title: The mechanistic overview of SARS-CoV-2 using angiotensin-converting enzyme 2 to enter the cell for replication: possible treatment options related to the renin–angiotensin system

text: The SARS-CoV-2 pandemic is a healthcare crisis caused by insufficient knowledge applicable to effectively combat the virus. Therefore, different scientific discovery strategies need to be connected, to generate a rational treatment which can be made available as rapidly as possible. This relies on a solid theoretical understanding of the mechanisms of SARS-CoV-2 infection and host responses, which is coupled to the practical experience of clinicians that are treating patients. Because SARS-CoV-2 enters the cell by binding to angiotensin-converting enzyme 2 (ACE2), targeting ACE2 to prevent such binding seems an obvious strategy to combat infection. However, ACE2 performs its functions outside the cell and was found to enter the cell only by angiotensin II type 1 receptor (AT1R)-induced endocytosis, after which ACE2 is destroyed. This means that preventing uptake of ACE2 into the cell by blocking AT1R would be a more logical approach to limit entry of SARS-CoV-2 into the cell. Since ACE2 plays an important protective role in maintaining key biological processes, treatments should not disrupt the functional capacity of ACE2, to counterbalance the negative effects of the infection. Based on known mechanisms and knowledge of the characteristics of SARS-CoV we propose the hypothesis that the immune system facilitates SARS-CoV-2 replication which disrupts immune regulatory mechanisms. The proposed mechanism by which SARS-CoV-2 causes disease immediately suggests a possible treatment, since the AT1R is a key player in this whole process. AT1R antagonists appear to be the ideal candidate for the treatment of SARS-CoV-2 infection. AT1R antagonists counterbalance the negative consequences of angiotesnin II and, in addition, they might even be involved in preventing the cellular uptake of the virus without interfering with ACE2 function. AT1R antagonists are widely available, cheap, and safe. Therefore, we propose to consider using AT1R antagonists in the treatment of SARS-CoV-2.


title: Severe COVID‐19 in a renal transplant recipient: A focus on pharmacokinetics

text: The current coronavirus disease 2019 (COVID‐19) pandemic requires extra attention for immunocompromised patients, including solid organ transplant recipients. We report on a case of a 35‐year‐old renal transplant recipient who suffered from a severe COVID‐19 pneumonia. The clinical course was complicated by extreme overexposure to the mammalian target of rapamycin inhibitor everolimus, following coadministration of chloroquine and lopinavir/ritonavir therapy. The case is illustrative for dilemmas that transplant professionals may face in the absence of evidence‐based COVID‐19 therapy and concurrent pressure for exploration of experimental pharmacological treatment options. However, the risk‐benefit balance of experimental or off‐label therapy may be weighed differently in organ transplant recipients than in otherwise healthy COVID‐19 patients, owing to their immunocompromised status and potential drug interactions with immunosuppressive therapy. With this case report, we aimed to achieve increased awareness and improved management of drug‐drug interactions associated with the various treatment options for COVID‐19 in renal transplant patients.


title: Recent Progress in Studies of Arterivirus- and Coronavirus-Host Interactions

text: Animal coronaviruses, such as infectious bronchitis virus (IBV), and arteriviruses, such as porcine reproductive and respiratory syndrome virus (PRRSV), are able to manifest highly contagious infections in their specific native hosts, thereby arising in critical economic damage to animal industries. This review discusses recent progress in studies of virus-host interactions during animal and human coronavirus and arterivirus infections, with emphasis on IBV-host cell interactions. These interactions may be directly involved in viral replication or lead to the alteration of certain signaling pathways, such as cell stress response and innate immunity, to facilitate viral replication and pathogenesis.


title: Characterization of the Role of Hexamer AGUAAA and Poly(A) Tail in Coronavirus Polyadenylation

text: Similar to eukaryotic mRNA, the positive-strand coronavirus genome of ~30 kilobases is 5’-capped and 3’-polyadenylated. It has been demonstrated that the length of the coronaviral poly(A) tail is not static but regulated during infection; however, little is known regarding the factors involved in coronaviral polyadenylation and its regulation. Here, we show that during infection, the level of coronavirus poly(A) tail lengthening depends on the initial length upon infection and that the minimum length to initiate lengthening may lie between 5 and 9 nucleotides. By mutagenesis analysis, it was found that (i) the hexamer AGUAAA and poly(A) tail are two important elements responsible for synthesis of the coronavirus poly(A) tail and may function in concert to accomplish polyadenylation and (ii) the function of the hexamer AGUAAA in coronaviral polyadenylation is position dependent. Based on these findings, we propose a process for how the coronaviral poly(A) tail is synthesized and undergoes variation. Our results provide the first genetic evidence to gain insight into coronaviral polyadenylation.


title: Development of small-molecule viral inhibitors targeting various stages of the life cycle of emerging and re-emerging viruses

text: In recent years, unexpected outbreaks of infectious diseases caused by emerging and re-emerging viruses have become more frequent, which is possibly due to environmental changes. These outbreaks result in the loss of life and economic hardship. Vaccines and therapeutics should be developed for the prevention and treatment of infectious diseases. In this review, we summarize and discuss the latest progress in the development of small-molecule viral inhibitors against highly pathogenic coronaviruses, including severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, Ebola virus, and Zika virus. These viruses can interfere with the specific steps of viral life cycle by blocking the binding between virus and host cells, disrupting viral endocytosis, disturbing membrane fusion, and interrupting viral RNA replication and translation, thereby demonstrating potent therapeutic effect against various emerging and re-emerging viruses. We also discuss some general strategies for developing small-molecule viral inhibitors.


title: Healthcare infrastructure capacity to respond to severe acute respiratory infection (SARI) and sepsis in Vietnam: A low-middle income country

text: Abstract Purpose This study investigated the availability of relevant structural and human resources needed for the clinical management of patients with severe acute respiratory infections and sepsis in critical care units in Vietnam. Material and methods A questionnaire survey was conducted by purposive sampling of 128 hospitals (36% of total hospitals in surveyed provinces), including 25 provincial and 103 district level hospitals, from 20 provinces in Vietnam. Data on availability of hospital characteristics, structural resources and health care workers was then analyzed. Results Most hospitals (>80%) reported having 60% of the relevant structural resources. Significant differences were observed between provincial hospitals when compared to district hospitals in regards to availability of central oxygen piping system (78.3% vs 38.7%, p =0.001) mechanical ventilation (100.0% vs 73.6%, p =0.003), mobile x-rays (80.0% vs 29.8%, p <0.001), carbapenem antibiotic (73.9% vs 17.4%, p <0.001) and norepinephrine (95.8% vs 56.3%, p <0.001). There was a limited availability of arterial blood gas analyzers (13.7%), oseltamivir (42.2%) and N95 respirators (54.6%) across all hospitals surveyed. Conclusions The limited availability of relevant structural and human resources in critical care units around Vietnam makes the implementation of quality critical care to patients with SARI and sepsis, according international guidelines, not universally possible.


docid: wnbqqzot

title: Cross-Sectional Study on Awareness and Knowledge of COVID-19 Among Senior pharmacy Students

text: Extraordinary actions have been implemented in an effort to control the rapid spread of the ongoing COVID-19 epidemic in Egypt. People’s adherence to control measures is influenced by their knowledge, attitudes and practices towards the disease. Therefore, in the present study we assessed pharmacy senior students’ knowledge, attitudes and practices towards the COVID-19 pandemic. An online questionnaire was created and it consisted of 12 questions testing their knowledge about COVID-19 clinical characteristics, transmission routes and prevention and control steps. Among senior pharmacy students (n = 238), 70% were females and 63% were living in greater Cairo. Their main source of information included social media (70%), published articles (48%) and television (48%). The overall correct knowledge score was 83%. Most of the students displayed a good COVID-19 knowledge level (72.5% of the students). The students were least informed when trying to answer questions about hyper-coagulation, as a major cause for death in patients with severe COVID-19, and about the timings on the necessity to wear masks. Assessment of students’ attitudes and practices towards COVID-19 reflected that 87% of them were confident that health care teams and scientists could win the fight against the virus. In addition, 72% of students agreed that COVID-19 will be controlled successfully. The greater the students’ knowledge, the more confident they felt that COVID-19 will be controlled successfully (OR 2.2, 95% confidence interval [CI] 1.03–4.72). Good behavioral practice towards COVID-19 control was confirmed when 87% of students answered that they didn’t go out to any crowded place. Females were 3.6 times (95% confidence interval [CI] 1.03–3.11) more likely to avoid going out than males. Bad behavioral practice became evident when approximately 50% of students admitted that they did not wear masks when they left their house. Therefore, more efforts should be taken to protect future pharmacists from this pandemic.


title: Impact of the 2020 COVID-19 pandemic on the workload of the orthopaedic service in a busy UK District General Hospital

text: The COVID -19 outbreak has had a profound effect on the management of healthcare service provision in the UK. Orthopaedic departments have been no exception to this and have needed to adapt to the changing circumstances by releasing resources and focusing on ‘essential’ activity. The aim of this study is to quantify the reduction in trauma and, in addition, describe any changes in the type of referrals to the trust which may have been affected by the pandemic itself and the social distancing measures employed by the UK government. Methods; The study was performed in a UK District Hospital which is also a Trauma Unit providing trauma and orthopaedic care to a population of 625,000 people. The trust based electronic database of trauma referrals was used to compare the numbers of, and types of referral to our trauma service during the COVID-19 pandemic and the corresponding time periods in the previous 3 years. Results; The mean number of referrals per week to the service reduced by 33% in the time period following the confirmation of the outbreak as a pandemic (p<0.0001). Number of operations performed per week reduced by 26% (p=0.001). There was no change in the number of referrals relating to domestic abuse or non-accidental injury. In addition, numbers of hip fractures, periprosthetic fractures and prosthetic joint dislocations were unchanged. There was a significant reduction in the number of referrals for simple fractures, native joint dislocations, wounds and soft tissue injuries. Within the paediatric population, similarly, a reduction in simple fracture referrals was demonstrated. Discussion; An association between the outbreak of the pandemic and a reduction in referral numbers to our department has been demonstrated. The direct cause of this may be multifactorial but proposing that it is, in part, due to the social distancing measures introduced by the government is certainly conceivable. The patterns of injury would reflect this also with low energy and fragility trauma persisting whilst injuries associated with younger people have reduced. We would suggest that information such as this could be useful in healthcare planning and resource allocation in future pandemic situations.


docid: gvenywfc

title: Unprotected stroke management in an undiagnosed case of Severe Acute Respiratory Syndrome Coronavirus 2 infection

text: Abstract Coronavirus disease 19 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this scenario, managing acute medical conditions, such as stroke, requires a timely treatment together with proper strategies that minimize the risk of infection spreading to health care workers and other patients. We report the case of a 79-year-old woman, who was admitted for a wake-up stroke due to occlusion of the left middle cerebral artery. She was treated outside the COVID-19-dedicated track of the hospital because she had no concomitant signs or symptoms suggestive of SARS-CoV-2 infection nor recent contact with other infected individuals. Post-mortem nasal and pharyngeal swab was positive for SARS-CoV-2 infection. We propose that hyperacute stroke patients should be tested for SARS-CoV-2 infection at admission and then managed as having COVID-19 until cleared by a negative result. We are aware that such measure results in some delay of the acute treatment of stroke, which could be minimal using well-exercised containment protocols.


Cardio‐Oncology services during the COVID‐19 pandemic: Practical considerations and challenges


title: Ca2+ ions promote fusion of Middle East Respiratory Syndrome coronavirus with host cells and increase infectivity

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a major emerging zoonotic infectious disease. Since its first outbreak in 2012, the virus has repeatedly transmitted from camels to humans with 2,468 confirmed cases, causing 851 deaths. To date, there are no efficacious drugs and vaccines against MERS-CoV, increasing its potential to cause a public health emergency. A critical step in the life cycle of MERS-CoV is the fusion with the host cell with its spike (S) protein as main determinant of viral entry. Proteolytic cleavage of S exposes its fusion peptide (FP), which initiates membrane fusion. Previous studies on the related severe acute respiratory syndrome coronavirus (SARS-CoV) FP have shown that calcium (Ca2+) plays an important role for fusogenic activity via a Ca2+ binding pocket with conserved glutamic acid (E) and aspartic acid (D) residues. SARS-CoV and MERS-CoV FP share a high sequence homology and here, we investigated whether Ca2+ is required for MERS-CoV fusion by substituting E and D residues in the MERS-CoV FP with neutrally charged alanines. Upon verifying mutant cell surface expression and proteolytic cleavage, we tested the mutants ability to mediate infection of pseudo-particles (PPs) on host cells without and with Ca2+. Our results demonstrate that intracellular Ca2+ enhances MERS-CoV WT PPs infection by approximately two-fold and that E891 is a crucial residue for Ca2+ interaction. Electron spin resonance revealed that this enhancement could be attributed to Ca2+ increasing MERS-CoV FP fusion-relevant membrane ordering. Intriguingly, isothermal calorimetry titration showed that MERS-CoV FP binds one Ca2+, as opposed to SARS-CoV FP which binds two. Our data suggests that there are significant differences in FP-Ca2+ interactions of MERS-CoV and SARS-CoV FP despite their high sequence similarity and that the number of Ca2+ ions interacting with the FP has implications on the fusion dynamics of the virus.


title: Alterations in sialic-acid O-acetylation glycoforms during murine erythrocyte development

text: We used Casd1-deficient mice to confirm that this enzyme is responsible for 9-O-acetylation of sialic acids in vivo. We observed a complete loss of 9-O-acetylation of sialic acid on the surface of myeloid, erythroid and CD4(+) T cells in Casd1-deficient mice. Although 9-O-acetylation of sialic acids on multiple hematopoietic lineages was lost, there were no obvious defects in hematopoiesis. Interestingly, erythrocytes from Casd1-deficient mice also lost reactivity to TER-119, a rat monoclonal antibody that is widely used to mark the murine erythroid lineage. The sialic acid glyco-epitope recognized by TER-119 on erythrocytes was sensitive to the sialic acid O-acetyl esterase activity of the hemagglutinin-esterase from bovine coronavirus but not to the corresponding enzyme from the influenza C virus. During erythrocyte development, TER-119(+) Ery-A and Ery-B cells could be stained by catalytically inactive bovine coronavirus hemagglutinin-esterase but not by the inactive influenza C hemagglutinin-esterase, while TER-119(+) Ery-C cells and mature erythrocytes were recognized by both virolectins. Although the structure of the sialoglycoconjugate recognized by TER-119 was not chemically demonstrated, its selective binding to virolectins suggests that it may be comprised of a 7,9-di-O-acetyl form of sialic acid. As erythrocytes mature, the surfaces of Ery-C cells and mature erythrocytes also acquire an additional distinct CASD1-dependent 9-O-acetyl sialic acid moiety that can be recognized by virolectins from both influenza C and bovine coronavirus.


Urgent development of effective therapeutic and prophylactic agents to control the emerging threat of Middle East respiratory syndrome (MERS)


title: The impact of unplanned school closure on children’s social contact: rapid evidence review

text: BACKGROUND: Emergency school closures are often used as public health interventions during infectious disease outbreaks to minimise the spread of infection. However, if children continue mixing with others outside the home during closures, the effect of these measures may be limited. AIM: This review aimed to summarise existing literature on children’s activities and contacts made outside the home during unplanned school closures. METHODS: In February 2020, we searched four databases, MEDLINE, PsycInfo, Embase and Web of Science, from inception to 5 February 2020 for papers published in English or Italian in peer-reviewed journals reporting on primary research exploring children’s social activities during unplanned school closures. Main findings were extracted. RESULTS: A total of 3,343 citations were screened and 19 included in the review. Activities and social contacts appeared to decrease during closures, but contact remained common. All studies reported children leaving the home or being cared for by non-household members. There was some evidence that older child age (two studies) and parental disagreement (two studies) with closure were predictive of children leaving the home, and mixed evidence regarding the relationship between infection status and such. Parental agreement with closure was generally high, but some disagreed because of perceived low risk of infection and issues regarding childcare and financial impact. CONCLUSION: Evidence suggests that many children continue to leave home and mix with others during school closures despite public health recommendations to avoid social contact. This review of behaviour during unplanned school closures could be used to improve infectious disease modelling.


title: The immunologic status of newborns born to SARS-CoV2-infected mothers in Wuhan, China

text: Background Immunologic dysfunction due to COVID-19 is closely related to clinical prognosis, and the inflammatory response of pregnant women may affect the directional differentiation and function of fetal immune cells. Objective To analyze the immune status of newborns from mothers with COVID-19 in the third trimester. Methods Along with collecting the clinical data from 51 newborns and their respective mothers, we also recorded the immunophenotypes and cytokine and immunoglobulin levels of the newborns. Results None of the 51 newborns showed fever or respiratory distress during hospitalization. Detection of SARS-CoV-2 nucleic acid in pharyngeal swabs was negative. Except for the low level of CD16-CD56 cells, the count and proportion of lymphocytes, CD3, CD4, CD8, and CD19 were all in the normal range. Moreover, the serum IgG and IgM levels were within the normal range, while IL-6 showed increased levels. There was no correlation between maternal COVID-19 duration and the lymphocyte subsets or cytokine levels (IFN-γ, IL-2, IL-4, IL-6, IL-10 and TNF-α). There was a positive correlation between IL-6 and IL-10 levels and CD16-CD56 cells. One (1.96%) infant with an extremely elevated IL-6 concentration developed necrotizing enterocolitis in the third week after birth, and the remaining 50 infants did not show abnormal symptoms through the end of the follow-up period. Conclusion COVID-19 in the third trimester did not significantly affect the cellular and humoral immunity of the fetus, and there was no evidence that the differentiation of lymphocyte subsets was seriously unbalanced.


title: Enhancing the Robustness of Smartphone Photoplethysmography: A Signal Quality Index Approach

text: Heart rate variability (HRV) provides essential health information such as the risks of heart attacks and mental disorders. However, inconvenience related to the accurate detection of HRV limits its potential applications. The ubiquitous use of smartphones makes them an excellent choice for regular and portable health monitoring. Following this trend, smartphone photoplethysmography (PPG) has recently garnered prominence; however, the lack of robustness has prevented both researchers and practitioners from embracing this technology. This study aimed to bridge the gap in the literature by developing a novel smartphone PPG quality index (SPQI) that can filter corrupted data. A total of 226 participants joined the study, and results from 1343 samples were used to validate the proposed sinusoidal function-based model. In both the correlation coefficient and Bland–Altman analyses, the agreement between HRV measurements generated by both the smartphone PPG and the reference electrocardiogram improved when data were filtered through the SPQI. Our results support not only the proposed approach but also the general value of using smartphone PPG in HRV analysis.


title: Use of data linkage to investigate the aetiology of acute lower respiratory infection hospitalisations in children

text: Aim: To document the aetiology of acute lower respiratory infection (ALRI) hospitalisations in Western Australian children by linking population‐based laboratory data with hospital morbidity data. Methods: Data from all ALRI hospitalisations and laboratory records related to respiratory pathogens between 2000 and 2005 were extracted and linked through a population‐based record linkage system. The proportion of specimens that were positive for each respiratory viral or bacterial pathogen was documented. Results: Eight thousand nine hundred and eighty (45.2%) ALRI hospitalisations were linked to a laboratory record. Admissions to a private hospital and admissions from non‐metropolitan areas were less likely to have a linked laboratory record. In 57.9% of linked hospitalisations, a respiratory virus and/or a bacterial pathogen was identified. Frequently identified viral pathogens included respiratory syncytial virus (RSV; n= 3226; 39.5% of those tested), influenza viruses (n= 664; 8.5%), parainfluenza virus type 3 (n= 348; 4.6%), picornaviruses (n= 292; 22.3%) and adenoviruses (n= 211; 2.7%). RSV was identified in 63.7% of bronchiolitis admissions in those aged under 6 months and 33.1% of pneumonia admissions in those aged under 12 months. Influenza viruses were identified in 81.6% of influenza‐coded admissions. When a test was requested, Bordetella pertussis was identified in 21.2% of ALRI hospitalisations (n= 354), including 86.8% of whooping cough‐coded admissions. Conclusions: This is the first report of population‐based data linkage between statewide laboratory data and hospitalisation records and demonstrates proof of principle. RSV continues to be an important pathogen in ALRI. As pathogens were identified across all diagnoses, relying on hospital diagnosis coding alone may not accurately estimate the burden of different categories of ALRI.


title: Concerns over UK advice

text: Key scientific data and advice to the UK government won't be published until the coronavirus pandemic ends, reports David Adam


title: Viral and Atypical Bacterial Etiology of Acute Respiratory Infections in Children under 5 Years Old Living in a Rural Tropical Area of Madagascar

text: BACKGROUND: In Madagascar, very little is known about the etiology and prevalence of acute respiratory infections (ARIs) in a rural tropical area. Recent data are needed to determine the viral and atypical bacterial etiologies in children with defined clinical manifestations of ARIs. METHODS: During one year, we conducted a prospective study on ARIs in children between 2 to 59 months in the community hospital of Ampasimanjeva, located in the south-east of Madagascar. Respiratory samples were analyzed by multiplex real-time RT-PCR, including 18 viruses and 2 atypical bacteria. The various episodes of ARI were grouped into four clinical manifestations with well-documented diagnosis: “Community Acquired Pneumonia”(CAP, group I), “Other acute lower respiratory infections (Other ALRIs, group II)”, “Upper respiratory tract infections with cough (URTIs with cough, group III)”and “Upper respiratory tract infections without cough (URTIs without cough, group IV)”. RESULTS: 295 children were included in the study between February 2010 and February 2011. Viruses and/or atypical bacteria respiratory pathogens were detected in 74.6% of samples, the rate of co-infection was 27.3%. Human rhinovirus (HRV; 20.5%), metapneumovirus (HMPV A/B, 13.8%), coronaviruses (HCoV, 12.5%), parainfluenza virus (HPIV, 11.8%) and respiratory syncytial virus A and B (RSV A/B, 11.8%) were the most detected. HRV was predominantly single detected (23.8%) in all the clinical groups while HMPV A/B (23.9%) was mainly related to CAP (group I), HPIV (17.3%) to the “Other ALRIs” (group II), RSV A/B (19.5%) predominated in the group “URTIs with cough” (group III) and Adenovirus (HAdV, 17.8%) was mainly detected in the “without cough” (group IV). INTERPRETATION: This study describes for the first time the etiology of respiratory infections in febrile children under 5 years in a malaria rural area of Madagascar and highlights the role of respiratory viruses in a well clinically defined population of ARIs.


title: Chapter 2 Basics of virology

text: Abstract Viruses are important pathogens of the nervous system. Here we describe the basic properties of viruses and the principles of virus classification, evolution, structure, and replication, with a focus on neurotropic viruses that are important neuropathogens of humans. These properties then provide the background for introductions to pathogenesis of viral diseases of the nervous system, host immune responses to virus infection, and the diagnosis and treatment of virus infections of the nervous system.


Point of no return: COVID-19 and the U.S. healthcare system: An emergency physician’s perspective


title: Long‐term consequences of the 2020 coronavirus pandemics: Historical global‐macro context

text: The COVID‐19 pandemics is likely to accelerate the trends of de‐globalization and de‐dollarization. Over the long term, the major financial consequence is likely to be the accelerated trend of rising inflation and long‐term interest rates. More broadly, the post‐pandemic environment will likely encompass difficult longer‐term economic and geopolitical challenges. Alternatively, the COVID‐19 pandemics also creates an opportunity for building a new trend of more sustainable globalization.


title: Patient characteristics and severity of human rhinovirus infections in children

text: Abstract Background It is increasingly recognized that human rhinoviruses (HRV) can be associated with severe infections. However, conflicting results have been reported on the relative prevalence and severity of the three HRV species. Objectives The relative prevalence and clinical characteristics of HRV-A, B and C, in children attending a South London teaching hospital were investigated retrospectively. Study design Children aged <16 years with episodes of respiratory tract infections and detectable entero/rhinovirus RNA in respiratory samples between November 2009 and December 2010 were investigated. Retrospective case review was performed and patients’ characteristics recorded. Results Entero/rhinoviruses were the commonest viral pathogens (498/2316; 21.5%). Amongst 204 infection episodes associated with entero/rhinovirus, 167 were typed HRV, HRV-C was the most prevalent (99/167, 59.3%) followed by HRV-A (60/167; 35.9%) and HRV-B (8/167, 4.8%). The severity spectrum of HRV-A and HRV-C infections were similar and affected all parts of the respiratory tract. Co-pathogens were observed in 54 (26.5%) episodes. Severity was increased in patients with non-viral co-pathogens and those with an underlying respiratory condition. Univariate and multiple regression analyses of potential prognostic variables including age, co-pathogens and underlying respiratory illnesses showed that mono-infection with HRV-C, as compared with other HRV species, was associated with more severe disease in young children <3 years. Conclusions HRV-C was the most prevalent species and on its own was associated with severe disease in children <3 years. The association between infection with HRV species and clinical presentation is complex and affected by many confounding factors.


title: Preliminary pragmatic lessons from the SARS-CoV-2 pandemic from France

text: Abstract The first wave of the SARS-CoV-2 pandemic required an unprecedented and historic increase in critical care capacity on a global scale in France. Authors and members from the ACUTE and REANIMATION committees of the French Society of Anaesthesiology and Critical Care (SFAR) wished to share experience and insights gained during the first weeks of this pandemic. These were summarised following the World Health Organisation Response Checklist and detailed according to the subsequent subheadings: 1. Command and Control, 2. Communication, 3. Safety and Security, 4. Triage, 5. Surge Capacity, 6. Continuity of essential services, 7. Human resources, 8. Logistics and supply management, 9. Training/Preparation, 10. Psychological comfort for patients and next of kin, 11. Learning and 12. Post disaster recovery. These experience-based recommendations, consensual across all members from both committees of our national society, establish a practical framework for medical teams, either spared by the first wave of severe COVID patients or preparing for the second one.


title: Lessons learned from the test-to-test variability of different types of wear data

text: Abstract Contrary to the established principles of the scientific method, a surprising number of experimentally-based papers submitted to tribology journals and conferences report only one test result for each material pair or set of applied conditions. However, like hardness, yield strength, fatigue life, and other material properties, wear data exhibit varying degrees of repeatability and reproducibility (R/R). Repeatability concerns the replication of experiments within the same laboratory using the same equipment and materials. Reproducibility concerns testing on different equipment, usually at a different location, but using the same lot of specimens and procedures. An important question is: How many replicate measurements are needed to validate trends in wear behavior or to relatively rank materials, surface treatments, or lubricants? Without repeatability information, it is virtually impossible to establish whether reported material rankings or the effects of variables are real or fall within normal data scatter. The purpose of this paper is to characterize and analyze the R/R of wear data that result from a variety of sources, including material homogeneity, choice of units of measure, and choice of experimental variables. Case studies compare R/R for different forms of wear and their test methods, including ASTM standards. Lessons learned are presented for five forms of wear: (1) cavitation erosion, (2) three-body abrasion, (3) solid particle erosion, (4) dry sliding wear, and (5) fuel lubricity using the ball-on-cylinder (BOCLE) test. Wear transitions can also affect R/R. These examples provide insights for validating wear models, deciding how many repeated tests to make, and when ranking wear-resistance.


title: Impact of international travel dynamics on domestic spread of 2019-nCoV in India: origin-based risk assessment in importation of infected travelers

text: The recent pandemic caused by the 2019 outbreak of novel coronavirus (2019-nCoV or COVID-19) has affected more than 3.0 million people resulting ~ 212,000 deaths across 215 countries/territories as on 28th April 2020. The importation of the cases owing to enormous international travels from the affected countries is the foremost reason for local cycle of transmission. For a country like India, the second most populous country in the world with ~ 1.35 billion population, the management and control of 2019-nCoV domestic spread heavily relied on effective screening and strict quarantine of passengers arriving at various international airports in India from affected countries. Here, by extracting the data from FLIRT, an online airline database for more than 800 airlines, and scanning more than 180,000 flights and 39.9 million corresponding passenger seats during 4th – 25th March, we show that India experienced the highest risk index of importing the passengers from middle eastern airports. Contrary to perception, travelers from China imposed lowest risk of importing the infected cases in India. This is clearly evident form the fact that while the number of infected cases were on the peak in China India was one of the least affected countries. The number of cases in India started exhibiting a sharp increase in the infected cases only after the European countries and USA recorded large number of infected cases. We further argue that while the number of cases in middle eastern countries may still be very low, the airports in middle eastern countries, particularly Dubai, being one of the largest transit hubs for international passengers, including arriving in India, might have posed a higher risk of getting infected with 2019-nCoV. We suggest that any future travel related disease infection screening at the airports should critically assess the passengers from major transit hubs in addition to affected country of origin.


title: How Flaviviruses Activate and Suppress the Interferon Response

text: The flavivirus genus includes viruses with a remarkable ability to produce disease on a large scale. The expansion and increased endemicity of dengue and West Nile viruses in the Americas exemplifies their medical and epidemiological importance. The rapid detection of viral infection and induction of the innate antiviral response are crucial to determining the outcome of infection. The intracellular pathogen receptors RIG-I and MDA5 play a central role in detecting flavivirus infections and initiating a robust antiviral response. Yet, these viruses are still capable of producing acute illness in humans. It is now clear that flaviviruses utilize a variety of mechanisms to modulate the interferon response. The non-structural proteins of the various flaviviruses reduce expression of interferon dependent genes by blocking phosphorylation, enhancing degradation or down-regulating expression of major components of the JAK/STAT pathway. Recent studies indicate that interferon modulation is an important factor in the development of severe flaviviral illness. This suggests that an increased understanding of viral-host interactions will facilitate the development of novel therapeutics to treat these viral infections and improved biological models to study flavivirus pathogenesis.


title: Is the reporting timeliness gap for avian flu and H1N1 outbreaks in global health surveillance systems associated with country transparency?

text: BACKGROUND: This study aims to evaluate the length of time elapsed between reports of the same incidents related to avian flu and H1N1 outbreaks published by the WHO and ProMED-mail, the two major global health surveillance systems, before and after the amendment of the International Health Regulations in 2005 (IHR 2005) and to explore the association between country transparency and this timeliness gap. METHODS: We recorded the initial release dates of each report related to avian flu or H1N1 listed on the WHO Disease Outbreak News site and the matching outbreak report from ProMED-mail, a non-governmental program for monitoring emerging diseases, from 2003 to the end of June 2009. The timeliness gap was calculated as the difference in days between the report release dates of the matching outbreaks in the WHO and ProMED-mail systems. Civil liberties scores were collected as indicators of the transparency of each country. The Human Development Index and data indicating the density of physicians and nurses were collected to reflect countries’ development and health workforce statuses. Then, logistic regression was performed to determine the correlation between the timeliness gap and civil liberties, human development, and health workforce status, controlling for year. RESULTS: The reporting timeliness gap for avian flu and H1N1 outbreaks significantly decreased after 2003. On average, reports were posted 4.09 (SD = 7.99) days earlier by ProMED-mail than by the WHO. Countries with partly free (OR = 5.77) and free civil liberties scores (OR = 10.57) had significantly higher likelihoods of longer timeliness gaps than non-free countries. Similarly, countries with very high human development status had significantly higher likelihoods of longer timeliness gaps than countries with middle or low human development status (OR = 5.30). However, no association between the timeliness gap and health workforce density was found. CONCLUSION: The study found that the adoption of IHR 2005, which contributed to countries’ awareness of the importance of timely reporting, had a significant impact in improving the reporting timeliness gap. In addition, the greater the civil liberties in a country (e.g., importance of freedom of the media), the longer the timeliness gap.


title: Novel Isoxazolidine and γ-Lactam Analogues of Homonucleosides

text: Homonucleoside analogues cis-16 and trans-17 having a (5-methoxycarbonyl)isoxazolidine framework were synthesized via the 1,3-dipolar cycloaddition of nucleobase-derived nitrones with methyl acrylate. Hydrogenolysis of the isoxazolidines containing thymine, dihydrouracil, theophylline and adenine moieties efficiently led to the formation of the respective γ-lactam analogues. γ-Lactam analogues having 5-bromouracil and 5-chlorouracil fragments were synthesized by treatment of uracil-containing γ-lactams with NBS and NCS. Isoxazolidine and γ-lactam analogues of homonucleosides obtained herein were evaluated for activity against a broad range of DNA and RNA viruses. None of the compounds that were tested exhibited antiviral or cytotoxic activity at concentrations up to 100 µM. The cytostatic activities of all compounds toward nine cancerous cell lines was tested. γ-Lactams trans-15e (Cl-Ura) and cis-15h (Theo) appeared the most active toward pancreatic adenocarcinoma cells (Capan-1), showing IC(50) values 21.5 and 18.2 µM, respectively. Isoxazolidine cis-15e (Cl-Ura) inhibited the proliferation of colorectal carcinoma (HCT-116).


title: The effects of group size and subtherapeutic antibiotic alternatives on growth performance and morbidity of nursery pigs: a model for feed additive evaluation

text: The objectives of this experiment were to evaluate the effects of alternatives to antibiotic growth promoters (AGP), two group sizes, and their interaction on nursery pig performance to serve as a model for future AGP alternative studies. A 41-d experiment was conducted in a commercial wean-to-finish barn; 1,300 piglets weaned at 21 d of age (weaned 2 or 4 d prior to experiment; 6.14 ± 0.18 kg BW; PIC 1050 sows and multiple sire lines) were blocked by sire, sex, and weaning date, then assigned to eight treatments: four dietary treatments each evaluated across two group sizes. The four dietary treatments were: negative control (NC), positive control (PC; NC + in-feed antibiotics), zinc oxide plus a dietary acidifier (blend of fumaric, citric, lactic, and phosphoric acid) (ZA; NC + ZnO + acid), and a Bacillus-based direct-fed-microbial (DFM) plus resistant potato starch (RS) (DR; NC + DFM + RS). The two group sizes were 31 or 11 pigs/pen; floor space was modified so area/pig was equal between the group sizes (0.42 m(2)/pig). There were 7 pens/diet with 11 pigs/pen and 8 pens/diet with 31 pigs/pen. Data were analyzed as a randomized complete block design with pen as the experimental unit. Diagnostic assessment of oral fluids, serum, and tissue samples was used to characterize health status. Pigs experienced natural challenges of acute diarrhea and septicemia in week 1 and porcine reproductive and respiratory syndrome virus (PRRSV) in weeks 4–6. There was a significant interaction between diet and group size for ADG (P = 0.012). PC increased ADG in large and small groups (P < 0.05) and ZA increased ADG only in large groups (P < 0.05). Small groups had improved ADG compared to large groups when fed NC or DR diets (P < 0.05). Similarly, PC increased ADFI (P < 0.05). Compared to NC, ZA improved ADFI in large groups only (P < 0.05; diet × group size: P = 0.015). Pigs fed PC had greater G:F than NC (P < 0.05), and small groups had greater G:F than large groups (P < 0.05). There was no effect of ZA or DR on G:F. Pigs fed PC required fewer individual medical treatments than NC and pigs fed ZA were intermediate (P = 0.024). More pigs were removed from large than small groups (P = 0.049), and there was no effect of diet on removals (P > 0.10). In conclusion, careful study design, protocol implementation, sample collection, and recording of important information allowed us to characterize the health status of this group of pigs and determine treatment effects on growth performance and morbidity.


Chapter 46 Passive Immunization: Systemic and Mucosal


title: Visual analytics of geo-social interaction patterns for epidemic control

text: BACKGROUND: Human interaction and population mobility determine the spatio-temporal course of the spread of an airborne disease. This research views such spreads as geo-social interaction problems, because population mobility connects different groups of people over geographical locations via which the viruses transmit. Previous research argued that geo-social interaction patterns identified from population movement data can provide great potential in designing effective pandemic mitigation. However, little work has been done to examine the effectiveness of designing control strategies taking into account geo-social interaction patterns. METHODS: To address this gap, this research proposes a new framework for effective disease control; specifically this framework proposes that disease control strategies should start from identifying geo-social interaction patterns, designing effective control measures accordingly, and evaluating the efficacy of different control measures. This framework is used to structure design of a new visual analytic tool that consists of three components: a reorderable matrix for geo-social mixing patterns, agent-based epidemic models, and combined visualization methods. RESULTS: With real world human interaction data in a French primary school as a proof of concept, this research compares the efficacy of vaccination strategies between the spatial–social interaction patterns and the whole areas. The simulation results show that locally targeted vaccination has the potential to keep infection to a small number and prevent spread to other regions. At some small probability, the local control strategies will fail; in these cases other control strategies will be needed. This research further explores the impact of varying spatial–social scales on the success of local vaccination strategies. The results show that a proper spatial–social scale can help achieve the best control efficacy with a limited number of vaccines. CONCLUSIONS: The case study shows how GS-EpiViz does support the design and testing of advanced control scenarios in airborne disease (e.g., influenza). The geo-social patterns identified through exploring human interaction data can help target critical individuals, locations, and clusters of locations for disease control purposes. The varying spatial–social scales can help geographically and socially prioritize limited resources (e.g., vaccines).


title: Anti-HFRS Human IgG Produced in Transchromosomic Bovines Has Potent Hantavirus Neutralizing Activity and Is Protective in Animal Models

text: We explored an emerging technology to produce anti-Hantaan virus (HTNV) and anti-Puumala virus (PUUV) neutralizing antibodies for use as pre- or post-exposure prophylactics. The technology involves hyperimmunization of transchomosomic bovines (TcB) engineered to express human polyclonal IgG antibodies with HTNV and PUUV DNA vaccines encoding G(n)G(c) glycoproteins. For the anti-HTNV product, TcB was hyperimmunized with HTNV DNA plus adjuvant or HTNV DNA formulated using lipid nanoparticles (LNP). The LNP-formulated vaccine yielded fivefold higher neutralizing antibody titers using 10-fold less DNA. Human IgG purified from the LNP-formulated animal (SAB-159), had anti-HTNV neutralizing antibody titers >100,000. SAB-159 was capable of neutralizing pseudovirions with monoclonal antibody escape mutations in G(n) and G(c) demonstrating neutralization escape resistance. SAB-159 protected hamsters from HTNV infection when administered pre- or post-exposure, and limited HTNV infection in a marmoset model. An LNP-formulated PUUV DNA vaccine generated purified anti-PUUV IgG, SAB-159P, with a neutralizing antibody titer >600,000. As little as 0.33 mg/kg of SAB-159P protected hamsters against PUUV infection for pre-exposure and 10 mg/kg SAB-159P protected PUUV-infected hamsters post-exposure. These data demonstrate that DNA vaccines combined with the TcB-based manufacturing platform can be used to rapidly produce potent, human, polyclonal, escape-resistant anti-HTNV, and anti-PUUV neutralizing antibodies that are protective in animal models.


docid: ktiwfcop

title: Patients with bullous disorders during COVID‐19 period: management and adherence to treatment


title: Factor structure of the General Health Questionnaire (GHQ-12) in subjects who had suffered from the 2004 Niigata-Chuetsu Earthquake in Japan: a community-based study

text: BACKGROUND: Factor structure of the 12-item General Health Questionnaire (GHQ-12) was studied by a survey of subjects who had experienced the 2004 Niigata-Chuetsu earthquake (6.8 on the Richter scale) in Japan. METHODS: Psychological distress was measured at two years after the earthquake by using GHQ-12 in 2,107 subjects (99.0% response rate) who suffered the earthquake. GHQ-12 was scored by binary, chronic and Likert scoring method. Confirmatory factor analysis was used to reveal the factor structure of GHQ-12. Categorical regression analysis was performed to evaluate the relationships between various background factors and GHQ-12 scores. RESULTS: Confirmatory factor analysis revealed that the model consisting of the two factors and using chronic method gave the best goodness-of-fit among the various models for factor structure. Recovery in the scale for the factor 'social dysfunction' was remarkably impaired compared with that of the factor 'dysphoria'. Categorical regression analysis revealed that various factors, including advanced age, were associated with psychological distress. Advanced age affected the impaired recovery of factor 'social dysfunction' score as well as total GHQ score. CONCLUSION: The two-factor structure of GHQ-12 was conserved between the survey at five month and that at two years after the earthquake. Impaired recovery in the ability to cope with daily problems in the subjects who had experienced the earthquake was remarkable even at two years after the earthquake.


title: Detection by Reverse Transcription–Polymerase Chain Reaction of Influenza C in Nasopharyngeal Secretions of Adults with a Common Cold

text: The lack of practical methods for a laboratory diagnosis of influenza C virus infections and the seemingly benign nature of the virus contribute to the fact that 50 years after its first isolation, relatively little is known about the epidemiology and the clinical impact of this virus. Reverse transcription–polymerase chain reaction (RT-PCR) was used to amplify influenza C RNA fragments from clinical specimens. Two hundred otherwise healthy adults with recent onset of a common cold were studied. Nasopharyngeal aspirates were collected at entry to the study and 1 week later. Serum samples for antibody determinations were obtained at the first visit and after 3 weeks. Influenza C was detected in 7 of the 200 patients by 2 different RT-PCR formats. All 7 patients had a significant increase in antibody titers between serum samples collected during the acute and convalescent phases of the illness. Influenza C appears to be one of the many viruses that cause acute upper respiratory tract infections in adults


title: How urbanization affects the epidemiology of emerging infectious diseases

text: The world is becoming more urban every day, and the process has been ongoing since the industrial revolution in the 18th century. The United Nations now estimates that 3.9 billion people live in urban centres. The rapid influx of residents is however not universal and the developed countries are already urban, but the big rise in urban population in the next 30 years is expected to be in Asia and Africa. Urbanization leads to many challenges for global health and the epidemiology of infectious diseases. New megacities can be incubators for new epidemics, and zoonotic diseases can spread in a more rapid manner and become worldwide threats. Adequate city planning and surveillance can be powerful tools to improve the global health and decrease the burden of communicable diseases.


title: Antiviral Action of Tryptanthrin Isolated from Strobilanthes cusia Leaf against Human Coronavirus NL63

text: Strobilanthes cusia (Nees) Kuntze is a Chinese herbal medicine used in the treatment of respiratory virus infections. The methanol extract of S. cusia leaf contains chemical components such as β-sitosterol, indirubin, tryptanthrin, betulin, indigodole A, and indigodole B that have diverse biological activities. However, the antiviral action of S. cusia leaf and its components against human coronavirus remains to be elucidated. Human coronavirus NL63 infection is frequent among immunocompromised individuals, young children, and in the elderly. This study investigated the anti-Human coronavirus NL63 (HCoV-NL63) activity of the methanol extract of S. cusia leaf and its major components. The methanol extract of S. cusia leaf effectively inhibited the cytopathic effect (CPE) and virus yield (IC(50) = 0.64 μg/mL) in HCoV-NL63-infected cells. Moreover, this extract potently inhibited the HCoV-NL63 infection in a concentration-dependent manner. Among the six components identified in the methanol extract of S. cusia leaf, tryptanthrin and indigodole B (5aR-ethyltryptanthrin) exhibited potent antiviral activity in reducing the CPE and progeny virus production. The IC(50) values against virus yield were 1.52 μM and 2.60 μM for tryptanthrin and indigodole B, respectively. Different modes of time-of-addition/removal assay indicated that tryptanthrin prevented the early and late stages of HCoV-NL63 replication, particularly by blocking viral RNA genome synthesis and papain-like protease 2 activity. Notably, tryptanthrin (IC(50) = 0.06 μM) and indigodole B (IC(50) = 2.09 μM) exhibited strong virucidal activity as well. This study identified tryptanthrin as the key active component of S. cusia leaf methanol extract that acted against HCoV-NL63 in a cell-type independent manner. The results specify that tryptanthrin possesses antiviral potential against HCoV-NL63 infection.


DR CONGO: Coronavirus Challenge


title: Solvability and stability of a fractional dynamical system of the growth of COVID-19 with approximate solution by fractional Chebyshev polynomials

text: Lately, many studies were offered to introduce the population dynamics of COVID-19. In this investigation, we extend different physical conditions of the growth by employing fractional calculus. We study a system of coupled differential equations, which describes the dynamics of the infection spreading between infected and asymptomatic styles. The healthy population properties are measured due to the social meeting. The result is associated with a macroscopic law for the population. This dynamic system is appropriate to describe the performance of growth rate of the infection and to verify if its control is appropriately employed. A unique solution, under self-mapping possessions, is investigated. Approximate solutions are presented by utilizing fractional integral of Chebyshev polynomials. Our methodology is based on the Atangana–Baleanu calculus, which provides various activity results in the simulation. We tested the suggested system by using live data. We found positive action in the graphs.


title: PCBP2 promotes the development of glioma by regulating FHL3/TGF‐β/Smad signaling pathway

text: The purpose of this study was to investigate the role of Poly (C)‐binding protein 2 (PCBP2) and the related signaling pathway in glioma progression. Quantitative real‐time polymerase chain reaction (qRT‐PCR) and immunohistochemistry (IHC) were performed to measure PCBP2 messenger RNA and protein expression in glioma tissues or cells. Cell transfection was completed using Lipofectamine 2000. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, Transwell assay and flow cytometry assay were used to explore the effects of PCBP2 expression on biological behaviors of glioma cells. Western blot assay was used for the detection of pathway related proteins. Expression of PCBP2 in glioma tissues and cells were higher than that in paracancerous tissues and normal cells (both p < .01). Moreover, the elevated expression of PCBP2 was significantly correlated with tumor size (p = .001) and WHO stage (p = .010). Knockdown of PCBP2 could suppress proliferation, migration and invasion of glioma cells and promote apoptosis. Besides, the expression of transforming growth factor‐β (TGF‐β) pathway related proteins TGF‐β1, p‐Smad2 and p‐Smad7 were decreased following the downregulation of PCBP2. PCBP2 also inhibited FHL3 expression by binding to FHL3‐3′UTR. The inhibition of FHL3 could reverse the antitumor action caused by PCBP2 silencing. In vivo assay, PCBP2 was also found to inhibit the tumor growth of glioma. PCBP2 activates TGF‐β/Smad signaling pathway by inhibiting FHL3 expression, thus promoting the development and progression of glioma.


title: Outbreak of Middle East Respiratory Syndrome at Tertiary Care Hospital, Jeddah, Saudi Arabia, 2014

text: During March–May 2014, a Middle East respiratory syndrome (MERS) outbreak occurred in Jeddah, Saudi Arabia, that included many persons who worked or received medical treatment at King Fahd General Hospital. We investigated 78 persons who had laboratory-confirmed MERS during March 2–May 10 and documented contact at this hospital. The 78 persons with MERS comprised 53 patients, 16 healthcare workers, and 9 visitors. Among the 53 patients, the most probable sites of acquisition were the emergency department (22 patients), inpatient areas (17), dialysis unit (11), and outpatient areas (3). Infection control deficiencies included limited separation of suspected MERS patients, patient crowding, and inconsistent use of infection control precautions; aggressive improvements in these deficiencies preceded a decline in cases. MERS coronavirus transmission probably was multifocal, occurring in multiple hospital settings. Continued vigilance and strict application of infection control precautions are necessary to prevent future MERS outbreaks.


From Chinese Science Bulletin to Science Bulletin: celebrate the coming 50th birthday


title: Clinical evaluation of a new single-tube multiplex reverse transcription PCR assay for simultaneous detection of 11 respiratory viruses, Mycoplasma pneumoniae and Chlamydia in hospitalized children with acute respiratory infections

text: Abstract Respiratory Pathogen 13 Detection Kit (13× kit) is able to simultaneously detect 11 respiratory viruses, Mycoplasma pneumoniae (MP) and Chlamydia in a single reaction. Using 572 Nasopharyngeal aspirates collected from hospitalized children, the clinical performance of 13× kit for detecting 11 respiratory viruses was evaluated in comparison with a routinely used 2-tube multiplex reverse transcription PCR assay (2-tube assay) at provincial Centers for Disease Control and Prevention in China. The clinical performance of 13× kit for detecting MP and Chlamydia was evaluated by commercial real-time quantitative PCR (qPCR) kits or sequencing. For tested viruses, the assay concordance was 95.98% and the kappa coefficient was 0.89. All the MP and Chlamydia positive samples detected by 13× kit were confirmed as true positives. The utilization of the 13× kit in clinical settings will be helpful for doctors to assess clinical outcome according to virus type or multiple infections, and to limit the use of antibiotics.


title: Mathematical and computational approaches to epidemic modeling: a comprehensive review

text: Mathematical and computational approaches are important tools for understanding epidemic spread patterns and evaluating policies of disease control. In recent years, epidemiology has become increasingly integrated with mathematics, sociology, management science, complexity science, and computer science. The cross of multiple disciplines has caused rapid development of mathematical and computational approaches to epidemic modeling. In this article, we carry out a comprehensive review of epidemic models to provide an insight into the literature of epidemic modeling and simulation. We introduce major epidemic models in three directions, including mathematical models, complex network models, and agent-based models. We discuss the principles, applications, advantages, and limitations of these models. Meanwhile, we also propose some future research directions in epidemic modeling.


title: Risk factors and pathogenic microorganism characteristics for pneumonia in convalescent patients with stroke: A retrospective study of 380 patients from a rehabilitation hospital: A retrospective study of risk factors and pathogenic microorganism characteristics for pneumonia in convalescent patients with stroke

text: BACKGROUND: Pneumonia is a major complication leading to death after stroke. The risk factors of pneumonia in convalescent patients who have experienced stroke remain poorly defined. METHODS: To identify the risk factors of pneumonia, we applied logistic regression as a statistical method using SPSS23.0 statistical software, based on a sample of 380 patients. And statistical description method was used to analyze pathogens’ characteristics and drug resistance. RESULTS: Ultimately, the obtained logistic model has statistical significance (χ(2)(13) = 91.560, P <0.0005). The sensitivity of the model is 41.7%, the specificity is 97.6%, the positive predictive value is 76.9%, and the negative predictive value is 89.8%. The Barthel index (BI) (OR=1.97, 95% CI: 1.01-3.87), basic lung diseases (OR=4.24, 95% CI: 1.02-17.61), trachea ventilation (OR=6.56, 95% CI: 1.18-36.34), feeding tube (OR=6.06, 95% CI: 2.59-14.18), and hypoproteinemia (OR=3.97, 95% CI: 1.56-10.10) were statistically significant (P<0.05). Among patients who have pneumonia, the proportion of gram-positive bacteria, gram-negative bacteria and fungal infection is 10.00%, 54.29%, 5.71% respectively. The study most frequently isolated Pseudomonas aeruginosa (18.57%), followed by Acinetobacter baumannii (10.00%,) and Klebsiella pneumoniae (10.00%). The drug resistance rate of Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae to different antibiotics ranged from 0.00-37.77%, 0.00-85.71% and 0.00-57.14%, respectively. CONCLUSIONS: The lower BI scores, basic lung diseases, trachea ventilation, tube feeding, and hypoproteinemia are independent risk factors of pneumonia among convalescent patients with stroke. The main pathogens that caused pneumonia were gram-negative bacteria, and such organisms have different degrees of resistance to drugs.


title: ACUTE AORTIC DISSECTION SURGERY IN PATIENT WITH COVID-19

text: Abstract Acute aortic dissection is one of the most common life-threatening disease which affects aortic vessel. We present a case of acute Stanford type A aortic dissection in a patient with covid-19 under treatment of ACE inhibitors. A 68-year-old female complaining of acute chest pain and dyspnea admitted to the emergency clinic of our hospital on May 6, 2020. She had history of diabetes and hypertension. This is one of the first acute aortic surgery case among patients with COVID-19.


title: Tight Junctions Go Viral!

text: Tight junctions (TJs) are highly specialized membrane domains involved in many important cellular processes such as the regulation of the passage of ions and macromolecules across the paracellular space and the establishment of cell polarity in epithelial cells. Over the past few years there has been increasing evidence that different components of the TJs can be hijacked by viruses in order to complete their infectious cycle. Viruses from at least nine different families of DNA and RNA viruses have been reported to use TJ proteins in their benefit. For example, TJ proteins such as JAM-A or some members of the claudin family of proteins are used by members of the Reoviridae family and hepatitis C virus as receptors or co-receptors during their entry into their host cells. Reovirus, in addition, takes advantage of the TJ protein Junction Adhesion Molecule-A (JAM-A) to achieve its hematogenous dissemination. Some other viruses are capable of regulating the expression or the localization of TJ proteins to induce cell transformation or to improve the efficiency of their exit process. This review encompasses the importance of TJs for viral entry, replication, dissemination, and egress, and makes a clear statement of the importance of studying these proteins to gain a better understanding of the replication strategies used by viruses that infect epithelial and/or endothelial cells.


title: RNA viruses in community-acquired childhood pneumonia in semi-urban Nepal; a cross-sectional study

text: BACKGROUND: Pneumonia is among the main causes of illness and death in children <5 years of age. There is a need to better describe the epidemiology of viral community-acquired pneumonia (CAP) in developing countries. METHODS: From July 2004 to June 2007, we examined nasopharyngeal aspirates (NPA) from 2,230 cases of pneumonia (World Health Organization criteria) in children 2 to 35 months old recruited in a randomized trial of zinc supplementation at a field clinic in Bhaktapur, Nepal. The specimens were examined for respiratory syncytial virus (RSV), influenza virus type A (InfA) and B (InfB), parainfluenza virus types 1, 2 and 3 (PIV1, PIV2, and PIV3), and human metapneumovirus (hMPV) using a multiplex reverse transcriptase polymerase chain reaction (PCR) assay. RESULTS: We identified 919 virus isolates in 887 (40.0%) of the 2,219 NPA specimens with a valid PCR result, of which 334 (15.1%) yielded RSV, 164 (7.4%) InfA, 129 (5.8%) PIV3, 98 (4.4%) PIV1, 93 (4.2%) hMPV, 84 (3.8%) InfB, and 17 (0.8%) PIV2. CAP occurred in an epidemic pattern with substantial temporal variation during the three years of study. The largest peaks of pneumonia occurrence coincided with peaks of RSV infection, which occurred in epidemics during the rainy season and in winter. The monthly number of RSV infections was positively correlated with relative humidity (r(s )= 0.40, P = 0.01), but not with temperature or rainfall. An hMPV epidemic occurred during one of the three winter seasons and the monthly number of hMPV cases was also associated with relative humidity (r(s )= 0.55, P = 0.0005). CONCLUSION: Respiratory RNA viruses were detected from NPA in 40% of CAP cases in our study. The most commonly isolated viruses were RSV, InfA, and PIV3. RSV infections contributed substantially to the observed CAP epidemics. The occurrence of viral CAP in this community seemed to reflect more or less overlapping micro-epidemics with several respiratory viruses, highlighting the challenges of developing and implementing effective public health control measures.


title: Intragastric administration of attenuated Salmonella typhimurium harbouring transmissible gastroenteritis virus (TGEV) DNA vaccine induced specific antibody production

text: Attenuated Salmonella typhimurium was selected as a transgenic vehicle for the development of live mucosal vaccines against transmissible gastroenteritis virus (TGEV). A 2.2 kb DNA fragment, encoding for N-terminal domain glycoprotein S of TGEV, was amplified by RT-PCR and cloned into eukaryotic expression vector pVAX1. The recombinant plasmid pVAX-S was transformed by electroporation into attenuated S. typhimurium SL7207, the expression and translation of the pVAX-S delivered by recombinant S. typhimurium SL7207 (pVAX-S) was detected in vitro and in vivo respectively. BALB/c mice were inoculated orally with SL7207 (pVAX-S) at different dosages, the bacterium was safe to mice at dosage of 2 × 10(9) CFU and eventually eliminated from the spleen and liver at week 4 post-immunization. Mice immunized with different dosages of SL7207 (pVAX-S) elicited specific anti-TGEV local mucosal and humoral responses as measured by indirect ELISA assay. Moreover, the immunogenicity of the DNA vaccine was highly dependent on the dosage of the attenuated bacteria used for oral administration, 10(9) CFU dosage group showed higher antibody response than 10(8) CFU and 10(7) CFU dosages groups during week 4–8 post-immunization. The results indicated that attenuated S. typhimurium could be used as a delivery vector for oral immunization of TGEV DNA vaccine.


title: A case of coronavirus disease 2019–infected liver transplant donor

text: Coronavirus disease 2019 (COVID‐19) is a novel infectious disease that continues to spread on a global scale. There has been growing concern about donor‐derived transmissions of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Herein, we present the case of a patient who underwent ABO‐incompatible living donor liver transplantation without knowing that the liver donor was infected with COVID‐19 during the donation procedure. In this case, the donor‐derived transmission to the recipient was not identified, and the liver donor was found to be recovering from a COVID‐19 infection. The donor‐derived transmission was not identified.


title: Occurrence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) across the Gulf Corporation Council countries: Four years update

text: The emergence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections has become a global issue of dire concerns. MERS-CoV infections have been identified in many countries all over the world whereas high level occurrences have been documented in the Middle East and Korea. MERS-CoV is mainly spreading across the geographical region of the Middle East, especially in the Arabian Peninsula, while some imported sporadic cases were reported from the Europe, North America, Africa, and lately Asia. The prevalence of MERS-CoV infections across the Gulf Corporation Council (GCC) countries still remains unclear. Therefore, the objective of the current study was to report the prevalence of MERS-CoV in the GCC countries and to also elucidate on its demographics in the Arabian Peninsula. To date, the World Health Organization (WHO) has reported 1,797 laboratory-confirmed cases of MERS-CoV infection since June 2012, involving 687 deaths in 27 different countries worldwide. Within a time span of 4 years from June 2012 to July 2016, we collect samples form MERS-CoV infected individuals from National Guard Hospital, Riyadh, and Ministry of health Saudi Arabia and other GCC countries. Our data comprise a total of 1550 cases (67.1% male and 32.9% female). The age-specific prevalence and distribution of MERS-CoV was as follow: <20 yrs (36 cases: 3.28%), 20–39 yrs (331 cases: 30.15%), 40–59 yrs (314 cases: 28.60%), and the highest-risk elderly group aged ≥60 yrs (417 cases: 37.98%). The case distribution among GCC countries was as follows: Saudi Arabia (1441 cases: 93%), Kuwait (4 cases: 0.3%), Bahrain (1 case: 0.1%), Oman (8 cases: 0.5%), Qatar (16 cases: 1.0%), and United Arab Emirates (80 cases: 5.2%). Thus, MERS-CoV was found to be more prevalent in Saudi Arabia especially in Riyadh, where 756 cases (52.4%) were the worst hit area of the country identified, followed by the western region Makkah where 298 cases (20.6%) were recorded. This prevalence update indicates that the Arabian Peninsula, particularly Saudi Arabia, is the hardest hit region regarding the emerging MERS-CoV infections worldwide. GCC countries including Saudi Arabia now have the infrastructure in place that allows physicians and scientific community to identify and immediately respond to the potential risks posed by new outbreaks of MERS-CoV infections in the region. Given the continuum of emergence and the large magnitude of the disease in our region, more studies will be required to bolster capabilities for timely detection and effective control and prevention of MERS-CoV in our region.


title: Law as a Tool for Preventing Chronic Diseases: Expanding the Spectrum of Effective Public Health Strategies

text: Law, which is a fundamental element of effective public health policy and practice, played a crucial role in many of public health's greatest achievements of the 20th century. Still, conceptual legal frameworks for the systematic application of law to chronic disease prevention and control have not been fully recognized and used to address public health needs. Development and implementation of legal frameworks could broaden the range of effective public health strategies and provide valuable tools for the public health workforce, especially for state and local health department program managers and state and national policy makers. In an effort to expand the range of effective public health interventions, the Centers for Disease Control and Prevention will work with its partners to explore the development of systematic legal frameworks as a tool for preventing chronic diseases and addressing the growing epidemic of obesity, heart disease, stroke, and other chronic diseases and their risk factors.


title: Severe Acute Respiratory Syndrome–associated Coronavirus in Lung Tissue

text: Efforts to contain severe acute respiratory syndrome (SARS) have been limited by the lack of a standardized, sensitive, and specific test for SARS-associated coronavirus (CoV). We used a standardized reverse transcription-polymerase chain reaction assay to detect SARS-CoV in lung samples obtained from well-characterized patients who died of SARS and from those who died of other reasons. SARS-CoV was detected in all 22 postmortem lung tissues (to 10(9) viral copies/g) from 11 patients with probable SARS but was not detected in any of the 23 lung control samples (sample analysis was blinded). The sensitivity and specificity (95% confidence interval) were 100% (84.6% to 100%) and 100% (85.1% to 100%), respectively. Viral loads were significantly associated with a shorter course of illness but not with the use of ribavirin or steroids. CoV was consistently identified in the lungs of all patients who died of SARS but not in control patients, supporting a primary role for CoV in deaths.


title: Effects of Solanum glaucophyllum toxicity on cell proliferation and apoptosis in the small and large intestine of rabbits

text: Abstract Vitamin D regulates mineral homeostases and enterocyte proliferation and differentiation. Hypervitaminosis D generates changes in cell proliferation, differentiation and apoptosis in several organs. We analysed morphometric parameters and proliferative and apoptotic indices in the intestinal epithelium of rabbits with hypervitaminosis D induced by the chronic treatment with the calcinogenic plant Solanum glaucophyllum. Rabbits were treated for 15 or 30days. A group was treated for 15days and led to possible recovery for 30days. Another group was nutritionally restricted for 30days. Morphological, morphometric, proliferative and apoptotic changes were found in the treated animals. Mild atrophy and reduced proliferation was found in the jejunum and ileum. Apoptosis increased in the crypts of the ileum and in the superficial epithelium and crypts of the rectum. Most of the alterations were partially recovered. The possible involvement in these changes of the hypervitaminosis D-like state induced by S. glaucophyllum is discussed.


title: COVID‐19 in dialysis patients in Japan: Current status and guidance on preventive measures

text: In Japan, the first case of COVID‐19 in dialysis patients was reported on March 1, 2020. A total of 31 cases were reported by April 10, and it increased to 95 by May 15. Thereafter, with the rapid increase in the number of COVID‐19 cases in the general population since late March, there was a not surprising increase in the number of COVID‐19 cases in dialysis patients. The mortality rate is 16.2% (16/99 cases) in dialysis patients, which is higher than 5.3% (874/16532 cases) in the general population. This higher mortality rate in dialysis patients with COVID‐19 might be related to their age; the majority of COVID‐19 cases are aged between 70 and 90 years in dialysis patients, compared with between 20 and 60 years in the general population. As COVID‐19 presents with severe symptoms and is associated with a high mortality rate in dialysis patients, dialysis patients who have contracted SARS‐CoV‐2 infection confirmed by polymerase chain reaction (PCR) testing are required to be hospitalized under Japanese government policy. In cases of COVID‐19 hospitalizations, it is essential to prevent nosocomial infection. Therefore, patients must be sufficiently instructed in infection prevention and robust measures to prevent contraction and spread of the infection must be taken at dialysis facilities. This article is protected by copyright. All rights reserved.


title: Prevalence of depression, anxiety, and insomnia among healthcare workers during the COVID-19 pandemic: A systematic review and meta-analysis

text: Abstract Background COVID-19 pandemic has the potential to significantly affect the mental health of healthcare workers (HCWs), who stand in the frontline of this crisis. It is, therefore, an immediate priority to monitor rates of mood, sleep and other mental health issues in order to understand mediating factors and inform tailored interventions. The aim of this review is to synthesize and analyze existing evidence on the prevalence of depression, anxiety and insomnia among HCWs during the Covid-19 outbreak. Methods A systematic search of literature databases was conducted up to April 17th, 2020. Two reviewers independently assessed full-text articles according to predefined criteria. Risk of bias for each individual study was assessed and data pooled using random-effects meta-analyses to estimate the prevalence of specific mental health problems. The review protocol is registered in PROSPERO and is available online. Findings Thirteen studies were included in the analysis with a combined total of 33062 participants. Anxiety was assessed in 12 studies, with a pooled prevalence of 23·2% and depression in 10 studies, with a prevalence rate of 22·8%. A subgroup analysis revealed gender and occupational differences with female HCPs and nurses exhibiting higher rates of affective symptoms compared to male and medical staff respectively. Finally, insomnia prevalence was estimated at 38·9% across 4 studies. Interpretation Early evidence suggests that a considerable proportion of HCWs experience mood and sleep disturbances during this outbreak, stressing the need to establish ways to mitigate mental health risks and adjust interventions under pandemic conditions.


title: Characterization of a novel orthoreovirus isolated from fruit bat, China

text: BACKGROUND: In recent years novel human respiratory disease agents have been described for Southeast Asia and Australia. The causative pathogens were classified as pteropine orthoreoviruses with a strong phylogenetic relationship to orthoreoviruses of bat origin. RESULTS: In this report, we isolated a novel Melaka-like reovirus (named “Cangyuan virus”) from intestinal content samples of one fruit bat residing in China’s Yunnan province. Phylogenetic analysis of the whole Cangyuan virus genome sequences of segments L, M and S demonstrated the genetic diversity of the Cangyuan virus. In contrast to the L and M segments, the phylogenetic trees for the S segments of Cangyuan virus demonstrated a greater degree of heterogeneity. CONCLUSIONS: Phylogenetic analysis indicated that the Cangyuan virus was a novel orthoreovirus and substantially different from currently known members of Pteropine orthoreovirus (PRV) species group. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12866-014-0293-4) contains supplementary material, which is available to authorized users.


title: The Need for the Right Socio-Economic and Cultural Fit in the COVID-19 Response in Sub-Saharan Africa: Examining Demographic, Economic Political, Health, and Socio-Cultural Differentials in COVID-19 Morbidity and Mortality

text: The coronavirus disease (COVID-19) has spread quickly across the globe with devastating effects on the global economy as well as the regional and societies’ socio-economic fabrics and the way of life for vast populations. The nonhomogeneous continent faces local contextual complexities that require locally relevant and culturally appropriate COVID-19 interventions. This paper examines demographic, economic, political, health, and socio-cultural differentials in COVID-19 morbidity and mortality. The health systems need to be strengthened through extending the health workforce by mobilizing and engaging the diaspora, and implementing the International Health Regulations (2005) core capacities. In the absence of adequate social protection and welfare programs targeting the poor during the pandemic, sub-Saharan African countries need to put in place flexible but effective policies and legislation approaches that harness and formalise the informal trade and remove supply chain barriers. This could include strengthening cross-border trade facilities such as adequate pro-poor, gender-sensitive, and streamlined cross-border customs, tax regimes, and information flow. The emphasis should be on cross-border infrastructure that not only facilitates trade through efficient border administration but can also effectively manage cross-border health threats. There is an urgent need to strengthen social protection systems to make them responsive to crises, and embed them within human rights-based approaches to better support vulnerable populations and enact health and social security benefits. The COVI-19 response needs to adhere to the well-established ‘do no harm’ principle to prevent further damage or suffering as a result of the pandemic and examined through local lenses to inform peace-building initiatives that may yield long-term gains in the post-COVID-19 recovery efforts.


title: Phylogenetic investigation of enteric bovine coronavirus in Ireland reveals partitioning between European and global strains

text: BACKGROUND: Bovine coronavirus is a primary cause of neonatal calf diarrhea worldwide, and is also associated with acute diarrhea in adult cattle during the winter season. There are no reports on molecular characterization of bovine coronavirus in Ireland, and little data exists apart from serological studies. FINDINGS: In this study, 11 neonatal (mean age 9 days) calf BCoV strains from the south of Ireland were collected over a one year period and characterized using molecular methods. The spike gene which encodes a protein involved in viral entry, infectivity and immune response shows the most variability amongst the isolates and was subsequently selected for in depth analysis. Phylogenetic analysis of the spike gene revealed that the Irish strains clustered with novel BCoV strains from Europe in a unique clade, possibly indicating lineage partitioning. Direct analysis of alignments identified amino acid changes in the spike protein unique to the Irish clade. CONCLUSION: Thus, monitoring of bovine coronavirus in Ireland is important as the current isolates in circulation in the south of Ireland may be diverging from the available vaccine strain, which may have implications regarding future BCoV vaccine efficacy.


title: Invasive pulmonary aspergillosis is a frequent complication of critically ill H1N1 patients: a retrospective study

text: PURPOSE: Despite their controversial role, corticosteroids (CS) are frequently administered to patients with H1N1 virus infection with severe respiratory failure secondary to viral pneumonia. We hypothesized that invasive pulmonary aspergillosis (IPA) is a frequent complication in critically ill patients with H1N1 virus infection and that CS may contribute to this complication. METHODS: We retrospectively selected all adult patients with confirmed H1N1 virus infection admitted to the intensive care unit (ICU) of two tertiary care hospitals from September 2009 to March 2011. Differences in baseline factors, risk factors, and outcome parameters were studied between patients with and without IPA. RESULTS: Of 40 critically ill patients with confirmed H1N1, 9 (23 %) developed IPA 3 days after ICU admission. Five patients had proven and four had probable IPA. Significantly more IPA patients received CS within 7 days before ICU admission (78 versus 23 %, p = 0.002). IPA patients also received significantly higher doses of CS before ICU admission [hydrocortisone equivalent 800 (360–2,635) versus 0 (0–0) mg, p = 0.005]. On multivariate analysis, use of CS before ICU admission was independently associated with IPA [odds ratio (OR) 14.4 (2.0–101.6), p = 0.007]. CONCLUSIONS: IPA was diagnosed in 23 % of critically ill patients with H1N1 virus infection after a median of 3 days after ICU admission. Our data suggest that use of CS 7 days before ICU admission is an independent risk factor for fungal superinfection. These findings may have consequences for clinical practice as they point out the need for increased awareness of IPA, especially in those critically ill H1N1 patients already receiving CS.


title: RNA pseudoknots: Translational frameshifting and readthrough on viral RNAs

text: Ribosomal frameshifting on retroviral RNAs has been proposed to be mediated by slippage of two adjacent tRNAs into the — 1 direction at a specific heptanucleotide sequence. Here we report a computer-aided analysis of the structure around the established or putative frameshift sites in a number of retroviral, coronaviral, toroviral, and luteoviral RNAs and two dsRNA yeast viruses. In almost all cases a stable hairpin was predicted four to nine nucleotides downstream of the shifty heptanucleotide. More than half of the resulting hairpin loops give rise to potential pseudoknotting with sequences downstream of this hairpin. Especially in the case of the shifty heptanucleotides U UUA AAC and G GGA AAC, stable downstream pseudoknots are present. Indications were also found for the presence of pseudoknots downstream of amber stop condons at readthrough sites in some retroviral RNAs.


title: An aurora of natural products-based drug discovery is coming

text: Natural products (NPs), a nature's reservoir possessing enormous structural and functional diversity far beyond the current ability of chemical synthesis, are now proving themselves as most wonderful gifts from mother nature for human beings. Many of them have been used successfully as medicines, as well as the most important sources of drug leads, food additives, and many industry relevant products for millennia. Most notably, more than half of the antibiotics and anti-cancer drugs currently in use are, or derived from, natural products. However, the speed and outputs of NP-based drug discovery has been slowing down dramatically after the fruitful harvest of the “low-hanging fruit” during the golden age of 1950s-1960s. With recent scientific advances combining metabolic sciences and technology, multi-omics, big data, combinatorial biosynthesis, synthetic biology, genome editing technology (such as CRISPR), artificial intelligence (AI), and 3D printing, the “high-hanging fruit” is becoming more and more accessible with reduced costs. We are now more and more confident that a new age of natural products discovery is dawning.


title: Rotaviruses: Immunological Determinants of Protection Against Infection and Disease

text: Publisher Summary This chapter focuses on four important questions that remain unanswered: (1) what is the importance of virus serotype in formulating an optimal vaccine? (2) which immunological effector arm most likely protects against rotavirus disease? (3) by what means is virus antigen best presented to the host to elicit a protective immune response? (4) what are the advantages and disadvantages of replicating agents as compared to nonreplicating agents as candidate rotavirus vaccines? Although two proteins (vp4 and vp7) are probably important in inducing protection against challenge, it has not been clearly demonstrated that inclusion of the epidemiologically important human P or G type is important in protection against human disease. No immunological effector arm clearly explains protection against heterotypic challenge. Protection against disease is not predicted by rotavirus-specific neutralizing antibodies in serum. Oral inoculation may not be necessary to induce a protective, virus-specific immune response at the intestinal mucosal surface, but parenteral inoculation of experimental animals with rotavirus induces an immune response at the intestinal mucosal surface that is protective against challenge. Induction of a rotavirus-specific protective immune response is probably associated with the presence of virus-specific T and B cells in intestinal lymphoid tissues and virus-specific sIgA or IgG at the intestinal mucosal surface. There is some experimental evidence to support the hypothesis that neither rotavirus replication nor presentation of rotavirus antigen to the intestinal mucosal surface is necessary to achieve this aim.


title: Not gene therapy, but genetic surgery—the right strategy to attack cancer

text: In this review, I will suggest to divide all the approaches united now under common term “gene therapy” into two broad strategies of which the first one uses the methodology of targeted therapy with all its characteristics, but with genes in the role of agents targeted at a certain molecular component(s) presumably crucial for cancer maintenance. In contrast, the techniques of the other strategy are aimed at the destruction of tumors as a whole using the features shared by all cancers, for example relatively fast mitotic cell division or active angiogenesis. While the first strategy is “true” gene therapy, the second one is more like genetic surgery when a surgeon just cuts off a tumor with his scalpel and has no interest in knowing delicate mechanisms of cancer emergence and progression. I will try to substantiate the idea that the last strategy is the only right one, and its simplicity is paradoxically adequate to the super-complexity of tumors that originates from general complexity of cell regulation, strongly disturbed in tumor cells, and especially from the complexity of tumors as evolving cell populations, affecting also their ecological niche formed by neighboring normal cells and tissues. An analysis of the most widely used for such a “surgery” suicide gene/prodrug combinations will be presented in some more details.


Bridging a false dichotomy in the COVID-19 response: a public health approach to the ‘lockdown’ debate


Ref. No. DLD-20-852: Onset of ulcerative colitis during SARS-Cov-2 infection


title: Increase in the risk of type 2 diabetes during lockdown for the COVID19 pandemic in India: A cohort analysis

text: Lockdown due to the Coronavirus disease 2019 (COVID 19) pandemic may cause weight gain and enhance the risk of type 2 diabetes mellitus (T2DM). We aimed to determine this risk in apparently non-diabetic individuals. MATERIAL METHODS: Baseline demographic and clinical data from 100 apparently non-diabetic household members (related or unrelated) of patients with type 2 diabetes mellitus were collected until 49 days of lockdown and analyzed using the XL-STAT statistical software. A two-pronged analytical strategy was employed. First, the metabolic risk profile related to age, sex, weight, family history, and exercise pattern was analyzed. This was followed by an assessment of the risk of developing type 2 diabetes using an established risk assessment engine. RESULTS: There was a trend towards weight gain seen in 40% of the cohort, with 16% of the population experiencing a 2.1–5 kg weight increment. When all the risk parameters were analyzed together using the ADA risk engine, there was an increase in the ADA diabetes risk score in 7% of the population, with 6.66% in the high-risk group. There was a further increase in weight among 3% of the population who were already obese at baseline. CONCLUSION: We show an increased risk of T2MD consequent to weight gain during 49 days of lockdown in India.


title: Air pollution, stock returns, and trading activities in China

text: Abstract The relationship between air pollution and stock pricing of locally headquartered firms is explored using firm-level data in China. Severe air pollution results in low returns, turnover, volatility, and high illiquidity, mainly through a home bias. The results remain robust after a series of checks. The relation between air pollution and local firm performance is insignificant, implying that the air pollution effects can be attributed to investor mood bias rather than to economic effects. The sensitivity of stock returns to air pollution is significantly large for high-growth stocks, distressed stocks, and stocks with high volatility.


title: Asymptomatic novel coronavirus pneumonia patient outside Wuhan: The value of CT images in the course of the disease

text: Abstract The purpose of this case report is to describe the imaging and associated clinical features of an asymptomatic novel coronavirus pneumonia (COVID-19) patient outside Wuhan, China. The principle findings are that in this patient with laboratory-confirmed COVID-19, CT findings preceded symptoms and included bilateral pleural effusions, previously not reported in association with COVID-19. The role of this case report is promotion of potential recognition amongst radiologists of this new disease, which has been declared a global health emergency by the World Health Organization (WHO).


title: Exogenous avian leukosis virus-induced activation of the ERK/AP1 pathway is required for virus replication and correlates with virus-induced tumorigenesis

text: A proteomics approach was used to reveal the up-regulated proteins involved in the targeted mitogen-activated protein kinase (MAPK) signal transduction pathway in DF-1 cells after ALV subgroup J (ALV-J) infection. Next, we found that ALV-J CHN06 strain infection of DF-1 cells correlated with extracellular signal-regulated kinase 2 (ERK2) activation, which was mainly induced within 15 min, a very early stage of infection, and at a late infection stage, from 108 h to 132 h post-infection. Infection with other ALV subgroup (A/B) strains also triggered ERK/MAPK activation. Moreover, when activating ERK2, ALV subgroups A, B and J simultaneously induced the phosphorylation of c-Jun, an AP1 family member and p38 activation but had no obvious effect on JNK activation at either 15 min or 120 h. Interestingly, only PD98059 inhibited the ALV-induced c-Jun phosphorylation while SP600125 or SB203580 had no influence on c-Jun activation. Furthermore, the viral gp85 and gag proteins were found to contribute to ERK2/AP1 activation. Additionally, the specific ERK inhibitor, PD980509, significantly suppressed ALV replication, as evidenced by extremely low levels of ALV promoter activity and ALV-J protein expression. In vivo analysis of ERK2 activation in tumor cells derived from ALV-J-infected chicken demonstrated a strong correlation between ERK/MAPK activation and virus-associated tumorigenesis.


Evidence for Quasi Species in Severe Acute Respiratory Syndrome-associated Coronavirus Deletion Mutants


title: Molecular characterization and biological activity of bovine interferon-omega3

text: Abstract Bovine interferon-omega3 (BoIFN-ω3) gene was amplified from bovine liver genomic DNA, which encodes a 195-amino acid protein containing a 23-amino acid signal peptide. Analysis of the molecular characteristics revealed that BoIFN-ω3 evolving from IFN-ω, contained four cysteine residues and five alpha helices, showing that BoIFN-ω3 presented the typical molecular characteristics of type I interferon. BoIFN-ω3 exhibited antiviral and antiproliferative activities, which exerted a protective effect against VSV in several mammalian cell lines, as well as against BEV, IBRV, and BVDV in MDBK cell. Moreover, BoIFN-ω3 was shown to be highly sensitive to trypsin, but remaining stable despite changes in pH and temperature. Additionally, BoIFN-ω3 induced the transcription of Mx1, ISG15, and ISG56 genes, as well as the expression of Mx1 protein in a time-dependent manner. These findings will be useful to further study BoIFN-ω in host's defence against infectious diseases, particularly viral infections. Furthermore, results will facilitate further research on the bovine interferon family.


title: Disaster Preparedness, Triage, and Surge Capacity for Hospital Definitive Care Areas: Optimizing Outcomes when Demands Exceed Resources

text: Disaster planning must anticipate how demands imposed by a disaster reconcile with the capacity of the treating facility. Resources must be organized before an event so that they are optimally used to treat as many victims as possible, as well as to avoid overwhelming available resources.


title: The phylogenomics of evolving virus virulence

text: How virulence evolves after a virus jumps to a new host species is central to disease emergence. Our current understanding of virulence evolution is based on insights drawn from two perspectives that have developed largely independently: long-standing evolutionary theory based on limited real data examples that often lack a genomic basis, and experimental studies of virulence-determining mutations using cell culture or animal models. A more comprehensive understanding of virulence mutations and their evolution can be achieved by bridging the gap between these two research pathways through the phylogenomic analysis of virus genome sequence data as a guide to experimental study.


title: Bat and pig IFN-induced transmembrane protein 3 restrict cell entry by influenza virus and lyssaviruses

text: IFN-induced transmembrane protein 3 (IFITM3) is a restriction factor that blocks cytosolic entry of numerous viruses that utilize acidic endosomal entry pathways. In humans and mice, IFITM3 limits influenza-induced morbidity and mortality. Although many IFITM3-sensitive viruses are zoonotic, whether IFITMs function as antiviral restriction factors in mammalian species other than humans and mice is unknown. Here, IFITM3 orthologues in the microbat (Myotis myotis) and pig (Sus scrofa domesticus) were identified using rapid amplification of cDNA ends. Amino acid residues known to be important for IFITM3 function were conserved in the pig and microbat orthologues. Ectopically expressed pig and microbat IFITM3 co-localized with transferrin (early endosomes) and CD63 (late endosomes/multivesicular bodies). Pig and microbat IFITM3 restricted cell entry mediated by multiple influenza haemagglutinin subtypes and lyssavirus glycoproteins. Expression of pig or microbat IFITM3 in A549 cells reduced influenza virus yields and nucleoprotein expression. Conversely, small interfering RNA knockdown of IFITM3 in pig NPTr cells and primary microbat cells enhanced virus replication, demonstrating that these genes are functional in their species of origin at endogenous levels. In summary, we showed that IFITMs function as potent broad-spectrum antiviral effectors in two mammals – pigs and bats – identified as major reservoirs for emerging viruses.


title: Aufgaben der Weaning-Zentren im Pandemiefall COVID-19: Unterstützende Handlungsempfehlung zur Sicherstellung dringend benötigter Intensivkapazitäten am Beispiel des Berlin-Brandenburger POST-SAVE-Konzepts

text: The enormous increase in patients with severe respiratory distress due to the COVID-19 pandemic outbreak requires a systematic approach to optimize ventilated patient at risk flow. A standardised algorithm called „SAVE“ was developed to distribute patients with COVID-19 respiratory distress syndrome requiring invasive ventilation. This program is established by now in Berlin. An instrumental bottleneck of this approach is the vacant slot assignment in the intensive care unit to guarantee constant patient flow. The transfer of the patients after acute care treatment is needed urgently to facilitate the weaning process. In a next step we developed a triage algorithm to identify patients at SAVE intensive care units with potential to wean and transfer to weaning institutions – we called POST SAVE. This manuscript highlights the algorithms including the use of a standardised digital evaluation tool, the use of trained navigators to facilitate the communication between SAVE intensive care units and weaning institutions and the establishment of a prospective data registry for patient assignment and reevaluation of the weaning potential in the future.