title: Targeting non-human coronaviruses to human cancer cells using a bispecific single-chain antibody

text: To explore the potential of using non-human coronaviruses for cancer therapy, we first established their ability to kill human tumor cells. We found that the feline infectious peritonitis virus (FIPV) and a felinized murine hepatitis virus (fMHV), both normally incapable of infecting human cells, could rapidly and effectively kill human cancer cells artificially expressing the feline coronavirus receptor aminopeptidase N. Also 3-D multilayer tumor spheroids established from such cells were effectively eradicated. Next, we investigated whether FIPV and fMHV could be targeted to human cancer cells by constructing a bispecific single-chain antibody directed on the one hand against the feline coronavirus spike protein – responsible for receptor binding and subsequent cell entry through virus–cell membrane fusion – and on the other hand against the human epidermal growth factor receptor (EGFR). The targeting antibody mediated specific infection of EGFR-expressing human cancer cells by both coronaviruses. Furthermore, in the presence of the targeting antibody, infected cancer cells formed syncytia typical of productive coronavirus infection. By their potent cytotoxicity, the selective targeting of non-human coronaviruses to human cancer cells provides a rationale for further investigations into the use of these viruses as anticancer agents.


title: Involvement of FOXO Transcription Factors, TRAIL-FasL/Fas, and Sirtuin Proteins Family in Canine Coronavirus Type II-Induced Apoptosis

text: n our previous study, we have shown that canine coronavirus type II (CCoV-II) activates both extrinsic and intrinsic apoptotic pathway in a canine fibrosarcoma cell line (A-72 cells). Herein we investigated the role of Sirtuin and Forkhead box O (FOXO) families in this experimental model using Nortern Blot and Western Blot analysis. Our results demonstrated that mitochondrial SIRT3 and SIRT4 protein expression increased from 12 and 24 h post infection (p.i.) onwards, respectively, whereas the nuclear SIRT1 expression increased during the first 12 h p.i. followed by a decrease after 36 h p.i., reaching the same level of control at 48 h p.i. Sirtuins interact with/and regulate the activity of FOXO family proteins, and we herein observed that FOXO3A and FOXO1 expression increased significantly and stably from 12 h p.i. onwards. In addition, CCoV-II induces a remarkable increase in the expression of TNF-related apoptosis-inducing ligand (TRAIL), while we observed a slight up-regulation of FasL/Fas at 36 p.i. with a decrease of both proteins at the end of infection. Furthermore, we found that virus infection increased both bax translocation into mitochondria and decreased bcl-2 expression in cytosol in a time-dependent manner. These data suggest that FOXO transcription factors mediate pro-apoptotic effects of CCoV-II, in part due to activation of extrinsic apoptosis pathway, while some Sirtuin family members (such as SIRT3 and SIRT4) may be involved in intrinsic apoptotic pathway. Moreover, these results propose that TRAIL is an important mediator of cell death induced by CCoV-II during in vitro infection.


title: Cellular Innate Immunity against PRRSV and Swine Influenza Viruses

text: Porcine respiratory disease complex (PRDC) is a polymicrobial syndrome that results from a combination of infectious agents, such as environmental stressors, population size, management strategies, age, and genetics. PRDC results in reduced performance as well as increased mortality rates and production costs in the pig industry worldwide. This review focuses on the interactions of two enveloped RNA viruses—porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza virus (SwIV)—as major etiological agents that contribute to PRDC within the porcine cellular innate immunity during infection. The innate immune system of the porcine lung includes alveolar and parenchymal/interstitial macrophages, neutrophils (PMN), conventional dendritic cells (DC) and plasmacytoid DC, natural killer cells, and γδ T cells, thus the in vitro and in vivo interactions between those cells and PRRSV and SwIV are reviewed. Likewise, the few studies regarding PRRSV-SwIV co-infection are illustrated together with the different modulation mechanisms that are induced by the two viruses. Alterations in responses by natural killer (NK), PMN, or γδ T cells have not received much attention within the scientific community as their counterpart antigen-presenting cells and there are numerous gaps in the knowledge regarding the role of those cells in both infections. This review will help in paving the way for future directions in PRRSV and SwIV research and enhancing the understanding of the innate mechanisms that are involved during infection with these viruses.


Physical activity and exercise for older people during and after the COVID-19 pandemic: A path to recovery


title: Developing 21(st )century accreditation standards for teaching hospitals: the Taiwan experience

text: BACKGROUND: The purpose of this study is to establish teaching hospital accreditation standards anew with the hope that Taiwan's teaching hospitals can live up to the expectations of our society and ensure quality teaching. METHODS: The development process lasted two years, 2005-2006, and was separated into three stages. The first stage centered on leadership meetings and consensus building, the second on drafting the new standards with expert focus groups, and the third on a pilot study and subsequent revision. RESULTS: Our new teaching hospital accreditation standards have six categories and 95 standards as follows: educational resources (20 items), teaching and training plans and outcomes (42 items), research and results (9 items), development of clinical faculty and continuing education (8 items), academic exchanges and community education (8 items), and administration (8 items). CONCLUSIONS: The new standards have proven feasible and posed reasonable challenges in the pilot study. We hope the new standards will strengthen teaching and research, and improve the quality of hospital services at the same time.


title: Clinical characteristics of severe acute respiratory syndrome coronavirus 2 reactivation

text: Summary Objectives Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were based on information from the general population. However, limited data was available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reactivation. This study aimed to evaluate the clinical characteristics of the SARS-CoV-2 reactivation. Methods Clinical records, laboratory results, and chest CT scans were retrospectively reviewed for 55 patients with laboratory-confirmed COVID-19 pneumonia (i.e., with throat swab samples that were positive for SARS-CoV-2) who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from Jan. 8 to Feb. 10, 2020. Results All 55 patients had a history of epidemiological exposure to COVID-19, and 5 (9%) patients who discharged from hospital presented with SARS-CoV-2 reactivation. Among the 5 reactivated patients, other symptoms were also observed, including fever, cough, sore throat, and fatigue. One of the 5 patients had progressive lymphopenia (from 1.3 to 0.56 × 109 cells per L) and progressive neutrophilia (from 4.5 to 18.28 × 109 cells per L). All 5 reactivated patients presented normal aminotransferase levels. Throat swab samples from the 5 reactivated patients were tested for SARS-CoV-2, indicating all positive for the virus. Conclusions Findings from this small group of cases suggested that there was currently evidence for reactivation of SARS-CoV-2 and there might be no specific clinical characteristics to distinguish them.


Sleep in a Time of Pandemic 'COVID 19′ - A Position Statement from the National Sleep Foundation


Anticipating the ‘Second Wave’ of Health Care Strain in COVID19 Pandemic


title: Ubiquitin–Proteasome System Is Required for Efficient Replication of Singapore Grouper Iridovirus

text: The ubiquitin–proteasome system (UPS) serves as the major intracellular pathway for protein degradation and plays crucial roles in several cellular processes. However, little is known about the potential actions of the UPS during fish virus infection. In this study, we elucidated the possible roles of UPS in the life cycle of Singapore grouper iridovirus (SGIV); a large DNA virus that usually causes serious systemic diseases with high mortality in groupers. Data from transcriptomic analysis of differentially expressed genes illustrated that expression of 65 genes within the UPS pathway, including ubiquitin encoding, ubiquitination, deubiquitination, and proteasome, were up- or down-regulated during SGIV infection. Using different proteasome inhibitors, inhibition of the proteasome decreased SGIV replication in vitro, accompanied by inhibition of virus assembly site formation, and viral gene transcription and protein transportation. Over-expression of ubiquitin partly rescued the inhibitory effect of ubiquitin inhibitor on SGIV replication, suggesting that UPS was required for fish iridovirus infection in vitro. Viral or host proteins regulated by proteasome inhibition during SGIV infection were investigated with two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Sixty-two differentially expressed proteins, including 15 viral and 47 host proteins, were identified after SGIV infection. The host proteins were involved in ubiquitin-mediated protein degradation, metabolism, cytoskeleton, macromolecular biosynthesis, and signal transduction. Among them, 11 proteins were negatively regulated upon MG132 treatment during SGIV infection. This is believed to be the first study to provide evidence that UPS was essential for fish virus infection and replication.


title: De la querelle du quinquina à la querelle de l’hydroxychloroquine, ou comment notre système de protection du médicament est mis à l’épreuve: une analyse historique, scientifique et juridique

text: Abstract The current dispute over the use of hydroxychloroquine in COVID-19 resonates with another dispute, that of cinchona, which took place in the 17th century. This historical aside is a reminder that scientific disputes have always existed, so it is not surprising that the properties of hydroxychloroquine are subject to controversy. However, the facts are the facts: its effectiveness is doubtful, while the risks are certain. That is why the Prime Minister has chosen to regulate its prescription by decree. But this decree, although surely the only possible option, raises many problems.


title: Evaluation of a panel of antibodies for the immunohistochemical identification of immune cells in paraffin-embedded lymphoid tissues of new- and old-world camelids

text: Abstract Different species of camelids play an important role in the epidemiology of various emerging infectious diseases such as Middle East respiratory syndrome. For precise investigations of the immunopathogenesis in these host species, appropriate immunohistochemical markers are highly needed in order to phenotype distinct immune cells populations in camelids. So far, specific immunohistochemical markers for camelid immune cells are rarely commercially available, and cross-reactivity studies are restricted to the use of frozen dromedary tissues. To bridge this gap, 14 commercially available primary antibodies were tested for their suitability to demonstrate immune cell populations on formalin fixed paraffin-embedded (FFPE) tissue sections of dromedaries, Bactrian camels, llamas, and alpacas in the present study. Out of these, 9 antibodies directed against CD3, CD20, CD79α, HLA-DR, Iba-1, myeloid/histiocyte antigen, CD204, CD208, and CD68 antigen exhibited distinct immunoreaction patterns to certain camelid immune cell subsets. The distribution of these antigens was comparatively evaluated in different anatomical compartments of thymus, spleen, mesenteric, and tracheobronchial lymph nodes. The presented results will provide a basis for further investigations in camelids, especially with respect to the role of the immune response in certain infectious diseases, which harbor a considerable risk to spill over to other species.


title: Examining the relationship between household air pollution and infant microbial nasal carriage in a Ghanaian cohort

text: BACKGROUND: Pneumonia, a leading cause of childhood mortality, is associated with household air pollution (HAP) exposure. Mechanisms between HAP and pneumonia are poorly understood, but studies suggest that HAP may increase the likelihood of bacterial, instead of viral, pneumonia. We assessed the relationship between HAP and infant microbial nasal carriage among 260 infants participating in the Ghana Randomized Air Pollution and Health Study (GRAPHS). METHODS: Data are from GRAPHS, a cluster-randomized controlled trial of cookstove interventions (improved biomass or LPG) versus the 3-stone (baseline) cookstove. Infants were surveyed for pneumonia during the first year of life and had routine personal exposure assessments. Nasopharyngeal swabs collected from pneumonia cases (n = 130) and healthy controls (n = 130) were analyzed for presence of 22 common respiratory microbes by MassTag polymerase chain reaction. Data analyses included intention-to-treat (ITT) comparisons of microbial species presence by study arm, and exposure-response relationships. RESULTS: In ITT analyses, 3-stone arm participants had a higher mean number of microbial species than the LPG (LPG: 2.71, 3-stone: 3.34, p < 0.0001, n = 260). This difference was driven by increased bacterial (p < 0.0001) rather than viral species presence (non-significant). Results were pronounced in pneumonia cases and attenuated in healthy controls. Higher prevalence bacterial species were Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Exposure-response relationships did not yield significant associations between measured CO and nasal microbial carriage. CONCLUSIONS: Our intention-to-treat findings are consistent with a link between HAP and bacterial nasal carriage. No relationships were found for viral carriage. Given the null results in exposure-response analysis, it is likely that a pollutant besides CO is driving these differences.


title: Business transformation: Leadership, integration and innovation – A case study

text: Abstract The Cornerstone Program represented a significant business transformation for Hydro One. Just as a cornerstone helps determine the position of an entire structure; the Cornerstone Program has helped shape the future strategic position of Hydro One. This strategy and vision includes supporting the business infrastructure through improvements to rapidly respond to business needs, enabling rapid access to information for strategic decisions, and streamlined business operations enabling the organization to deal with growing requirements. This case study introduces a conceptual framework that draws from theoretical change models but is also grounded in the reality of the change environment at this organization. Realizing major organizational change is a complex process influenced by the characteristics of an organization, the integrated project and change management framework, and the importance of key leadership roles throughout the change process. Results from this study suggest that effective change implementation was enabled by leadership, program management, and change ownership, integrated with project implementation.


COVID-19, confinement et addictions


title: Evaluation of Elevated Liver Enzymes

text: Liver enzymes, including aminotransferases and alkaline phosphatase, are some of the most commonly ordered blood tests in a physician's practice. These enzymes have been valuable in screening for liver disease, as well as in diagnosing and monitoring patients with acute and chronic hepatobiliary disorders. Patients with predominantly aminotransferase elevations are thought to have acute or chronic hepatitis from a variety of causes. In patients with predominantly alkaline phosphatase elevations, imaging evaluation is undertaken upfront to exclude large bile duct disorders and infiltrative/mass lesions. A liver biopsy may be reserved for patients for whom these less invasive investigations are unfruitful.


title: RT-PCR and Electrospray Ionization Mass Spectrometry (RT-PCR/ESI-MS) for Identifying Acute Viral Upper Respiratory Tract Infections

text: Diagnosis of respiratory viruses traditionally relies on culture or antigen detection.We aimed to demonstrate capacity of the RT-PCR/ESI-MS platform to identify clinical relevant respiratory viruses in nasopharyngeal aspirate (NPA) samples and compare the diagnostic performance characteristics relative to conventional culture- and antigen-based methods. A RT-PCR/ESI-MS respiratory virus surveillance kit designed to detect respiratory syncytial virus, influenza A and B, parainfluenza types 1-4, adenoviridae types A-F, coronaviridae, human bocavirus, and human metapneumovirus was evaluated using both mock-ups and frozen archived NPA (N=280), 95 of which were positive by clinical virology methods. RT-PCR/ESI-MS detected 74/95 (77.9%) known positive samples and identified an additional 13/185 (7%) from culture negative samples. Viruses that are non-detectable with conventional methods were also identified. Viral load was semi-quantifiable and ranged from 2,400 to >320,000copies/ml. Time to results was 8hrs. RT-PCR/ESI-MS showed promise in rapid detection of respiratory viruses, merits further evaluation for use in clinical settings.


title: Critical review of social, environmental and health risk factors in the Mexican indigenous population and their capacity to respond to the COVID-19

text: Abstract The objective of this study was to conduct a critical analysis of the social, environmental and health risk factors in the Mexican indigenous population in the context of the COVID-19 disease pandemic, and to propose strategies to mitigate the impacts on these communities. Regarding social factors, we identified the return of indigenous people to their communities, poor access to water, language barriers, and limited access to the Internet, as factors that will not allow them to take the minimum preventive measures against the disease. Additionally, environmental risk factors associated with pollutants from biomass burning were identified. In health, the lack of coverage in these areas and comorbidities such as diabetes mellitus, hypertension, respiratory tract infections, and chronic pulmonary diseases were identified. Some existing government programmes were identified that could be supported to address these social, environmental and health gaps. We believe that the best way to address these issues is to strengthen the health system with a community-based approach. Health is the best element of cohesion for inserting development and progress proposals in indigenous communities, given the vulnerability to which they are exposed in the face of the COVID-19 pandemic. In this review, all information is provided (as possible) on risk factors and potential solutions in indigenous communities in the hope of providing solutions to this pandemic and providing a reference for future studies.


title: Severe COVID-19 and aging: are monocytes the key?

text: The ongoing pandemic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a disproportionate number of severe cases and deaths in older adults. Severe SARS-CoV-2-associated disease (coronavirus disease 2019 (COVID-19)) was declared a pandemic by the World Health Organization in March 2020 and is characterized by cytokine storm, acute respiratory distress syndrome, and in some cases by systemic inflammation–related pathology. Currently, our knowledge of the determinants of severe COVID-19 is primarily observational. Here, I review emerging evidence to argue that monocytes, a circulating innate immune cell, are principal players in cytokine storm and associated pathologies in COVID-19. I also describe changes in monocyte function and phenotype that are characteristic of both aging and severe COVID-19, which suggests a potential mechanism underlying increased morbidity and mortality due to SARS-CoV-2 infection in older adults. The innate immune system is therefore a potentially important target for therapeutic treatment of COVID-19, but experimental studies are needed, and SARS-CoV-2 presents unique challenges for pre-clinical and mechanistic studies in vivo. The immediate establishment of colonies of SARS-CoV-2-susceptible animal models for aging studies, as well as strong collaborative efforts in the geroscience community, will be required in order to develop the therapies needed to combat severe COVID-19 in older adult populations.


title: CD46 is a potent co-stimulatory receptor for expansion of human IFN-γ-producing CD8+ T cells

text: Abstract Similar to CD4+ T cells, precursor CD8+ T cells are thought to depend on a co-stimulatory signal through CD28 for proliferation and differentiation into effector cells. CD46 is another co-stimulatory receptor that promotes differentiation of CD4+ T-helper cells type 1 (Th1 cells) into a regulatory phenotype with a switch from IFN-γ towards IL-10-secretion over time. Whether CD46 exerts a similar function on CD8+ T cells remains to be fully elucidated. Here, we demonstrate that CD46 co-stimulation induced secretion of IFN-γ as well as expansion of IFN-γ-secreting CD8+ T cells. In contrast to CD46 co-stimulation of CD4+ T cells, CD8+ T cells did not differentiate into a regulatory IL-10-secreting phenotype. This demonstrates that CD46 is a co-stimulatory receptor on CD8+ T cells, and that it exerts separate functions during CD4+ and CD8+ T-cell differentiation.


title: Home dampness-related exposures increase the risk of common colds among preschool children in Shanghai, China: Modified by household ventilation

text: Abstract Few studies have estimated the effects of dampness-related exposures and its interaction effects with poor household ventilation on common colds of preschool children. During April 2011–April 2012, we conducted a cross-sectional survey on home environment and childhood health and collected 13,335 parents-reported questionnaires of 4–6 year-old children in Shanghai, China. In this paper, we investigated associations between the incidence and duration of common colds among these children during the past 12 months before the survey and frequency of opening windows, as well as household dampness-related exposures (indicated by six dampness indicators). Significantly higher incidence (≥3 times) and longer duration (≥2 weeks) of common cold were found among children with than without these dampness exposures (p-value <0.01 for mold spots and p-value <0.001 for all other indicators). The number of dampness-related indicators had a positive and strong dose-response relationship with common colds (p-trend <0.01). Low frequency of ventilation was also a risk factor for children common colds. After adjusted for the potential confounders in the multiple logistic regression analyses, all dampness-related indicators were significantly associated with the increased odds of common colds and the highest odds ratios was 1.21 (95% CI: 1.16–1.27). We also found that dampness-related exposures and household ventilation habits (p-value for interaction <0.001) had a strong interaction effect on the incidence and duration of common cold. The stratified analysis of ventilation condition displays that the influence of dampness-related exposures has been modified by ventilation. Therefore, good household ventilation habits may have an effect of modification for dampness-related exposures.


title: Identification of a novel dual-target scaffold for 3CLpro and RdRp proteins of SARS-CoV-2 using 3D-similarity search, molecular docking, molecular dynamics and ADMET evaluation

text: The new SARS-CoV-2 coronavirus is the causative agent of the COVID-19 pandemic outbreak that affected whole the world with more than 6 million confirmed cases and over 370,000 deaths. At present, there are no effective treatments or vaccine for this disease, which constitutes a serious global health crisis. As the pandemic still spreading around the globe, it is of interest to use computational methods to identify potential inhibitors for the virus. The crystallographic structures of 3CLpro (PDB: 6LU7) and RdRp (PDB 6ML7) were used in virtual screening of 50000 chemical compounds obtained from the CAS Antiviral COVID19 database using 3D-similarity search and standard molecular docking followed by ranking and selection of compounds based on their binding affinity, computational techniques for the sake of details on the binding interactions, absorption, distribution, metabolism, excretion, and toxicity prediction; we report three 4-(morpholin-4-yl)-1,3,5-triazin-2-amine derivatives; two compounds (2001083-68-5 and 2001083-69-6) with optimal binding features to the active site of the main protease and one compound (833463-19-7) with optimal binding features to the active site of the polymerase for further consideration to fight COVID-19. The structural stability and dynamics of lead compounds at the active site of 3CLpro and RdRp were examined using molecular dynamics (MD) simulation. Essential dynamics demonstrated that the three complexes remain stable during simulation of 20 ns, which may be suitable candidates for further experimental analysis. As the identified leads share the same scaffold, they may serve as promising leads in the development of dual 3CLpro and RdRp inhibitors against SARS-CoV-2. Communicated by Ramaswamy H. Sarma.


title: Structure-based Design, Synthesis and Biological Evaluation of Peptidomimetic SARS-CoV 3CLpro Inhibitors

text: Structure-based design, synthesis and biological evaluation of a series of peptidomimetic severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors is described. These inhibitors were designed and synthesized based upon our X-ray crystal structure of inhibitor 1 bound to SARS-CoV 3CLpro. Incorporation of Boc-Ser as the P4-ligand resulted in enhanced SARS-CoV 3CLpro inhibitory activity. Structural analysis of inhibitor-bound X-ray structure revealed high binding affinity towards the enzyme.


title: Laboratory Investigation of a Nosocomial Transmission of Tuberculosis at a District General Hospital

text: Background/Purpose Nosocomial outbreak of tuberculosis (TB) is rarely documented and the transmission is usually difficult to confirm because of the long incubation period of the mycobacterial infection. In this report, we demonstrated the use of molecular genotyping methods together with contact tracing to identify the source case, the causative outbreak strain and transmission dynamics of Mycobacterium tuberculosis, and for the definite confirmation of a suspected outbreak. Methods M. tuberculosis strains were genotyped with IS6110 restriction fragment length polymorphism, spacer oligonucleotide typing and minisatellite interspersed repetitive unit–variable number tandem repeat methods. Clinical data and contact tracing results were collected from medical records and the National TB Registry. Results In this episode, 66 health care workers (HCWs) were notified as TB cases. A total of 18 M. tuberculosis isolates from HCWs and patients were collected. IS6110 RFLP results revealed that 9 out of 10 HCWs' and 7 out of 8 patients' isolates shared the same genotype. The causative isolate was identified as the Beijing genotype. The index case was a hospitalized respirator-dependent patient. Conclusion Thorough collection along with molecular diagnosis and genotyping of all M. tuberculosis isolates are recommended for the confirmation of any suspected nosocomial TB outbreak.


title: Long-term strategies to control COVID-19 in low and middle-income countries: an options overview of community-based, non-pharmacological interventions

text: In low and middle-income countries (LMICs), strict social distancing measures (e.g., nationwide lockdown) in response to the COVID-19 pandemic are unsustainable in the long-term due to knock-on socioeconomic and psychological effects. However, an optimal epidemiology-focused strategy for ‘safe-reopening’ (i.e., balancing between the economic and health consequences) remain unclear, particularly given the suboptimal disease surveillance and diagnostic infrastructure in these settings. As the lockdown is now being relaxed in many LMICs, in this paper, we have (1) conducted an epidemiology-based “options appraisal” of various available non-pharmacological intervention options that can be employed to safely lift the lockdowns (namely, sustained mitigation, zonal lockdown and rolling lockdown strategies), and (2) propose suitable application, pre-requisites, and inherent limitations for each measure. Among these, a sustained mitigation-only approach (adopted in many high-income countries) may not be feasible in most LMIC settings given the absence of nationwide population surveillance, generalised testing, contact tracing and critical care infrastructure needed to tackle the likely resurgence of infections. By contrast, zonal or local lockdowns may be suitable for some countries where systematic identification of new outbreak clusters in real-time would be feasible. This requires a generalised testing and surveillance structure, and a well-thought out (and executed) zone management plan. Finally, an intermittent, rolling lockdown strategy has recently been suggested by the World Health Organization as a potential strategy to get the epidemic under control in some LMI settings, where generalised mitigation and zonal containment is unfeasible. This strategy, however, needs to be carefully considered for economic costs and necessary supply chain reforms. In conclusion, while we propose three community-based, non-pharmacological options for LMICs, a suitable measure should be context-specific and based on: (1) epidemiological considerations, (2) social and economic costs, (3) existing health systems capabilities and (4) future-proof plans to implement and sustain the strategy.


title: A re-analysis of studies regarding the use of Glycyrrhiza spp. in women during pregnancy

text: Abstract The use of herbal medicines as a form of primary and adjunctive healthcare continues to grow internationally. It is therefore important that healthcare practitioners stay abreast of potential contraindications that may arise when these medicines are taken together with orthodox treatment or are prescribed during pregnancy. This article analyses the most popularly cited clinical research concerning the use of Glycyrrhiza spp. during pregnancy. It also aims to serve as guidance for healthcare professionals who either prescribe herbal medicines or have cause to advise patients in relation to the use of glycyrrhiza by women during pregnancy.


title: Health sector spending and spending on HIV/AIDS, tuberculosis, and malaria, and development assistance for health: progress towards Sustainable Development Goal 3

text: Summary Background Sustainable Development Goal (SDG) 3 aims to “ensure healthy lives and promote well-being for all at all ages”. While a substantial effort has been made to quantify progress towards SDG3, less research has focused on tracking spending towards this goal. We used spending estimates to measure progress in financing the priority areas of SDG3, examine the association between outcomes and financing, and identify where resource gains are most needed to achieve the SDG3 indicators for which data are available. Methods We estimated domestic health spending, disaggregated by source (government, out-of-pocket, and prepaid private) from 1995 to 2017 for 195 countries and territories. For disease-specific health spending, we estimated spending for HIV/AIDS and tuberculosis for 135 low-income and middle-income countries, and malaria in 106 malaria-endemic countries, from 2000 to 2017. We also estimated development assistance for health (DAH) from 1990 to 2019, by source, disbursing development agency, recipient, and health focus area, including DAH for pandemic preparedness. Finally, we estimated future health spending for 195 countries and territories from 2018 until 2030. We report all spending estimates in inflation-adjusted 2019 US$, unless otherwise stated. Findings Since the development and implementation of the SDGs in 2015, global health spending has increased, reaching $7·9 trillion (95% uncertainty interval 7·8–8·0) in 2017 and is expected to increase to $11·0 trillion (10·7–11·2) by 2030. In 2017, in low-income and middle-income countries spending on HIV/AIDS was $20·2 billion (17·0–25·0) and on tuberculosis it was $10·9 billion (10·3–11·8), and in malaria-endemic countries spending on malaria was $5·1 billion (4·9–5·4). Development assistance for health was $40·6 billion in 2019 and HIV/AIDS has been the health focus area to receive the highest contribution since 2004. In 2019, $374 million of DAH was provided for pandemic preparedness, less than 1% of DAH. Although spending has increased across HIV/AIDS, tuberculosis, and malaria since 2015, spending has not increased in all countries, and outcomes in terms of prevalence, incidence, and per-capita spending have been mixed. The proportion of health spending from pooled sources is expected to increase from 81·6% (81·6–81·7) in 2015 to 83·1% (82·8–83·3) in 2030. Interpretation Health spending on SDG3 priority areas has increased, but not in all countries, and progress towards meeting the SDG3 targets has been mixed and has varied by country and by target. The evidence on the scale-up of spending and improvements in health outcomes suggest a nuanced relationship, such that increases in spending do not always results in improvements in outcomes. Although countries will probably need more resources to achieve SDG3, other constraints in the broader health system such as inefficient allocation of resources across interventions and populations, weak governance systems, human resource shortages, and drug shortages, will also need to be addressed. Funding The Bill & Melinda Gates Foundation.


title: Antiviral activities of ISG20 in positive-strand RNA virus infections

text: Abstract ISG20 is an interferon-inducible 3′–5′ exonuclease that inhibits replication of several human and animal RNA viruses. However, the specificities of ISG20's antiviral action remain poorly defined. Here we determine the impact of ectopic expression of ISG20 on replication of several positive-strand RNA viruses from distinct viral families. ISG20 inhibited infections by cell culture-derived hepatitis C virus (HCV) and a pestivirus, bovine viral diarrhea virus and a picornavirus, hepatitis A virus. Moreover, ISG20 demonstrated cell-type specific antiviral activity against yellow fever virus, a classical flavivirus. Overexpression of ISG20, however, did not inhibit propagation of severe acute respiratory syndrome coronavirus, a highly-pathogenic human coronavirus in Huh7.5 cells. The antiviral effects of ISG20 were all dependent on its exonuclease activity. The closely related cellular exonucleases, ISG20L1 and ISG20L2, did not inhibit HCV replication. Together, these data may help better understand the antiviral specificity and action of ISG20.


title: Kinome-Wide RNA Interference Screening Identifies Mitogen-Activated Protein Kinases and Phosphatidylinositol Metabolism as Key Factors for Rabies Virus Infection

text: Throughout the rabies virus (RABV) infectious cycle, host-virus interactions define its capacity to replicate, escape the immune response, and spread. As phosphorylation is a key regulatory mechanism involved in most cellular processes, kinases represent a target of choice to identify host factors required for viral replication. A kinase and phosphatase small interfering RNA (siRNA) high-content screening was performed on a fluorescent protein-recombinant field isolate (Tha RABV). We identified 57 high-confidence key host factors important for RABV replication with a readout set at 18 h postinfection and 73 with a readout set at 36 h postinfection, including 24 common factors at all stages of the infection. Amongst them, gene clusters of the most prominent pathways were determined. Up to 15 mitogen-activated protein kinases (MAPKs) and effectors, including MKK7 (associated with Jun N-terminal protein kinase [JNK] signalization) and DUSP5, as well as 17 phosphatidylinositol (PI)-related proteins, including PIP5K1C and MTM1, were found to be involved in the later stage of RABV infection. The importance of these pathways was further validated, as small molecules Ro 31-8820 and PD 198306 inhibited RABV replication in human neurons. IMPORTANCE Rabies virus relies on cellular machinery for its replication while simultaneously evading the host immune response. Despite their importance, little is known about the key host factors required for rabies virus infection. Here, we focused on the human kinome, at the core of many cellular pathways, to unveil a new understanding of the rabies virus infectious cycle and to discover new potential therapeutic targets in a small interfering RNA screening. The mitogen-activated protein kinase pathway and phosphatidylinositol metabolism were identified as prominent factors involved in rabies virus infection, and those findings were further confirmed in human neurons. While bringing a new insight into rabies virus biology, we also provide a new list of host factors involved in rabies virus infection.


title: Unmasking the information encoded as structural motifs of viral RNA genomes: a potential antiviral target

text: RNA viruses show enormous capacity to evolve and adapt to new cellular and molecular contexts, a consequence of mutations arising from errors made by viral RNA‐dependent RNA polymerase during replication. Sequence variation must occur, however, without compromising functions essential for the completion of the viral cycle. RNA viruses are safeguarded in this respect by their genome carrying conserved information that does not code only for proteins but also for the formation of structurally conserved RNA domains that directly perform these critical functions. Functional RNA domains can interact with other regions of the viral genome and/or proteins to direct viral translation, replication and encapsidation. They are therefore potential targets for novel therapeutic strategies. This review summarises our knowledge of the functional RNA domains of human RNA viruses and examines the achievements made in the design of antiviral compounds that interfere with their folding and therefore their function. Copyright © 2013 John Wiley & Sons, Ltd.


title: Cancer history is an independent risk factor for mortality in hospitalized COVID-19 patients: a propensity score-matched analysis

text: BACKGROUND: Although research on the effects of comorbidities on coronavirus disease 2019 (COVID-19) patients is increasing, the risk of cancer history has not been evaluated for the mortality of patients with COVID-19. METHODS: In this retrospective study, we included 3232 patients with pathogen-confirmed COVID-19 who were hospitalized between January 18th and March 27th, 2020, at Tongji Hospital in Wuhan, China. Propensity score matching was used to minimize selection bias. RESULTS: In total, 2665 patients with complete clinical outcomes were analyzed. The impacts of age, sex, and comorbidities were evaluated separately using binary logistic regression analysis. The results showed that age, sex, and cancer history are independent risk factors for mortality in hospitalized COVID-19 patients. COVID-19 patients with cancer exhibited a significant increase in mortality rate (29.4% vs. 10.2%, P < 0.0001). Furthermore, the clinical outcomes of patients with hematological malignancies were worse, with a mortality rate twice that of patients with solid tumors (50% vs. 26.1%). Importantly, cancer patients with complications had a significantly higher risk of poor outcomes. One hundred nine cancer patients were matched to noncancer controls in a 1:3 ratio by propensity score matching. After propensity score matching, the cancer patients still had a higher risk of mortality than the matched noncancer patients (odds ratio (OR) 2.98, 95% confidence interval (95% CI) 1.76–5.06). Additionally, elevations in ferritin, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, procalcitonin, prothrombin time, interleukin-2 (IL-2) receptor, and interleukin-6 (IL-6) were observed in cancer patients. CONCLUSIONS: We evaluated prognostic factors with epidemiological analysis and highlighted a higher risk of mortality for cancer patients with COVID-19. Importantly, cancer history was the only independent risk factor for COVID-19 among common comorbidities, while other comorbidities may act through other factors. Moreover, several laboratory parameters were significantly different between cancer patients and matched noncancer patients, which may indicate specific immune and inflammatory reactions in COVID-19 patients with cancer.


title: Human bocavirus and other respiratory viral infections in a 2‐year cohort of hospitalized children

text: Human bocavirus (HBoV) infection is reported worldwide and may cause severe respiratory tract infections. The aim of the present study was to assess the prevalence of HBoV, and other respiratory viral pathogens, in a 2‐year retrospective study of children admitted to hospital, and to investigate whether viral loads of HBoV DNA were associated with severity of infection. Between April 2007 and March 2009, 891 respiratory samples from 760 children admitted to hospital with acute respiratory tract infection were tested for the presence of respiratory viruses by real‐time PCR or direct immunofluorescence testing. HBoV DNA was detected by using internally controlled real‐time quantitative PCR assay and 25 samples selected at random were sequenced. The virus detected most frequently was rhinovirus, followed by respiratory syncytial virus, HBoV, and human metapneumovirus. HBoV DNA was detected in 18.4% of children admitted to hospital. HBoV was the only viral pathogen detected in 66/164 (40.2%) of HBoV DNA‐positive children and in 7.4% of all 891 samples. Ninety‐seven percent (64/66) of children with an HBoV single infection were diagnosed as having lower respiratory tract infection. Median HBoV DNA viral load was significantly higher in children when HBoV was detected as a single pathogen. Higher HBoV DNA viral loads were associated with prematurity and age. HBoV seems to be an important and frequent pathogen in respiratory tract infections in children, and it is likely that the severity of illness is comparable to the severity of RSV illness. J. Med. Virol. 84:99–108, 2011. © 2011 Wiley Periodicals, Inc.


title: Structural and simulation analysis of hotspot residues interactions of SARS-CoV 2 with human ACE2 receptor

text: The novel corona virus disease 2019 (SARS-CoV 2) pandemic outbreak was alarming. The binding of SARS-CoV (CoV) spike protein (S-Protein) Receptor Binding Domain (RBD) to Angiotensin converting enzyme 2 (ACE2) receptor initiates the entry of corona virus into the host cells leading to the infection. However, considering the mutations reported in the SARS-CoV 2 (nCoV), the structural changes and the binding interactions of the S-protein RBD of nCoV were not clear. The present study was designed to elucidate the structural changes, hot spot binding residues and their interactions between the nCoV S-protein RBD and ACE2 receptor through computational approaches. Based on the sequence alignment, a total of 58 residues were found mutated in nCoV S-protein RBD. These mutations led to the structural changes in the nCoV S-protein RBD 3d structure with 4 helices, 10 sheets and intermittent loops. The nCoV RBD was found binding to ACE2 receptor with 11 hydrogen bonds and 1 salt bridge. The major hot spot amino acids involved in the binding identified by interaction analysis after simulations includes Glu 35, Tyr 83, Asp 38, Lys 31, Glu 37, His 34 amino acid residues of ACE2 receptor and Gln 493, Gln 498, Asn 487, Tyr 505 and Lys 417 residues in nCoV S-protein RBD. Based on the hydrogen bonding, RMSD and RMSF, total and potential energies, the nCoV was found binding to ACE2 receptor with higher stability and rigidity. Concluding, the hotspots information will be useful in designing blockers for the nCoV spike protein RBD. [Image: see text] Communicated by Ramaswamy H. Sarma


title: The SARS-CoV-2, a new pandemic zoonosis that threatens the world

text: Abstract On December 31, 2019, an outbreak of pneumonia of unknown etiology was detected in the city of Wuhan (China). A week later, a new coronavirus was isolated in these patients, initially designated as 2019-nCoV and subsequently SARS-CoV-2. This is a new virus that is much closer genetically to the coronavirus of bats than to human SARS. The new virus infects and replicates in the lung parenchyma pneumocytes and macrophages in which the ACE-2 cell receptor resides. He has now infected many more people than his predecessors (>85,000). From the clinical point of view, those infected have an average age of 55 years; the main symptoms are fever, dry cough, lymphopenia, dyspnea, and pneumonia in its severe form. The overall lethality rate is 2-3% in China and 0.1% in cases detected outside of this country. The incubation period has been set at about 3 days (0-24 days). There are no specific antivirals or vaccines.


title: Virus susceptibility of Chinese hamster ovary (CHO) cells and detection of viral contaminations by adventitious agent testing

text: Biopharmaceuticals are of increasing importance in the treatment of a variety of diseases. A remaining concern associated with their production is the potential introduction of adventitious agents into their manufacturing process, which may compromise the pathogen safety of a product and potentially cause stock‐out situations for important medical supplies. To ensure the safety of biological therapeutics, regulatory guidance requires adventitious agent testing (AAT) of the bulk harvest. AAT is a deliberately promiscuous assay procedure which has been developed to indicate, ideally, the presence of any viral contaminant. One of the most important cell lines used in the production of biopharmaceuticals is Chinese hamster ovary (CHO) cells and while viral infections of CHO cells have occurred, a systematic screen of their virus susceptibility has never been published. We investigated the susceptibility of CHO cells to infection by 14 different viruses, including members of 12 families and representatives or the very species that were implicated in previously reported production cell infections. Based on our results, four different infection outcomes were distinguished, based on the possible combinations of the two factors (i) the induction, or not, of a cytopathic effect and (ii) the ability, or not, to replicate in CHO cells. Our results demonstrate that the current AAT is effective for the detection of viruses which are able to replicate in CHO cells. Due to the restricted virus susceptibility of CHO cells and the routine AAT of bulk harvests, our results provide re‐assurance for the very high safety margins of CHO cell‐derived biopharmaceuticals. Biotechnol. Bioeng. 2010;106: 598–607. © 2010 Wiley Periodicals, Inc.


title: Global coronavirus disease 2019: what has daily cumulative index taught us?

text: ABSTRACT In addition to the absolute case number, a rapid increase in the number of COVID-19 cases within a short time was supposed to result in insufficiency of the healthcare system and further negatively affect patients’ outcomes. This study was conducted to investigate the association between the outcomes of COVID-19 patients and daily cumulative index (DCI), which was defined as the average daily number of new cases of COVID-19 and calculated by cumulative cases/number of days between the first reported case and March 6, 2020 by country. Spearman's rank correlation analyses were conducted to evaluate the relationship between mortality, incidence, and DCI. In this study, we found that DCI was positively correlated with incidence (adjusted risk ratio [aRR] = 1.01, 95% [confidence interval, CI] = 1.00-1.02, p < 0.01). Higher correlation between mortality and DCI (mortality rate: r = 0.397, p = 0.018; mortality per 1,000,000 people: r = 0.0.428, p = 0.004) was observed than disease incidence. DCI remained statistically associated with mortality per 1,000,000 people after adjustment of Health Care Index (aRR = 1.02, 95% CI = 1.01-1.03, p < 0.001) or Healthcare Access and Quality Index (aRR = 1.02, 95% CI = 1.01-1.04, p < 0.01. Reducing DCI through strict infection control measures can help slow the increasing number of COVID-19 cases and further improve outcome in COVID-19 patients.


title: Genome sequencing and characterization analysis of a Beijing isolate of chicken coronavirus infectious bronchitis virus

text: Avian infectious bronchitis virus (AIBV) is classified as a member of the genus coronavirus in the family coronaviridae. The enveloped virus has a positive-sense, single-stranded RNA genome of approximately 28 kilo-bases, which has a 5′ cap structure and 3′ polyadenylation tract. The complete genome sequence of infectious bronchitis virus (IBV), Beijing isolate, was determined by cloning sequencing and primer walking. The whole genome is 27733 nucleotides in length, has ten open reading frames: 5′ -orf1a-orf1ab-s-3a-3b-e-m-6a-6b-n-3′. Alignments of the genome sequence of IBV Beijing isolate with those of two AIBV strains and one SARS coronavirus were performed respectively. The genome sequence of IBV Beijing isolate compared with that of the IBV strain LX4 (uncompleted, 19440 bp in size) was 91.2% similarity. However, the full-length genome sequence of IBV Beijing isolate was 85.2% identity to that of IBV Strain Beaudette, and was only 50.8% homology to that of SARS coronavirus. The results showed that the genome of IBV has remarkable variation. And IBV Beijing isolate is not closely related to SARS coronavirus. Phylogenetic analyses based on the whole genome sequence, S protein, M protein and N protein, also showed that AIBV Beijing isolate is lone virus in group III and is distant from SARS coronavirus. In conclusion, this study will contribute to the studies of diagnosis and diseases control on IBV in China.


title: Age-associated impaired plasmacytoid dendritic cell functions lead to decreased CD4 and CD8 T cell immunity

text: Increased susceptibility to infections, particularly respiratory viral infections, is a hallmark of advancing age. The underlying mechanisms are not well understood, and there is a scarcity of information regarding the contribution of the innate immune system, which is the first line of defense against infections. In the present study, we have investigated the effect of advancing age on plasmacytoid dendritic cell (PDC) function because they are critical in generating a robust antiviral response via the secretion of interferons (IFN). Our results indicate that PDCs from the aged are impaired in their capacity to secrete IFN-I in response to influenza virus and CPG stimulation. Additionally, we observed a severe reduction in the production of IFN-III, which plays an important role in defense against viral infections at respiratory mucosal surfaces. This reduction in IFN-I and IFN-III were a result of age-associated impaired phosphorylation of transcription factor, IRF-7. Furthermore, aged PDCs were observed to be impaired in their capacity to induce perforin and granzyme in CD8 T cells. Comparison of the antigen-presenting capacity of aged PDC with young PDC revealed that PDCs from aged subjects display reduced capacity to induce proliferation and IFN-gamma secretion in CD4 and CD8 T cells as compared with PDCs from young subjects. In summary, our study demonstrates that advancing age has a profound effect on PDC function at multiple levels and may therefore, be responsible for the increased susceptibility to infections in the elderly.


title: Polymers in the Delivery of siRNA for the Treatment of Virus Infections

text: Viral diseases remain a major cause of death worldwide. Despite advances in vaccine and antiviral drug technology, each year over three million people die from a range of viral infections. Predominant viruses include human immunodeficiency virus, hepatitis viruses, and gastrointestinal and respiratory viruses. Now more than ever, robust, easily mobilised and cost-effective antiviral strategies are needed to combat both known and emerging disease threats. RNA interference and small interfering (si)RNAs were initially hailed as a “magic bullet”, due to their ability to inhibit the synthesis of any protein via the degradation of its complementary messenger RNA sequence. Of particular interest was the potential for attenuating viral mRNAs contributing to the pathogenesis of disease that were not able to be targeted by vaccines or antiviral drugs. However, it was soon discovered that delivery of active siRNA molecules to the infection site in vivo was considerably more difficult than anticipated, due to a number of physiological barriers in the body. This spurred a new wave of investigation into nucleic acid delivery vehicles which could facilitate safe, targeted and effective administration of the siRNA as therapy. Amongst these, cationic polymer delivery vehicles have emerged as a promising candidate as they are low-cost and easy to produce at an industrial scale, and bind to the siRNA by non-specific electrostatic interactions. These nanoparticles (NPs) can be functionally designed to target the infection site, improve uptake in infected cells, release the siRNA inside the endosome and facilitate delivery into the cell cytoplasm. They may also have the added benefit of acting as adjuvants. This chapter provides a background around problems associated with the translation of siRNA as antiviral treatments, reviews the progress made in nucleic acid therapeutics and discusses current methods and progress in overcoming these challenges. It also addresses the importance of combining physicochemical characterisation of the NPs with in vitro and in vivo data.


Add on the next level—the time point of the type I IFN response orchestrates the immune response


title: Clinical and Epidemiologic Patterns of Chikungunya Virus Infection and Coincident Arboviral Disease in a School Cohort in Haiti, 2014–2015

text: BACKGROUND: Beginning in December 2013, an epidemic of chikungunya virus (CHIKV) infection spread across the Caribbean and into virtually all countries in the Western hemisphere, with >2.4 million cases reported through the end of 2017. METHODS: We monitored a cohort of school children in rural Haiti from May 2014, through February 2015, for occurrence of acute undifferentiated febrile illness, with clinical and laboratory data available for 252 illness episodes. RESULTS: Our findings document passage of the major CHIKV epidemic between May and July 2014, with 82 laboratory-confirmed cases. Subsequent peaks of febrile illness were found to incorporate smaller outbreaks of dengue virus serotypes 1 and 4 and Zika virus, with identification of additional infections with Mayaro virus, enterovirus D68, and coronavirus NL63. CHIKV and dengue virus serotype 1 infections were more common in older children, with a complaint of arthralgia serving as a significant predictor for infection with CHIKV (odds ratio, 16.2; 95% confidence interval, 8.0–34.4; positive predictive value, 66%; negative predictive value, 80%). CONCLUSIONS: Viral/arboviral infections were characterized by a pattern of recurrent outbreaks and case clusters, with the CHIKV epidemic representing just one of several arboviral agents moving through the population. Although clinical presentations of these agents are similar, arthralgias are highly suggestive of CHIKV infection.


Paediatric burns epidemiology during COVID-19 pandemic and ‘stay home’ era


title: (18)F-FDG PET/CT Metabolic Behavior of COVID-19 Pneumonia: A Series of 4 Patients With RT-PCR Confirmation

text: Between March 26 and April 6, among 80 patients who underwent (18)F-FDG PET/CT in our department (Brescia, Italy), 4 showed the presence of an interstitial pneumonia suspected for COVID-19 with reverse transcriptase polymerase chain reaction confirmation. All patients except one had bilateral ground-glass opacities and/or lung consolidations in at least 2 pulmonary lobes. Inferior lobes and basal segments were the most frequent site of disease. All lung lesions had an increased FDG uptake corresponding to the interstitial pneumonia, and in one case, mediastinal nodal involvement was registered.


title: A case report of the enterovirus-D68 associated severe acute respiratory illness in a pediatric case from India

text: Abstract Since, early 2000s, there have been several clusters of enterovirus-D68 (EV D68) associated respiratory illness reported from various countries. Recent largest and most wide-spread outbreak of EV-D68 associated severe acute respiratory illness (SARI) occurred in North America. Present report describes a case of EV-D68 associated severe acute respiratory illness from India with a whole genome sequence. The case was identified through retrospective analysis of Influenza SARI surveillance sample collected during September 2017 using Next Generation sequencing. EV D68 positive child aged two years and presented with asthma like symptoms for which he was admitted to ICU. The child tested negative for Influenza, RSV, Rhinovirus, PIV, hMPV and adenovirus, on real time RT-PCR. And on NGS full EV D68 genome was retrieved belonging to sub-clade B3. In ICU, child received anti-bacterial and anti-viral therapy. The child recovered with-out any sequelae and was discharged one week later. Present report highlights the importance of studying this emergent virus EV-D68 through prospective studies to understand the burden and epidemiological pattern in the country and its implications.


title: Does a low-cost carrier lead the domestic tourism demand and growth of New Zealand?

text: This study aims to provide a better understanding of the impact of New Zealand's low-cost carrier (LCC) on domestic tourism demand and growth. The panel data regression model and the two-stage least-square (2SLS) model (aims to control for the endogeneity effects) are used to empirically investigate the impact of LCC and the key determinants affecting New Zealand's domestic tourism using five regions (Auckland, Canterbury/Christchurch, Dunedin, Queenstown, and Wellington) from June 2009 to July 2015. The findings suggested that the LCC's services, GDP per capita, the regional tourism indicators (accommodation, and food and beverage), and land transport costs affected New Zealand's domestic tourism. The policy implications of the key finding regarding the significance of the LCC's operations on New Zealand's domestic tourism (local/regional tourism authorities and tourism operators), airline competition between incumbent airline (Air New Zealand) and the LCC (Jetstar), and airport authorities are discussed.


title: Production, purification, and evaluation of quail immunoglobulin Y against Salmonella typhimurium and Salmonella enteritidis

text: Abstract Salmonella species have been the major foodborne problems in food production systems, with Salmonella enterica serovars typhimurium (S. typhimurium) and enteritidis (S. enteritidis) being among the more common isolates. The oral administration of chicken egg yolk specific antibodies (IgYs) has been established as an efficient alternative for treatment and prevention of gastrointestinal pathogens including Salmonella. The present study was aimed to investigate the possible production of specific IgYs against Salmonella typhimurium and Salmonella enteritidis in quail egg yolks. Salmonella spp.-free female Japanese quails (Coturnix coturnix japonica) were intramuscularly immunized with formalin or heat-inactivated Salmonella immunogens (1.0 × 109 CFU/mL) emulsified with Freund adjuvants. Egg yolk IgYs were purified using ammonium sulfate precipitation method. Anti-Salmonella IgYs titer and specificity were determined using enzyme-linked immunosorbent assay (ELISA) and western blot analysis. Salmonella specific IgYs detected in the immunized quails were significantly higher than those of the control group, which confirmed the immunization procedure. Specific IgYs against S. typhimurium and S. enteritidis were identified in both groups immunized with heat or formalin-inactivated immunogens. However, formalin-inactivated immunogens induced relatively higher immune responses over the heat-inactivated ones. Quail anti-Salmonella IgYs showed a high specificity to their corresponding immunogens, with moderate cross-reactivity to other members of Enterobacteriaceae family. Quail can be regarded as a valuable and inexpensive source for producing large-scale of specific antibodies that can be used for immunodiagnostic and immunotherapeutic purposes.


title: How Architecture Fails in Conditions of Crisis: a Discussion on the Value of Interior Design over the COVID-19 Outbreak

text: Architecture, that was invented to offer shelter and security from critical natural conditions, is nowadays required to come for the rescue. But it fails. Fight-or-flight is the reaction to danger for survival in the jungle. Humans are part of this. Although some humans are able to remain indoors in critical life-threatening conditions, some others rush towards a new—seemingly natural—horizon, i.e., a village or an island. Is it that architecture in cities fails in offering the adequate natural environmental conditions in order to keep its population indoors or might this behavior be attributed to a more complicated archetypical reason? The best way out of a crisis like COVID-19 is through dwelling indoors. Humans have lived longer in nature than indoors over the timespan of their existence and this might be one of the reasons why some members of society flee towards it in conditions of crisis. However, is this truly the case?


title: The Gut Microbiota-Host Partnership as a Potential Driver of Kawasaki Syndrome

text: Kawasaki syndrome (KS) is a necrotizing vasculitis of small- and medium-sized vessels mostly affecting children under 5 years of age; a host of clinical and epidemiological data supports the notion that KS might result from an infectious disease. However, many efforts have failed to identify a potentially universal trigger of KS. The contribution of the intestinal microbial community—called the “microbiota”—to KS has been evaluated by an increasing number of studies, though limited to small cohorts of patients. Differences in the microbiota composition were found in children with KS, both its acute and non-acute phase, with abnormal colonization by Streptococcus species in the intestinal tract and a wider presence of Gram-positive cocci in jejunal biopsies. In particular, a higher number of Gram-positive cocci (of the genera Streptococcus and Staphylococcus), Eubacterium, Peptostreptococcus, and HSP60-producing Gram-negative microbes have been found in the stools of KS children, and their effects on the antigenic repertoire of specific T cells and Vβ2 T cell expansion have been assessed. Conversely, Lactobacilli were lacking in most children with KS compared with other febrile illnesses and healthy controls. All studies available to date have confirmed that an imbalance in the gut microbiota might indirectly interfere with the normal function of innate and adaptive immunity, and that variable microbiota interactions with environmental factors, mainly infectious agents, might selectively drive the development of KS in genetically susceptible children. Further investigations of the intestinal microflora in larger cohorts of KS patients will provide clues to disentangle the pathogenesis of this disease and probably indicate disease-modifying agents or more rational KS-specific therapies.


From crisis to utopia: crafting new public–private articulation at territorial level to design sustainable food systems


title: Seroprevalence and risk factors for infection with equine coronavirus in healthy horses in the USA

text: Abstract Equine coronavirus (ECoV) is considered an enteric pathogen of foals and has only recently been associated with infections in adult horses. Seroprevalence data is needed to better understand the epidemiology of ECoV in adult horses, evaluate diagnostic modalities and develop preventive measures. The objective of this study was to investigate the seroprevalence and selective risk factors for ECoV in 5247 healthy adult horses in the USA, using a recently established and validated IgG enzyme-linked immunosorbent assay. Prevalence factors analysed in this study included geographic region, age, breed, sex and use. A total of 504/5247 horses (9.6%) horses tested seropositive. Geographic region (Mid-West; P = 0.008), breed (Draft horses; P = 0.003) and specific uses of horses (ranch/farm, P = 0.034; breeding use, P = 0.016) were all statistically significant risk factors for seropositivity.


title: Myasthenic crisis in COVID-19

text: • Myasthenic crises is a potentially severe complication of COVID-19. • Hydroxychloroquine can aggravate myasthenia crises. • IVIg is a potential treatment for both Myasthenic crises and COVID-19. • IVIg treatment may cause thrombosis in susceptible patients.


title: Dynamic change process of target genes by RT-PCR testing of SARS-Cov-2 during the course of a Coronavirus Disease 2019 patient

text: Abstract We report the dynamic change process of target genes by RT-PCR testing of SARS-Cov-2 during the course of a COVID-19 patient: from successive negative results to successive single positive nucleocapsid gene, to two positive target genes (orf1ab and nucleocapsid) by RT-PCR testing of SARS-Cov-2, and describe the diagnosis, clinical course, and management of the case. In this case, negative results of RT-PCR testing was not excluded to diagnose a suspected COVID-19 patient, clinical signs and symptoms, other laboratory findings, and chest CT images should be taken into account for the absence of enough positive evidence. This case highlights the importance of successive sampling and testing SARS-Cov-2 by RT-PCR as well as the increased value of single positive target gene from pending to positive in two specimens to diagnose laboratory-confirmed COVID-19.


title: Efficient Reverse Genetic Systems for Rapid Genetic Manipulation of Emergent and Preemergent Infectious Coronaviruses

text: Emergent and preemergent coronaviruses (CoVs) pose a global threat that requires immediate intervention. Rapid intervention necessitates the capacity to generate, grow, and genetically manipulate infectious CoVs in order to rapidly evaluate pathogenic mechanisms, host and tissue permissibility, and candidate antiviral therapeutic efficacy. CoVs encode the largest viral RNA genomes at about 28–32,000 nucleotides in length, and thereby complicate efficient engineering of the genome. Deconstructing the genome into manageable fragments affords the plasticity necessary to rapidly introduce targeted genetic changes in parallel and assort mutated fragments while maximizing genome stability over time. In this protocol we describe a well-developed reverse genetic platform strategy for CoVs that is comprised of partitioning the viral genome into 5–7 independent DNA fragments (depending on the CoV genome), each subcloned into a plasmid for increased stability and ease of genetic manipulation and amplification. Coronavirus genomes are conveniently partitioned by introducing type IIS or IIG restriction enzyme recognition sites that confer directional cloning. Since each restriction site leaves a unique overhang between adjoining fragments, reconstruction of the full-length genome can be achieved through a standard DNA ligation comprised of equal molar ratios of each fragment. Using this method, recombinant CoVs can be rapidly generated and used to investigate host range, gene function, pathogenesis, and candidate therapeutics for emerging and preemergent CoVs both in vitro and in vivo.


Conducting phase 1 cancer clinical trials during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–related disease pandemic


Emergence of clear pathways for treatment of HIV/hepatitis co-infection


title: Human Respiratory Syncytial Virus and Streptococcus pneumoniae Infection in Wild Bonobos

text: Despite being important conservation tools, tourism and research may cause transmission of pathogens to wild great apes. Investigating respiratory disease outbreaks in wild bonobos, we identified human respiratory syncytial virus and Streptococcus pneumoniae as causative agents. A One Health approach to disease control should become part of great ape programs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10393-018-1319-4) contains supplementary material, which is available to authorized users.


title: Effective inhibition of hepatitis E virus replication in A549 cells and piglets by RNA interference (RNAi) targeting RNA-dependent RNA polymerase

text: Abstract RNA interference (RNAi) is a natural mechanism for suppressing or silencing expression of aberrant or foreign genes. It is a powerful antiviral strategy that has been widely employed to protect hosts from viral infection. Hepatitis E (HE) is an acute fulminant hepatitis in adults that has particularly high mortality in pregnant women. At this point in time, there is no vaccine or antiviral treatment that is effective against the infectious agent, HEV. The nonstructural polyprotein region possesses an RNA-dependent RNA polymerase (RdRp) that is responsible for the replication of the viral RNA genome. RdRp is therefore regarded as one of the most attractive candidates for RNA interference (RNAi). In the present study, the high efficiency and specificity of siRNA were evaluated by Real-Time quantitative PCR and Western blot assays. Protective effects against HEV infection were achieved in A549 cells and in piglets. In piglets treated with a shRNA-RdRp-1 expression plasmid prior to HEV inoculation, HEV antigens were significantly reduced in the liver, spleen, and kidneys, and the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were clearly decreased. These results suggested that RNAi is a potentially effective antiviral strategy against HEV replication and infection.


title: Primary structure and post-translational processing of the berne virus peplomer protein

text: Abstract The nucleotide sequence of the peplomer (P) protein gene of Berne virus (BEV), the torovirus prototype, was determined. The gene encodes an apoprotein of 1581 amino acids with an Mr of about 178K. The open reading frame was cloned behind the T7 RNA polymerase promoter and its translation product was identified as the BEV P protein precursor by in vivo expression and immunoprecipitation. The deduced amino acid sequence contains a number of domains which are typical for type I membrane glycoproteins: an N-terminal signal sequence, a putative C-terminal transmembrane anchor, and a cytoplasmic tail. Eighteen potential N-glycosylation sites, two heptad repeat domains, and a possible “trypsin-like” cleavage site were identified. The mature P protein consists of two subunits and their electrophoretic mobility upon endoglycosidase F treatment strongly suggests that the predicted cleavage site is functional in vivo. The heptad repeat domains are probably involved in the generation of an intra-chain coiled-coil secondary structure; similar inter-chain interactions can play a role in P protein oligomerization. Using a sucrose gradient assay the P protein was indeed shown to form dimers. The intra- and inter-chain coiled-coil interactions may stabilize the elongated BEV peplomers.


title: Henipaviruses: Emerging Paramyxoviruses Associated with Fruit Bats

text: Two related, novel, zoonotic paramyxoviruses have been described recently. Hendra virus was first reported in horses and thence humans in Australia in 1994; Nipah virus was first reported in pigs and thence humans in Malaysia in 1998. Human cases of Nipah virus infection, apparently unassociated with infection in livestock, have been reported in Bangladesh since 2001. Species of fruit bats (genus Pteropus ) have been identified as natural hosts of both agents. Anthropogenic changes (habitat loss, hunting) that have impacted the population dynamics of Pteropus species across much of their range are hypothesised to have facilitated emergence. Current strategies for the management of henipaviruses are directed at minimising contact with the natural hosts, monitoring identified intermediate hosts, improving biosecurity on farms, and better disease recognition and diagnosis. Investigation of the emergence and ecology of henipaviruses warrants a broad, cross-disciplinary ecosystem health approach that recognises the critical linkages between human activity, ecological change, and livestock and human health.


title: COVID-19 in Pregnant Women and Neonates: A Systematic Review of the Literature with Quality Assessment of the Studies

text: The SARS-CoV-2 virus emerged in December 2019 and then spread globally. Little is still known about the impact of COVID-19 on pregnant women and neonates. A review of the literature was performed according to the PRISMA guideline recommendations, searching the MEDLINE and EMBASE databases. Studies’ quality assessments were performed using the JBI Critical Appraisal Checklist. A total of 37 studies were included, involving 275 pregnant women with COVID-19 and 248 neonates. The majority of pregnant women presented with mild to moderate symptoms, only 10 were admitted in the ICU, and one died. Two stillbirths were reported and the incidence of prematurity was 28%. Sixteen neonates were tested positive for SARS-CoV-2 by RT-PCR, and nine of them were born from mothers infected during pregnancy. Neonatal outcomes were generally good: all the affected neonates recovered. RT-PCR for SARS-CoV-2 yielded negative results on amniotic fluid, vaginal/cervical fluids, placenta tissue, and breast milk samples. SARS-CoV-2 infection in pregnant women appeared associated with mild or moderate disease in most cases, with a low morbidity and mortality rate. The outcomes of neonates born from infected women were mainly favorable, although neonates at risk should be closely monitored. Further studies are needed to investigate the possibility of vertical transmission.


title: Implications of Host Genetic Variation on the Risk and Prevalence of Infectious Diseases Transmitted Through the Environment

text: Previous studies have shown that host genetic heterogeneity in the response to infectious challenge can affect the emergence risk and the severity of diseases transmitted through direct contact between individuals. However, there is substantial uncertainty about the degree and direction of influence owing to different definitions of genetic variation, most of which are not in line with the current understanding of the genetic architecture of disease traits. Also, the relevance of previous results for diseases transmitted through environmental sources is unclear. In this article a compartmental genetic–epidemiological model was developed to quantify the impact of host genetic diversity on epidemiological characteristics of diseases transmitted through a contaminated environment. The model was parameterized for footrot in sheep. Genetic variation was defined through continuous distributions with varying shape and degree of dispersion for different disease traits. The model predicts a strong impact of genetic heterogeneity on the disease risk and its progression and severity, as well as on observable host phenotypes, when dispersion in key epidemiological parameters is high. The impact of host variation depends on the disease trait for which variation occurs and on environmental conditions affecting pathogen survival. In particular, compared to homogeneous populations with the same average susceptibility, disease risk and severity are substantially higher in populations containing a large proportion of highly susceptible individuals, and the differences are strongest when environmental contamination is low. The implications of our results for the recording and analysis of disease data and for predicting response to selection are discussed.


Winning Together: Novel Coronavirus (COVID-19) Infographic


title: Exchange protein directly activated by cAMP encoded by the mammalian rapgef3 gene: Structure, function and therapeutics

text: Mammalian exchange protein directly activated by cAMP isoform 1 (EPAC1), encoded by the RAPGEF3 gene, is one of the two-membered family of cAMP sensors that mediate the intracellular functions of cAMP by acting as guanine nucleotide exchange factors for the Ras-like Rap small GTPases. Extensive studies have revealed that EPAC1-mediated cAMP signaling is highly coordinated spatiotemporally through the formation of dynamic signalosomes by interacting with a diverse array of cellular partners. Recent functional analyses of genetically engineered mouse models further suggest that EPAC1 functions as an important stress response switch and is involved in pathophysiological conditions of cardiac stresses, chronic pain, cancer and infectious diseases. These findings, coupled with the development of EPAC specific small molecule modulators, validate EPAC1 as a promising target for therapeutic interventions.


title: Dual Use of Biotechnology

text: Abstract This article addresses issues that are central to the dual use of biotechnology, such as the public perception of risk and the need for physical containment to prevent the release of potentially dangerous microorganisms. It also examines the public and media perception of the scientists who handle and manipulate these pathogens and discusses the controls that are currently in place to ensure that scientists engaged in defense-related dual-use medical research act in a transparent and ethical manner. Finally, the article discusses what can be done by scientists to allay the fears of their fellow citizens.


title: Population-Based Pertussis Incidence and Risk Factors in Infants Less Than 6 Months in Nepal

text: BACKGROUND: Pertussis is estimated to cause 2 percent of childhood deaths globally and is a growing public health problem in developed countries despite high vaccination coverage. Infants are at greatest risk of morbidity and mortality. Maternal vaccination during pregnancy may be effective to prevent pertussis in young infants, but population-based estimates of disease burden in infants are lacking, particularly in low-income countries. The objective of this study was to estimate the incidence of pertussis in infants less than 6 months of age in Sarlahi District, Nepal. METHODS: Nested within a population-based randomized controlled trial of influenza vaccination during pregnancy, infants were visited weekly from birth through 6 months to assess respiratory illness in the prior week. If any respiratory symptoms had occurred, a nasal swab was collected and tested with a multitarget pertussis polymerase chain reaction (PCR) assay. The prospective cohort study includes infants observed between May 2011 and August 2014. RESULTS: The incidence of PCR-confirmed Bordetella pertussis was 13.3 cases per 1000 infant-years (95% confidence interval, 7.7–21.3) in a cohort of 3483 infants with at least 1 day of follow-up. CONCLUSIONS: In a population-based active home surveillance for respiratory illness, a low risk for pertussis was estimated among infants in rural Nepal. Nepal’s immunization program, which includes a childhood whole cell pertussis vaccine, may be effective in controlling pertussis in infants.


Predicting the potential for within-flight transmission and global dissemination of MERS


Authors’ response: SARS-CoV-2 detection by real-time RT-PCR


title: A high-throughput inhibition assay to study MERS-CoV antibody interactions using image cytometry

text: Abstract The emergence of new pathogens, such as Middle East respiratory syndrome coronavirus (MERS-CoV), poses serious challenges to global public health and highlights the urgent need for methods to rapidly identify and characterize potential therapeutic or prevention options, such as neutralizing antibodies. Spike (S) proteins are present on the surface of MERS-CoV virions and mediate viral entry. S is the primary target for MERS-CoV vaccine and antibody development, and it has become increasingly important to understand MERS-CoV antibody binding specificity and function. Commonly used serological methods like ELISA, biolayer interferometry, and flow cytometry are informative, but limited. Here, we demonstrate a high-throughput protein binding inhibition assay using image cytometry. The image cytometry-based high-throughput screening method was developed by selecting a cell type with high DPP4 expression and defining optimal seeding density and protein binding conditions. The ability of monoclonal antibodies to inhibit MERS-CoV S binding was then tested. Binding inhibition results were comparable with those described in previous literature for MERS-CoV spike monomer and showed similar patterns as neutralization results. The coefficient of variation (CV) of our cell-based assay was <10%. The proposed image cytometry method provides an efficient approach for characterizing potential therapeutic antibodies for combating MERS-CoV that compares favorably with current methods. The ability to rapidly determine direct antibody binding to host cells in a high-throughput manner can be applied to study other pathogen-antibody interactions and thus can impact future research on viral pathogens.


title: The ontogeny of the porcine immune system

text: Cellular and humoral aspects of the immune response develop sequentially in the fetus. During the ontogeny, the pluripotent stem cells emerge and differentiate into all hematopoietic lineages. Basic questions including the identification of the first lympho-hematopoietic sites, the origin of T and B lymphocytes, the development of different subpopulations of αβ T, γδ T and B lymphocytes as well as development of innate immunity and the acquisition of full immunological capacities are discussed here for swine and compared with other species. The description of related topics such as fertilization, morphogenesis, maternal-fetal-neonatal physiology and early neonatal development are also discussed.


title: The Relationship between the COVID-19 Prevalence Trend and Transportation Trend in South Korea

text: Abstract Objective World Health Organization (WHO) declared a pandemic on March 12th, 2020. Several studies indicate that these densely populated urban environments and the heavy dependence on traffic could increase the potential spread of COVID-19. This study investigated the association between changes in traffic volume and the spread of COVID-19 in South Korea. Methods This study analyzed the daily national traffic and traffic trend for 3 months from January 1st, 2020. Traffic data was measured by the 6,307 vehicle detection system (VDS). This study analyzed the traffic gap between 2019 and 2020. And non-linear regression was performed to analyze the change in traffic trend in 2020. The relationship between traffic and COVID-19 confirmed cases was analyzed using single linear regression. Results The mean daily nationwide in 2020 was 143,655,563 vehicles, which was 9.7% lower than the same period in 2019 (159,044,566 vehicles). All regions showed a decreasing trend for traffic in February, which shifted to an increasing trend from March. In Incheon, there only was a positive but insignificant (β = 43,146, p = .056) linear relationship with the increasing numbers of new confirmed cases associated with increased traffic. Conclusions New confirmed COVID-19 patients have been decreasing since March, while the traffic has been increasing. Particularly, the fact that traffic is increasing indicates greater contact between people, which in turn increases the risk of COVID-19 spread. Therefore, the government will need to devise suitable policies, such as total social distancing.


title: Structural Basis of Nanobodies Targeting the Prototype Norovirus

text: Human norovirus infections are a major disease burden. In this study, we analyzed three new norovirus-specific Nanobodies that interacted with the prototype human norovirus (i.e., genogroup I genotype 1 [GI.1]). We showed that the Nanobodies bound on the side (Nano-7 and Nano-62) and top (Nano-94) of the capsid-protruding (P) domain using X-ray crystallography. Nano-7 and Nano-62 bound at a similar region on the P domain, but the orientations of these two Nanobodies clashed with the shell (S) domain and neighboring P domains on intact particles. This finding suggested that the P domains on the particles should shift in order for Nano-7 and Nano-62 to bind to intact particles. Interestingly, both Nano-7 and Nano-94 were capable of blocking norovirus virus-like particles (VLPs) from binding to histo-blood group antigens (HBGAs), which are important cofactors for norovirus infection. Previously, we showed that the GI.1 HBGA pocket could be blocked with the soluble human milk oligosaccharide 2-fucosyllactose (2′FL). In the current study, we showed that a combined treatment of Nano-7 or Nano-94 with 2′FL enhanced the blocking potential with an additive (Nano-7) or synergistic (Nano-94) effect. We also found that GII Nanobodies with 2′FL also enhanced inhibition. The Nanobody inhibition likely occurred by different mechanisms, including particle aggregation or particle disassembly, whereas 2′FL blocked the HBGA binding site. Overall, these new data showed that the positive effect of the addition of 2′FL was not limited to a single mode of action of Nanobodies or to a single norovirus genogroup. IMPORTANCE The discovery of vulnerable regions on norovirus particles is instrumental in the development of effective inhibitors, particularly for GI noroviruses that are genetically diverse. Analysis of these GI.1-specific Nanobodies has shown that similar to GII norovirus particles, the GI particles have vulnerable regions. The only known cofactor region, the HBGA binding pocket, represents the main target for inhibition. With a combination treatment, i.e., the addition of Nano-7 or Nano-94 with 2′FL, the effect of inhibition was increased. Therefore, combination drug treatments might offer a better approach to combat norovirus infections, especially since the GI genotypes are highly diverse and are continually changing the capsid landscape, and few conserved epitopes have so far been identified.


title: Histological findings in chilblain‐lupus like COVID lesions: in search of an answer to understand their etiology

text: We read with great interest the article by Piccolo et al(1). describing chilblain‐like lesions (CLL) on feet and hands during the COVID‐19 Pandemic. They mention the rate of association to autoimmune conditions was very low, which led the to exclude a note autoimmune disorder as main cause of CLL. Here, we hypothesize the possible relationship between the development of these lesions and immune‐chained phenomena following viral infection in a certain group of patients.


title: Covid-19 And The Uk Labour Market

text: This article considers policy responses to the COVID-19 crisis as they affect the labour market, how these policies are evolving and some of the design issues they face. The concentration is on the UK, but other countries are also discussed for comparative purposes. The Job Retention Scheme is a successful innovation to keep temporarily stopped workers attached to their employers. However, since economic recovery will be slow, it is not sustainable in its current form. A sustained rise in unemployment is inevitable and alternative policies to mitigate this and the dangers of scarring are discussed. The structure of output will change, as therefore will the composition of jobs. A comprehensive active manpower policy will be needed to efficiently match job seekers to available jobs. The young are likely to suffer disproportionately from the recession and this makes it essential to introduce radical policies to boost work-based training and to enhance the contribution made by further and higher education institutions.


title: Knowledge and information sources on standard precautions and infection control of health sciences students at King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia, Riyadh

text: Abstract Background Only one study has been conducted in Saudi Arabia to assess medical students’ knowledge of standard precautions (SPs) and infection control (IC). In this study, we examined knowledge of SPs and IC among clinical students attending the King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. Methods In this cross-sectional study, we targeted clinical students from the following five colleges: Medicine (fifth and sixth years); Dentistry (second semester of the third, fourth, fifth, and sixth years); Applied Medical Sciences (third and fourth years); Nursing (third and fourth years); and Pharmacy (third, fourth, and fifth years). The data collection instrument was an adopted 41-item questionnaire that measured knowledge of SPs and IC in five domains. A score of ≥24 (60%) indicated sufficient knowledge. Results The participants comprised 129 students (67 men). The proportions of participants from each college were: Medicine, 58.1% (n =75); Dentistry, 14% (n =18); Applied Medical Sciences, 13.2% (n =17); Nursing, 10.9% (n =14); and Pharmacy, 3.9% (n =5). Most students (73.6%) demonstrated sufficient knowledge (men, 67.2% and women, 80.6%). The highest scores were obtained for the domains “general concept of SPs”, “hand hygiene”, and “personal protective equipment”, whereas the lowest scores were obtained for “disposal of and injuries from sharp objects” and “health-care providers’ care”. The main information source was formal curricular teaching. Conclusions In Saudi Arabia, students’ knowledge of SPs and IC is satisfactory, with no significant differences between the sexes or between colleges. Thus, formal curricular teaching is an effective way to increase students’ knowledge of SPs and IC.


title: Genomic characterization of a proventriculitis-associated infectious bronchitis coronavirus

text: Transmissible proventriculitis associated with infectious bronchitis virus (IBV) was at first seen in eastern China in mid-1995, and is now endemic in China. Herein, the complete genome sequence of a proventiculitis-associated infectious bronchitis coronavirus (ZJ971) was sequenced and analyzed. Compared with the genome of the vaccine strain H120, ZJ971 had 54 nucleotide substitutions and a deletion in the 3′-UTR. The substitutions were in the regions of nsp2–nsp5, nsp7, nsp12, nsp13, nsp15, S and N genes, and the untranslating region. The results indicated that ZJ971 could be a variant of IBV strain H120.


title: RNA sequencing demonstrates large-scale temporal dysregulation of gene expression in stimulated macrophages derived from MHC-defined chicken haplotypes

text: Discovering genetic biomarkers associated with disease resistance and enhanced immunity is critical to developing advanced strategies for controlling viral and bacterial infections in different species. Macrophages, important cells of innate immunity, are directly involved in cellular interactions with pathogens, the release of cytokines activating other immune cells and antigen presentation to cells of the adaptive immune response. IFNγ is a potent activator of macrophages and increased production has been associated with disease resistance in several species. This study characterizes the molecular basis for dramatically different nitric oxide production and immune function between the B2 and the B19 haplotype chicken macrophages.A large-scale RNA sequencing approach was employed to sequence the RNA of purified macrophages from each haplotype group (B2 vs. B19) during differentiation and after stimulation. Our results demonstrate that a large number of genes exhibit divergent expression between B2 and B19 haplotype cells both prior and after stimulation. These differences in gene expression appear to be regulated by complex epigenetic mechanisms that need further investigation.