title: The relationship of serum vitamins A, D, E and LL-37 levels with allergic status, tonsillar virus detection and immune response

text: BACKGROUND: Tonsils have an active role in immune defence and inducing and maintaining tolerance to allergens. Vitamins A, D, and E, and antimicrobial peptide LL-37 may have immunomodulatory effects. We studied how their serum levels were associated with allergy status, intratonsillar/nasopharyngeal virus detection and intratonsillar expression of T cell- and innate immune response-specific cytokines, transcription factors and type I/II/III interferons in patients undergoing tonsillectomy. METHODS: 110 elective tonsillectomy patients participated. Serum levels of vitamins A, 25(OH)D, and E, LL-37 and allergen-specific IgE as well as nasopharyngeal/intratonsillar respiratory viruses were analyzed. The mRNA expression of IFN-α, IFN-β, IFN-γ, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-β, FOXP3, GATA3, RORC2 and Tbet in tonsils were analyzed by quantitative RT-PCR. RESULTS: The median age of the patients was 16 years (range 3–60), 28% of subjects had atopy, and 57% carried ≥1 respiratory virus in nasopharynx. Detection of viruses decreased by age. Higher vitamin A levels showed borderline significance with less viral detection (P = 0.056). Higher 25(OH)D was associated with less allergic rhinitis and atopy (P < 0.05) and higher vitamin E with less self-reported allergy (P < 0.05). In gene expression analyses, 25(OH)D was associated with higher IL-37, vitamin A with higher IFN-γ and vitamin E with less IL-28 (P < 0.05). LL-37 was associated with less FOXP3, RORC2 and IL-17 in tonsils (P < 0.05). CONCLUSIONS: Vitamin D and E levels were associated with less allergic disorders. Vitamin A was linked to antiviral and vitamin D with anti-inflammatory activity. LL-37 and was linked to T regulatory cell effects.


docid: eyobjalw

title: Revitalization of integrated disease surveillance and response in Sierra Leone post Ebola virus disease outbreak

text: BACKGROUND: The Ministry of Health and Sanitation (MOHS) in Sierra Leone partially rolled out the implementation of Integrated Disease Surveillance and Response (IDSR) in 2003. After the Ebola virus disease outbreak in 2014–2015, there was need to strengthen IDSR to ensure prompt detection and response to epidemic-prone diseases. We describe the processes, successes and challenges of revitalizing public health surveillance in a country recovering from a protracted Ebola virus disease outbreak. METHODS: The revitalization process began with adaptation of the revised IDSR guidelines and development of customized guidelines to suit the health care systems in Sierra Leone. Public health experts defined data flow, system operations, case definitions, frequency and channels of reporting and dissemination. Next, phased training of IDSR focal persons in each health facility and the distribution of data collection and reporting tools was done. Monitoring activities included periodic supportive supervision and data quality assessments. Rapid response teams were formed to investigate and respond to disease outbreak alerts in all districts. RESULTS: Submission of reports through the IDSR system began in mid-2015 and by the 35th epidemiologic week, all district health teams were submitting reports. The key performance indicators measuring the functionality of the IDSR system in 2016 and 2017 were achieved (WHO Africa Region target ≥80%); the annual average proportion of timely weekly health facility reports submitted to the next level was 93% in 2016 and 97% in 2017; the proportion of suspected outbreaks and public health events detected through the IDSR system was 96% (n = 87) in 2016 and 100% (n = 85) in 2017. CONCLUSION: With proper planning, phased implementation and adequate investment of resources, it is possible to establish a functional IDSR system in a country recovering from a public health crisis. A functional IDSR system requires well trained workforce, provision of the necessary tools and guidelines, information, communication and technology infrastructure to support data transmission, provision of timely feedback as well as logistical support. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-019-6636-1) contains supplementary material, which is available to authorized users.


title: Mitochondria and viruses

text: Abstract Mitochondria are involved in a variety of cellular metabolic processes, and their functions are regulated by extrinsic and intrinsic stimuli including viruses. Recent studies have shown that mitochondria play a central role in the primary host defense mechanisms against viral infections, and a number of novel viral and mitochondrial proteins are involved in these processes. Some viral proteins localize in mitochondria and interact with mitochondrial proteins to regulate cellular responses. This review summarizes recent findings on the functions and roles of these molecules as well as mitochondrial responses to viral infections.


title: The long‐term impact of severe acute respiratory syndrome on pulmonary function, exercise capacity and health status

text: Background and objective: Severe acute respiratory syndrome (SARS) emerged in 2003 and its long‐term sequelae remain largely unclear. This study examined the long‐term outcome of pulmonary function, exercise capacity, health and work status among SARS survivors. Methods: A prospective cohort study of SARS patients at the Prince of Wales Hospital, Hong Kong was conducted, with serial assessments of lung function, 6MWD and 36 item Short Form General Health Survey at 3, 6, 12, 18 and 24 months after disease onset. The work status was also recorded. Results: Serial assessments were completed by 55 of the 123 (39.9%) subjects, of whom 27 were health‐care workers (HCW). The mean age of the group was 44.4 (SD 13.2) years and 19 (34.5%) were males. At 24 months, 10 (18.2%), 9 (16.4%), 6 (10.9%) and 29 (52.7%) subjects had FEV(1), FVC, TLC and DL(CO) < 80% of predicted values, respectively. The mean (SD) 6MWD increased significantly from 439.0 (89.1) m at 3 months to 460.1 (102.8) m at 6 months (P 0.016) and became steady after 6 months. However, 6MWD and 36 item Short Form General Health Survey scores were lower than the normal population throughout the study. Moreover, 29.6% of HCW and 7.1% of non‐HCW had not returned to work 2 years after illness onset. Conclusions: This 2‐year study of a selected population of SARS survivors, showed significant impairment of DL(CO), exercise capacity and health status persisted, with a more marked adverse impact among HCW.


title: Extremes in Context: A Life-Course Approach to Disaster Mental Health

text: Exposure to disasters has a range of adverse mental-health consequences. This Commentary argues that to understand variation in post-disaster mental health, we must look beyond the disaster itself to other sources of vulnerability throughout the life course, as well as the developmental stage at which the disaster was experienced.


title: Epidemiology of Enterovirus D68 in Ontario

text: In August 2014, children’s hospitals in Kansas City, Missouri and Chicago, Illinois notified the Centers for Disease Control and Prevention (CDC) about increased numbers of pediatric patients hospitalized with severe respiratory illness (SRI). In response to CDC reports, Public Health Ontario Laboratories (PHOL) launched an investigation of patients being tested for enterovirus D-68 (EV-D68) in Ontario, Canada. The purpose of this investigation was to enhance our understanding of EV-D68 epidemiology and clinical features. Data for this study included specimens submitted for EV-D68 testing at PHOL from September 1, 2014 to October 31, 2014. Comparisons were made between patients who tested positive for the virus (cases) and those testing negative (controls). EV-D68 was identified in 153/907 (16.8%) of patients tested. In the logistic regression model adjusting for age, sex, setting and time to specimen collection, individuals younger than 20 years of age were more likely to be diagnosed with EV-D68 compared to those 20 and over, with peak positivity at ages 5–9 years. Cases were not more likely to be hospitalized than controls. Cases were more likely to be identified in September than October (OR 8.07; 95% CI 5.15 to 12.64). Routine viral culture and multiplex PCR were inadequate methods to identify EV-D68 due to poor sensitivity and inability to differentiate EV-D68 from other enterovirus serotypes or rhinovirus. Testing for EV-D68 in Ontario from July to December, 2014 detected the presence of EV-D68 virus among young children during September-October, 2014, with most cases detected in September. There was no difference in hospitalization status between cases and controls. In order to better understand the epidemiology of this virus, surveillance for EV-D68 should include testing of symptomatic individuals from all treatment settings and patient age groups, with collection and analysis of comprehensive clinical and epidemiological data.


title: Blood immune transcriptome analysis of artificially fed dairy calves and naturally suckled beef calves from birth to 7 days of age

text: Neonatal calves possess a very immature and naïve immune system and are reliant on the intake of maternal colostrum for passive transfer of immunoglobulins. Variation in colostrum management of beef and dairy calves is thought to affect early immune development. Therefore, the objective of this study was to examine changes in gene expression and investigate molecular pathways involved in the immune-competence development of neonatal Holstein dairy calves and naturally suckled beef calves using next generation RNA-sequencing during the first week of life. Jugular whole blood samples were collected from Holstein (H) dairy calves (n = 8) artificially fed 5% B.W. colostrum, and from beef calves which were the progenies of Charolais-Limousin (CL; n = 7) and Limousin-Friesian beef suckler cows (LF; n = 7), for subsequent RNA isolation. In dairy calves, there was a surge in pro-inflammatory cytokine gene expression possibly due to the stress of separation from the dam. LF calves exhibited early signs of humoral immune development with observed increases in the expression genes coding for Ig receptors, which was not evident in the other breeds by 7 days of age. Immune and health related DEGs identified as upregulated in beef calves are prospective contender genes for the classification of biomarkers for immune-competence development, and will contribute towards a greater understanding of the development of an immune response in neonatal calves.


title: Novel Coronavirus in Cape Town Informal Settlements: Feasibility of Using Informal Dwelling Outlines to Identify High Risk Areas for COVID-19 Transmission From A Social Distancing Perspective

text: BACKGROUND: The challenges faced by the Global South during the coronavirus disease (COVID-19) pandemic are compounded by the presence of informal settlements, which are typically densely populated and lacking in formalized sanitation infrastructure. Social distancing measures in informal settlements may be difficult to implement due to the density and layout of settlements. This study measures the distance between dwellings in informal settlements in Cape Town to identify the risk of COVID-19 transmission. OBJECTIVE: The aim of this paper is to determine if social distancing measures are achievable in informal settlements in Cape Town, using two settlements as an example. We will first examine the distance between dwellings and their first, second, and third nearest neighbors and then identify clusters of dwellings in which residents would be unable to effectively practice social isolation due to the close proximity of their homes. METHODS: Dwellings in the settlements of Masiphumelele and Klipfontein Glebe were extracted from a geographic information system data set of outlines of all informal dwellings in Cape Town. The distance to each dwelling’s first, second, and third nearest neighbors was calculated for each settlement. A social distance measure of 2 m was used (buffer of 1 m, as dwellings less than 2 m apart are joined) to identify clusters of dwellings that are unable to effectively practice social distancing in each settlement. RESULTS: The distance to each dwelling’s first 3 nearest neighbors illustrates that the settlement of Masiphumelele is constructed in a denser fashion as compared to the Klipfontein Glebe settlement. This implies that implementing social distancing will likely be more challenging in Masiphumelele than in Klipfontein Glebe. However, using a 2-m social distancing measure, it was demonstrated that large portions of Klipfontein Glebe would also be unable to effectively implement social distancing. CONCLUSIONS: Effectively implementing social distancing may be a challenge in informal settlements due to their density. This paper uses dwelling outlines for informal settlements in the city of Cape Town to demonstrate that with a 2 m measure, effective social distancing will be challenging.


title: Apolipoprotein D deficiency is associated to high bone turnover, low bone mass and impaired osteoblastic function in aged female mice

text: Abstract Background Apolipoprotein D (ApoD) is a member of the lipocalin family known to transport small hydrophobic ligands. A major site of ApoD expression in mice is the central nervous system where evidence suggests that it plays a protective role. Gene expression of ApoD was reported in bone-forming osteoblasts but its impact on bone metabolism remains undocumented. Methods We compared basic bone parameters of ApoD −/− (null) and transgenic (tg) mice to wild-type (wt) littermates through microCT and histochemistry, as well as ApoD expression and secretion in osteoblasts under various culture conditions through real-time PCR and immunoblotting. Results ApoD-null females displayed progressive bone loss with aging, resulting in a 50% reduction in trabecular bone volume and a 23% reduction in cortical bone volume by 9months of age. Only cortical bone volume was significantly reduced in ApoD-null males by an average of 24%. Histochemistry indicated significantly higher osteoblast surface and number of osteoclasts in femora from ApoD-null females. ApoD gene expression was confirmed in primary cultures of bone marrow mesenchymal cells (MSC), with higher expression levels in MSC from females compared to males. ApoD-null MSC exhibited impaired proliferation and differentiation potentials. Moreover, exogenous ApoD partially rescued the osteogenic potential of null MSC, which were shown to readily uptake the protein from media. ApoD expression was upregulated under low proliferation conditions, by contact inhibition and osteoblastic differentiation in MC3T3-E1 osteoblast-like cells. Conclusion Our results indicate that ApoD influences bone metabolism in mice in a gender-specific manner, potentially through an auto-/paracrine pathway.


title: Epidemiologic analysis of respiratory viral infections among Singapore military servicemen in 2016

text: BACKGROUND: Respiratory illnesses have been identified as a significant factor leading to lost training time and morbidity among Singapore military recruits. A surveillance programme has been put in place to determine etiological agents responsible for febrile, as well as afebrile respiratory illnesses in a military camp. The goal of the study is to better understand the epidemiology of these diseases and identify potential countermeasures to protect military recruits against them. METHODS: From Jan 2016 - Jan 2017, a total of 2647 respiratory cases were enrolled into the surveillance programme. The cases were further stratified into Febrile Respiratory Illness (FRI, with body temperature > 37.5 °C) or Acute Respiratory Illness (ARI, with body temperature < 37.5 °C). Nasal washes were collected and tested by multiplex PCR to detect 26 different pathogens. RESULTS: One thousand ninety five cases (41% of total cases) met the criteria of FRI in which 932 cases (85% of FRI cases) were screened positive for at least one virus. The most common etiological agents for FRI mono-infection cases were Adenovirus E and Rhinovirus. Recruits infected with H3N2 influenza, Influenza B and Adenovirus E viruses were most likely presented as FRI cases. Notably, H3N2 influenza resulted in the greatest rise in body temperature. The remaining 1552 cases (59% of total cases) met the criteria of ARI in which 1198 cases (77% of ARI cases) were screened positive for at least one virus. The most common etiological agent for ARI mono-infection was Rhinovirus. The distribution pattern for dual infections was different for ARI and FRI cases. Maximum number of pathogens detected in a sample was five for both groups. CONCLUSION: Previous studies on respiratory diseases in military focused largely on FRI cases. With the expanded surveillance to ARI cases, this study allows unbiased evaluation of the impact of respiratory disease pathogens among recruits in a military environment. The results show that several pathogens have a much bigger role in causing respiratory diseases in this cohort. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3040-x) contains supplementary material, which is available to authorized users.


title: A systematic review of MERS-CoV (Middle East Respiratory Syndrome Coronavirus) seroprevalence and viral RNA prevalence in dromedary camels: implications for animal vaccination

text: Human infection with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is driven by recurring dromedary-to-human spill-over events, leading decision-makers to consider dromedary vaccination. Dromedary vaccine candidates in the development pipeline are showing hopeful results, but gaps in our understanding of the epidemiology of MERS-CoV in dromedaries must be addressed to design and evaluate potential vaccination strategies. We systematically reviewed the published literature reporting seroprevalence and/or prevalence of active MERS-CoV infection in dromedary populations from both cross-sectional and longitudinal studies, including 60 studies in our qualitative syntheses. MERS-CoV seroprevalence increased with age up to 80-100% in adult dromedaries supporting geographically wide spread endemicity of MERS-CoV in dromedaries in both the Arabian Peninsula and countries exporting dromedaries from Africa. The high prevalence of active infection measured in juveniles and at sites where dromedary populations mix should guide further investigation – particularly of dromedary movement – and inform vaccination strategy design.


title: Modern Biomolecular Mass Spectrometry and its Role in Studying Virus Structure, Dynamics, and Assembly

text: Over a century since its development, the analytical technique of mass spectrometry is blooming more than ever, and applied in nearly all aspects of the natural and life sciences. In the last two decades mass spectrometry has also become amenable to the analysis of proteins and even intact protein complexes, and thus begun to make a significant impact in the field of structural biology. In this Review, we describe the emerging role of mass spectrometry, with its different technical facets, in structural biology, focusing especially on structural virology. We describe how mass spectrometry has evolved into a tool that can provide unique structural and functional information about viral‐protein and protein‐complex structure, conformation, assembly, and topology, extending to the direct analysis of intact virus capsids of several million Dalton in mass. Mass spectrometry is now used to address important questions in virology ranging from how viruses assemble to how they interact with their host.


title: Chapter 20 Ethics, Legality, and Education in the Practice of Cardiology

text: Advances in diagnostics, drugs, and devices have revolutionized cardiology practice, and improved quality of life of the patients. However, awareness, achievements, and advances in cardiac health care have enhanced the demands and expectations of the community, which lacks awareness about the social, economic, administrative, professional, and technical constraints or limitations of implementation. Being unfamiliar with medical ethics and legal aspects of care, and suboptimal virtues among physicians, have led to patients and the public utilizing legal remedies. In addition, sophistication of medical practice, increasing costs of health care, involvement of insurance systems, increased awareness and high expectations from the community and patients, and increased participation of the media have altered the attitude toward claiming compensation and acquisition of health care delivery among the public. In view of the changing trends of consumers and emerging areas in health care, providers must get accustomed to patient empowerment and come up to their expectations. Interactive programs on these aspects in medical education will help students understand not only the intricacies of medical ethics and the laws and shortcomings of health professionals and/or health systems, but also strengthen their knowledge of ethics and laws to improve their practice. Principles of ethics and legal issues have to be discussed at every stage of medical education. To improve the quality of the physician–patient encounter, we need to develop formal and informal curricula about effective communication skills. This chapter also highlights preventive measures and educational aspects of cardiology practice.


title: 65 years of influenza surveillance by a World Health Organization‐coordinated global network

text: The 1918 devastating influenza pandemic left a lasting impact on influenza experts and the public, and the importance of global influenza surveillance was soon recognized. The World Health Organization (WHO) Global Influenza Surveillance Network (GISN) was founded in 1952 and renamed to Global Influenza Surveillance and Response System in 2011 upon the adoption by the World Health Assembly, of the Pandemic Influenza Preparedness Framework for the Sharing of Influenza Viruses and Access to Vaccines and Other Benefits (“PIP Framework”). The importance of influenza surveillance had been recognized and promoted by experts prior to the years leading up to the establishment of WHO. In the 65 years of its existence, the Network has grown to comprise 143 National Influenza Centers recognized by WHO, 6 WHO Collaborating Centers, 4 Essential Regulatory Laboratories, and 13 H5 Reference Laboratories. The Network has proven its excellence throughout these 65 years, providing detailed information on circulating seasonal influenza viruses, as well as immediate response to the influenza pandemics in 1957, 1968, and 2009, and to threats caused by animal influenza viruses and by zoonotic transmission of coronaviruses. For its central role in global public health, the Network has been highly recognized by its many partners and by international bodies. Several generations of world‐renowned influenza scientists have brought the Network to where it is now and they will take it forward to the future, as influenza will remain a preeminent threat to humans and to animals.


title: Molecular characterization of hepatitis E virus ORF1 gene supports a papain-like cysteine protease (PCP)-domain activity

text: Abstract Hepatitis E Virus (HEV) ORF1 encodes the nonstructural polyprotein wherein a role of PCP-domain in ORF1 proteolysis and/or RNA replication still remains contested. A series of ORF1 mutants of HEV-SAR55 replicon were constructed and tested for viability in S10-3 cells. Six of PCP-‘cysteine’ (C457A, C459A, C471A, C472A, C481A and C483A) and three ‘histidine’ (H443L, H497L and H590L) mutants were lethal. Further, a highly conserved ‘glycine-triad’ (G815-G816-G817) in downstream X-domain, homologous to rubella virus protease-substrate (G1299-G1300-G1301) was identified where two of X-mutants (G816V and G817V) turned lethal. However, all ORF1 sequential nucleotide-mutants conserving the amino acids were viable, which clearly showed post-translational regulation of HEV replication by PCP- and X-domains. Moreover, while vector-expressed ORF1-fusion polyprotein yielded a ∼191kDa band in vitro, it produced ∼78 and ∼35kDa fragments ex vivo. Collectively, the indispensability and functional effects of ‘PCP-catalytic’ and ‘X-substrate’ residues on HEV replication strongly supported a viral protease.


COVID-19 en migrantes y minorías étnicas


title: Comparison of Subcutaneous versus Intravenous Alemtuzumab for Graft-versus-Host Disease Prophylaxis with Fludarabine/Melphalan–Based Conditioning in Matched Unrelated Donor Allogeneic Stem Cell Transplantation

text: Abstract The objective of this study was to compare infusion-related reactions and outcomes of using subcutaneous (subQ) alemtuzumab versus intravenous (i.v.) alemtuzumab as graft-versus-host disease (GVHD) prophylaxis for matched unrelated donor stem cell transplantations. Outcomes include incidence of cytomegalovirus (CMV)/Epstein-Barr (EBV) viremia, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, acute and chronic GVHD, time to engraftment, relapse rate, and survival. We conducted a retrospective study of all adult matched unrelated donor stem cell transplantations patients who received fludarabine/melphalan with subQ or i.v. alemtuzumab in combination with tacrolimus as part of their conditioning for unrelated donor transplantation at New York-Presbyterian/Weill Cornell Medical Center from January 1, 2012 to March 21, 2014. Alemtuzumab was administered at a total cumulative dose of 100 mg (divided over days −7 to −3). Forty-six patients received an unrelated donor stem cell transplantation with fludarabine/melphalan and either subQ (n = 26) or i.v. (n = 20) alemtuzumab in combination with tacrolimus. Within the evaluable population, 130 subQ and 100 i.v. alemtuzumab doses were administered. For the primary outcome, ≥grade 2 infusion-related reactions occurred in 11 (8%) versus 25 (25%) infusions in the subQ and i.v. cohorts, respectively (P = .001). Overall, 12 injections (9%) in the subQ arm versus 26 infusions (26%) in the i.v. arm experienced an infusion-related reaction of any grade (P = .001). There were no significant differences between the subQ and i.v. arms in rates of reactivation of CMV/EBV, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, acute and chronic GVHD, relapse, or survival. Subcutaneous administration of alemtuzumab for GVHD prophylaxis was associated with fewer infusion-related reactions compared with i.v. administration in the SCT setting. Incidences of acute and chronic GVHD were similar between both arms. There was also no difference in reactivation of CMV/EBV viremia, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, relapse, or survival.


The role of CT for Covid-19 patient's management remains poorly defined.


title: The Rationale for Potential Pharmacotherapy of COVID-19

text: On 11 March 2020, the coronavirus disease (COVID-19) was defined by the World Health Organization as a pandemic. Severe acute respiratory syndrome-2 (SARS-CoV-2) is the newly evolving human coronavirus infection that causes COVID-19, and it first appeared in Wuhan, China in December 2019 and spread rapidly all over the world. COVID-19 is being increasingly investigated through virology, epidemiology, and clinical management strategies. There is currently no established consensus on the standard of care in the pharmacological treatment of COVID-19 patients. However, certain medications suggested for other diseases have been shown to be potentially effective for treating this infection, though there has yet to be clear evidence. Therapies include new agents that are currently tested in several clinical trials, in addition to other medications that have been repurposed as antiviral and immune-modulating therapies. Previous high-morbidity human coronavirus epidemics such as the 2003 SARS-CoV and the 2012 Middle East respiratory syndrome coronavirus (MERS-CoV) prompted the identification of compounds that could theoretically be active against the emerging coronavirus SARS-CoV-2. Moreover, advances in molecular biology techniques and computational analysis have allowed for the better recognition of the virus structure and the quicker screening of chemical libraries to suggest potential therapies. This review aims to summarize rationalized pharmacotherapy considerations in COVID-19 patients in order to serve as a tool for health care professionals at the forefront of clinical care during this pandemic. All the reviewed therapies require either additional drug development or randomized large-scale clinical trials to be justified for clinical use.


title: The Potential Role of Th17 Immune Responses in Coronavirus Immunopathology and Vaccine-induced Immune Enhancement

text: Abstract Increasing evidence points to host Th17 inflammatory responses as contributing to the severe lung pathology and mortality of lower respiratory tract infections from coronaviruses. This includes host inflammatory and cytokine responses to COVID-19 caused by the SARS-2 coronavirus (SARS CoV2). From studies conducted in laboratory animals, there are additional concerns about immune enhancement and the role of potential host immunopathology resulting from experimental human COVID-19 vaccines. Here we summarize evidence suggesting there may be partial overlap between the underlying immunopathologic processes linked to both coronavirus infection and vaccination, and a role for Th17 in immune enhancement and eosinophilic pulmonary immunopathology. Such findings help explain the link between viral-vectored coronavirus vaccines and immune enhancement and its reduction through alum adjuvants. Additional research may also clarify links between COVID-19 pulmonary immunopathology and heart disease.


docid: ssnlfjap

title: Etiology, clinical, and epidemiological characteristics of severe respiratory infection in people living with HIV

text: People living with HIV (PLWH) are more prone to severe respiratory infections. We used the severe acute respiratory infection (SARI) definition to describe the etiology, clinical, and epidemiological characteristics in this population. This was a prospective observational study including PLWH hospitalized with fever and cough. Those with symptom onset up to 10 days were classified as severe acute respiratory infection and 11–30 days as non-severe acute respiratory infection. Blood, urine samples and nasopharyngeal swabs were collected. Data were extracted from patient charts during their hospital stay. Forty-nine patients were included, median CD4 cell count: 80 cells/mm(3), median time since HIV diagnosis and hospital admission: 84 months and 80% were antiretroviral therapy exposed. Twenty-seven patients were classified as SARI. Etiology was identified in 69%, 47% were polymicrobial. Respiratory virus (9 SARI vs. 13 non-SARI), bacteria (5 SARI vs. 4 non-SARI), Mycobacterium tuberculosis (6 SARI group vs. 7 non-SARI group), Pneumocystis jirovecii (4 SARI vs. 1 non-SARI), Cryptococcus neoformans (1 SARI vs. 3 non-SARI), and influenza A (1 SARI vs. 2 non-SARI). Dyspnea was statistically more prevalent in SARI (78% vs. 36%, p = 0.011) but the risk of death was higher in the non-SARI (4% vs. 36%, p = 0.0067). In the severely immunocompromised PLWH, severe acute respiratory infection can be caused by multiple pathogens and codetection is a common feature.


title: Core Outcome Set for Clinical Trials on Coronavirus Disease 2019 (COS-COVID)

text: Abstract Since its outbreak in December 2019, a series of clinical trials on Coronavirus Disease 2019 (COVID-19) have been registered or carried out. However, the significant heterogeneity and less critical outcomes of such trials may be leading to a waste of research resources. This study aimed to develop a core outcome set (COS) for clinical trials on COVID-19 in order to tackle the outcome issues. The study was conducted according to the Core Outcome Measures in Effectiveness Trials (COMET) handbook (version 1.0), a guideline for COS development. A research group was set up that included experts in respiratory and critical medicine, traditional Chinese medicine, evidence-based medicine, clinical pharmacology, and statistics, in addition to medical journal editors. Clinical trial registry websites (chictr.org.cn and clinicaltrials.gov) were searched to retrieve clinical trial protocols and outcomes in order to form an outcome pool. A total of 78 clinical trial protocols on COVID-19 were included and 259 outcomes were collected. After standardization, 132 outcomes were identified within seven different categories, of which 58 were selected to develop a preliminary outcome list for further consensus. After two rounds of Delphi survey and one consensus meeting, the most important outcomes for the different clinical classifications of COVID-19 were identified and determined to constitute the COS for clinical trials on COVID-19 (COS-COVID). The COS-COVID includes one outcome for the mild type (time to 2019-nCoV reverse transcription-polymerase chain reaction (RT-PCR) negativity), four outcomes for the ordinary type (length of hospital stay, composite events, score of clinical symptoms, and time to 2019-nCoV RT-PCR negativity), five outcomes for the severe type (composite events, length of hospital stay, arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2), duration of mechanical ventilation, and time to 2019-nCoV RT-PCR negativity), one outcome for critical type (all-cause mortality), and one outcome for rehabilitation period (pulmonary function). The COS-COVID is currently the most valuable and practical clinical outcome set for the evaluation of intervention effect, and is useful for evidence assessment and decision-making. With a deepening understanding of COVID-19 and application feedback, the COS-COVID should be continuously updated.


Management of Upper Airway Bleeding in COVID‐19 Patients on Extracorporeal Membrane Oxygenation


title: Induction and sequencing of Rousette bat interferon α and β genes

text: Abstract Bats are considered to be natural reservoirs for several viruses of clinical importance, including rabies virus, Nipah virus, and Hendra virus. Type I interferons (IFNs) is an important part of the immune system in the defense against viral infection. To investigate the function of type I IFNs upon viral infection in bats, the nucleic acid, and amino acid sequences of Egyptian Rousette (Rousettus aegyptiacus) IFN-α and -β were characterized. Sequence data indicated that bat IFN-α consists of 562-bp encoded 187-aa, and IFN-β consisted of 558-bp encoded 186-aa. Phylogenetic analysis of the overall identity of IFN-β shared the highest sequence homology with pig IFN-β in both nucleotide and amino acid level. Stimulation of bat primary kidney cells (BPKCs) and bat lung cell lines, Tb-1 Lu, with polyinosinic–polycytidylic acid (poly(I:C)) or exogenous bat type I IFNs resulted in increased type I IFNs mRNA expression in BPKCs, but not in Tb-1 Lu. Characterization of the bat IFN-α and -β genes allows understanding of the immune responses upon stimulation in different tissues, thus providing practical strategies for control and treatment of clinically important diseases. These results are important especially for the virus infection, and suggest that future molecular studies on virus infection experiment of bats in vitro will require careful consideration of the differences of type I IFN expression patterns in different cell types.


title: Psychological support in times of COVID-19: the Essen community-based CoPE concept

text: The SARS CoV-2-virus (COVID-19) pandemic is pushing national and international structures to their limits. Little is known about treatment options to combat the novel virus, but the same applies to the effects of COVID-19 on people’s mental health. In Germany, as in many other countries, governmental actions impact peoples’ individual freedom. These highly necessary actions to slow down the spread of the virus, however, are a burden to the community. We established a structured concept to support psychological burdened people in Essen, which is located in the Ruhr area, a metropolitan region with more than 5.1 million inhabitants in the heart of the federal state North Rhine Westphalia. The psychological burden following the spread of the virus and individual restrictions should not be neglected.


title: Imaging evaluation of COVID-19 in the emergency department

text: PURPOSE: The purpose of this study is to elucidate the chest imaging findings of suspected COVID-19 patients presenting to the emergency department and the relationship with their demographics and RT-PCR testing results. METHODS: Patients presenting to the ED between March 12 and March 28, 2020, with symptoms suspicious for COVID-19 and subsequent CXR and/or CT exam were selected. Patients imaged for other reasons with findings suspicious for COVID-19 were also included. Demographics, laboratory test results, and history were extracted from the medical record. Descriptive statistics were used to explore the relationship between imaging and these factors. RESULTS: A total of 227 patients from the emergency department were analyzed (224 CXRs and 25 CTs). Of the 192 patients with COVID-19 results, 173 (90.1%) had COVID-19 RT-PCR (+). Abnormal imaging (CXR, 85.7% and/or CT, 100%) was noted in 155 (89.6%) of COVID-19 RT-PCR (+) cases. The most common imaging findings were mixed airspace/interstitial opacities (39.8%) on CXR and peripheral GGOs on CT (92%). The most common demographic were African Americans (76.8%). Furthermore, 97.1% of African Americans were RT-PCR (+) compared to 65.8% of Caucasians. CONCLUSION: We found a similar spectrum of thoracic imaging findings in COVID-19 patients as previous studies. The most common demographic were African Americans (76.8%). Furthermore, 97.1% of African Americans were RT-PCR (+) compared to 65.8% of Caucasians. Both CT and CXR can accurately identify COVID-19 pneumonitis in 89.6% of RT-PCR (+) cases, 89.5% of false negatives, and 72.7% of cases with no RT-PCR result. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10140-020-01787-0) contains supplementary material, which is available to authorized users.


title: Comparison of three multiplex PCR assays for detection of respiratory viruses: Anyplex II RV16, AdvanSure RV, and Real‐Q RV

text: BACKGROUND: Due to its great sensitivity, the nucleic acid amplification test (NAAT) is widely used for detection of respiratory viruses (RV). However, few reports have described a direct comparison between multiplex RT‐PCR assays for RV. The objective of this study was to perform a direct comparison of three multiplex RT‐PCR assays for the detection of respiratory viruses. METHODS: A total of 201 respiratory samples (161 nasopharyngeal swab samples and 40 sputum samples) were tested with three commercial RV assays: Seegene Anyplex II RV16 (AP), LG AdvanSure RV (AD), and Biosewoom Real‐Q RV (RQ). The additional tests for the discrepant results were conducted by repeat RV assay or monoplex PCR coupled direct sequencing. Data analysis using percent agreement, kappa, and prevalence‐adjusted and bias‐adjusted kappa (PABAK) values was performed for comparisons among the three RV assays. RESULTS: Of the 201 samples, AP, AD, and RQ detected 105 (52.2%), 99 (49.3%), and 95 (47.3%) positive cases respectively. The overall agreement, kappa, and PABAK values for the three assays ranged between 97%‐98%, 0.76‐0.86, and 0.93‐0.96 respectively. The performance of the three assays was very similar, with 94%‐100% agreement for all comparisons, each virus types. The additional testing of samples showed discrepant results demonstrating that AD assay had the highest rate of concordance with original results. CONCLUSIONS: We suggest that all multiplex assay would be suitable for the detection of for respiratory viruses in clinical setting.


SARS-CoV-2 infection in liver-Author’s reply


Tocilizumab, an anti-IL6 receptor antibody, to treat Covid-19-related respiratory failure: a case report


title: Biosafety Level 3 Laboratory for Autopsies of Patients with Severe Acute Respiratory Syndrome: Principles, Practices, and Prospects

text: Background. During the outbreak of the emergent severe acute respiratory syndrome (SARS) infection, >30% of the ∼8000 infected persons were health care workers. The highly infectious nature of SARS coronavirus (SARS-CoV) compelled our pathologists to consider biosafety issues in the autopsy room and for tissue processing procedures. Methods. A specially designed biosafety level 3 (BSL-3) autopsy laboratory was constructed and divided into a clean area, a semicontaminated area, a contaminated area, and 2 buffer zones. High-efficiency particulate air filters were placed in the air supply and exhaust systems. Laminar air flow was from the clean areas to the less clean areas. The negative pressures of the contaminated, semicontaminated, and clean areas were approximately -50 pa, -25 pa, and -5 pa, respectively. Personal protective equipment, including gas mask, impermeable protective clothing, and 3 layers of gloves worn during autopsies; the equipment was decontaminated before it was allowed to exit the facility. Strict BSL-3 practices were followed. Results. When a given concentration of particulate sarin simulant was introduced into the contaminated area, it could not be detected in either the semicontaminated area or clean area, and particles >0.3 μm in size were not detected in the exhaust air. A total of 16 complete postmortem examinations for probable and suspected SARS were performed during a 2-month period. Of these, 7 reported confirmed cases of SARS. None of the 23 pathologists and technicians who participated in these autopsies was infected with SARS-CoV. Conclusions. Our experience suggests that BSL-3 laboratory operating principles should be among the special requirements for performing autopsies of contaminated bodies and that they can safeguard the clinicians and the environment involved in these procedures.


docid: vhxlyigz

title: Hospital response to the COVID‐19 outbreak: The experience in Shanghai, China

text: On 20th January 2020, the first COVID-19 case was reported in Shanghai, China. As of 12th March 2020, 344 cases with laboratory-confirmed COVID-19 infection have been detected in Shanghai, of which three died, 321 patients are discharged, 20 patients still receive ongoing treatments (Shanghai Municipal Health Commission, 2020).


title: Health shocks and their long-lasting impact on health behaviors: Evidence from the 2009 H1N1 pandemic in Mexico

text: Abstract Worldwide, the leading causes of death could be avoided with health behaviors that are low-cost but also difficult to adopt. We show that exogenous health shocks could facilitate the adoption of these behaviors and provide long-lasting effects on health outcomes. Specifically, we exploit the spatial and temporal variation of the 2009 H1N1 influenza pandemic in Mexico and show that areas with a higher incidence of H1N1 experienced larger reductions in diarrhea-related cases among young children. These reductions continue even three years after the shock ended. Health improvements and evidence of information seeking via Google searches were consistent with changes in hand washing behaviors. Several robustness checks validate our findings and mechanism.


title: SARS-CoV-2 pneumonia in hospitalized asthmatic patients did not induce severe exacerbation

text: Abstract Background Viral infections are known to exacerbate asthma in adults. Previous studies have found few asthmatics among SARS-CoV-2 pneumonia cases. However, the relationship between SARS-CoV-2 infection and severe asthma exacerbation is not known. Objective We assessed the frequency of asthma exacerbation in asthmatic patients hospitalized for SARS-CoV-2 pneumonia and compared symptoms laboratory and radiological findings in asthmatic and non-asthmatic patients with SARS-CoV-2 pneumonia. Methods We included 106 patients between March 4 and April 6, 2020, who were hospitalized in the Chest Diseases Department of Strasbourg University Hospital; 23 were asthmatics. To assess the patients’ asthma status, three periods were defined: the last month before the onset of COVID-19 symptoms (p1), pre-hospitalization (p2) and during hospitalization (p3). Severe asthma exacerbations were defined according to GINA guidelines during p1 and p2. During p3, we defined severe asthma deterioration as the onset of breathlessness and wheezing requiring systemic corticosteroids and inhaled beta-2-agonist. Results We found no significant difference between asthmatics and non-asthmatics in terms of severity (length of stay, maximal oxygen flow needed, non-invasive ventilation requirement and ICU transfer). 52.2% of the asthmatic patients were Gina 1. One patient had a severe exacerbation during p1, two patients during p2, and five patients were treated with systemic corticosteroids and inhaled beta-2-agonist during p3. Conclusion Our results demonstrate that asthmatic patients appeared not to be at risk for severe SARS-CoV-2 pneumonia. Moreover, SARS-CoV-2 pneumonia did not induce severe asthma exacerbation.


title: Estimating Influenza Vaccine Effectiveness With the Test-Negative Design Using Alternative Control Groups: A Systematic Review and Meta-Analysis

text: One important assumption in case-control studies is that control selection should be independent of exposure. Nevertheless, it has been hypothesized that virus interference might lead to a correlation between receipt of influenza vaccination and increased risk of infection with other respiratory viruses. We investigated whether such a phenomenon might affect a study design commonly used to estimate influenza vaccine effectiveness (VE). We searched publications in MEDLINE, PubMed, and Web of Science. We identified 12 studies using the test-negative design (2011–2017) that reported VE estimates separately derived by 3 alternative control groups: 1) all patients testing negative for influenza (FLU), VE(FLU−); 2) patients who tested positive for other/another respiratory virus (ORV), VE(ORV+); and 3) patients who tested negative for all viruses in the panel (PAN), VE(PAN−). These included VE estimates from 7 countries for all age groups from 2003/2004 to 2013/2014. We observed no difference in vaccination coverage between the ORV-positive and PAN-negative control groups. A total of 63 VE(FLU−) estimates, 62 VE(ORV+) estimates, and 33 VE(PAN−) estimates were extracted. Pooled estimates of the difference in VE (ΔVE) were very similar between groups. In meta-regression, no association was found between the selection of control group and VE estimates. In conclusion, we did not find any differences in VE estimates based on the choice of control group.


docid: hsbkltsn

title: Chapter 6 Bat Rabies

text: The lyssaviruses are a diverse group of viruses capable of causing rabies, which is an invariably fatal encephalitic disease in both humans and animals. Currently, the lyssavirus genus consists of 12 species with 11 of these distinct species having been isolated from bats. The basis for the apparent geographical segregation of bat lyssavirus infection between the Old and New World is poorly understood. In the New World species of insectivorous, frugivorous, and hematophagous bats, all represent important reservoirs of rabies virus. In contrast, rabies virus has never been detected in Old World bat populations, despite being endemic in terrestrial mammals. Instead, both insectivorous and frugivorous bat species across the Old World appear to act as reservoirs for the non-rabies lyssaviruses. In this chapter, we describe the association of the different lyssaviruses with different bat species across the world, classifying bat species by their feeding behavior.


“Everything is a Mess”: How COVID-19 is Impacting Engagement with HIV Testing Services in Rural Southwestern Uganda


title: Chromatography of complex protein mixtures

text: Abstract This review has shown that a variety of chromatographic techniques are available for fractionating proteins. Fortunately, high-quality columns of every type described in this review are commercially available. Most water-soluble proteins may be eluted from size-exclusion, hydrophobic-interaction, ion-exchange, metal chelate, and bioaffinity columns with ease. When this is the case, high recovery and retention of biological activity are the norm. The exception is reversed-phase chromatography where the organic solvents and acids used in polypeptide elution denature many proteins. When problems do occur, they are generally the result of unique structural features of the protein. Very hydrophobic proteins have presented the biggest problem in that they are difficult to solubilize, particularly with retention of biological activity. It has been found that zwitterionic an non-ionic detergents are the most suitable solubilizing agents, but area has also been used in cases where hydrophobic interacts are not as strong. Unfortunately, there is still an element of trial-and-error in selecting the most suitable solubilizing agent. Heterogeneous glycosylation of proteins also presents a problem. Both neutral and charged monosaccharides can be incorporated into proteins through multiple steps at several sites. Thus, there is the potential in a sample for a large number of glycoprotein species which have the same polypeptide backbone and differing amounts of oligosaccharide. A problem arises when size-exclusion, ion-exchange, hydrophobic-interaction, reversed-phase and bioaffinity systems begin to discriminate between these very similar glycoprotein species. Chromatographic peaks can become very load, due to incomplete fractionation, and the polypeptide chain of interest can be associated with multiple peaks. The separation of glycoproteins requires much more study before logical procedures can be suggested for column selection and operation. Aggregated species are another class of proteins which present occasional problems. Multimeric proteins are adsorbed to sorbents by a series of forces, among which are hydrogen bonding, hydrophobic interactions, and electrostatic forces. These forces are also responsible for the maintenance of quaternary structure in proteins. When the same forces dominate both retention of protein structure and adsorption at the sorbent surface, the quaternary structure of the protein can be disrupted during elution. Very basic proteins also present a problem in some cases. Columns with residual negative charges, such as a silica-based reversed-phase column, adsorb anionic species so strongly that they are difficult to elute. This is the case with ribosomal and nucleoproteins. The solution is to use exhaustively end-capped columns which diminish electrostatic interactions.


title: Does energy and CO2 emissions performance of China benefit from regional integration?

text: Abstract Low energy and carbon efficiency and widespread market segmentation are two stylized facts of China's regional economies. This paper evaluates energy and CO2 emissions performance using a newly developed non-radial directional distance function, and China's regional integration is investigated using a price approach. The study points to evidence that: (1) most provinces do not perform efficiently in terms of energy use and CO2 emissions with performance gaps among regions becoming larger, indicating regional segmentation; (2) magnitude of regional integration has increased dramatically, while China's eastern provinces are less integrated in domestic side due to their convenience to international openness; (3) regional integration has significant and robust positive effects on energy and CO2 emissions performance with over 70% of effects coming from artificial barriers, rather than geographical distance; (4) international openness is also beneficial for promoting energy and CO2 emissions performance, but cannot substitute for regional integration because of China's specialization in energy-intensive manufacturing in the global economy. Based on the empirical findings, we suggest that central government should continue to encourage regional integration given that local governments have incentives to fragment because it is a way of promoting energy and CO2 emissions performance and stimulating economy at the same time.


title: Protein analysis based on molecular beacon probes and biofunctionalized nanoparticles

text: With the completion of the human genome-sequencing project, there has been a resulting change in the focus of studies from genomics to proteomics. By utilizing the inherent advantages of molecular beacon probes and biofunctionalized nanoparticles, a series of novel principles, methods and techniques have been exploited for bioanalytical and biomedical studies. This review mainly discusses the applications of molecular beacon probes and biofunctionalized nanoparticles-based technologies for real-time, in-situ, highly sensitive and highly selective protein analysis, including the nonspecific or specific protein detection and separation, protein/DNA interaction studies, cell surface protein recognition, and antigen-antibody binding process-based bacteria assays. The introduction of molecular beacon probes and biofunctionalized nanoparticles into the protein analysis area would necessarily advance the proteomics research.


title: Nonsteroidal Anti-Inflammatory Drug without Antibiotics for Acute Viral Infection Increases the Empyema Risk in Children: A Matched Case-Control Study

text: Objective To investigate the risk factors of empyema after acute viral infection and to clarify the hypothesized association(s) between empyema and some viruses and/or the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Study design A case-control study was conducted in 15 centers. Cases and controls were enrolled for a source population of children 3-15 years of age with acute viral infections between 2006 and 2009. Results Among 215 empyemas, 83 cases (children with empyema and acute viral infection within the 15 preceding days) were included, and 83 controls (children with acute viral infection) were matched to cases. Considering the intake of any drug within 72 hours after acute viral infection onset and at least 6 consecutive days of antibiotic use and at least 1 day of NSAIDs exposure, the multivariable analysis retained an increased risk of empyema associated with NSAIDs exposure (aOR 2.79, 95% CI 1.4-5.58, P = .004), and a decreased risk associated with antibiotic use (aOR 0.32, 95% CI 0.11-0.97, P = .04). The risk of empyema associated with NSAIDs exposure was greater for children not prescribed an antibiotic and antibiotic intake diminished that risk for children given NSAIDs. Conclusions NSAIDs use during acute viral infection is associated with an increased risk of empyema in children, and antibiotics are associated with a decreased risk. The presence of antibiotic-NSAIDs interaction with this risk is suggested. These findings suggest that NSAIDs should not be recommended as a first-line antipyretic treatment during acute viral infections in children.


title: Obesity, the most common comorbidity in SARS-CoV-2: is leptin the link?

text: Overweight and obesity are major risk factors for diabetes, cardiovascular disease, and lung disease. These diseases are the most commonly reported health conditions that predispose individuals with SARS-CoV-2 infection to require hospitalization including intensive care unit admissions. The innate immune response is the host’s first line of defense against a human coronavirus infection. However, most coronaviruses are armed with one strategy or another to overcome host antiviral defense, and the pathogenicity of the virus is related to its capacity to suppress host immunity. The multifaceted nature of obesity including its effects on immunity can fundamentally alter the pathogenesis of acute respiratory distress syndrome and pneumonia, which are the major causes of death due to SARS-CoV-2 infection. Elevated circulating leptin concentrations are a hallmark of obesity, which is associated with a leptin-resistant state. Leptin is secreted by adipocytes in proportion to body fat and regulates appetite and metabolism through signaling in the hypothalamus. However, leptin also signals through the Jak/STAT and Akt pathways, among others, to modulate T cell number and function. Thus, leptin connects metabolism with the immune response. Therefore, it seems appropriate that its dysregulation would have serious consequences during an infection. We propose that leptin may be the link between obesity and its high prevalence as a comorbidity of the SARS-CoV-2 infection. In this article, we present a synthesis of the mechanisms underpinning susceptibility to respiratory viral infections and the contribution of the immunomodulatory effects of obesity to the outcome.


title: The Development of an AIDS Mucosal Vaccine

text: It is well known that mucosal tissues contain the largest surface area of the human body and are the front line of natural host defense against various pathogens. In fact, more than 80% of infectious disease pathogens probably gain entry into the susceptible human hosts through open mucosal surfaces. Human immunodeficiency virus type one (HIV-1), a mainly sexually transmitted virus, also primarily targets the vaginal and gastrointestinal mucosa as entry sites for viral transmission, seeding, replication and amplification. Since HIV-1 establishes its early replication in vaginal or rectal mucosal tissues, the induction of sufficient mucosal immunity at the initial site of HIV-1 transmission becomes essential for a protective vaccine. However, despite the fact that current conventional vaccine strategies have remained unsuccessful in preventing HIV-1 infection, sufficient financial support and resources have yet to be given to develop a vaccine able to elicit protective mucosal immunity against sexual transmissions. Interestingly, Chinese ancestors invented variolation through intranasal administration about one thousand years ago, which led to the discovery of a successful smallpox vaccine and the final eradication of the disease. It is the hope for all mankind that the development of a mucosal AIDS vaccine will ultimately help control the AIDS pandemic. In order to discover an effective mucosal AIDS vaccine, it is necessary to have a deep understanding of mucosal immunology and to test various mucosal vaccination strategies.


title: Mutation in the cytoplasmic retrieval signal of porcine epidemic diarrhea virus spike (S) protein is responsible for enhanced fusion activity

text: Abstract Murine-adapted porcine epidemic diarrhea virus (PEDV), MK-p10, shows high neurovirulence and increased fusion activity compared with a non-adapted MK strain. MK-p10 S protein had four mutations relative to the original virus S, and one of these (H→R at position 1381, H1381R) in the cytoplasmic tail (CT) was suggested to be responsible for the increased fusion activity. To explore this, we examined fusion activity using recombinant S proteins. We expressed and compared the fusion activity of MK-p10 S, S with the H1381R mutation, S with the three other mutations that were not thought to be involved in high fusion activity, and the original S protein. The MK-p10 and MK-H1381R S proteins induced larger cell fusions than others. We also examined the distribution of these S proteins; the MK-p10 and MK-H1381R S proteins were transported onto the cell surface more efficiently than others. These findings suggest that the H1381R mutation is responsible for enhanced fusion activity, which may be attributed to the efficient transfer of S onto the cell surface. H1381 is a component of the KxHxx motif in the CT region, which is a retrieval signal of the S protein for the endoplasmic reticulum–Golgi intermediate compartment (ERGIC). Loss of this motif could allow for the efficient transfer of S proteins from ERGIC onto the cell surface and subsequent increased fusion activity.


title: Characterization of the cold-sensitive murine hepatitis virus mutants rescued from latently infected cells by cell fusion

text: Abstract Mouse hepatitis virus, a coronavirus, was rescued from latently infected mouse neuroblastoma cells by polyethylene glycol-induced fusion to permissive cells. The isolated viruses grew to equal or higher titers than parental JHM virus at 39° but were restricted in replication at 32° and hence were cold-sensitive mutants. Neither isolate synthesized RNA at the nonpermissive temperature (32°), and temperature shift experiments indicated that the restrictive cold-sensitive step in replication occurred during an early viral function. The isolates were unable to complement each other at 32°. Although coinfection between each mutant and parental JHM virus often resulted in decreased yields of both infecting viruses, interference could not be convincingly demonstrated. Both mutants were more thermostable than parental JHM virus and could be distinguished from each other and from parental JHM virus by their thermal inactivation kinetics. The isolates were obtained from single cell clones and therefore presumed to be homogeneous; however, thermal inactivation of one (S-3JHM) indicated the possible existence of a second population. Subclones of virus prepared from each isolate were also found to be thermally stable and to retain the cold sensitive defect. No indication of a second population of S-3JHM virus was detected.


title: SIRT1 Activating compounds reduce oxidative stress mediated neuronal loss in viral induced CNS demyelinating disease

text: BACKGROUND: Multiple sclerosis (MS) is characterized by central nervous system inflammation and demyelination, and increasing evidence demonstrates significant neuronal damage also occurs and is associated with permanent functional impairment. Current MS therapies have limited ability to prevent neuronal damage, suggesting additional neuroprotective therapies are needed. Compounds that activate the NAD(+)-dependent SIRT1 deacetylase prevent neuronal loss in an autoimmune-mediated MS model, but the mechanism of this effect is unknown, and it is unclear whether SIRT1 activating compounds exert similar effects in demyelinating disease induced by other etiologies. We measured neuronal loss in C57BL/6 mice inoculated with a neurotropic strain of mouse hepatitis virus, MHV-A59, that induces an MS-like disease. RESULTS: Oral treatment with the SIRT1 activating compound SRTAW04 significantly increased SIRT1 activity within optic nerves and prevented neuronal loss during optic neuritis, an inflammatory demyelinating optic nerve lesion that occurs in MS and its animal models. MHV-A59 induced neuronal loss was associated with reactive oxygen species (ROS) accumulation, and SRTAW04 treatment significantly reduced ROS levels while promoting increased expression of enzymes involved in mitochondrial function and reduction of ROS. SRTAW04 exerted similar protective effects in EAE spinal cords, with decreased demyelination. CONCLUSIONS: Results demonstrate that SIRT1 activating compounds prevent neuronal loss in viral-induced demyelinating disease similar to their effects in autoimmune-mediated disease. One mechanism of this neuroprotective effect involves increasing mitochondrial biogenesis with reduction of oxidative stress. SIRT1 activators represent a potential neuroprotective therapy for MS. Understanding common mechanisms of these effects in distinct disease models will help identify targets for more specific therapies.


Infectious diseases: a call for manuscripts in an interdisciplinary era


title: Interferon-β-1a Inhibition of Severe Acute Respiratory Syndrome–Coronavirus 2 In Vitro When Administered After Virus Infection

text: The ongoing coronavirus disease 2019 pandemic has forced the clinical and scientific community to try drug repurposing of existing antiviral agents as a quick option against severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2). Under this scenario, interferon (IFN) β-1a, whose antiviral potential is already known, and which is a drug currently used in the clinical management of multiple sclerosis, may represent as a potential candidate. In this report, we demonstrate that IFN-β-1a was highly effective in inhibiting in vitro SARS-CoV-2 replication at clinically achievable concentration when administered after virus infection.


title: A baculovirus dual expression system-based vaccine confers complete protection against lethal challenge with H9N2 avian influenza virus in mice

text: BACKGROUND: Avian influenza viruses of H9N2 subtype have become highly prevalent in avian species. Although these viruses generally cause only mild to moderate disease, they can infect a wide variety of species, including chickens, quail, turkeys, ducks, geese, pheasant, partridge, and pigeon, even transmitted to mammalian species, including humans, accelerating the efforts to devise protective strategies against them. RESULTS: The results showed that stronger immune responses were induced in a mouse model immunized with BV-Dual-HA than in those vaccinated with a DNA vaccine encoding the same antigen. Moreover, complete protection against lethal challenge with H9N2 virus was observed in mice. CONCLUSION: BV-Dual-HA could be utilized as a vaccine candidate against H9N2 virus infection.


title: Baculovirus Surface Display of Immunogenic Proteins for Vaccine Development

text: Vaccination is an efficient way to prevent the occurrence of many infectious diseases in humans. To date, several viral vectors have been utilized for the generation of vaccines. Among them, baculovirus—categorized as a nonhuman viral vector—has been used in wider applications. Its versatile features, like large cloning capacity, nonreplicative nature in mammalian cells, and broad tissue tropism, hold it at an excellent position among vaccine vectors. In addition to ease and safety during swift production, recent key improvements to existing baculovirus vectors (such as inclusion of hybrid promoters, immunostimulatory elements, etc.) have led to significant improvements in immunogenicity and efficacy of surface-displayed antigens. Furthermore, some promising preclinical results have been reported that mirror the scope and practicality of baculovirus as a vaccine vector for human applications in the near future. Herein, this review provides an overview of the induced immune responses by baculovirus surface-displayed vaccines against influenza and other infectious diseases in animal models, and highlights the strategies applied to enhance the protective immune responses against the displayed antigens.


Is COVID-19-related Guillain-Barré Syndrome Different?


title: Synthesis, anti-varicella-zoster virus and anti-cytomegalovirus activity of quinazoline-2,4-diones containing isoxazolidine and phosphonate substructures

text: Cycloadditions of N-substituted C-(diethoxyphosphoryl)nitrones to N-allylated quinazoline-2,4-diones functionalized at N3 with substituted benzoyl or benzyl groups proceeded with moderate to good diastereoselectivities (d.e. 28–68%). The synthesized isoxazolidine phosphonates were assessed for the antiviral activity against a broad range of DNA and RNA viruses. Compounds trans-13c, cis-13c/trans-13c (86:14), cis-15b/trans-15b (87:13) and trans-15d/cis-15d (95:5) exhibited the highest activity toward both TK(+) and TK(−) VZV strains (mean EC(50) values in the range of 3.0–8.7 μM). The EC(50)'s for isoxazolidines trans-12a, cis-12a, cis-13a, trans-13d, cis-15a/trans-15a (50:50) ranged between 6.9 and 8.5 μM for VZV TK(+) strain and between 10.7 and 13.2 μM for VZV TK(–) strain. The isoxazolidine phosphonates cis-15/trans-15 having benzyl substituents both at N3 of the quinazoline-2,4-dione skeleton and at N2 of the isoxazolidine ring displayed some anti-cytomegalovirus potency but at the same time showed significant cytostatic activity for human embryonic lung fibroblasts (used to carry out the antiviral assays) as well as for other cell lines (i.e. CEM, L1210, HeLa and HMEC-1).


title: National outreach of telepalliative medicine volunteers for a New York City safety net system COVID-19 pandemic response

text: The COVID-19 surge in New York City created an increased demand for palliative care (PC) services. In staff-limited settings such as safety net systems, and amid growing reports of healthcare worker illness, leveraging help from less-affected areas around the country may provide an untapped source of support. A national social media outreach effort recruited 413 telepalliative medicine volunteers (TPMV). After expedited credentialing and onboarding of 67 TPMV, a 2-week pilot was initiated in partnership with five public health hospitals without any previous existing telehealth structure. The volunteers completed 109 PC consults in the pilot period. Survey feedback from TPMV and on-site PC providers was largely positive, with areas of improvement identified around electronic health record navigation and continuity of care. This was a successful, proof of concept, quality improvement initiative leveraging TPMV from across the nation for a PC pandemic response in a safety net system.


title: COVID-19 pandemic: every day feels like a weekday to most

text: The COVID-19 outbreak has clear clinical and economic impacts, but also affects behaviors e.g. through social distancing, and may increase stress and anxiety. However, while case numbers are tracked daily, we know little about the psychological effects of the outbreak on individuals in the moment. Here we examine the psychological and behavioral shifts over the initial stages of the outbreak in the United States in an observational longitudinal study. Through GPS phone data we find that homestay is increasing, while being at work dropped precipitously. Using regular real-time experiential surveys we observe an overall increase in stress and mood levels which is similar in size to the weekend vs. weekday differences. As there is a significant difference between weekday and weekend mood and stress levels, this is an important decrease in wellbeing. For some, especially those affected by job loss, the mental health impact is severe.


title: Fragment-based discovery of a new family of non-peptidic small-molecule cyclophilin inhibitors with potent antiviral activities

text: Cyclophilins are peptidyl-prolyl cis/trans isomerases (PPIase) that catalyse the interconversion of the peptide bond at proline residues. Several cyclophilins play a pivotal role in the life cycle of a number of viruses. The existing cyclophilin inhibitors, all derived from cyclosporine A or sanglifehrin A, have disadvantages, including their size, potential for side effects unrelated to cyclophilin inhibition and drug–drug interactions, unclear antiviral spectrum and manufacturing issues. Here we use a fragment-based drug discovery approach using nucleic magnetic resonance, X-ray crystallography and structure-based compound optimization to generate a new family of non-peptidic, small-molecule cyclophilin inhibitors with potent in vitro PPIase inhibitory activity and antiviral activity against hepatitis C virus, human immunodeficiency virus and coronaviruses. This family of compounds has the potential for broad-spectrum, high-barrier-to-resistance treatment of viral infections.


title: Opportunities and Challenges for Biosensors and Nanoscale Analytical Tools for Pandemics: COVID-19

text: [Image: see text] Biosensors and nanoscale analytical tools have shown huge growth in literature in the past 20 years, with a large number of reports on the topic of ‘ultrasensitive’, ‘cost-effective’, and ‘early detection’ tools with a potential of ‘mass-production’ cited on the web of science. Yet none of these tools are commercially available in the market or practically viable for mass production and use in pandemic diseases such as coronavirus disease 2019 (COVID-19). In this context, we review the technological challenges and opportunities of current bio/chemical sensors and analytical tools by critically analyzing the bottlenecks which have hindered the implementation of advanced sensing technologies in pandemic diseases. We also describe in brief COVID-19 by comparing it with other pandemic strains such as that of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) for the identification of features that enable biosensing. Moreover, we discuss visualization and characterization tools that can potentially be used not only for sensing applications but also to assist in speeding up the drug discovery and vaccine development process. Furthermore, we discuss the emerging monitoring mechanism, namely wastewater-based epidemiology, for early warning of the outbreak, focusing on sensors for rapid and on-site analysis of SARS-CoV2 in sewage. To conclude, we provide holistic insights into challenges associated with the quick translation of sensing technologies, policies, ethical issues, technology adoption, and an overall outlook of the role of the sensing technologies in pandemics.


title: Marmota himalayana in the Qinghai–Tibetan plateau as a special host for bi-segmented and unsegmented picobirnaviruses

text: Wildlife has been considered the main source of novel viruses causing emerging infectious diseases. Marmota himalayana is endemic to the Qinghai–Tibetan Plateau, China. Here, based on a high-throughput method using Illumina RNA sequencing, we studied the RNA virome of M. himalayana and discovered multiple novel viruses, especially picobirnaviruses (PBVs), which have a bi-segmented genome and belong to the family Picobirnaviridae. A total of 63% of the viral contigs corresponded to PBVs, comprising 274 segment 1 and 56 segment 2 sequences. Unexpectedly, four unsegmented PBV genomes were also detected and confirmed by PCR and resequencing. According to the phylogenetic analysis, the following nine PBV assortment types are proposed: C1:GI, C2:GIV, C4:GI, C4:GV, C5:GI, C7:GI, C8:GIV, C8:GV and C8:GII. We hypothesize a model of segmentation for the PBV genome, mediated by a 6-bp direct repeat sequence, GAAAGG. The model is supported by detection of the segmentation-associated sequence GAAAGG not only in the 5′ untranslated regions of segment 1 (221 in 289) and segment 2 (57 in 80) of bi-segmented PBVs but also in the 5′ untranslated regions and junction sequences between the capsid and RdRp genes of unsegmented PBVs. Therefore, with RNA sequencing, we found an unexpected biodiversity of PBVs in M. himalayana, indicating that M. himalayana is a special host for PBVs. We also proposed a putative model of how bi-segmented PBVs could be converted into unsegmented PBVs, which sheds new light on the processes of RNA virus genome evolution.


title: A dynamic compartmental model for the Middle East respiratory syndrome outbreak in the Republic of Korea: A retrospective analysis on control interventions and superspreading events

text: Abstract The 2015 Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea has provided an opportunity to improve our understanding of the spread of MERS linked to healthcare settings. Here we designed a dynamic transmission model to analyze the MERS outbreak in the Republic of Korea based on confirmed cases reported during the period May 20–July 4, 2015. Our model explicitly incorporates superspreading events and time-dependent transmission and isolation rates. Our model was able to provide a good fit to the trajectory of the outbreak and was useful to analyze the role of hypothetical control scenarios. Specifically, we assessed the impact of the timing of control measures, especially associated with a reduction of the transmission rate and diagnostic delays on outbreak size and duration. Early interventions within 1week after the epidemic onset, for instance, including the initial government announcement to the public about the list of hospitals exposed to MERS coronavirus (MERS-CoV), show a promising means to reduce the size ( > 71 % ) and duration ( > 35 % ) of the MERS epidemic. Finally, we also present results of an uncertainty analysis focused on the role of superspreading events.


title: Evaluation of the Xpert Flu A Panel nucleic acid amplification-based point-of-care test for influenza A virus detection and pandemic H1 subtyping

text: Abstract Background Influenza antigenic point-of-care (POC) tests are too insensitive for individual reliable diagnosis of influenza virus infections without additional laboratory confirmation. Molecular POC tests could be a valuable alternative. Objectives To evaluate the first influenza molecular POC test commercially available, the Cepheid Xpert Flu A Panel designed to simultaneously detect influenza A virus and subtype A(H1N1) 2009 pandemic virus, and compare it with in-house real-time RT-PCR (qRT-PCR). Study design Clinical specimens positive for influenza virus and influenza virus isolates with different viral loads and of different type and subtype were used to determine the analytical reactivity and sensitivity. A panel of pathogen negative specimens and isolates of 19 different respiratory pathogens were used to determine the analytical specificity. Results Except A(H9N2) virus the Xpert Flu A Panel detected A(H1N1) seasonal and 2009 pandemic, A(H3N2), A(H5N2), A(H5N1) and A(H7N7) viruses and correctly subtyped A(H1N1) 2009 virus. Analytical sensitivity was similar to qRT-PCR in the range of 400–5000 viral particles per ml. However, of most subtypes some specimens with cycle threshold values greater than 30 in qRT-PCR and A(H1N1) 2009 specimens with inconsistent results in the qRT-PCR due to primer or probe mismatches were not detected in the Xpert Flu A Panel. Analytical specificity was 100%. Conclusions The Xpert Flu A Panel is the first commercially available POC molecular test for detection of influenza A virus and determination of the H1 2009 subtype and is analytically reasonable sensitive compared with qRT-PCR and highly specific and therefore a welcome alternative to antigenic POC tests.


title: Cross-crystal averaging with search models to improve molecular replacement phases

text: The application of molecular replacement (MR) in macromolecular crystallography can be limited by the “model bias” problem. Here we propose a strategy to reduce model bias when only part of a new structure is known: after the MR search, structure determination of the unknown part of the new structure can be facilitated by cross-crystal averaging of the known part of the new structure with the search model. This strategy dramatically improves electron density in the unknown part of the new structure. It has enabled us to determine the structures of two coronavirus receptor-binding domains each complexed with their receptor at moderate resolutions. In a test case, it also enabled automated model building when over 50% of an antigen-antibody complex was absent. These results suggest that this averaging strategy can be routinely used after MR to enhance the interpretability of electron density associated with missing model.


title: Synergistic antiviral effect of a combination of mouse interferon‐α and interferon‐γ on mouse hepatitis virus

text: Although interferon (IFN)‐α and IFN‐γ have been reported to exhibit a synergistic antiviral effect through the different signaling pathways in vitro, their therapeutic efficacy is not well defined in vivo. The current study was carried out to investigate the combined antiviral effect in a model of mouse hepatitis virus Type 2 (MHV‐2) infection, in which fulminant hepatitis is developed. MHV‐2 was injected intraperitoneally into 4‐week‐old ICR mice, IFN or the vehicle was administered intramuscularly for 5 days, and the antiviral effect was evaluated based on survival periods, liver histology, serum alanine transaminase (ALT) levels, and MHV‐2 virus titers in the liver tissues. The animals in the group treated with a combination of IFN‐α and IFN‐γ survived for longer periods than the groups treated with IFN‐α alone and IFN‐γ alone (IFN‐α 10(3) (IU/mouse)/‐γ 10(3) vs. IFN‐α 10(3), P < 0.005; IFN‐α 10(3)/‐γ 10(3) vs. IFN‐γ 10(3), P < 0.001). This is consistent with the lower levels of hepatocellular necrosis and serum ALT and the decreased titers of MHV‐2 virus in the liver tissues (48 hr, P < 0.001; 72 hr, P < 0.001). These findings indicate that a combination of IFN‐α and IFN‐γ exhibits a synergistic antiviral effect on MHV‐2 infection. The biology of MHV‐2 is quite different from that of human hepatitis viruses; however, these results suggest the beneficial combined therapy of IFN‐α and IFN‐γ for the treatment of human viral hepatitis. J. Med. Virol. 69:188–194, 2003. © 2003 Wiley‐Liss, Inc.


title: Clinical Screening Tools to Diagnose Group A Streptococcal Pharyngotonsillitis in Primary Care Clinics to Improve Prescribing Habits

text: This review highlights the clinical scoring tools used for the management of acute pharyngotonsillitis in primary care clinics. It will include the prevalence of group A pharyngotonsillitis among children and adults worldwide and the selective tests employed for diagnosing group A streptococcal pharyngotonsillitis. Pharyngotonsillitis is one of the common reasons for visits to primary care clinics worldwide, and physicians tend to prescribe antibiotics according to the clinical symptoms, which leads to overprescribing antibiotics. This in turn may lead to serious health impacts and severe reactions and may promote antibiotic resistance. These significantly add on to the health care costs. The available information from health organisations and previous studies has indicated the need to manage the diagnosis of pharyngotonsillitis to improve prescribing habits in primary care clinics.


title: Modifiable Areal Unit Problem

text: Abstract The modifiable areal unit problem, MAUP, is ever-present although not always appreciated. Through real examples, this article outlines the basic causes of MAUP, namely changes in the size, shape, and/or orientation of spatial categories/polygons used to map areal data. The visual effects of changes to mapped data are obvious even though the impacts on our understanding of the world are profound. The article concludes with a discussion of technical and broader strategic approaches for confronting the effects of MAUP on our treatment and interpretation of areal data.


title: Characteristics of physical blocking on co-occupant’s exposure to respiratory droplet residuals

text: Existed evidences show that airborne transmission of human respiratory droplets may be related with the spread of some infectious disease, such as severe acute respiratory syndrome (SARS) and H1N1 pandemic. Non-pharmaceutical approaches, including ventilation system and personal protection, are believed to have certain positive effects on the reduction of co-occupant’s inhalation. This work then aims to numerically study the performances of mouth covering on co-occupant’s exposure under mixing ventilation (MV), under-floor air distribution (UFAD) and displacement ventilation (DV) system, using drift-flux model. Desk partition, as one generally employed arrangement in plan office, is also investigated under MV. The dispersion of 1, 5 and 10 μm droplet residuals are numerically calculated and CO(2) is used to represent tracer gas. The results show that using mouth covering by the infected person can reduce the co-occupant’s inhalation greatly by interrupting direct spread of the expelled droplets, and best performance can be achieved under DV since the coughed air is mainly confined in the microenvironment of the infected person. The researches under MV show that the two interventions, mouth covering and desk partition, achieve almost the same inhalation for fine droplets while the inhalation of the co-occupant is lower when using mouth covering for large droplets.


title: Returning to paradise: Investigating issues of tourism crisis and disaster recovery on the island of Bali

text: Abstract The past decade has seen the rapid proliferation of theory, literature, and research, in the field of tourism disaster and crisis management, however very few empirical studies of destination recovery consider the pre-crisis context, or extend beyond a particular crisis catalyst and subsequent return to “business as usual”. As a longitudinal case study, the island destination of Bali provides insight into tourism crisis vulnerability, particularly in relation to issues of unplanned development and host community over-dependence on tourism revenue. Furthermore, the experience of two separate targeted terrorist attacks on the island reveals a number of challenges and tangible lessons for stakeholders engaged in destination disaster management and crisis recovery. While the restoration of consumer confidence and arrival numbers are often considered to be indicators of successful tourism recovery, the broader disaster management literature advocates for proactive vulnerability reduction premised in sustainable development and comprehensive, integrated disaster risk reduction.


Chilblains are a common cutaneous finding during the COVID-19 pandemic: a retrospective nationwide study from France


title: The development of a GeXP-based multiplex reverse transcription-PCR assay for simultaneous detection of sixteen human respiratory virus types/subtypes

text: BACKGROUND: Existing standard non-molecular diagnostic methods such as viral culture and immunofluorescent (DFA) are time-consuming, labor intensive or limited sensitivity. Several multiplex molecular assays are costly. Therefore, there is a need for the development of a rapid and sensitive diagnosis of respiratory viral pathogens. METHODS: A GeXP-based multiplex RT-PCR assay (GeXP assay) was developed to detect simultaneously sixteen different respiratory virus types/subtypes. Seventeen sets of chimeric primers were used to initiate the RT-PCR, and one pair of universal primers was used for the subsequent cycles of the RT-PCR. The specificity of the GeXP assay was examined with positive controls for each virus type/subtype. The sensitivity was evaluated by performing the assay on serial ten-fold dilutions of in vitro-transcribed RNA of all RNA viruses and the plasmids containing the Adv and HBoV target sequence. GeXP assay was further evaluated using 126 clinical specimens and compared with Luminex xTAG RVP Fast assay. RESULTS: The GeXP assay achieved a sensitivity of 20–200 copies for a single virus and 1000 copies when all of the 16 pre-mixed viral targets were present. Analyses of 126 clinical specimens using the GeXP assay demonstrated that GeXP assay and the RVP Fast assay were in complete agreement for 109/126 (88.51%) of the specimens. GeXP assay was more sensitive than the RVP Fast assay for the detection of HRV and PIV3, and slightly less sensitive for the detection of HMPV, Adv, RSVB and HBoV. The whole process of the GeXP assay for the detection of 12 samples was completed within 2.5 hours. CONCLUSIONS: In conclusion, the GeXP assay is a rapid, cost-effective, sensitive, specific and high throughput method for the detection of respiratory virus infections.


title: SARS vaccine based on a replication-defective recombinant vesicular stomatitis virus is more potent than one based on a replication-competent vector

text: Abstract A SARS vaccine based on a live-attenuated vesicular stomatitis virus (VSV) recombinant expressing the SARS-CoV S protein provides long-term protection of immunized mice from SARS-CoV infection (Kapadia, S.U., Rose, J. K., Lamirande, E., Vogel, L., Subbarao, K., Roberts, A., 2005. Long-term protection from SARS coronavirus infection conferred by a single immunization with an attenuated VSV-based vaccine. Virology 340(2), 174–82.). Because it is difficult to obtain regulatory approval of vaccine based on live viruses, we constructed a replication-defective single-cycle VSV vector in which we replaced the VSV glycoprotein (G) gene with the SARS-CoV S gene. The virus was only able to infect cells when pseudotyped with the VSV G protein. We measured the effectiveness of immunization with the single-cycle vaccine in mice. We found that the vaccine given intramuscularly induced a neutralizing antibody response to SARS-CoV that was approximately ten-fold greater than that required for the protection from SARS-CoV infection, and significantly greater than that generated by the replication-competent vector expressing SARS-CoV S protein given by the same route. Our results, along with earlier studies showing potent induction of T-cell responses by single-cycle vectors, indicate that these vectors are excellent alternatives to live-attenuated VSV.


title: Asymmetric dependence between stock market returns and news during COVID19 financial turmoil

text: • I investigate the stock market's reaction to coronavirus news in the top six most affected countries by the pandemic. • The fake news exerts a negative nonlinear influence on the inferior and the middle quantiles throughout the distribution of returns. • The media coverage leads to a decrease in returns across middle and superior quantiles and has no effects on the inferior ones. • During COVID19 turmoil superior quantiles of returns distribution exhibit negative dependence on past performances, while inferior and middle quantiles are not affected by this phenomenon. • The gold return has a positive correlation with the stock markets, which amplifies during extreme bearish and bullish periods indicating that it does not behave as a “Safe Havens” asset.


title: Global comparison of changes in the number of test-positive cases and deaths by coronavirus infection (COVID-19) in the world

text: Global differences in changes in the numbers of population-adjusted daily test-positive cases (NPDP) and deaths (NPDD) by COVID-19 were analyzed for 49 countries, including developed and developing countries. The changes as a proportion of national population were compared, adjusting by the beginning of test-positive cases increase (BPI) or deaths increase (BDI). Remarkable regional differences of more than 100-fold in NPDP and NPDD were observed. The trajectories of NPDD after BDI increased exponentially within 20 days in most countries. Machine learning analysis suggested that NPDD on 30 days after BDI was the highest in developed Western countries (1180 persons per hundred million), followed by countries in the Middle East (128), Latin America (97), and Asia (7). Furthermore, in Western countries with positive rates of the PCR test of less than 7.0%, the increase in NPDP was slowing-down two weeks after BPI, and subsequent NPDD was only 15% compared with those with higher positive rates, which suggested that the situation of testing might have affected the velocity of COVID-19 spread. The causes behind remarkable differences between regions possibly include genetic factors of inhabitants because distributions of the race and of the observed infection increasing rates were in good agreement globally.


title: Sequence analysis of human coronavirus 229E mRNAs 4 and 5: evidence for polymorphism and homology with myelin basic protein

text: Abstract Human coronaviruses (HCV) are important pathogens responsible for respiratory, gastrointestinal and possibly neurological disorders. To better understand the molecular biology of the prototype HCV-229E strain, the nucleotide sequence of the 5'-unique regions of mRNAs 4 and 5 were determined from cloned cDNAs. Sequence analysis of the cDNAs synthesized from mRNA 4 revealed a major difference with previously published results. However, polymerase chain reaction amplification of this region showed that the sequenced cDNAs were produced from minor RNA species, an indication of possible genetic polymorphism in this region of the viral genome. The mutated messenger RNA 4 contains two ORFs: (1) ORF4a consisting of 132 nucleotides which potentially encodes a 44-amino acid polypeptide of 4653 Da; this coding sequence is preceded by a consensus transcriptional initiation sequence, CUAAACU, similar to the ones found upstream of the N and M genes; (2) ORF4b of 249 nucleotides potentially encoding an 83-amino acid basic and leucine-rich polypeptide of 9550 Da. On the other hand, mRNA 5 contains one single ORF of 231 nucleotides which could encode a 77-amino acid basic and leucine-rich polypeptide of 9046 Da. This putative protein presents a significant degree of amino acid homology (33%) with its counterpart found in transmissible gastroenteritis coronavirus (TGEV). The proteins in the two different viruses exhibit similar molecular weights and are extremely hydrophobic. Interestingly, a sequence homology of five amino acids was found between the protein encoded by ORF4b of HCV-229E and an immunologically important region of human myelin basic protein.


title: Human arrogance and epidemics Michael Merson Stephen Inrig

text: Unknown


title: Advocacy to provide good quality oncology services during the COVID-19 pandemic – Actions at 3-Levels

text: Abstract The COVID-19 pandemic is a devastating catastrophe to the whole world, China is the first country seriously affected. This review shows that it is possible to stop wide-spread infection in the country and to provide good quality oncology services even during this challenging period, through concerted efforts with well-organized actions at all levels (National/Municipal, Hospital and Department). The key strategies leading to successful impacts are summarized for sharing. In addition to making practice changes to cope with the adverse realities, oncologists should also work together to raise pragmatic suggestions to policy makers and be strong advocates to protect our patients from the detrimental effect of delay or compromised treatment.


title: Quantitative assay for measuring the Taura syndrome virus and yellow head virus load in shrimp by real-time RT-PCR using SYBR Green chemistry

text: Abstract Taura syndrome virus (TSV) and yellow head virus (YHV) are the two RNA viruses infecting penaeid shrimp (Penaeus sp.) that have caused major economic losses to shrimp aquaculture. A rapid and highly sensitive detection and quantification method for TSV and YHV was developed using the GeneAmp® 5700 Sequence Detection System and SYBR Green chemistry. The reverse transcriptase polymerase chain reaction (RT-PCR) mixture contained a fluorescent dye, SYBR Green, which exhibits fluorescence enhancement upon binding to double strand cDNA. The enhancement of fluorescence was found to be proportional to the initial concentration of the template cDNA. A linear relationship was observed between input plasmid DNA and cycle threshold (C T) values for 106 down to a single copy of both viruses. To control for the variation in sample processing and in reverse transcription reaction among samples, shrimp β-actin and elongation factor-1α (EF-1α) genes were amplified in parallel with the viral cDNA. The sensitivity and the efficiency of amplification of EF-1α was greater than β-actin when compared to TSV and YHV amplification efficiency suggesting that EF-1α is a better internal control for the RT-PCR detection of TSV and YHV. In addition, sample to sample variation in EF-1α C T value was lower than the variation in β-actin C T value of the corresponding samples. The specificity of TSV, YHV, EF-1α and β-actin amplifications was confirmed by analyzing the dissociation curves of the target amplicon. The C T values of TSV and YHV samples were normalized against EF-1α C T values for determining the absolute copy number from the standard curve of the corresponding virus. The method described here is highly robust and is amenable to high throughput assays making it a useful tool for diagnostic, epidemiological and genetic studies in shrimp aquaculture.


title: Preparedness and vulnerability of African countries against importations of COVID-19: a modelling study

text: BACKGROUND: The novel coronavirus disease 2019 (COVID-19) epidemic has spread from China to 25 countries. Local cycles of transmission have already occurred in 12 countries after case importation. In Africa, Egypt has so far confirmed one case. The management and control of COVID-19 importations heavily rely on a country's health capacity. Here we evaluate the preparedness and vulnerability of African countries against their risk of importation of COVID-19. METHODS: We used data on the volume of air travel departing from airports in the infected provinces in China and directed to Africa to estimate the risk of importation per country. We determined the country's capacity to detect and respond to cases with two indicators: preparedness, using the WHO International Health Regulations Monitoring and Evaluation Framework; and vulnerability, using the Infectious Disease Vulnerability Index. Countries were clustered according to the Chinese regions contributing most to their risk. FINDINGS: Countries with the highest importation risk (ie, Egypt, Algeria, and South Africa) have moderate to high capacity to respond to outbreaks. Countries at moderate risk (ie, Nigeria, Ethiopia, Sudan, Angola, Tanzania, Ghana, and Kenya) have variable capacity and high vulnerability. We identified three clusters of countries that share the same exposure to the risk originating from the provinces of Guangdong, Fujian, and the city of Beijing, respectively. INTERPRETATION: Many countries in Africa are stepping up their preparedness to detect and cope with COVID-19 importations. Resources, intensified surveillance, and capacity building should be urgently prioritised in countries with moderate risk that might be ill-prepared to detect imported cases and to limit onward transmission. FUNDING: EU Framework Programme for Research and Innovation Horizon 2020, Agence Nationale de la Recherche.