title: Measuring psychological resilience to disasters: are evidence-based indicators an achievable goal?

text: Despite rising interest on the concept of societal resilience and its measurement, little has been done to provide operational indicators. Importantly, an evidence-based approach to assess the suitability of indicators remains unexplored. Furthermore few approaches that exist do not investigate indicators of psychological resilience, which is emerging as an important component of societal resilience to disasters. Disasters are events which overwhelm local capacities, often producing human losses, injury and damage to the affected communities. As climate hazards and disasters are likely to increase in the coming decades, strengthening the capacity of societies to withstand these shocks and recover quickly is vital. In this review, we search the Web of Knowledge to summarize the evidence on indicators of psychological resilience to disasters and provided a qualitative assessment of six selected studies. We find that an evidence-based approach using features from systematic reviews is useful to compile, select and assess the evidence and elucidate robust indicators. We conclude that strong social support received after a disaster is associated with an increased psychological resilience whereas a female gender is connected with a decrease in the likelihood of a resilient outcome. These results are consistent across disaster settings and cultures and are representative of approximately 13 million disaster-exposed civilians of adult age. An approach such as this that collects and evaluates evidence will allow indicators of resilience to be much more revealing and useful in the future. They will provide a robust basis to prioritize indicators to act upon through intersectoral policies and post-disaster public health interventions.


CoViD-19 and Ortho and Trauma Surgery: the Italian Experience.


title: REASSURED diagnostics to inform disease control strategies, strengthen health systems and improve patient outcomes

text: Lack of access to quality diagnostics remains a major contributor to health burden in resource-limited settings. It has been more than 10 years since ASSURED (affordable, sensitive, specific, user-friendly, rapid, equipment-free, delivered) was coined to describe the ideal test to meet the needs of the developing world. Since its initial publication, technological innovations have led to the development of diagnostics that address the ASSURED criteria, but challenges remain. From this perspective, we assess factors contributing to the success and failure of ASSURED diagnostics, lessons learnt in the implementation of ASSURED tests over the past decade, and highlight additional conditions that should be considered in addressing point-of-care needs. With rapid advances in digital technology and mobile health (m-health), future diagnostics should incorporate these elements to give us REASSURED diagnostic systems that can inform disease control strategies in real-time, strengthen the efficiency of health care systems and improve patient outcomes.


title: The influence of terrorism in tourism arrivals: A longitudinal approach in a Mediterranean country

text: Abstract This longitudinal study examines the impact that terrorist attacks within a representative group of European countries can have on the tourism demand of a South European country with no record of terrorism attacks. In order to analyze the connections between terrorist attacks and tourists' arrivals, occurred between 2002 and the end of 2016, an Unrestricted Vector Autoregressive model was used for multivariate time series analysis. The main results show that terrorist attacks have a strong impact on tourist arrivals and confirm the existence of terrorism spillover, namely the substitution and generalization effects phenomena.


Cardiovascular collateral damages at the time of COVID-19


Dissemination of COVID-19: questions for science


title: Thrombotic thrombocytopenic purpura secondary to Streptococcus

text: Abstract We describe a 16 year old female who developed thrombotic thrombocytopenic purpura (TTP) following infection due to Streptococcus. Initially presenting a fever and systemic upset she progressed to develop dialysis dependent acute renal failure, seizures, thrombocytopenia and a haemolytic anaemia—the pentad of features seen in TTP. Prior to the diagnosis she was found to have unexplained and previously undescribed MRI findings of diffuse increased signal intensity in the white matter of the left cerebellar hemisphere posteriorly and also increased signal intensity in the overlying cortex. She was commenced on plasmapheresis, and her anaemia, thrombocytopenia, creatinine and LDH all fully responded. In addition, she had no further seizures following plasmapheresis and has not relapsed to date. We review both the rare association of TTP and streptococcal infection, and the neuroradiological findings described in the literature. This is only the third case report describing TTP following streptococcal infection, and only the second in the era of plasmapheresis.


SARS-CoV-2 and gastrointestinal tract: the dark side of the pandemic


title: Characterization of the Transcriptome and Gene Expression of Brain Tissue in Sevenband Grouper (Hyporthodus septemfasciatus) in Response to NNV Infection

text: Grouper is one of the favorite sea food resources in Southeast Asia. However, the outbreaks of the viral nervous necrosis (VNN) disease due to nervous necrosis virus (NNV) infection have caused mass mortality of grouper larvae. Many aqua-farms have suffered substantial financial loss due to the occurrence of VNN. To better understand the infection mechanism of NNV, we performed the transcriptome analysis of sevenband grouper brain tissue, the main target of NNV infection. After artificial NNV challenge, transcriptome of brain tissues of sevenband grouper was subjected to next generation sequencing (NGS) using an Illumina Hi-seq 2500 system. Both mRNAs from pooled samples of mock and NNV-infected sevenband grouper brains were sequenced. Clean reads of mock and NNV-infected samples were de novo assembled and obtained 104,348 unigenes. In addition, 628 differentially expressed genes (DEGs) in response to NNV infection were identified. This result could provide critical information not only for the identification of genes involved in NNV infection, but for the understanding of the response of sevenband groupers to NNV infection.


title: Regulatory T Cells in Arterivirus and Coronavirus Infections: Do They Protect Against Disease or Enhance it?

text: Regulatory T cells (T(regs)) are a subset of T cells that are responsible for maintaining peripheral immune tolerance and homeostasis. The hallmark of T(regs) is the expression of the forkhead box P3 (FoxP3) transcription factor. Natural regulatory T cells (nT(regs)) are a distinct population of T cells that express CD4 and FoxP3. nTregs develop in the thymus and function in maintaining peripheral immune tolerance. Other CD4(+), CD4(-)CD8(-), and CD8(+)CD28(-) T cells can be induced to acquire regulatory function by antigenic stimulation, depending on the cytokine milieu. Inducible (or adaptive) T(regs) frequently express high levels of the interleukin 2 receptor (CD25). Atypical T(regs) express FoxP3 and CD4 but have no surface expression of CD25. Type 1 regulatory T cells (Tr1 cells) produce IL-10, while T helper 3 cells (Th3) produce TGF-β. The function of inducible T(regs) is presumably to maintain immune homeostasis, especially in the context of chronic inflammation or infection. Induction of T(regs) in coronaviral infections protects against the more severe forms of the disease attributable to the host response. However, arteriviruses have exploited these T cell subsets as a means to dampen the immune response allowing for viral persistence. T(reg) induction or activation in the pathogenesis of disease has been described in both porcine reproductive and respiratory syndrome virus, lactate dehydrogenase elevating virus, and mouse hepatitis virus. This review discusses the development and biology of regulatory T cells in the context of arteriviral and coronaviral infection.


title: Middle Eastern Respiratory Syndrome Corona Virus (MERS CoV): case reports from a tertiary care hospital in Saudi Arabia

text: BACKGROUND AND OBJECTIVES: Middle Eastern respiratory syndrome caused by novel coronavirus (MERS CoV) has been a major public health challenge since it was first described in 2012 in Saudi Arabia. So far, there is no effective treatment for this serious illness, which features a high mortality rate. We report an initial experience of the use of ribavirin and interferon (IFN)-α2b in the management of MERS CoV at a tertiary care hospital. DESIGN AND SETTINGS: A case series of 6 patients admitted with a confirmed diagnosis of MERS CoV were treated with ribavirin and IFN-α2b in addition to supportive management. The patients’ demographics, clinical parameters, and outcomes were recorded. Fifty-four close contacts of these patients were screened for MERS CoV. METHODS: Six patients with MERS CoV infection were included in this study. Four cases featured symptomatic disease, including pneumonia and respiratory failure, while 2 were asymptomatic close contacts of the MERS CoV patients. The MERS CoV infection was confirmed by reverse transcription–polymerase chain reaction detection of the consensus viral RNA targets upstream of the E gene (UPE) and open reading frame (ORF1b) on a sputum sample. The patients’ demographics, comorbid conditions, time to diagnosis and initiation of treatment, and clinical outcomes were recorded. RESULTS: Three out of 6 patients who had comorbid conditions died during the study period, while 3 had successful outcomes. The diagnosis and treatment was delayed by an average of 15 days in those patients who died. Only 2 close contacts out of the 54 screened (3.7%) were positive for MERS CoV. CONCLUSION: Treatment with ribavirin and IFN-α2b may be effective in patients infected with MERS CoV. There appears to be a low infectivity rate among close contacts of MERS CoV patients.


title: New insights about the regulation of Nidovirus subgenomic mRNA synthesis

text: Abstract The members of the Order Nidovirales share a similar genome organization with two overlapping nonstructural polyproteins encoded in the 5′ two-thirds and the structural proteins encoded in the 3′ third. They also express their 3′ region proteins from a nested set of 3′ co-terminal subgenomic messenger RNAs (sg mRNAs). Some but not all of the Nidovirus sg mRNAs also have a common 5′ leader sequence that is acquired by a discontinuous RNA synthesis mechanism regulated by multiple 3′ body transcription regulating sequences (TRSs) and the 5′ leader TRS. Initial studies detected a single major body TRS for each 3′ sg mRNA with a few alternative functional TRSs reported. The recent application of advanced techniques, such as next generation sequencing and ribosomal profiling, in studies of arteriviruses and coronaviruses has revealed an expanded sg mRNA transcriptome and coding capacity.


Prevention is better than the cure, but the cure cannot be worse than the disease


title: Looking for a needle in a haystack: Cellular proteins that may interact with the tyrosine-based sorting signal of the TGEV S protein

text: Abstract The spike protein S of transmissible gastroenteritis virus, an Alphacoronavirus, contains a tyrosine-based sorting signal that is responsible for ERGIC retention and may be important for a correct viral assembly process. To find out whether the S protein interacts with cellular proteins via this sorting signal, a pulldown assay with GST fusion proteins was performed. Filamin A has been identified as a putative interaction candidate. Immunofluorescence assays confirmed a co-localization between the TGEV S protein and filamin A. Further experiments have to be performed to prove a significant impact of filamin A on TGEV infection. Different approaches of several researchers for the identification of cellular interaction candidates relevant for coronavirus replication are summarized. These results may help in the future to identify the role of cellular proteins during coronavirus assembly at the ER-Golgi intermediate compartment.


title: Zinc pyrithione in alcohol-based products for skin antisepsis: Persistence of antimicrobial effects

text: Alcohol-based products for skin antisepsis have a long history of safety and efficacy in the United States and abroad. However, alcohol alone lacks the required antimicrobial persistence to provide for the sustained periods of skin antisepsis desired in the clinical environment. Therefore, alcohol-based products must have a preservative agent such as iodine/iodophor compounds, chlorhexidine gluconate, or zinc pyrithione, to extend its antimicrobial effects. Iodine, iodophors, and chlorhexidine gluconate are well-characterized antimicrobials and preservatives. The thrust of our effort was to examine the characteristics of the lesser-known zinc pyrithione and to evaluate its utility as a preservative in the formulation of alcohol-based products for skin antisepsis. This work includes a literature review of current zinc pyrithione applications in drugs and cosmetics, a safety and toxicity evaluation, consideration of the proposed mechanisms of antimicrobial action, in vitro and in vivo efficacy data, and a discussion of the mechanisms that confer the desired antimicrobial persistence. In addition, alcohol-based, zinc pyrithione-preserved, commercially available products of skin antisepsis are compared with other commercially available antimicrobials used for skin antisepsis and with additional alcohol-based products with different preservatives. The authors' conclusion is that zinc pyrithione is not only a safe and effective antimicrobial but that its use in certain alcohol-based formulations results in antimicrobial efficacy exceeding that of iodine and chlorhexidine gluconate.


title: Suggestions on the prevention of COVID-19 for health care workers in department of otorhinolaryngology head and neck surgery

text: Abstract The epidemic of the Coronavirus Disease 2019 (COVID-19) has presented as a grim and complex situation recently. More than 77,000 cases of COVID-19 has been confirmed in China until February 25th, 2020, which are causing great impact on economy and society, as well as seriously interfering with ordinary medical practice in the department of otorhinolaryngology head and neck surgery. This article discussed medical precautions required in the clinic, inpatient ward and operation room of otorhinolaryngology head and neck department, which aims to protect health care workers from COVID-19.


title: Long-term infection of SARS-CoV-2 changed the body's immune status

text: The outbreak of SARS-CoV-2-associated pneumonia, a disease called COVID-19, has caused a pandemic worldwide. To investigate the immune responses after infection of SARS-CoV-2 in non-critical patients may help to better understand the disease progression. We collected 334 confirmed COVID-19 cases including 212 still in hospital with nucleic acid test positive on halfway for SARS-CoV-2 and 122 discharged from hospital, compared specific antibodies, immune cells, and cytokine changes between the hospitalized and discharged patients. The hospitalized patients had a longer illness time compared with discharged patients. Analysis of viral loads explained long-term or persistent infection of SARS-CoV-2, which existed with the median time of 18.5 days of the positive nucleic acid test. Serum analysis showed that the specific anti-N IgG antibody was positive in all detected patients after infection of two weeks. Neutrophils, Monocytes, NK cells, and CD4(+) T cells significantly increased, while total lymphocytes and CD8(+) T cells decreased from non-critical hospitalized patients after longer-term infection. Further analysis of the cytokines showed that IL-6, TNF-α, IFN-γ, IL-2, IL-4, and IL-10 from the hospitalized patients were significantly higher, indicating a potential of the increased CD4(+) T cell differentiation.


title: The invisible university is COVID-19 positive

text: Abstract Within the ivory tower, the COVID-19 pandemic stands to disproportionately impact the invisible workforce of postdoctoral researchers. Faced with university closures, hiring freezes and a general lack of support and benefits, an entire generation of Ph.Ds. and their knowledge and skills may be lost to academia without intervention.


title: Salmonella in Dairy Cattle

text: As an infectious, contagious pathogen, Salmonella is probably rivaled by only bovine viral diarrhea virus in its ability to cause clinical disease, such as enteritis, septicemia, pneumonia, and reproductive losses. The increasing prevalence of Salmonella, particularly Salmonella Dublin, on dairies presents new challenges to producers and veterinarians. No current discussion of bovine salmonellosis is complete without acknowledging the increasing public health concern. Increasing antimicrobial resistance among enteric pathogens brings the use of antimicrobials by veterinarians and producers under ever stricter scrutiny. This article provides a comprehensive review of Salmonella etiology, prevalence, pathogenesis, diagnostics, treatment, and control.


title: A Community Letter Regarding Sharing Biomolecular Simulation Data for COVID-19

text: There is an urgent need to share our methods, models, and results openly and quickly to test findings, ensure reproducibility, test significance, eliminate dead-ends, and accelerate discovery. Sharing of data for COVID-19 applications will help connect scientists across the global biomolecular simulation community, and also improve connection and communication between simulation and experimental and clinical data and investigators. We, as a community, commit to the following principles and offer our support to others already working on open data efforts in the hope that others working on COVID-19 in biomolecular simulation and other areas will adopt similar best practices.


title: Detection of Middle East respiratory syndrome coronavirus using reverse transcription loop-mediated isothermal amplification (RT-LAMP)

text: BACKGROUND: The first documented case of Middle East Respiratory Syndrome coronavirus (MERS-CoV) occurred in 2012, and outbreaks have continued ever since, mainly in Saudi Arabia. MERS-CoV is primarily diagnosed using a real-time RT-PCR assay, with at least two different genomic targets required for a positive diagnosis according to the case definition of The World Health Organization (WHO) as of 3 July 2013. Therefore, it is urgently necessary to develop as many specific genetic diagnostic methods as possible to allow stable diagnosis of MERS-CoV infections. METHODS: Reverse transcription-loop-mediated isothermal amplification (RT-LAMP) is a genetic diagnostic method used widely for the detection of viral pathogens, which requires only a single temperature for amplification, and can be completed in less than 1 h. This study developed a novel RT-LAMP assay for detecting MERS-CoV using primer sets targeting a conserved nucleocapsid protein region. RESULTS: The RT-LAMP assay was capable of detecting as few as 3.4 copies of MERS-CoV RNA, and was highly specific, with no cross-reaction to other respiratory viruses. Pilot experiments to detect MERS-CoV from medium containing pharyngeal swabs inoculated with pre-titrated viruses were also performed. The RT-LAMP assay exhibited sensitivity similar to that of MERS-CoV real-time RT-PCR. CONCLUSIONS: These results suggest that the RT-LAMP assay described here is a useful tool for the diagnosis and epidemiologic surveillance of human MERS-CoV infections.


title: Message in a bottle: lessons learned from antagonism of STING signalling during RNA virus infection

text: STING has emerged in recent years as an important signalling adaptor in the activation of type I interferon responses during infection with DNA viruses and bacteria. An increasing body of evidence suggests that STING also modulates responses to RNA viruses, though the mechanisms remain less clear. In this review, we give a brief overview of the ways in which STING facilitates sensing of RNA viruses. These include modulation of RIG-I-dependent responses through STING's interaction with MAVS, and more speculative mechanisms involving the DNA sensor cGAS and sensing of membrane remodelling events. We then provide an in-depth literature review to summarise the known mechanisms by which RNA viruses of the families Flaviviridae and Coronaviridae evade sensing through STING. Our own work has shown that the NS2B/3 protease complex of the flavivirus dengue virus binds and cleaves STING, and that an inability to degrade murine STING may contribute to host restriction in this virus. We contrast this to the mechanism employed by the distantly related hepacivirus hepatitis C virus, in which STING is bound and inactivated by the NS4B protein. Finally, we discuss STING antagonism in the coronaviruses SARS coronavirus and human coronavirus NL63, which disrupt K63-linked polyubiquitination and dimerisation of STING (both of which are required for STING-mediated activation of IRF-3) via their papain-like proteases. We draw parallels with less-well characterised mechanisms of STING antagonism in related viruses, and place our current knowledge in the context of species tropism restrictions that potentially affect the emergence of new human pathogens.


title: Incidental Finding of COVID-19 Lung Infection in (18)F-FDG PET/CT: What Should We Do?

text: We report the case of an asymptomatic (no fever, no cough, no dyspnea) 80-year-old woman who had an (18)F-FDG PET/CT scan for initial staging of Lieberkühnian adenocarcinoma located on anal canal. Chest analysis incidentally revealed bilateral diffuse patchy ground-glass opacity with mild increasing (18)F-FDG uptake, consistent with incidental COVID-19 infection finding during the March 2020 pandemic. The infection was confirmed by reverse transcription–polymerase chain reaction. It led us to improve patient flow and to undertake broader measures to avoid patient clinical issues and potential disease spreading.


title: Computational prediction and identification of dengue virus-specific CD4+ T-cell epitopes

text: Abstract In this study, we tried to identify dengue virus-specific CD4+ T-cell epitopes, which can induce PBMC (peripheral blood mononuclear cells) isolated from DF convalescent patients (dengue virus type 1 infection) to secrete IFN-γ. PBMC of DF convalescent patients were stimulated in vitro with dengue virus-derived peptides, which were prepared based on the prediction of dengue virus-specific CD4+ T-cell epitopes by using RANKpep online software. Subsequently, the frequency of IFN-γ producing T cells and percentage of IFN-γ+ CD4+ T cells were measured by using ELISPOT assay and ICS assay (intracellular cytokine straining), respectively. The positive response of PBMC by ELISPOT showed that the numbers of SFC (spots forming cells) ranged from 50 to 310 SFC/1×106 PBMC. The positive response of PBMC by ICS assay showed that the percentage of IFN-γ+ CD4+ T cells ranged from 0.03 to 0.27%. As a result, C45-57 (KLVMAFIAFLRFL), E396-408 (SSIGKMFEATARG), NS323-35 (YRILQRGLLGRSQ), and NS3141-155 (NREGKIVGLYGNGVV) were identified as dengue virus-specific CD4+ T-cell epitopes.


title: Potential Impact of Pandemic Influenza on Blood Safety and Availability

text: The spread of H5N1, an avian influenza A virus, to many countries and the direct infection of humans by this virus have increased awareness of the likelihood of a pandemic among humans. The potential impact of pandemic influenza on the safety of the blood supply should be small because of the limited viremia and the nature of respiratory tract infection of influenza viruses. However, the potential impact of pandemic influenza on the availability of the blood supply could be significant because of reduced donation from blood donors and reduced staff capacity at blood centers during a pandemic. On the other hand, there could be reduced hospital admissions and reduced transfusions, at least for certain blood products, which should result in reduced demand for blood products. Studies are needed to further assess the likely impact of a pandemic on the blood supply and also of the possible intervention options.


title: Staphylococcus aureus colonization and non-influenza respiratory viruses: Interactions and synergism mechanisms

text: Viral infections of the respiratory tract can be complicated by bacterial superinfection, resulting in a significantly longer duration of illness and even a fatal outcome. In this review, we focused on interactions between S. aureus and non-influenza viruses. Clinical data evidenced that rhinovirus infection may increase the S. aureus carriage load in humans and its spread. In children, respiratory syncytial virus infection is associated with S. aureus carriage. The mechanisms by which some non-influenza respiratory viruses predispose host cells to S. aureus superinfection can be summarized in three categories: i) modifying expression levels of cellular patterns involved in S. aureus adhesion and/or internalization, ii) inducing S. aureus invasion of epithelial cells due to the disruption of tight junctions, and iii) decreasing S. aureus clearance by altering the immune response. The comprehension of pathways involved in S. aureus-respiratory virus interactions may help developing new strategies of preventive and curative therapy.


title: The challenges and opportunities of a global health crisis: the management and business implications of COVID-19 from an Asian perspective

text: On March 11, 2020, the World Health Organization (WHO) declared the coronavirus (COVID-19) outbreak a pandemic. As the evolution and implications of the COVID-19 crisis are still unfolding, we posit that exploring the experiences and strategic responses of Asian countries may shed light on ways to combat COVID-19 for the rest of the world. In this paper, we first articulate the importance of resilience, strategic agility, and entrepreneurship in the context of the fight against COVID-19. Then, with the focus on China, South Korea, and Singapore, we discuss the impact COVID-19 is having on economies and businesses, governmental support for businesses and societies, and implications for global supply chain disruptions. We hope that the global health system will recover quickly, and that the world economy will be revitalized with the contributions and collaboration of science (including social science), industry, and governments.


“ANESTHESIA STAT” TO INTUBATE A COVID-19 PATIENT: IMPLICATIONS FOR THE ANESTHESIOLOGIST


title: Middle East respiratory syndrome coronavirus (MERS-CoV): what lessons can we learn?

text: Summary The Middle East Respiratory Coronavirus (MERS-CoV) was first isolated from a patient who died with severe pneumonia in June 2012. As of 19 June 2015, a total of 1,338 MERS-CoV infections have been notified to the World Health Organization (WHO). Clinical illness associated with MERS-CoV ranges from mild upper respiratory symptoms to rapidly progressive pneumonia and multi-organ failure. A significant proportion of patients present with non-respiratory symptoms such as headache, myalgia, vomiting and diarrhoea. A few potential therapeutic agents have been identified but none have been conclusively shown to be clinically effective. Human to human transmission is well documented, but the epidemic potential of MERS-CoV remains limited at present. Healthcare-associated clusters of MERS-CoV have been responsible for the majority of reported cases. The largest outbreaks have been driven by delayed diagnosis, overcrowding and poor infection control practices. However, chains of MERS-CoV transmission can be readily interrupted with implementation of appropriate control measures. As with any emerging infectious disease, guidelines for MERS-CoV case identification and surveillance evolved as new data became available. Sound clinical judgment is required to identify unusual presentations and trigger appropriate control precautions. Evidence from multiple sources implicates dromedary camels as natural hosts of MERS-CoV. Camel to human transmission has been demonstrated, but the exact mechanism of infection remains uncertain. The ubiquitously available social media have facilitated communication and networking amongst healthcare professionals and eventually proved to be important channels for presenting the public with factual material, timely updates and relevant advice.


title: EGR1 upregulation following Venezuelan equine encephalitis virus infection is regulated by ERK and PERK pathways contributing to cell death

text: Abstract Venezuelan equine encephalitis virus (VEEV) is a neurotropic virus that causes significant disease in both humans and equines. Here we characterized the impact of VEEV on signaling pathways regulating cell death in human primary astrocytes. VEEV productively infected primary astrocytes and caused an upregulation of early growth response 1 (EGR1) gene expression at 9 and 18 h post infection. EGR1 induction was dependent on extracellular signal-regulated kinase1/2 (ERK1/2) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), but not on p38 mitogen activated protein kinase (MAPK) or phosphoinositide 3-kinase (PI3K) signaling. Knockdown of EGR1 significantly reduced VEEV-induced apoptosis and impacted viral replication. Knockdown of ERK1/2 or PERK significantly reduced EGR1 gene expression, dramatically reduced viral replication, and increased cell survival as well as rescued cells from VEEV-induced apoptosis. These data indicate that EGR1 activation and subsequent cell death are regulated through ERK and PERK pathways in VEEV infected primary astrocytes.


title: PERSONAS MAYORES, DEPENDENCIA Y VULNERABILIDAD EN LA PANDEMIA POR CORONAVIRUS: EMERGENCIA DE UNA INTEGRACIÓN SOCIAL Y SANITARIA

text: Resumen La pandemia actual por SARS-CoV-2 (COVID-19) afecta con mayor incidencia y gravedad a las personas mayores en todo el mundo. En España, el 68% del total de hospitalizaciones por coronavirus, corresponden a mayores de 60 años. Este trabajo tiene como objetivo incrementar la evidencia sobre las medidas a implementar con directrices actuales y futuras en diferentes escenarios. Destaca la necesidad de prepararnos para la acción mediante la implementación de protocolos de carácter internacional. Existe una tendencia hacia la atención biopsicosocial de las personas mayores en todos los entornos donde se encuentran, adecuando la atención y personalizando decisiones de ingresos hospitalarios, cuidados paliativos, atendiendo, entre otros criterios, a los años ajustados a la calidad de vida, así como alternativas para el monitoreo y tratamiento de la patología por COVID-19 y otras ya existentes. Son necesarias medidas de reducción de la transmisión del virus a través de la higiene y el distanciamiento, atendiendo a la salud biopsicosocial de los mayores aislados. Como alternativas innovadoras se propone la comunicación intersectorial, y el uso de herramientas tecnológicas, acompañado de una adecuada alfabetización digital en salud. Las líneas futuras se centran en garantizar los derechos sociales y sanitarios, equiparando al mismo nivel el sistema social y de salud, y consiguiendo una coordinación real. Un nuevo marco de atención centrada en la persona podría ser un gran aliado para conseguir una atención integrada a los mayores, guiada por un aumento de los recursos destinados a la financiación de proyectos de investigación sobre longevidad. Abstract The current SARS-CoV-2 pandemic (COVID-19) is affecting elderly people worldwide with greater incidence and severity. In Spain, 68% of all coronavirus hospitalizations correspond to those over 60 years of age. This work aims to highlight the evidence about the measures to be implemented through current and future guidelines. The need to prepare for action by implementing international protocols stand out. There is a trend towards biopsychosocial care of elderly people in all settings where they are, adapting care and personalizing decisions on hospital admissions, palliative care, among other criteria, to years adjusted to quality of life, as well as alternatives for monitoring and treatment of COVID-19 pathology and others existing in this population group. Measures to reduce the transmission of the virus through hygiene and social distancing are necessary, attending to biopsychosocial health of the elderly isolated. Intersectoral communication is proposed as innovative alternatives, and the use of technological tools, accompanied by adequate digital health literacy. Future lines focus on guaranteeing social and health rights, equating the social and health system at the same level, and achieving real coordination. A new framework of person-centered care could be a great ally to achieve integrated care for the elderly, guided by an increase in resources bound to funding longevity research projects.


title: Computational analysis of protein interaction networks for infectious diseases

text: Infectious diseases caused by pathogens, including viruses, bacteria and parasites, pose a serious threat to human health worldwide. Frequent changes in the pattern of infection mechanisms and the emergence of multidrug-resistant strains among pathogens have weakened the current treatment regimen. This necessitates the development of new therapeutic interventions to prevent and control such diseases. To cater to the need, analysis of protein interaction networks (PINs) has gained importance as one of the promising strategies. The present review aims to discuss various computational approaches to analyse the PINs in context to infectious diseases. Topology and modularity analysis of the network with their biological relevance, and the scenario till date about host–pathogen and intra-pathogenic protein interaction studies were delineated. This would provide useful insights to the research community, thereby enabling them to design novel biomedicine against such infectious diseases.


title: The impact of ethnicity on clinical outcomes in COVID-19: A systematic review

text: BACKGROUND: The relationship between ethnicity and COVID-19 is uncertain. We performed a systematic review to assess whether ethnicity has been reported in patients with COVID-19 and its relation to clinical outcomes. METHODS: We searched EMBASE, MEDLINE, Cochrane Library and PROSPERO for English-language citations on ethnicity and COVID-19 (1(st) December 2019-15(th) May 2020). We also reviewed: COVID-19 articles in NEJM, Lancet, BMJ, JAMA, clinical trial protocols, grey literature, surveillance data and preprint articles on COVID-19 in MedRxiv to evaluate if the association between ethnicity and clinical outcomes were reported and what they showed. PROSPERO:180654. FINDINGS: Of 207 articles in the database search, five reported ethnicity; two reported no association between ethnicity and mortality. Of 690 articles identified from medical journals, 12 reported ethnicity; three reported no association between ethnicity and mortality. Of 209 preprints, 34 reported ethnicity – 13 found Black, Asian and Minority Ethnic (BAME) individuals had an increased risk of infection with SARS-CoV-2 and 12 reported worse clinical outcomes, including ITU admission and mortality, in BAME patients compared to White patients. Of 12 grey literature reports, seven with original data reported poorer clinical outcomes in BAME groups compared to White groups. INTERPRETATION: Data on ethnicity in patients with COVID-19 in the published medical literature remains limited. However, emerging data from the grey literature and preprint articles suggest BAME individuals are at an increased risk of acquiring SARS-CoV-2 infection compared to White individuals and also worse clinical outcomes from COVID-19. Further work on the role of ethnicity in the current pandemic is of urgent public health importance. FUNDING: NIHR


title: Unknown SARS-CoV-2 pneumonia detected by PET/CT in patients with cancer

text: INTRODUCTION: In January 2020, the coronavirus disease 2019 (COVID-19) outbreak in Italy necessitated rigorous application of more restrictive safety procedures in the management and treatment of patients with cancer to ensure patient and staff protection. Identification of respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was a challenge during the pandemic owing to a large number of asymptomatic or mildly symptomatic patients. METHODS: We report 5 patients with unknown SARS-CoV-2 infection undergoing positron emission tomography (PET)/computed tomography (CT) with radiopharmaceuticals targeting different tumor processes: (18)F-FDG, (18)F-choline (FCH), and (68)Ga-PSMA. RESULTS: In all patients, PET/CT showed increased tracer uptake in the lungs corresponding to CT findings of SARS-CoV-2 pneumonia. Quantitative assessment of tracer uptake showed more elevated values for the glucose analogue (18)F-FDG (mean SUVmax 5.4) than for the other tracers (mean SUVmax 3.5). CONCLUSIONS: Our findings suggest that PET/CT is a sensitive modality to hypothesize SARS-CoV-2 pneumonia in patients with cancer, even when asymptomatic. More data are needed to verify the correlation among immune response to SARS-CoV-2 infection, clinical evolution, and PET results. Under the strict safety measures implemented at the PET center, the number of potentially SARS-CoV-2–positive patients undergoing PET/CT was very low (1.6%), and no staff member has been diagnosed with infection as of April 30, 2020.


title: Modulation of Protease Activated Receptor 1 Influences Human Metapneumovirus Disease Severity in a Mouse Model

text: Human metapneumovirus (hMPV) infection causes acute respiratory tract infections (RTI) which can result in hospitalization of both children and adults. To date, no antiviral or vaccine is available for this common viral infection. Immunomodulators could represent an interesting strategy for the treatment of severe viral infection. Recently, the role of protease-activated receptors (PAR) in inflammation, coagulation and infection processes has been of growing interest. Herein, the effects of a PAR1 agonist and a PAR1 antagonist on hMPV infection were investigated in BALB/c mice. Intranasal administration of the PAR1 agonist resulted in increased weight loss and mortality of infected mice. Conversely, the PAR1 antagonist was beneficial to hMPV infection by decreasing weight loss and clinical signs and by significantly reducing pulmonary inflammation, pro-inflammatory cytokine levels (including IL-6, KC and MCP-1) and recruitment of immune cells to the lungs. In addition, a significant reduction in pulmonary viral titers was also observed in the lungs of PAR1 antagonist-treated mice. Despite no apparent direct effect on virus replication during in vitro experiments, an important role for PAR1 in the regulation of furin expression in the lungs was shown for the first time. Further experiments indicated that the hMPV fusion protein can be cleaved by furin thus suggesting that PAR1 could have an effect on viral infectivity in addition to its immunomodulatory properties. Thus, inhibition of PAR1 by selected antagonists could represent an interesting strategy for decreasing the severity of paramyxovirus infections.


title: Characterization of a Bivalent Vaccine Capable of Inducing Protection Against Both Ebola and Cross-clade H5N1 Influenza in Mice

text: Background. Ebola virus (EBOV) is a lethal pathogen that causes up to 90% mortality in humans, whereas H5N1 avian influenza has a 60% fatality rate. Both viruses are considered pandemic threats. The objective was to evaluate the protective efficacy of a bivalent, recombinant vesicular stomatitis virus vaccine expressing both the A/Hanoi/30408/2005 H5N1 hemagglutinin and the EBOV glycoprotein (VSVΔG-HA-ZGP) in a lethal mouse model of infection. Methods. Mice were vaccinated 28 days before or 30 minutes after a lethal challenge with mouse-adapted EBOV or selected H5N1 influenza viruses from clades 0, 1, and 2. Animals were monitored for weight loss and survival, in addition to humoral and cell-mediated responses after immunization. Results. A single VSVΔG-HA-ZGP injection was efficacious when administered 28 days before a homologous H5N1 and/or mouse-adapted EBOV challenge, as well as a heterologous H5N1 challenge. Postexposure protection was only observed in vaccinated animals challenged with homologous H5N1 and/or mouse-adapted EBOV. Analysis of the adaptive immune response postvaccination revealed robust specific T- and B-cell responses, including a potent hemagglutinin inhibition antibody response against all H5N1 strains tested. Conclusions. The results highlight the ability of vesicular stomatitis virus–vectored vaccines to rapidly confer protection against 2 unrelated pathogens and stimulate cross-protection against H5N1 influenza viruses.


title: Inhibition of Hepatitis B virus gene expression by single and dual small interfering RNA treatment

text: Abstract RNA interference (RNAi) has been successfully applied in suppression of Hepatitis B virus (HBV) replication. To circumvent the problem that mutation in HBV genome may result in resistance when siRNA is further developed as an anti-viral drug, in this study, we established a dual small interfering RNA (siRNA) expression system, which could simultaneously express two different siRNA molecules that can specifically target two genes. To test the effectiveness of this system, we applied this new approach to express simultaneously two different 21-bp hairpin siRNA duplexes that specifically attack the HBs and HBx genes of HBV, respectively, in Bel-7402 and HepG2.2.15 cells. Results indicated that dual siRNA could simultaneously inhibit the expression of HBs and HBx gene by 83.7% and 87.5%, respectively, based on luciferase assays. In addition, dual siRNA molecules were able to significantly reduce the amount of HBV core associated DNA, which is considered as an intracellular replicative intermediate, and the viral DNA in culture supernatant. Therefore, this dual siRNA system provides a more powerful tool for the study of gene function and implicates a potential application in the treatment of viral infection.


title: Overview of preparedness and response for Middle East respiratory syndrome coronavirus (MERS-CoV) in Oman

text: Summary Several countries in the Middle East and around 22 countries worldwide have reported cases of human infection with the Middle East respiratory syndrome coronavirus (MERS-CoV). The exceptionally high fatality rate resulting from MERS-CoV infection in conjunction with the paucity of knowledge about this emerging virus has led to major public and international concern. Within the framework of the national acute respiratory illness surveillance, the Ministry of Health in the Sultanate of Oman has announced two confirmed cases of MERS-CoV to date. The aim of this report is to describe the epidemiological aspects of these two cases and to highlight the importance of public health preparedness and response. The absence of secondary cases among contacts of the reported cases can be seen as evidence of the effectiveness of infection prevention and control precautions as an important pillar of the national preparedness and response plan applied in the health care institutions in Oman.


title: Diagnosing Viral and Atypical Pathogens in the Setting of Community-Acquired Pneumonia

text: The ‘atypical’ pathogens causing pneumonia have long been problematic for physicians because we have had to rely on serologic tests to make a diagnosis. The introduction of polymerase chain reaction techniques revolutionized the diagnosis of respiratory infections and now a new wave of technologies promising faster, cheaper, and more comprehensive testing are becoming available. This review focuses principally on the diagnosis of Legionella, Mycoplasma, and influenza infections, but also covers recent publications on the cutting edge of diagnostic tools likely to transform the field of infectious diseases over the coming decade.


title: Scoring system to triage patients for spine surgery in the setting of limited resources: Application to the COVID-19 pandemic and beyond

text: Abstract Background As of May 04, 2020, the COVID-19 pandemic has affected over 3.5 million people and touched every inhabited continent. Accordingly, it has stressed health systems the world over leading to the cancellation of elective surgical cases and discussions regarding healthcare resource rationing. It is expected that rationing of surgical resources will continue even after the pandemic peak, and may recur with future pandemics, creating a need for a means of triaging emergent and elective spine surgery patients. Methods Using a modified Delphi technique, a cohort of 16 fellowship-trained spine surgeons from 10 academic medical centers constructed a scoring system for the triage and prioritization of emergent and elective spine surgeries. Three separate rounds of videoconferencing and written correspondence were used to reach a final scoring system. Sixteen test cases were used to optimize the scoring system so that it could categorize cases as requiring emergent, urgent, high-priority elective, or low-priority elective scheduling. Results The devised scoring system included 8 independent components: neurological status, underlying spine stability, presentation of a high-risk post-operative complication, patient medical comorbidities, expected hospital course, expected discharge disposition, facility resource limitations, and local disease burden. The resultant calculator was deployed as a freely-available web-based calculator (https://jhuspine3.shinyapps.io/SpineUrgencyCalculator/). Conclusion Here we present the first quantitative urgency scoring system for the triage and prioritizing of spine surgery cases in resource-limited settings. We believe that our scoring system, while not all-encompassing, has potential value as a guide for triaging spine surgical cases during the COVID pandemic and post-COVID period.


title: High incidence of venous thromboembolic events in anticoagulated severe COVID‐19 patients

text: BACKGROUND: Coagulopathy is a common abnormality in patients with COVID‐19. However, the exact incidence of venous thromboembolic event is unknown in anticoagulated, severe COVID‐19 patients. OBJECTIVES: Systematic assessment of venous thromboembolism (VTE) using complete duplex ultrasound (CDU) in anticoagulated COVID‐19 patients. PATIENTS AND METHODS: We performed a retrospective study in 2 French intensive care units (ICU) where CDU is performed as a standard of care. A CDU from thigh to ankle at selected sites with Doppler waveforms and images was performed early during ICU stay in patients admitted with COVID‐19. Anticoagulation dose was left to the discretion of the treating physician based on the individual risk of thrombosis. Patients were classified as treated with prophylactic anticoagulation or therapeutic anticoagulation. Pulmonary embolism was systematically searched in patients with persistent hypoxemia or secondary deterioration. RESULTS: From March 19 to April 11, 2020, 26 consecutive patients with severe COVID‐19 were screened for VTE. Eight patients (31%) were treated with prophylactic anticoagulation, whereas 18 patients (69%) were treated with therapeutic anticoagulation. The overall rate of VTE in patients was 69%. The proportion of VTE was significantly higher in patients treated with prophylactic anticoagulation when compared with the other group (100% vs 56%, respectively, P = .03). Surprisingly, we found a high rate of thromboembolic events in COVID‐19 patients treated with therapeutic anticoagulation, with 56% of VTE and 6 pulmonary embolisms. CONCLUSION: Our results suggest considering both systematic screening of VTE and early therapeutic anticoagulation in severe ICU COVID‐19 patients.


title: Cell-Penetrating Peptides for Antiviral Drug Development

text: Viral diseases affect hundreds of millions of people worldwide, and the few available drugs to treat these diseases often come with limitations. The key obstacle to the development of new antiviral agents is their delivery into infected cells in vivo. Cell-penetrating peptides (CPPs) are short peptides that can cross the cellular lipid bilayer with the remarkable capability to shuttle conjugated cargoes into cells. CPPs have been successfully utilized to enhance the cellular uptake and intracellular trafficking of antiviral molecules, and thereby increase the inhibitory activity of potential antiviral proteins and oligonucleotide analogues, both in cultured cells and in animal models. This review will address the notable findings of these studies, highlighting some promising results and discussing the challenges CPP technology has to overcome for further clinical applications.


title: Gene expression profiling to identify potentially relevant disease outcomes and support human health risk assessment for carbon black nanoparticle exposure

text: Abstract New approaches are urgently needed to evaluate potential hazards posed by exposure to nanomaterials. Gene expression profiling provides information on potential modes of action and human relevance, and tools have recently become available for pathway-based quantitative risk assessment. The objective of this study was to use toxicogenomics in the context of human health risk assessment. We explore the utility of toxicogenomics in risk assessment, using published gene expression data from C57BL/6 mice exposed to 18, 54 and 162μg Printex 90 carbon black nanoparticles (CBNP). Analysis of CBNP-perturbed pathways, networks and transcription factors revealed concomitant changes in predicted phenotypes (e.g., pulmonary inflammation and genotoxicity), that correlated with dose and time. Benchmark doses (BMDs) for apical endpoints were comparable to minimum BMDs for relevant pathway-specific expression changes. Comparison to inflammatory lung disease models (i.e., allergic airway inflammation, bacterial infection and tissue injury and fibrosis) and human disease profiles revealed that induced gene expression changes in Printex 90 exposed mice were similar to those typical for pulmonary injury and fibrosis. Very similar fibrotic pathways were perturbed in CBNP-exposed mice and human fibrosis disease models. Our synthesis demonstrates how toxicogenomic profiles may be used in human health risk assessment of nanoparticles and constitutes an important step forward in the ultimate recognition of toxicogenomic endpoints in human health risk. As our knowledge of molecular pathways, dose–response characteristics and relevance to human disease continues to grow, we anticipate that toxicogenomics will become increasingly useful in assessing chemical toxicities and in human health risk assessment.


title: Development of a SYBR green I-based quantitative RT-PCR for Ross River virus: Application in vector competence studies and antiviral drug evaluation

text: Abstract Ross River virus (RRV) is an emerging Alphavirus and is presently endemic in many parts of Oceania. Keeping in mind its emergence, we developed a molecular detection system and utilized it to study vector competence and evaluate activity of antiviral compounds against RRV. A SYBR Green I-based quantitative RT-PCR for detection of RRV was developed targeting the E2 gene, with a detection limit of 100 RNA copies/reaction. The specificity was confirmed with closely related Alphaviruses and Flaviviruses. The assay was applied to study the vector competence of Indian Aedes aegypti for RRV, which revealed 100% infection and dissemination rate with 75% transmission rate. Viral RNA was found in saliva as early as 3day post infection (dpi). Further application of the assay in antiviral drug evaluation revealed the superior in vitro activity of ribavirin compared to chloroquine in Vero cells. Successful demonstration of this assay to detect RRV in low titre mosquito samples makes it a sensitive tool in vector surveillance. This study also showed that Indian Ae. aegypti are well competent to transmit RRV highlighting the risk of its introduction to naïve territories across continents. Further validation of this assay, revealed its utility in screening of potential antivirals against RRV.


title: Blocking ELISA for distinguishing infectious bovine rhinotracheitis virus (IBRV)-infected animals from those vaccinated with a gene-deleted marker vaccine

text: Abstract A sensitive and specific blocking enzyme-linked immunosorbent assay (ELISA) was developed to distinguish infectious bovine rhinotracheitis virus (IBRV)-infected animals from those immunized with a glycoprotein gIII deletion mutant, IBRV(NG)dltkdlgIII. For this ELISA, undiluted test sera are used to block the binding of an anti-IBRV gIII monoclonal antibody (mAbgIII)-horseradish peroxidase (HRPO) conjugate to gIII antigen. TMB substrate is used for color development. Negative S/N values (defined as the absorbance at 650 nm of test sera/absorbance at 650 nm of negative control sera) of >0.80 were obtained with immune sera from gnotobiotic cattle immunized with several bovine viruses, with bovine antisera to bovine herpesvirus-2, and vesicular stomatitis virus, with porcine antisera to pseudorabies virus and parvovirus, and with normal sera from heterologous species. Negative S/N values were also obtained with sera from rabbits twice vaccinated with IBRV(NG)dltkdlgIII. However, the S/N values became positive (S/N <0.8) 10 to 17 days after the rabbits were challenge exposed to virulent IBRV(Cooper). Most of 116 sera (84%) from feedlot cattle with virus neutralization (VN) titers of < 1:2 or < 1:4 had negative S/N values >0.8, but 18 sera with negative VN titers had positive S/N values, consistent with observations indicating that an IBRV outbreak was occurring in one of the feedlot herds. Thirty nine sera (98%) from feedlot cattle with VN titers of 1:2 to 1:128 had positive S/N values (<0.8). One serum with a VN titer of 1:2 had a borderline (±) S/N value of 0.81. After immunization with a commercial gIII-positive IBRV vaccine, 115 116 sera with VN titers of 1:2 to 1:256 had positive S/N values (<0.8). One serum with a VN titer of 1:2 had a negative S/N value of 0.83. Serum from one vaccinated animal that failed to seroconvert after vaccination (VN < 1:4) showed a strongly positive ELISA S/N of 0.48.


title: Comparative Research for the Healthcare Budget and Burden of Disease in Perspective Resource Allocation

text: BACKGROUND: Burden of disease can be used to prioritize the healthcare budget allocation. We analyzed the research and development (R&D) budget of the Ministry of Health and Welfare (MOHW) in 2018 and compared the results with those of the 2015 Korean National Burden of Disease (KNBD) study. METHODS: The 2018 MOHW R&D Project integrated implementation plan was used to analyze the R&D budget of the MOHW. The budget was allocated according to the KNBD disease group and according to the budget lines. The allocated budget was compared with the economic burden and the disability adjusted life years (DALYs) in 2015. Also, for budget targets for risk factors, DALYs of attributable risk factors were compared with corresponding budgets. RESULTS: In 2018, the MOHW major R&D budget of USD 435.1 million accounted for 3% of the total government budget. Within the disease specific R&D budget, 35.9% was allocated to communicable disease groups, 64.1% to non-communicable diseases, and 0% to injury and violence. Among level 2 disease groups, neoplasm was ranked first. Among risk factors, climate change and behavioral risk were targeted for R&D. CONCLUSIONS: It would be difficult to say that current R&D allocations focus to minimize the burden of disease. A mismatch was observed between the R&D budget and the burden of disease in terms of economic burden and DALYs. There was a similar finding for risk factors R&D. A novel approach for allocating government R&D funding that is based on the goal of minimizing the disease burden in the Korean population should be considered.


title: Fluorescence based fiber optic and planar waveguide biosensors. A review

text: Abstract The application of optical biosensors, specifically those that use optical fibers and planar waveguides, has escalated throughout the years in many fields, including environmental analysis, food safety and clinical diagnosis. Fluorescence is, without doubt, the most popular transducer signal used in these devices because of its higher selectivity and sensitivity, but most of all due to its wide versatility. This paper focuses on the working principles and configurations of fluorescence-based fiber optic and planar waveguide biosensors and will review biological recognition elements, sensing schemes, as well as some major and recent applications, published in the last ten years. The main goal is to provide the reader a general overview of a field that requires the joint collaboration of researchers of many different areas, including chemistry, physics, biology, engineering, and material science.


title: Establishing research priorities to improve the One Health efficacy of Australian general practitioners and veterinarians with regard to zoonoses: A modified Delphi survey

text: While general medical practitioners (GPs) and veterinarians are often the first line responders in the face of a disease outbreak, pathways to improving the One Health efficacy of these clinicians remain unclear. A two-phase modified Delphi survey of professionals with known expertise in One Health (‘expert panel’) was used to 1) identify key knowledge, attitudes and practices (KAPs) of GPs and veterinarians that would be consistent with a One Health approach to zoonoses; and 2) determine priorities for future surveys with Australian GPs and veterinarians to identify important gaps that impede effective diagnosis and management of zoonoses. A list of 13 topics/sub-topics, as well as a list of 25 specific zoonotic diseases/agents emerged from the first phase of the survey. In the second phase the expert panel identified general knowledge of the clinical aspects and epidemiological aspects of zoonoses, as well as risk management practices, as the most important KAPs and research priorities for both GPs and veterinarians. In terms of diseases, the expert panel regarded knowledge of Hendra virus, Q fever, Australian bat lyssavirus (ABLV), anthrax and Brucella suis most important for veterinarians, whilst for GPs, Q fever, gastrointestinal/foodborne diseases, influenza, ABLV and local vector-borne diseases were found to be most important by the expert panel. Some differences were noted in terms of prioritization of topics/sub-topics and diseases/agents according to expert background (veterinary and non-veterinary). The Delphi survey technique enabled efficient collection of data from a diverse range of One Health ‘experts’/specialists and provided clear priorities for proposed future research, and potentially for educational interventions to improve One Health efficacy of clinicians.


title: Topographical aspects of airborne contamination caused by the use of dental handpieces in the operative environment.

text: ABSTRACT Background The use of dental handpieces produces aerosols containing microbial agents, bacteria and viruses representing a high-risk situation for airborne cross-infections. This study aimed to map and quantify the biological contamination of a dental operatory environment using a biological tracer. Methods Streptococcus mutans suspension was infused into the mouth of a phantom, and an operator performed standardized dental procedures using an air turbine, a contra-angle handpiece or an ultrasonic scaler. The presence of the tracer was measured at 90 sites on the dental unit and the surrounding surfaces of the operatory environment. Results All tested instruments spread the tracer over the entire dental unit and the surrounding environment, including the walls and ceiling. The pattern and degree of contamination were related to the distance from the infection source. The maximum distance of tracer detection was 360 cm for air turbine, 300 cm for contra-angle and 240 cm for scaler (11.8, 9.8 and 7.9 ft, respectively). No surface of the operative environment was free from the tracer after the use of the air turbine. Conclusions Attention should be paid to minimize or avoid the use of rotary and ultrasonic instruments when concerns for the airborne spreading of pandemic disease agents are present. Practical Implications. The present study supports the recommendations of dental associations to avoid treatments generating aerosols, especially during pandemic periods. Guidelines for the management of dental procedures involving aerosols are urgently needed, as well as methods for the aerosols modification aimed to inactivate the infective agent.


title: Live Cell Reporter Systems for Positive-Sense Single Strand RNA Viruses

text: Cell-based reporter systems have facilitated studies of viral replication and pathogenesis, virus detection, and drug susceptibility testing. There are three types of cell-based reporter systems that express certain reporter protein for positive-sense single strand RNA virus infections. The first type is classical reporter system, which relies on recombinant virus, reporter virus particle, or subgenomic replicon. During infection with the recombinant virus or reporter virus particle, the reporter protein is expressed and can be detected in real time in a dose-dependent manner. Using subgenomic replicon, which are genetically engineered viral RNA molecules that are capable of replication but incapable of producing virions, the translation and replication of the replicon could be tracked by the accumulation of reporter protein. The second type of reporter system involves genetically engineered cells bearing virus-specific protease cleavage sequences, which can sense the incoming viral protease. The third type is based on viral replicase, which can report the specific virus infection via detection of the incoming viral replicase. This review specifically focuses on the major technical breakthroughs in the design of cell-based reporter systems and the application of these systems to the further understanding and control of viruses over the past few decades.


title: Virus safety of intravenous immunoglobulin: Future challenges

text: Patients with immunodeficiencies or some types of autoimmune diseases are dependent on safe therapy with intravenous immunoglobulins. State-of-the-art manufacturing processes provide a high safety standard by incorporating virus elimination procedures into the manufacturing process. Based on their mechanism, these procedures are grouped into three classes: partitioning, inactivation, and removal based on size. Because of current socioeconomic and ecological changes, emerging pathogens continue to be expected. Such pathogens may spread very quickly because of increased intercontinental traffic. Severe acute respiratory syndrome-coronavirus and the West Nile virus are recent examples. Currently, it is not possible to predict the impact such a pathogen will have on blood safety because the capacity for a globally coordinated reaction to such a threat is also evolving. The worst-case scenario would be the emergence of a transmissible, small, nonenveloped virus in the blood donor population. Examples of small nonenveloped viruses, which change host and tissue tropism, are discussed, with focus on parvoviridae. Although today’s immunoglobulins are safer than ever, in preparation for future challenges it is a high priority for the plasma industry to proactively investigate such viruses on a molecular and cellular level to identify their vulnerabilities.


title: Early identification of pneumonia patients at increased risk of Middle East respiratory syndrome coronavirus infection in Saudi Arabia

text: Abstract Background The rapid and accurate identification of individuals who are at high risk of Middle East respiratory syndrome coronavirus (MERS-CoV) infection remains a major challenge for the medical and scientific communities. The aim of this study was to develop and validate a risk prediction model for the screening of suspected cases of MERS-CoV infection in patients who have developed pneumonia. Methods A two-center, retrospective case–control study was performed. A total of 360 patients with confirmed pneumonia who were evaluated for MERS-CoV infection by real-time reverse transcription polymerase chain reaction (rRT-PCR) between September 1, 2012 and June 1, 2016 at King Abdulaziz Medical City in Riyadh and King Fahad General Hospital in Jeddah, were included. According to the rRT-PCR results, 135 patients were positive for MERS-CoV and 225 were negative. Demographic characteristics, clinical presentations, and radiological and laboratory findings were collected for each subject. Results A risk prediction model to identify pneumonia patients at increased risk of MERS-CoV was developed. The model included male sex, contact with a sick patient or camel, diabetes, severe illness, low white blood cell (WBC) count, low alanine aminotransferase (ALT), and high aspartate aminotransferase (AST). The model performed well in predicting MERS-CoV infection (area under the receiver operating characteristics curves (AUC) 0.8162), on internal validation (AUC 0.8037), and on a goodness-of-fit test (p =0.592). The risk prediction model, which produced an optimal probability cut-off of 0.33, had a sensitivity of 0.716 and specificity of 0.783. Conclusions This study provides a simple, practical, and valid algorithm to identify pneumonia patients at increased risk of MERS-CoV infection. This risk prediction model could be useful for the early identification of patients at the highest risk of MERS-CoV infection. Further validation of the prediction model on a large prospective cohort of representative patients with pneumonia is necessary.


Corticosteroid use in selected patients with severe Acute Respiratory Distress Syndrome related to Covid-19


title: Epidemiological study of people living in rural North Carolina for novel respiratory viruses

text: During the last 10 years, scientists have grown increasingly aware that emerging respiratory viruses are often zoonotic in their origin. These infections can originate from or be amplified in livestock. Less commonly recognized are instances when humans have transmitted their respiratory pathogens to animals (reverse zoonoses). Even with this knowledge of viral exchange at the human–livestock interface, few studies have been conducted to understand this cross‐over. In this pilot study, we examined persons with influenza‐like illness at an outpatient clinic for evidence of infection with novel zoonotic respiratory pathogens in rural North Carolina where there are dense swine and poultry farming. Environmental air sampling was also conducted. From July 2016 to March 2017, a total of 14 human subjects were enrolled and sampled, and 192 bioaerosol samples were collected. Of the 14 human subject samples molecularly tested, three (21.4%) were positive for influenza A, one (7.1%) for influenza B and one (7.1%) for human enterovirus. Of the 192 bioaerosol samples collected and tested by real‐time RT‐PCR or PCR, three (1.6%) were positive for influenza A and two (1.0%) for adenovirus. No evidence was found for novel zoonotic respiratory viruses.


title: The V5A13.1 envelope glycoprotein deletion mutant of mouse hepatitis virus type-4 is neuroattenuated by its reduced rate of spread in the central nervous system

text: Abstract Following intracerebral inoculation of adult Balb/c Byj mice, the MHV-4 strain of mouse hepatitis virus (MHV) had an LD50 of <0.1 PFU, whereas its monoclonal antibody resistant variant V5A13.1 had an LD50 of 104.2 PFU. To determine the basis for this difference in neurovirulence we have studied the acute central nervous system (CNS) infection of these two viruses by in situ hybridization. Both viruses infected the same, specific neuroanatomical areas, predominantly neurons, and spread via the cerebrospinal fluid, along neuronal pathways and between adjacent cells. The neuronal nuclei infected and the spread of virus within the brain are described. The main difference between the parental and variant viruses was the rate at which the infection spread. MHV-4 spread rapidly, destroying large numbers of neurons and the animals died within 4 days of infection. The variant virus spread to the same areas of the brain but at a slower rate. This difference in the rate of virus spread was also apparent from the brain virus titers. The slower rate of spread of the variant virus appears to allow intervention by the immune response. Consistent with this, the variant virus spread slowly in athymic nu/nu mice, but in the absence of an intact immune response, infection and destruction of neurons eventually reached the same extent as that of the parental virus and the mice died within 6 days of infection. We conclude that the V5A13.1 variant of MHV-4 is neuroattenuated by its slower rate of spread in the CNS.


title: Clinical Characteristics of Patients Who Died of Coronavirus Disease 2019 in China

text: This case series describes the characteristics of a cohort of patients who died of coronavirus disease 2019 in China.


title: Chapter 8 Control of intestinal diseases by dietary supplementation with antibodies

text: Publisher Summary The chapter discusses the control of intestinal diseases by dietary supplementation with antibodies. This chapter presents the most important principles of prophylactic and therapeutic, and oral application of immunoglobulins. Because of the production conditions today about 20–40% of newborn farm animals (cattle, pigs, horses, goats, sheep) exhibit failure of passive transfer (FPT). The direct consequence of this is an increased susceptibility to diseases during the first weeks of life, which necessitates the wide use of antibiotics. As a further consequence, an increasing antibiotic-resistance of diarrheal strains of bacteria has become a fact. An alternative to using antibiotic is oral application of immunoglobulin products in the periods of greatest risk that is within the first days of life and in the postweaning period. Air-dried egg yolk immunoglobulin (IgY), cow colostrum and swine serum, which can be produced on a large scale, provide the greatest chance for mass application. The most important protective role is played by specific antibodies against antigens present in the neonate's environment. The chapter discusses application of xenogenic antibodies. There are several indications for the application of cow colostrum to foals, lambs and kids, such as lack of, or low quality of maternal colostrum, mastitis, twins or multiple fetuses, and so on. Serum produced from the blood of slaughtered swine allows the large-scale production of immunoglobulins. An important problem with oral administration is proteolysis of the immunoglobulins by digestive enzymes, while another problem is caused by inactivation of antibody activity because of low pH.


title: Design, synthesis and biological evaluation of phosphorodiamidate prodrugs of antiviral and anticancer nucleosides

text: We herein report the application of the phosphorodiamidate phosphate prodrug approach to a series of thirteen nucleoside analogs with antiviral or anticancer activity. Twenty-five symmetrical phosphorodiamidates were synthesized, bearing esterified l-Alanine (and in one case d-alanine) in the prodrug moiety, each as single stereoisomer. The presence of an achiral phosphorus represents a potential advantage over the phosphoramidate ProTide approach, where diastereoisomeric mixtures are routinely obtained, and different biological profiles may be expected from the diastereoisomers. Optimization of the synthetic pathway allowed us to identify two general methods depending on the particular nucleoside analogs. All the compounds were biologically evaluated in antiviral and anticancer assays and several showed improvement of activity compared to their parent nucleosides, as in the case of ddA, d4T, abacavir and acyclovir against HIV-1 and/or HIV-2. The biological results were supported by metabolism studies with carboxypeptidase Y monitored by (31)P NMR to investigate their bioactivation. This work further validates the phosphorodiamidate approach as a monophosphate prodrug motif with broad application in the antiviral and anticancer fields.


title: Association of Digestive Symptoms and Hospitalization in Patients With SARS-CoV-2 Infection

text: INTRODUCTION: High rates of concurrent gastrointestinal manifestations have been noted in patients with corona virus disease 2019 (COVID-19); however, the association between these digestive manifestations and need for hospitalization has not been established. METHODS: This is a retrospective review of consecutive patients diagnosed with COVID-19. A total of 207 patients were identified; 34.5% of patients noted concurrent gastrointestinal symptoms, with 90% of gastrointestinal symptoms being mild. RESULTS: In a multivariate regression model controlled for demographics and disease severity, an increased risk of hospitalization was noted in patients with any digestive symptom (adjusted odds ratio 4.84, 95% confidence interval: 1.68–13.94). DISCUSSION: The presence of digestive symptoms in COVID-19 is associated with a need for hospitalization.


title: Sporadic cases of adult measles: a research article

text: BACKGROUND: Measles caused by a paramyxovirus, characterized by fever, malaise, cough, coryza conjunctivitis, a maculopapular rash is known to result in pneumonia, encephalitis and death. Fatal cases of measles in Sri Lanka are rare after implementation of the National Immunization Programme in 1984. Thereafter 0.1% case fatality rate was observed during October 1999–June 2000 which is a very low figure compared to other regional countries. Immunization guidelines were further revised in 2001, 2011 and in 2012 when additional immunization was recommended to age group 4–21 years; who are likely to have inadequate immunization, in order to achieve elimination of Measles by 2020. However, in 2013–2014, 4690 cases were reported and the majority were children less than 1 year of age. The occurrence in adults is hard to retrieve in published epidemiological reports, however had been 38% (out of 1008 patients) in the 3rd quarter of 2013. During this outbreak 73/101 (72%) reported from the North Central Province of Sri Lanka had been more than 12 years of age with 50% being more than 29 years. 14 Sri lankan adult patients [median age 32 years (range 25–48)] who presented sporadically from June 2014 to March 2016, with confirmed measles infection were enrolled retrospectively after informed consent. Details with regards to their clinical presentation, immunization and other relevant areas were collected using an interviewer administered questionnaire or using patient management records. RESULTS: The patients presented with high fever, headache, severe body aches, sore throat, dry cough, intense tearing, red eyes and posterior cervical lymphadenopathy over 3–5 days duration. Later they developed discrete maculopapular rash helping the diagnosis. They had a variable degree of leucopenia, lymphocytosis, thrombocytopenia and derangements in the liver functions mimicking any other acute febrile illnesses such as dengue, chikungunya, leptospirosis or Zika virus infection. CONCLUSION: At least a 3–5 day delay in the diagnosis was observed (even after the appearance of the rash in some patients), due to non-awareness of its occurrence, unfamiliarity of measles in adults, non-specific nature of the illness and non-availability of rapid diagnostics, risking transmission to the immune-compromised or non-immune staff or patients. Identification of the source of infection in these sporadic adult cases and their virologic surveillance and molecular epidemiology will be important to interrupt the transmission and to achieve the targeted elimination of measles from Sri Lanka by 2020.


title: Polyomaviruses KI and WU in children with respiratory tract infection

text: The polyomaviruses KI (KIPyV) and WU (WUPyV) have recently been discovered in specimens from patients with respiratory tract infections. To analyze the frequency and clinical impact in a cohort of pediatric patients in a German University Children’s Hospital. Nasopharyngeal aspirates or bronchoalveolar lavage specimens of 229 children with acute respiratory tract infection were screened for KIPyV and WUPyV using polymerase chain reaction-based methods. KIPyV was detected in 2 (0.9%) and WUPyV in 1 (0.4%) patients, without co-infections with other respiratory viruses but with co-detection of CMV, EBV and HHV 6 in one immunocompromised patient. Only a very small proportion (1.3%) of positive samples for KIPyV and WUPyV was documented in this study; the clinical relevance of these viruses remains unclear and requires further evaluation.


title: Glass Wool Concentration Optimization for the Detection of Enveloped and Non-enveloped Waterborne Viruses

text: An extremely affordable virus concentration method based on adsorption-elution to glass wool and subsequent reconcentration through polyethylene glycol 6000 (PEG) precipitation was optimized to recover not only non-enveloped viruses but also enveloped viruses. Hepatitis A virus (HAV) and transmissible gastroenteritis virus (TGEV) were employed as surrogates for naked and enveloped viruses, respectively, to set up the methodology. Initial experimentation in small-volume samples showed that both types of particles readily adsorbed to the positively charged glass wool but were poorly detached from it through standard elution with 0.05 M glycine with 3% of beef extract buffer, pH 9.5, with elution efficiencies of 7.2% and 2.6%, for HAV and TGEV, respectively. To improve the recovery of enveloped viruses, several modifications in the elution were assayed: increasing the elution pH, extending glass wool and eluent contact time, adding a detergent, or performing the elution by recirculation or under agitation. Considering practicability and performance, recircularization of the eluent at pH 11.0 for 20 min was the elution procedure of choice, with efficiencies of 25.7% and 18.8% for HAV and TGEV in 50 L of water. Additionally, employing 20% PEG instead of 10% for virus reconcentration improved recoveries up to 47% and 51%, respectively. The optimized procedure was applied to detect naturally occurring HAV and coronaviruses in surface water of Wadi Hanifa, Riyadh. HAV was detected in 38% of the samples, while one sample was positive for an alphacoronavirus. This cheap virus detection system enables the comprehensive surveillance of viruses present in water samples.


title: Innate immune modulation by RNA viruses: emerging insights from functional genomics

text: Although often encoding fewer than a dozen genes, RNA viruses can overcome host antiviral responses and wreak havoc on the cells they infect. Some manage to evade host antiviral defences, whereas others elicit an aberrant or disproportional immune response. Both scenarios can result in the disruption of intracellular signalling pathways and significant pathology in the host. Systems-biology approaches are increasingly being used to study the processes of viral triggering and regulation of host immune responses. By providing a global and integrated view of cellular events, these approaches are beginning to unravel some of the complexities of virus–host interactions and provide new insights into how RNA viruses cause disease.


title: Contactless Vital Signs Measurement System Using RGB-Thermal Image Sensors and Its Clinical Screening Test on Patients with Seasonal Influenza

text: Background: In the last two decades, infrared thermography (IRT) has been applied in quarantine stations for the screening of patients with suspected infectious disease. However, the fever-based screening procedure employing IRT suffers from low sensitivity, because monitoring body temperature alone is insufficient for detecting infected patients. To overcome the drawbacks of fever-based screening, this study aims to develop and evaluate a multiple vital sign (i.e., body temperature, heart rate and respiration rate) measurement system using RGB-thermal image sensors. Methods: The RGB camera measures blood volume pulse (BVP) through variations in the light absorption from human facial areas. IRT is used to estimate the respiration rate by measuring the change in temperature near the nostrils or mouth accompanying respiration. To enable a stable and reliable system, the following image and signal processing methods were proposed and implemented: (1) an RGB-thermal image fusion approach to achieve highly reliable facial region-of-interest tracking, (2) a heart rate estimation method including a tapered window for reducing noise caused by the face tracker, reconstruction of a BVP signal with three RGB channels to optimize a linear function, thereby improving the signal-to-noise ratio and multiple signal classification (MUSIC) algorithm for estimating the pseudo-spectrum from limited time-domain BVP signals within 15 s and (3) a respiration rate estimation method implementing nasal or oral breathing signal selection based on signal quality index for stable measurement and MUSIC algorithm for rapid measurement. We tested the system on 22 healthy subjects and 28 patients with seasonal influenza, using the support vector machine (SVM) classification method. Results: The body temperature, heart rate and respiration rate measured in a non-contact manner were highly similarity to those measured via contact-type reference devices (i.e., thermometer, ECG and respiration belt), with Pearson correlation coefficients of 0.71, 0.87 and 0.87, respectively. Moreover, the optimized SVM model with three vital signs yielded sensitivity and specificity values of 85.7% and 90.1%, respectively. Conclusion: For contactless vital sign measurement, the system achieved a performance similar to that of the reference devices. The multiple vital sign-based screening achieved higher sensitivity than fever-based screening. Thus, this system represents a promising alternative for further quarantine procedures to prevent the spread of infectious diseases.


title: Health Care Associated Middle East Respiratory Syndrome (MERS): A Case from Iran

text: Middle East respiratory syndrome coronavirus (MERS-CoV) Infection, has caused recurrent outbreaks worldwide. It is associated with severe morbidity and mortality, and is not treatable with the currently available antiviral therapies. We present a case of a 43 year-old male healthcare provider, who admitted with productive cough, dyspnea, myalgia, pleuritic chest pain and fever. Computed tomography (CT) showed bilateral ground glass opacities and consolidation. Sputum polymerase chain reaction (PCR) for MERS-coronavirus was positive.


title: Design and biological activities of novel inhibitory peptides for SARS-CoV spike protein and angiotensin-converting enzyme 2 interaction

text: Abstract Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel coronavirus (SARS-CoV). The binding of SARS-CoV spike (S) protein to cellular angiotensin-converting enzyme 2 (ACE2) is the first step in SARS-CoV infection. Therefore, we assayed the inhibitory effects of small peptides derived from S protein on the binding of S protein to ACE2 and on the S-protein-pseudotyped retrovirus infectivity. SP-4 (residues 192–203), SP-8 (residues 483–494), and SP-10 (residues 668–679) significantly blocked the interaction between S protein and ACE2 by biotinylated enzyme-linked immunosorbent assay, with IC50 values of 4.30±2.18, 6.99±0.71, and 1.88±0.52nmol, respectively. Peptide scanning suggested the region spanning residues 660–683 might act as a receptor-binding domain. SP-10 blocked both binding of the S protein and infectivity of S protein-pseudotyped retrovirus to Vero E6 cells. In conclusion, this is the first report of small peptides designed to disrupt the binding of SARS-CoV S protein to ACE2. Our findings suggest that SP-10 may be developed as an anti-SARS-CoV agent for the treatment of SARS-CoV infection.


title: Prognosis of COVID-19 in Patients with Liver and Kidney Diseases: An Early Systematic Review and Meta-Analysis

text: The mortality and severity in COVID-19 is increased in patients with comorbidities. The aim of this study was to evaluate the severity and mortality in COVID-19 patients with underlying kidney and liver diseases. We retrieved data on the clinical features and primary composite end point of COVID-19 patients from Medline and Embase which had been released from inception by the April 16, 2020. The data on two comorbidities, liver diseases and chronic kidney disease, were pooled and statistically analysed to explain the associated severity and mortality rate. One hundred and forty-two abstracts were screened, and 41 full articles were then read. In total, 22 studies including 5595 COVID-19 patients were included in this study with case fatality rate of 16%. The prevalence of liver diseases and chronic kidney disease (CKD) were 3% (95% CI; 2–3%) and 1% (95% CI; 1–2%), respectively. In patients with COVID-19 and underlying liver diseases, 57.33% (43/75) of cases were severe, with 17.65% mortality, while in CKD patients, 83.93% (47/56) of cases were severe and 53.33% (8/15) mortality was reported. This study found an increased risk of severity and mortality in COVID-19 patients with liver diseases or CKD. This will lead to better clinical management and inform the process of implementing more stringent preventative measures for this group of patients.


title: Renyi entropy and mutual information measurement of market expectations and investor fear during the COVID-19 pandemic

text: The COVID-19 pandemic has seriously affected world economies. In this regard, it is expected that information level and sharing between equity, digital currency, and energy markets has been altered due to the pandemic outbreak. Specifically, the resulting twisted risk among markets is presumed to rise during the abnormal state of world economy. The purpose of the current study is twofold. First, by using Renyi entropy, we analyze the multiscale entropy function in the return time series of Bitcoin, S&P500, WTI, Brent, Gas, Gold, Silver, and investor fear index represented by VIX. Second, by estimating mutual information, we analyze the information sharing between these markets. The analyses are conducted before and during the COVID-19 pandemic. The empirical results from Renyi entropy indicate that for all market indices, randomness and disorder are more concentrated in less probable events. The empirical results from mutual information showed that the information sharing network between markets has changed during the COVID-19 pandemic. From a managerial perspective, we conclude that during the pandemic (i) portfolios composed of Bitcoin and Silver, Bitcoin and WTI, Bitcoin and Gold, Bitcoin and Brent, or Bitcoin and S&P500 could be risky, (ii) diversification opportunities exist by investing in portfolios composed of Gas and Silver, Gold and Silver, Gold and Gas, Brent and Silver, Brent and Gold, or Bitcoin and Gas, and that (iii) the VIX exhibited the lowest level of information disorder at all scales before and during the pandemic. Thus, it seems that the pandemic has not influenced the expectations of investors. Our results provide an insight of the response of stocks, cryptocurrencies, energy, precious metal markets, to expectations of investors in the aftermath of the COVID-19 pandemic in terms of information ordering and sharing.


title: Antimicrobial susceptibility of Histophilus somni isolated from clinically affected cattle in Australia

text: Abstract This study investigated antimicrobial resistance traits, clonal relationships and epidemiology of Histophilus somni isolated from clinically affected cattle in Queensland and New South Wales, Australia. Isolates (n = 53) were subjected to antimicrobial susceptibility testing against six antimicrobial agents (ceftiofur, enrofloxacin, florfenicol, tetracycline, tilmicosin and tulathromycin) using disc diffusion and minimum inhibitory concentration (MIC) assays. Clonal relationships were assessed using repetitive sequence PCR and descriptive epidemiological analysis was performed. The H. somni isolates appeared to be geographically clonal, with 27/53 (47%) isolates grouping in one cluster from one Australian state. On the basis of disc diffusion, 34/53 (64%) isolates were susceptible to all antimicrobial agents tested; there was intermediate susceptibility to tulathromycin in 12 isolates, tilmicosin in seven isolates and resistance to tilmicosin in one isolate. Using MIC, all but one isolate was susceptible to all antimicrobial agents tested; the non-susceptible isolate was resistant to tetracycline, but this MIC result could not be compared to disc diffusion, since there are no interpretative guidelines for disc diffusion for H. somni against tetracycline. In this study, there was little evidence of antimicrobial resistance in H. somni isolates from Australian cattle. Disc diffusion susceptibility testing results were comparable to MIC results for most antimicrobial agents tested; however, results for isolates with intermediate susceptibility or resistance to tilmicosin and tulathromycin on disc diffusion should be interpreted with caution in the absence of MIC results.


title: Chapter 19 Orthomyxoviruses of Fish

text: Abstract The family Orthomyxoviridae is well known for containing influenza viruses with a segmented RNA genome that is prone to gene reassortment in mixed infections (known as antigenic shift) resulting in new virus subtypes that cause pandemics, and cumulative mutations (known as antigenic drift), resulting in new virus strains that cause epidemics. This family also contains infectious salmon anemia virus (ISAV) and tilapia lake virus (TiLV), which are a unique orthomyxoviruses that infect fish and is unable to replicate above room temperature (24°C). This chapter describes the comparative virology of members in the family Orthomyxoviridae in general, helping to understand the emergent teleost orthomyxoviruses, ISAV and TiLV. The most current information on virus–host interactions of the fish orthomyxoviruses, particularly ISAV, as they relate to variations in virus structure, virulence, persistence, host range and immunological aspects is presented in detail.


title: Antibiotics in acute bronchitis: a meta-analysis

text: Abstract PURPOSE: Most patients with acute bronchitis who seek medical care are treated with antibiotics, although the effectiveness of this intervention is uncertain. We performed a meta-analysis of randomized, controlled trials to estimate the effectiveness of antibiotics in the treatment of acute bronchitis. SUBJECTS AND METHODS: English-language studies published January 1966 to April 1998 were retrieved using MEDLINE, bibliographies, and consultation with experts. Only randomized trials that enrolled otherwise healthy patients with a diagnosis of acute bronchitis, used an antibiotic in the treatment group and a placebo in the control group, and provided sufficient data to calculate an effect size were included. RESULTS: We identified eight randomized controlled trials that satisfied all inclusion criteria. These studies used one of three antibiotics (erythromycin, doxycycline, trimethoprim/sulfamethoxazole). The use of antibiotics decreased the duration of cough and sputum production by approximately one-half day (summary effect size 0.21; 95% CI, 0.05 to 0.36). For specific symptoms, there were nonsignificant trends favoring the use of antibiotics: a decrease of 0.4 days of purulent sputum (95% CI, −0.1 to 0.8), a decrease of 0.5 days of cough (95% CI, −0.1 to 1.1), and a decrease of 0.3 days lost from work (95% CI, −0.6 to 1.1). CONCLUSION: This meta-analysis suggests a small benefit from the use of the antibiotics erythromycin, doxycycline, or trimethoprim/sulfamethoxazole in the treatment of acute bronchitis in otherwise healthy patients. As this small benefit must be weighed against the risk of side effects and the societal cost of increasing antibiotic resistance, we believe that the use of antibiotics is not justified in these patients.


title: Assessment of synthetic peptides of severe acute respiratory syndrome coronavirus recognized by long‐lasting immunity

text: Abstract: In order to determine highly immunogenic severe acute respiratory syndrome coronavirus (SARS‐CoV) epitope peptides capable of inducing long‐lasting immunity, we first screened immunoglobulin‐G (IgG) antibodies reactive to 197 different overlapping 15‐mers from the SARS‐CoV proteins in the sera of three infected patients. Forty‐two peptides among them were reactive to the sera from all three patients. Consequently, we tested for the reactivity of these 42 peptides to patients' sera (n = 45) at 6‐month post‐infection. The significantly higher levels of IgG antibodies specific to three (S791, M207 and N161) of 42 peptides were detectable in the post‐infection sera from 23 (51%), 27 (60%) and 19 (42%) of 45 patients, respectively. These three peptides, recognized by their long‐lasting immunity, may provide a better understanding of the immunogenicity of SARS‐CoV.


title: Sea Turtles: Old Viruses and New Tricks

text: Abstract Recent years have seen an inexplicable increase in the frequency of an appalling disease in sea turtles: fibropapillomatosis, which is likely caused by a herpesvirus and causes tumors to grow throughout the turtle's body. New research has led to the disturbing conclusion that recent, human-induced environmental changes are responsible.


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title: New Respiratory Viruses and the Elderly

text: The diagnostics of respiratory viral infections has improved markedly during the last 15 years with the development of PCR techniques. Since 1997, several new respiratory viruses and their subgroups have been discovered: influenza A viruses H5N1 and H1N1, human metapneumovirus, coronaviruses SARS, NL63 and HKU1, human bocavirus, human rhinoviruses C and D and potential respiratory pathogens, the KI and WU polyomaviruses and the torque teno virus. The detection of previously known viruses has also improved. Currently, a viral cause of respiratory illness is almost exclusively identifiable in children, but in the elderly, the detection rates of a viral etiology are below 40%, and this holds also true for exacerbations of chronic respiratory illnesses. The new viruses cause respiratory symptoms like the common cold, cough, bronchitis, bronchiolitis, exacerbations of asthma and chronic obstructive pulmonary disease and pneumonia. Acute respiratory failure may occur. These viruses are distributed throughout the globe and affect people of all ages. Data regarding these viruses and the elderly are scarce. This review introduces these new viruses and reviews their clinical significance, especially with regard to the elderly population.


title: European Society for Neurogastroenterology and Motility (ESNM) recommendations for conducting gastrointestinal motility and function testing in the recovery phase of the COVID‐19 pandemic

text: BACKGROUND: During the peak of the COronaVIrus Disease 2019 (COVID‐19) pandemic, care for patients with gastrointestinal motility and functional disorders was largely suspended. In the recovery phases of the pandemic, non‐urgent medical care is resumed, but there is a lack of guidance for restarting and safely conducting motility and function testing. Breath tests and insertion of manometry and pH monitoring probes carry a risk for SARS‐CoV‐2 spread through droplet formation. METHODS: A panel of experts from the European Society for Neurogastroenterology and Motility (ESNM) evaluated emerging national and single center recommendations to provide the best current evidence and a pragmatic approach to ensure the safe conduct of motility and function testing for both healthcare professionals and patients. RESULTS: At a general level, this involves evaluation of the urgency of the procedure, evaluation of the infectious risk associated with the patient, the investigation and the health care professional(s) involved, provision of the test planning and test units, education and training of staff and use of personnel protection equipment. Additional guidance is provided for specific procedures such as esophageal manometry, pH monitoring and breath tests. CONCLUSIONS AND INFERENCES: The ESNM guidelines provide pragmatic and appropriate guidance for the safe conduct of motility and function testing in the COVID‐19 pandemic and early recovery phase.


title: Assessing air quality changes in large cities during COVID-19 lockdowns: The impacts of traffic-free urban conditions in Almaty, Kazakhstan

text: Abstract Number of cities worlwide experienced air quality improvements during COVID-19 lockdowns; however, such changes may have been different in places with major contributions from nontraffic related sources. In Almaty, a city-scale quarantine came into force on March 19, 2020, which was a week after the first COVID-19 case was registered in Kazakhstan. This study aims to analyze the effect of the lockdown from March 19 to April 14, 2020 (27 days), on the concentrations of air pollutants in Almaty. Daily concentrations of PM2.5, NO2, SO2, CO, O3, and BTEX were compared between the periods before and during the lockdown. During the lockdown, the PM2.5 concentration was reduced by 21% with spatial variations of 6–34% compared to the average on the same days in 2018–2019, and still, it exceeded WHO daily limit values for 18 days. There were also substantial reductions in CO and NO2 concentrations by 49% and 35%, respectively, but an increase in O3 levels by 15% compared to the prior 17 days before the lockdown. The concentrations of benzene and toluene were 2–3 times higher than those during in the same seasons of 2015–2019. The temporal reductions may not be directly attributed to the lockdown due to favorable meteorological variations during the period, but the spatial effects of the quarantine on the pollution levels are evidenced. The results demonstrate the impact of traffic on the complex nature of air pollution in Almaty, which is substantially contributed by various nontraffic related sources, mainly coal-fired combined heat and power plants and household heating systems, as well as possible small irregular sources such as garbage burning and bathhouses.