title: Biochemical principles and inhibitors to interfere with viral capping pathways

text: Messenger RNAs are decorated by a cap structure, which is essential for their translation into proteins. Many viruses have developed strategies in order to cap their mRNAs. The cap is either synthetized by a subset of viral or cellular enzymes, or stolen from capped cellular mRNAs by viral endonucleases (‘cap-snatching’). Reverse genetic studies provide evidence that inhibition of viral enzymes belonging to the capping pathway leads to inhibition of virus replication. The replication defect results from reduced protein synthesis as well as from detection of incompletely capped RNAs by cellular innate immunity sensors. Thus, it is now admitted that capping enzymes are validated antiviral targets, as their inhibition will support an antiviral response in addition to the attenuation of viral mRNA translation. In this review, we describe the different viral enzymes involved in mRNA capping together with relevant inhibitors, and their biochemical features useful in inhibitor discovery.


title: The current state of cardiology in China

text: Abstract Cardiology in China has shown significant changes in the last decade or so. Interventional cardiology, in particular, has shown remarkable advances, especially in the management of coronary artery disease, which, unfortunately, has shown a disconcerting increase in incidence in a country traditionally known for very low incidence of coronary artery disease. Important contributing factors include increasing affluence, westernization of dietary habit and lifestyle, and rampant cigarette smoking. At present, the Chinese population has an annual coronary mortality of one sixth of that reported in the West, an incidence of acute myocardial infarction of one tenth to one eighth, and a mortality of acute myocardial infarction of one eighth. The prevalence of coronary artery disease among the general Chinese population (3–7%) is roughly one quarter of that among the Caucasians in the West, but this will get worse for sure. China still has a lot of catching up to do to reach full modernization. There is a price that every developing country must pay for modernization. However, let the price the Chinese pay not exceed the benefits derived from modernization. Can we achieve a utopian stage in the 21st century in which the modern Chinese retain their ancestral low rates of coronary artery disease while adapting the positive aspects of a modern western lifestyle?


The National Children’s Study: A Critical National Investment


title: Detection of a new bat gammaherpesvirus in the Philippines

text: A new bat herpesvirus was detected in the spleen of an insectivorous bat (Hipposideros diadema, family Hipposideridae) collected on Panay Island, the Philippines. PCR analyses were performed using COnsensus-DEgenerate Hybrid Oligonucleotide Primers (CODEHOPs) targeting the herpesvirus DNA polymerase (DPOL) gene. Although we obtained PCR products with CODEHOPs, direct sequencing using the primers was not possible because of high degree of degeneracy. Direct sequencing technology developed in our rapid determination system of viral RNA sequences (RDV) was applied in this study, and a partial DPOL nucleotide sequence was determined. In addition, a partial gB gene nucleotide sequence was also determined using the same strategy. We connected the partial gB and DPOL sequences with long-distance PCR, and a 3741-bp nucleotide fragment, including the 3′ part of the gB gene and the 5′ part of the DPOL gene, was finally determined. Phylogenetic analysis showed that the sequence was novel and most similar to those of the subfamily Gammaherpesvirinae.


title: Thrombotic occlusive vasculopathy in skin biopsy from a livedoid lesion of a COVID‐19 patient

text: Some authors have reported the presence of cutaneous lesions related to new COronaVirus Disease 2019 (CoViD‐19) caused by SARS‐CoV‐2, in up to 20.4% of the cases; however, these lesions are not well characterized either clinically or histopathologically.(1) Recently, it has been highlighted the finding of congested and edematous blood vessels in the alveolar septum along with hyaline thrombi, and also in the heart, liver and kidney of autopsies of 3 patients deceased due to severe infection by SARS‐CoV‐2.


title: Coronavirus Disease 19 Infection Does Not Result in Acute Kidney Injury: An Analysis of 116 Hospitalized Patients from Wuhan, China

text: BACKGROUND: Whether the patients with coronavirus disease 19 (COVID-19) infected by severe acute respiratory syndrome (SARS)-CoV-2 would commonly develop acute kidney injury (AKI) is an important issue worthy of clinical attention. This study aimed to explore the effects of SARS-CoV-2 infection on renal function through analyzing the clinical data of 116 hospitalized COVID-19-confirmed patients. METHODS: One hundred sixteen COVID-19-confirmed patients enrolled in this study were hospitalized in the Department of Infectious Diseases, Renmin Hospital of Wuhan University from January 14 to February 13, 2020. The recorded information includes demographic data, medical history, contact history, potential comorbidities, symptoms, signs, laboratory test results, chest computer tomography scans, and treatment measures. SARS-CoV-2 RNA in 53 urine sediments of enrolled patients was detected by real-time reverse transcription-polymerase chain reaction. RESULTS: Twelve (10.8%) patients showed mild increase of blood urea nitrogen or creatinine (<26 μmol/L within 48 h), and 8 (7.2%) patients showed trace or 1+ albuminuria in 111 COVID-19-confirmed patients without chronic kidney disease (CKD). All these patients did not meet the diagnostic criteria of AKI. In addition, 5 patients with CKD who were undergone regular continuous renal replacement therapy (CRRT) before admission were confirmed infection of SARS-CoV-2 and diagnosed as COVID-19. In addition to therapy for COVID-19, CRRT was also applied 3 times weekly during hospitalization for these 5 patients with CKD. In the course of treatment, the renal function indicators showed stable state in all 5 patients with CKD, without exacerbation of CKD, and pulmonary inflammation was gradually absorbed. All 5 patients with CKD were survived. Moreover, SARS-CoV-2 RNA in urine sediments was positive only in 3 patients from 48 cases without CKD, and 1 patient had a positive for SARS-CoV-2 open reading frame 1ab from 5 cases with CKD. CONCLUSION: AKI was uncommon in COVID-19. SARS-CoV-2 infection does not result in AKI, or aggravate CKD in the COVID-19 patients.


title: Double-antigen sandwich ELISA for detection of antibodies to SARS-associated coronavirus in human serum

text: The study presented here was conducted to evaluate the performance of a double-antigen sandwich ELISA to detect antibodies in human serum against the coronavirus associated with severe acute respiratory syndrome (SARS). A recombinant partial nucleocapsid protein of SARS-associated coronavirus was used as a serodiagnostic antigen in the ELISA. A total of 2892 clinical serum samples were tested with the ELISA kit, which positively identified 25 of 35 (71.4%) samples of patients with confirmed SARS infection, 286 of 407 (70%) samples of patients suspected of having SARS, 229 of 302 (75.8%) samples of convalescent SARS patients, and 0 of 544 samples obtained from healthcare workers; only 1 of 1604 clinical samples obtained from patients with other diseases demonstrated a weakly positive result. These results indicate that the double-antigen sandwich ELISA is an effective screening method for the serodiagnosis of SARS-associated coronavirus.


title: Rapid Modification of Workflows and Fellow Staffing at a Single Transplant Center to Address the COVID-19 Crisis

text: Abstract Background Although hospital systems have largely halted elective surgical practices in preparing their response to the SARS-CoV-2 pandemic, transplantation remains an essential and lifesaving surgical practice. In order to continue transplantation while protecting immunocompromised patients and healthcare workers, significant restructuring of normal patient care practice habits is required. Methods This is a non-randomized, descriptive study of the abdominal transplant program at one academic center (University of California, San Francisco) and the programmatic changes undertaken to safely continue transplantations. Patient transfers, fellow utilization, and patient discharge education were identified as key areas requiring significant reorganization. Results The University of California, San Francisco abdominal transplant program took an early and aggressive approach to restructuring inpatient workflows and healthcare worker staffing. We formalized a COVID-19 transfer system to address patients in need of services at our institution while minimizing the risk of SARS-CoV-2 on our transplant ward and utilized technological approaches to provide virtual telehealth where possible, We also modified our transplant fellow staffing and responsibilities to develop an adequate backup system in the case of potential exposures. Conclusion Every transplant program is unique, and an individualized plan to adapt and modify standard clinical practices will be required to continue providing essential transplantation services. Our experience highlights areas of attention specific to transplant programs, and may provide generalizable solutions to support continued transplantation in the COVID-19 era.


Confronting the New Challenge in Travel Medicine: SARS


title: Operational issues and network effects in vaccine markets

text: One of the most important concerns for managing public health is the prevention of infectious diseases. Although vaccines provide the most effective means for preventing infectious diseases, there are two main reasons why it is often difficult to reach a socially optimal level of vaccine coverage: (i) the emergence of operational issues (such as yield uncertainty) on the supply side, and (ii) the existence of negative network effects on the consumption side. In particular, uncertainties about production yield and vaccine imperfections often make manufacturing some vaccines a risky process and may lead the manufacturer to produce below the socially optimal level. At the same time, negative network effects provide incentives to potential consumers to free ride off the immunity of the vaccinated population. In this research, we consider how a central policy-maker can induce a socially optimal vaccine coverage through the use of incentives to both consumers and the vaccine manufacturer. We consider a monopoly market for an imperfect vaccine; we show that a fixed two-part subsidy is unable to coordinate the market, but derive a two-part menu of subsidies that leads to a socially efficient level of coverage.


title: Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates, April 2014

text: Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. We describe the histopathologic, immunohistochemical, and ultrastructural findings from the first autopsy performed on a fatal case of MERS-CoV in the world, which was related to a hospital outbreak in the United Arab Emirates in April 2014. The main histopathologic finding in the lungs was diffuse alveolar damage. Evidence of chronic disease, including severe peripheral vascular disease, patchy cardiac fibrosis, and hepatic steatosis, was noted in the other organs. Double staining immunoassays that used anti–MERS-CoV antibodies paired with immunohistochemistry for cytokeratin and surfactant identified pneumocytes and epithelial syncytial cells as important targets of MERS-CoV antigen; double immunostaining with dipeptidyl peptidase 4 showed colocalization in scattered pneumocytes and syncytial cells. No evidence of extrapulmonary MERS-CoV antigens were detected, including the kidney. These results provide critical insights into the pathogenesis of MERS-CoV in humans.


title: Community-acquired adenovirus pneumonia in a patient with chronic lymphatic leukaemia

text: Described here is a severe case of community-acquired adenovirus pneumonia that occurred in a previously healthy 54-year-old male who was later determined to have stage A chronic lymphatic leukemia. The clinical presentation was consistent with that of atypical pneumonia. Testing with PCR revealed adenovirus in a bronchoalveolar lavage sample, while all other tests to determine a bacterial or virological etiology were negative. Further examination of the patient revealed the previously undiagnosed chronic lymphatic leukemia. Following treatment with human immunoglobulin and oxygen therapy with continuous positive airway pressure support the patient recovered from the pneumonia completely.


title: An inactivated West Nile Virus vaccine derived from a chemically synthesized cDNA system

text: A cDNA comprising the complete genome of West Nile Virus (WNV) was generated by chemical synthesis using published sequence data, independent of any preformed viral components. The synthetic WNV, produced by transfection of in vitro transcribed RNA into cell culture, exhibited undistinguishable biological properties compared to the corresponding animal-derived wild-type virus. No differences were found concerning viral growth in mammalian and insect cell lines and concerning expression of viral proteins in cells. There were also no significant differences in virulence in mice following intranasal challenge. After immunizations of mice with experimental vaccines derived from the synthetic and wild-type viruses, protection from lethal challenge was achieved with similar amounts of antigen. Both vaccine preparations also induced comparable levels of neutralizing antibodies in mice. In addition, the synthetic approach turned out to be very accurate, since the rescued WNV genome contained no undesired mutations. Thus, the first flavivirus based on chemical gene synthesis was indistinguishable from the parent virus. This demonstrates that virus isolates from animal sources are dispensable to derive seed viruses for vaccine production or research.


title: Things That Go Bump in the Literature: An Environmental Appraisal of “Haunted Houses”

text: This paper contains a narrative overview of the past 20-years of environmental research on anomalous experiences attributed to “haunted house.” This exercise served as a much-needed update to an anthology of noteworthy overviews on ghosts, haunts, and poltergeists (Houran and Lange, 2001b). We also considered whether new studies had incorporated certain recommendations made in this anthology. Our search revealed a relative paucity of studies (n = 66) on environmental factors that ostensibly stimulate haunt-type experiences. This literature was diverse and often lacked methodological consistency and adherence to the prior suggestions. However, critical consideration of the content revealed a recurring focus on six ambient variables: embedded (static) cues, lighting levels, air quality, temperature, infrasound, and electromagnetic fields. Their relation to the onset or structure of witness reports showed mostly null, though sometimes inconsistent or weak outcomes. However, such research as related to haunts is arguably in its infancy and new designs are needed to account better for environmental and architectural phenomenology. Future studies should therefore address four areas: (i) more consistent and precise measurements of discrete ambient variables; (ii) the potential role of “Gestalt influences” that involve holistic environment-person interactions; (iii) individual differences in attentional or perceptual sensitivities of percipients to environmental variables; and (iv) the role of attitudinal and normative influences in the interpretation of environmental stimuli. Focused scrutiny on these issues should clarify the explanatory power of evolutionary-environmental models for these and related anomalous experiences.


title: Inhibitory effect of mizoribine and ribavirin on the replication of severe acute respiratory syndrome (SARS)-associated coronavirus

text: Abstract The activity of inosine-5′-monophosphate dehydrogenase (IMPDH) inhibitors, mizoribine and ribavirin, against severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) was determined by plaque reduction and yield reduction assays. Mizoribine and ribavirin selectively inhibited replication of SARS-CoV. The 50% inhibitory concentration (IC50) of mizoribine for SARS-CoV Frankfurt-1 and SARS-CoV HKU39849, as determined by plaque reduction was 3.5μg/ml and 16μg/ml, respectively, and the IC50 of ribavirin for SARS-CoV Frankfurt-1 and SARS-CoV HKU39849 was 20μg/ml and 80μg/ml, while the 50% cytotoxic concentration of mizoribine and ribavirin for Vero E6 cells exceeded 200μg/ml. In a yield reduction assay, mizoribine (10μg/ml) and ribavirin (40μg/ml) inhibited the replication of SARS-CoV and reduced the infectious SARS-CoV titers to one-tenth or less. Mizoribine inhibited replication of SARS-CoV more strongly than ribavirin. However, neither drug could completely inhibit replication of SARS-CoV even at concentrations up to 100μg/ml.


title: Evaluation and Comparison of the Pathogenicity and Host Immune Responses Induced by a G2b Taiwan Porcine Epidemic Diarrhea Virus (Strain Pintung 52) and Its Highly Cell-Culture Passaged Strain in Conventional 5-Week-Old Pigs

text: A genogroup 2b (G2b) porcine epidemic diarrhea virus (PEDV) Taiwan Pintung 52 (PEDVPT) strain was isolated in 2014. The pathogenicity and host antibody responses elicited by low-passage (passage 5; PEDVPT-P5) and high-passage (passage 96; PEDVPT-P96) PEDVPT strains were compared in post-weaning PEDV-seronegative pigs by oral inoculation. PEDVPT-P5-inoculation induced typical diarrhea during 1–9 days post inoculation with fecal viral shedding persisting for 26 days. Compared to PEDVPT-P5, PEDVPT-P96 inoculation induced none-to-mild diarrhea and lower, delayed fecal viral shedding. Although PEDVPT-P96 elicited slightly lower neutralizing antibodies and PEDV-specific immunoglobulin G (IgG) and immunoglobulin A (IgA) titers, a reduction in pathogenicity and viral shedding of the subsequent challenge with PEDVPT-P5 were noted in both PEDVPT-P5- and PEDVPT-P96-inoculated pigs. Alignment and comparison of full-length sequences of PEDVPT-P5 and PEDVPT-P96 revealed 23 nucleotide changes and resultant 19 amino acid substitutions in non-structure proteins 2, 3, 4, 9, 14, 15, spike, open reading frame 3 (ORF3), and membrane proteins with no detectable deletion or insertion. The present study confirmed the pathogenicity of the PEDVPT isolate in conventional post-weaning pigs. Moreover, data regarding viral attenuation and potency of induced antibodies against PEDVPT-P5 identified PEDVPT-P96 as a potential live-attenuated vaccine candidate.


title: A relational perspective on media relations strategies: The Chinese government's news conferences from 2001 to 2009

text: Abstract This study used the conceptual framework of organizational–public relationship cultivation strategies to quantitatively evaluate how the Chinese government's international media relationship cultivation strategies at news conferences changed from 2001 to 2009. It found that the Chinese government has begun to enhance its international media relations efforts but that there is room for further improvement.


title: Toward a Symbiotic Perspective on Public Health: Recognizing the Ambivalence of Microbes in the Anthropocene

text: Microbes evolve in complex environments that are often fashioned, in part, by human desires. In a global perspective, public health has played major roles in structuring how microbes are perceived, cultivated, and destroyed. The germ theory of disease cast microbes as enemies of the body and the body politic. Antibiotics have altered microbial development by providing stringent natural selection on bacterial species, and this has led to the formation of antibiotic-resistant bacterial strains. Public health perspectives such as “Precision Public Health” and “One Health” have recently been proposed to further manage microbial populations. However, neither of these take into account the symbiotic relationships that exist between bacterial species and between bacteria, viruses, and their eukaryotic hosts. We propose a perspective on public health that recognizes microbial evolution through symbiotic associations (the hologenome theory) and through lateral gene transfer. This perspective has the advantage of including both the pathogenic and beneficial interactions of humans with bacteria, as well as combining the outlook of the “One Health” model with the genomic methodologies utilized in the “Precision Public Health” model. In the Anthropocene, the conditions for microbial evolution have been altered by human interventions, and public health initiatives must recognize both the beneficial (indeed, necessary) interactions of microbes with their hosts as well as their pathogenic interactions.


title: Acid-Induced Membrane Fusion by the Hemagglutinin Protein and Its Role in Influenza Virus Biology

text: Membrane fusion is not spontaneous. Therefore, enveloped viruses have evolved membrane-fusion mediating glycoproteins that, once activated, refold, and release energy that fuses viral and cellular membranes. The influenza A virus hemagglutinin (HA) protein is a prototypic structural class I viral fusion glycoprotein that, once primed by proteolytic cleavage, is activated by endosomal low pH to form a fusogenic “leash-in-grooves” hairpin structure. Low-pH induced HA protein refolding is an irreversible process, so acid exposure in the absence of a target membrane leads to virus inactivation. The HA proteins of diverse influenza virus subtypes isolated from a variety of species differ in their acid stabilities, or pH values at which irreversible HA protein conformational changes are triggered. Recently, efficient replication of highly pathogenic avian influenza (HPAI) viruses such as H5N1 in avian species has been associated with a relatively high HA activation pH. In contrast, a decrease in H5N1 HA activation pH has been shown to enhance replication and airborne transmission in mammals. Mutations that alter the acid stabilities of H1 and H3 HA proteins have also been discovered that influence the amantadine susceptibilities, replication rates, and pathogenicities of human influenza viruses. An understanding of the role of HA acid stability in influenza virus biology is expected to aid in identifying emerging viruses with increased pandemic potential and assist in developing live attenuated virus vaccines. Acid-induced HA protein activation, which has provided a paradigm for protein-mediated membrane fusion, is now identified as a novel determinant of influenza virus biology.


title: The impact of social media on risk perceptions during the MERS outbreak in South Korea

text: Abstract Analyzing nationally representative online panel survey data during the MERS outbreak in South Korea, this study examined the role of social media exposure in shaping public's risk perceptions of MERS. The present study also investigated the moderating role of heuristic-systematic processing and self-efficacy in the relationship between social media exposure and risk perceptions. The findings of this study showed that social media exposure was positively related to forming risk perceptions. Moreover, heuristic-systematic processing and self-efficacy were found to moderate the impact of social media on risk perceptions. The interaction effects suggested that the role of social media in increasing risk perceptions of MERS was heighted by heuristic-systematic processing and self-efficacy. The results and implications of this study are discussed in greater details.


Is the Debate and “Pause” on Experiments That Alter Pathogens with Pandemic Potential Influencing Future Plans of Graduate Students and Postdoctoral Fellows?


title: U.S. county-level characteristics to inform equitable COVID-19 response

text: BACKGROUND: The spread of Coronavirus Disease 2019 (COVID-19) across the United States confirms that not all Americans are equally at risk of infection, severe disease, or mortality. A range of intersecting biological, demographic, and socioeconomic factors are likely to determine an individual’s susceptibility to COVID-19. These factors vary significantly across counties in the United States, and often reflect the structural inequities in our society. Recognizing this vast inter-county variation in risks will be critical to mounting an adequate response strategy. METHODS AND FINDINGS: Using publicly available county-specific data we identified key biological, demographic, and socioeconomic factors influencing susceptibility to COVID-19, guided by international experiences and consideration of epidemiological parameters of importance. We created bivariate county-level maps to summarize examples of key relationships across these categories, grouping age and poverty; comorbidities and lack of health insurance; proximity, density and bed capacity; and race and ethnicity, and premature death. We have also made available an interactive online tool that allows public health officials to query risk factors most relevant to their local context. Our data demonstrate significant inter-county variation in key epidemiological risk factors, with a clustering of counties in certain states, which will result in an increased demand on their public health system. While the East and West coast cities are particularly vulnerable owing to their densities (and travel routes), a large number of counties in the Southeastern states have a high proportion of at-risk populations, with high levels of poverty, comorbidities, and premature death at baseline, and low levels of health insurance coverage. The list of variables we have examined is by no means comprehensive, and several of them are interrelated and magnify underlying vulnerabilities. The online tool allows readers to explore additional combinations of risk factors, set categorical thresholds for each covariate, and filter counties above different population thresholds. CONCLUSION: COVID-19 responses and decision making in the United States remain decentralized. Both the federal and state governments will benefit from recognizing high intra-state, inter-county variation in population risks and response capacity. Many of the factors that are likely to exacerbate the burden of COVID-19 and the demand on healthcare systems are the compounded result of long-standing structural inequalities in US society. Strategies to protect those in the most vulnerable counties will require urgent measures to better support communities’ attempts at social distancing and to accelerate cooperation across jurisdictions to supply personnel and equipment to counties that will experience high demand.


title: Contact tracing to control infectious disease: when enough is enough

text: Contact tracing (also known as partner notification) is a primary means of controlling infectious diseases such as tuberculosis (TB), human immunodeficiency virus (HIV), and sexually transmitted diseases (STDs). However, little work has been done to determine the optimal level of investment in contact tracing. In this paper, we present a methodology for evaluating the appropriate level of investment in contact tracing. We develop and apply a simulation model of contact tracing and the spread of an infectious disease among a network of individuals in order to evaluate the cost and effectiveness of different levels of contact tracing. We show that contact tracing is likely to have diminishing returns to scale in investment: incremental investments in contact tracing yield diminishing reductions in disease prevalence. In conjunction with a cost-effectiveness threshold, we then determine the optimal amount that should be invested in contact tracing. We first assume that the only incremental disease control is contact tracing. We then extend the analysis to consider the optimal allocation of a budget between contact tracing and screening for exogenous infection, and between contact tracing and screening for endogenous infection. We discuss how a simulation model of this type, appropriately tailored, could be used as a policy tool for determining the appropriate level of investment in contact tracing for a specific disease in a specific population. We present an example application to contact tracing for chlamydia control.


CONTINUING CHRONIC DISEASE CARE DURING COVID-19 AND BEYOND


title: Regulatory T cells as adjuvant target for enhancing the viral disease vaccine efficacy

text: CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) are critical for immune homeostasis and tolerance. However, because of their capacity to suppress antigen presenting cells (APC), T and B cells, Tregs could also inhibit protective immune responses to viruses and vaccines. Several viruses have been shown to exploit Tregs to evade immune response. By modulating APC and in particular by weakening the functions of dendritic cells such as their ability to secrete polarizing cytokines and expression of co-stimulatory molecules, viruses could support differentiation and expansion of Tregs. Of note, as a proof of concept, depletion of Tregs significantly enhanced the protective immune response to viruses and vaccines suggesting that Tregs are viable targets to enhance immunogenicity of vaccines. As Treg depletion or inhibition of their functions could lead to deleterious autoimmune and inflammatory disorders, any Treg-based approach for vaccination should not aim at depletion of Tregs and inhibition of their functions should be transient. Recent studies have targeted the interaction between CCR4 expressed on Tregs and its ligands CCL22 and CCL17 to inhibit transiently the recruitment of Tregs at the site of immunization. Importantly, use of CCR4 antagonists as ‘molecular adjuvants’ in vivo in experimental models, amplified cellular and humoral immune responses when injected in combination with various vaccine antigens. The significant adjuvant activity observed in diverse models without noticeable side effects provided strong evidence that CCR4 is a sustainable target for rational adjuvant design.


title: Applications of digital technology in COVID-19 pandemic planning and response

text: With high transmissibility and no effective vaccine or therapy, COVID-19 is now a global pandemic. Government-coordinated efforts across the globe have focused on containment and mitigation, with varying degrees of success. Countries that have maintained low COVID-19 per-capita mortality rates appear to share strategies that include early surveillance, testing, contact tracing, and strict quarantine. The scale of coordination and data management required for effective implementation of these strategies has—in most successful countries—relied on adopting digital technology and integrating it into policy and health care. This Viewpoint provides a framework for the application of digital technologies in pandemic management and response, highlighting ways in which successful countries have adopted these technologies for pandemic planning, surveillance, testing, contact tracing, quarantine, and health care.


title: Malaria and the mobile and migrant population in Cambodia: a population movement framework to inform strategies for malaria control and elimination

text: BACKGROUND: The relationships between human population movement (HPM) and health are a concern at global level. In the case of malaria, those links are crucial in relation to the spread of drug resistant parasites and to the elimination of malaria in the Greater Mekong sub-Region (GMS) and beyond. The mobile and migrant populations (MMP) who are involved in forest related activities are both at high risk of being infected with malaria and at risk of receiving late and sub-standard treatment due to poor access to health services. In Cambodia, in 2012, the National Malaria Control Programme (NMCP) identified, as a key objective, the development of a specific strategy for MMPs in order to address these challenges. A population movement framework (PMF) for malaria was developed and operationalized in order to contribute to this strategy. METHODS: A review of the published and unpublished literature was conducted. Based on a synthesis of the results, information was presented and discussed with experienced researchers and programme managers in the Cambodian NMCP and led to the development and refinement of a PMF for malaria. The framework was “tested” for face and content validity with national experts through a workshop approach. RESULTS: In the literature, HPM has been described using various spatial and temporal dimensions both in the context of the spread of anti-malarial drug resistance, and in the context of malaria elimination and previous classifications have categorized MMPs in Cambodia and the GMS through using a number of different criteria. Building on these previous models, the PMF was developed and then refined and populated with in-depth information relevant to Cambodia collected from social science research and field experiences in Cambodia. The framework comprises of the PMF itself, MMP activity profiles and a Malaria Risk Index which is a summation of three related indices: a vulnerability index, an exposure index and an access index which allow a qualitative ranking of malaria risk in the MMP population. Application of currently available data to the framework illustrates that the highest risk population are those highly mobile populations engaged in forest work. CONCLUSION: This paper describes the process of defining MMPs in Cambodia, identifying the different activities and related risks to appropriately target and tailor interventions to the highest risk groups. The framework has been used to develop more targeted behaviour change and outreach interventions for MMPs in Cambodia and its utility and effectiveness will be evaluated as part of those interventions.


title: Case Report: Viral Shedding for 60 Days in a Woman with COVID-19

text: Novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has become a public health emergency of international concern. This was first noted in Wuhan, Hubei Province, China, and since then has become widespread globally. We report a 71-year-old woman with documented viral shedding (based on reverse transcription–polymerase chain reaction (RT-PCR) testing) of SARS-CoV-2 for 60 days from the onset of symptoms (55 days from her first positive test and 36 days after complete resolution of symptoms). This is to our knowledge the longest duration of viral shedding reported to date. This case demonstrates that viral shedding after COVID-19 diagnosis can be prolonged.


title: A 5'-proximal Stem-loop Structure of 5' Untranslated Region of Porcine Reproductive and Respiratory Syndrome Virus Genome Is Key for Virus Replication

text: BACKGROUND: It has been well documented that the 5' untranslated region (5' UTR) of many positive-stranded RNA viruses contain key cis-acting regulatory sequences, as well as high-order structural elements. Little is known for such regulatory elements controlling porcine arterivirus replication. We investigated the roles of a conserved stem-loop 2 (SL2) that resides in the 5'UTR of the genome of a type II porcine reproductive and respiratory syndrome virus (PRRSV). RESULTS: We provided genetic evidences demonstrating that 1) the SL2 in type II PRRSV 5' UTR, N-SL2, could be structurally and functionally substituted by its counterpart in type I PRRSV, E-SL2; 2) the functionality of N-SL2 was dependent upon the G-C rich stem structure, while the ternary-loop size was irrelevant to RNA synthesis; 3) serial deletions showed that the stem integrity of N-SL2 was crucial for subgenomic mRNA synthesis; and 4) when extensive base-pairs in the stem region was deleted, an alternative N-SL2-like structure with different sequence was utilized for virus replication. CONCLUSION: Taken together, we concluded that the phylogenetically conserved SL2 in the 5' UTR was crucial for PRRSV virus replication, subgenomic mRNA synthesis in particular.


title: The impact of the COVID‐19 pandemic on the utilization of emergency urological services

text: OBJECTIVES: To compare the number of patients attending the Urology ED of Centro Hospitalar Universitário do Porto (CHUP), as well as their demographic characteristics, the reasons for admission, the clinical severity under the Manchester triage system (MTS), and the need for emergency surgery or hospitalization, during the pandemic and the equivalent period in 2019. Patients and Methods: Data were collected from patients attending the Urology emergency ward of CHUP during three weeks ‐ from March 11th 2020 to April 1st 2020 ‐ and from the same period the previous year (from March 11th to April 1st 2019). RESULTS: During the pandemic, 46.4% fewer patients visited our urological ED (122 vs 263). There was no significant difference of the mean age or the number of old patients (with 65 or more years old) between the two periods. However, significantly fewer female patients sought emergency urological services during the COVID‐19 pandemic period (32.7% vs. 14.8%, p<0.05). No significant differences were noted between different clinical severity groups under the MTS. In 2019, significantly less patients required hospitalization. The most common reasons for admission, during both periods, were hematuria, renal colic and urinary tract infections (UTI). The authors recognize that the study has several limitations, namely, those inherent to its retrospective nature. CONCLUSION: COVID‐19 significantly influenced people’s urological care‐seeking behaviour. Understanding the present situation is helpful for the prediction of future urological needs. Based on the results of this study, we have reasons to speculate that people’s requirements for urological services might grow explosively in the post‐COVID‐19 period. There should be further studies about the real state of long‐term urological services and the consequences that this pandemic may have in terms of morbimortality not directly related to the virus.


title: A real-time PCR for SARS-coronavirus incorporating target gene pre-amplification

text: Abstract An enhanced polymerase chain reaction (PCR) assay to detect the coronavirus associated with severe acute respiratory syndrome (SARS-CoV) was developed in which a target gene pre-amplification step preceded TaqMan real-time fluorescent PCR. Clinical samples were collected from 120 patients diagnosed as suspected or probable SARS cases and analyzed by conventional PCR followed by agarose gel electrophoresis, conventional TaqMan real-time PCR, and our enhanced TaqMan real-time PCR assays. An amplicon of the size expected from SARS-CoV was obtained from 28/120 samples using the enhanced real-time PCR method. Conventional PCR and real-time PCR alone identified fewer SARS-CoV positive cases. Results were confirmed by viral culture in 3/28 cases. The limit of detection of the enhanced real-time PCR method was 102-fold higher than the standard real-time PCR assay and 107-fold higher than conventional PCR methods. The increased sensitivity of the assay may help control the spread of the disease during future SARS outbreaks.


title: Variability in viral pathogenesis: modeling the dynamic of acute and persistent infections

text: Virus infection often results in diverse outcomes. This variability of virus pathogenesis is not well understood. Here we revise theoretical arguments to further our understanding of factors controlling infection and its severity. We propose that variability in these factors results in different clinical outcomes, which ultimately ensure virus reproduction.


title: Early Epidemic Dynamics of the West African 2014 Ebola Outbreak: Estimates Derived with a Simple Two-Parameter Model

text: The 2014 West African Ebola virus outbreak, now more correctly referred to as an epidemic, is the largest ever to occur. As of August 28, 2014, concerns have been raised that control efforts, particularly in Liberia, have been ineffective, as reported case counts continue to increase. Limited data are available on the epidemiology of the outbreak. However, reported cumulative incidence data as well as death counts are available for Guinea, Sierra Leone, Liberia and Nigeria. We utilized a simple, two parameter mathematical model of epidemic growth and control, to characterize epidemic growth patterns in West Africa, to evaluate the degree to which the epidemic is being controlled, and to assess the potential implications of growth patterns for epidemic size. Models demonstrated good fits to data. Overall basic reproductive number (R0) for the epidemic was estimated to be between 1.6 and 2.0, consistent with prior outbreaks. However, we identified only weak evidence for the occurrence of epidemic control in West Africa as a whole, and essentially no evidence for control in Liberia (though slowing of growth was seen in Guinea and Sierra Leone). It is projected that small reductions in transmission would prevent tens of thousands of future infections. These findings suggest that there is an extraordinary need for improved control measures for the 2014 Ebola epidemic, especially in Liberia, if catastrophe is to be averted.


title: Carbon black nanoparticles induce biphasic gene expression changes associated with inflammatory responses in the lungs of C57BL/6 mice following a single intratracheal instillation

text: Abstract Inhalation of carbon black nanoparticles (CBNPs) causes pulmonary inflammation; however, time course data to evaluate the detailed evolution of lung inflammatory responses are lacking. Here we establish a time-series of lung inflammatory response to CBNPs. Female C57BL/6 mice were intratracheally instilled with 162μg CBNPs alongside vehicle controls. Lung tissues were examined 3h, and 1, 2, 3, 4, 5, 14, and 42days (d) post-exposure. Global gene expression and pulmonary inflammation were assessed. DNA damage was evaluated in bronchoalveolar lavage (BAL) cells and lung tissue using the comet assay. Increased neutrophil influx was observed at all time-points. DNA strand breaks were increased in BAL cells 3h post-exposure, and in lung tissues 2–5d post-exposure. Approximately 2600 genes were differentially expressed (±1.5 fold; p≤0.05) across all time-points in the lungs of exposed mice. Altered transcript levels were associated with immune-inflammatory response and acute phase response pathways, consistent with the BAL profiles and expression changes found in common respiratory infectious diseases. Genes involved in DNA repair, apoptosis, cell cycle regulation, and muscle contraction were also differentially expressed. Gene expression changes associated with inflammatory response followed a biphasic pattern, with initial changes at 3h post-exposure declining to base-levels by 3d, increasing again at 14d, and then persisting to 42d post-exposure. Thus, this single CBNP exposure that was equivalent to nine 8-h working days at the current Danish occupational exposure limit induced biphasic inflammatory response in gene expression that lasted until 42d post-exposure, raising concern over the chronic effects of CBNP exposure.


title: Protease inhibitors and their peptidomimetic derivatives as potential drugs

text: Abstract Precise spatial and temporal regulation of proteolytic activity is essential to human physiology. Modulation of protease activity with synthetic peptidomimetic inhibitors has proven to be clinically useful for treating human immunodeficiency virus (HIV) and hypertension and shows potential for medicinal application in cancer, obesity, cardiovascular, inflammatory, neurodegenerative diseases, and various infectious and parasitic diseases. Exploration of natural inhibitors and synthesis of peptidomimetic molecules has provided many promising compounds performing successfully in animal studies. Several protease inhibitors are undergoing further evaluation in human clinical trials. New research strategies are now focusing on the need for improved comprehension of protease-regulated cascades, along with precise selection of targets and improved inhibitor specificity. It remains to be seen which second generation agents will evolve into approved drugs or complementary therapies.


title: The S gene of canine coronavirus, strain UCD-1, is more closely related to the S gene of transmissible gastroenteritis virus than to that of feline infectious peritonitis virus

text: To gain insight into the genetic relationships among six canine coronavirus (CCV) strains, the variable region of the spike (S) protein gene was sequenced. The CCV strains were: two ATCC reference strains, the Insavc-1 vaccine strain, the National Veterinary Services Laboratories (Ames, IA) challenge strain, and two California field isolates (UCD-1 and UCD-2) from the 1970s. All six strains, downstream of the nucleocapsid (N) protein gene, had sufficient size for an ORF 7b, and thus, none were transmissible gastroenteritis virus (TGEV)-like since TGEV lacks ORF 7b. By sequence analysis of the variable domain at the 5′ end of the S gene, five of the six CCV strains had a high degree of identity with feline infectious peritonitis virus (FIPV). However, one CCV field isolate (UCD-1) was different and had a high degree of identity with the 5′ end of the TGEV S gene. This suggests that RNA recombination occurred at this site between antigenically related coronaviruses. The low passage field isolates, UCD-1 and UCD-2, varied in their initial infectivity for swine testicular cells suggesting that sequence differences in the variable domain of the S gene may account for biological variation among CCVs.


title: Primary health care policy and vision for community pharmacy and pharmacists in Spain

text: From a political and governance perspective Spain is a decentralized country with 17 states [comunidades autónomas] resulting in a governmental structure similar to a federal state. The various state regional health services organizational and management structures are focused on caring for acute illnesses and are dominated by hospitals and technology. In a review by the Interstate Council, a body for intercommunication and cooperation between the state health care services and national government, there is a move to improve health care through an integrative approach between specialized care and primary care at the state level. Community pharmacy does not appear to have a major role in this review. Primary health care is becoming more important and leading the change to improve the roles of the health care teams. Primary care pharmacists as the rest of public health professionals are employed by the respective states and are considered public servants. Total health care expenditure is 9.0% of its GDP with the public health sector accounting for the 71% and the private sector 29% of this expenditure. Community pharmacy contracts with each state health administration for the supply and dispensing of medicines and a very limited number of services. There are approximately 22,000 community pharmacies and 52,000 community pharmacists for a population of 47 million people. All community pharmacies are privately owned with only pharmacists owning a single pharmacy. Pharmacy chain stores are not legally permitted. Community pharmacy practice is based on dispensing of medications and dealing with consumer minor symptoms and requests for nonprescription medications although extensive philosophical deep debates on the conceptual and practical development of new clinical services have resulted in national consensually agreed classifications, definitions and protocolized services. There are a few remunerated services in Spain and these are funded at state, provincial or municipal level. There are no health services approved or funded at a national level. Although the profession promulgates a patient orientated community pharmacy it appears to be reluctant to advocate for a change in the remuneration model. The profession as a whole should reflect on the role of community pharmacy and advocate for a change to practice that is patient orientated alongside the maintenance of its stance on being a medication supplier. The future strategic position of community pharmacy in Spain as a primary health care partner with government would then be enhanced.


title: Practical diagnosis and treatment of suspected venous thromboembolism during COVID-19 Pandemic

text: Abstract A markedly increased demand for vascular ultrasound laboratory and other imaging studies in COVID-19 positive patients has occurred, due to most with markedly elevated D-dimer, and a presumed prothrombotic state in many of the very ill patients. This article summarizes a broad institutional consensus focusing on evaluation and recommended empirical therapy for COVID-19 positive patients. We recommend following the algorithms with the idea that as more data becomes available that this may well change.


title: Emerging infections in animals—potential new zoonoses?

text: It is well recognized that most emerging diseases of humans are zoonotic, and that the forces working to create emerging diseases in humans are also operating in animal populations. However, what is often overlooked is that emerging human diseases are usually preceded by the emergence of the same pathogen in an animal population. In fact, the developing disease in animals acts as a link allowing the disease to take hold and wreck havoc in public health. Numerous examples--Rift Valley fever, monkeypox, Nipah, and Ebola--serve to underscore this linkage and to highlight the increasing interconnectedness of animal and human health.


Human Bocavirus: Developing Evidence for Pathogenicity


title: Specific Management of Patients with Acute Abdomen during the COVID-19 Pandemic: A Surgical Perspective from Germany

text: During the current COVID-19 pandemic, the triage, assessment, and management of patients presenting to the emergency department with critical conditions has become challenging. The clinical features of COVID-19 are heterogeneous and subtle in many cases. They may easily be overlooked in the case of other acute diseases. Gastrointestinal symptoms are common in patients with COVID-19 as SARS-CoV-2 is able to enter gastrointestinal epithelial cells. However, these complaints can also be caused by a COVID-19-independent concomitant abdominal pathology. Therefore, patients with acute abdominal pain and fever need to be assessed very thoroughly. Based on a clinical case, we present our approach of managing emergency patients with acute abdomen and concomitant suspicion of COVID-19.


title: Human Parainfluenza Virus-Associated Respiratory Tract Infection among Children and Genetic Analysis of HPIV-3 Strains in Beijing, China

text: The relevance of human parainfluenza viruses (HPIVs) to the epidemiology of acute respiratory infections (ARI) in China is unclear. From May 2008 to September 2010, 443 nasopharyngeal aspirates (NPAs) from hospitalized pediatric patients (age from 1 to 93 months) in Beijing were collected and screened for HPIVs and other common respiratory viruses by real-time RT-PCR. Sixty-two of 443 samples were positive for HPIVs with 4 positive for HPIV-2 and 58 positive for HPIV-3, indicating that HPIV-3 was the predominant virus present during the study period. A phylogenetic tree based on all the available HN (hemagglutinin-neuraminidase) sequences of HPIV-3 indicated that three distinct clusters (A,B, and C) were circulating with some temporal and regional clustering. Cluster C was further divided into sub-clusters, C1, C2, C3 and C4. HPIV-3 from Beijing isolates belonged to sub-cluster C3, and were grouped with the isolates from two Provinces of China and the neighboring country of Japan. Genetic analysis based on entire HN gene revealed that the HPIV-3 isolates from Beijing were highly similar with 97.2%–100% identity at the nucleotide level and these could be divided into two closely related lineages, C3a and C3b. These findings suggested that there was co-circulation of multiple lineages of HPIV-3 in the Beijing region during the study period. This is the first study to describe the epidemiology and molecular characterization of HPIVs in China.


title: Verifying the Stability of Selected Genes for Normalization in Q PCR Experiments of Spodoptera frugiperda Cells during AcMNPV Infection

text: It is challenging to find genes with stable transcripts for use as reference genes for quantitative realtime polymerase chain reaction (qRT-PCR) during viral infection. Autographa californica nucleopolyhedrovirus (AcMNPV) is known to globally shut off host gene transcription in Sf21 cells and to modify their cytoskeletons. In this study, seven host genes were selected for validation as references for gene expression experiments using qRT-PCR. Two of them, ecdysoneless (ECD) and myosin showed stable RNA levels in our previous microarray study at 6, 12, and 24 hpi for both genes and 48 hpi for ECD. The others, actin, tubulin, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and 28S ribosome (28S), are commonly employed as reference genes for qRT-PCR. Ribosomal protein L35 (L35) gene was selected to test if ribosomal protein genes show stable RNA transcript levels similar to 28S and 18S rRNA and to validate the microarray data. In addition to 28S, previously known to have stable transcript levels, qRT-PCR showed that ECD transcript levels remained constant throughout the time course of AcMNPV infection. Transcripts of cytoskeleton genes such as actin, tubulin, and myosin declined dramatically as the infection progressed. GAPDH and L35 transcripts also declined over time. These results indicate that ECD is a reliable reference gene for qRT-PCR experiments during AcMNPV infection of Spodoptera frugiperda cells. Although 28S could be used as a reference gene for these experiments, it is less useful than ECD because of its abundance, which might make it difficult to establish an accurate baseline value for data analysis.


title: Estimated Inactivation of Coronaviruses by Solar Radiation With Special Reference to COVID‐19

text: Using a model developed for estimating solar inactivation of viruses of biodefense concerns, we calculated the expected inactivation of SARS‐CoV‐2 virus, cause of COVID‐19 pandemic, by artificial UVC and by solar ultraviolet radiation in several cities of the world during different times of the year. The UV sensitivity estimated here for SARS‐CoV‐2 is compared with those reported for other ssRNA viruses, including influenza A virus. The results indicate that SARS‐CoV‐2 aerosolized from infected patients and deposited on surfaces could remain infectious outdoors for considerable time during the winter in many temperate‐zone cities, with continued risk for re‐aerosolization and human infection. Conversely, the presented data indicate that SARS‐CoV‐2 should be inactivated relatively fast (faster than influenza A) during summer in many populous cities of the world, indicating that sunlight should have a role in the occurrence, spread rate, and duration of coronavirus pandemics.


title: Exit through the App Store?

text: This Preview summarizes the Ada Lovelace Institute rapid evidence review Exit through the App Store?, which sets out proposals for whether, and how, the UK government should use technology to transition from the COVID-19 global public health crisis. It examines the potential development and implementation of technical solutions to support symptom tracking, contact tracing, and immunity certification. The full rapid evidence review takes into account societal, political, legal, and ethical perspectives and gives findings and recommendations for the transition and rebuild phases that follow containment, delay, and mitigation.


title: Replication of MERS and SARS coronaviruses in bat cells offers insights to their ancestral origins

text: Previous findings of Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses in bats, and the ability of Tylonycteris-BatCoV HKU4 spike protein to utilize MERS-CoV receptor, human dipeptidyl peptidase 4 hDPP4, suggest a bat ancestral origin of MERS-CoV. We developed 12 primary bat cell lines from seven bat species, including Tylonycteris pachypus, Pipistrellus abramus and Rhinolophus sinicus (hosts of Tylonycteris-BatCoV HKU4, Pipistrellus-BatCoV HKU5 and SARS-related-CoV respectively), and tested their susceptibilities to MERS-CoVs, SARS-CoV and human coronavirus 229E (HCoV-229E). Five cell lines, including P. abramus and R. sinicus but not T. pachypus cells, were susceptible to human MERS-CoV EMC/2012. However, three tested camel MERS-CoV strains showed different infectivities, with only two strains capable of infecting three and one cell lines respectively. SARS-CoV can only replicate in R. sinicus cells, while HCoV-229E cannot replicate in any bat cells. Bat dipeptidyl peptidase 4 (DPP4) sequences were closely related to those of human and non-human primates but distinct from dromedary DPP4 sequence. Critical residues for binding to MERS-CoV spike protein were mostly conserved in bat DPP4. DPP4 was expressed in the five bat cells susceptible to MERS-CoV, with significantly higher mRNA expression levels than those in non-susceptible cells (P=0.0174), supporting that DPP4 expression is critical for MERS-CoV infection in bats. However, overexpression of T. pachypus DPP4 failed to confer MERS-CoV susceptibility in T. pachypus cells, suggesting other cellular factors in determining viral replication. The broad cellular tropism of MERS-CoV should prompt further exploration of host diversity of related viruses to identify its ancestral origin.


title: Diabetes and COVID-19: Global and Regional Perspectives

text: Abstract The coronavirus disease-2019 (COVID-19) has been designated as a highly contagious infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) since December 2019, when an outbreak of pneumonia cases emerged in Wuhan, China. The COVID-19 pandemic has led to a global health crisis, devastating the social, economic and political aspects of life. Many clinicians, health professionals, scientists, organizations, and governments have actively defeated COVID-19 and shared their experiences of the SARS-CoV2. Diabetes is one of the major risk factors for fatal outcomes from COVID-19. Patients with diabetes are vulnerable to infection because of hyperglycemia; impaired immune function; vascular complications; and comorbidities such as hypertension, dyslipidemia, and cardiovascular disease. In addition, angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV-2 in the human body. Hence, the use of angiotensin-directed medications in patients with diabetes requires attention. The severity and mortality from COVID-19 was significantly higher in patients with diabetes than in those without. Thus, the patients with diabetes should take precautions during the COVID-19 pandemic. Therefore, we review the current knowledge of COVID-19 including the global and regional epidemiology, virology, impact of diabetes on COVID-19, treatment of COVID-19, and standard of care in the management of diabetes during this critical period.


title: Study of peptide fingerprints of parasite proteins and drug–DNA interactions with Markov-Mean-Energy invariants of biopolymer molecular-dynamic lattice networks

text: Abstract Since the advent of Molecular Dynamics (MD) in biopolymers science with the study by Karplus et al. on protein dynamics, MD has become the by foremost well established, computational technique to investigate structure and function of biomolecules and their respective complexes and interactions. The analysis of the MD trajectories (MDTs) remains, however, the greatest challenge and requires a great deal of insight, experience, and effort. Here, we introduce a new class of invariants for MDTs based on the spatial distribution of Mean-Energy values ξk (L) on a 2D Euclidean space representation of the MDTs. The procedure forces one MD trajectory to fold into a 2D Cartesian coordinates system using a step-by-step procedure driven by simple rules. The ξk (L) values are invariants of a Markov matrix (1 Π), which describes the probabilities of transition between two states in the new 2D space; which is associated to a graph representation of MDTs similar to the lattice networks (LNs) of DNA and protein sequences. We also introduce a new algorithm to perform phylogenetic analysis of peptides based on MDTs instead of the sequence of the polypeptide. In a first experiment, we illustrate this algorithm for 35 peptides present on the Peptide Mass Fingerprint (PMF) of a new protein of Leishmania infantum studied in this work. We report, by the first time, 2D Electrophoresis isolation, MALDI TOF Mass Spectroscopy characterization, and MASCOT search results for this PMF. In a second experiment, we construct the LNs for 422 MDTs obtained in DNA–Drug Docking simulations of the interaction of 57 anticancer furocoumarins with a DNA oligonucleotide. We calculated the respective ξk (L) values for all these LNs and used them as inputs to train a new classifier with Accuracy=85.44% and 84.91% in training and validation respectively. The new model can be used as scoring function to guide DNA–Drug Docking studies in drug design of new coumarins for PUVA therapy. The new phylogenetics analysis algorithms encode information different from sequence similarity and may be used to analyze MDTs obtained in Docking or modeling experiments for any classes of biopolymers. The work opens new perspective on the analysis and applications of MD in polymer sciences.


title: Respiratory Diseases of Gallinaceous Birds

text: Respiratory conditions constitute many of the diseases affecting all avian species, including gallinaceous birds. Clinical signs and gross lesions of different respiratory diseases are often similar, and establishing a definitive diagnosis may require ancillary laboratory testing. Determination of a specific diagnosis allows practitioners to select the most effective therapies and to prescribe a management program that prevents recurrence.


title: Five Questions for Residency Leadership in the Time of COVID-19: Reflections of Chief Medical Residents From an Internal Medicine Program

text: The COVID-19 pandemic has drastically affected the traditional methods residency programs use to train their residents. Chief residents serve a unique role as part of the residency leadership to foster the education and development of the residents. Given the rapid shift in demands on physicians in the face of the pandemic, the responsibilities of the chief residents have also shifted to help prepare the residents to meet these demands as frontline providers. There is not a precedent for how residency programs respond to this crisis while maintaining their primary role to develop and train physicians. The authors have identified 5 questions chief residents can ask to guide their program’s response to the demands of COVID-19 during this uncertain time in health care.


title: Chapter Two Molecular Biology and Epidemiology of Dianthoviruses

text: Abstract The genus Dianthovirus is one of eight genera in the family Tombusviridae. All the genera have monopartite positive-stranded RNA genomes, except the dianthoviruses which have bipartite genomes. The dianthoviruses are distributed worldwide. Although they share common structural features with the other Tombusviridae viruses in their virions and the terminal structure of the genomic RNAs, the bipartite nature of the dianthovirus genome offers an ideal experimental system with which to study basic issues of virology. The two genomic RNAs seem to use distinct strategies to regulate their translation, transcription, genome replication, genome packaging, and cell-to-cell movement during infection. This review summarizes the current state of our knowledge of the dianthoviruses, with its main emphasis on the molecular biology of the virus, including the viral and host factors required for its infection of host plants. The epidemiology of the virus and the possible viral impacts on agriculture and the environment are also discussed.


title: Tracking the Covid‐19 conversation

text: As the coronavirus pandemic took hold, there was little time for much else


title: Correlation between recombination junctions and RNA secondary structure elements in poliovirus Sabin strains

text: In order to test the hypothesis that RNA structural elements promote the distribution of certain types of recombination junctions in each one of the 2C and 3D poliovirus genomic regions (Sabin 3/Sabin 2 or Sabin 1 in 2C and Sabin 2/Sabin 1 or Sabin 3 in 3D), we searched in 2C and 3D regions of reference Sabin strains for high probability RNA structural elements that could promote recombination. Recombination junctions that were identified in clinical strains of this study, as well as in clinical strains of previous studies, were superimposed on RNA secondary structure models of 2C and 3D genomic regions. Furthermore, we created an in vitro model, based on double infection of cell-culture with two poliovirus strains, for the production and identification of recombinant Sabin strains in 2C and 3D regions. Our intention was to compare the results that refer to the correlation of recombination junctions and RNA secondary structures in 2C and 3D regions of clinical strains, with the respective results of the in vitro model. Most of the recombination junctions of the clinical strains were correlated with RNA secondary structure elements, which were identical between recombining Sabin strains, and also presented high predictive value. In consensus were, the respective results originated from the in vitro model. We propose that the distribution of specific types of recombination junctions in certain regions of Sabin strains is not fortuitous and is correlated with RNA secondary structure elements identical to both recombination partners. Furthermore, results of this study highlight an important role for the stem region of the RNA structure elements in promoting recombination. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11262-010-0512-5) contains supplementary material, which is available to authorized users.


title: Analyze the psychological impact of COVID-19 among the elderly population in China and make corresponding suggestions

text: Abstract To understand the emotional changes in the elderly population during the pneumonia epidemic caused by novel coronavirus infection, and to lay a foundation for the study of the psychology, intervention and nursing of the elderly.A total of 1556 elderly people were selected to conduct an epidemiological survey, and standardized survey methods were used to investigate the depression screening scale (PHQ-9) and anxiety self-rating scale (GAD-7).The anxiety and depression of different genders were different.Anxiety and depression are different in different age groups.The outbreak of pneumonia caused by novel coronavirus infection has an effect on the psychology of the elderly people, resulting in anxiety and depression.


title: Current literature in mass spectrometry

text: In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of mass spectrometry. Each bibliography is divided into 11 sections: 1 Books, Reviews & Symposia; 2 Instrumental Techniques & Methods; 3 Gas Phase Ion Chemistry; 4 Biology/Biochemistry: Amino Acids, Peptides & Proteins; Carbohydrates; Lipids; Nucleic Acids; 5 Pharmacology/Toxicology; 6 Natural Products; 7 Analysis of Organic Compounds; 8 Analysis of Inorganics/Organometallics; 9 Surface Analysis; 10 Environmental Analysis; 11 Elemental Analysis. Within each section, articles are listed in alphabetical order with respect to author (5 Weeks journals ‐ Search completed at 8th. Sept. 2004)


title: Targeting malaria parasite invasion of red blood cells as an antimalarial strategy

text: Plasmodium spp. parasites that cause malaria disease remain a significant global-health burden. With the spread of parasites resistant to artemisinin combination therapies in Southeast Asia, there is a growing need to develop new antimalarials with novel targets. Invasion of the red blood cell by Plasmodium merozoites is essential for parasite survival and proliferation, thus representing an attractive target for therapeutic development. Red blood cell invasion requires a co-ordinated series of protein/protein interactions, protease cleavage events, intracellular signals, organelle release and engagement of an actin-myosin motor, which provide many potential targets for drug development. As these steps occur in the bloodstream, they are directly susceptible and exposed to drugs. A number of invasion inhibitors against a diverse range of parasite proteins involved in these different processes of invasion have been identified, with several showing potential to be optimised for improved drug-like properties. In this review, we discuss red blood cell invasion as a drug target and highlight a number of approaches for developing antimalarials with invasion inhibitory activity to use in future combination therapies.


title: Challenges to Athletes During the Home Confinement Caused by the COVID-19 Pandemic

text: The world is currently facing a serious coronavirus pandemic (COVID-19). This novel coronavirus is a new virus for which effective drugs and vaccines have not yet been developed. Amateur and professional athletic events around the world have been stopped, and teams and athletes have had to adopt social withdrawal measures, interrupting their training and preparation routines for competitions. Given this alarming scenario, this article aims to alert athletes to the importance of maintaining a conditioning routine during this confinement period.


title: Work stress among Chinese nurses to support Wuhan in fighting against COVID‐19 epidemic

text: AIMS: To investigate the work stress among Chinese nurses who are supporting Wuhan in fighting against Coronavirus Disease 2019 (COVID‐19) infection and to explore the relevant influencing factors. BACKGROUND: The COVID‐19 epidemic has posed a major threat to public health. Nurses have always played an important role in infection prevention, infection control, isolation, containment and public health. However, available data on the work stress among these nurses are limited. METHODS: A cross‐sectional survey. An online questionnaire was completed by 180 anti‐epidemic nurses from Guangxi. Data collection tools, including the Chinese version of the Stress Overload Scale (SOS) and the Self‐rating Anxiety Scale (SAS), were used. Descriptive single factor correlation and multiple regression analyses were used in exploring the related influencing factors. RESULTS: The SOS (39.91 ± 12.92) and SAS (32.19 ± 7.56) scores of this nurse group were positively correlated (r = 0.676, p < .05). Multiple regression analysis showed that only children, working hours per week and anxiety were the main factors affecting nurse stress (p = .000, .048, .000, respectively). CONCLUSIONS: Nurses who fight against COVID‐19 were generally under pressure. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse leaders should pay attention to the work stress and the influencing factors of the nurses who are fighting against COVID‐19 infection, and offer solutions to retain mental health among these nurses.


title: Glecaprevir and Maraviroc are high-affinity inhibitors of SARS-CoV-2 main protease: possible implication in COVID-19 therapy

text: Due to the lack of efficient therapeutic options and clinical trial limitations, the FDA-approved drugs can be a good choice to handle Coronavirus disease (COVID-19). Many reports have enough evidence for the use of FDA-approved drugs which have inhibitory potential against target proteins of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Here, we utilized a structure-based drug design approach to find possible drug candidates from the existing pool of FDA-approved drugs and checked their effectiveness against the SARS-CoV-2. We performed virtual screening of the FDA-approved drugs against the main protease (M(pro)) of SARS-CoV-2, an essential enzyme, and a potential drug target. Using well-defined computational methods, we identified Glecaprevir and Maraviroc (MVC) as the best inhibitors of SARS-CoV-2 M(pro). Both drugs bind to the substrate-binding pocket of SARS-CoV-2 M(pro) and form a significant number of non-covalent interactions. Glecaprevir and MVC bind to the conserved residues of substrate-binding pocket of SARS-CoV-2 M(pro). This work provides sufficient evidence for the use of Glecaprevir and MVC for the therapeutic management of COVID-19 after experimental validation and clinical manifestations.


title: Drug repositioning is an alternative for the treatment of coronavirus COVID-19

text: Abstract Given the extreme importance of the current pandemic caused by COVID-19, and as scientists agree there is no identified pharmacological treatment, where possible, therapeutic alternatives are raised through drug repositioning. This paper presents a selection of studies involving drugs from different pharmaceutical classes with activity against SARS-CoV-2 and SARS-CoV, with the potential for use in the treatment of COVID-19 disease.


title: Events postponed or cancelled because of the coronavirus outbreak

text: A number of events that cover developments in sealing technology and related products have been postponed, or even cancelled, in response to the rapidly changing circumstances associated with the coronavirus (COVID-19) outbreak.


title: Seroprevalence of Rotavirus infection in pig population of Arunachal Pradesh

text: AIM: This study was conducted to find out the seroprevalence of Rotavirus(RV) infection among the pig population of Arunachal Pradesh. MATERIALS AND METHODS: Serums samples were collected from piglets of age ranging from 1 week to 6 months and the sows associated with the piglets that were reared under organized and unorganized system of management in six different districts of Arunachal Pradesh. The prevalence of RV specific antibodies was detected using a polyclonal antibody-based indirect enzyme-linked immunosorbent assay (i-ELISA). RESULTS: The study revealed that out of 394 serum samples, 255 (64.72%) samples were found to be positive for RV-specific antibody in i-ELISA. Considering the samples from different districts, Papumpare district of Arunachal Pradesh showed highest numbers of seropositive animals (68.75%) followed by upper Subansiri (64.91%) while West Siang district showed lowest positivity rate (61.22%). CONCLUSION: As considerable seropositivity was recorded among pig population of Arunachal Pradesh in this study, there is urgent need to establish high-impact and cost-effective public health intervention tools, key among them being the introduction of strict hygiene practice and RV vaccination program, to greatly reduce the number of deaths due to diarrheal diseases. To the authors’ knowledge, this is the first report on the prevalence of RV infection from pigs of Arunachal Pradesh.


title: RNA Interference Technologies and Therapeutics: From Basic Research to Products

text: RNA interference (RNAi) is a natural cellular process that regulates gene expression by a highly precise mechanism of sequence-directed gene silencing at the stage of translation by degrading specific messenger RNAs or blocking translation. In recent years, the use of RNAi for therapeutic applications has gained considerable momentum. It has been suggested that most of the novel disease-associated targets that have been identified are not ‘druggable’ with conventional approaches. However, any disease-causing gene and any cell type or tissue can potentially be targeted with RNAi. This review focuses on the current knowledge of RNAi mechanisms and the safety issues associated with its potential use in a therapeutic setting. Some of the most important aspects to consider when working towards the application of RNAi-based products in a clinical setting have been related to achieving high efficacies and enhanced stability profiles through a careful design of the nucleic acid sequence and the introduction of chemical modifications, but most of all, to developing improved delivery systems, both viral and non-viral. These new delivery systems allow for these products to reach the desired target cells, tissues or organs in a highly specific manner and after administration of the lowest possible doses. Various routes of application and target locations are currently being addressed in order to develop effective delivery systems for different targets and pathologies, including infectious pathologies, genetic pathologies and diseases associated with dysregulation of endogenous microRNAs. As with any new technology, several challenges and important aspects to be considered have risen on the road to clinical intervention, e.g. correct design of preclinical toxicology studies, regulatory concerns, and intellectual property protection. The main advantages related to the use of RNAi-based products in a clinical setting, and the latest clinical and preclinical studies using these compounds, are reviewed.


title: Outbreak of Streptococcus equi subsp. zooepidemicus infections in cats

text: Abstract Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) is a commensal of the mucous membranes and skin of animals, notably equine, and is associated with various infections in animals and humans. Here, we describe an outbreak of respiratory disease in a cattery, which, to the best of our knowledge, is the first report of S. zooepidemicus infection in cats. Clinical disease was characterized firstly by abundant purulent nasal discharges and cough, progressing to sinusitis, dyspnea, symptoms of pneumonia and death. Pathological examination revealed different degrees of inflammation of the lower respiratory tract. S. zooepidemicus was the main bacteria isolated. Sequencing of the V2 fragment of the 16S gene revealed that the isolates were distributed in two previously described genogroups.


title: Influenza A Virus Hemagglutinin–Neuraminidase–Receptor Balance: Preserving Virus Motility

text: Influenza A viruses (IAVs) occasionally cross the species barrier and adapt to novel host species. This requires readjustment of the functional balance of the sialic acid receptor-binding hemagglutinin (HA) and the receptor-destroying neuraminidase (NA) to the sialoglycan-receptor repertoire of the new host. Novel techniques have revealed mechanistic details of this HA–NA–receptor balance, emphasizing a previously underappreciated crucial role for NA in driving the motility of receptor-associated IAV particles. Motility enables virion penetration of the sialylated mucus layer as well as attachment to, and uptake into, underlying epithelial cells. As IAVs are essentially irreversibly bound in the absence of NA activity, the fine-tuning of the HA–NA–receptor balance rather than the binding avidity of IAV particles per se is an important factor in determining host species tropism.


Children hospitalized for coronavirus disease 2019 (COVID-19): a multicenter retrospective descriptive study


title: A quantile regression analysis of tourism market growth effect on the hotel industry

text: Abstract This study used the quantile regression method to investigate how inbound tourism market growth proxied by the growth rate of total foreign tourist arrivals (GTA) affects the growth rate of sales (GS) and financial performance of hotel firms in Taiwan. The ordinary least squares estimation results of panel regression test revealed that GTA significantly affects GS, but has no significant effect on financial performance (proxied by hotel equity return). However, quantile regression tests revealed new and interesting results. GTA has a significant effect on GS at the different quantiles of GS. In comparison, although hotel equity return was not significantly related to GTA at the median and high quantiles, the effect of GTA on hotel equity return was statistically significant at the low quantiles. These results suggest that the effect of GTA on hotel equity return is asymmetric and state-dependent, conditional on the distributions of hotel equity return. The study further identified that GTA has a significant influence only on equity returns of hotels with a small size.


title: Neutralizing antibody and protective immunity to SARS coronavirus infection of mice induced by a soluble recombinant polypeptide containing an N-terminal segment of the spike glycoprotein

text: Abstract A secreted, glycosylated polypeptide containing amino acids 14 to 762 of the SARS coronavirus (SARS-CoV) spike protein and a polyhistidine tag was expressed in recombinant baculovirus-infected insect cells. Mice received the affinity-purified protein with either a saponin (QS21) or a Ribi (MPL + TDM) adjuvant subcutaneously and were challenged intranasally with SARS-CoV. Both regimens induced binding and neutralizing antibodies and protection against SARS-CoV intranasal infection. However, the best results were obtained with QS21 and protein, which provided the highest antibody as well as complete protection of the upper and lower respiratory tract.


Therapeutic Strategy for Coronavirus Disease 2019 in Patients on Durable Left Ventricular Assist Device Support


title: Role of India’s wildlife in the emergence and re-emergence of zoonotic pathogens, risk factors and public health implications

text: Abstract Evolving land use practices have led to an increase in interactions at the human/wildlife interface. The presence and poor knowledge of zoonotic pathogens in India's wildlife and the occurrence of enormous human populations interfacing with, and critically linked to, forest ecosystems warrant attention. Factors such as diverse migratory bird populations, climate change, expanding human population and shrinking wildlife habitats play a significant role in the emergence and re-emergence of zoonotic pathogens from India's wildlife. The introduction of a novel Kyasanur forest disease virus (family flaviviridae) into human populations in 1957 and subsequent occurrence of seasonal outbreaks illustrate the key role that India's wild animals play in the emergence and reemergence of zoonotic pathogens. Other high priority zoonotic diseases of wildlife origin which could affect both livestock and humans include influenza, Nipah, Japanese encephalitis, rabies, plague, leptospirosis, anthrax and leishmaniasis. Continuous monitoring of India's extensively diverse and dispersed wildlife is challenging, but their use as indicators should facilitate efficient and rapid disease-outbreak response across the region and occasionally the globe. Defining and prioritizing research on zoonotic pathogens in wildlife are essential, particularly in a multidisciplinary one-world one-health approach which includes human and veterinary medical studies at the wildlife-livestock-human interfaces. This review indicates that wild animals play an important role in the emergence and re-emergence of zoonotic pathogens and provides brief summaries of the zoonotic diseases that have occurred in wild animals in India.


title: Pathogen Transmission and Clinic Scheduling

text: We developed a model of pathogen dissemination in the outpatient clinic that incorporates key kinetic aspects of the transmission process, as well as uncertainty regarding whether or not each incident patient is contagious. Assigning appointments late in the day to patients suspected of being infectious should decrease pathogen dissemination.


title: Enrichment of Viral Nucleic Acids by Solution Hybrid Selection with Genus Specific Oligonucleotides

text: Despite recent advances, our knowledge of potential and rare human pathogens is far from exhaustive. Current molecular diagnostic tools mainly rely on the specific amplification of marker sequences and may overlook infections caused by unknown and rare pathogens. Using high-throughput sequencing (HTS) can solve this problem; but, due to the extremely low fraction of pathogen genetic material in clinical samples, its application is only cost-effective in special, rather than routine, cases. In this study, we present a method for the semi-specific enrichment of viral conservative sequences in a HTS library by hybridization in solution with genus-specific degenerate biotinylated oligonucleotides. Nucleic acids of the test viruses (yellow fever virus and Japanese encephalitis virus) were enriched by solution hybrid selection using pan-flavivirus oligonucleotides. Moreover, enterovirus (family: Picornaviridae, genus: Enterovirus) sequences were successfully enriched using foot-and-mouth disease virus (family: Picornaviridae, genus: Aphthovirus) oligonucleotide. The enrichment factor relative to the background nucleic acid was about 1,000-fold. As hybridization has less stringent oligonucleotide match requirements than PCR, few oligonucleotides are sufficient to cover the potential sequence variation in the whole genus and may even enrich nucleic acids of viruses of other related genera. Efficient enrichment of viral sequences makes its use in diagnostics cost-efficient.


title: The role of seabirds of the Iles Eparses as reservoirs and disseminators of parasites and pathogens

text: Abstract The role of birds as reservoirs and disseminators of parasites and pathogens has received much attention over the past several years due to their high vagility. Seabirds are particularly interesting hosts in this respect. In addition to incredible long-distance movements during migration, foraging and prospecting, these birds are long-lived, site faithful and breed in dense aggregations in specific colony locations. These different characteristics can favor both the local maintenance and large-scale dissemination of parasites and pathogens. The Iles Eparses provide breeding and feeding grounds for more than 3 million breeding pairs of seabirds including at least 13 species. Breeding colonies on these islands are relatively undisturbed by human activities and represent natural metapopulations in which seabird population dynamics, movement and dispersal can be studied in relation to that of circulating parasites and pathogens. In this review, we summarize previous knowledge and recently-acquired data on the parasites and pathogens found in association with seabirds of the Iles Eparses. These studies have revealed the presence of a rich diversity of infectious agents (viruses, bacteria and parasites) carried by the birds and/or their local ectoparasites (ticks and louse flies). Many of these agents are widespread and found in other ecosystems confirming a role for seabirds in their large scale dissemination and maintenance. The heterogeneous distribution of parasites and infectious agents among islands and seabird species suggests that relatively independent metacommunities of interacting species may exist within the western Indian Ocean. In this context, we discuss how the patterns and determinants of seabird movements may alter parasite and pathogen circulation. We conclude by outlining key aspects for future research given the baseline data now available and current concerns in eco-epidemiology and biodiversity conservation.


title: Beware: Gastrointestinal symptoms can be a manifestation of COVID-19

text: Abstract Background There is a growing number of reports of COVID-19 cases presenting gastrointestinal (GI) symptoms. Aims To review studies reporting GI symptoms among COVID-19 patients. Results Fifteen papers (2800 patients) were identified. Frequency of GI symptoms varied from 3.0% to 39.6%, including diarrhea: 7.5%, nausea: 4.5%, anorexia: 4.4%, vomiting: 1.3%, abdominal pain: 0.5%, belching/reflux: 0.3%. These may be the first manifestation of COVID-19, however, there is controversy whether these reflect better or worst prognosis. Finally, the potential relationship with the angiotensin converting enzyme 2 (ACE2) cell receptor in the digestive tract as the virus entry route, is discussed. Conclusions GI symptoms may be common in COVID-19 may be the first manifestation before fever and respiratory symptoms. Therefore, clinicians and gastroenterologists need to be aware of these atypical cases during the current pandemic and of the fecal–oral transmission, and preventive measures may be implemented.


title: A new coronavirus associated with human respiratory disease in China

text: Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health(1–3). Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing(4) of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here ‘WH-Human 1’ coronavirus (and has also been referred to as ‘2019-nCoV’). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China(5). This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.


title: Analysis of the codon usage of the ORF2 gene of feline calicivirus

text: Abstract Feline calicivirus (FCV) is a highly prevalent pathogen of the domestic cat that causes acute infections of the oral and upper respiratory tract. The E region of the ORF2 protein is responsible for the induction of virus-neutralizing antibodies, thus it is important to understand the codon usage of this gene. Here, analysed 90 coding sequences of ORF2 and show that it undergoes a low codon usage bias. In addition, although mutational bias is one of the factors shaping the codon usage bias of this gene, natural selection plays a more significant role. Our results reveal part of the mechanisms driving FCV evolution, which will lay foundation for the further research of FCV.


The Respiratory Virus Network – An initiative to collect and provide data on respiratory virus diseases via internet


Pulmonary embolism and Sars-Cov-2 infection: a new indication for surgical pulmonary endarterectomy?


title: Chapter 2 Nanomaterial-Based Photocatalysis

text: In this chapter, an introduction about nanostructured materials (NsM) and their applications is presented. Semiconducting nanomaterials are attractive because their physical properties are different from those of the bulk due to the quantum-size effect. Also, they provide opportunities to study the effect of spatial confinement and problems related to surfaces or interfaces, which is important for chemistry. Recently, one-dimensional (1D) nanomaterials, such as nanowires, nanobelts, nanorods, and nanotubes, have become the focus of intensive research owing to their potential applications in electronic, optoelectronic, electrochemical, electromechanical, and other fields. Further, various outstanding properties of NsM, such as optical absorbance, improved magnetism, and specific surface area, for efficient device fabrication have been summarized. Finally, applications of photocatalysis in different fields reported in the literature have been presented.


Global Polio Eradication: Espionage, Disinformation, and the Politics of Vaccination


title: How do viruses control mitochondria-mediated apoptosis?

text: Abstract There is no doubt that viruses require cells to successfully reproduce and effectively infect the next host. The question is what is the fate of the infected cells? All eukaryotic cells can “sense” viral infections and exhibit defence strategies to oppose viral replication and spread. This often leads to the elimination of the infected cells by programmed cell death or apoptosis. This “sacrifice” of infected cells represents the most primordial response of multicellular organisms to viruses. Subverting host cell apoptosis, at least for some time, is therefore a crucial strategy of viruses to ensure their replication, the production of essential viral proteins, virus assembly and the spreading to new hosts. For that reason many viruses harbor apoptosis inhibitory genes, which once inside infected cells are expressed to circumvent apoptosis induction during the virus reproduction phase. On the other hand, viruses can take advantage of stimulating apoptosis to (i) facilitate shedding and hence dissemination, (ii) to prevent infected cells from presenting viral antigens to the immune system or (iii) to kill non-infected bystander and immune cells which would limit viral propagation. Hence the decision whether an infected host cell undergoes apoptosis or not depends on virus type and pathogenicity, its capacity to oppose antiviral responses of the infected cells and/or to evade any attack from immune cells. Viral genomes have therefore been adapted throughout evolution to satisfy the need of a particular virus to induce or inhibit apoptosis during its life cycle. Here we review the different strategies used by viruses to interfere with the two major apoptosis as well as with the innate immune signaling pathways in mammalian cells. We will focus on the intrinsic mitochondrial pathway and discuss new ideas about how particular viruses could activately engage mitochondria to induce apoptosis of their host.


title: Cloning and sequencing of the matrix protein (M) gene of turkey rhinotracheitis virus reveal a gene order different from that of respiratory syncytial virus

text: Abstract Several biochemical properties and the sequence of the fusion glycoprotein (F) have indicated that turkey rhinotracheitis virus (TRTV) is a pneumovirus, subfamily Pneumovirinae of the Paramyxoviridae family. As TRTV was known to generate polycistronic mRNAs, cDNA was generated from TRTV strain U K/3 BV/85-infected Vero cell mRNAs using an oligonucleotide primer corresponding to a region of the F gene. Sequencing of four cDNAs revealed that the gene adjacent to the beginning (3′ end) of the F gene was that for the matrix (M) protein, i.e., that TRTV had the partial gene order 3′-M-F-5′. This was unexpected as human respiratory syncytial (RS) virus, the type species of the genus Pneumovirus, has the partial gene order 3′-M-SH-G-F-5′, where SH and G are the small hydrophobic protein and attachment glycoprotein, respectively. Instead TRTV resembled the Morbillivirus and Paramyxovirus genera of the Paramyxoviridae (subfamily Paramyxoviridae) which have the partial gene order 3′-M-F-5′. Two further oligonucleotides, one corresponding to a sequence near the end of the M gene and the other (oligo B) to a sequence near the beginning of the F gene, with their 5′ ends spaced 300 nucleotides apart on the basis of the cDNA sequence, were used in a polymerase chain reaction (PCR) using genomic RNA as template. Only a PCR product of 0.3 kb was obtained. The same sized product was also obtained using these oligonucleotides and genomic RNA from three other TRTV strains (SA/91 /78, UK/8544/85, and SA/2381/88) which had been grown in chicken tracheal organ cultures. In addition PCR was performed using genomic RNA from TRTV-3BV and SA/2381/88 with oligo B and another oligonucleotide near the 5′ end of the gene upstream from M, spaced 1141 nucleotides apart on the basis of the sequence data. Only a 1.14-kb PCR product was obtained. Larger products would have been expected if another gene had been situated between M and F. The absence of such larger products, plus the demonstration that infected cells contained M-F dicistronic mRNAs, supported the conclusion that in the TRTV genome the M gene is adjacent to the F gene in the order 3'-M-F-5′. The 5′ termini of the M and F mRNAs were confirmed by mRNA mapping. The TRTV M gene encoded a protein of 254 amino acids, very similar to that of RS virus (256 residues; 37% amino acid identity) but very different from that of the morbilliviruses and paramyxoviruses (approximately 350 residues). Thus, on the basis of the sequences of both the M and the F genes, TRTV is more closely related to the pneumoviruses than to the paramyxoviruses and morbilliviruses.


title: Chapter 4 Global Genomics and Proteomics Approaches to Identify Host Factors as Targets to Induce Resistance Against Tomato Bushy Stunt Virus

text: Abstract The success of RNA viruses as pathogens of plants, animals, and humans depends on their ability to reprogram the host cell metabolism to support the viral infection cycle and to suppress host defense mechanisms. Plus-strand (+)RNA viruses have limited coding potential necessitating that they co-opt an unknown number of host factors to facilitate their replication in host cells. Global genomics and proteomics approaches performed with Tomato bushy stunt virus (TBSV) and yeast (Saccharomyces cerevisiae) as a model host have led to the identification of 250 host factors affecting TBSV RNA replication and recombination or bound to the viral replicase, replication proteins, or the viral RNA. The roles of a dozen host factors involved in various steps of the replication process have been validated in yeast as well as a plant host. Altogether, the large number of host factors identified and the great variety of cellular functions performed by these factors indicate the existence of a truly complex interaction between TBSV and the host cell. This review summarizes the advantages of using a simple plant virus and yeast as a model host to advance our understanding of virus–host interactions at the molecular and cellular levels. The knowledge of host factors gained can potentially be used to inhibit virus replication via gene silencing, expression of dominant negative mutants, or design of specific chemical inhibitors leading to novel specific or broad-range resistance and antiviral tools against (+)RNA plant viruses.