title: Financial implications of fourth industrial revolution: Can bitcoin improve prospects of energy investment?

text: Bitcoin and the blockchain technology on which it is based are the key drivers behind the accelerated pace of Fourth Industrial Revolution in the domain of Finance. The offshoots of this technology however are not limited and are rapidly spreading in other domains such as oil market. This paper investigates the causality or influences that both markets, Bitcoin price (BP) and oil price (OP) have on each other by applying the bootstrap Granger causal relationship tests considering full as well as sub-samples. Our analysis reveals that shocks originated in OP and transmitted towards BP can be both positive or negative. The positive impact indicates that Bitcoin can be viewed as an asset helpful in avoiding the risks of the high OP, which also indicates that Bitcoin and oil are in the same boat, however, the negative effects cannot support this view. The negative influence of OP on BP can be explained by the burst of the Bitcoin bubble which has weakened its hedging ability. In turn, there is also a negative influence or reverse causality running from BP to OP, highlighting that the demand for oil by investors can be threatened by the increasing BP. Keeping in view the more integrated and complexed financial dynamics which are the results of Fourth Industrial Revolution, investors can benefit from this interrelationship to diversify the risks and optimize their investment by building a more balanced portfolio. Also, governments could promote and protect the healthy development of the Bitcoin and energy market by preventing the Bitcoin bubbles and understanding the reasons of oil price volatility.


title: Taming wildlife disease: bridging the gap between science and management

text: 1. Parasites and pathogens of wildlife can threaten biodiversity, infect humans and domestic animals, and cause significant economic losses, providing incentives to manage wildlife diseases. Recent insights from disease ecology have helped transform our understanding of infectious disease dynamics and yielded new strategies to better manage wildlife diseases. Simultaneously, wildlife disease management (WDM) presents opportunities for large‐scale empirical tests of disease ecology theory in diverse natural systems. 2. To assess whether the potential complementarity between WDM and disease ecology theory has been realized, we evaluate the extent to which specific concepts in disease ecology theory have been explicitly applied in peer‐reviewed WDM literature. 3. While only half of WDM articles published in the past decade incorporated disease ecology theory, theory has been incorporated with increasing frequency over the past 40 years. Contrary to expectations, articles authored by academics were no more likely to apply disease ecology theory, but articles that explain unsuccessful management often do so in terms of theory. 4. Some theoretical concepts such as density‐dependent transmission have been commonly applied, whereas emerging concepts such as pathogen evolutionary responses to management, biodiversity–disease relationships and within‐host parasite interactions have not yet been fully integrated as management considerations. 5. Synthesis and applications. Theory‐based disease management can meet the needs of both academics and managers by testing disease ecology theory and improving disease interventions. Theoretical concepts that have received limited attention to date in wildlife disease management could provide a basis for improving management and advancing disease ecology in the future.


Raoult, social distancing and the rebelious French ‐ A reflection on COVID‐19 treatments online debates


title: Commentary on Ferguson, et al., “Impact of Non-pharmaceutical Interventions (NPIs) to Reduce COVID-19 Mortality and Healthcare Demand”

text: A recent manuscript (Ferguson et al. in Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand, Imperial College COVID-19 Response Team, London, 2020. https://www.imperial.ac.uk/media/imperial-college/medicine/sph/ide/gida-fellowships/Imperial-College-COVID19-NPI-modelling-16-03-2020.pdf) from Imperial College modelers examining ways to mitigate and control the spread of COVID-19 has attracted much attention. In this paper, we will discuss a coarse taxonomy of models and explore the context and significance of the Imperial College and other models in contributing to the analysis of COVID-19.


title: Physiological Level Production of Antigen-Specific Human Immunoglobulin in Cloned Transchromosomic Cattle

text: Therapeutic human polyclonal antibodies (hpAbs) derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc) cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH) and kappa-chain (hIGK) germline loci (named as κHAC) are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO). However, B lymphocyte development in these Tc cattle is compromised, and the overall production of hpAbs is low. Here, we report the construction of an improved HAC, designated as cKSL-HACΔ, by incorporating all of the human immunoglobulin germline loci into the HAC. Furthermore, for avoiding the possible human-bovine interspecies incompatibility between the human immunoglobulin mu chain protein (hIgM) and bovine transmembrane α and β immunoglobulins (bIgα and bIgβ) in the pre-B cell receptor (pre-BCR) complex, we partially replaced (bovinized) the hIgM constant domain with the counterpart of bovine IgM (bIgM) that is involved in the interaction between bIgM and bIgα/Igβ; human IgM bovinization would also improve the functionality of hIgM in supporting B cell activation and proliferation. We also report the successful production of DKO Tc cattle carrying the cKSL-HACΔ (cKSL-HACΔ/DKO), the dramatic improvement of B cell development in these cattle and the high level production of hpAbs (as measured for the human IgG isotype) in the plasma. We further demonstrate that, upon immunization by tumor immunogens, high titer tumor immunogen-specific human IgG (hIgG) can be produced from such Tc cattle.


title: Xenosurveillance: A Novel Mosquito-Based Approach for Examining the Human-Pathogen Landscape

text: BACKGROUND: Globally, regions at the highest risk for emerging infectious diseases are often the ones with the fewest resources. As a result, implementing sustainable infectious disease surveillance systems in these regions is challenging. The cost of these programs and difficulties associated with collecting, storing and transporting relevant samples have hindered them in the regions where they are most needed. Therefore, we tested the sensitivity and feasibility of a novel surveillance technique called xenosurveillance. This approach utilizes the host feeding preferences and behaviors of Anopheles gambiae, which are highly anthropophilic and rest indoors after feeding, to sample viruses in human beings. We hypothesized that mosquito bloodmeals could be used to detect vertebrate viral pathogens within realistic field collection timeframes and clinically relevant concentrations. METHODOLOGY/PRINCIPAL FINDINGS: To validate this approach, we examined variables influencing virus detection such as the duration between mosquito blood feeding and mosquito processing, the pathogen nucleic acid stability in the mosquito gut and the pathogen load present in the host’s blood at the time of bloodmeal ingestion using our laboratory model. Our findings revealed that viral nucleic acids, at clinically relevant concentrations, could be detected from engorged mosquitoes for up to 24 hours post feeding by qRT-PCR. Subsequently, we tested this approach in the field by examining blood from engorged mosquitoes from two field sites in Liberia. Using next-generation sequencing and PCR we were able to detect the genetic signatures of multiple viral pathogens including Epstein-Barr virus and canine distemper virus. CONCLUSIONS/SIGNIFICANCE: Together, these data demonstrate the feasibility of xenosurveillance and in doing so validated a simple and non-invasive surveillance tool that could be used to complement current biosurveillance efforts.


title: The Hepatitis E virus intraviral interactome

text: Hepatitis E virus (HEV) is an emerging virus causing epidemic acute hepatitis in developing countries as well as sporadic cases in industrialized countries. The life cycle of HEV is still poorly understood and the lack of efficient cell culture systems and animal models are the principal limitations for a detailed study of the viral replication cycle. Here we exhaustively examine all possible intraviral protein-protein interactions (PPIs) of HEV by systematic Yeast two-hybrid (Y2H) and LuMPIS screens, providing a basis for studying the function of these proteins in the viral replication cycle. Key PPIs correlate with the already published HEV 3D structure. Furthermore, we report 20 novel PPIs including the homodimerization of the RNA dependent RNA polymerase (RdRp), the self-interaction of the papain like protease, and ORF3 interactions with the papain-like protease and putative replicase components: RdRp, methylase and helicase. Furthermore, we determined the dissociation constant (K(d)) of ORF3 interactions with the viral helicase, papain-like protease and methylase, which suggest a regulatory function for ORF3 in orchestrating the formation of the replicase complex. These interactions may represent new targets for antiviral drugs.


title: Chitosan elicitation of Isatis tinctoria L. hairy root cultures for enhancing flavonoid productivity and gene expression and related antioxidant activity

text: Abstract Elicitation for phytochemical enhancement via cost-effective elicitors can overcome the limitation of commercial application faced by plant cell and organ culture technology. Chitosan is a natural, low-cost, and nontoxic elicitor that can trigger plant defense responses with the concomitant enhancement in phytochemical biosynthesis. In this work, the elicitation of Isatis tinctoria L. hairy root cultures by chitosan was conducted to enhance the production of pharmacologically active flavonoids. In comparison with control (2.31 ± 0.29 mg/g DW), a 7.08-fold enhancement of total flavonoids (16.35 ± 0.88 mg/g DW) was achieved in 24 day-old I. tinctoria hairy root cultures elicited by 150 mg/L chitosan for 36 h. Interestingly, the multiple hydroxyl-substituted ﬂavonoids (rutin, quercetin, isorhamnetin, and isoliquiritigenin) were noticed to increase significantly in chitosan-elicited I. tinctoria hairy root cultures. Moreover, the transcription of associated genes involved in flavonoid biosynthesis pathway was significantly up-regulated underlying chitosan elicitation, among which chalcone synthase and flavonoid 3′-hydroxylase might play an important role in flavonoid enhancement. Additionally, extracts from chitosan-elicited I. tinctoria hairy root cultures exhibited higher antioxidant activities with lower IC50 values as compared with control. Overall, a cost-effective strategy via the simple chitosan elicitation is provided here to enhance the production of high-added value flavonoids in I. tinctoria hairy root cultures, which paves the way toward the successful commercialization of this in vitro culture system in the future.


Involvement of ADAMTS13 and von Willebrand factor in thromboembolic events in patients infected with SARS‐CoV‐2


title: Emerging diseases, zoonoses and vaccines to control them

text: Vaccination, when available, is undoubtedly the most cost-effective means of preventing and controlling, and even eradicating, infectious diseases. In recent years vaccination has also been used for other purposes in animal health, production and welfare, e.g. immunocastration. Vaccination of animals serves many different purposes, such as controlling animal infections and infestations, thus improving animal health and welfare; controlling anthropozoonoses and food poisoning in humans, thereby protecting public health; solving problems associated with antibiotic and anthelmintic resistance; helping to leave food-producing animals free of chemical residues; protecting the environment and biodiversity and ensuring animal farming sustainability. The problem is nevertheless more complex when facing emerging or re-emerging infections particularly zoonotic ones.


title: Detection rate and clinical impact of respiratory viruses in children with Kawasaki disease

text: PURPOSE: The purpose of this prospective case-control study was to survey the detection rate of respiratory viruses in children with Kawasaki disease (KD) by using multiplex reverse transcriptase-polymerase chain reaction (RT-PCR), and to investigate the clinical implications of the prevalence of respiratory viruses during the acute phase of KD. METHODS: RT-PCR assays were carried out to screen for the presence of respiratory syncytial virus A and B, adenovirus, rhinovirus, parainfluenza viruses 1 to 4, influenza virus A and B, metapneumovirus, bocavirus, coronavirus OC43/229E and NL63, and enterovirus in nasopharyngeal secretions of 55 KD patients and 78 control subjects. RESULTS: Virus detection rates in KD patients and control subjects were 32.7% and 30.8%, respectively (P=0.811). However, there was no significant association between the presence of any of the 15 viruses and the incidence of KD. Comparisons between the 18 patients with positive RT-PCR results and the other 37 KD patients revealed no significant differences in terms of clinical findings (including the prevalence of incomplete presentation of the disease) and coronary artery diameter. CONCLUSION: A positive RT-PCR for currently epidemic respiratory viruses should not be used as an evidence against the diagnosis of KD. These viruses were not associated with the incomplete presentation of KD and coronary artery dilatation.


title: ORBiT: Oak Ridge biosurveillance toolkit for public health dynamics

text: BACKGROUND: The digitization of health-related information through electronic health records (EHR) and electronic healthcare reimbursement claims and the continued growth of self-reported health information through social media provides both tremendous opportunities and challenges in developing effective biosurveillance tools. With novel emerging infectious diseases being reported across different parts of the world, there is a need to build systems that can track, monitor and report such events in a timely manner. Further, it is also important to identify susceptible geographic regions and populations where emerging diseases may have a significant impact. METHODS: In this paper, we present an overview of Oak Ridge Biosurveillance Toolkit (ORBiT), which we have developed specifically to address data analytic challenges in the realm of public health surveillance. In particular, ORBiT provides an extensible environment to pull together diverse, large-scale datasets and analyze them to identify spatial and temporal patterns for various biosurveillance-related tasks. RESULTS: We demonstrate the utility of ORBiT in automatically extracting a small number of spatial and temporal patterns during the 2009-2010 pandemic H1N1 flu season using claims data. These patterns provide quantitative insights into the dynamics of how the pandemic flu spread across different parts of the country. We discovered that the claims data exhibits multi-scale patterns from which we could identify a small number of states in the United States (US) that act as "bridge regions" contributing to one or more specific influenza spread patterns. Similar to previous studies, the patterns show that the south-eastern regions of the US were widely affected by the H1N1 flu pandemic. Several of these south-eastern states act as bridge regions, which connect the north-east and central US in terms of flu occurrences. CONCLUSIONS: These quantitative insights show how the claims data combined with novel analytical techniques can provide important information to decision makers when an epidemic spreads throughout the country. Taken together ORBiT provides a scalable and extensible platform for public health surveillance.


title: Current knowledge about the antivirals remdesivir (GS-5734) and GS-441524 as therapeutic options for coronaviruses

text: Abstract Recent international epidemics of coronavirus-associated illnesses underscore the urgent medical and public health need for vaccine development and regulatory body approved therapies. In particular, the current coronavirus disease 2019 (COVID-19) pandemic has quickly intensified interest in developing treatment options to mitigate impact on human life. Remdesivir (GS-5734™) is a broad-spectrum antiviral drug that is now being tested as a potential treatment for COVID-19 in international, multi-site clinical trials. Currently available evidence about the antiviral effects of remdesivir against coronaviruses is primarily based on in vitro and in vivo studies (including some on a chemically related compound, GS-441524™), which have demonstrated largely favorable findings. As the pandemic progresses, information from human compassionate use cases will continue to accumulate before the clinical trials are concluded. It is imperative for public health practitioners and the One Health community to stay up to date on the most promising potential therapeutic options that are under investigation. Thus, the purpose of this review is to synthesize the knowledge to date about remdesivir as a therapeutic option for coronaviruses, with a special focus on information relevant to the One Health community.


Protecting the Homeless During The COVID-19 Pandemic


title: Utilization of deceased donors during a pandemic: An argument against using SARS‐CoV‐2 positive donors

text: SARS‐CoV‐2 has rapidly become an unprecedented pandemic that has impacted society, disrupted hospital functions, strained healthcare resources and impacted the lives of transplant professionals. Despite this, organ failure and the need for transplantation continues throughout the United States. Considering the perpetual scarcity of deceased donor organs, Kates et al present a viewpoint that advocates for the utilization of COVID‐19 positive donors in selected cases. We present a review of the current literature that details the potential negative consequences of COVID‐19 positive donors. The factors we consider include: 1) the risk of blood transmission SARS‐CoV‐2, 2) involvement of donor organs, 3) lack of effective therapies, 4) exposure of healthcare and recovery teams, 5) disease transmission and propagation, and 6) hospital resource utilization. While we acknowledge that transplantation fulfills the mission of saving lives, it is imperative to consider the consequences not only to our recipients, but also to the community and to healthcare workers, particularly in the absence of effective preventative or curative therapies. For these reasons, we believe the evidence and risks show that COVID‐19 infection should continue to remain a contraindication for donation, as has been the initial response of donation and transplantation societies.


title: Reducing SARS‐CoV‐2 transmission in the UK: A behavioural science approach to identifying options for increasing adherence to social distancing and shielding vulnerable people

text: PURPOSE: To describe and discuss a systematic method for producing a very rapid response (3 days) to a UK government policy question in the context of reducing SARS‐CoV‐2 transmission. METHODS: A group of behavioural and social scientists advising the UK government on COVID‐19 contributed to the analysis and writing of advice through the Government Office for Science. The question was as follows: What are the options for increasing adherence to social distancing (staying at home except for essential journeys and work) and shielding vulnerable people (keeping them at home and away from others)? This was prior to social distancing legislation being implemented. The first two authors produced a draft, based on analysis of the current government guidance and the application of the Behaviour Change Wheel (BCW) framework to identify and evaluate the options. RESULTS: For promoting social distancing, 10 options were identified for improving adherence. They covered improvements in ways of achieving the BCW intervention types of education, persuasion, incentivization, and coercion. For promoting shielding of vulnerable people, four options were identified covering the BCW intervention types of incentivization, coercion, and enablement. CONCLUSIONS: Responding to policymakers very rapidly as has been necessary during the COVID‐19 pandemic can be facilitated by using a framework to structure the thinking and reporting of multidisciplinary academics and policymakers.


Potentiating health and the crisis of the immune system: integrative approaches to prevention and healing of modern diseases


title: Improving rheumatic fever surveillance in New Zealand: results of a surveillance sector review

text: BACKGROUND: The New Zealand (NZ) Government has made a strong commitment to reduce the incidence of rheumatic fever (RF) by two thirds, to 1.4 cases per 100,000, by mid-2017. We reviewed the NZ RF surveillance sector, aiming to identify potential improvements which would support optimal RF control and prevention activities. METHODS: This review used a recently developed surveillance sector review method. Interviews with 36 key informants were used to describe the sector, assess it and identify its gaps. Priorities for improvement and implementation strategies were determined following discussion with these key informants, with policy advisors and within the research team. RESULTS: Key improvements identified included the need for a comprehensive RF surveillance strategy, integrated reporting and an online national RF register. At a managerial level this review provided evidence for system change and built support for this across the surveillance sector. CONCLUSIONS: The surveillance sector review approach can be added to the small set of tools currently available for developing and evaluating surveillance systems. This new approach is likely to prove useful as we confront the challenges of combating new emerging infectious diseases, responding to global environmental changes, and reducing health inequalities.


title: Lung ultrasonography in COVID‐19: a gamechanger in the Stroke Unit?

text: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) is rapidly spreading worldwide, and the WHO declared its pandemic nature on 11(th) March 2020(1). The outbreak has hit Europe and, as of April 19, 2020, Italy has the third largest number of confirmed cases, namely a total of 175,925 cases and 23,227 deaths according to the John Hopkins University (2). This is the largest health and economic emergency of our country since the post‐war period, and many hospitals are now dedicated exclusively to COVID‐19 assistance. Our University Hub Stroke Unit of Cattinara Hospital is in the northeaster Italian region of Friuli Venezia Giulia which enlisted 2,731 cases and 222 deaths at the time of writing(3).


title: Coronavirus infections and immune responses

text: Coronaviruses (CoVs) are by far the largest group of known positive‐sense RNA viruses having an extensive range of natural hosts. In the past few decades, newly evolved Coronaviruses have posed a global threat to public health. The immune response is essential to control and eliminate CoV infections, however, maladjusted immune responses may result in immunopathology and impaired pulmonary gas exchange. Gaining a deeper understanding of the interaction between Coronaviruses and the innate immune systems of the hosts may shed light on the development and persistence of inflammation in the lungs and hopefully can reduce the risk of lung inflammation caused by CoVs. In this review, we provide an update on CoV infections and relevant diseases, particularly the host defense against CoV‐induced inflammation of lung tissue, as well as the role of the innate immune system in the pathogenesis and clinical treatment.


Virtual dermatopathology: A potential educational tool during COVID‐19 pandemic


Prevention and Treatment of Skin Damage Caused by Personal Protective Equipment: Experience of the First-Line Clinicians Treating 2019-nCoV Infection


title: Solid phase synthesis and biological evaluation of probestin as an angiogenesis inhibitor

text: Probestin is a potent aminopeptidase N (APN) inhibitor originally isolated from the bacterial culture broth. Here, we report probestin synthesis by solid phase peptide synthesis (SPPS) method and evaluated its activity to inhibit angiogenesis using a chicken embryo chorioallantoic membrane (CAM) assay and a CAM tumor xenograft model. Results from these studies demonstrate that probestin inhibits the angiogenic activity and tumor growth.


title: Risk Factors for Primary Middle East Respiratory Syndrome Coronavirus Illness in Humans, Saudi Arabia, 2014

text: Risk factors for primary Middle East respiratory syndrome coronavirus (MERS-CoV) illness in humans are incompletely understood. We identified all primary MERS-CoV cases reported in Saudi Arabia during March–November 2014 by excluding those with history of exposure to other cases of MERS-CoV or acute respiratory illness of unknown cause or exposure to healthcare settings within 14 days before illness onset. Using a case–control design, we assessed differences in underlying medical conditions and environmental exposures among primary case-patients and 2–4 controls matched by age, sex, and neighborhood. Using multivariable analysis, we found that direct exposure to dromedary camels during the 2 weeks before illness onset, as well as diabetes mellitus, heart disease, and smoking, were each independently associated with MERS-CoV illness. Further investigation is needed to better understand animal-to-human transmission of MERS-CoV.


title: Ramping Up the Delivery of Cardiac Surgery During the COVID-19 Pandemic: A Guidance Statement from the Canadian Society of Cardiac Surgeons

text: Abstract The coronavirus disease 2019 (COVID-19) has had a profound global impact. Its rapid transmissibility has forced whole countries to adopt strict measures to contain its spread. As part of necessary pandemic planning, the majority of Canadian cardiac surgical programs have prioritized and delayed elective procedures in an effort to reduce the burden on the health care system and to mobilize resources in the event of a pandemic surge. While the number of COVID-19 cases continue to increase worldwide, new cases have begun to decline in many jurisdictions. This “flattening of the curve” has inevitably prompted discussions around re-opening of the economy, relaxing some public health restrictions and resuming non-urgent health care delivery.


title: The Role of Complement in Transfusion-Related Acute Lung Injury

text: Abstract Transfusion-related acute lung injury (TRALI) is a life-threatening complication of acute respiratory distress occurring within 6 hours of blood transfusion. TRALI is one of the leading causes of transfusion-related fatalities and specific therapies are unavailable. Neutrophils are recognized as the major pathogenic cells, whereas T regulatory cells and dendritic cells appear to be important for protection against TRALI. The pathogenesis, however, is complex and incompletely understood. It is frequently postulated that the complement system plays an important role in the TRALI pathogenesis. In this article, we assess the evidence regarding the involvement of complement in TRALI from both human and animal studies. We hypothesize about the potential connection between the complement system and neutrophils in TRALI. Additionally, we draw parallels between TRALI and other acute pulmonary disorders of acute lung injury and acute respiratory distress syndrome regarding the involvement of complement. We conclude that, even though a role for complement in the TRALI pathogenesis seems plausible, studies investigating the role of complement in TRALI are remarkably limited in number and also present conflicting findings. Different types of TRALI animal models, diverse experimental conditions, and the composition of the gastrointestinal microbiota may perhaps all be factors which contribute to these discrepancies. More systematic studies are warranted to shed light on the contribution of the complement cascade in TRALI. The underlying clinical condition of the patient, which influences the susceptibility to TRALI, as well as the transfusion factor (antibody-mediated vs non–antibody-mediated), will be important to take into consideration when researching the contribution of complement. This should significantly increase our understanding of the role of complement in TRALI and may potentially result in promising new treatment strategies.


title: Host endomembrane recruitment for plant RNA virus replication

text: Although there is a significant amount of literature that deals with the identification of plant viral proteins involved in membrane remodeling and vesicle production in infected cells, there are very few investigations that report on the impact that infection has on the overall architecture and dynamics of the early secretory endomembranes. Recent investigations have shown that for some viruses the endoplasmic reticulum, Golgi bodies and other organelles are heavily recruited into virus-induced perinuclear structures. These structures are not isolated organelles and are dynamically connected to the bulk of non-modified endomembranes. They also have a functional link with peripheral motile vesicles involved in virus intracellular movement. The full molecular events that consubstantiate with this endomembrane recruitment in virus-induced structures remain to be elucidated but viral genome replication and virion assembly are probably taking place within these structures.


title: Herbal Medicine for the Treatment of Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis of Randomized Controlled Trials

text: Background: The coronavirus disease 2019 (COVID-19) pandemic has caused a worldwide outbreak of respiratory illness. This review aims to evaluate the effectiveness and adverse events of herbal medicines for the treatment of COVID-19. Methods: Twelve databases were searched through 12 May 2020. Randomized controlled trials (RCTs) and quasi-RCTs assessing the effects of herbal medicines for the treatment of COVID-19 were eligible. The study selection and data extraction were performed by two independent reviewers. The Cochrane risk of bias tool was used for the assessment of the risk of bias in all included RCTs. Mean differences (MDs), risk ratios (RRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, and the effect sizes of the studies were pooled. Results: Seven RCTs with a total of 855 patients were included. All included trials compared the combined therapy of herbal medicine with Western medicine to Western medicine alone. The combined therapy significantly improved the total effective rate (RR 1.23, 95% CI 1.13 to 1.34, p < 0.001), cough symptom disappearance rate (RR 1.45, 95% CI 1.12 to 1.89, p = 0.005), and sputum production symptom disappearance rate (RR 1.73, 95% CI 1.19 to 2.50, p = 0.004). Beneficial effects of the combined therapy were also seen in TCM syndrome score of cough (MD −1.18, 95% CI −1.34 to −1.03, p < 0.001), fever (MD −0.62, 95% CI −0.79 to −0.45, p < 0.001), dry and sore throat (MD −0.83, 95% CI −1.45 to −0.20, p = 0.009), and fatigue (MD −0.60, 95% CI −1.04 to −0.17, p = 0.007). The overall risk of bias of the included studies was unclear. No serious adverse events were reported. Conclusion: Significant effects of the combined therapy of herbal medicine with Western medicine were found, and revealed the potential role of herbal medicine in treating COVID-19. More high-quality RCTs are needed to further validate the effectiveness and adverse events of herbal medicine in the treatment of COVID-19.


title: Innate immune restriction and antagonism of viral RNA lacking 2׳-O methylation

text: Abstract N-7 and 2′-O methylation of host cell mRNA occurs in the nucleus and results in the generation of cap structures (cap 0, m7GpppN; cap 1, m7GpppNm) that control gene expression by modulating nuclear export, splicing, turnover, and protein synthesis. Remarkably, RNA cap modification also contributes to mammalian cell host defense as viral RNA lacking 2′-O methylation is sensed and inhibited by IFIT1, an interferon (IFN) stimulated gene (ISG). Accordingly, pathogenic viruses that replicate in the cytoplasm have evolved mechanisms to circumvent IFIT1 restriction and facilitate infection of mammalian cells. These include: (a) generating cap 1 structures on their RNA through cap-snatching or virally-encoded 2′-O methyltransferases, (b) using cap-independent means of translation, or (c) using RNA secondary structural motifs to antagonize IFIT1 binding. This review will discuss new insights as to how specific modifications at the 5′-end of viral RNA modulate host pathogen recognition responses to promote infection and disease.


title: Neurological dysfunction in three dogs and one cat following attenuation of intrahepatic portosystemic shunts

text: Neurological dysfunction is an uncommon complication following extrahepatic portosystemic shunt ligation. Three dogs and one cat are described that developed neurological signs within 21 to 42 hours of attenuation of intrahepatic portosystemic shunts. None of these cases had biochemical evidence of hepatic encephalopathy postoperatively. Two dogs died during management of status epilepticus following aspiration of food. One dog died six months postoperatively. The cat had persistent neurological dysfunction at discharge, but was alive and had recovered most of its neurological function at the time of writing, 37 months after surgery. This report demonstrates the potential for animals with intrahepatic portosystemic shunts to develop postoperative neurological signs and highlights the difficulty of managing such cases. Two dogs had both intrahepatic and extrahepatic portosystemic shunts. Large intestinal malrotation (partial situs inversus) may have been linked to the development of a portosystemic shunt in the remaining dog.


title: Ecosystem-centric business continuity planning (eco-centric BCP): A post COVID19 new normal

text: Abstract This article views the COVID-19 pandemic as an opportunity leading to a significant reduction in pollution levels, clean waters in rivers, improved visibility, and other tangible benefit to humanity and the environment. In Post-COVID scenario, to restore the margins and regain the lost production, industries are likely to increase their production leading to a quantum jump in the pollution levels. Having precedence of such a scenario in 2008–09, this article looks at what are the possible avenues to engage the city government and business houses through an a new normal ECO-BCP concept for long term sustainability. All economic stimulus needs to be tied down with the stringent reduction in the emission norms. The Ten Principles for the Eco-centric BCP guide the reopening of MSMEs after lockdown period called to check the spread of the COVID-19 pandemic. The Eco-centric BCP model will help the MSMEs to adopt the new-normal business strategies to align with the country-specific commitments to SDGs, SFDRR and Paris declaration.


title: The Influence of Social-Cognitive Factors on Personal Hygiene Practices to Protect Against Influenzas: Using Modelling to Compare Avian A/H5N1 and 2009 Pandemic A/H1N1 Influenzas in Hong Kong

text: BACKGROUND: Understanding population responses to influenza helps optimize public health interventions. Relevant theoretical frameworks remain nascent. PURPOSE: To model associations between trust in information, perceived hygiene effectiveness, knowledge about the causes of influenza, perceived susceptibility and worry, and personal hygiene practices (PHPs) associated with influenza. METHODS: Cross-sectional household telephone surveys on avian influenza A/H5N1 (2006) and pandemic influenza A/H1N1 (2009) gathered comparable data on trust in formal and informal sources of influenza information, influenza-related knowledge, perceived hygiene effectiveness, worry, perceived susceptibility, and PHPs. Exploratory factor analysis confirmed domain content while confirmatory factor analysis was used to evaluate the extracted factors. The hypothesized model, compiled from different theoretical frameworks, was optimized with structural equation modelling using the A/H5N1 data. The optimized model was then tested against the A/H1N1 dataset. RESULTS: The model was robust across datasets though corresponding path weights differed. Trust in formal information was positively associated with perceived hygiene effectiveness which was positively associated with PHPs in both datasets. Trust in formal information was positively associated with influenza worry in A/H5N1 data, and with knowledge of influenza cause in A/H1N1 data, both variables being positively associated with PHPs. Trust in informal information was positively associated with influenza worry in both datasets. Independent of information trust, perceived influenza susceptibility associated with influenza worry. Worry associated with PHPs in A/H5N1 data only. CONCLUSIONS: Knowledge of influenza cause and perceived PHP effectiveness were associated with PHPs. Improving trust in formal information should increase PHPs. Worry was significantly associated with PHPs in A/H5N1.


title: Chapter 4 Regulation of Translation by Stress Granules and Processing Bodies

text: Abstract Stress necessitates rapid reprogramming of translation in order to facilitate an adaptive response and promote survival. Cytoplasmic stress granules (SGs) and processing bodies (PBs) are dynamic structures that form in response to stress-induced translational arrest. PBs are linked to mRNA silencing and decay, while SGs are more closely linked to translation and the sorting of specific mRNAs for different fates. While they share some components and can interact physically, SGs and PBs are regulated independently, house separate functions, and contain unique markers. SG formation is associated with numerous disease states, and the expanding list of SG-associated proteins integrates SG formation with other processes such as transcription, splicing, and survival. Growing evidence suggests that SG assembly is initiated by translational arrest, and mediates cross talk with many other signaling pathways.


title: Pandemic Influenza: Impact on Perianesthesia Nursing Areas

text: As our readers are aware, these pages are typically used by the editors. However, in light of the recent events and concerns surrounding the swine flu, the editors have elected to quickly substitute an informative piece regarding influenza for the usual editorial. We thank Dr. Daphne Stannard for her willingness to disseminate her knowledge on the topic. The Editors


title: The first case of COVID-19 treated with the complement C3 inhibitor AMY-101

text: Abstract Acute respiratory distress syndrome (ARDS) is a devastating clinical manifestation of COVID-19 pneumonia and is mainly based on an immune-driven pathology. Mounting evidence suggests that COVID-19 is fueled by a maladaptive host inflammatory response that involves excessive activation of innate immune pathways. While a “cytokine storm” involving IL-6 and other cytokines has been documented, complement C3 activation has been implicated as an initial effector mechanism that exacerbates lung injury in preclinical models of SARS-CoV infection. C3-targeted intervention may provide broader therapeutic control of complement-mediated inflammatory damage in COVID-19 patients. Herein, we report the clinical course of a patient with severe ARDS due to COVID-19 pneumonia who was safely and successfully treated with the compstatin-based complement C3 inhibitor AMY-101.


title: Governing the Sick City: Urban Governance in the Age of Emerging Infectious Disease

text: Abstract: Based on a case study of the 2003 severe acute respiratory syndrome (SARS) outbreak in Toronto, Canada, this article suggests that we may have to rethink our common perception of what urban governance entails. Rather than operating solely in the conceptual proximity of social cohesion and economic competitiveness, urban governance may soon prove to be more centrally concerned with questions of widespread disease, life and death and the construction of new internal boundaries and regulations just at the time that globalization seems to suggest the breakdown of some traditional scalar incisions such as national boundaries in a post‐Westphalian environment. We argue that urban governance must face the new (or reemerging) challenge of dealing with infectious disease in the context of the “new normal” and that global health governance may be better off by taking the possibilities that rest in metropolitan governance more seriously.


title: Ethnic and regional variations in hospital mortality from COVID-19 in Brazil: a cross-sectional observational study

text: BACKGROUND: Brazil ranks second worldwide in total number of COVID-19 cases and deaths. Understanding the possible socioeconomic and ethnic health inequities is particularly important given the diverse population and fragile political and economic situation. We aimed to characterise the COVID-19 pandemic in Brazil and assess variations in mortality according to region, ethnicity, comorbidities, and symptoms. METHODS: We conducted a cross-sectional observational study of COVID-19 hospital mortality using data from the SIVEP-Gripe (Sistema de Informação de Vigilância Epidemiológica da Gripe) dataset to characterise the COVID-19 pandemic in Brazil. In the study, we included hospitalised patients who had a positive RT-PCR test for severe acute respiratory syndrome coronavirus 2 and who had ethnicity information in the dataset. Ethnicity of participants was classified according to the five categories used by the Brazilian Institute of Geography and Statistics: Branco (White), Preto (Black), Amarelo (East Asian), Indígeno (Indigenous), or Pardo (mixed ethnicity). We assessed regional variations in patients with COVID-19 admitted to hospital by state and by two socioeconomically grouped regions (north and central-south). We used mixed-effects Cox regression survival analysis to estimate the effects of ethnicity and comorbidity at an individual level in the context of regional variation. FINDINGS: Of 99 557 patients in the SIVEP-Gripe dataset, we included 11 321 patients in our study. 9278 (82·0%) of these patients were from the central-south region, and 2043 (18·0%) were from the north region. Compared with White Brazilians, Pardo and Black Brazilians with COVID-19 who were admitted to hospital had significantly higher risk of mortality (hazard ratio [HR] 1·45, 95% CI 1·33–1·58 for Pardo Brazilians; 1·32, 1·15–1·52 for Black Brazilians). Pardo ethnicity was the second most important risk factor (after age) for death. Comorbidities were more common in Brazilians admitted to hospital in the north region than in the central-south, with similar proportions between the various ethnic groups. States in the north had higher HRs compared with those of the central-south, except for Rio de Janeiro, which had a much higher HR than that of the other central-south states. INTERPRETATION: We found evidence of two distinct but associated effects: increased mortality in the north region (regional effect) and in the Pardo and Black populations (ethnicity effect). We speculate that the regional effect is driven by increasing comorbidity burden in regions with lower levels of socioeconomic development. The ethnicity effect might be related to differences in susceptibility to COVID-19 and access to health care (including intensive care) across ethnicities. Our analysis supports an urgent effort on the part of Brazilian authorities to consider how the national response to COVID-19 can better protect Pardo and Black Brazilians, as well as the population of poorer states, from their higher risk of dying of COVID-19. FUNDING: None.


title: Schiff Bases: A Short Survey on an Evergreen Chemistry Tool

text: The review reports a short biography of the Italian naturalized chemist Hugo Schiff and an outline on the synthesis and use of his most popular discovery: the imines, very well known and popular as Schiff Bases. Recent developments on their “metallo-imines” variants have been described. The applications of Schiff bases in organic synthesis as partner in Staudinger and hetero Diels-Alder reactions, as “privileged” ligands in the organometallic complexes and as biological active Schiff intermediates/targets have been reported as well.


title: Hypothermia, hypoglycemia, and hypothyrosis associated with poult enteritis and mortality syndrome

text: Abstract A metabolic dysfunction contributes to the poor performance and mortality associated with Poult Enteritis and Mortality Syndrome (PEMS). Within 2 d after contact-exposed poults were removed from the presence of PEMS-infected poults and returned to their respective treatment rooms to infect experimental poults, the experimental poults began to huddle together and show signs of the disease. When separated from the huddle, body temperatures of exposure poults were depressed significantly. Body temperatures decreased progressively through 8 d after exposure with a maximum depression of 2 C and returned to a normal level at 18 d after PEMS exposure. Similar decreasing patterns in serum glucose, inorganic phosphorus, triiodothyronine, and thyroxine were observed, with maximum decreases in these serum constituents being found between 8 and 13 d after PEMS exposure. There were significant correlations among decreasing body temperatures, decreasing serum constituents, and mortality in the PEMS-exposed poults. Daily mortality rates associated with PEMS began at 6 d and peaked at 9 d after PEMS exposure. Mortality rates decreased from 9 to 15 d after experimental PEMS exposure. Depressions in serum constituents, body temperature, and increased mortality rates did not coincide with decreased feed intake associated with PEMS. Therefore, it was concluded that the agent(s) causing PEMS may have a direct effect on energy metabolism in afflicted poults.


title: Can China’s ‘standard of care’ for COVID-19 be replicated in Europe?

text: The Director-General of the WHO has suggested that China’s approach to the COVID-19 crisis could be the standard of care for global epidemics. However, as remarkable as the Chinese strategy might be, it cannot be replicated in other countries and certainly not in Europe. In Europe, there is a distribution of power between the European Union and its member states. In contrast, China’s political power is concentrated in the central government. This enables it to take immediate measures that affect the entire country, such as massive quarantines or closing borders. Moreover, the Chinese legal framework includes restrictions on privacy and other human rights that are unknown in Europe. In addition, China has the technological power to easily impose such restrictions. In most European countries, that would be science fiction. These conditions have enabled China to combat epidemics like no other country can. However, the WHO might have been overoptimistic. The Chinese standard of care for treating COVID-19 also raises problematic issues for human rights, and the real consequences of these actions remain to be seen.


title: The innate antiviral immune system of the cat: Molecular tools for the measurement of its state of activation

text: Abstract The innate immune system plays a central role in host defence against viruses. While many studies portray mechanisms in early antiviral immune responses of humans and mice, much remains to be discovered about these mechanisms in the cat. With the objective of shedding light on early host–virus interactions in felids, we have developed 12 real-time TaqMan® qPCR systems for feline genes relevant to innate responses to viral infection, including those encoding for various IFNα and IFNω subtypes, IFNβ, intracellular antiviral factor Mx, NK cell stimulator IL-15 and effectors perforin and granzyme B, as well as Toll-like receptors (TLRs) 3 and 8. Using these newly developed assays and others previously described, we measured the relative expression of selected markers at early time points after viral infection in vitro and in vivo. Feline embryonic fibroblasts (FEA) inoculated with feline leukemia virus (FeLV) indicated peak levels of IFNα, IFNβ and Mx expression already 6h after infection. In contrast, Crandell-Rees feline kidney (CrFK) cells inoculated with feline herpes virus (FHV) responded to infection with high levels of IFNα and IFNβ only after 24h, and no induction of Mx could be detected. In feline PBMCs challenged in vitro with feline immunodeficiency virus (FIV), maximal expression levels of IFNα, β and ω subtype genes as well as IL-15 and TLRs 3, 7 and 8 were measured between 12 and 24h after infection, whereas expression levels of proinflammatory cytokine gene IL-6 were consistently downregulated until 48h post inoculation. A marginal upregulation of granzyme B was also observed within 3h after infection. In an in vivo experiment, cats challenged with FIV exhibited a 2.4-fold increase in IFNα expression in blood 1 week post infection. We furthermore demonstrate the possibility of stimulating feline immune cells in vitro with various immune response modifiers (IRMs) already known for their immunostimulatory properties in mice and humans, namely Poly IC, Resiquimod (R-848) and dSLIM™, a synthetic oligonucleotide containing several unmethylated CpG motifs. Stimulation of feline PBMCs with dSLIM™ and R-848 effectively enhanced expression of IFNα within 12h by factors of 6 and 12, respectively, and Poly IC induced an increase in Mx mRNA expression of 28-fold. Altogether, we describe new molecular tools and their successful use for the characterization of innate immune responses against viruses in the cat and provide evidence that feline cells can be stimulated by synthetic molecules to enhance their antiviral defence mechanisms.


title: The incidence of salmonellosis among dairy herds in the northeastern United States

text: Abstract The objectives of this study were to estimate the incidence of salmonellosis among a large sample of dairy herds in the northeastern United States (both at the animal level and the herd level), to describe the serotypes and antimicrobial resistance profiles of the positive samples, and to determine whether various herd-level factors were important predictors of incidence. Participating veterinarians enrolled 831 dairy herds and submitted fecal samples from 2,565 female dairy cattle for Salmonella culture because of suspicion of clinical disease. Estimates of animal-level incidence rates were calculated for each age group as the number of cases per animal time at risk, and an estimate of herd-level incidence rate was calculated as the number of positive herds per herd time at risk. Descriptive analysis of serotype data and level of antimicrobial resistance was performed, and Poisson regression analysis was used to study associations between the within-herd incidence of salmonellosis and certain predictor variables (herd size, housing type, vaccination status, and prior history of Salmonella infection). Salmonella was isolated from 576 (22.5%) samples representing 93 herds. The animal-level incidence rates for preweaned female calves, heifers, and adult cows were 8.1, 0.04, and 1.8 cases per 1,000 animal-years, respectively. The herd-level incidence rate was 8.6 positive herds per 100 herd-years. Salmonella Newport was the predominant serotype, accounting for 41% of the cases, followed by Salmonella Typhimurium. Over 68% of all isolates were resistant to 5 or more antimicrobial agents. Herd size was the only significant predictor of the incidence of salmonellosis in a multivariable model; herds with at least 400 female dairy cattle had a higher incidence rate than smaller herds. Our results shed light on the impact of salmonellosis on the dairy industry in the northeastern United States, and they help clarify the role of dairy cattle as a source of Salmonella serotypes that are also important human pathogens.


title: Development of a hyena immunology toolbox

text: Animals that hunt and scavenge are often exposed to a broad array of pathogens. Theory predicts the immune systems of animals specialized for scavenging should have been molded by selective pressures associated with surviving microbial assaults from their food. Spotted hyenas (Crocuta crocuta) are capable hunters that have recently descended from carrion feeding ancestors. Hyenas have been documented to survive anthrax and rabies infections, and outbreaks of several other viral diseases that decimated populations of sympatric carnivores. In light of the extreme disease resistance manifested by spotted hyenas, our objective was to identify tools available for studying immune function in spotted hyenas and use these tools to document the hyena antibody response to immunization. Domestic cats (Felis catus) are the closest phylogenetic relatives of hyenas that have been studied in detail immunologically, and we hypothesized that anti-cat isotype-specific antibodies would cross react with hyena immunoglobulin epitopes. We used ELISA and Western blots to test isotype-specific anti-feline antibodies for specific cross-reaction to hyena Ig epitopes. Molecular weights of heavy (IgA, IgG, IgM) and light chains of hyena immunoglobulins were determined by protein electrophoresis, and as expected, they were found to be similar to feline immunoglobulins. In order to further validate the cross-reactivity of the anti-feline antibodies and document the hyena humoral response, eight spotted hyenas were immunized with dinitrophenol conjugated keyhole limpet hemocyanin (DNP-KLH) and serum anti-DNP responses were monitored by enzyme-linked immunosorbent assay (ELISA) for one year. The full array of isotype-specific antibodies identified here will allow veterinarians and other researchers to thoroughly investigate the hyena antibody response, and can be used in future studies to test hypotheses about pathogen exposure and immune function in this species.


title: Pulmonary melanoma and “crazy paving” patterns in chest images: a case report and literature review

text: BACKGROUND: In the lung, melanoma is mostly arranged as patterns of multiple nodules, solitary nodules, or miliary invasions. Very rarely, it also displays a “crazy paving” pattern (also described as a “paving stone,” “flagstone,” or “slabstone” pattern), which is rarer still in discrete bilateral nodules. This pattern is considered to be caused by pulmonary alveolar proteinosis, but its association with various diseases is unclear. CASE PRESENTATION: A 60-year-old man was diagnosed with pulmonary melanoma. Computed tomography revealed discrete bilateral nodules surrounded by a “paving” pattern. A literature review found more than 40 types of diseases that have presented with “paving” patterns in the lung—predominantly pulmonary alveolar proteinosis, viral pneumonia, exogenous lipoid pneumonia, bacterial pneumonia, pulmonary alveolar microlithiasis, interstitial pneumonia, ARDS, squalene aspiration pneumonia, radiation pneumonitis, drug-induced pneumonitis, pulmonary leptospirosis, pulmonary hemorrhage, and pulmonary nocardiosis. CONCLUSIONS: We describe the first case of pulmonary melanoma in the form of discrete bilateral nodules accompanied with a computed tomography paving pattern. Although pulmonary paving patterns are rare, more than 40 diseases reportedly display them; clinicians should consider melanoma of the lung in differential diagnoses for patients who show such a pattern.


title: A novel two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein

text: Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression, including type I interferon production, by promoting host mRNA degradation and inhibiting host translation, in infected cells. We present evidence that nsp1 uses a novel, two-pronged strategy to inhibit host translation/gene expression. Nsp1 bound to the 40S ribosomal subunit and inactivated the translational activity of the 40S subunits. Furthermore, the nsp1-40S ribosome complex induced the modification of the 5'-region of capped mRNA template and rendered the template RNA translationally incompetent. Nsp1 also induced RNA cleavage in templates carrying the internal ribosome entry site (IRES) from encephalomyocarditis virus, but not in those carrying IRESs from hepatitis C and cricket paralysis viruses, demonstrating that the nsp1-induced RNA modification was template-dependent. We speculate that the mRNAs that underwent the nsp1-mediated modification are marked for rapid turnover by the host RNA degradation machinery.


title: COVID-19 pandemic lockdown: An emotional health perspective of Indians on Twitter

text: BACKGROUND: Novel corona virus (2019-nCoV) has spread in the world since its first human infection in December 2019. India has also witnessed a rising number of infections since March 2020. The Indian government imposed lockdowns in the nation to control the movement of its citizens thereby confining the spread of the virus. Tweeters resorted to usage of social media platform to express their mind. AIM: Through this article, an attempt has been made to understand the mind-set of Indian people using Python and R statistical software, during the recent lockdown 2.0 (15 April 2020 to 3 May 2020) and lockdown 3.0 (4 May 2020 to 17 May 2020) through their tweets on the social media platform Twitter. Also, opinion on e-commerce during this pandemic has been analysed. METHOD: Analysis has been performed using Python and R statistical software. Also, recent articles related to COVID-19 have been considered and reviewed. RESULT: Although the country had a positive approach in lockdown 2.0 with only few instances of sadness, disgust and others, the majority of the people had a negative approach in lockdown 3.0. CONCLUSION: This analysis can help the health specialists to understand people’s mind-set, the authorities to take further corresponding measures in washing out the virus and the e-commerce stakeholders to adapt to the changing attitudes by adjusting demand and supply plans accordingly.


title: Viruses and bacteria in sputum samples of children with community-acquired pneumonia

text: Few comprehensive studies have searched for viruses and bacteria in children with community-acquired pneumonia (CAP). We identified 76 children hospitalized for pneumonia. Induced sputum samples were analysed for 18 viruses by antigen detection and PCR, and for six bacteria by culture and PCR. Viruses were found in 72% of samples, bacteria in 91%, and both in 66%. Rhinovirus (30%), human bocavirus (18%) and human metapneumovirus (14%) were the most commonly detected viruses. Two viruses were found in 22% of samples and three in 8%. The most common bacteria found were Streptococcus pneumoniae (50%), Haemophilus influenzae (38%), and Moraxella catarrhalis (28%). Rhinovirus–S. pneumoniae was the most commonly found combination of virus and bacterium (16%). All six children with treatment failure had both viruses and bacteria detected in the sputum. Otherwise, we found no special clinical characteristics in those with mixed viral–bacterial detections. With modern molecular diagnostic techniques, there are high rates of both viral and bacterial identification in childhood CAP. The clinical significance of mixed viral–bacterial infections remains unclear, although we found a potential association between them and treatment failure.


title: Antioxidant and anti-inflammatory activities of Lonicera japonica Thunb. var. sempervillosa Hayata flower bud extracts prepared by water, ethanol and supercritical fluid extraction techniques

text: Abstract Lonicera japonica Thunberg (LJ) has long been used as an antipyretic, anti-inflammatory and anti-infectious agent in East Asia. The subspecies L. japonica Thunb. var. sempervillosa Hayata (LJv) is a variant that mainly grows in Taiwan. This study examined the antioxidant and anti-inflammatory activities of the extracts from the flower buds of these two species. The extracts were obtained by three extraction methods: water extraction, ethanol extraction, and supercritical-CO2 fluid extraction (SFE). The antioxidant activities of dry LJ (dLJ) extracts were superior to those of LJv extracts. Water extracts possessed higher activities than that prepared by ethanol or SFE. The total polyphenols content, total flavonoids content, and the amount of chlorogenic acid and luteolin-7-O-glucoside were all higher in the water extracts compared to the other two. The SFE extracts of these two species all exhibited excellent anti-inflammatory activities. Although the water and ethanol extracts of dLJ extracts had higher anti-inflammatory activity than that of LJv extracts, the SFE extracts prepared from fresh LJv flower buds (fLJv) exhibited the highest activity among all extracts. The SFE effectively isolates the bioactive components of L. japonica and can obtain the L. japonica extracts with high anti-inflammatory activity.


title: School closure and management practices during coronavirus outbreaks including COVID-19: a rapid systematic review

text: In response to the coronavirus disease 2019 (COVID-19) pandemic, 107 countries had implemented national school closures by March 18, 2020. It is unknown whether school measures are effective in coronavirus outbreaks (eg, due to severe acute respiratory syndrome [SARS], Middle East respiratory syndrome, or COVID-19). We undertook a systematic review by searching three electronic databases to identify what is known about the effectiveness of school closures and other school social distancing practices during coronavirus outbreaks. We included 16 of 616 identified articles. School closures were deployed rapidly across mainland China and Hong Kong for COVID-19. However, there are no data on the relative contribution of school closures to transmission control. Data from the SARS outbreak in mainland China, Hong Kong, and Singapore suggest that school closures did not contribute to the control of the epidemic. Modelling studies of SARS produced conflicting results. Recent modelling studies of COVID-19 predict that school closures alone would prevent only 2–4% of deaths, much less than other social distancing interventions. Policy makers need to be aware of the equivocal evidence when considering school closures for COVID-19, and that combinations of social distancing measures should be considered. Other less disruptive social distancing interventions in schools require further consideration if restrictive social distancing policies are implemented for long periods.


title: Use of nitric oxide nanoparticulate platform for the treatment of skin and soft tissue infections

text: The incidence of skin and soft tissue infections (SSTI) due to multi‐drug resistant pathogens is increasing. The concomitant increase in antibiotic use along with the ease with which organisms develop mechanisms of resistance have together become a medical crisis, underscoring the importance of developing innovative and effective antimicrobial strategies. Nitric oxide (NO) is an endogenously produced molecule with many physiologic functions, including broad spectrum antimicrobial activity and immunomodulatory properties. The risk of resistance to NO is minimized because NO has multiple mechanisms of antimicrobial action. NO's clinical utility has been limited largely because it is highly reactive and lacks appropriate vehicles for storage and delivery. To harness NO's antimicrobial potential, a variety exogenous NO delivery platforms have been developed and evaluated, yet limitations preclude their use in the clinical setting. Nanotechnology represents a paradigm through which these limitations can be overcome, allowing for the encapsulation, controlled release, and focused delivery of NO for the treatment of SSTI. WIREs Nanomed Nanobiotechnol 2013. doi: 10.1002/wnan.1230 1.. Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease; 2.. Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.


title: COVID‐19 is a Real Headache!

text: After the emergence of a novel coronavirus named SARS‐CoV‐2, coronavirus disease 2019 (COVID‐19) was initially characterized by fever, sore throat, cough, and dyspnea, mainly manifestations of respiratory system. However, other manifestations such as headache, abdominal pain, diarrhea, loss of taste and smell were added to the clinical spectrum, during the course of the COVID‐19 pandemic. The reports on the neurological findings are increasing rapidly and headache seems to be the leader on the symptom list. Headache was reported in 11%‐34% of the hospitalized COVID‐19 patients, but clinical features of these headaches were totally missing in available publications. According to our initial experience, significant features of headache presentation in the symptomatic COVID‐19 patients were new‐onset, moderate‐severe, bilateral headache with pulsating or pressing quality in the temporoparietal, forehead or periorbital region. The most striking features of the headache were sudden to gradual onset and poor response to common analgesics, or high relapse rate, that was limited to the active phase of the COVID‐19. Symptomatic COVID‐19 patients, around 6%‐10%, also reported headache as a presenting symptom. The possible pathophysiological mechanisms of headache include activation of peripheral trigeminal nerve endings by the SARS‐CoV‐2 directly or through the vasculopathy and/or increased circulating pro‐inflammatory cytokines and hypoxia. We concluded that as a common non‐respiratory symptom of COVID‐19, headache should not be overlooked, and its characteristics should be recorded with scrutiny.


COVID-19 and ischemic stroke: should we systematically look for lupus anticoagulant and antiphospholipid antibodies?


title: Conservation and Variability of Dengue Virus Proteins: Implications for Vaccine Design

text: BACKGROUND: Genetic variation and rapid evolution are hallmarks of RNA viruses, the result of high mutation rates in RNA replication and selection of mutants that enhance viral adaptation, including the escape from host immune responses. Variability is uneven across the genome because mutations resulting in a deleterious effect on viral fitness are restricted. RNA viruses are thus marked by protein sites permissive to multiple mutations and sites critical to viral structure-function that are evolutionarily robust and highly conserved. Identification and characterization of the historical dynamics of the conserved sites have relevance to multiple applications, including potential targets for diagnosis, and prophylactic and therapeutic purposes. METHODOLOGY/PRINCIPAL FINDINGS: We describe a large-scale identification and analysis of evolutionarily highly conserved amino acid sequences of the entire dengue virus (DENV) proteome, with a focus on sequences of 9 amino acids or more, and thus immune-relevant as potential T-cell determinants. DENV protein sequence data were collected from the NCBI Entrez protein database in 2005 (9,512 sequences) and again in 2007 (12,404 sequences). Forty-four (44) sequences (pan-DENV sequences), mainly those of nonstructural proteins and representing ∼15% of the DENV polyprotein length, were identical in 80% or more of all recorded DENV sequences. Of these 44 sequences, 34 (∼77%) were present in ≥95% of sequences of each DENV type, and 27 (∼61%) were conserved in other Flaviviruses. The frequencies of variants of the pan-DENV sequences were low (0 to ∼5%), as compared to variant frequencies of ∼60 to ∼85% in the non pan-DENV sequence regions. We further showed that the majority of the conserved sequences were immunologically relevant: 34 contained numerous predicted human leukocyte antigen (HLA) supertype-restricted peptide sequences, and 26 contained T-cell determinants identified by studies with HLA-transgenic mice and/or reported to be immunogenic in humans. CONCLUSIONS/SIGNIFICANCE: Forty-four (44) pan-DENV sequences of at least 9 amino acids were highly conserved and identical in 80% or more of all recorded DENV sequences, and the majority were found to be immune-relevant by their correspondence to known or putative HLA-restricted T-cell determinants. The conservation of these sequences through the entire recorded DENV genetic history supports their possible value for diagnosis, prophylactic and/or therapeutic applications. The combination of bioinformatics and experimental approaches applied herein provides a framework for large-scale and systematic analysis of conserved and variable sequences of other pathogens, in particular, for rapidly mutating viruses, such as influenza A virus and HIV.


title: Headache Virtual Visit Toolbox: The Transition From Bedside Manners to Webside Manners

text: The COVID‐19 health emergency has led many Headache providers to transition to virtual care overnight without preparation. We review our experience and discuss tips to bring humanity to the virtual visits.


title: Potent and persistent antibody responses against the receptor-binding domain of SARS-CoV spike protein in recovered patients

text: BACKGROUND: The spike (S) protein of SARS-CoV not only mediates receptor-binding but also induces neutralizing antibodies. We previously identified the receptor-binding domain (RBD) of S protein as a major target of neutralizing antibodies in animal models and thus proposed a RBD-based vaccine. However, the antigenicity and immunogenicity of RBD in humans need to be characterized. RESULTS: Two panels of serum samples from recovered SARS patients were included and the antibody responses against the RBD were measured by ELISA and micro-neutralization assays. We found that the RBD of S protein induced potent antibody responses in the recovered SARS patients and RBD-specific antibodies could persist at high titers over three year follow-up. Furthermore, affinity purified anti-RBD antibodies possessed robust neutralizing activity. CONCLUSION: The RBD of SARS-CoV is highly immunogenic in humans and mediates protective responses and RBD-based vaccines and diagnostic approaches can be further developed.


title: Current pharmacological modalities for management of novel coronavirus disease 2019 (COVID‐19) and the rationale for their utilization: A review

text: SARS‐CoV‐2 has caused a pandemic which is putting strain on the health‐care system and global economy. There is much pressure to develop both preventative and curative therapies for SARS‐CoV‐2 as there is no evidence to support therapies to improve outcomes in patients with SARS‐CoV‐2. Medications that inhibit certain steps of virus life cycle that are currently used to treat other illnesses such as Malaria, Ebola, HIV and Hepatitis C are being studied for use against SARS‐CoV‐2. To date, data is limited for medications that facilitate clinical improvement of COVID‐19 infections.


title: Laboratory-Proven Asymptomatic SARS-CoV-2 (COVID-19) Infection on (18)F-FDG PET/CT

text: An 87-year-old man with primary salivary duct carcinoma and hepatic metastases was referred for restaging. (18)F-FDG PET/CT demonstrated new FDG-avid ground-glass opacities with intralobular septal thickening in both lungs with a peripheral dominant distribution. This was interpreted as a pattern highly suggestive of COVID-19 pneumonia, and the referring physician was contacted. The patient was currently asymptomatic and without clinical evidence of active pneumonia. However, the patient tested positive for COVID-19 using real-time reverse transcription–polymerase chain reaction. This case demonstrates that even asymptomatic outpatients undergoing PET/CT should be evaluated for radiologic findings suggestive of COVID-19 during this pandemic.


title: Validation of Syndromic Surveillance for Respiratory Infections

text: STUDY OBJECTIVE: A key public health question is whether syndromic surveillance data provide early warning of infectious outbreaks. One cause for skepticism is that biological correlates of the administrative and clinical data used in these systems have not been rigorously assessed. This study measures the value of respiratory data currently used in syndromic surveillance systems to detect respiratory infections by comparing it against criterion standard viral testing within a pediatric population. METHODS: We conducted a longitudinal study with prospective validation in the emergency department (ED) of a tertiary care children’s hospital. Children aged 7 years or younger who presented with a respiratory syndrome or who were tested for respiratory syncytial virus (RSV), influenza virus, parainfluenza virus, adenovirus, or enterovirus between January 1993 and June 2004 were included. We assessed the predictive ability of the viral tests by fitting generalized linear models to respiratory syndrome counts. RESULTS: Of 582,635 patient visits, 89,432 (15.4%) were for respiratory syndromes, and of these, 7,206 (8.1%) patients were tested for the viruses of interest. RSV was significantly related to respiratory syndrome counts (adjusted rate ratio [RR] 1.33; 95% confidence interval [CI] 1.04 to 1.71). In multivariate models including all viruses tested, influenza virus was also a significant predictor of respiratory syndrome counts (RR 1.47; 95% CI 1.03 to 2.10). This model accounted for 81.6% of the observed variability in respiratory syndrome counts. CONCLUSION: Respiratory syndromic surveillance data strongly correlate with virologic test results in a pediatric population, providing evidence of the biologic validity of such surveillance systems. Real-time outbreak detection systems relying on syndromic data may be an important adjunct to the current set of public health systems for the detection and surveillance of respiratory infections.


title: Wind tunnel tests of inter-flat pollutant transmission characteristics in a rectangular multi-storey residential building, part A: Effect of wind direction

text: Abstract The inter-flat dispersion of hazardous air pollutants in residential built environment has become a growing concern, especially in crowed urban areas. The purpose of present study is to investigate the wind induced air pollutant transmission and cross contamination routes in typical buildings. In this paper, a series of experiments was carried out in a boundary layer wind tunnel using a 1:30 scaled model that represented the typical configuration of rectangular multi-storey residential buildings in Shanghai. Sulfur hexafluoride (SF6) was employed as tracer gas in the wind tunnel tests. The conditions under two ventilation modes, i.e. single-sided natural ventilation and cross natural ventilation, were compared. The tracer gas concentration distributions under four approaching wind angles were monitored and analyzed. Computational Fluid Dynamics (CFD) method was adopted to assist in analyzing airflow patterns. The experiment results elucidated that in the two ventilation scenarios, both of the vertical and horizontal inter-flat airborne transmission could proceed. The wind direction played a key role on the pollutant concentration distribution. Compared with the single-sided ventilation mode, cross ventilation could weaken the air pollutant dispersion along the vertical direction when the contamination source was on the windward or on the leeward unit. When the wind blowing parallelly to the source unit window, namely the source room was on the sideward, cross ventilation would not suppress the vertical transport on one hand, but reinforce the horizontal transmission on the other hand. The study is helpful for the analysis of infection risk of respiratory diseases in the residential buildings.


title: High-Capacity Adenoviral Vectors: Expanding the Scope of Gene Therapy

text: The adaptation of adenoviruses as gene delivery tools has resulted in the development of high-capacity adenoviral vectors (HC-AdVs), also known, helper-dependent or “gutless”. Compared with earlier generations (E1/E3-deleted vectors), HC-AdVs retain relevant features such as genetic stability, remarkable efficacy of in vivo transduction, and production at high titers. More importantly, the lack of viral coding sequences in the genomes of HC-AdVs extends the cloning capacity up to 37 Kb, and allows long-term episomal persistence of transgenes in non-dividing cells. These properties open a wide repertoire of therapeutic opportunities in the fields of gene supplementation and gene correction, which have been explored at the preclinical level over the past two decades. During this time, production methods have been optimized to obtain the yield, purity, and reliability required for clinical implementation. Better understanding of inflammatory responses and the implementation of methods to control them have increased the safety of these vectors. We will review the most significant achievements that are turning an interesting research tool into a sound vector platform, which could contribute to overcome current limitations in the gene therapy field.


title: Impact of preceding respiratory viral infections on the clinical severity of patients with pneumococcal pneumonia

text: BACKGROUND: This study aimed to investigate the impact of preceding respiratory viral infections (RVI) on the clinical severity of pneumococcal pneumonia patients. METHODS: A retrospective observational study was conducted at a university hospital from January 2009 to March 2013. Study subjects included adults (aged ≥18 years) with pneumococcal pneumonia who had undergone laboratory tests for RVI. Multivariate logistic regression analysis was performed to identify risk factors associated with severe pneumococcal pneumonia, defined as severity with the Pneumonia Severity Index (PSI) score ≥91. RESULTS: In total, 191 patients with pneumococcal pneumonia were included for analysis and stratified into 2 groups: the severe group with a PSI score ≥91 (n = 99) and the non-severe group with a PSI score <91 (n = 92). Preceding RVIs were detected in 48 patients, including influenza A virus (n = 20), influenza B virus (n = 4), parainfluenza viruses (n = 5), metapneumovirus (n = 4), rhinovirus (n = 4), respiratory syncytial viruses (n = 6), coronaviruses (n = 2), and mixed viral infections (n = 3). In the multivariate logistic regression analysis, preceding RVIs (odds ratio [OR], 2·49; 95% confidence interval [CI], 1·10–5·60), male sex (OR, 2·58; 95% CI, 1·24–5·38), old age (OR, 2·92; 95% CI, 1·37–6·24), hypoalbuminemia (OR, 3·26; 95% CI, 1·56–6·84)], and azotemia (OR, 2·24; 95% CI, 1·08–4·67) were significantly associated with severe pneumococcal pneumonia. CONCLUSION: This study suggests that preceding RVIs might be one of the risk factors affecting the clinical severity of pneumococcal pneumonia.


title: Community Case Clusters of Middle East Respiratory Syndrome Coronavirus in Hafr Al-Batin, Kingdom of Saudi Arabia: A Descriptive Genomic study

text: The Middle East respiratory syndrome coronavirus (MERS-CoV) was first described in September 2012 and to date 86 deaths from a total of 206 cases of MERS-CoV infection have been reported to the WHO. Camels have been implicated as the reservoir of MERS-CoV, but the exact source and mode of transmission for most patients remain unknown. During a 3 month period, June to August 2013, there were 12 positive MERS-CoV cases reported from the Hafr Al-Batin region district in the north east region of the Kingdom of Saudi Arabia. In addition to the different regional camel festivals in neighboring countries, Hafr Al-Batin has the biggest camel market in the entire Kingdom and hosts an annual camel festival. Thus, we conducted a detailed epidemiological, clinical and genomic study to ascertain common exposure and transmission patterns of all cases of MERS-CoV reported from Hafr Al-Batin. Analysis of previously reported genetic data indicated that at least two of the infected contacts could not have been directly infected from the index patient and alternate source should be considered. While camels appear as the likely source, other sources have not been ruled out. More detailed case control studies with detailed case histories, epidemiological information and genomic analysis are being conducted to delineate the missing pieces in the transmission dynamics of MERS-CoV outbreak.


title: Middle East respiratory syndrome in South Korea during 2015: Risk-related perceptions and quarantine attitudes

text: A telephone survey involving 200 household members in and around Seoul, South Korea, was completed during the maturity stage of the outbreak of Middle East respiratory syndrome (MERS) in Korea during June 2015. The study found that respondents perceived low risk from contracting MERS, had low trust in government in controlling MERS, and generally held unfavorable attitudes toward quarantine.


Physical Activity And Reducing Sedentary Behavior During The Coronavirus Pandemic/ Atividade Fisica e Reducao do Comportamento Sedentario durante a Pandemia do Coronavirus


title: Can post-exposure prophylaxis for COVID-19 be considered as one of outbreak response strategies in long-term care hospitals?

text: ABSTRACT With ongoing global outbreak of coronavirus disease 2019 (COVID-19), management of exposure events is a concern. Long-term care hospitals (LTCHs) are especially vulnerable to cluster outbreaks, since it is difficult to find facilities and healthcare personnel for their separate isolation care in a large outbreak situation. Although several drugs have been proposed as treatment regimens, there are no data on the effectiveness and safety of post-exposure prophylaxis (PEP) for COVID-19. After a large COVID-19 exposure event in a LTCH in Korea, PEP using hydroxychloroquine (HCQ) was conducted to 211 persons including 189 patients and 22 careworkers, whose baseline polymerase chain reaction (PCR) tests for COVID-19 were negative. PEP was completed in 184 (97.4%) patients and 21 (95.5%) careworkers without serious adverse events. At the end of 14 days of quarantine, follow-up PCR tests were all negative. Based on our experience, further clinical studies would be conducted for COVID-19 PEP.


title: Characterization of the spike protein of human coronavirus NL63 in receptor binding and pseudotype virus entry

text: Abstract The spike (S) protein of human coronavirus NL63 (HCoV-NL63) mediates both cell attachment by binding to its receptor hACE2 and membrane fusion during virus entry. We have previously identified the receptor-binding domain (RBD) and residues important for RBD–hACE2 association. Here, we further characterized the S protein by investigating the roles of the cytoplasmic tail and 19 residues located in the RBD in protein accumulation, receptor binding, and pseudotype virus entry. For these purposes, we first identified an entry-efficient S gene template from a pool of gene variants and used it as a backbone to generate a series of cytoplasmic tail deletion and single residue substitution mutants. Our results showed that: (i) deletion of 18aa from the C-terminus enhanced the S protein accumulation and virus entry, which might be due to the deletion of intracellular retention signals; (ii) further deletion to residue 29 also enhanced the amount of S protein on the cell surface and in virion, but reduced virus entry by 25%, suggesting that residues 19–29 contributes to membrane fusion; (iii) a 29aa-deletion mutant had a defect in anchoring on the plasma membrane, which led to a dramatic decrease of S protein in virion and virus entry; (iv) a total of 15 residues (Y498, V499, V531, G534, G537, D538, S540, G575, S576, E582, W585, Y590, T591, V593 and G594) within RBD were important for receptor binding and virus entry. They probably form three receptor binding motifs, and the third motif is conserved between NL63 and SARS-CoV.


title: “Hydroxychloroquine in patients with COVID-19: A Systematic Review and meta-analysis.”

text: BACKGROUNDS AND AIMS: The role of hydroxychloroquine (HCQ) in the treatment of COVID-19 is not fully known. We studied the efficacy of HCQ compared to the control in COVID-19 subjects on a. viral clearance measured by reverse transcriptase polymerase chain reaction (RT-PCR) and, b. death due to all cause. METHODS: PubMed, Scopus, Cochrane and MedRxiv database were searched using the specific keywords up to April 30, 2020. Studies that met our objectives were assessed for the risk of bias applying various tools as indicated. Three studies each that reported the outcome of viral clearance by RT-PCR and death due to all cause, were meta-analyzed by applying inverse variance-weighted averages of logarithmic risk ratio (RR) using a random effects model. Heterogeneity and publication bias were assessed using the I(2) statistic and funnel plots, respectively. RESULTS: Meta-analysis of 3 studies (n = 210) on viral clearance assessed by RT-PCR showed no benefit (RR, 1.05; 95% CI, 0.79 to 1.38; p = 0.74), although with a moderate heterogeneity (I(2) = 61.7%, p = 0.07). While meta-analysis of 3 studies (n = 474) showed a significant increase in death with HCQ, compared to the control (RR, 2.17; 95% 1.32 to 3.57; p = 0.002), without any heterogeneity (I(2) = 0.0%, p = 0.43). CONCLUSIONS: No benefit on viral clearance but a significant increase in mortality was observed with HCQ compared to control in patients with COVID-19.


title: First COVID-19 mortality case in Taiwan with bacterial co-infection by national surveillance of critically ill patients with influenza-negative pneumonia

text: Abstract A 63-year-old diabetic smoker with alcoholism was the first mortality case of coronavirus disease 2019 (COVID-19) in Taiwan. As concurrently infected with Klebsiella pneumoniae and subsequently with Klebsiella aerogenes, he was exposed by a national survey of patients with critically influenza-negative pneumonia. We recommend COVID-19 screening for patients with severe flu-like syndrome and protecting health-care workers from being infected.


The epilepsy unit during the COVID-19 epidemic: The role of telemedicine and the effects of confinement on patients with epilepsy


title: Organic Carbamates in Drug Design and Medicinal Chemistry

text: [Image: see text] The carbamate group is a key structural motif in many approved drugs and prodrugs. There is an increasing use of carbamates in medicinal chemistry and many derivatives are specifically designed to make drug–target interactions through their carbamate moiety. In this Perspective, we present properties and stabilities of carbamates, reagents and chemical methodologies for the synthesis of carbamates, and recent applications of carbamates in drug design and medicinal chemistry.


title: Opportunistic bacterial, viral and fungal infections of the lung

text: Abstract Opportunistic infections are a major cause of morbidity and mortality in severely immunocompromised patients, such as those given chemotherapy or biological therapies, and those with haematological malignancy, aplastic anaemia or HIV infection, or recipients of solid organ or stem cell transplants. The type and degree of immune defect dictates the profile of potential opportunistic pathogens; T-cell-mediated defects increase the risk of viral (cytomegalovirus, respiratory viruses) and Pneumocystis jirovecii infections, whereas neutrophil defects are associated with bacterial pneumonia and invasive aspergillosis. However, patients often have combinations of immune defects, and a wide range of other opportunistic infections can cause pneumonia. Importantly, conventional non-opportunistic pathogens are frequently encountered in immunocompromised hosts and should not be overlooked The radiological pattern of disease (best assessed by computed tomography) and speed of onset help identify the likely pathogen(s); this can then be supported by targeted investigation including early use of bronchoscopy in selected patients. Rapid and expert clinical assessment can identify the most likely pathogens, allowing timely appropriate therapy.


title: Inmunosupresión en el trasplante hepático en la era Covid-19

text: Abstract SARS CoV-2 infection has produced a pandemic with serious consequences for our health care system. Although liver transplant patients represent only a minority of the population, the hepatologists who follow these patients have tried to coordinate efforts to produce a protocol the management of immunosuppression during SARS Cov-2 infection. Although there are no solid studies to support general recommendations, experiences with other viral infections (hepatitis C, cytomegalovirus) suggest that management of immunosuppression without mycophenolate mofetil or m-Tor inhibitors (drugs that are also associated with leukopenia and lymphopenia) may be beneficial. It is also important to pay attention to possible drug interactions, especially in the case of tacrolimus, with some of the treatments with antiviral effect given in the context of COVID 19 (lopinavir/ritonavir, azithromycin). Finally, the immunosuppressive effect of immunomodulating drugs (tocilizumab and similar) administered to patients with severe lung disease should be taken into account. The mechanisms of action of the different immunosuppressive drugs are reviewed in this article, as well as their potential effect on Cov-2 SARS infection, and suggests guidelines for the management of immunosuppression.


title: Serological assays for emerging coronaviruses: Challenges and pitfalls

text: Abstract More than a decade after the emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002/2003 the occurrence of a novel CoV termed Middle East respiratory syndrome (MERS) CoV challenges researchers and public health authorities. To control spread and finally contain novel viruses, rapid identification and subsequent isolation of infected individuals and their contacts is of utmost importance. Next to methods for nucleic acid detection, validated serological assays are particularly important as the timeframe for antibody detection is less restricted. During the SARS-CoV epidemic a wide variety of serological diagnostic assays were established using multiple methods as well as different viral antigens. Even though the majority of the developed assays showed high sensitivity and specificity, numerous studies reported on cross-reactive antibodies to antigens from wide-spread common cold associated CoVs. In order to improve preparedness and responsiveness during future outbreaks of novel CoVs, information and problems regarding serological diagnosis that occurred during the SARS-CoV should be acknowledged. In this review we summarize the performance of different serological assays as well as the applicability of the two main applied antigens (spike and nucleocapsid protein) used during the SARS-CoV outbreak. We highlight challenges and potential pitfalls that occur when dealing with a novel emerging coronavirus like MERS-CoV. In addition we describe problems that might occur when animal sera are tested in serological assays for the identification of putative reservoirs. Finally, we give a recommendation for a serological testing scheme and outline necessary improvements that should be implemented for a better preparedness.


title: The dilemma of rare events: Porcine epidemic diarrhea virus in North America

text: Abstract Porcine epidemic diarrhea virus (PEDV) has been recognized as a swine pathogen for 40 years, but until 2013 had not been detected in the Western Hemisphere. From originally causing a relatively mild and sporadic disease, PEDV has been more recently associated with severe outbreaks of diarrheal disease in Asia, and subsequently North America. PEDV shares some important characteristics with two major pandemic viruses (porcine reproductive and respiratory virus; porcine circovirus type 2) of pigs that have high rates of mutation and high host specificity, and appear to have been present in the swine virome for decades prior to emerging to cause severe clinical disease. A unique feature of the PEDV in North America has been the implication of feed as a vehicle for transmission, with particular concerns related to ingredients of porcine origin. The importance of relatively rare events in contributing to both the emergence and transmission of PEDV is discussed in relation to approaches for managing the associated risks.


title: Early transmission dynamics of COVID-19 in a southern hemisphere setting: Lima-Peru: February 29(th)–March 30(th), 2020.

text: The COVID-19 pandemic that emerged in Wuhan China has generated substantial morbidity and mortality impact around the world during the last four months. The daily trend in reported cases has been rapidly rising in Latin America since March 2020 with the great majority of the cases reported in Brazil followed by Peru as of April 15(th), 2020. Although Peru implemented a range of social distancing measures soon after the confirmation of its first case on March 6(th), 2020, the daily number of new COVID-19 cases continues to accumulate in this country. We assessed the early COVID-19 transmission dynamics and the effect of social distancing interventions in Lima, Peru. We estimated the reproduction number, R, during the early transmission phase in Lima from the daily series of imported and autochthonous cases by the date of symptoms onset as of March 30(th), 2020. We also assessed the effect of social distancing interventions in Lima by generating short-term forecasts grounded on the early transmission dynamics before interventions were put in place. Prior to the implementation of the social distancing measures in Lima, the local incidence curve by the date of symptoms onset displays near exponential growth dynamics with the mean scaling of growth parameter, p, estimated at 0.9 (95%CI: 0.9,1.0) and the reproduction number at 2.3 (95% CI: 2.0, 2.5). Our analysis indicates that school closures and other social distancing interventions have helped slow down the spread of the novel coronavirus, with the nearly exponential growth trend shifting to an approximately linear growth trend soon after the broad scale social distancing interventions were put in place by the government. While the interventions appear to have slowed the transmission rate in Lima, the number of new COVID-19 cases continue to accumulate, highlighting the need to strengthen social distancing and active case finding efforts to mitigate disease transmission in the region.


title: Suspected phenobarbital-induced fever in a cat

text: CASE SUMMARY: A 3-year-old spayed female domestic shorthair cat developed a fever 1 week after starting the anticonvulsant phenobarbital. A diagnostic work-up for seizures and subsequent onset of fever of unknown origin, consisting of MRI of the brain, cerebrospinal fluid analysis and infectious disease testing, was unremarkable. The cat was switched from phenobarbital onto pregabalin with complete resolution of the fever within 24 h, consistent with a drug-induced fever following phenobarbital administration. RELEVANCE AND NOVEL INFORMATION: While anticonvulsant hypersensitivities have been reported and studied in veterinary medicine, phenobarbital-induced fever outside of the context of systemic clinical signs has not been documented in the veterinary scientific literature. Drug-induced fever secondary to anticonvulsants should be considered in patients that develop a fever after starting anticonvulsant therapy with an unrewarding diagnostic work-up for fever of unknown origin.


title: Clearance and Persistence of SARS‐CoV‐2 RNA in COVID‐19 patients

text: COVID‐19 patients may be discharged based on clinical resolution of symptoms, and evidence for viral RNA clearance from the upper respiratory tract. Understanding the SARS‐CoV‐2 viral clearance profile is crucial to establish a re‐testing plan on discharge and ending isolation of patients. We aimed to evaluate the number of days that a patient needed to achieve undetectable levels of SARS‐CoV‐2 in upper respiratory tract specimens (nasopharyngeal swab and/or an oropharyngeal swab). The clearance and persistence of viral RNA was evaluated in two groups of positive patients: those who achieved two negative RT‐PCR tests and those who kept testing positive. Patients were organized thereafter in two subgroups, mild illness patients discharged home and inpatients who had moderate to severe illness. Results from RT‐PCR tests were then correlated with results from the evaluation of the immune response. The study evidenced that most patients tested positive for more than two weeks and that persistence of viral RNA is not necessarily associated with severe disease but may result from a weaker immune response instead. This article is protected by copyright. All rights reserved.