title: Establishment of Primary Transgenic Human Airway Epithelial Cell Cultures to Study Respiratory Virus–Host Interactions

text: Primary human airway epithelial cell (hAEC) cultures represent a universal platform to propagate respiratory viruses and characterize their host interactions in authentic target cells. To further elucidate specific interactions between human respiratory viruses and important host factors in the airway epithelium, it is important to make hAEC cultures amenable to genetic modification. However, the short and finite lifespan of primary cells in cell culture creates a bottleneck for the genetic modification of these cultures. In the current study, we show that the incorporation of the Rho-associated protein kinase (ROCK) inhibitor (Y-27632) during cell propagation extends the life span of primary human cells in vitro and thereby facilitates the incorporation of lentivirus-based expression systems. Using fluorescent reporters for fluorescence-activated cell sorting (FACS)-based sorting, we generated homogenously fluorescent hAEC cultures that differentiate normally after lentiviral transduction. As a proof-of-principle, we demonstrate that host gene expression can be modulated post-differentiation via inducible short hairpin (sh)RNA-mediated knockdown. Importantly, functional characterization of these transgenic hAEC cultures with exogenous poly (I:C), as a proxy for virus infection, demonstrates that such modifications do not influence the host innate immune response. Moreover, the propagation kinetics of both human coronavirus 229E (HCoV-229E) and human respiratory syncytial virus (hRSV) were not affected. Combined, these results validate our newly established protocol for the genetic modification of hAEC cultures, thereby unlocking a unique potential for detailed molecular characterization of virus–host interactions in human respiratory epithelium.


title: The impact of COVID‐19 on the grains and oilseeds sector

text: While downstream distribution and demand is likely to be hampered by the labour and income effects of COVID‐19, Canada is expected to produce over 88 million tonnes of grains and oilseeds in 2020. Canadians have valid concerns about delays related to their changing needs as millions move their purchases from food services to retail groceries, but they should not worry about our overall supply of calories. Despite some shortages, the supply chains for flour and cooking oil are not likely to be blocked for an extended period. Learning from the coordinated needs of the BSE crisis in the beef sector, the federal government developed Value Chain Roundtables in 2003, including one for grains. These roundtables bring together government and industry to tackle the issues that face each sector's major needs, including food safety, transportation infrastructure, and market access. A working group made up of various roundtable members was set up specifically to deal with COVID‐19‐related supply chain challenges. This gives both industry and government a venue to attack any choke point or breakdown within our agri‐food supply chains – the exact response we need at this time. A pre‐established forum for discussion of critical issues at these roundtables, assuming the right players are active and present, cannot hurt, but it would useful for future planners and researchers if the federal government could clarify any positive impact they have. This article is protected by copyright. All rights reserved


title: Personal protective equipment and possible routes of airborne spread during the COVID‐19 pandemic

text: We welcomed Professor Cook's article clarifying the use of personal protective equipment (PPE) in protecting staff during the current COVID-19 pandemic [1]. There remains considerable debate about the extent to which airborne spread of SARS-CoV-2 occurs. Small droplets (< 5µm) are thought to remain suspended in the air and could theoretically be inhaled into the lungs causing infection [2]. Loose fitting "surgical" masks will not prevent such inhalation and only a tight-fitting filtering mask is adequate. Conversely larger (> 5µm) particles do not remain suspended in the air [2] and can only cause infection if they are immediately inhaled, or after contact with a surface they land on.


title: Coronavirus infectious bronchitis virus non-structural proteins 8 and 12 form stable complex independent of the non-translated regions of viral RNA and other viral proteins

text: Abstract The cleavage products from coronavirus polyproteins, known as the non-structural proteins (nsps), are believed to make up the major components of the viral replication/transcription complex. In this study, several nsps encoded by avian gammacoronavirus infectious bronchitis virus (IBV) were screened for RNA-binding activity and interaction with its RNA-dependent RNA polymerase, nsp12. Nsp2, nsp5, nsp8, nsp9 and nsp10 were found to bind to untranslated regions (UTRs), while nsp8 was confirmed to interact with nsp12. Nsp8 has been reported to interact with nsp7 and functions as a primase synthesizing RNA primers for nsp12. Further characterization revealed that nsp8-nsp12 interaction is independent of the UTRs of viral RNA, and nsp8 interacts with both the N- and C-terminal regions of nsp12. These results have prompted a proposal of how the nsp7-nsp8 complex could possibly function in tandem with nsp12, forming a highly efficient complex that could synthesize both the RNA primer and viral RNA during coronavirus infection.


title: Human parainfluenza virus infection in severe acute respiratory infection cases in Beijing, 2014‐2016: A molecular epidemiological study

text: BACKGROUND: Severe acute respiratory infection (SARI) threatens human health and even survival, causing a huge number of hospitalized patients every year. However, as one of the most common respiratory viruses circulated worldwide, the epidemiological and phylogenetic characteristics of human parainfluenza virus (HPIV) in these cases were not well known. OBJECTIVES: To reveal the epidemiological features of HPIV infection in SARIs in Beijing area from September 2014 to August 2016. METHODS: A total of 1229 SARI cases in Beijing area were enrolled, investigated, sampled, and tested by multiplex real‐time PCR to identify HPIVs and other common respiratory viruses. Eighteen HPIV‐3 viruses isolated from all HPIV‐positive samples in these SARI cases were sequenced and analyzed. RESULTS: Among all enrolled cases, 0.81%, 0.73%, 4.48%, and 0.57% were positive for HPIV‐1 to HPIV‐4, respectively. The highest yield rate of HPIV infection occurred in children under 5 years old (9.07%), followed by the patients over 60 years old (6.02%). The phylogenetic information of HPIV‐3 showed that all viruses belonged to Cluster C3a. CONCLUSIONS: Besides the young children, the elders older than 60 years also showed a relatively high infection rate of HPIVs, which should be given comparable attentions. Moreover, the HPIV‐3 circulating in China undergoes continued evolution, suggesting the potential risk of evolved HPIV infection should not be overlooked.


title: Influence of country of study on student responsiveness to the H1N1 pandemic

text: Summary Objectives University students, both travelling abroad on holiday or exchange students entering a country, can serve as mobile carriers of infectious diseases during a pandemic, and thus require special attention when considering preventive measures. The objectives of this study were to evaluate student compliance and opinions on preventive measures of a university before and during an H1N1 influenza pandemic, and to explore environmental and behavioural factors that might contribute towards compliance. Study design Cross-sectional, self-administered questionnaire. Methods Local and foreign students attending an international summer school programme were invited to participate in a self-administered survey. Results Respondents complied with most of the preventive measures, excluding website viewing and mask wearing. Significant differences in compliance and perceived necessity were found amongst students from Singapore, Hong Kong and the USA. Singaporean students were significantly more likely to comply with all measures and consume antiviral medication in response to the pandemic than students studying in the US. Conclusions Students’ responses towards university pandemic measures were largely positive, but sensitivity towards these measures varied between groups by country of study. This should be considered in further comparative studies.


title: Review of Initiatives and Methodologies to Reduce CO(2) Emissions and Climate Change Effects in Ports

text: Ports are important infrastructures for economic growth and development. Among the most significant environmental aspects of ports that contribute to the issue of climate change are those due to carbon dioxide emissions generated by port activities. Given the importance of this topic, this paper gathers initiatives and methodologies that have been undertaken to calculate and reduce CO(2) emissions and climate change effects in ports. After studying these methodologies, their strengths and opportunities for further enhancement have been analyzed. The results show that, in recent years, several ports have started to calculate their carbon footprint and report it. However, in some of the cases, not all the sources of GHG gases that are occurring actually in ports are taken into account, such as emissions from waste treatment operations and employees’ commuting. On other occasions, scopes are not defined following standard guidelines. Furthermore, each authority or operator uses its own method to calculate CO(2) emissions, which makes the comparison of results difficult. For these reasons, this paper suggests the need for creating a standardized tool to calculate carbon footprint in ports, which will make it possible to establish a benchmark and a potential comparison of results among ports.


title: Coronavirus disease 2019 (COVID-19) in the radiology department: What radiographers need to know

text: OBJECTIVES: The aim is to review current literature related to the diagnosis, management, and follow-up of suspected and confirmed Covid-19 cases. KEY FINDINGS: Medical Imaging plays an important auxiliary role in the diagnosis of Covid-19 patients, mainly those most seriously affected. Practice differs widely among different countries, mainly due to the variability of access to resources (viral testing and imaging equipment, specialised staff, protective equipment). It has been now well-documented that chest radiographs should be the first-line imaging tool and chest CT should only be reserved for critically ill patients, or when chest radiograph and clinical presentation may be inconclusive. CONCLUSION: As radiographers work on the frontline, they should be aware of the potential risks associated with Covid-19 and engage in optimal strategies to reduce these. Their role in vetting, conducting and often reporting the imaging examinations is vital as well as their contribution in patient safety and care. Medical Imaging should be limited to critically ill patients, and where it may have an impact on the patient management plan. IMPLICATIONS FOR PRACTICE: At the time of publication, this review offers the most up-to-date recommendations for clinical practitioners in radiology departments, including radiographers. Radiography practice has to significantly adjust to these new requirements to support optimal and safe imaging practices for the diagnosis of Covid-19. The adoption of low dose CT, rigorous infection control protocols and optimal use of personal protective equipment may reduce the potential risks of radiation exposure and infection, respectively, within Radiology departments.


title: Recent increase of surface particulate matter concentrations in the Seoul Metropolitan Area, Korea

text: Recent changes of surface particulate matter (PM) concentration in the Seoul Metropolitan Area (SMA), South Korea, are puzzling. The long-term trend of surface PM concentration in the SMA declined in the 2000s, but since 2012 its concentrations have tended to incline, which is coincident with frequent severe hazes in South Korea. This increase puts the Korean government’s emission reduction efforts in jeopardy. This study reports that interannual variation of surface PM concentration in South Korea is closely linked with the interannual variations of wind speed. A 12-year (2004–2015) regional air quality simulation was conducted over East Asia (27-km) and over South Korea (9-km) to assess the impact of meteorology under constant anthropogenic emissions. Simulated PM concentrations show a strong negative correlation (i.e. R = −0.86) with regional wind speed, implying that reduced regional ventilation is likely associated with more stagnant conditions that cause severe pollutant episodes in South Korea. We conclude that the current PM concentration trend in South Korea is a combination of long-term decline by emission control efforts and short-term fluctuation of regional wind speed interannual variability. When the meteorology-driven variations are removed, PM concentrations in South Korea have declined continuously even after 2012.


title: The effect of travel restrictions on the spread of a moderately contagious disease

text: BACKGROUND: Much research in epidemiology has been focused on evaluating conventional methods of control strategies in the event of an epidemic or pandemic. Travel restrictions are often suggested as an efficient way to reduce the spread of a contagious disease that threatens public health, but few papers have studied in depth the effects of travel restrictions. In this study, we investigated what effect different levels of travel restrictions might have on the speed and geographical spread of an outbreak of a disease similar to severe acute respiratory syndrome (SARS). METHODS: We used a stochastic simulation model incorporating survey data of travel patterns between municipalities in Sweden collected over 3 years. We tested scenarios of travel restrictions in which travel over distances >50 km and 20 km would be banned, taking into account different levels of compliance. RESULTS: We found that a ban on journeys >50 km would drastically reduce the speed and geographical spread of outbreaks, even when compliance is < 100%. The result was found to be robust for different rates of intermunicipality transmission intensities. CONCLUSION: This study supports travel restrictions as an effective way to mitigate the effect of a future disease outbreak.


title: Human DNA tumor viruses and oncogenesis

text: DNA tumor viruses induce tumors in animals and humans by transforming the infected host cells. These oncogenic viruses encode viral proteins, which deregulate the integrated framework of host cellular processes, while preventing cell death. Studies revealed newer insights as to how specific tumor targets could be modulated for tumor therapy.


title: Myeloablation-associated deletion of 0RF4 in a human coronavirus 229E infection

text: We describe metagenomic next-generation sequencing (mNGS) of a human coronavirus 229E from a patient with AML and persistent upper respiratory symptoms, who underwent hematopoietic cell transplantation (HCT). mNGS revealed a 548-nucleotide deletion, which comprised the near entirety of the 0RF4 gene, and no minor allele variants were detected to suggest a mixed infection. As part of her pre-HCT conditioning regimen, the patient received myeloablative treatment with cyclophosphamide and 12 Gy total body irradiation. Iterative sequencing and RT-PCR confirmation of 4 respiratory samples over the 4-week peritransplant period revealed that the pre-conditioning strain contained an intact 0RF4 gene, while the deletion strain appeared Just after conditioning and persisted over a 2.5-week period. This sequence represents one of the largest genomic deletions detected in a human RNA virus and is the first description of large-scale viral mutation associated with myeloablation for HCT.


title: How Inhomogeneous Site Percolation Works on Bethe Lattices: Theory and Application

text: Inhomogeneous percolation, for its closer relationship with real-life, can be more useful and reasonable than homogeneous percolation to illustrate the critical phenomena and dynamical behaviour of complex networks. However, due to its intricacy, the theoretical framework of inhomogeneous percolation is far from being complete and many challenging problems are still open. In this paper, we first investigate inhomogeneous site percolation on Bethe Lattices with two occupation probabilities, and then extend the result to percolation with m occupation probabilities. The critical behaviour of this inhomogeneous percolation is shown clearly by formulating the percolation probability [Image: see text] with given occupation probability p, the critical occupation probability [Image: see text], and the average cluster size [Image: see text] where p is subject to [Image: see text]. Moreover, using the above theory, we discuss in detail the diffusion behaviour of an infectious disease (SARS) and present specific disease-control strategies in consideration of groups with different infection probabilities.


title: COVID19 Infection in Health Care Professionals: Risks, Work-Safety and Psychological Issues

text: COVID-19 infection has spread widely over past 5 months to become a pandemic of global proportions affecting almost every country. While HCPs are expected to tackle this crisis by working in hospital and intensive care setting, there is real risk of them contracting infection and even dying. This article aims to report cases of healthcare personnel (HCPs) contracting COVID19 in various settings in a tertiary care hospital, a designated COVID centre, with view to disseminate information and review safety and psychological health issues of healthcare professionals. This study is a cross-sectional hospital-based survey from April 2020-June 2020. Data on demographics, workplace safety and psychological parameters from HCPs was collected by both interview and an online questionnaire form. A total of 40 healthcare workers were infected in the hospital in a period of 2 months since the first COVID case was admitted in the hospital. Almost 57.5% reported positive on several psychological parameters like anxiety, fear, anger, irritability and insomnia. About 42.5% had no psychological counselling after testing positive. These cases illustrate work-place risks for healthcare workers of acquiring COVID19 and highlight the problems faced in terms of risks of transmission to patients and colleagues, isolation of contacts in departments leading to near-breakdown of services and psychological stress to healthcare workers. Healthcare workers being at frontline of exposure to corona patients are at increased risk of developing COVID19 infections. Healthcare workers are working under tremendous stress in this pandemic and it is necessary to combat fear with facts and work towards safe work atmosphere so that they can discharge their duties to best of their ability.


title: Outbreak of COVID-19: An emerging global pandemic threat

text: Since the first outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Wuhan, Hubei, China in December 2019, it is now recognized as a pandemic by the World Health Organization (WHO) as more than 200 countries and territories worldwide are affected with an increasing incidence. The SARS-CoV-2 infection results in a spectrum of non-specific signs and symptoms, ranging from asymptomatic infection, to flu-like illness such as fever, cough, dry cough and fatigue, to pneumonia, acute respiratory distress syndrome, and even multi-organ failures with high morbidity and mortality. SARS-CoV-2 is mainly transmitted through respiratory droplets that infected people exhale during incubation and onset period. By 12 June 2020, over 7.5 million confirmed cases of Coronavirus disease 2019 (COVID-19) with more than 421,000 deaths in the world have been reported to the WHO. No specific medication is approved to treat COVID-19, raising the urgent need for antiviral drug development. By 12 June 2020, there are over 1000 clinical trials registered in clinicaltrials.gov for treatment of COVID-19. This review summarizes the epidemiology, virology, clinical presentation, pathophysiology, diagnosis, and particularly the antiviral drugs currently under clinical trials for treatment of SARS-CoV-2 infection, together with the challenges and perspectives of this disease are also discussed.


title: Emerging Ferret Diseases

text: Abstract There are a number of newly described and emerging disease syndromes affecting the domestic ferret, and the purpose of this article is to make veterinarians aware of these diseases. A recently described systemic coronavirus infection appears to be a variant of the ferret enteric coronavirus and is currently termed “ferret infectious peritonitis.” Disseminated immunopathologic myositis, aplastic anemia/bone marrow aplasia, acute hemorrhagic syndrome, and oral ulcerations are also described, although the exact etiologies for these diseases have yet to be determined. There appears to be at least 2 important amino acid metabolism deficiencies in ferrets: hindlimb weakness in older ferrets (L-carnitine) and cysteine urolithiasis. Ferrets have recently been found to be susceptible to H1N1 influenza, so knowledge regarding this zoonotic disease is essential for veterinarians working with these animals. A novel Mycoplasma spp. has also recently been identified in ferrets with chronic respiratory problems that originated from one breeding colony. Because these diseases are still being investigated, practitioners who treat a ferret patient exhibiting clinical signs consistent with any of the conditions mentioned are encouraged to contact people who are knowledgeable of that particular illness.


title: PRRSV structure, replication and recombination: Origin of phenotype and genotype diversity

text: Abstract Porcine reproductive and respiratory disease virus (PRRSV) has the intrinsic ability to adapt and evolve. After 25 years of study, this persistent pathogen has continued to frustrate efforts to eliminate infection of herds through vaccination or other elimination strategies. The purpose of this review is to summarize the research on the virion structure, replication and recombination properties of PRRSV that have led to the extraordinary phenotype and genotype diversity that exists worldwide.


title: SARS and its impact on current and future Emergency Department operations

text: A long-standing concern for international spread of new, virulent pathogens became a reality with the advent of Severe Acute Respiratory Syndrome (SARS). This respiratory syndrome, caused by a coronavirus, spread rapidly across 30 nations since its first recognition in late 2002. SARS has presented the greatest recent threat to U.S. public health, and has come at a time when purposeful introduction of pathogens by terrorists is also of heightened concern. SARS has forced the international medical establishment to reexamine how best to manage such incidents.


docid: bslkogub

title: Globalization and Infectious Diseases

text: This article discusses the nature of the health challenges created by globalization and proposes new forms of international cooperation to confront them. The discussion of global health challenges includes both the transfer of health risks, with an emphasis on infectious diseases, and the international dissemination of health opportunities, including the transfer of knowledge and technology. The authors argue that the health-related challenges and opportunities of an increasingly interdependent world demand new forms of international cooperation. The authors suggest the promotion of 3 elements that, in their essence, contain the idea of collaboration: exchange, evidence, and empathy.


title: An antifungal defensin from Phaseolus vulgaris cv. ‘Cloud Bean’

text: Abstract An antifungal peptide with a defensin-like sequence and exhibiting a molecular mass of 7.3kDa was purified from dried seeds of Phaseolus vulgaris ‘Cloud Bean’. The isolation procedure entailed anion exchange chromatography on DEAE-cellulose, affinity chromatography an Affi-gel blue gel, cation exchange chromatography on SP-Sepharose, and gel filtration by fast protein liquid chromatography on Superdex 75. Although the antifungal peptide was unadsorbed on DEAE-cellulose, it was adsorbed on both Affi-gel blue gel and SP-Sepharose. The antifungal peptide exerted antifungal activity against Mycosphaerella arachidicola with an IC50 value of 1.8μM. It was also active against Fusarium oxysporum with an IC50 value of 2.2μM. It had no inhibitory effect on HIV-1 reverse transcriptase when tested up to 100μM. Proliferation of L1210 mouse leukemia cells and MBL2 lymphoma cells was inhibited by the antifungal peptide with an IC50 of 10μM and 40μM, respectively.


title: Disparate Effects of Acute and Chronic Infection with SIVmac239 or SHIV-89.6P on Macaque Plasmacytoid Dendritic Cells

text: Blood plasmacytoid dendritic cells (pDCs) contribute to both innate and adaptive immune responses by secreting high levels of IFN-α following acute bacterial and viral infections and indirectly by augmenting cell-mediated immunity. Cross-sectional studies have shown that the number of circulating pDCs in HIV patients, compared to that in uninfected individuals, is reduced. However, since the time of infection is usually unknown in HIV-infected patients, pDC-virus interactions that occur immediately after virus exposure are poorly understood. The current study investigated pDC dynamics during acute and chronic infections of macaques with either SIVmac239 or the pathogenic SIV-HIV chimera, SHIV-89.6P, as models for HIV infection. In three rhesus and three pig-tailed macaques infected intravenously with SIVmac239, the percentages of pDCs in blood declined 2- to 6-fold during the first 6 weeks after infection and remained depressed throughout the disease course. Surprisingly, no consistent, comparable decline in peripheral blood pDCs was observed in six macaques infected with SHIV-89.6P. In this latter group, percentages of pDCs did not correlate with CD4(+) T cells, but there was an inverse relationship with viral load. In addition, when compared to naïve controls, the percentages of pDCs were reduced in spleens and peripheral lymph nodes of SIVmac239- but not SHIV-89.6P-infected animals that had progressed to AIDS. Proviral DNA was detected during the acute phase in pDCs isolated from macaques infected with either virus. These results imply that, even though macaque pDCs can be infected by both SIVmac239 and SHIV-89.6P, the subsequent effects on in vivo pathogenesis differ. The underlying mechanism(s) for these differences is unclear, but the selection of SIV or SHIV as a challenge virus might influence the outcome of some studies, such as those evaluating vaccines or the therapeutic efficacy of drugs.


Curso atípico o incompleto de la enfermedad de Kawasaki en edades pediátricas


docid: czheitbc

title: A poxvirus-based vaccine reduces virus excretion after MERS coronavirus infection in dromedary camels


title: Impact of MBL and MASP-2 gene polymorphism and its interaction on susceptibility to tuberculosis

text: BACKGROUND: Mannose-binding lectin (MBL) and MBL-associated serine proteases 2 (MASP-2) are important proteins in the lectin pathway of the immune system. Polymorphism of MBL and MASP-2 genes may affect the serum concentration of MBL and MASP-2. This study explores the association between MBL and MASP-2 gene polymorphism and their interactions and the susceptibility to tuberculosis (TB). METHOD: A total of 503 patients with TB and 419 healthy controls were recruited to participate in this case-control study. PCR-SSP technology was applied to genotype rs7096206 of MBL genes and rs2273346 and rs6695096 of MASP-2 genes. Demographic data and some exposure information were also obtained from study participants. Unconditional logistic regression analysis was used to identify association between the various factors and TB whilst Marginal Structural Linear Odds Models were used to estimate the interactions. RESULTS: Both genotype GC at rs7096206 of MBL genes and genotype TC at rs2273346 and rs6695096 of MASP-2 genes were more prevalent in the TB patient group than the healthy control group (P < 0.05, OR 1.393, 1.302 and 1.426 respectively). The relative excess risk of interaction (RERI) between rs7096206 of MBL genes and rs2273346 and rs6695096 of MASP-2 genes was 0.897 (95% CI: 0.282, 1.513) and 1.142 (95% CI: 0.755, 1.530) respectively (P < 0.05). CONCLUSION: Polymorphisms of MBL (rs7096206) and MASP-2 (rs2273346 and rs6695096) were associated with the susceptibility of TB, and there were gene-gene interactions among them.


title: Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

text: Photodynamic inactivation (PDI) has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i) summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii) discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process.


title: Epidemiologie des Ebolafiebers und anderer, in Deutschland seltener hochkontagiöser, lebensbedrohlicher Erkrankungen

text: Apart from sporadic exported cases, the occurrence of Ebola, Marburg and Lassa virus diseases is limited to the African continent. Crimean-Congo Hemorrhagic Fever occurs in Southeastern Europe but, so far, not in Germany. Other hemorrhagic fever disease-viruses occur in distinct regions in South America. Pulmonary plague is the bacterial infectious disease with the most contagious and lethal course and it is endemic to Madagascar and East Africa, but also occurs in other countries (e.g. India, USA). Monkey pox epidemics have occurred in remote areas of the Congo Basin. Such outbreaks could potentially become more common with the discontinuation of the cross-protective smallpox vaccination. The Severe Acute Respiratory Syndrome (SARS) that emerged in 2002/2003 is another pathogen with significant epidemic potential. Typical for these diseases is a natural circulation between reservoir animals in remote areas. Sporadic transmission to humans can occur through contact with an infected animal. Subsequent human-to-human transmission can lead to epidemics, such as the current outbreak of Ebola virus disease in West Africa.


title: Major reduction of rotavirus, but not norovirus, gastroenteritis in children seen in hospital after the introduction of RotaTeq vaccine into the National Immunization Programme in Finland

text: Universal rotavirus (RV) vaccination is expected to reduce hospitalizations for acute gastroenteritis (GE) of children by eliminating most of severe RVGE, but it does not have any effect on norovirus (NV), the second most common causative agent of GE in children. After the introduction of the RV vaccine into the National Immunization Programme (NIP) of Finland in 2009, we conducted a prospective 2-year survey of GE in children seen in Tampere University Hospital either as outpatients or inpatients and compared the results with a similar 2-year survey conducted prior to NIP in the years 2006–2008. Compared with the pre-NIP 2-year period, in 2009–2011, hospitalizations for RVGE were reduced by 76 % and outpatient clinic visits were reduced by 81 %. NVGE showed a slight decreasing trend and accounted for 34 % of all cases of GE seen in hospital in pursuance of RVGE having decreased to 26 % (down from 52 %). In cases admitted to the hospital ward, RV accounted for 28 % and NV accounted for 37 %.The impact of RV vaccination was reflected as a 57 % decrease in all hospital admissions and 62 % decrease in all outpatient clinic visits for GE of any cause. Conclusion: RV vaccination in NIP has led to a major reduction of hospital admissions and clinic visits due to RVGE, but has had no effect on NVGE. After 2 years of NIP, NV has become the leading cause of acute GE in children seen in hospital.


title: Rapid pre-clinical detection of classical swine fever by reverse transcription loop-mediated isothermal amplification

text: Abstract The usefulness of reverse transcription loop-mediated isothermal amplification (RT-LAMP) for rapid pre-clinical detection of classical swine fever virus (CSFV) infection was evaluated. The RT-LAMP reaction could be finished in 60min under isothermal condition at 65°C by employing a set of four primers targeting the 5′ untranslated region of CSFV. The RT-LAMP assay of CSFV showed higher sensitivities than that of RT-PCR, with a detection limit of 5 copies per reaction. No cross-reactivity was observed from the samples of other related viruses including porcine circovirus type 2, porcine parvovirus, porcine pseudorabies virus, Japanese encephalitis virus, and porcine reproductive and respiratory syndrome virus. The detection rates of CSFV RT-LAMP, RT-PCR and virus isolation for samples including blood, tonsil, nasal and rectal swabs from uninoculated pigs without any clear clinical symptom were 89%, 78% and 71%, respectively. Furthermore, all of the assays showed higher sensitivity for blood and tonsil swabs samples than nasal and rectal swabs. These results indicate that the CSFV RT-LAMP assay is a valuable tool for its rapid, cost-effective detection and has potential usefulness for rapid pre-clinical detection and surveillance of classical swine fever in developing countries.


title: Aquatic invasive species: challenges for the future

text: Humans have effectively transported thousands of species around the globe and, with accelerated trade; the rate of introductions has increased over time. Aquatic ecosystems seem at particular risk from invasive species because of threats to biodiversity and human needs for water resources. Here, we review some known aspects of aquatic invasive species (AIS) and explore several new questions. We describe impacts of AIS, factors limiting their dispersal, and the role that humans play in transporting AIS. We also review the characteristics of species that should be the greatest threat for future invasions, including those that pave the way for invasions by other species (“invasional meltdown”). Susceptible aquatic communities, such as reservoirs, may serve as stepping stones for invasions of new landscapes. Some microbes disperse long distance, infect new hosts and grow in the external aquatic medium, a process that has consequences for human health. We also discuss the interaction between species invasions and other human impacts (climate change, landscape conversion), as well as the possible connection of invasions with regime shifts in lakes. Since many invaders become permanent features of the environment, we discuss how humans live with invasive species, and conclude with questions for future research.


title: Preparation and development of equine hyperimmune globulin F(ab′)(2) against severe acute respiratory syndrome coronavirus

text: AIM: The resurgence of severe acute respiratory syndrome (SARS) is still a threat because the causative agent remaining in animal reservoirs is not fully understood, and sporadic cases continue to be reported. Developing high titers of anti-SARS hyperimmune globulin to provide an alternative pathway for emergent future prevention and treatment of SARS. METHODS: SARS coronavirus (CoV)F69 (AY313906) and Z2-Y3 (AY394989) were isolated and identified from 2 different Cantonese onset SARS patients. Immunogen was prepared from SARS-CoV F69 strain. Six health horses were immunized 4 times and serum was collected periodically to measure the profile of specific IgG and neutralizing antibodies using indirect enzyme-linked immunosorbent assay and a microneutralization test. Sera were collected in large amounts at the peak, where IgG was precipitated using ammonium sulphate and subsequently digested with pepsin. The product was then purified using anion-exchange chromatography to obtain F(ab′)(2) fragments. RESULTS: The specific IgG and neutralizing antibody titers peaked at approximately week 7 after the first immunization, with a maximum value of 1:14210. The sera collected at the peak were then purified. Fragment of approximately 15 g F(ab′)(2) was obtained from 1 litre antiserum and the purity was above 90% with the titer of 1:5120, which could neutralize the other strain (SARS-CoV Z2-Y3) as well. CONCLUSION: This research provides a viable strategy for the prevention and treatment of SARS coronavirus infection with equine hyperimmune globulin, with the purpose of combating any resurgence of SARS.


title: Transcriptome analysis reveals a classical interferon signature induced by IFNλ4 in human primary cells

text: The IFNL4 gene is negatively associated with spontaneous and treatment-induced clearance of hepatitis C virus infection. The activity of IFNλ4 has an important causal role in the pathogenesis, but the molecular details are not fully understood. One possible reason for the detrimental effect of IFNλ4 could be a tissue-specific regulation of an unknown subset of genes. To address both tissue and subtype specificity in the interferon response, we treated primary human hepatocytes and airway epithelial cells with IFNα, IFNλ3 or IFNλ4 and assessed interferon mediated gene regulation using transcriptome sequencing. Our data show a surprisingly similar response to all three subtypes of interferon. We also addressed the tissue specificity of the response, and identified a subset of tissue-specific genes. However, the interferon response is robust in both tissues with the majority of the identified genes being regulated in hepatocytes as well as airway epithelial cells. Thus we provide an in-depth analysis of the liver interferon response seen over an array of interferon subtypes and compare it to the response in the lung epithelium. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/gene.2015.23) contains supplementary material, which is available to authorized users.


Thyroid surgery during COVID‐19 pandemic: Principles and philosophies


title: Subchapter 29C Other Angiotensins

text: Abstract Besides the major role of angiotensin II (Ang II) in the renin-angiotensin system (RAS), other angiotensin peptides with different lengths were recently discovered to be biologically active and they possess individual receptors and signaling pathways. Ang III stimulates AT1 and AT2 receptors and its signaling pathway is similar to that of Ang II but has a specific role on aldosterone stimulation in adrenal cortex. The Ang(1–7)/Mas receptor axis is known to antagonize the effects of the AT1 axis. These include anti-hypertrophic action, anti-thrombotic and anti-fibrotic effect, and vasodilation via stimulation of NO synthesis in endothelium and potentiation of the bradykinin effect. Ang IV stimulates insulin-regulated aminopeptidase (IRAP) or AT4 receptor and is involved in facilitation of memory such as reversing memory deficits caused by alcohol abuse and ischemia. AT4 antagonist decreases renal blood flow and increases urinary sodium excretion, and these effects are independent of the AT1 pathway.


title: Neonatal Intensive Care Unit Preparedness for the Novel Coronavirus Disease-2019 Pandemic: A New York City Hospital Perspective

text: In January 2020, China reported a cluster of cases of pneumonia associated with a novel pathogenic coronavirus provisionally named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2). Since then, Coronavirus Disease 2019 (COVID-19) has been reported in more than 180 countries with approximately 3 million known infections and more than 210,000 deaths attributed to this disease. The majority of confirmed COVID-19 cases have been reported in adults, especially older individuals with co-morbidities. Children have had a relatively lower rate and a less serious course of infection as reported in the literature to date. One of the most vulnerable pediatric patient populations is cared for in the neonatal intensive care unit. There is limited data on the effect of COVID-19 in fetal life, and among neonates after birth. Therefore there is an urgent need for proactive preparation, and planning to combat COVID-19, as well as to safeguard patients, their families, and healthcare personnel. This review article is based on the Centers for Disease Control and Prevention's (CDC) current recommendations for COVID-19 and its adaptation to our local resources. The aim of this article is to provide basic consolidated guidance and checklists to clinicians in the neonatal intensive care units in key aspects of preparation needed to counter exposure or infection with COVID-19. We anticipate that CDC will continue to update their guidelines regarding COVID-19 as the situation evolves, and we recommend monitoring CDC's updates for the most current information.


docid: svssrkze

title: Targeting Vascular Leakage for Novel Biomarker Diagnosis and Therapy of Severe Pulmonary Infections


title: Natural products as LSD1 inhibitors for cancer therapy

text: Natural products generally fall into the biologically relevant chemical space and always possess novel biological activities, thus making them a rich source of lead compounds for new drug discovery. With the recent technological advances, natural product-based drug discovery is now reaching a new era. Natural products have also shown promise in epigenetic drug discovery, some of them have advanced into clinical trials or are presently being used in clinic. The histone lysine specific demethylase 1 (LSD1), an important class of histone demethylases, has fundamental roles in the development of various pathological conditions. Targeting LSD1 has been recognized as a promising therapeutic option for cancer treatment. Notably, some natural products with different chemotypes including protoberberine alkaloids, flavones, polyphenols, and cyclic peptides have shown effectiveness against LSD1. These natural products provide novel scaffolds for developing new LSD1 inhibitors. In this review, we mainly discuss the identification of natural LSD1 inhibitors, analysis of the co-crystal structures of LSD1/natural product complex, antitumor activity and their modes of action. We also briefly discuss the challenges faced in this field. We believe this review will provide a landscape of natural LSD1 inhibitors.


title: Pertussis in infants: an underestimated disease

text: BACKGROUND: The clinical diagnosis of pertussis is not easy in early infancy since clinical manifestations can overlap with several different diseases. Many cases are often misclassified and underdiagnosed. We conducted a retrospective study on infants to assess how often physicians suspected pertussis and the actual frequency of Bordetella pertussis infections. METHODS: We analyzed all infants with age ≤90 days hospitalized from March 2011 until September 2013 for acute respiratory symptoms tested with a Real Time Polymerase Chain Reaction able to detect Bordetella pertussis and with a Real Time Polymerase Chain Reaction for a multipanel respiratory virus. Therefore, we compared patients with pertussis positive aspirate, patients with respiratory virus positive aspirate and patients with negative aspirate to identify symptoms or clinical findings predictive of pertussis. RESULTS: Out of 215 patients analyzed, 53 were positive for pertussis (24.7 %), 119 were positive for respiratory virus (55.3 %) and 43 had a negative aspirate (20 %). Pertussis was suspected in 22 patients at admission and 16 of them were confirmed by laboratory tests, while 37 infants with different admission diagnosis resulted positive for pertussis. The sensitivity of clinical diagnosis was 30.2 % and the specificity 96.3 %. Infants with pertussis had more often paroxysmal cough, absence of fever and a higher absolute lymphocyte count than infants without pertussis. CONCLUSIONS: Pertussis is a serious disease in infants and it is often unrecognized; some features should help pediatricians to suspect pertussis, but clinical suspicion has a low sensitivity. We suggest a systematic use of Real Time Polymerase Chain Reaction to support the clinical suspicion of pertussis in patients with less than 3 months of age hospitalized with acute respiratory symptoms.


title: Antiviral RNAi: Translating Science Towards Therapeutic Success

text: Viruses continuously evolve to contend with an ever-changing environment that involves transmission between hosts and sometimes species, immune responses, and in some cases therapeutic interventions. Given the high mutation rate of viruses relative to the timescales of host evolution and drug development, novel drug classes that are readily screened and translated to the clinic are needed. RNA interference (RNAi)—a natural mechanism for specific degradation of target RNAs that is conserved from plants to invertebrates and vertebrates—can potentially be harnessed to yield therapies with extensive specificity, ease of design, and broad application. In this review, we discuss basic mechanisms of action and therapeutic applications of RNAi, including design considerations and areas for future development in the field.


title: The 3.1-Angstrom Cryo-electron Microscopy Structure of the Porcine Epidemic Diarrhea Virus Spike Protein in the Prefusion Conformation

text: Porcine epidemic diarrhea virus (PEDV) is an alphacoronavirus that has a significant agricultural and economic impact due to the high mortality rate associated with infection of neonatal piglets. Like other coronaviruses, PEDV makes use of a large, trimeric spike (S) glycoprotein to mediate membrane fusion and gain entry into host cells. Despite the importance of the spike protein in viral entry and host immune responses, high-resolution structural information concerning this large macromolecular machine has been difficult to obtain. Here, we report the cryo-electron microscopy structure of the PEDV S protein in the prefusion conformation at a resolution of 3.1 Å. Our studies revealed that the sialic acid-binding domain at the N terminus of the S1 subunit has an orientation that is substantially different from that observed in the previously determined spike structure from human alphacoronavirus NL63. We also observed dissociated S1 subunit trimers wherein the putative receptor-binding domains exist in a conformation differing from that observed in the intact spike proteins, suggesting that the PEDV receptor-binding domain undergoes conformational rearrangements akin to those that have been described in the related betacoronaviruses. Collectively, these data provide new insights into the biological processes that mediate alphacoronavirus attachment, receptor engagement, and fusion triggering while also identifying a source of conformational heterogeneity that could be manipulated to improve PEDV vaccine antigens. IMPORTANCE Coronavirus spike proteins are large, densely glycosylated macromolecular machines that mediate receptor binding and membrane fusion to facilitate entry into host cells. This report describes the atomic-resolution structure of the spike protein from porcine epidemic diarrhea virus, a pathogenic alphacoronavirus that causes severe agricultural damage. The structure reveals a novel position for the sialic acid-binding attachment domain in the intact spike. We also observed shed fusion-suppressive capping subunits that displayed the putative receptor-binding domain in an accessible conformation. These observations provide a basis for understanding the molecular mechanisms that drive the earliest stages of alphacoronavirus infection and will inform future efforts to rationally design vaccines.


title: Proinflammatory Cytokines in the Olfactory Mucosa Result in COVID-19 Induced Anosmia

text: [Image: see text] Studies have found increased rates of dysosmia in patients with Novel Coronavirus disease 2019 (COVID-19). However, the mechanism that causes olfactory loss is unknown. The primary objective of this study was to explore local proinflammatory cytokine levels in the olfactory epithelium in patients with COVID-19. Biopsies of the olfactory epithelium were taken from patients with confirmed COVID-19 as well as uninfected controls. Levels of tumor necrosis factor α (TNF-α) and interleukin-1-beta (IL-1β) were assessed using ELISA and compared between groups. Average TNF-α levels were significantly increased in the olfactory epithelium of the COVID-19 group compared to the control group (P < 0.05). However, no differences in IL-1β were seen between groups. Elevated levels of the proinflammatory cytokine TNF-α were seen in the olfactory epithelium in patients with COVID-19. This suggests that direct inflammation of the olfactory epithelium could play a role in the acute olfactory loss described in many patients with COVID-19.


docid: dcmyugmz

title: Why Did Outbreaks of Severe Acute Respiratory Syndrome Occur in Some Hospital Wards but Not in Others?

text: Background. Most documented “superspreading events” of severe acute respiratory syndrome (SARS) occurred in hospitals, but the underlying causes remain unclear. We systematically analyzed the risk factors for nosocomial outbreaks of SARS among hospital wards in Guangzhou and Hong Kong, China. Methods. A case-control study was conducted. Case wards were hospital wards in which superspreading events of SARS occurred, and control wards were wards in which patients with SARS were admitted, but no subsequent nosocomial outbreaks occurred. Information on environmental and administrative factors was obtained through visits to the wards and interviews with ward managers or nursing officers. Relevant information about host factors was abstracted from the medical records. Logistic regression analyses were used to identify the major risk factors for superspreading events. Results. Eighty-six wards in 21 hospitals in Guangzhou and 38 wards in 5 hospitals in Hong Kong were included in the study. Six risk factors were significant in the final multiple-logistic regression model: minimum distance between beds of ≤1 m (odds ratio [OR], 6.94; 95% confidence interval [CI], 1.68–28.75), availability of washing or changing facilities for staff (OR, 0.12; 95% CI, 0.02–0.97), whether resuscitation was ever performed in the ward (OR, 3.81; 95% CI, 1.04–13.87), whether staff members worked while experiencing symptoms (OR, 10.55; 95% CI, 2.28–48.87), whether any host patients (index patient or the first patient with SARS admitted to a ward) required oxygen therapy (OR, 4.30; 95% CI, 1.00–18.43), and whether any host patients required bi-level positive airway pressure ventilation (OR, 11.82; 95% CI, 1.97–70.80). Conclusions. Our results revealed that factors that were associated with the ward environment and administration were important in nosocomial outbreaks of SARS. The lessons learned from this study remain very important and highly relevant to the daily operation of hospital wards if we are to prevent nosocomial outbreaks of other respiratory infections in the future.


title: Redesigning a large school-based clinical trial in response to changes in community practice

text: Background Asthma exacerbations are seasonal with the greatest risk in elementary-age students occurring shortly after returning to school following summer break. Recent research suggests that this seasonality in children is primarily related to viral respiratory tract infections. Regular hand washing is the most effective method to prevent the spread of viral respiratory infections; unfortunately, achieving hand washing recommendations in schools is difficult. Therefore, we designed a study to evaluate the effect of hand sanitizer use in elementary schools on exacerbations among children with asthma. Purpose To describe the process of redesigning the trial in response to changes in the safety profile of the hand sanitizer as well as changes in hand hygiene practice in the schools. Methods The original trial was a randomized, longitudinal, subject-blinded, placebo-controlled, community-based crossover trial. The primary aim was to evaluate the incremental effectiveness of hand sanitizer use in addition to usual hand hygiene practices to decrease asthma exacerbations in elementary-age children. Three events occurred that required major modifications to the original study protocol: (1) safety concerns arose regarding the hand sanitizer’s active ingredient; (2) no substitute placebo hand sanitizer was available; and (3) community preferences changed regarding hand hygiene practices in the schools. Results The revised protocol is a randomized, longitudinal, community-based crossover trial. The primary aim is to evaluate the incremental effectiveness of a two-step hand hygiene process (hand hygiene education plus institutionally provided alcohol-based hand sanitizer) versus usual care to decrease asthma exacerbations. Enrollment was completed in May 2009 with 527 students from 30 schools. The intervention began in August 2009 and will continue through May 2011. Study results should be available at the end of 2011. Limitations The changed design does not allow us to directly measure the effectiveness of hand sanitizer use as a supplement to traditional hand washing practices. Conclusions The need to balance a rigorous study design with one that is acceptable to the community requires investigators to be actively involved with community collaborators and able to adapt study protocols to fit changing community practices.


title: Infectious bronchitis viruses with naturally occurring genomic rearrangement and gene deletion

text: Infectious bronchitis viruses (IBVs) are group III coronaviruses that infect poultry worldwide. Genetic variations, including whole-gene deletions, are key to IBV evolution. Australian subgroup 2 IBVs contain sequence insertions and multiple gene deletions that have resulted in a substantial genomic divergence from international IBVs. The genomic variations present in Australian IBVs were investigated and compared to those of another group III coronavirus, turkey coronavirus (TCoV). Open reading frames (ORFs) found throughout the genome of Australian IBVs were analogous in sequence and position to TCoV ORFs, except for ORF 4b, which appeared to be translocated to a different position in the subgroup 2 strains. Subgroup 2 strains were previously reported to lack genes 3a, 3b and 5a, with some also lacking 5b. Of these, however, genes 3b and 5b were found to be present but contained various mutations that may affect transcription. In this study, it was found that subgroup 2 IBVs have undergone a more substantial genomic rearrangements than previously thought.


title: Comparison of enzyme-linked immunosorbent assay systems using rift valley fever virus nucleocapsid protein and inactivated virus as antigens

text: BACKGROUND: Rift Valley Fever (RVF) is a mosquito-borne viral zoonosis. To detect RVF virus (RVFV) infection, indirect immunoglobulin G (IgG) and immunoglobulin M (IgM) enzyme linked immunosorbent assays (ELISAs) which utilize recombinant RVFV nucleocapsid (RVFV-N) protein as assay antigen, have reportedly been used, however, there is still a need to develop more sensitive and specific methods of detection. METHODS: RVFV-N protein was expressed in Escherichia coli (E. coli) and purified by histidine-tag based affinity chromatography. This recombinant RVFV-N (rRVFV-N) protein was then used as antigen to develop an IgG sandwich ELISA and IgM capture ELISAs for human sera. Ninety six serum samples collected from healthy volunteers during the RVF surveillance programme in Kenya in 2013, and 93 serum samples collected from RVF-suspected patients during the 2006–2007 RVF outbreak in Kenya were used respectively, to evaluate the newly established rRVFV-N protein-based IgG sandwich ELISA and IgM capture ELISA systems in comparison with the inactivated virus-based ELISA systems. RESULTS: rRVFV-N protein-based-IgG sandwich ELISA and IgM capture ELISA for human sera were established. Both the new ELISA systems were in 100% concordance with the inactivated virus-based ELISA systems, with a sensitivity and specificity of 100%. CONCLUSIONS: Recombinant RVFV-N is a safe and affordable antigen for RVF diagnosis. Our rRVFV-N-based ELISA systems are safe and reliable tools for diagnosis of RVFV infection in humans and especially useful in large-scale epidemiological investigation and for application in developing countries.


docid: oohsvvcb

title: Blood Donor Recruitment in Guangzhou, China, during the 2019 Novel Coronavirus (COVID‐19) Epidemic

text: BACKGROUND: The coronavirus disease 2019 (COVID‐19) epidemic affected blood collection in Guangzhou, China. STUDY DESIGN AND METHODS: This paper included three studies. The observational study reported the trends of blood collection during the epidemic in Guangzhou, China. The cross‐sectional survey investigated factors influencing blood donation during the COVID‐19 epidemic, and a self‐administered questionnaire was given to 1,584 street whole blood donors (SWBDs) who donated during the epidemic. The randomized controlled trial involved 19,491 SWBDs who donated in 2019 but did not donate during the epidemic. Trial participants were randomly assigned to two intervention groups: group 1 completed Questionnaire 1, which contained precautionary measures in response to COVID‐19 and other messages about blood donation during the epidemic; and group 2 completed Questionnaire 2, which did not include this information. A control group did not receive any questionnaire. RESULTS: As measures implemented, the number of blood donors increased accordingly. Both first‐time and repeat SWBDs perceived the same level of blood need and donated blood because it would save lives. SWBDs who completed Questionnaire 1 expressed a greater intention to donate during the epidemic. Enabling blood donors to perceive a higher level of blood need and a lower level of COVID‐19 infection risk related to blood donation mobilized experienced SWBDs to donate within three weeks. Intention‐to‐treat analyses and average‐treatment‐effect‐on‐the‐treated estimations confirmed that Questionnaire 1 could motivate SWBDs to actually donate blood. CONCLUSION: Various measures could ease blood shortage during the COVID‐19 epidemic. Administration of Questionnaire 1 could increase blood donations during the epidemic. This article is protected by copyright. All rights reserved.


Comment on Psychological Interventions During COVID-19: Challenges for Iraqi Kurdistan


docid: kvugftgu

title: Rapid Tests for Influenza, Respiratory Syncytial Virus, and Other Respiratory Viruses: A Systematic Review and Meta-analysis

text: Rapid diagnosis of respiratory virus infections contributes to patient care. This systematic review evaluates the diagnostic accuracy of rapid tests for the detection of respiratory viruses. We searched Medline and EMBASE for studies evaluating these tests against polymerase chain reaction as the reference standard. Of 179 studies included, 134 evaluated rapid tests for influenza viruses, 32 for respiratory syncytial virus (RSV), and 13 for other respiratory viruses. We used the bivariate random effects model for quantitative meta-analysis of the results. Most tests detected only influenza viruses or RSV. Summary sensitivity and specificity estimates of tests for influenza were 61.1% and 98.9%. For RSV, summary sensitivity was 75.3%, and specificity, 98.7%. We assessed the quality of studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist. Because of incomplete reporting, the risk of bias was often unclear. Despite their intended use at the point of care, 26.3% of tests were evaluated in a laboratory setting. Although newly developed tests seem more sensitive, high-quality evaluations of these tests are lacking.


title: Human Bocavirus in Very Young Infants Hospitalized with Acute Respiratory Infection in Northeast Brazil

text: A cross-sectional study was carried out over a period of 12 months to investigate the occurrence of human bocavirus (HBoV) infection in infants hospitalized for respiratory infections in a teaching hospital in Salvador, Brazil, and to describe the clinical manifestations of this infection. Nasopharyngeal aspirates were collected from the children and immunofluorescence and polymerase chain reaction were performed to investigate the presence of respiratory viruses. HBoV was detected in 4 out of 66 patients. Two of the HBoV-positive infants were co-infected with other viruses. The principal clinical findings in HBoV-positive children were: nasal obstruction, catarrh, cough, fever and dyspnea. This study revealed HBoV infection in children aged <2 months, suggesting that the infection may occur at a very early age.


Coronavirus Spike Proteins in Viral Entry and Pathogenesis


title: Defining and quantifying China's ocean economy

text: In recent years, the Chinese government has been increasingly supportive of the development of the ocean economy, implementing several national ocean-related strategies. For the first time, China's 12th five-year Plan for National and Social Development (2011—2015) includes “developing the ocean economy” as a key national development strategy for the country. Because of this, the demand for ocean economic statistics and indicators is growing rapidly. The aim of this paper is to define and quantify the value of the major ocean industries in China and to examine the growth in the major Chinese ocean industries in the period 2001 to 2010. The paper also outlines a methodology that provides a robust quantification of the marine sector over time. It finds that in 2010 the major ocean industries in China contributed $239.09 billion to the national economy and employed over 9 million individuals.


title: Severe Acute Respiratory Syndrome and Sport: Facts and Fallacies

text: Severe Acute Respiratory Syndrome (SARS) not only paralysed economic activities in SARS-affected cities, it also affected sporting activities. SARS was identified in Hong Kong in late February 2003 and the WHO issued a global alert on 12 March, 2003. The incubation period of SARS is usually 4–6 days and patients commonly present with high fever (temperature >38°C), dry cough, chills and rigor, dyspnoea and diarrhoea. Although a specific antiviral agent and vaccines for SARS are not available at the time of writing, a standard treatment protocol for SARS has been developed. The average mortality rate is about 16% in Hong Kong. The coronavirus is a common pathogen for upper respiratory tract infection and is the most probable pathogen for SARS. Transmission methods may, therefore, be similar for both these infections. Transmission is possible when aerosolised viral particles come into contact with the susceptible host’s mucous membrane, most commonly the nose, but also the mouth and eyes. With appropriate preventive measures to avoid contact with virus, the probability of infection is minimal. Isolation of those who have had close contact with confirmed or suspected SARS patients and/or who have persistent fever will be the most effective and practical method of avoiding contact. Maintaining personal hygiene and frequent hand washing can also reduce the risk of infection. Using diluted bleach (1 part bleach in 99 parts water) to cleanse training areas and equipment is also recommended. With proper event planning to conform with quarantine measures, special travel arrangements, facility sterilisation and use of venues with good ventilation and filtering systems, sport competition can still proceed.


Letter: Beyond COVID-19 emergency: are brachial plexus and nerve transfer surgeries really deferrable?


title: Distributions of respiratory contaminants from a patient with different postures and exhaling modes in a single-bed inpatient room

text: Abstract This study investigated contaminant transport and evaluated the ventilation performance in a single-bed inpatient room. The study performed comparative experimental analysis on the distributions of respiratory contaminants breathed out and coughed out by a patient in a full-scale chamber, which simulated a single-bed inpatient room. The contaminant exhaled by the patient was simulated by an SF6 tracer gas and 3-μm particles at steady-state conditions. The differences in the contaminant distribution between the coughing and breathing cases were insignificant for the mixing ventilation case, while for the displacement ventilation, the contaminant concentrations in the upper part of the room were higher for the coughing case. The contaminant concentrations in the inpatient room for the case with the patient sitting on the bed were lower than those for the patient supine on the bed for the displacement ventilation under the same supply airflow rate. The SF6 tracer gas and 3-μm particles released at a notable initial velocity for simulating a cough could give similar contaminant distributions in the inpatient room. Therefore, the experimental data can be used to validate a CFD model, and the validated CFD model can be used to investigate transient coughing and breathing processes.


title: The emergency reaction questionnaire – First steps towards a new method

text: During emergencies, people are more or less capable of performing adequately. Knowledge about human behavior while facing emergencies has become more significant nowadays. This knowledge can help improving our already present defensive responses and natural coping mechanisms when facing imminent dangers, natural disasters, and catastrophes. A new method is here offered to explore the core points of this topic. The Emergency Reaction Questionnaire (ERQ), is proposed for predicting one's reaction and behaviour in an emergency. First, a large item pool was created based on interviews with people facing emergencies on a weekly basis and related literature. The factor structure, reliability and validity were assessed on a large sample of lay people (N = 1115, 440 males) and specific groups of firefighters and people doing extreme sports (N = 85, all males). Participants were Caucasian with an age range of 18–70. We also used measures of anxiety, depression, and sensation seeking, behavioral inhibition and activation and coping in stressful situations. The ERQ was proved to be reliable and consistent in time and having sound psychometric properties both on the community and special samples. Results show that psychometric properties are satisfying; the test has excellent validity ratings. Consequently, the ERQ can be used in future research effectively and facilitate a better understanding of how people react in a highly dangerous situation. Future directions in the utilization of the new method are discussed.


title: Entry of Enveloped Viruses into Host Cells: Membrane Fusion

text: Viruses are intracellular parasites that hijack the cellular machinery for their own replication. Therefore, an obligatory step in the virus life cycle is the delivery of the viral genome inside the cell. Enveloped viruses (i.e., viruses with a lipid envelope) use a two-step procedure to release their genetic material into the cell: (i) they first bind to specific surface receptors of the target cell membrane and then, (ii) they fuse the viral and cell membranes. This last step may occur at the cell surface or after internalization of the virus particle by endocytosis or by some other route (e.g., macropinocytosis). Remarkably, the virus-cell membrane fusion process goes essentially along the same intermediate steps as other membrane fusions that occur for instance in vesicular fusion at the nerve synapsis or cell-cell fusion in yeast mating. Specialized viral proteins, fusogens, promote virus-cell membrane fusion. The viral fusogens experience drastic structural rearrangements during fusion, liberating the energy required to overcome the repulsive forces that prevent spontaneous fusion of the two membranes. This chapter describes the different types of viral fusogens and their mode of action, as are currently known.


title: Tackling the challenges to health equity in China

text: Summary In terms of economic development, China is widely acclaimed as a miracle economy. Over a period of rapid economic growth, however, China's reputation for health has been slipping. In the 1970s China was a shining example of health development, but no longer. Government and public concerns about health equity have grown. China's health-equity challenges are truly daunting because of a vicious cycle of three synergistic factors: the social determinants of health have become more inequitable; imbalances in the roles of the market and government have developed; and concerns among the public have grown about fairness in health. With economic boom and growing government revenues, China is unlike other countries challenged by health inequities and can afford the necessary reforms so that economic development goes hand-in-hand with improved health equity. Reforms to improve health equity will receive immense popular support, governmental commitment, and interest from the public-health community worldwide.


title: Severe COVID-19 After Recent Heart Transplantation Complicated by Allograft Dysfunction

text: Abstract A 50-year-old male presented with atrial flutter 25 days after heart and kidney transplantation. Rejection was excluded, however, he developed severe COVID-19 with cardiac allograft dysfunction. Despite continued corticosteroids and tacrolimus, he remained aviremic. Respiratory and myocardial function recovered after a week of mechanical ventilation. The cardiomyopathy was stress induced.


docid: sbryreho

title: Recruitment to randomised studies


title: Pneumonia in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

text: These guidelines from the AST Infectious Diseases Community of Practice review the diagnosis and management of pneumonia in the post‐transplant period. Clinical presentations and differential diagnosis for pneumonia in the solid organ transplant recipient are reviewed. A two‐tier approach is proposed based on the net state of immunosuppression and the severity of presentation. With a lower risk of opportunistic, hospital‐acquired, or exposure‐specific pathogens and a non‐severe presentation, empirical therapy may be initiated under close clinical observation. In all other patients, or those not responding to the initial therapy, a more aggressive diagnostic approach including sampling of tissue for microbiological and pathological testing is warranted. Given the broad range of potential pathogens, a microbiological diagnosis is often key for optimal care. Given the limited literature comparatively evaluating diagnostic approaches to pneumonia in the solid organ transplant recipient, much of the proposed diagnostic algorithm reflects clinical experience rather than evidence‐based data. It should serve as a template which may be modified according to local needs. The same holds true for the suggested empiric therapies, which need to be adapted to the local resistance patterns. Further study is needed to comparatively evaluate diagnostic and empiric treatment strategies in SOT recipients.


Patients with the novel Sars-Cov-2 disease require a novel standard of care – med-psych


title: Reduced-Intensity Conditioning and Dual T Lymphocyte Suppression with Antithymocyte Globulin and Post-Transplant Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Haploidentical Hematopoietic Stem Cell Transplants for Hematological Malignancies

text: Abstract Haploidentical hematopoietic stem cell transplantation (haploHSCT) with conditioning regimens using post-transplant cyclophosphamide (PTCy) for peripheral blood stem cell (PBSC) grafts is limited by comparably higher rates of acute and chronic graft-versus-host disease (GVHD). Antithymocyte globulin (ATG) may mitigate this risk. We evaluated haploHSCT after reduced-intensity conditioning (RIC) with ATG, PTCy, and cyclosporine to prevent rejection and GVHD. Fifty adults underwent haploHSCT from August 2016 to February 2018. RIC included fludarabine (30 mg/m2/day on days –5 to –2), busulfan (3.2 mg/m2/day on days –3 and –2), and total body irradiation (200 cGy) on day –1. Unmanipulated PBSCs were infused on day 0. GVHD prophylaxis included ATG (4.5 mg/kg over days –3 to –1), PTCy (50 mg/kg/day on days +3 and +4), and cyclosporine from day +5. Median age was 56 years (range, 22 to 70 years); 25 (73.5%) patients were in first complete remission (CR1), 5 (14.7%) were in second complete remission (CR2), and 8 (23.5%) had active disease. Median time to neutrophil engraftment was 16 days (range, 8 to 43 days). At day +100, the cumulative incidence of acute GVHD of any grade, and grades III to IV was 38.3% and 5.2%, respectively. Mild chronic GVHD was seen in 15.5%. Cytomegalovirus (CMV) reactivation occurred in 37 (74%) cases and CMV disease occurred in 4 (11.5%) cases. Epstein-Barr virus (EBV) reactivation occurred in 21 (61.8%) patients. The incidence of histologically confirmed post-transplantation lymphoproliferative disorder (PTLD) was 5.8%. Four patients received rituximab. There were no CMV, EBV, or PTLD-related deaths. Six-month and 1-year overall survival (OS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM) were 73.9%, 10.2%, and 19.4%, respectively, and 48.1%, 16% and 38.2%, respectively. Infection was the most common cause of death (18%). Unmanipulated haploidentical PBSC transplantation following RIC with ATG, PTCy, and cyclosporine as a GVHD prevention strategy results in low rates of acute and chronic GVHD.


title: Estimation of reproduction numbers of COVID-19 in typical countries and epidemic trends under different prevention and control scenarios

text: The coronavirus disease 2019 (COVID-19) has become a life-threatening pandemic. The epidemic trends in different countries vary considerably due to different policy-making and resources mobilization. We calculated basic reproduction number (R(0)) and the time-varying estimate of the effective reproductive number (R(t)) of COVID-19 by using the maximum likelihood method and the sequential Bayesian method, respectively. European and North American countries possessed higher R(0) and unsteady R(t) fluctuations, whereas some heavily affected Asian countries showed relatively low R(0) and declining R(t) now. The numbers of patients in Africa and Latin America are still low, but the potential risk of huge outbreaks cannot be ignored. Three scenarios were then simulated, generating distinct outcomes by using SEIR (susceptible, exposed, infectious, and removed) model. First, evidence-based prompt responses yield lower transmission rate followed by decreasing R(t). Second, implementation of effective control policies at a relatively late stage, in spite of huge casualties at early phase, can still achieve containment and mitigation. Third, wisely taking advantage of the time-window for developing countries in Africa and Latin America to adopt adequate measures can save more people’s life. Our mathematical modeling provides evidence for international communities to develop sound design of containment and mitigation policies for COVID-19. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available in the online version of this article at 10.1007/s11684-020-0787-4 and is accessible for authorized users.


title: Salt Effects on the Thermodynamics of a Frameshifting RNA Pseudoknot under Tension

text: Because of the potential link between -1 programmed ribosomal frameshifting and response of a pseudoknot (PK) RNA to force, a number of single molecule pulling experiments have been performed on PKs to decipher the mechanism of programmed ribosomal frameshifting. Motivated in part by these experiments, we performed simulations using a coarse-grained model of RNA to describe the response of a PK over a range of mechanical forces ($f$s) and monovalent salt concentrations ($C$s). The coarse-grained simulations quantitatively reproduce the multistep thermal melting observed in experiments, thus validating our model. The free energy changes obtained in simulations are in excellent agreement with experiments. By varying $f$ and $C$, we calculated the phase diagram that shows a sequence of structural transitions, populating distinct intermediate states. As $f$ and $C$ are changed, the stem-loop tertiary interactions rupture first, followed by unfolding of the $3^{\prime}$-end hairpin ($\textrm{I}\rightleftharpoons\textrm{F}$). Finally, the $5^{\prime}$-end hairpin unravels, producing an extended state ($\textrm{E}\rightleftharpoons\textrm{I}$). A theoretical analysis of the phase boundaries shows that the critical force for rupture scales as $\left(\log C_{\textrm{m}}\right)^{\alpha}$ with $\alpha=1\,(0.5)$ for $\textrm{E}\rightleftharpoons\textrm{I}$ ($\textrm{I}\rightleftharpoons\textrm{F}$) transition. This relation is used to obtain the preferential ion-RNA interaction coefficient, which can be quantitatively measured in single-molecule experiments, as done previously for DNA hairpins. A by-product of our work is the suggestion that the frameshift efficiency is likely determined by the stability of the $5^{\prime}$-end hairpin that the ribosome first encounters during translation.


title: Positive immunostaining for feline infectious peritonitis (FIP) in a Sphinx cat with cutaneous lesions and bilateral panuveitis

text: Feline infectious peritonitis (FIP) is a common, fatal, systemic disease of cats. This case report describes the antemortem diagnosis of FIP in a 2‐year‐old spayed female Sphinx cat that presented with a bilateral panuveitis and multiple papular cutaneous lesions. Histopathologically, the skin lesions were characterized by perivascular infiltrates of macrophages, neutrophils, with fewer plasma cells, mast cells, and small lymphocytes in the mid‐ to deep dermis. Immunohistochemistry for intracellular feline coronavirus (FeCoV) antigen demonstrated positive staining in dermal macrophages providing an antemortem diagnosis of a moderate, nodular to diffuse, pyogranulomatous perivascular dermatitis due to FIP infection. Obtaining an antemortem diagnosis of FIP can be a challenge and cutaneous lesions are rare in the disease. Recognition and biopsy of any cutaneous lesions in cats with panuveitis and suspected FIP can help establish an antemortem diagnosis of the disease.


title: An increasing risk of family violence during the Covid-19 pandemic: Strengthening community collaborations to save lives

text: Abstract Though necessary to slow the spread of the novel Coronavirus (Covid-19), actions such as social-distancing, sheltering in-place, restricted travel, and closures of key community foundations are likely to dramatically increase the risk for family violence around the globe. In fact many countries are already indicating a dramatic increase in reported cases of domestic violence. While no clear precedent for the current crisis exists in academic literature, exploring the impact of natural disasters on family violence reports may provide important insight for family violence victim-serving professionals. Improving collaborations between human welfare and animal welfare agencies, expanding community partnerships, and informing the public of the great importance of reporting any concerns of abuse are all critical at this time.


title: COVID‐19: Important Therapy Considerations and Approaches in this Hour of Need

text: We are living in unprecedented times. While we had near pandemic events in the recent past with SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome), we have never experienced anything like coronavirus (COVID-19), also known as SARS-CoV-2 infection, since the Spanish flu. In contrast to the Spanish flu where medical care was limited, we are equipped to combat COVID-19 but there is considerable work ahead with many uncertainties. At this critical time, we must come together as one united country and world to stop the spread and provide the best care possible for individuals who contract the virus and develop infection. A number of novel and repurposed therapies agents with activity against SARS-CoV-2 have been identified and most institutions have developed clinical pathways to operationalize their use in appropriate COVID-19 patients.1-3 However, optimal drug therapy decisions for those with moderate to severe COVID-19 infections are extremely challenging at this time as evidence is limited.


title: Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China

text: Although the respiratory and immune systems are the major targets of Coronavirus Disease 2019 (COVID-19), acute kidney injury and proteinuria have also been observed. Currently, detailed pathologic examination of kidney damage in critically ill patients with COVID-19 has been lacking. To help define this we analyzed kidney abnormalities in 26 autopsies of patients with COVID-19 by light microscopy, ultrastructural observation and immunostaining. Patients were on average 69 years (19 male and 7 female) with respiratory failure associated with multiple organ dysfunction syndrome as the cause of death. Nine of the 26 showed clinical signs of kidney injury that included increased serum creatinine and/or new-onset proteinuria. By light microscopy, diffuse proximal tubule injury with the loss of brush border, non-isometric vacuolar degeneration, and even frank necrosis was observed. Occasional hemosiderin granules and pigmented casts were identified. There were prominent erythrocyte aggregates obstructing the lumen of capillaries without platelet or fibrinoid material. Evidence of vasculitis, interstitial inflammation or hemorrhage was absent. Electron microscopic examination showed clusters of coronavirus particles with distinctive spikes in the tubular epithelium and podocytes. Furthermore, the receptor of SARS-CoV-2, ACE2 was found to be upregulated in patients with COVID-19, and immunostaining with SARS-CoV nucleoprotein antibody was positive in tubules. In addition to the direct virulence of SARS-CoV-2, factors contributing to acute kidney injury included systemic hypoxia, abnormal coagulation, and possible drug or hyperventilation-relevant rhabdomyolysis. Thus, our studies provide direct evidence of the invasion of SARSCoV-2 into kidney tissue. These findings will greatly add to the current understanding of SARS-CoV-2 infection.


title: Interventions to prevent chronic obstructive pulmonary disease exacerbations

text: Exacerbations of chronic obstructive pulmonary disease (COPD) have a profound effect on the patient’s health status and decline in lung function; they also impose a significant burden on healthcare resource utilization. Prevention and treatment of exacerbations is listed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) as among the major objectives of COPD management, and it is therefore an important outcome measure when studying any new agent. This article discusses pharmacologic therapy and other measures for preventing exacerbations and hospitalizations due to exacerbations of COPD.


The importance of assessing the self-reported impact of COVID-19 on clinician mental health


title: Chapter 30 The National Bioforensic Analysis Center

text: Abstract The National Bioforensic Analysis Center has been central to the nation's biodefense strategy since its inception in 2004 and provides ISO 17025 accredited bioforensic capabilities at BSL-0 through BSL-4 for the FBI and other federal partners. NBFAC is continually expanding to maintain cutting edge capabilities in the face of expanding threat landscapes and rapidly evolving technology, and it works with partners in academia, industry, and government to ensure that federal bioterror/biocrime investigations have the best possible scientific support.


title: Detection and characterization of bovine-like coronaviruses from four species of zoo ruminants

text: Abstract Five coronaviruses (CoVs) were detected in diarrheal feces from four zoo ruminant species: one wisent (Bison bonasus), two Himalayan tahr (Hemitragus jemlahicus), one sitatunga (Tragelaphus spekii), and one nyala (Tragelaphus angasii). We sequenced and analyzed the spike (S) and hemagglutinin/esterase (HE) genes of these viruses and compared the nucleotide (nt) and deduced amino acid (aa) sequences with those of other bovine CoV (BcoV) strains. Comparison of the entire deduced aa sequences of the S and HE glycoproteins revealed no specific differences that would account for discrimination between bovine-like CoV strains from zoo ruminants and BcoVs strains. In addition, the 99.9% aa identity among the five CoV strains revealed that the ruminants were infected by the same strain. Phylogenetically, bovine-like CoVs belong to group 2a CoVs, which are related most closely to the BcoV strains recently isolated in Korea. These data suggest that cattle are potential reservoirs for CoVs that are capable of infecting zoo ruminants.


title: Novel Coronavirus (nCoV): a Bitter Old Enemy in a New Avatar

text: Currently, pandemic coronavirus disease 2019 (COVID-19) is the biggest threat to all human beings globally. Till June 8, 2020, it has infected 6,931,000 people and caused 400,857 deaths worldwide. The first case was identified in a patient with influenza-like symptoms along with severe acute respiratory syndrome in Wuhan, China, in December 2019 and now it has spread in more than 200 countries. Since there is no approved cure for this disease until now, there is a lot of mass fear, apprehensions, and questions globally regarding (i) genetic origin and history of the novel coronavirus, (ii) what are the first-line therapies for those who contract this disease, and (iii) what could be the potential vaccine targets. In this short review, we have tried to address these queries in the simplest manner and compiled the history of previous coronaviruses, recent developments in the COVID-19 research, potential future therapeutics, and possible targets to cure the disease.


title: Prevalence of human metapneumovirus in children with acute lower respiratory infection in Changsha, China

text: Human metapneumovirus (hMPV) causes acute respiratory infections in children. The prevalence and clinical characteristics of hMPV were determined in nasopharyngeal aspirates of children in Changsha, China. Reverse transcription‐polymerase chain reaction (RT‐PCR) or PCR was employed to screen for both hMPV and other common respiratory viruses in 1,165 nasopharyngeal aspirate specimens collected from children with lower respiratory tract infections from September 2007 to August 2008. All PCR products were sequenced, and demographic and clinical data were collected from all patients. Seventy‐six of 1,165 (6.5%) specimens were positive for hMPV, of which 85.5% (65/76) occurred in the winter and spring seasons. The hMPV coinfection rate was 57.9% (44/76), and human bocavirus was the most common virus detected in conjunction with hMPV. Phylogenetic analysis revealed that 94.7% of the hMPV detected were of subgroup A2, 5.3% were subgroup B2, and none belonged to either the A1 or B1 subgroups. No significant differences were found in terms of the frequency of diagnosis and clinical signs between either the co‐ and mono‐infection groups, or between patients with and without underlying diseases. It was concluded that hMPV is an important viral pathogen in pediatric patients with lower respiratory tract infections in Changsha. Only hMPV genotypes A2 and B2 were co‐circulating in this locality; human bocavirus was the most common coinfecting virus, and coinfection did not affect disease severity. J. Med. Virol. 85:546–553, 2013. © 2013 Wiley Periodicals, Inc.


title: Acute pancreatic injuries: A complication of Stevens-Johnson syndrome/toxic epidermal necrolysis associated with cytotoxic immune cell activation

text: Abstract Background Complications involving internal organs are usually present in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, pancreatic complications are rarely reported and studied. Objective To summarize clinical characteristics of SJS/TEN-associated acute pancreatic injuries (API) and to investigate underlying inflammatory mechanisms. Methods Clinical records of 124 inpatients with SJS/TEN were reviewed. Serum levels of tumor necrosis factor-α, interleukin (IL)-6, IL-18, IL-15, IL-12p70, and soluble CD56 were determined in 18 healthy donors and 17 patients with SJS/TEN, including three patients with API. Results API was diagnosed in 7.3% (9/124) of patients in the SJS/TEN cohort. Serum transaminase elevation and hypoalbuminemia occurred more frequently in patients with API compared to those without pancreatic symptoms (P = 0.004, P = 0.0002, respectively). Although API did not alter mortality rate of SJS/TEN, it was associated with longer hospitalization stays (P = 0.008). Within the serum cytokines that were elevated in SJS/TEN, only IL-18 was found to be selectively increased in patients with API compared to those without pancreatic injuries (P = 0.032). Limitations Cohort size is small. Conclusion API is a gastrointestinal complication of SJS/TEN in which hepatotoxicity is more likely to occur. Overexpression of IL-18 might be involved in this unique entity.


title: Lockdown timing and efficacy in controlling COVID-19 using mobile phone tracking

text: BACKGROUND: Italy's severe COVID-19 outbreak was addressed by a lockdown that gradually increased in space, time and intensity. The effectiveness of the lockdown has not been precisely assessed with respect to the intensity of mobility restriction and the time until the outbreak receded. METHODS: We used processed mobile phone tracking data to measure mobility restriction, and related those data to the number of new SARS-CoV-2 positive cases detected on a daily base in the three most affected Italian regions, Lombardy, Veneto and Emilia-Romagna, from February 1 through April 6, 2020, when two subsequent lockdowns with increasing intensity were implemented by the Italian government. FINDINGS: During the study period, mobility restriction was inversely related to the daily number of newly diagnosed SARS-CoV-2 positive cases only after the second, more effective lockdown, with a peak in the curve of diagnosed cases of infection occurring 14 to 18 days from lockdown in the three regions and 9 to 25 days in the included provinces. An effective reduction in transmission must have occurred nearly immediately after the tighter lockdown, given the lag time of around 10 days from asymptomatic infection to diagnosis. The period from lockdown to peak was shorter in the areas with the highest prevalence of the infection. This effect was seen within slightly more than one week in the most severely affected areas. INTERPRETATION: It appears that the less rigid lockdown led to an insufficient decrease in mobility to reverse an outbreak such as COVID-19. With a tighter lockdown, mobility decreased enough to bring down transmission promptly below the level needed to sustain the epidemic. FUNDING: No funding sources have been used for this work.


title: The UPR Branch IRE1-bZIP60 in Plants Plays an Essential Role in Viral Infection and Is Complementary to the Only UPR Pathway in Yeast

text: The unfolded protein response (UPR) signaling network encompasses two pathways in plants, one mediated by inositol-requiring protein-1 (IRE1)-bZIP60 mRNA and the other by site-1/site-2 proteases (S1P/S2P)-bZIP17/bZIP28. As the major sensor of UPR in eukaryotes, IRE1, in response to endoplasmic reticulum (ER) stress, catalyzes the unconventional splicing of HAC1 in yeast, bZIP60 in plants and XBP1 in metazoans. Recent studies suggest that IRE1p and HAC1 mRNA, the only UPR pathway found in yeast, evolves as a cognate system responsible for the robust UPR induction. However, the functional connectivity of IRE1 and its splicing target in multicellular eukaryotes as well as the degree of conservation of IRE1 downstream signaling effectors across eukaryotes remains to be established. Here, we report that IRE1 and its substrate bZIP60 function as a strictly cognate enzyme-substrate pair to control viral pathogenesis in plants. Moreover, we show that the S1P/S2P-bZIP17/bZIP28 pathway, the other known branch of UPR in plants, does not play a detectable role in virus infection, demonstrating the distinct function of the IRE1-bZIP60 pathway in plants. Furthermore, we provide evidence that bZIP60 and HAC1, products of the enzyme-substrate duet, rather than IRE1, are functionally replaceable to cope with ER stress in yeast. Taken together, we conclude that the downstream signaling of the IRE1-mediated splicing is evolutionarily conserved in yeast and plants, and that the IRE1-bZIP60 UPR pathway not only confers overlapping functions with the other UPR branch in fundamental biology but also may exert a unique role in certain biological processes such as virus-plant interactions.


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title: Lactoferrin: Lactoferrin: a modulator of immune and inflammatory responses

text: Lactoferrin is an iron-binding glycoprotein of the transferrin family. Abundant expression and secretion of lactoferrin, in particular in milk and fluids of the digestive tract, are related to its implication in the first line of host defense. Lactoferrin is also a prominent component of the secondary granules of neutrophils (PMNs) and is released in infected tissues and blood during the inflammatory process. In addition to its direct antimicrobial properties, the abilities of lactoferrin to regulate the immune response and to protect against infection and septic shock have been described in numerous in vitro and in vivo studies. Although the cellular and molecular mechanisms that account for the modulation of the inflammatory and immune responses by lactoferrin are not yet totally elucidated, many are now established. At the cellular level, lactoferrin modulates the migration, maturation and function of immune cells. At the molecular level and in addition to iron binding, interactions of lactoferrin with a plethora of compounds, either soluble or membrane molecules, account for its modulatory properties. This paper reviews our current understanding of the cellular and molecular mechanisms that explain the regulatory properties of lactoferrin in host defence.


title: Severity and risk of COVID‐19 in cancer patients: An evidence based learning

text: The immune system of cancer patient gets compromised because of cancer therapy, surgery and malignancy and thus the probability of infection are increased than the general patients. Immunosuppression can expose cancer patients to serious complications which can lead to delay in diagnosis and unnecessary hospitalizations that may adversely affect the prognosis of the disease. Patients who received chemotherapy or surgery within the 30 days before COVID‐19 pandemic have more risk of infection than the patients who had not undergone chemotherapy or surgery. This article is protected by copyright. All rights reserved.


title: Phylogenetic analysis of avian infectious bronchitis virus strains isolated in Japan

text: To define the origin and evolution of recent avian infectious bronchitis virus (IBV) in Japan, a genetic analysis was performed. By phylogenetic analysis based on the S1 gene including the sequence of the hypervariable regions, IBV isolates in Japan were classified into five genetic groups, which included two already-known groups (Mass and Gray). Among them, three major genetic groups were associated with the recent outbreaks of IB in Japan. One group is indigenous to Japan and could not be placed within the known existing groups in other countries. The remaining two groups, which have emerged recently, are related to isolates in China and Taiwan.


title: Influence of hydrophobic and electrostatic residues on SARS-coronavirus S2 protein stability: Insights into mechanisms of general viral fusion and inhibitor design

text: Severe acute respiratory syndrome (SARS) is an acute respiratory disease caused by the SARS-coronavirus (SARS-CoV). SARS-CoV entry is facilitated by the spike protein (S), which consists of an N-terminal domain (S1) responsible for cellular attachment and a C-terminal domain (S2) that mediates viral and host cell membrane fusion. The SARS-CoV S2 is a potential drug target, as peptidomimetics against S2 act as potent fusion inhibitors. In this study, site-directed mutagenesis and thermal stability experiments on electrostatic, hydrophobic, and polar residues to dissect their roles in stabilizing the S2 postfusion conformation was performed. It was shown that unlike the pH-independent retroviral fusion proteins, SARS-CoV S2 is stable over a wide pH range, supporting its ability to fuse at both the plasma membrane and endosome. A comprehensive SARS-CoV S2 analysis showed that specific hydrophobic positions at the C-terminal end of the HR2, rather than electrostatics are critical for fusion protein stabilization. Disruption of the conserved C-terminal hydrophobic residues destabilized the fusion core and reduced the melting temperature by 30°C. The importance of the C-terminal hydrophobic residues led us to identify a 42-residue substructure on the central core that is structurally conserved in all existing CoV S2 fusion proteins (root mean squared deviation = 0.4 Å). This is the first study to identify such a conserved substructure and likely represents a common foundation to facilitate viral fusion. We have discussed the role of key residues in the design of fusion inhibitors and the potential of the substructure as a general target for the development of novel therapeutics against CoV infections.