assessment, Prevention, and Manage pain; “B” for Both Spontaneous Awakening Trials and Spontaneous Breathing Trials; “C” for Choice of Analgesia and Sedation; “D” for Delirium Assess, Prevent, and Manage; “E” for Early Mobility and Exercise; and “F” for Family Engagement and Empowerment [ABCDEF]) Bundle, a proven ICU care approach that reduces delirium, shortens mechanical ventilation duration, prevents post-ICU syndrome, and reduces healthcare costs. This narrative review acknowledges barriers and offers strategies to optimize Bundle performance in coronavirus disease 2019 patients requiring mechanical ventilation. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: The most relevant literature, media reports, and author experiences were assessed for inclusion in this narrative review including PubMed, national newspapers, and critical care/pharmacology textbooks. DATA SYNTHESIS: Uncertainty regarding coronavirus disease 2019 clinical course, shifts in attitude, and changes in routine behavior have hindered Bundle use. A domino effect results from: 1) changes to critical care hierarchy, priorities, and ICU team composition; 2) significant personal protective equipment shortages cause; 3) reduced/restricted physical bedside presence favoring; 4) increased depth of sedation and use of neuromuscular blockade; 5) which exacerbate drug shortages; and 6) which require prolonged use of limited ventilator resources. Other identified barriers include manageable knowledge deficits among non-ICU clinicians unfamiliar with the Bundle or among PICU specialists deploying pediatric-based Bundle approaches who are unfamiliar with adult medicine. Both groups have been enlisted to augment the adult ICU work force to meet demand. Strategies were identified to facilitate Bundle performance to liberate patients from the ICU. CONCLUSIONS: We acknowledge current challenges that interfere with comprehensive management of critically ill patients during the coronavirus disease 2019 pandemic. Rapid response to new circumstances precisely requires established safety mechanisms and protocols like the ABCDEF Bundle to increase ICU and ventilator capacity and help survivors maximize recovery from coronavirus disease 2019 as early as possible.


title: Non‐Contagious, Second COVID‐19 Infection: Implications for Organ Donation Eligibility

text: As of May 19, 2020, the Korea Centers for Disease Control and Prevention (KCDC) shared evidence indicating an inability for COVID‐19 patients having contracted a second infection to spread the virus. Viral samples from re‐infected patients could not be grown in culture, a sign of dead virus particles, attributable to neutralizing antibodies. Accordingly, a negative COVID‐19 test may no longer be mandated for returning to school or work, or even donating organs. The transplant community should consider lifting donation constraints on patients testing positive for a second COVID‐19 infection.


title: Nosocomial infections in psychiatric hospitals during the new coronavirus pneumonia outbreak

text: Abstract Since mid-December 2019, a new coronavirus pneumonia (NCP) has emerged in China. It was reported that Wuhan Mental Health Center in China was affected from the very beginning of the outbreak. Coincidentally, another large-scale nosocomial infection occurred at the psychiatric ward of the Daenam Hospital in South Korea. It is important for the policymakers to pay full attention on this aspect worldwide and corresponding prevention recommendations should be provided.


title: A conditional-lethal murine coronavirus mutant that fails to incorporate the spike glycoprotein into assembled virions

text: Abstract The coronavirus spike glycoprotein (S) mediates both the attachment of virus to the host cell receptor and membrane fusion. We describe here the characterization of a temperature-sensitive mutant of the coronavirus mouse hepatitis virus A59 (MHV-A59) having multiple S protein-related defects. The most remarkable of these was that the mutant, designated Albany 18 (Alb 18), assembled virions devoid of the S glycoprotein at the nonpermissive temperature. Alb18 also failed to bring about syncytia formation in cells infected at the nonpermissive temperature. Virions of the mutant assembled at the permissive temperature were much more thermolabile than wild type. Moreover, mutant S protein that was incorporated into virions at the permissive temperature showed enhanced pH-dependent thermolability in its ability to bind to the MHV receptor. Alb18 was found to have a single point mutation in S resulting in a change of serine 287 to isoleucine, and it was shown by revertant analysis that this was the lesion responsible for the phenotype of the mutant.


title: Therapeutic and biotechnological applications of substrate specific microbial aminopeptidases

text: Aminopeptidases (EC 3.4.11.) belongs to exoprotease family, which can catalyze the cleavage of peptide bond which connects the N-terminal amino acid to the penultimate residue in a protein. Aminopeptidases catalyze the process of removal of the N-terminal amino acids of target substrates by sequential cleavage of one amino acid residue at a time. Microbial aminopeptidase are of great acceptance as industrial enzymes with varying applications in food and pharma industry since these enzymes possess unique characteristics than aminopeptidases from other sources. This review describes the various applications of microbial aminopeptidases in different industrial sectors. These enzymes are widely used in food industry as a debittering agent as well as in the preparation of protein hydrolysates. In baking, brewing, and cheese making aminopeptidases are extensively used for removing the bitterness of peptides. The inhibitors of these enzymes are found great clinical applications against various diseases such as cancer, diabetes, and viral infections. Aminopeptidases are widely used for the synthesis of biopeptides and amino acids, and found to be efficient than chemical synthesis. These enzymes are capable of hydrolyzing organophosphate compounds, thus having biological as well as environmental significance.


title: Detection and genetic characterization of feline kobuviruses

text: In order to survey for feline kobuviruses infection, fecal samples (n = 39) of cats with diarrhea were collected during 2011–2012. Six (14.5 %) of the fecal samples tested were positive for feline kobuviruses. The partial nucleotide sequences of feline kobuviruses based on the RNA-dependent RNA polymerase gene were compared to those of other species. Feline kobuviruses were most closely related to canine kobuvirus in terms of their amino acid and nucleotide levels. In a phylogenetic tree, feline kobuviruses were also closely clustered with canine kobuvirus, Aichi virus (human), and mouse kobuvirus. This is the first report of the detection and genetic characterization of feline kobuviruses.


title: Source apportionment of wide range particle size spectra and black carbon collected at the airport of Venice (Italy)

text: Abstract Atmospheric particles are of high concern due to their toxic properties and effects on climate, and large airports are known as significant sources of particles. This study investigates the contribution of the Airport of Venice (Italy) to black carbon (BC), total particle number concentrations (PNC) and particle number size distributions (PNSD) over a large range (14 nm–20 μm). Continuous measurements were conducted between April and June 2014 at a site located 110 m from the main taxiway and 300 m from the runway. Results revealed no significantly elevated levels of BC and PNC, but exhibited characteristic diurnal profiles. PNSD were then analysed using both k-means cluster analysis and positive matrix factorization. Five clusters were extracted and identified as midday nucleation events, road traffic, aircraft, airport and nighttime pollution. Six factors were apportioned and identified as probable sources according to the size profiles, directional association, diurnal variation, road and airport traffic volumes and their relationships to micrometeorology and common air pollutants. Photochemical nucleation accounted for ∼44% of total number, followed by road + shipping traffic (26%). Airport-related emissions accounted for ∼20% of total PNC and showed a main mode at 80 nm and a second mode beyond the lower limit of the SMPS (<14 nm). The remaining factors accounted for less than 10% of number counts, but were relevant for total volume concentrations: nighttime nitrate, regional pollution and local resuspension. An analysis of BC levels over different wind sectors revealed no especially significant contributions from specific directions associated with the main local sources, but a potentially significant role of diurnal dynamics of the mixing layer on BC levels. The approaches adopted in this study have identified and apportioned the main sources of particles and BC at an international airport located in area affected by a complex emission scenario. The results may underpin measures for improving local and regional air quality, and health impact assessment studies.


title: Global Disparity and Solidarity in a Pandemic

text: While the domestic effect of structural racism and other social vulnerabilities on Covid‐19 mortality in the United States has received some attention, there has been much less discussion (with some notable exceptions) of how structural global inequalities will further exacerbate Covid‐related health disparity across the world. This may be partially due to the delayed availability of accurate and comparable data from overwhelmed systems, particularly in low‐ and middle‐income countries. However, early methods to procure and develop treatments and vaccines by some high‐income countries reflect ongoing protectionist and nationalistic attitudes that can systemically exclude access for people in regions with weaker health systems. What's needed is a global coordinated effort, based on the principle of solidarity, to foster equitable health care access.


title: Human Rhinovirus Infections in Hematopoietic Cell Transplant Recipients: Risk Score for Progression to Lower Respiratory Tract Infection

text: Abstract Human rhinovirus lower respiratory tract infection (LRTI) is associated with mortality after hematopoietic cell transplantation (HCT); however, risk factors for LRTI are not well characterized. We sought to develop a risk score for progression to LRTI from upper respiratory tract infection (URTI) in HCT recipients. Risk factors for LRTI within 90 days were analyzed using Cox regression among HCT recipients with rhinovirus URTI between January 2009 and March 2016. The final multivariable model included factors with a meaningful effect on the bootstrapped optimism corrected concordance statistic. Weighted score contributions based on hazard ratios were determined. Cumulative incidence curves estimated the probability of LRTI at various score cut-offs. Of 588 rhinovirus URTI events, 100 (17%) progressed to LRTI. In a final multivariable model allogeneic grafts, prior rhinovirus URTI, low lymphocyte count, low albumin, positive cytomegalovirus serostatus, recipient statin use, and steroid use ≥2 mg/kg/day were associated with progression to LRTI. A weighted risk score cut-off with the highest sensitivity and specificity was determined. Risk scores above this cut-off were associated with progression to LRTI (cumulative incidence 28% versus 11% below cut-off; P < .001). The weighted risk score for progression to rhinovirus LRTI can help identify and stratify patients for clinical management and for future clinical trials of therapeutics in HCT recipients.


title: Predictive factors for disease progression in hospitalized patients with Coronavirus Disease 2019 in Wuhan, China

text: Abstract Background A few studies have revealed the clinical characteristics of hospitalized patients with COVID-19. However, predictive factors for the outcomes remain unclear. Objective Attempted to determine the predictive factors for the poor outcomes of patients with COVID-19. Study design This is a single-center, retrospective study. Clinical, laboratory, and treatment data were collected and analyzed from 111 hospitalized patients with laboratory-confirmed COVID-19 in Union Hospital. The gathered data of discharged and deteriorated patients were compared. Results Among these 111 patients, 93 patients were discharged and 18 patients were deteriorated. The lymphocyte count (0.56 G/L [0.47-0.63] vs 1.30 G/L [0.95-1.65]) was lower in the deteriorated group than those in the discharged group. The numbers of pulmonary lobe involved (5.00 [5.00–5.00] vs 4.00 [2.00-5.00]), serum C‐reactive protein (CRP, 79.52 mg/L [61.25-102.98] vs 7.93 mg/L [3.14-22.50]), IL-6 (35.72 pg/ml [9.24-85.19] vs 5.09 pg/ml [3.16-9.72]), and IL-10 (5.35 pg/ml [4.48-7.84] vs 3.97 pg/ml [3.34-4.79]) concentrations in deteriorated patients were elevated compared with discharged patients. Multivariate logistic regression analysis showed that male gender (OR, 24.8 [1.8-342.1]), comorbidity (OR, 52.6 [3.6-776.4]), lymphopenia (OR, 17.3 [1.1-261.8]), and elevated CRP (OR, 96.5 [4.6-2017.6]) were the independent risk factors for the poor prognosis in COVID-19 patients. Conclusions This finding would facilitate the early identification of high-risk COVID-19 patients.


title: Antigenic Drift of A/H3N2/Virus and Circulation of Influenza-Like Viruses During the 2014/2015 Influenza Season in Poland

text: Morbidity rates of influenza could be greatly reduced due to vaccination. However, the virus is able to evolve through genetic mutations, which is why vaccines with updated composition are necessary every season. Their effectiveness depends on whether there is a good antigenic match between circulating viruses and vaccine strains. In Poland, the 2014/2015 influenza epidemic started in week 5 (January/February) of 2015 and continued until week 17 (April) of 2015. The influenza activity was moderate with the highest incidence of influence-like illness at week 10/2015 (March). During that season, antigenic drift of influenza virus A/H3N2/ occurred causing higher rates of A/H3N2/ infections. Among the 2416 tested specimens, 22.6 % of influenza cases were positive for A/H3N2/, while A/H1N1/pdm09 constituted 14.6 % cases. Influenza A viruses were detected in co-circulation with influenza B viruses; the latter amounted to 34.1 % of all influenza detections. Other detected causes of influenza-like illness consisted of respiratory syncytial virus (RSV), being predominant, and, sporadically, human coronavirus, parainfluenza 1–3, rhinovirus, and adenovirus. Despite low vaccine effectiveness of solely one component, A/H3N2/, the vaccine could mitigate or shorten the length of influenza infection and reduce the number of severe outcomes and mortality. Thus, vaccination against influenza remains the most effective way to prevent illness and possibly fatal outcomes.


title: Relationship between clinical types and radiological subgroups defined by latent class analysis in 2019 novel coronavirus pneumonia caused by SARS-CoV-2

text: OBJECTIVES: To investigate whether meaningful subgroups sharing the CT features of patients with COVID-19 pneumonia could be identified using latent class analysis (LCA) and explore the relationship between the LCA-derived subgroups and clinical types. METHODS: This retrospective review included 499 patients with confirmed COVID-19 pneumonia between February 11 and March 8, 2020. Subgroups sharing the CT features were identified using LCA. Univariate and multivariate logistic regression models were utilized to analyze the association between clinical types and the LCA-derived subgroups. RESULTS: Two radiological subgroups were identified using LCA. There were 228 subjects (45.69%) in class 1 and 271 subjects (54.31%) in class 2. The CT findings of class 1 were smaller pulmonary infection volume, more peripheral distribution, more GGO, more maximum lesion range ≤ 5 cm, a smaller number of lesions, less involvement of lobes, less air bronchogram, less dilatation of vessels, less hilar and mediastinal lymph node enlargement, and less pleural effusion than the CT findings of class 2. Univariate analysis demonstrated that older age, therapy, presence of fever, presence of hypertension, decreased lymphocyte count, and increased CRP levels were significant parameters associated with an increased risk for class 2. Multivariate analyses revealed that the patients with clinically severe type disease had a 1.97-fold risk of class 2 than the patients with clinically moderate-type disease. CONCLUSIONS: The demographic and clinical differences between the two radiological subgroups based on the LCA were significantly different. Two radiological subgroups were significantly associated with clinical moderate and severe types. KEY POINTS: • Two radiological subgroups were identified using LCA. • Older age, therapy, presence of fever, presence of hypertension, decreased lymphocyte count, and increased CRP levels were significant parameters with an increased risk for class 2 defined by LCA. • Patients with clinically severe type had a 1.97-fold higher risk of class 2 defined by LCA in comparison with patients showing clinically moderate-type disease.


title: Time Course of Evolving Ventilator-Induced Lung Injury: The “Shrinking Baby Lung”

text: OBJECTIVES: To examine the potentially modifiable drivers that injure and heal the “baby lung” of acute respiratory distress syndrome and describe a rational clinical approach to favor benefit. DATA SOURCES: Published experimental studies and clinical papers that address varied aspects of ventilator-induced lung injury pathogenesis and its consequences. STUDY SELECTION: Published information relevant to the novel hypothesis of progressive lung vulnerability and to the biophysical responses of lung injury and repair. DATA EXTRACTION: None. DATA SYNTHESIS: In acute respiratory distress syndrome, the reduced size and capacity for gas exchange of the functioning “baby lung” imply loss of ventilatory capability that dwindles in proportion to severity of lung injury. Concentrating the entire ventilation workload and increasing perfusion to these already overtaxed units accentuates their potential for progressive injury. Unlike static airspace pressures, which, in theory, apply universally to aerated structures of all dimensions, the components of tidal inflation that relate to power (which include frequency and flow) progressively intensify their tissue-stressing effects on parenchyma and microvasculature as the ventilated compartment shrinks further, especially during the first phase of the evolving injury. This “ventilator-induced lung injury vortex” of the shrinking baby lung is opposed by reactive, adaptive, and reparative processes. In this context, relatively little attention has been paid to the evolving interactions between lung injury and response and to the timing of interventions that worsen, limit or reverse a potentially accelerating ventilator-induced lung injury process. Although universal and modifiable drivers hold the potential to progressively injure the functional lung units of acute respiratory distress syndrome in a positive feedback cycle, measures can be taken to interrupt that process and encourage growth and healing of the “baby lung” of severe acute respiratory distress syndrome.


title: SARS‐CoV‐2 spike protein favors ACE2 from Bovidae and Cricetidae

text: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causes the recent COVID‐19 public health crisis. Bat is the widely believed original host of SARS‐CoV‐2. However, its intermediate host before transmitting to humans is not clear. Some studies proposed pangolin, snake, or turtle as the intermediate hosts. Angiotensin‐converting enzyme 2 (ACE2) is the receptor for SARS‐CoV‐2, which determines the potential host range for SARS‐CoV‐2. On the basis of structural information of the complex of human ACE2 and SARS‐CoV‐2 receptor‐binding domain (RBD), we analyzed the affinity to S protein of the 20 key residues in ACE2 from mammal, bird, turtle, and snake. Several ACE2 proteins from Primates, Bovidae, Cricetidae, and Cetacea maintained the majority of key residues in ACE2 for associating with SARS‐CoV‐2 RBD. The simulated structures indicated that ACE2 proteins from Bovidae and Cricetidae were able to associate with SARS‐CoV‐2 RBD. We found that nearly half of the key residues in turtle, snake, and bird were changed. The simulated structures showed several key contacts with SARS‐CoV‐2 RBD in turtle and snake ACE2 were abolished. This study demonstrated that neither snake nor turtle was the intermediate hosts for SARS‐CoV‐2, which further reinforced the concept that the reptiles are resistant against infection of coronavirus. This study suggested that Bovidae and Cricetidae should be included in the screening of intermediate hosts for SARS‐CoV‐2.


title: On the solution of fractional order SIS epidemic model

text: Abstract We consider the fractional order epidemic model based on assumption that people will recover after disease and may be infected again on a time interval of non fatal disease. Our mathematical formulation is based on the fractional Caputo derivative. The existence and uniqueness of the solution is discussed. Furthermore, numerical solution is studied by variational iteration method and Euler method. Consequently, some numerical results are presented within.


title: When Is Quarantine a Useful Control Strategy for Emerging Infectious Diseases?

text: The isolation and treatment of symptomatic individuals, coupled with the quarantining of individuals that have a high risk of having been infected, constitute two commonly used epidemic control measures. Although isolation is probably always a desirable public health measure, quarantine is more controversial. Mass quarantine can inflict significant social, psychological, and economic costs without resulting in the detection of many infected individuals. The authors use probabilistic models to determine the conditions under which quarantine is expected to be useful. Results demonstrate that the number of infections averted (per initially infected individual) through the use of quarantine is expected to be very low provided that isolation is effective, but it increases abruptly and at an accelerating rate as the effectiveness of isolation diminishes. When isolation is ineffective, the use of quarantine will be most beneficial when there is significant asymptomatic transmission and if the asymptomatic period is neither very long nor very short.


title: Emerging Trends in COVID-19 Treatment: Learning from Inflammatory Conditions Associated with Cellular Therapies

text: Coronavirus disease 2019 (SARS-CoV2) is an active global health threat for which treatments are desperately being sought. Even though most people infected experience mild to moderate respiratory symptoms and recover with supportive care, certain vulnerable hosts develop severe clinical deterioration. While several drugs are currently being investigated in clinical trials, there are currently no approved treatments or vaccines for COVID-19 and hence there is an unmet need to explore additional therapeutic options. At least three inflammatory disorders or syndromes associated with immune dysfunction have been described in the context of cellular therapy. Specifically, Cytokine Release Syndrome (CRS), Immune Reconstitution Inflammatory Syndrome (IRIS), and Secondary Hemophagocytic Lymphohistiocytosis (sHLH) all have clinical and laboratory characteristics in common with COVID19 and associated therapies that could be worth testing in the context of clinical trials. Here we discuss these diseases, their management, and potential applications of these treatment in the context of COVID-19. We also discuss current cellular therapies that are being evaluated for the treatment of COVID-19 and/or its associated symptoms.


title: Preliminary Results of Initial Testing for Coronavirus (COVID-19) in the Emergency Department

text: INTRODUCTION: On March 10, 2020, the World Health Organization declared a global pandemic due to widespread infection of the novel coronavirus 2019 (COVID-19). We report the preliminary results of a targeted program of COVID-19 infection testing in the ED in the first 10 days of its initiation at our institution. METHODS: We conducted a review of prospectively collected data on all ED patients who had targeted testing for acute COVID-19 infection at two EDs during the initial 10 days of testing (March 10–19, 2020). During this initial period with limited resources, testing was targeted toward high-risk patients per Centers for Disease Control and Prevention guidelines. Data collected from patients who were tested included demographics, clinical characteristics, and test qualifying criteria. We present the data overall and by test results with descriptive statistics. RESULTS: During the 10-day study period, the combined census of the study EDs was 2157 patient encounters. A total of 283 tests were ordered in the ED. The majority of patients were 18–64 years of age, male, non-Hispanic white, had an Emergency Severity Index score of three, did not have a fever, and were discharged from the ED. A total of 29 (10.2%) tested positive. Symptoms-based criteria most associated with COVID-19 were the most common criteria identified for testing (90.6%). All other criteria were reported in 5.51–43.0% of persons being tested. Having contact with a person under investigation was significantly more common in those who tested positive compared to those who tested negative (63% vs 24.5%, respectively). The majority of patients in both results groups had at least two qualifying criteria for testing (75.2%). CONCLUSION: In this review of prospectively collected data on all ED patients who had targeted testing for acute COVID-19 infection at two EDs in the first 10 days of testing, we found that 10.2% of those tested were identified as positive. The continued monitoring of testing and results will help providers understand how COVID-19 is progressing in the community.


UK's MHRA publishes guidance for valproate PPP during pandemic


title: Orsay virus utilizes ribosomal frameshifting to express a novel protein that is incorporated into virions()

text: Orsay virus is the first identified virus that is capable of naturally infecting Caenorhabditis elegans. Although it is most closely related to nodaviruses, Orsay virus differs from nodaviruses in its genome organization. In particular, the Orsay virus RNA2 segment encodes a putative novel protein of unknown function, termed delta, which is absent from all known nodaviruses. Here we present evidence that Orsay virus utilizes a ribosomal frameshifting strategy to express a novel fusion protein from the viral capsid (alpha) and delta ORFs. Moreover, the fusion protein was detected in purified virus fractions, demonstrating that it is most likely incorporated into Orsay virions. Furthermore, N-terminal sequencing of both the fusion protein and the capsid protein demonstrated that these proteins must be translated from a non-canonical initiation site. While the function of the alpha–delta fusion remains cryptic, these studies provide novel insights into the fundamental properties of this new clade of viruses.


title: Viral quasispecies

text: Viral quasispecies refers to a population structure that consists of extremely large numbers of variant genomes, termed mutant spectra, mutant swarms or mutant clouds. Fueled by high mutation rates, mutants arise continually, and they change in relative frequency as viral replication proceeds. The term quasispecies was adopted from a theory of the origin of life in which primitive replicons) consisted of mutant distributions, as found experimentally with present day RNA viruses. The theory provided a new definition of wild type, and a conceptual framework for the interpretation of the adaptive potential of RNA viruses that contrasted with classical studies based on consensus sequences. Standard clonal analyses and deep sequencing methodologies have confirmed the presence of myriads of mutant genomes in viral populations, and their participation in adaptive processes. The quasispecies concept applies to any biological entity, but its impact is more evident when the genome size is limited and the mutation rate is high. This is the case of the RNA viruses, ubiquitous in our biosphere, and that comprise many important pathogens. In virology, quasispecies are defined as complex distributions of closely related variant genomes subjected to genetic variation, competition and selection, and that may act as a unit of selection. Despite being an integral part of their replication, high mutation rates have an upper limit compatible with inheritable information. Crossing such a limit leads to RNA virus extinction, a transition that is the basis of an antiviral design termed lethal mutagenesis.


title: Author Correction: Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing

text: [This corrects the article DOI: 10.1038/s41421-020-0168-9.].


title: Protective immune responses against West Nile virus are primed by distinct complement activation pathways

text: West Nile virus (WNV) causes a severe infection of the central nervous system in several vertebrate animals including humans. Prior studies have shown that complement plays a critical role in controlling WNV infection in complement (C) 3(−/−) and complement receptor 1/2(−/−) mice. Here, we dissect the contributions of the individual complement activation pathways to the protection from WNV disease. Genetic deficiencies in C1q, C4, factor B, or factor D all resulted in increased mortality in mice, suggesting that all activation pathways function together to limit WNV spread. In the absence of alternative pathway complement activation, WNV disseminated into the central nervous system at earlier times and was associated with reduced CD8(+) T cell responses yet near normal anti-WNV antibody profiles. Animals lacking the classical and lectin pathways had deficits in both B and T cell responses to WNV. Finally, and somewhat surprisingly, C1q was required for productive infection in the spleen but not for development of adaptive immune responses after WNV infection. Our results suggest that individual pathways of complement activation control WNV infection by priming adaptive immune responses through distinct mechanisms.


title: Wearable Cardiorespiratory Monitoring Employing a Multimodal Digital Patch Stethoscope: Estimation of ECG, PEP, LVET and Respiration Using a 55 mm Single-Lead ECG and Phonocardiogram

text: Cardiovascular diseases are the main cause of death worldwide, with sleep disordered breathing being a further aggravating factor. Respiratory illnesses are the third leading cause of death amongst the noncommunicable diseases. The current COVID-19 pandemic, however, also highlights the impact of communicable respiratory syndromes. In the clinical routine, prolonged postanesthetic respiratory instability worsens the patient outcome. Even though early and continuous, long-term cardiorespiratory monitoring has been proposed or even proven to be beneficial in several situations, implementations thereof are sparse. We employed our recently presented, multimodal patch stethoscope to estimate Einthoven electrocardiogram (ECG) Lead I and II from a single 55 mm ECG lead. Using the stethoscope and ECG subsystems, the pre-ejection period (PEP) and left ventricular ejection time (LVET) were estimated. ECG-derived respiration techniques were used in conjunction with a novel, phonocardiogram-derived respiration approach to extract respiratory parameters. Medical-grade references were the SOMNOmedics SOMNO HD(TM) and Osypka ICON-Core(TM). In a study including 10 healthy subjects, we analyzed the performances in the supine, lateral, and prone position. Einthoven I and II estimations yielded correlations exceeding 0.97. LVET and PEP estimation errors were 10% and 21%, respectively. Respiratory rates were estimated with mean absolute errors below 1.2 bpm, and the respiratory signal yielded a correlation of 0.66. We conclude that the estimation of ECG, PEP, LVET, and respiratory parameters is feasible using a wearable, multimodal acquisition device and encourage further research in multimodal signal fusion for respiratory signal estimation.


title: Viral bronchiolitis in children: A common condition with few therapeutic options

text: Abstract Even though bronchiolitis is a disease that has been recognized for many years, there are still few therapeutic strategies beyond supportive therapies. Bronchiolitis is the most frequent cause of hospital admission in children less than 1 year of age. The incidence is estimated to be about 150° million cases a year worldwide, and 2–3% of these cases require hospitalization. It is acknowledged that viruses cause bronchiolitis, but most of the studies focus on RSV. The RSV causes a more severe form of bronchiolitis in children with risk factors including prematurity, cardiovascular disease and immunodeficiency. Other viruses involved in causing bronchiolitis include RV, hMPV, hBoV and co-infections. The RV seems to be associated with a less severe acute disease, but there is a correlation between the early infection and subsequent wheezing bronchitis and asthma in later childhood and adulthood. The supportive therapies used are intravenous fluids and oxygen supplement administered by nasal cannula or CPAP in most complicated patients. Additional pharmacological therapies include epinephrine, 3% hypertonic saline and corticosteroids. The Epinephrine seems to have the greatest short-term benefits and reduces the need of hospital admission, whereas hypertonic saline and corticosteroids seem to reduce the length of hospital stay. As bronchiolitis is such a prevalent disease in children and RV seems to play an important role, perhaps more studies should center around the RV's contribution to the initial disease and following pathology.


title: Response of genetically susceptible and resistant mice to intranasal inoculation with mouse hepatitis virus JHM

text: Abstract Mouse hepatitis virus (MHV)-JHM infection was studied in genetically susceptible (BALB/cByJ) and resistant (SJL/J) mice following intranasal inoculation at 1, 3, 6 or 12 wk of age. Markers of infection included histology, immunohistochemistry, virus quantification and virus serology. All BALE mice developed severe disseminated disease with high mortality due to encephalitis and hepatitis. Peak MHV titers appeared in brain, liver, spleen and intestine on days 3 or 5. Age at inoculation did not influence virus titers in brain, spleen or intestine, but virus titers in liver were inversely proportional to age at inoculation. In 6-wk-old BALE mice, virus was cleared from spleen, intestine and liver by day 30 and from brain by day 60. In intestine, MHV was localized to lymphoid tissue, without fecal excretion. SJL mice of all ages developed remarkably milder disease with low mortality occurring only among mice inoculated at 1 wk of age. SJL mice inoculated at 1 wk had disseminated infection at day 3, but lesions and antigen were cleared from most organs by day 5. Mice inoculated at 3 and 6 wk of age had minimal or no involvement of peripheral organs, and mice inoculated at 12 wk of age had infections restricted to the nose. At day 5, MHV titers in brain, liver, spleen and intestine were significantly lower or undetectable in SJL mice of all ages compared to age-matched BALB mice. In 6-wk-old mice, MHV was cleared from all organs by day 10. Serum antibody titers to MHV were many-fold higher in BALB mice, compared to SJL mice, which mounted only a modest response.


title: Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by chloroquine: Involvement of p38 MAPK and ERK

text: Abstract The antiviral effects of chloroquine (CQ) on human coronavirus 229E (HCoV-229E) infection of human fetal lung cell line, L132 are reported. CQ significantly decreased the viral replication at concentrations lower than in clinical usage. We demonstrated that CQ affects the activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK). Furthermore, p38 MAPK inhibitor, SB203580, inhibits CPE induced by HCoV-229E infection and viral replication. Our findings suggest that CQ affects the activation of MAPKs, involved in the replication of HCoV-229E.


title: Bone sarcoma surgery in times of COVID-19 pandemic lockdown-early experience from a tertiary centre in India

text: Abstract Background and Objectives Coronavirus disease 2019 (COVID-19) lockdown has presented a unique challenge for sarcoma care The purpose of this study is to evaluate the early results and feasibility of surgeries for bone sarcomas during the COVID-19 lockdown Methods Our prospectively collected orthopaedic oncological database was reviewed to include two groups of patients- those who underwent surgery in the immediate 4 weeks before lockdown (non-lockdown group) and those operated in the first 4 weeks of lockdown (lockdown group) All patients were followed-up clinically and telephonically to collect the outcome data Results Out of the 91 patients who qualified for inclusion, fifty were classified into the non-lockdown group while 41 patients formed the lockdown group Both the groups were comparable with respect to baseline demographic parameters However, during the lockdown period 37 patients (90%) had undergone a major surgical intervention as against 24 patients (48%) in the non-lockdown group (P?<? 001) There was no significant difference in type of anaesthesia, median estimated blood loss and procedure duration None of the patients/health care workers had evidence of severe acute respiratory syndrome-coronavirus 2 infection at 15 days follow-up Conclusion Our study results suggest that appendicular bone tumours can be safely operated with adequate precautions during the lockdown period


title: Chapter 1 Seeds of Destruction

text: Abstract This chapter provides the reader with an understanding and appreciation for the scope and importance of biological threats and the opportunity to see where they may be and have become the desire of terrorist groups and the makings of weapons of mass destruction. The history of biological warfare is covered in depth. These major events are important in helping us understand the issues related to using biological substances against an adversary. The difference between biosecurity and biodefense are explained and then related to homeland security and homeland defense, respectively. This chapter also details how expensive these programs are, with nearly $80billion having been spent on civilian biodefense since fiscal year 2001 in the United States alone. As discussed herein, there is a significant difference in the reality and the potential of bioterrorism. Bioterrorism on a large scale is a low-probability event. Bioterrorism on a small scale is a fairly routine occurrence with little potential. Biological threats remain very much in the news. Recent examples, such as laboratory incidents, the Ebola outbreak of 2014, and other emerging threats, are covered in this chapter.


title: Ecological niche modeling to determine potential niche of Vaccinia virus: a case only study

text: BACKGROUND: Emerging and understudied pathogens often lack information that most commonly used analytical tools require, such as negative controls or baseline data; thus, new analytical strategies are needed to analyze transmission patterns and drivers of disease emergence. Zoonotic infections with Vaccinia virus (VACV) were first reported in Brazil in 1999, VACV is an emerging zoonotic Orthopoxvirus, which primarily infects dairy cattle and farmers in close contact with infected cows. Prospective studies of emerging pathogens could provide critical data that would inform public health planning and response to outbreaks. By using the location of 87-recorded outbreaks and publicly available bioclimatic data, we demonstrate one such approach. Using an ecological niche model (ENM) algorithm, we identify the environmental conditions under which VACV outbreaks have occurred, and determine additional locations in two affected countries that may be susceptible to transmission. Further, we show how suitability for the virus responds to different levels of various environmental factors and highlight the most important factors in determining its transmission. METHODS: A literature review was performed and the geospatial coordinates of 87 molecularly confirmed VACV outbreaks in Brazil were identified. An ENM was generated using MaxENT software by combining principal component analysis results of 19 bioclim spatial layers, and 25 randomly selected subsets of the original list of 87 outbreaks. RESULTS: The final ENM predicted all areas where Brazilian outbreaks occurred, one out of five of the Colombian outbreak regions and identified new regions within Brazil that are suitable for transmission based on bioclimatic factors. Further, the most important factors in determining transmission suitability are precipitation of the wettest quarter, annual precipitation, mean temperature of the coldest quarter and mean diurnal range. CONCLUSION: The analyses here provide a means by which to study patterns of an emerging infectious disease and identify regions that are potentially suitable for its transmission, in spite of the paucity of high-quality critical data. Policy and methods for the control of infectious diseases often use a reactionary model, addressing diseases only after significant impact on human health has ensued. The methodology used in the present work allows the identification of areas where disease is likely to appear, which could be used for directed intervention. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12942-017-0100-1) contains supplementary material, which is available to authorized users.


title: Kinetics of viral load and cytokines in severe fever with thrombocytopenia syndrome

text: Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease in China, Japan, and Korea, which is characterized by high fever, thrombocytopenia, and high mortality. It is hypothesized that a cytokine storm plays an important role in the pathophysiology of SFTS. However, limited data have been published on the detailed kinetics of the viral load and cytokine profiles throughout the course of this disease. Objectives We investigated the patterns of changes in cytokines and viral load in SFTS patients. Study design During the admission period of patients, RNA was extracted from plasma and quantified by reverse transcription polymerase chain reaction. In addition, cytokine bead arrays were performed for the 18 cytokines and chemokines selected for testing. Results The median time from admission to the negative conversion of SFTS viremia was 17.0 days. When censored patients were found to be negative for viral load at discharge, the median duration of viral shedding was 13.0 days (95% CI, 5.4–20.6). Interferon (IFN)-α, interleukin (IL)-10, and IFN-γ-induced protein (IP)-10 concentrations significantly increased in the early course of disease and then decreased during the hospital stay. However, the concentrations of tumor necrosis factor-α, IL-1β, IL-12p40, IL-13, IL-17A, Regulated on Activation and Normally T-cell Expressed and Secreted (RANTES), and vascular endothelial growth factor (VEGF) increased during the late course of disease. Initial IP-10 levels during hospital days 1–4 were the most significantly correlated with initial viral load (r = 0.88, P < .01). Conclusion SFTS viremia persisted until weeks 2–3 and was highly correlated with initial plasma IP-10 levels. In addition, IFN-α, IL-10, and IP-10 were associated with the initial cytokine storm in SFTS.


title: Clinical role of lung ultrasound for the diagnosis and monitoring of COVID‐19 pneumonia in pregnant women

text: Lung ultrasound has recently been suggested by the Chinese Critical Care Ultrasound Study Group and Italian Academy of Thoracic Ultrasound as an accurate tool to detect lung involvement during COVID‐19. Although chest Computer Tomography (CT) represents the gold standard to assess lung involvement, with a specificity even superior to the nasal/pharyngeal swab for diagnosis, lung ultrasound examination can be a valid alternative to CT scan, with some advantages, particularly desirable for pregnant women. Indeed, ultrasound can be performed directly at bed side by a single operator, reducing the risk of spreading the outbreak among health professionals, as well as it is a radiation free exam making to be easier monitoring those patients who require serial exams. In the present study, we reported four cases of pregnant women affectd by COVID‐19 infection who have been monitoring with lung ultrasound examination. All patients showed ultrasound features indicative of COVID‐19 pneumonia at admission: irregular pleural lines and vertical artifacts (B‐lines) were observed in all four cases, whereas patchy areas of white lung in two cases. LUS was more sensitive than chest X‐ray in detecting COVID‐19. Three patients had resolution of lung pathology at ultrasound after 96 h of admission. Two pregnancies are ongoing, whereas two patients had cesarean delivery with no fetal complications. PCR testing of both cord blood and newborn swabs were negative in both cases. This article is protected by copyright. All rights reserved.


title: What can we predict about viral evolution and emergence?

text: Predicting the emergence of infectious diseases has been touted as one of the most important goals of biomedical science, with an array of funding schemes and research projects. However, evolutionary biology generally has a dim view of prediction, and there is a danger that erroneous predictions will mean a misuse of resources and undermine public confidence. Herein, I outline what can be realistically predicted about viral evolution and emergence, argue that any success in predicting what may emerge is likely to be limited, but that forecasting how viruses might evolve and spread following emergence is more tractable. I also emphasize that a properly grounded research program in disease prediction must involve a synthesis of ecological and genetic perspectives.


title: Angiotensin-Converting Enzyme 2 and Antihypertensives (Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors) in Coronavirus Disease 2019

text: Abstract Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is being defined as the worst pandemic disease of modern times. Several professional health organizations have published position papers stating that there is no evidence to change the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in the management of elevated blood pressure in the context of avoiding or treating COVID-19 infection. In this article, we review the evidence on the relationship between the renin-angiotensin-aldosterone system and COVID-19 infection. In agreement with current guidelines, patients with hypertension should continue taking antihypertensive medications as prescribed without interruption. Because ACEIs and ARBs are also used to retard the progression of chronic kidney disease, we suggest that these recommendations also apply to the use of these agents in chronic kidney disease. No differences generally exist between ARBs and ACEIs in terms of efficacy in decreasing blood pressure and improving other outcomes, such as all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease. The ACEIs are associated with cough secondary to accumulation of bradykinin and angioedema, and withdrawal rates due to adverse events are lower with ARBs. Given their equal efficacy but fewer adverse events, ARBs could potentially be a more favorable treatment option in patients with COVID-19 at higher risk for severe forms of disease.


COVID-19 in patients with HIV – Authors' reply


title: A systematic review of FTA cards® as a tool for viral RNA preservation in fieldwork: Are they safe and effective?

text: Abstract BackgroundDetection and characterization of viral RNA pathogens from fieldwork are challenging due to the instability of the RNA molecule. FTA cards® have proved useful for sample storage and latter identification of pathogens with importance for agricultural, animal and human health: however, for optimal handling, processing, and biosafety measures are not well-established. ObjectiveThis systematic review aims to summarize the reported effectiveness of FTA cards® for storage and transport of viral RNA, as well as the conditions for their handling and use in downstream processes. Finally, the biosafety measures required to protect researchers and clinical lab workers are considered. MethodsWe performed a systematic review following the PRISMA statement. We searched MEDLINE (PubMed), Scopus and Web of Science using the keywords “FTA cards” AND “RNA”. Articles were screened by title and abstract, and after examination of inclusion and exclusion criteria, relevant information was extracted. The quality of the studies was assessed, and the evidence was qualitatively summarized. ResultsA total of 175 records were retrieved, and 11 additional documents were found by checking references of the eligible articles. A total of 47 articles were included. Samples from animals accounted for 38.3% of the publications, which identified viruses that cause disease in poultry, wild birds, suids, or bovids. Three different methods for RNA extraction were reported. Other factors that vary across reports include the size of RNA amplicon, storage temperature, and duration of storage. Only fourteen articles tested the inactivation of the virus on the FTA card®, and in one case, the virus remained infective. ConclusionFTA cards® could be a suitable option for RNA virus storage and transport for fieldwork in areas where proper conditions for RNA preservation are difficult to achieve. Three different protocols have been used for RNA detection from this matrix. Biospecimens in the form of dried blood spots should be considered potentially infectious unless specifically treated to inactivate viral pathogens.


title: BBMRI-ERIC’s contributions to research and knowledge exchange on COVID-19

text: During the COVID-19 pandemic, the European biobanking infrastructure is in a unique position to preserve valuable biological material complemented with detailed data for future research purposes. Biobanks can be either integrated into healthcare, where preservation of the biological material is a fork in clinical routine diagnostics and medical treatment processes or they can also host prospective cohorts or material related to clinical trials. The paper discussed objectives of BBMRI-ERIC, the European research infrastructure established to facilitate access to quality-defined biological materials and data for research purposes, with respect to the COVID-19 crisis: (a) to collect information on available European as well as non-European COVID-19-relevant biobanking resources in BBMRI-ERIC Directory and to facilitate access to these via BBMRI-ERIC Negotiator platform; (b) to help harmonizing guidelines on how data and biological material is to be collected to maximize utility for future research, including large-scale data processing in artificial intelligence, by participating in activities such as COVID-19 Host Genetics Initiative; (c) to minimize risks for all involved parties dealing with (potentially) infectious material by developing recommendations and guidelines; (d) to provide a European-wide platform of exchange in relation to ethical, legal, and societal issues (ELSI) specific to the collection of biological material and data during the COVID-19 pandemic.


Should you disinfect your online shopping?


title: Unipolar ion emission enhances respiratory protection against fine and ultrafine particles

text: Abstract We developed a novel concept that allows to considerably improve the performance of conventionally used filtering-facepiece respirators against fine and ultrafine aerosols including airborne viral and bacterial agents. The concept is based on the continuous emission of unipolar ions. The effect was evaluated through the real-time monitoring of the concentration and size distribution of fine and ultrafine aerosol particles. The measurements were conducted inside and outside of a respiratory mask that was face sealed on a breathing manikin. A commonly used Type N95 respirator and surgical mask were utilized for the tests. The manikin was placed in a 24.3-m3 indoor test chamber and exposed to polydisperse surrogate aerosols simulating viral and bacterial particles with respect to the aerodynamic size. The particle penetration through the mask was found to decrease by one-to-two orders of magnitude as a result of continuous unipolar ion emission in the chamber. The flux of air ions migrated to the breathing zone and imparted electrical charges of the same polarity to the aerosol particles and the respirator filter surface. This created an electrostatic shield along the external surface of the filter, thus enhancing the protection characteristics provided by the respirator. The above performance enhancement effect is crucial for minimizing the infectious risk in the cases when the conventional filtering-facepiece respirators are not able to provide an adequate protection against airborne viruses and bacteria.


title: SARS-CoV-2 Infection and COVID-19 During Pregnancy: A Multidisciplinary Review

text: Abstract The global pandemic of SARS-CoV-2, the cause of Coronavirus disease 2019 (COVID-19), has been associated with worse outcomes in several patient populations, including the elderly and those with chronic comorbidities. Data from previous pandemics and seasonal influenza suggest that pregnant women may be at increased risk for infection-associated morbidity and mortality. Physiological changes in normal pregnancy and metabolic and vascular changes of high-risk pregnancies may affect pathogenesis or exacerbate the clinical presentation of COVID-19. Specifically, SARS-CoV-2 enters the cell via the angiotensin converting enzyme 2 (ACE2) receptor, which is upregulated in normal pregnancy. Upregulation of ACE2 mediates conversion of Angiotensin II (vasoconstrictor) to Angiotensin 1-7 (vasodilator) and contributes to relatively low blood pressures, despite upregulation of other components of the renin angiotensin aldosterone system. As a result of higher ACE2 expression, pregnant women may be at an elevated risk of complications from SARS-CoV-2 infection. Upon binding to ACE2, SARS-CoV-2 causes its downregulation, thus lowering Angiotensin 1-7 levels, which can mimic/worsen vasoconstriction, inflammation, and pro-coagulopathic effects that occur in preeclampsia. Indeed, early reports suggest that, among other adverse outcomes, preeclampsia may be more common in pregnant women with COVID-19. Medical therapy, during both pregnancy and breast feeding, relies on medications with proven safety, but safety data are often missing for medications in the early stages of clinical trials. We summarize guidelines for medical/obstetric care and outline future directions for optimization of treatment and preventive strategies for pregnant patients with COVID-19 with the understanding that relevant data are limited and rapidly changing.


title: May patients receiving 5-alpha-reductase inhibitors be in higher risk of COVID-19 complications ?

text: Abstract COVID-19 pandemic is a major challenge for global and national healthcare providers. Number of new cases is continuously increasing with an emerging trend showing worse prognosis in males in comparison to females. Based on this observation, our proposed hypothesis is that 5-alpha-reductase inhibitors, that are commonly used for BPH treatment, may be one of the factors contributing to poorer prognosis in males. Background With increasing number of COVID-19 cases, an evident sex- dependent difference in disease outcomes can be observed. Based on published studies with short term follow-up, males have 65% higher mortality rate (1). The question remains, whether long term observational studies will confirm improved recovery in females.


title: Using a novel rapid viral test to improve triage of emergency department patients with acute respiratory illness during flu season

text: Abstract Background Acute respiratory illnesses (ARI) are mostly viral in etiology and cause significant morbidity and mortality. Point of care PCR (POC-PCR) is a promising new technology for rapid virus identification but utility in the Emergency Department (ED) is not yet defined. Objectives Primarily, to investigate the value of POC-PCR in rapidly identifying RSV and influenza in the setting of ED triage. Additionally, to assess whether rapid knowledge of accurate test results would improve patient management by preventing nosocomial transmission and optimizing the prescription of antimicrobials for ARIs. Study Design A prospective cohort study of consecutive ED patients with ARI symptoms during peak flu season was conducted. Patient nasopharyngeal swabs were collected and tested using a POC-PCR device; physicians and patients were blinded to results. Virus positive and negative groups were compared by ED patient room placement and antimicrobial therapy ordered. Specificity and sensitivity were calculated using laboratory-PCR as the gold standard. Results Of 119 participants, 52.9% were POC-PCR positive - Influenza A (42.9%), RSV (41.3%), influenza B (15.9%). Nearly 70% of virus positive patients were placed rooms shared with non-ARI patients. Antibiotics were prescribed for 27.3% of virus positive patients, and 77.8% of oseltamivir-eligible patients did not receive therapy. POC-PCR was 100% sensitive (95% CI, 80.5–100.0%) and 95.2% specific (95% CI, 76.2–99.9%). Conclusions Rapid POC-PCR for influenza and RSV in ED triage has excellent sensitivity and specificity and the potential to improve social distancing practices through better triage and increase appropriate prescription of antimicrobials.


title: Proteomic analysis of serum, plasma, and lymph for the identification of biomarkers

text: Probably no topic has generated more excitement in the world of proteomics than the search for biomarkers. This excitement has been generated by two realities: the constant need for better biomarkers that can be used for disease diagnosis and prognosis, and the recent developments in proteomic technologies that are capable of scanning the individual proteins within varying complex clinical samples. Ideally a biomarker would be assayable from a noninvasively collected sample, therefore, much of the focus in proteomics has been on the analysis of biofluids such as serum, plasma, urine, cerebrospinal fluid, lymph, etc. While the discovery of biomarkers has been elusive, there have been many advances made in the understanding of the proteome content of various biofluids, and in the technologies used for their analysis, that continues to point the research community toward new methods for achieving the ultimate goal of identifying novel disease‐specific biomarkers. In this review, we will describe and discuss many of the proteomic approaches taken in an attempt to find novel biomarkers in serum, plasma, and lymph.


title: Mechanisms and impact of the frequent exacerbator phenotype in chronic obstructive pulmonary disease

text: Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients. Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype. This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes. These patients are therefore a priority for research and treatment. The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection. Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment. Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype. This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.


title: The new frontier of diagnostics: Molecular assays and their role in infection prevention and control

text: Recent advances in technology over the last decade have propelled the microbiology laboratory into a pivotal role in infection prevention and control. The rapid adaptation of molecular technologies to the field of clinical microbiology now greatly influences infectious disease management and significantly impacts infection control practices. This review discusses recent developments in molecular techniques in the diagnosis of infectious diseases. It describes the basic concepts of molecular assays, discusses their advantages and limitations, and characterizes currently available commercial assays with respect to cost, interpretive requirements, and clinical utility.


title: SEQUENCE OF MURINE CORONAVIRUS JHM INDUCED NEUROPATHOLOGICAL CHANGES IN RATS

text: Infection of 21–25‐day‐old rats with the murine coronavirus JHM was followed either by an acute encephalomyelitis (AE) or subacute demyelinating encephalomyelitis (SDE). The major neuropathological finding in AE, which developed within 6–12 days pi. consisted of necrotizing lesions distributed mainly in the grey matter of the central nervous system (CNS). SDE developed 14–30 days pi. and affected rats revealed lesions of primary demyelination with predilection sites in the white matter. The time‐course for the development of lesions, virus replication and neutralizing antiviral antibody production within the first 3 weeks p.i. were studied. Within the first 2 weeks p.i., most rats showed no clinical signs but nevertheless revealed lesions typical of AE. In parallel to these neuropathological changes infectious virus could be isolated from brain and spinal cord. However, coinciding with multiplication of neutralizing JHM antibodies 10–12 days after infection no infectious virus was recoverable from CNS material. At this time many of the clinically healthy rats showed demyelinating lesions which were located at the typical predilection sites of SDE. These observations indicated that SDE was preceded by clinically silent AE lesions.


title: Detection of Sirtuin-1 protein expression in peripheral blood leukocytes in dogs

text: Sirtuin-1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD(+))-dependent histone deacetylase with a large number of protein substrates. It has attracted a lot of attention in association with extending lifespan. The objective of this study was to enable the evaluation of SIRT1 expression in peripheral blood mononuclear cells (PBMCs) from dogs by flow cytometry. Three transcript variants were amplified from PBMCs by reverse transcription PCR and the nucleotide sequences were analyzed. On the basis of deduced amino acid sequence, a monoclonal antibody against human SIRT1, 1F3, was selected to detect canine SIRT1. Canine SIRT1 in peripheral blood mononuclear cells was successfully detected by western blotting using this antibody. Intracellular canine SIRT1 was also detected in permeabilized 293T cells transfected with a canine SIRT1 expression plasmid by flow cytometry using this antibody. SIRT1 was detected in all leukocyte subsets including lymphocytes, granulocytes and monocytes. The expression level was markedly different among individual dogs. These results indicated that the method applied in this study is useful for evaluating canine SIRT1 levels in PBMCs from dogs.