title: Clinical observations in the very elderly patients with COVID‐19 in Wuhan

text: BACKGROUND: In December 2019, the outbreak of coronavirus disease 2019 (COVID‐19) was initiated in Wuhan, now causing a worldwide pandemic. However, the experience in the very elderly patients is very limited, which has important implications for the surveillances of hospital infection in medical and health institutions. METHODS: Seven patients with confirmed COVID‐19 infection in the Department of Geriatrics at Zhongnan Hospital of Wuhan University were included. Clinical data were retrospectively collected and analyzed. The laboratory test and chest CT images from the patients before and after the COVID‐19 infection were compared. RESULTS: The median age of patients was 91 years old (from 87 to 96). Six patients had pneumonia in the last six months. Dyspnea occurred in one patient 64 hours after the onset of the disease. The rest six patients only manifested minor fatigue with low fever. Lymphopenia and a significant reduction in plasma globulin level has been observed compared to the levels before the onset of the disease. None had typical chest CT phenotypes at the early stage, except the mentioned critically ill patient who had a “white lung” development and died. One even showed an absorption of inflammation compared with previous hypostatic pneumonia. CONCLUSIONS: The ratio of fatal cases in the very elderly COVID‐19 infected patients is not higher to that reported in the non‐elderly patients, probably due to low immune response. The elderly patients, however, manifested minor clinical symptoms and atypical changes in chest CT images, which usually lead to misdiagnosis or delayed diagnosis.


title: Acute viral bronchiolitis in children- a very common condition with few therapeutic options

text: Summary Acute viral bronchiolitis remains a cause of substantial morbidity and health care costs in young infants. It is the most common lower respiratory tract condition and most common reason for admission to hospital in infants. Many respiratory viruses have been associated with acute viral bronchiolitis although respiratory syncytial virus (RSV) remains the most frequently identified virus. Most infants have a mild self limiting illness while others have more severe illness and require hospital admission and some will need ventilatory support. Differences in innate immune function in response to the respiratory viral insult as well as differences in the geometry of the airways may explain some of the variability in clinical pattern. Young age and history of prematurity remain the most important risk factors although male gender, indigenous status, exposure to tobacco smoke, poor socioeconomic factors and associated co-morbidities such as chronic lung disease and congenital heart disease increase the risks of more severe illness. Supportive therapy remains the major treatment option as no specific treatments to date have been shown to provide clinically important benefits except for inhaled hypertonic saline. Prophylaxis of high risk infants with palivizumab should be considered although the cost effectiveness is still unclear. Many questions remain regarding optimal management approaches for infants requiring hospitalisation with bronchiolitis including use of nasogastric feeding, the optimal role of supplemental oxygen, optimal use of hypertonic saline and the role of combinations of therapies, the use of heliox or modern physiotherapy approaches.


title: Respiratory health issues in the Asia–Pacific region: An overview

text: The Asia–Pacific region is home to a large heterogeneous population whose respiratory health is influenced by diverse social, economic and environmental factors. Despite this variability, the most prevalent causes of respiratory morbidity and mortality are tobacco smoking, infection, and air pollution. This review aims to summarize current respiratory health issues in the region including smoking‐related diseases especially COPD, lung cancer and infectious problems such as pandemic influenza, the severe acute respiratory syndrome coronavirus, bacterial pneumonia and tuberculosis, as well as the contribution of air pollution to respiratory disease. Published data on trends in the epidemiology and management of respiratory diseases and are summarized; finally, the limitations of available data and projections for the future of respiratory health in the region are discussed.


title: Air quality changes in New York City during the COVID-19 pandemic

text: Abstract In December 2019, a new, severe coronavirus (COVID-19) appeared in Wuhan, China. Shortly after, the first COVID-19 case was confirmed in the United States. The emergence of this virus led many United States governors to enact executive orders in an effort to limit the person-to-person spread of the virus. One state that utilized such measures was New York, which contains New York City (NYC), the most populous city in the United States. Many reports have shown that due to the government-backed shutdowns, the air quality in major global cities improved. However, there has been only limited work on whether this same trend is seen throughout the United States, specifically within the densely populated NYC area. Thus, the focus of this study was to examine whether changes in air quality were observed in NYC resulting from New York State's COVID-19-associated shutdown measures. To do this, daily concentrations of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were obtained from 15 central monitoring stations throughout the five NYC boroughs for the first 17 weeks (January through May) of 2015–2020. Decreases in PM2.5 (36%) and NO2 (51%) concentrations were observed shortly after the shutdown took place; however, using a linear time lag model, when changes in these pollutant concentrations were compared to those measured during the same span of time in 2015–2019, no significant difference between the years were found. Therefore, we highlight the importance of considering temporal variability and long-term trends of pollutant concentrations when analyzing for short-term differences in air pollutant concentrations related to the COVID-19 shutdowns.


title: Zika virus: Epidemiology, current phobia and preparedness for upcoming mass gatherings, with examples from World Olympics and Pilgrimage

text: OBJECTIVE: To describe Zika Virus (ZIKV) epidemiology, current phobia, and the required preparedness for its prevention during the upcoming Mass Gathering (MG) events. METHODS: Electronic databases of PubMed, WHO, CDC, Pan American Health Organization (PAHO), Google, and Cochrane library were extensively searched for ZIKV. Articles were reviewed, scrutinized and critically appraised and the most relevant articles were utilized. RESULTS: ZIKV is an emerging Flavivirus which was first isolated from Uganda in 1947. It is transmitted mainly through bite of Aedes mosquitoes. Sexual, perinatal and blood-borne transmissions are implicated. ZIKV is incriminated to cause microcephaly and Guillain-Barré syndrome. The spiky spread of ZIKV and its epidemic potential are especially problematic in countries which host big MGs with endogenous ZIKV circulation. This put millions of international travelers and local inhabitants at risk of acquiring ZIKV, especially in absence of vaccine until now. Brazil Olympic and Paralympics Games, and Muslims Hajj in Saudi Arabia are important upcoming MGs. Regarding Brazil, swiftly epidemic of ZIKV causes phobia and provokes claims and counter-claims about possible postponing or cancellation of such events. RECOMMENDATIONS: Intensifying ZIKV epidemiological surveillance (sentinel, syndromic, environmental, laboratory and electronic), and conduction of educational programs are required. Controlling Aedes vector (chemically & biologically) is essential. Multidisciplinary cooperation is required to win the war against ZIKV.


title: Developing and financing neglected disease vaccines in our new era of “blue marble health” and the anthropocene epoch

text: New findings of widespread neglected diseases among the poor living in wealthy group of 20 (G20) economies and the concept of “blue marble health” offer innovative mechanisms for financing urgently new vaccines, especially for vector-borne neglected tropical diseases (NTDs). This approach could complement or parallel a recently suggested global vaccine development fund for pandemic threats.


title: Nanoengineering of vaccines using natural polysaccharides

text: Abstract Currently, there are over 70 licensed vaccines, which prevent the pathogenesis of around 30 viruses and bacteria. Nevertheless, there are still important challenges in this area, which include the development of more active, non-invasive, and thermo-resistant vaccines. Important biotechnological advances have led to safer subunit antigens, such as proteins, peptides, and nucleic acids. However, their limited immunogenicity has demanded potent adjuvants that can strengthen the immune response. Particulate nanocarriers hold a high potential as adjuvants in vaccination. Due to their pathogen-like size and structure, they can enhance immune responses by mimicking the natural infection process. Additionally, they can be tailored for non-invasive mucosal administration (needle-free vaccination), and control the delivery of the associated antigens to a specific location and for prolonged times, opening room for single-dose vaccination. Moreover, they allow co-association of immunostimulatory molecules to improve the overall adjuvant capacity. The natural and ubiquitous character of polysaccharides, together with their intrinsic immunomodulating properties, their biocompatibility, and biodegradability, justify their interest in the engineering of nanovaccines. In this review, we aim to provide a state-of-the-art overview regarding the application of nanotechnology in vaccine delivery, with a focus on the most recent advances in the development and application of polysaccharide-based antigen nanocarriers.


title: Clinical Characteristics of Re‐hospitalized Patients with COVID‐19 in China

text: BACKGROUND: This study aims to observe the clinical characteristics of recovered patients from Coronavirus Disease 2019 (COVID 19) with positive in RT‐PCR or serum antibody. METHODS: The profile, clinical symptoms, laboratory outcomes and radiologic assessments were extracted on 11 patients, who tested positive for COVID‐19 with RT‐PCR or serum antibody after discharged and was admitted to Hubei No. 3 People's Hospital of Jianghan University for a second treatment in March 2020. RESULTS: The average interval time between the first discharge and the second admission measured 16.00 ± 7.14 days, ranging from 6 to 27 days. In the second hospitalization, 1 patient was positive for RT‐PCR and serum antibody IgM‐IgG, 5 patients were positive for both IgM and IgG but negative for RT‐PCR. 3 patients were positive for both RT‐PCR and IgG but negative for IgM. The main symptoms were cough (54.5%), fever (27.3%) and feeble (27.3%) in the second hospitalization. Compared with the first hospitalization, there were significant decreases in gastrointestinal symptoms (5 vs. 0, P=0.035), elevated levels of both white blood cell count(P=0.036) and lymphocyte count (P=0.002), remarkedly decreases in CRP and SAA (P<0.05) in the second hospitalization. Additionally, 6 patients' chest CT exhibited notable improvements in acute exudative lesions CONCLUSION: There could be the positive results for RT‐PCR analysis or serum IgM‐IgG in discharged patients, even with mild clinical symptoms, however, their laboratory outcomes and chest CT images would not indicate the on‐going development in those patients. This article is protected by copyright. All rights reserved.


title: COVID-19 Vaccine: Vaccinate the Young to Protect the Old?

text: When we have a vaccine against COVID-19, who should be vaccinated first? The question is relevant because, initially, vaccine availability will likely be limited. After healthcare and some other essential workers, it might seem the most obvious candidates are the elderly and other groups that are more vulnerable to the virus. However, we argue that this is not necessarily the case. Protecting the most vulnerable might require prioritizing vaccinating children in order to maximize the benefits of indirect immunity for the elderly and the other vulnerable groups. Whether this will be the best strategy from a public health perspective will depend on characteristics of the vaccine and of the virus, which are currently unknown. Here, we assess this possibility from an ethical point of view, by drawing comparisons and analogies with the case of the flu vaccination and with other examples of health policies and practices. We conclude that there are strong ethical reasons to vaccinate the young to protect the old, provided that the risks imposed on children are reasonable, even if that implies using children as a means to protect the elderly and the vulnerable.


title: Methicillin-resistant Staphylococcus aureus, Clostridium difficile, and extended-spectrum β-lactamase–producing Escherichia coli in the community: Assessing the problem and controlling the spread

text: Although health care-associated methicillin resistant staphylococcus aureus and clostridium difficile strains are primarily a risk to hospital patients, people are increasingly concerned about their potential to circulate in the community and the home. They are thus looking for support in order to understand the extent of the risk, and guidance on how to deal with situations where preventing infection from these species becomes their responsibility. A further concern are the community-acquired MRSA and C. difficile strains, and other antibiotic resistant strains circulating in the community such as the Extended-spectrum β-lactamase (ESBL) Escherichia coli. In response to concerns about such organisms in the community, the International Scientific Forum on Home Hygiene has produced a report evaluating MRSA, C. difficile, and ESBL-producing E. coli from a community viewpoint. The report summarizes what is known about their prevalence in the community, their mode of transmission in the home, and the extent to which they represent a risk. It also includes “advice sheets” giving practical guidance on what to do when there is a risk of infection transmission in the home.


title: Seasonal Incidence of Medically Attended Respiratory Syncytial Virus Infection in a Community Cohort of Adults ≥50 Years Old

text: BACKGROUND: Diagnostic testing for respiratory syncytial virus (RSV) is not routinely performed in adults. We estimated medically attended RSV seasonal incidence in a community cohort of adults ≥50 years old during four influenza seasons (2006–07 through 2009–10). METHODS: Patients seeking care for acute respiratory illness (ARI) were prospectively enrolled and tested for RSV by multiplex RT-PCR. Results from enrolled patients were used to estimate projected cases among non-enrolled patients with ARI. The seasonal incidence of medically attended RSV was the sum of actual and projected cases divided by the community cohort denominator. Since each enrollment period did not include the entire RSV season, incidence estimates were adjusted to account for the statewide proportion of RSV occurring outside the study enrollment period. RESULTS: There were 16,088 to 17,694 adults in the cohort each season and 164 RSV cases in all 4 seasons. The overall seasonal incidence of medically attended RSV was 154 episodes (95% CI, 132–180) per 10,000 persons; the incidence was highest in 2007–08 (179) and lowest in 2006–07 (110). Among persons 50–59, 60–69, and ≥70 years old, RSV incidence was 124 (95% CI, 99–156), 147 (95% CI, 110–196), and 199 (95% CI, 153–258), respectively. CONCLUSIONS: The incidence of medically attended RSV increased with age and was similar during four seasons.


title: Efficacy of glucocorticoids for the treatment of macrolide refractory mycoplasma pneumonia in children: meta-analysis of randomized controlled trials

text: BACKGROUND: Mycoplasma pneumoniae is one of the most common pathogens causing community acquired pneumonia in children. Although the rate of macrolide-refractory Mycoplasma pneumoniae (MRMP) has increased, systemic glucocorticoids as a treatment option has not been validated yet. The purpose of this study was to assess the efficacy of glucocorticoids add-on in the treatment of MRMP in children through systematic review and meta-analysis. METHODS: Data sources A systematic literature search was conducted using ten electronic bibliographic databases including English, Korean, Chinese and Japanese languages, up to March 8, 2018. Study selection The study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist and selected randomized control trials which compared the efficacy of glucocorticoids add-on to macrolide in the treatment of MRMP in children. Data extraction Two independent reviewers extracted: primary outcomes as hospital days, fever duration, and change in C-reactive protein (CRP) and main analysis was performed through meta-analysis with random effects model. RESULTS: Twenty-four unique randomized controlled trials met the inclusion criteria. The mean length of hospital stay in glucocorticoids treatment group was significantly shorter than that in conventional macrolide-treatment group (Weighted mean difference (WMD) = − 4.03 days). The mean length of fever duration was significantly shorter in the glucocorticoid treatment group in comparison with the conventional treatment group (WMD = -3.32 days). Level of CRP after treatment was significantly lower in the glucocorticoid treatment group than that in the conventional treatment group (WMD = -16.03). Sensitivity analysis and subgroup analysis showed no significant improvement in heterogeneity. As limitations of the study, most of the studies included were from a single country and we were unable to control for heterogeneity across interventions, lack of standardized measures, and different time points of assessments across studies. CONCLUSIONS: Glucocorticoid add-on treatment for MRMP can significantly shorten the duration of fever and hospital stay and decrease the level of CRP. These results should be confirmed by adequately powered studies in the future.


“Keep It Going if You Can”: HIV Service Provision for Priority Populations During the COVID-19 Pandemic in Seattle, WA


title: Bovine Neonatal Pancytopenia: Is this alloimmune syndrome caused by vaccine-induced alloreactive antibodies?

text: Bovine Neonatal Pancytopenia (BNP) is a new emerging disease observed since 2007 in Germany and neighbouring countries. The syndrome affects newborn calves and is characterized by pancytopenia, severe bleeding and high lethality. So far, a causative role of infectious or toxic agents has been ruled out. Instead, the syndrome is induced after ingestion of colostrum, the first milk that supplies the calf with maternal antibodies. In analogy to similar diseases in humans it has therefore been postulated that BNP is caused by alloreactive, maternal antibodies. There is a striking association between BNP and a previous vaccination of the respective dams with a particular vaccine against Bovine Virus Diarrhoea (BVD). This association has led to a suspension of the marketing authorisation for the vaccine, by the European Commission. The current study investigates the role of this vaccine in the pathogenesis of BNP. By flow cytometry we were able to demonstrate that sera of BNP dams (dams that gave birth to a BNP calf) harbour alloreactive antibodies binding to surface antigens on bovine leukocytes. A significantly weaker alloreactivity was observed with sera of non-BNP dams that have been vaccinated with the same vaccine but delivered healthy calves. No binding was seen with non-BVD-vaccinated control cows and animals that were vaccinated with other inactivated BVD vaccines so far not associated with BNP. The binding is functionally relevant, because opsonization of bovine leukocytes with alloantibodies led to an elevated cytophagocytosis by bovine macrophages. To test whether the vaccine induces alloreactive antibodies two strategies were employed: Guinea pigs were vaccinated with a panel of commercially available BVD-vaccines. Only the incriminated vaccine induced antibodies binding surface antigens on bovine leukocytes. Additionally, two calves were repeatedly vaccinated with the suspected vaccine and the development of alloreactivity was monitored. In dependence of the number of booster immunizations the induction of alloreactive antibodies could be observed. Finally, by affinity purification we were able to directly demonstrate that BNP associated alloantibodies cross react with the bovine kidney cell line used for vaccine production. Together this provides strong evidence that this particular BVD vaccine has the potential to induce BNP associated alloantibodies.


title: Design and methods of a social network isolation study for reducing respiratory infection transmission: The eX-FLU cluster randomized trial

text: Abstract Background Social networks are increasingly recognized as important points of intervention, yet relatively few intervention studies of respiratory infection transmission have utilized a network design. Here we describe the design, methods, and social network structure of a randomized intervention for isolating respiratory infection cases in a university setting over a 10-week period. Methodology/principal findings 590 students in six residence halls enrolled in the eX-FLU study during a chain-referral recruitment process from September 2012–January 2013. Of these, 262 joined as “seed” participants, who nominated their social contacts to join the study, of which 328 “nominees” enrolled. Participants were cluster-randomized by 117 residence halls. Participants were asked to respond to weekly surveys on health behaviors, social interactions, and influenza-like illness (ILI) symptoms. Participants were randomized to either a 3-Day dorm room isolation intervention or a control group (no isolation) upon illness onset. ILI cases reported on their isolation behavior during illness and provided throat and nasal swab specimens at onset, day-three, and day-six of illness. A subsample of individuals (N =103) participated in a sub-study using a novel smartphone application, iEpi, which collected sensor and contextually-dependent survey data on social interactions. Within the social network, participants were significantly positively assortative by intervention group, enrollment type, residence hall, iEpi participation, age, gender, race, and alcohol use (all P <0.002). Conclusions/significance We identified a feasible study design for testing the impact of isolation from social networks in a university setting. These data provide an unparalleled opportunity to address questions about isolation and infection transmission, as well as insights into social networks and behaviors among college-aged students. Several important lessons were learned over the course of this project, including feasible isolation durations, the need for extensive organizational efforts, as well as the need for specialized programmers and server space for managing survey and smartphone data.


title: Coronavirus disease 2019 (COVID-19) pandemic and pregnancy

text: The current coronavirus disease 2019 (COVID-19) pneumonia pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading globally at an accelerated rate, with a basic reproduction number (R0) of 2–2.5, indicating that 2–3 persons will be infected from an index patient. A serious public health emergency, it is particularly deadly in vulnerable populations and communities in which healthcare providers are insufficiently prepared to manage the infection. As of March 16, 2020, there are more than 180,000 confirmed cases of COVID-19 worldwide, with more than 7000 related deaths. The SARS-CoV-2 virus has been isolated from asymptomatic individuals, and affected patients continue to be infectious 2 weeks after cessation of symptoms. The substantial morbidity and socioeconomic impact have necessitated drastic measures across all continents, including nationwide lockdowns and border closures. Pregnant women and their fetuses represent a high-risk population during infectious disease outbreaks. To date, the outcomes of 55 pregnant women infected with COVID-19 and 46 neonates have been reported in the literature, with no definite evidence of vertical transmission. Physiological and mechanical changes in pregnancy increase susceptibility to infections in general, particularly when the cardiorespiratory system is affected, and encourage rapid progression to respiratory failure in the gravida. Furthermore, the pregnancy bias toward T-helper 2 (Th2) system dominance, which protects the fetus, leaves the mother vulnerable to viral infections, which are more effectively contained by the Th1 system. These unique challenges mandate an integrated approach to pregnancies affected by SARS-CoV-2. Here we present a review of COVID-19 in pregnancy, bringing together the various factors integral to the understanding of pathophysiology and susceptibility, diagnostic challenges with real-time reverse transcription polymerase chain reaction (RT-PCR) assays, therapeutic controversies, intrauterine transmission, and maternal−fetal complications. We discuss the latest options in antiviral therapy and vaccine development, including the novel use of chloroquine in the management of COVID-19. Fetal surveillance, in view of the predisposition to growth restriction and special considerations during labor and delivery, is addressed. In addition, we focus on keeping frontline obstetric care providers safe while continuing to provide essential services. Our clinical service model is built around the principles of workplace segregation, responsible social distancing, containment of cross-infection to healthcare providers, judicious use of personal protective equipment, and telemedicine. Our aim is to share a framework that can be adopted by tertiary maternity units managing pregnant women in the flux of a pandemic while maintaining the safety of the patient and healthcare provider at its core.


title: Chapter 6 Hepatitis Caused by Other Viruses

text: Abstract Liver injury is commonly observed in the setting of many systemic viral infections. The severity of this injury can range from mild, transient elevations in liver enzymes to acute liver failure. Understanding the rate of liver injury in these infections as well as the appropriate diagnostic evaluations can add clarity to the clinical management of infected patients and in many cases helps direct therapy. This chapter reviews hepatitis caused by viruses other than classical viral hepatitis with an emphasis on epidemiology, patterns of injury, and diagnostic and therapeutic strategies. Agents discussed include cytomegalovirus, Epstein-Barr virus, herpes simplex virus, and various others that can be associated with hepatic manifestations.


title: Clinical impact of pre-admission antithrombotic therapy in hospitalized patients with COVID-19: a multicenter observational study

text: Little is still known about the clinical features associated with the occurrence of acute respiratory distress syndrome (ARDS) in hospitalized patients with Coronavirus disease 2019 (COVID-19). The aim of the present study was to describe the prevalence of pre-admission antithrombotic therapies in patients with COVID-19 and to investigate the potential association between antithrombotic therapy and ARDS, as disease clinical presentation, or in-hospital mortality. We enrolled 192 consecutive patients with laboratory-confirmed COVID-19 admitted to emergency department of five Italian hospitals. The study population was divided in two groups according to the evidence of ARDS at chest computed tomography at admission. Propensity score weighting adjusted regression analysis was performed to assess the risk ARDS at admission, and death during hospitalization, in patients treated or not with antiplatelet and anticoagulant agents. ARDS was reported in 73 cases (38%), who showed more likely hypertension compared to those without ARDS (57.8 % vs 49.6 %; P = 0.005). Thirty-five patients (18.5%) died during the hospitalization. Not survived COVID-19 patients showed a statistically significant increased age (77 ± 8.31 vs 65.57 ± 8.31; P = 0.001), hypertension (77.1% vs 53.5%; P = 0.018) and coronary artery disease prevalence (28.6% vs 10.2%; P = 0.009). Both unadjusted and adjusted regression analyses showed no difference in the risk of ARDS at admission, or death during hospitalization, between patients treated or not with antiplatelets or anticoagulants. Pre-admission antithrombotic therapy, both antiplatelet and anticoagulant, does not seem to show a protective effect in severe forms of COVID-19 with ARDS at presentation and rapidly evolving toward death.


title: Feline Spinal Cord Diseases

text: The objective of this article is to review the recent literature that reports on the most common diseases affecting the spinal cord of cats, and to draw some general conclusions that will be useful to formulate diagnosis and prognosis for feline spinal patients. The most common types of feline spinal cord diseases documented were inflammatory/infectious diseases, and feline infectious peritonitis was the most common disease, representing approximately 50% of all feline myelitis. Neoplasms were documented in approximately 25% of cases; lymphosarcoma was the most common tumor affecting the spinal cord of cats, with reported prevalence between 28% and 40%. Cats diagnosed with spinal lymphosarcoma were significantly younger (median age 4 years) than cats with other spinal cord tumors (median age 10 years). Cats with clinical signs of intervertebral disc disease had a median age of 8 years, and 67% had Hansen type I disc protrusions. The most commonly affected intervertebral disc was at the L4 to L5 intervertebral disc space. Fibrocartilaginous embolism-affected older cats (median age 10 years), seemed to predominate in the cervicothoracic intumescence, and clinical signs were markedly lateralized, especially when the cervical region was affected.


title: New prodrugs of Adefovir and Cidofovir

text: Abstract New Adefovir (PMEA) prodrugs with a pro-moiety consisting of decyl or decyloxyethyl chain bearing hydroxyl function(s), hexaethyleneglycol or a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl unit were prepared starting from the tetrabutylammonium salt of the phosphonate drug and an appropriate alkyl bromide or tosylate. Analogously, two esters of Cidofovir [(S)-HPMPC] bearing a hexaethyleneglycol moiety were prepared. The activity of the prodrugs was evaluated in vitro against different virus families. A loss in the antiviral activities of the hydroxylated decyl or decyloxyethyl esters and hexaethyleneglycol esters of PMEA against human immunodeficiency virus (HIV) and herpesviruses [including herpes simplex virus (HSV), varicella-zoster virus (VZV), and human cytomegalovirus (CMV)] occurred in comparison with the parent compound. On the other hand, the (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl ester of PMEA showed significant activities against HIV and herpesviruses. (S)-HPMPC prodrugs exhibited anti-cytomegalovirus activities in the same range as the parent drug, whereas the anti-HSV and anti-VZV activities were one- to seven-fold lower than that of Cidofovir.


title: Data mining and analysis of scientific research data records on covid 19 mortality, immunity, and vaccine development - In the first wave of the Covid-19 pandemic

text: BACKGROUND AND AIMS: Covid-19 is a global pandemic that requires a global and integrated response of all national medical and healthcare systems. Covid-19 exposed the need for timely response and data sharing on fast spreading global pandemics. In this study, we investigate the scientific research response from the early stages of the pandemic, and we review key findings on how the early warning systems developed in previous epidemics responded to contain the virus. METHODS: We conducted data mining of scientific literature records from the Web of Science Core Collection, using the topics Covid-19, mortality, immunity, and vaccine. The individual records are analysed in isolation, and the analysis is compared with records on all Covid-19 research topics combined. The data records are analysed with commutable statistical methods, including R Studio, Bibliometrix package, and the Web of Science data mining tool. RESULTS: From historical analysis of scientific data records on viruses, pandemics and mortality, we identified that Chinese universities have not been leading on these topics historically. However, during the early stages of the Covid-19 pandemic, the Chinese universities are strongly dominating the research on these topics. Despite the current political and trade disputes, we found strong collaboration in Covid-19 research between the US and China. From the analysis on Covid-19 and immunity, we wanted to identify the relationship between different risk factors discussed in the news media. We identified few different clusters, containing references to exercise, inflammation, smoking, obesity and many additional factors. From the analysis on Covid-19 and vaccine, we discovered that although the USA is leading in volume of scientific research on Covid-19 vaccine, the leading 3 research institutions (Fudan, Melbourne, Oxford) are not based in the USA. Hence, it is difficult to predict which country would be first to produce a Covid-19 vaccine. CONCLUSIONS: We analysed the conceptual structure maps with factorial analysis and multiple correspondence analysis (MCA), and identified multiple relationships between keywords, synonyms and concepts, related to Covid-19 mortality, immunity, and vaccine development. We present integrated and corelated knowledge from 276 records on Covid-19 and mortality, 71 records on Covid-19 and immunity, and 189 records on Covid-19 vaccine.


title: Detection of SARS Coronavirus in Patients with Severe Acute Respiratory Syndrome by Conventional and Real-Time Quantitative Reverse Transcription-PCR Assays

text: Background: A novel coronavirus (CoV) was recently identified as the agent for severe acute respiratory syndrome (SARS). We compared the abilities of conventional and real-time reverse transcription-PCR (RT-PCR) assays to detect SARS CoV in clinical specimens. Methods: RNA samples isolated from nasopharyngeal aspirate (NPA; n = 170) and stool (n = 44) were reverse-transcribed and tested by our in-house conventional RT-PCR assay. We selected 98 NPA and 37 stool samples collected at different times after the onset of disease and tested them in a real-time quantitative RT-PCR specific for the open reading frame (ORF) 1b region of SARS CoV. Detection rates for the conventional and real-time quantitative RT-PCR assays were compared. To investigate the nature of viral RNA molecules in these clinical samples, we determined copy numbers of ORF 1b and nucleocapsid (N) gene sequences of SARS CoV. Results: The quantitative real-time RT-PCR assay was more sensitive than the conventional RT-PCR assay for detecting SARS CoV in samples collected early in the course of the disease. Real-time assays targeted at the ORF 1b region and the N gene revealed that copy numbers of ORF 1b and N gene sequences in clinical samples were similar. Conclusions: NPA and stool samples can be used for early diagnosis of SARS. The real-time quantitative RT-PCR assay for SARS CoV is potentially useful for early detection of SARS CoV. Our results suggest that genomic RNA is the predominant viral RNA species in clinical samples.


title: A convenient cell fusion assay for the study of SARS‐CoV entry and inhibition

text: SARS‐CoV spike (S) protein‐mediated cell fusion is important for the viral entry mechanism and identification of SARS‐CoV entry inhibitors. In order to avoid the high risks involved in handling SARS‐CoV and to facilitate the study of viral fusion mechanism, we established the cell lines: SR‐COS7 cells that stably express both SARS‐CoV S protein and red fluorescence protein, R‐COS7 cells that stably express red fluorescence protein, and AG‐COS7 cells that stably express both ACE2 and green fluorescence protein, respectively. When SR‐COS7 cells or R‐COS7 cells were cocultured with AG‐COS7 cells, syncytia with yellow fluorescence were conveniently observed after 12 h in SR‐COS7 cells plus AG‐COS7 cells, but not in R‐COS7 cells plus AG‐COS7 cells. The cell‐to‐cell fusion efficiency was simply determined for quantitative analysis based on the number of syncytium detected by flow cytometry. Such new cell‐to‐cell fusion model was further assessed by the potent HR2 peptide inhibitor, which led to the obvious decrease of the cell‐to‐cell fusion efficiency. The successful fusion and inhibition of cell‐based binding assay shows that it can be well used for the study of SARS‐CoV entry and inhibition. iubmb Life, 58: 480 ‐ 486, 2006


title: Extensive multiplex PCR diagnostics reveal new insights into the epidemiology of viral respiratory infections

text: Viral respiratory infections continue to pose a major global healthcare burden. At the community level, the co-circulation of respiratory viruses is common and yet studies generally focus on single aetiologies. We conducted the first comprehensive epidemiological analysis to encompass all major respiratory viruses in a single population. Using extensive multiplex PCR diagnostic data generated by the largest NHS board in Scotland, we analysed 44230 patient episodes of respiratory illness that were simultaneously tested for 11 virus groups between 2005 and 2013, spanning the 2009 influenza A pandemic. We measured viral infection prevalence, described co-infections, and identified factors independently associated with viral infection using multivariable logistic regression. Our study provides baseline measures and reveals new insights that will direct future research into the epidemiological consequences of virus co-circulation. In particular, our study shows that (i) human coronavirus infections are more common during influenza seasons and in co-infections than previously recognized, (ii) factors associated with co-infection differ from those associated with viral infection overall, (iii) virus prevalence has increased over time especially in infants aged <1 year, and (iv) viral infection risk is greater in the post-2009 pandemic era, likely reflecting a widespread change in the viral population that warrants further investigation.


title: Intravenous Anakinra for Macrophage Activation Syndrome May Hold Lessons for Treatment of Cytokine Storm in the Setting of Coronavirus Disease 2019

text: Macrophage activation syndrome (MAS) and hemophagocytic lymphohistiocytosis (HLH) are increasingly recognized as being on a continuum of cytokine storm syndromes, with different initiating pathways culminating in cytotoxic dysfunction and uncontrolled activation and proliferation of T lymphocytes and macrophages. The activated immune cells produce large amounts of proinflammatory cytokines, including interleukin 1β (IL)‐1β. Management depends on the recognized diagnosis. In the setting of a cytokine storm syndrome and infection, collaborative involvement of specialists, including infectious disease and rheumatology is ideal. Anakinra, a recombinant IL‐1 receptor antagonist, has been used subcutaneously and intravenously in pediatric patients and is considered a first‐line treatment for MAS and secondary HLH (sHLH) among many pediatric rheumatologists. Previous reports of anakinra used in adults for treatment of MAS or sHLH are limited to subcutaneous administration. In this issue, Moneagudo et al. present a series of adult patients with sHLH treated with intravenous anakinra, including patients in whom subcutaneous anakinra was insufficient. As the authors suggest, there is a potential therapeutic use for anakinra in sHLH or the cytokine storm syndrome triggered by COVID19. Trial design will be key, with the patient subpopulation, timing of intervention, and doses tested important.


title: Orthopaedic Walk-In Clinics: A model to lessen the burden on Emergency Departments during the COVID-19 pandemic()

text: OBJECTIVE: Operating duties for orthopaedic surgeons decreased during the COVID-19 pandemic, while Emergency Department (ED) cases surged. Orthopaedic Walk-In Clinics (OWICs) were implemented to manage urgent musculoskeletal cases. METHODS: OWICs, organized in three days, were staffed by one orthopaedic surgeon, one triage person, three medical assistants, and a physician assistant/nurse practitioner. RESULTS: Musculoskeletal non-emergency ED referrals decreased by 40.6% (p < 0.001) after initiation of the OWICs, allowing optimal use of resources to address the COVID-19 surge. CONCLUSION: This paper describes the OWIC model and its preliminary impact. The OWICs could serve as a template for other orthopaedic departments during the pandemic.


Commentary: A Breath of Fresh Air for Thoracic Surgeons in the Covid Era


title: Design and prototype of a mechanism for active on-line emerging/notifiable infectious diseases control, tracking and surveillance, based on a national healthcare card system

text: Abstract Timeliness is a critical issue in preventing the spread of emerging/notifiable infectious diseases, such as severe acute respiratory syndrome (SARS) or avian influenza (bird flu). Current computerized surveillance systems in many countries have demonstrated their usefulness in detecting specified communicable-diseases. However, the off-line, daily or weekly data reporting mode induces a time lag in data collection, transmission, processing, and responses. This paper proposes an on-line real-time mechanism, named EDICTS, for emerging/notifiable infectious diseases control, tracking and surveillance. It is based on the on-line health IC card system and works at the registration process of primary care practices and emergency departments. Hence, should a disease defined by CDC (Center for disease control) be detected at the registration station, EDICTS responds in real time. Note that EDICTS is a mechanism; it is CDC that determines the policy and activates it. A prototype is designed and implemented on a simulated environment of the Taiwan's national health insurance IC card system. The proposed policy and rules are defined according to the CDC regulations. Timely, sensitive and cost-effective, EDICTS complements the existing successive level of CDC reporting system as a fast-response control channel.


title: Fast degrading polyesters as siRNA nano-carriers for pulmonary gene therapy

text: Abstract A potential siRNA carrier for pulmonary gene delivery was assessed by encapsulating siRNA into biodegradable polyester nanoparticles consisting of tertiary-amine-modified polyvinyl alcohol (PVA) backbones grafted to poly(d,l-lactide-co-glycolide) (PLGA). The resulting siRNA nanoparticles were prepared using a solvent displacement method that offers the advantage of forming small nanoparticles without using shear forces. The nanoparticles were characterized with regard to particle size, zeta-potential, and degradation at pH 7.4 using dynamic and static light scattering. SiRNA release studies were performed and correlated to the nanoparticle degradation. In vitro knockdown of firefly luciferase reporter gene was used to assess the potential of the nanoparticles as siRNA carriers in a human lung epithelial cell line, H1299 luc. The amine-modified-PVA–PLGA/siRNA nanoparticles form 150–200 nm particles with zeta-potentials of +15–+20 mV in phosphate buffered saline (PBS). Break down of the nanoparticles was seen within 4 h in PBS with sustained release of siRNA. These nanoparticles have achieved 80–90% knockdown of a luciferase reporter gene with only 5 pmol anti-luc siRNA, even after nebulization. Hence we conclude that amine-modified-PVA–PLGA/siRNA nanoparticles could be a promising siRNA carrier for pulmonary gene delivery due to their fast degradation and potent gene knockdown profile.


title: Orthoretroviral-like prototype foamy virus gag-pol expression is compatible with viral replication

text: BACKGROUND: Foamy viruses (FVs) unlike orthoretroviruses express Pol as a separate precursor protein and not as a Gag-Pol fusion protein. A unique packaging strategy, involving recognition of briding viral RNA by both Pol precursor and Gag as well as potential Gag-Pol protein interactions, ensures Pol particle encapsidation. RESULTS: Several Prototype FV (PFV) Gag-Pol fusion protein constructs were generated to examine whether PFV replication is compatible with an orthoretroviral-like Pol expression. During their analysis, non-particle-associated secreted Pol precursor protein was discovered in extracellular wild type PFV particle preparations of different origin, copurifying in simple virion enrichment protocols. Different analysis methods suggest that extracellular wild type PFV particles contain predominantly mature p85(PR-RT )and p40(IN )Pol subunits. Characterization of various PFV Gag-Pol fusion constructs revealed that PFV Pol expression in an orthoretroviral manner is compatible with PFV replication as long as a proteolytic processing between Gag and Pol proteins is possible. PFV Gag-Pol translation by a HIV-1 like ribosomal frameshift signal resulted in production of replication-competent virions, although cell- and particle-associated Pol levels were reduced in comparison to wild type. In-frame fusion of PFV Gag and Pol ORFs led to increased cellular Pol levels, but particle incorporation was only marginally elevated. Unlike that reported for similar orthoretroviral constructs, a full-length in-frame PFV Gag-Pol fusion construct showed wildtype-like particle release and infectivity characteristics. In contrast, in-frame PFV Gag-Pol fusion with C-terminal Gag ORF truncations or non-removable Gag peptide addition to Pol displayed wildtype particle release, but reduced particle infectivity. PFV Gag-Pol precursor fusion proteins with inactivated protease were highly deficient in regular particle release, although coexpression of p71(Gag )resulted in a significant copackaging of these proteins. CONCLUSIONS: Non-particle associated PFV Pol appears to be naturally released from infected cells by a yet unknown mechanism. The absence of particle-associated Pol precursor suggests its rapid processing upon particle incorporation. Analysis of different PFV Gag-Pol fusion constructs demonstrates that orthoretroviral-like Pol expression is compatible with FV replication in principal as long as fusion protein processing is possible. Furthermore, unlike orthoretroviruses, PFV particle release and infectivity tolerate larger differences in relative cellular Gag/Pol levels.


title: Topology and biological function of enterovirus non-structural protein 2B as a member of the viroporin family

text: Viroporins are a group of transmembrane proteins with low molecular weight that are encoded by many animal viruses. Generally, viroporins are composed of 50–120 amino acid residues and possess a minimum of one hydrophobic region that interacts with the lipid bilayer and leads to dispersion. Viroporins are involved in destroying the morphology of host cells and disturbing their biological functions to complete the life cycle of the virus. The 2B proteins encoded by enteroviruses, which belong to the family Picornaviridae, can form transmembrane pores by oligomerization, increase the permeability of plasma membranes, disturb the homeostasis of calcium in cells, induce apoptosis, and cause autophagy; these abilities are shared among viroporins. The present paper introduces the structure and biological characteristics of various 2B proteins encoded by enteroviruses of the family Picornaviridae and may provide a novel idea for developing antiviral drugs.


Multiscale Computational Models for Respiratory Aerosol Dynamics with Medical Applications


title: Pharmacokinetic properties and bioequivalence of two formulations of arbidol: An open-label, single-dose, randomized-sequence, two-period crossover study in healthy chinese male volunteers

text: Abstract Background: Arbidol is an antiviral drug indicated for the prevention and treatment of all types of influenza infection and some other kinds of acute respiratory infections, specifically against influenza groups A and B, and severe acute respiratory syndrome. It is used to help prevent influenza infection as long as necessary with little risk for influenza mutation rendering it less effective. Objective: The aim of this study was to compare the pharmacokinetic properties and tolerability, and to determine bioequivalence, of a newly developed generic dispersible tablet formulation (test) and a branded capsule formulation (reference) of arbidol 200 mg in healthy Chinese fasted male volunteers. Methods: This open-label, single-dose, randomized-sequence, 2-period crossover study was conducted in healthy native Chinese male volunteers. Eligible subjects were randomly assigned in a 1:1 ratio to receive a single 200-mg dose of the test or reference formulation, followed by a 1-week washout period and administration of the alternate formulation. The study drugs were administered after a 12-hour overnight fast. After the study drug administration, serial blood samples were collected for 72 hours after administration. Plasma drug concentrations were determined using high-performance liquid chromatography coupled with tandem mass spectrometry. Several pharmacokinetic pararameters, including Cmax, Tmax, t½, AUC0-t, and AUC0-∞, were determined from the plasma concentrations of the 2 formulations of arbidol using noncom-partmental analysis. The formulations were to be considered bioequivalent if the log-transformed ratios of Cmax and AUC were within the predetermined bioequivalence range of 80% to 125% established by the State Food and Drug Administration (SFDA) of the People's Republic of China. Tolerability was assessed by monitoring vital signs (blood pressure, heart rate, temperature, and electrocardiography), laboratory analysis (hematology, blood biochemistry, hepatic function, and urinalysis), and subject interview on adverse events. Results: Twenty subjects were enrolled and completed the study (mean [SD] age, 21.1 [1.1] years; weight, 64.7 [5.1] kg; and height, 172.3 [3.1] cm). Neither period nor sequence effect was observed. The main pharmacokinetic properties with the test and reference formulations were as follows: Cmax, 417.4 (107.6) and 414.8 (95.1) ng/mL, respectively (P = NS); median (range) Tmax, 0.63 (0.25–1.0) and 0.75 (0.5–1.5) hours (P = 0.035); AUC0-t, 2033.6 (564.9) and 1992.0 (483.3) ng/mL/h (P = NS); AUC0-∞, 2285.4 (597.7) and 2215.2 (604.0) ng/mL/h (P = NS); and t1/2, 6.9 (4.2) and 6.1 (5.2) hours (P = NS). The 90% CIs for the log-transformed ratios of Cmax, AUC0-t, and AUC0-∞ were 91.7% to 109.7%, 91.0% to 112.8%, and 92.0% to 116.3%, respectively (all, P < 0.05), which were within the predetermined range for bioequivalence. No adverse events were found on analysis of vital signs or laboratory tests or reported by subjects in this study. Conclusion: In this study in healthy Chinese male volunteers, the dispersible tablet formulation and the 200-mg capsule formulation of arbidol met the SFDA's regulatory definition of bioequivalence based on the rate and extent of absorption.


title: Two Fatal Cases of Hidden Pneumonia in Young People

text: Abstract: Acute respiratory distress syndrome (ARDS) is a severe lung disease characterized by inflammation of the lung parenchyma leading to impaired gas exchange. This condition is often lethal, usually requiring mechanical ventilation and admission to an intensive care unit. We present two fatal cases of hidden pneumonia in young people and discuss the pathophysiological mechanism of ARDS with reference to the histological pattern. A complete forensic approach by means of autopsy and histological, immunohistochemical, and microbiological, examination was carried out. In both cases the cause of death was cardio‐respiratory failure following an acute bilateral pneumonia with diffuse alveolar damage and ARDS associated with sepsis and disseminated intravascular coagulation. Our cases suggest on one side the importance of an early diagnosis to avoid unexpected death while on the other that the diagnosis of ARDS has to be confirmed on the basis of a careful postmortem examination and a complete microscopy and microbiological study.


Don't panic, it is only an emergency


title: Clinical Features and Molecular Diagnosis of Chikungunya Fever from South India

text: An epidemic of Chikungunya fever of unprecedented magnitude occurred in many parts of India in early 2006 after an interval of 33 years, and there has been a resurgence in some parts of South India since June 2007. The article highlights clinical manifestations of infection and various molecular tests that were used for diagnoses of Chikungunya virus infection. Of particular interest is the real-time loop-mediated isothermal amplification (RT LAMP) assay, which is rapid and cost-effective and can be adopted at ill-equipped laboratories. Clinical symptoms were characterized by a triad of fever, rash, and severe rheumatic manifestations. RT LAMP identified 20 additional Chikungunya virus—positive cases, compared with reverse-transcriptase polymerase chain reaction. Chikungunya virus was isolated from 20 randomly selected samples. Genotyping of the virus isolates revealed that the East Central South African genotype of Chikungunya virus was the etiologic agent of this epidemic. Molecular diagnosis is an important tool to identify such new vectorborne viral illnesses.


title: Managing Sickle Cell Patients With COVID‐19 Infection: The Need to Pool Our Collective Experience

text: Coronavirus disease 19 (COVID‐19) has posed unparalleled challenges for health care communities, the general population, and in particular, for patients suffering from various comorbidities. Patients with hematological disorders, both benign and malignant need special attention during this crisis time to ensure uninterrupted delivery of optimal care (Sahu & Siddiqui, 2020).


Australia keeps a lid on covid-19 – for now


title: Differences among Ophthalmology Patients Referred to Tertiary Medical Centers according to Referral Hospital

text: PURPOSE: This study aimed to investigate the diagnosis and severity of patients who were referred to tertiary medical centers according to the type and function of the referral hospitals. METHODS: First-visit patients referred from July 2015 to June 2016 were retrospectively reviewed with regard to referral hospital, final diagnosis, treatment necessity, and medical fees for the six months after their first hospital visit. Based on these data, differences in type and function of medical institution were examined. RESULTS: In a comparison of hospitals according to their number of beds, clinics, hospitals and, tertiary hospitals had no differences in the ratio of patients who needed treatment (p = 0.075) and their medical fees over six months (p = 0.372). When hospitals were classified by functional capability in terms of doctors' medical specialty, increasing ratios of patients requiring medical treatment (p < 0.001) and medical fees for six months (p < 0.001) were found in the order of non-eye specialists, eye specialists, and eye specialists in trainee hospital. CONCLUSIONS: Efficient healthcare delivery systems should classify medical institutions by functionality capability based on medical specialties rather than hospital size according to the number of beds.


Shocking effects of endothelial bradykinin B1 receptors


title: Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths

text: The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D(3) for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/mL (100–150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D(3) doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.


title: Risks and burden of viral respiratory tract infections in patients with multiple myeloma in the era of immunomodulatory drugs and bortezomib: experience at an Australian Cancer Hospital

text: INTRODUCTION: Infections are a leading cause of morbidity and mortality in patients with multiple myeloma. The epidemiology, risk factors and outcomes of viral respiratory tract infections (vRTI) are not well described in patients with multiple myeloma managed with novel agents, the current standard of care. METHODS: Patients with myeloma from 2009 to 2012 who tested positive on respiratory virus multiplex polymerase chain reaction had clinical, radiological and microbiological records reviewed. The Fourth European Conference on Infections in Leukaemia (ECIL-4) definitions of RTI were applied. Univariate and multivariate regression analysis of risk factors was performed using vRTI as the evaluable outcome. RESULTS: Of 330 patients, 75 (22.7 %) tested positive for a total of 100 vRTI episodes. All patients received thalidomide, lenalidomide or bortezomib in combination with myeloma therapies (median of three treatment regimens). vRTI occurred most commonly in patients with progressive disease, and receipt of more than three lines of myeloma therapy was associated with an increased risk of vRTI (p < 0.01). Amongst key respiratory pathogens, influenza was associated with the highest hospital admission rate (66.7 %), ICU admission rate (41.6 %) and mortality (33.3 %) whilst RSV was associated with prolonged hospital stay. CONCLUSION: Patients with multiple myeloma and advanced disease managed with multiple lines of therapy are at risk for vRTI, and targeted interventions for prevention/treatment are required.


title: Xrn1 activity broadly represses RNA polymerase II occupancy at mammalian but not viral promoters during herpesvirus infection

text: In mammalian cells, widespread acceleration of cytoplasmic mRNA degradation is linked to impaired RNA polymerase II (Pol II) transcription. This mRNA decay-induced transcriptional repression occurs during infection with gammaherpesviruses including Kaposi’s sarcoma-associated herpesvirus (KSHV) and murine gammaherpesvirus 68 (MHV68), which encode an mRNA endonuclease that initiates widespread RNA decay. Here, we show that MHV68-induced mRNA decay leads to a genome-wide reduction of Pol II occupancy at mammalian promoters, which requires the cellular 5’-3’ exonuclease Xrn1. Viral genes, despite the fact that they require Pol II for transcription, escape this transcriptional repression. Protection is not governed by viral promoter sequences; instead, location on the viral genome is both necessary and sufficient to escape the transcriptional repression effects of mRNA decay. We hypothesize that the ability to escape from transcriptional repression is linked to the conformation of viral DNA in replication compartments, providing a means for these viruses to counteract decay-induced viral transcript loss.


title: Infection preventionists' experience during the first months of the 2009 novel H1N1 influenza A pandemic

text: BACKGROUND: A novel strain of influenza A (H1N1) was identified in April 2009 and developed into a pandemic by June 2009. This rapid and unexpected event had enormous implications for infection preventionists (IP) internationally. Lessons learned from this event should guide future pandemic planning efforts. METHODS: Focus groups were conducted at the Association for Professionals in Infection Control and Epidemiology, Inc, (APIC) 2009 conference to evaluate IPs' experience with the novel H1N1 influenza pandemic and assess their perceived needs related to novel H1N1 topics and products required for future education and reference materials. RESULTS: Forty IPs (37 from the United States and 3 international) participated in the focus groups. Needed reference materials identified by attendees included infection prevention guidance for nonacute care settings; occupational health polices; and brief, multilanguage patient/family educational materials. Educational topics on which IPs need to be trained include isolation precautions/personal protective equipment recommendations for novel H1N1 patients, coordination between hospitals and community response agencies, and surge management. The rapidly changing and conflicting recommendations related to patient management made responding to this event challenging. IPs require synthesized infection prevention guidelines developed in a concise, real-time format. CONCLUSION: IPs must continue to partner with public health and other response agencies to address gaps in pandemic planning.


Maxillofacial services in the COVID-19 (SARS-CoV-2) pandemic – early lessons from the Italian experience


title: Molecular Diagnosis of a Novel Coronavirus (2019-nCoV) Causing an Outbreak of Pneumonia

text: BACKGROUND: A novel coronavirus of zoonotic origin (2019-nCoV) has recently been identified in patients with acute respiratory disease. This virus is genetically similar to SARS coronavirus and bat SARS-like coronaviruses. The outbreak was initially detected in Wuhan, a major city of China, but has subsequently been detected in other provinces of China. Travel-associated cases have also been reported in a few other countries. Outbreaks in health care workers indicate human-to-human transmission. Molecular tests for rapid detection of this virus are urgently needed for early identification of infected patients. METHODS: We developed two 1-step quantitative real-time reverse-transcription PCR assays to detect two different regions (ORF1b and N) of the viral genome. The primer and probe sets were designed to react with this novel coronavirus and its closely related viruses, such as SARS coronavirus. These assays were evaluated using a panel of positive and negative controls. In addition, respiratory specimens from two 2019-nCoV-infected patients were tested. RESULTS: Using RNA extracted from cells infected by SARS coronavirus as a positive control, these assays were shown to have a dynamic range of at least seven orders of magnitude (2x10(−4)-2000 TCID(50)/reaction). Using DNA plasmids as positive standards, the detection limits of these assays were found to be below 10 copies per reaction. All negative control samples were negative in the assays. Samples from two 2019-nCoV-infected patients were positive in the tests. CONCLUSIONS: The established assays can achieve a rapid detection of 2019n-CoV in human samples, thereby allowing early identification of patients.


title: Oral immunization of mice with recombinant Lactococcus lactis expressing porcine transmissible gastroenteritis virus spike glycoprotein

text: Lactococcus lactis NZ9000 was selected as an antigen delivery vehicle for mucosal immunization against porcine transmissible gastroenteritis virus (TGEV) infection. An approximately 70 kDa fragment of the N-terminal globular domain of the spike (S) protein (S(N) protein) from the coronavirus TGEV was used as the transmissible gastroenteritis virus antigen model. Recombinant L. lactis, expressing the S(N) protein, was constructed with the pNZ8112 plasmid. Expression and localization of the transcribed S(N) protein from the recombinant L(NZ)9000-rTGEV-S(N) were detected via SDS-PAGE, Western blot, and immunofluorescence. BALB/c mice, orally immunized with L(NZ)9000-rTGEV-S(N), produced local mucosal immune responses against TGEV. The induced antibodies demonstrated neutralizing effects on TGEV infection. These data indicated that the recombinant L. lactis could be a valuable tool in the development of future vaccines against TGEV.


title: Complex positive selection pressures drive the evolution of HIV-1 with different co-receptor tropisms

text: HIV-1 co-receptor tropism is central for understanding the transmission and pathogenesis of HIV-1 infection. We performed a genome-wide comparison between the adaptive evolution of R5 and X4 variants from HIV-1 subtypes B and C. The results showed that R5 and X4 variants experienced differential evolutionary patterns and different HIV-1 genes encountered various positive selection pressures, suggesting that complex selection pressures are driving HIV-1 evolution. Compared with other hypervariable regions of Gp120, significantly more positively selected sites were detected in the V3 region of subtype B X4 variants, V2 region of subtype B R5 variants, and V1 and V4 regions of subtype C X4 variants, indicating an association of positive selection with co-receptor recognition/binding. Intriguingly, a significantly higher proportion (33.3% and 55.6%, P<0.05) of positively selected sites were identified in the C3 region than other conserved regions of Gp120 in all the analyzed HIV-1 variants, indicating that the C3 region might be more important to HIV-1 adaptation than previously thought. Approximately half of the positively selected sites identified in the env gene were identical between R5 and X4 variants. There were three common positively selected sites (96, 113 and 281) identified in Gp41 of all X4 and R5 variants from subtypes B and C. These sites might not only suggest a functional importance in viral survival and adaptation, but also imply a potential cross-immunogenicity between HIV-1 R5 and X4 variants, which has important implications for AIDS vaccine development.


title: Feline infectious peritonitis. ABCD guidelines on prevention and management

text: Overview Feline coronavirus infection is ubiquitous in domestic cats, and is particularly common where conditions are crowded. While most FCoV-infected cats are healthy or display only a mild enteritis, some go on to develop feline infectious peritonitis, a disease that is especially common in young cats and multi-cat environments. Up to 12% of FCoV-infected cats may succumb to FIP, with stress predisposing to the development of disease. Disease signs The ‘wet’ or effusive form, characterised by polyserositis (abdominal and/or thoracic effusion) and vasculitis, and the ‘dry’ or non-effusive form (pyogranulomatous lesions in organs) reflect clinical extremes of a continuum. The clinical picture of FIP is highly variable, depending on the distribution of the vasculitis and pyogranulomatous lesions. Fever refractory to antibiotics, lethargy, anorexia and weight loss are common non-specific signs. Ascites is the most obvious manifestation of the effusive form. Diagnosis The aetiological diagnosis of FIP ante-mortem may be difficult, if not impossible. The background of the cat, its history, the clinical signs, laboratory changes, antibody titres and effusion analysis should all be used to help in decision-making about further diagnostic procedures. At the time of writing, there is no non-invasive confirmatory test available for cats without effusion. Disease management In most cases FIP is fatal. Supportive treatment is aimed at suppressing the inflammatory and detrimental immune response. However, there are no controlled studies to prove any beneficial effect of corticosteroids. Vaccination recommendations At present, only one (intranasal) FIP vaccine is available, which is considered as being non-core. Kittens may profit from vaccination when they have not been exposed to FCoV (eg, in an early-weaning programme), particularly if they enter a FCoV-endemic environment.


title: 1H-1,2,3-triazole tethered isatin-ferrocene conjugates: Synthesis and in vitro antimalarial evaluation

text: 1H-1,2,3-triazole tethered isatin-ferrocene conjugates were synthesized and evaluated for their antiplasmodial activities against chloroquine-susceptible (3D7) and chloroquine-resistant (W2) strains of Plasmodium falciparum. The conjugates 5f and 5h with an optimum combination of electron-withdrawing halogen substituent at C-5 position of isatin ring and a propyl chain, introduced as linker, proved to be most potent and non-cytotoxic among the series with IC(50) values of 3.76 and 4.58 μM against 3D7 and W2 strains, respectively.


title: ‘Scientific Strabismus’ or two related pandemics: coronavirus disease and vitamin D deficiency

text: [Figure: see text]


Experience of Remote Cardiac Care during Covid‐19 Pandemic: the V‐LAP™ device in advanced heart failure


title: Common variants of chemokine receptor gene CXCR3 and its ligands CXCL10 and CXCL11 associated with vascular permeability of dengue infection in peninsular Malaysia

text: Dengue causes significantly more human disease than any other arboviruses. It causes a spectrum of illness, ranging from mild self-limited fever, to severe and fatal dengue hemorrhagic fever, as evidenced by vascular leakage and multifactorial hemostatic abnormalities. There is no specific treatment available till date. Evidence shows that chemokines CXCL10, CXCL11 and their receptor CXCR3 are involved in severity of dengue, but their genetic association with the susceptibility of vascular leakage during dengue infection has not been reported. We genotyped 14 common variants of these candidate genes in 176 patients infected with dengue. rs4859584 and rs8878 (CXCL10) were significantly associated with vascular permeability of dengue infection (P < 0.05); while variants of CXCL11 showed moderate significance of association (P = 0.0527). Haplotype blocks were constructed for genes CXCL10 and CXCL11 (5 and 7 common variants respectively). Haplotype association tests performed revealed that, “CCCCA” of gene CXCL10 and “AGTTTAC” of CXCL11 were found to be significantly associated with vascular leakage (P = 0.0154 and 0.0366 respectively). In summary, our association study further strengthens the evidence of the involvement of CXCL10 and CXCL11 in the pathogenesis of dengue infection.


title: A novel defective recombinant porcine enterovirus G virus carrying a porcine torovirus papain-like cysteine protease gene and a putative anti-apoptosis gene in place of viral structural protein genes

text: Abstract Enterovirus G (EV-G) belongs to the family of Picornaviridae. Two types of recombinant porcine EV-Gs carrying papain-like cysteine protease (PLCP) gene of porcine torovirus, a virus in Coronaviridae, are reported. Type 1 recombinant EV-Gs are detected in pig feces in Japan, USA, and Belgium and carry the PLPC gene at the junction site of 2C/3A genes, while PLPC gene replaces the viral structural genes in type 2 recombinant EV-G detected in pig feces in a Chinese farm. We identified a novel type 2 recombinant EV-G carrying the PLCP gene with flanking sequences in place of the viral structural genes in pig feces in Japan. The ~0.3 kb-long upstream flanking sequence had no sequence homology with any proteins deposited in GenBank, while the downstream ~0.9 kb-long flanking sequence included a domain having high amino acid sequence homology with a baculoviral inhibitor of apoptosis repeat superfamily. The pig feces, where the novel type 2 recombinant EV-G was detected, also carried type 1 recombinant EV-G. The amount of type 1 and type 2 recombinant EV-G genomes was almost same in the pig feces. Although the phylogenetic analysis suggested that these two recombinant EV-Gs have independently evolved, type 1 recombinant EV-G might have served as a helper virus by providing viral structural proteins for dissemination of the type 2 recombinant EV-G.


La Universidad en el CORONACENO (post COVID-19)


title: Synanthropy of Wild Mammals as a Determinant of Emerging Infectious Diseases in the Asian–Australasian Region

text: Humans create ecologically simplified landscapes that favour some wildlife species, but not others. Here, we explore the possibility that those species that tolerate or do well in human-modified environments, or ‘synanthropic’ species, are predominantly the hosts of zoonotic emerging and re-emerging infectious diseases (EIDs). We do this using global wildlife conservation data and wildlife host information extracted from systematically reviewed emerging infectious disease literature. The evidence for this relationship is examined with special emphasis on the Australasian, South East Asian and East Asian regions. We find that synanthropic wildlife hosts are approximately 15 times more likely than other wildlife in this region to be the source of emerging infectious diseases, and this association is essentially independent of the taxonomy of the species. A significant positive association with EIDs is also evident for those wildlife species of low conservation risk. Since the increase and spread of native and introduced species able to adapt to human-induced landscape change is at the expense of those species most vulnerable to habitat loss, our findings suggest a mechanism linking land conversion, global decline in biodiversity and a rise in EIDs of wildlife origin.


title: Compartmental Models of the COVID-19 Pandemic for Physicians and Physician-Scientists

text: As the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection spreads globally, physicians and physician-scientists are confronted with an enlarging body of literature about the nature of this pandemic. Understanding the current epidemiological models for disease spread, mortality, and recovery is more important than ever before. One of the most relevant mathematical models relating to the spread of a pandemic is the susceptible-infectious-removed (SIR) model. Other models worth exploring are the susceptible-exposed-infectious-removed (SEIR) and the susceptible-unquarantined-quarantined-confirmed (SUQC) model.


title: What has luck got to do with economic development? An interpretation of resurgent Asia’s growth experience

text: Abstract This paper critically reexamines the belief, currently gathering strength in the literature, that economic development depends on good luck rather than on good policy, and that Prometheus is “unchained by chance”. While it is impossible to disprove the role of luck in growth, we argue that luck is endogenous, and good luck is a function of good policy. Luck favours those who strive. Again contrary to common belief, we show that resurgent Asian economies have endured more, not less, than their fair share of economic volatility. They learned their lessons by success and failures, and luck is endogenous through learning-by-investing.


title: ANTIVIRAL EFFECTS OF SAIKOSAPONINS ON HUMAN CORONAVIRUS 229E IN VITRO

text: 1.. Saikosaponins represent a group of oleanane derivatives, usually as glucosides, that are found in a number of plant families. Saikosaponins isolated from medicinal plants such as Bupleurum spp., Heteromorpha spp. and Scrophularia scorodonia have been reported to possess various biological activities, specifically antihepatitis, antinephritis, antihepatoma, anti‐inflammation, immunomodulation and antibacterial effects. 2.. The aim of the present study was to examine the anticoronaviral activity of saikosaponins (A, B(2), C and D) and their mode of action. Using the 2,3‐bis[2‐methoxy‐4‐nitro‐5‐sulfophenyl]‐5‐[(phenylamino) carbonyl‐2H‐tetrazolium hydroxide] (XTT) assay, results showed that all saikosaponins tested demonstrated antiviral activity at concentrations of 0.25–25 µmol/L, with the strongest activity being noted for saikosaponin B(2) (IC(50) = 1.7 ± 0.1 µmol/L). Interestingly, both saikosaponins A (50% cellular cytotoxicity (CC(50)) concentration = 228.1 ± 3.8 µmol/L; selectivity index (SI) = 26.6) and B(2) (CC(50) = 383.3 ± 0.2 µmol/L; SI = 221.9) exhibited no cytotoxic effects on target cells at concentrations that achieved antiviral activity. In the time‐of‐addition studies, saikosaponin B(2), at 6 µmol/L, significantly inhibited human coronavirus 229E infection following its addition at various time pre‐infection (−4 to −1 h), coinfection (0 h) and post‐infection (1–4 h). Furthermore, saikosaponin B(2) also showed an inhibitory effect on viral attachment and penetration. 3.. The present results indicate that saikosaponin B(2) has potent anticoronaviral activity and that its mode of action possibly involves interference in the early stage of viral replication, such as absorption and penetration of the virus.


title: Characterization of the hypersensitive response‐like cell death phenomenon induced by targeting antiviral lectin griffithsin to the secretory pathway

text: Griffithsin (GRFT) is an antiviral lectin, originally derived from a red alga, which is currently being investigated as a topical microbicide to prevent transmission of human immunodeficiency virus (HIV). Targeting GRFT to the apoplast for production in Nicotiana benthamiana resulted in necrotic symptoms associated with a hypersensitive response (HR)‐like cell death, accompanied by H(2)O(2) generation and increased PR1 expression. Mannose‐binding lectins surfactant protein D (SP‐D), cyanovirin‐N (CV‐N) and human mannose‐binding lectin (hMBL) also induce salicylic acid (SA)‐dependent HR‐like cell death in N. benthamiana, and this effect is mediated by the lectin's glycan binding activity. We found that secreted GRFT interacts with an endogenous glycoprotein, α‐xylosidase (XYL1), which is involved in cell wall organization. The necrotic effect could be mitigated by overexpression of Arabidopsis XYL1, and by co‐expression of SA‐degrading enzyme NahG, providing strategies for enhancing expression of oligomannose‐binding lectins in plants.


title: Kaempferol – A dietary anticancer molecule with multiple mechanisms of action: Recent trends and advancements

text: Abstract The consumption of diet-based naturally bioactive metabolites is preferred to synthetic material in order to avert health-associated disorders. Among the plant-derived polyphenols, kaempferol (KMF) is considered as a valuable functional food ingredient with a broad range of therapeutic applications such as anti-cancer, antioxidant and anti-inflammatory uses. KMF acts on a range of intracellular as well as extracellular targets involved in the cell signaling pathways that in turn are known to regulate the hallmarks of cancer growth progressions like apoptosis, cell cycle, invasion or metastasis, angiogenesis and inflammation. Importantly, the understanding of mechanisms of action of KMF-mediated therapeutic effects may help the scientific community to design novel strategies for the treatment of dreadful diseases. The current review summarizes the various types of molecular targets of KMF in cancer cells as well as other health-associated disorders. In addition, this review also highlights the absorption, metabolism and epidemiological findings.


title: Cytosolic Sensing of Viruses

text: Cells are equipped with mechanisms that allow them to rapidly detect and respond to viruses. These defense mechanisms rely partly on receptors that monitor the cytosol for the presence of atypical nucleic acids associated with virus infection. RIG-I-like receptors detect RNA molecules that are absent from the uninfected host. DNA receptors alert the cell to the abnormal presence of that nucleic acid in the cytosol. Signaling by RNA and DNA receptors results in the induction of restriction factors that prevent virus replication and establish cell-intrinsic antiviral immunity. In light of these formidable obstacles, viruses have evolved mechanisms of evasion, masking nucleic acid structures recognized by the host, sequestering themselves away from the cytosol or targeting host sensors, and signaling adaptors for deactivation or degradation. Here, we detail recent advances in the molecular understanding of cytosolic nucleic acid detection and its evasion by viruses.


title: Evaluation of the AdvanSure™ real-time RT-PCR compared with culture and Seeplex RV15 for simultaneous detection of respiratory viruses

text: Abstract Recently, AdvanSure™ kit based on multiplex real-time PCR was developed for simultaneous detection of 14 respiratory viruses (RVs). We compared the performance of AdvanSure with those of Seeplex® RV 15 ACE and culture by determining their sensitivities and specificities against a composite reference standard. Four hundred thirty-seven respiratory samples were tested by modified shell vial culture method, RV 15 ACE, and AdvanSure. One hundred fourteen samples (26.2%) out of 437 samples were positive by culture, while additional 91 (20.8%) were positive by AdvanSure or RV15. One hundred twelve of 114 culture-positive samples were positive by AdvanSure except 2 samples (1 adenovirus, 1 respiratory syncytial virus [RSV]). Overall, the sensitivities of culture, RV15, and AdvanSure were 74.5%, 89.8%, and 95.1%, respectively. Sensitivities of culture, RV15, and AdvanSure for each virus tested were as follows: 91/100/96% for influenza A, 60/0/100% for influenza B, 63/95/97% for RSV, 69/81/89% for adenovirus, and 87/93/93% for parainfluenza virus. For viruses not covered by culture, sensitivities of RV15 and AdvanSure were as follows: 77/88% for rhinovirus, 100/100% for coronavirus OC43, 40/100% for coronavirus 229E/NL63, 13/100% for metapneumovirus, and 44/100% for bocavirus. The overall specificities of culture, RV15, and AdvanSure were 100/98.9/99.5%, respectively. Of 45 coinfected specimens, AdvanSure detected 41 specimens (91.1%) as coinfected, while RV15 detected 27 specimens (60.0%) as coinfected. AdvanSure assay demonstrated exquisite performance for the detection of RVs and will be a valuable tool for the management of RV infection.


title: Viral etiology of influenza-like illnesses in Huizhou, China, from 2011 to 2013

text: Little information is available on the etiology and prevalence of viruses other than influenza viruses causing influenza-like illnesses (ILIs) in China. This study was conducted for simultaneous detection and identification of 14 respiratory viruses in Huizhou using real-time PCR. In total, viruses were detected in 48.66 % of ILI patient samples, in which influenza virus (19.98 %) was the most commonly detected, followed by rhinovirus (7.46 %), human coronaviruses (3.63 %), human metapneumovirus (3.06 %), parainfluenza virus (3.06 %), respiratory syncytial virus (2.39 %), adenovirus (2.29 %), and human bocavirus (1.43 %). Co-infections occurred in 5.35 % of all tested specimens and 11.00 % (56/509) of infected patients. Children under 5 years and adults older than 60 years were more likely to have one or more detectable viruses associated with their ILI (OR=1.75, 95 % CI: 1.37; 2.23). Influenza virus was detected during each month of each year, and increased viral activity was observed in 2013. Infections with adenovirus and human metapneumovirus had characteristic seasonal patterns. No significant differences were found in positive the rate between the gender groups, while significantly differences in positive rate were found among the different age groups (P-value<0.001). This study confirmed that multiple respiratory viruses may circulate concurrently in the population and play an important role in the etiology of ILI. The most frequent symptoms associated with respiratory viruses were sore throat, rhinorrhea and headache. This information needs to be considered by clinicians when treating patients presenting with ILI, and it could serve as a reference for government officers when designing and implementing effective intervention plans.


title: Middle East Respiratory Syndrome Coronavirus Transmission in Extended Family, Saudi Arabia, 2014

text: Risk factors for human-to-human transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) are largely unknown. After MERS-CoV infections occurred in an extended family in Saudi Arabia in 2014, relatives were tested by using real-time reverse transcription PCR (rRT-PCR) and serologic methods. Among 79 relatives, 19 (24%) were MERS-CoV positive; 11 were hospitalized, and 2 died. Eleven (58%) tested positive by rRT-PCR; 8 (42%) tested negative by rRT-PCR but positive by serology. Compared with MERS-CoV–negative adult relatives, MERS-CoV–positive adult relatives were older and more likely to be male and to have chronic medical conditions. Risk factors for household transmission included sleeping in an index patient’s room and touching respiratory secretions from an index patient. Casual contact and simple proximity were not associated with transmission. Serology was more sensitive than standard rRT-PCR for identifying infected relatives, highlighting the value of including serology in future investigations.


Radiothérapie mammaire dans le contexte de la pandémie de covid-19: astuces pratiques en période épidémique et conseils pour la reprise de l’activité en fin de crise


title: Airway inflammation and anti‐protease defences rapidly improve during treatment of an acute exacerbation of COPD

text: Background and objective: There are few data on the short‐term natural history of airway inflammation during severe episodes of acute exacerbation of COPD (AECOPD). An observational study was performed to determine how rapidly conventional treatment improves airway inflammation in patients admitted to hospital with AECOPD. Methods: Twenty‐four consecutive patients with AECOPD were recruited and changes in sputum inflammatory indices were assessed after 2 and 4 days of treatment. The primary end‐points included presence of bacteria and viruses, changes in sputum total cell counts (TCC) and polymorphonuclear leukocyte (PMN) differential counts, and levels of secretory leukocyte protease inhibitor (SLPI), IL‐8 and TNF‐α. Results: All patients received oral corticosteroids and 17 (71%) were also treated with oral antibiotics. A bacterial or viral pathogen was isolated from 12 patients (50%), and Aspergillus fumigatus was isolated from one. A positive bacterial culture was associated with increased sputum TCC and PMN count (P < 0.05), as well as higher levels of IL‐8 and TNF‐α (P < 0.05), and a trend towards lower sputum SLPI levels (P = 0.06). Sputum PMN numbers fell by 70% within the first 48 h of admission (P < 0.05), accompanied by an increase in sputum SLPI (P < 0.001) and reductions in the levels of TNF‐α (P < 0.005) and IL‐8 (P = 0.06), with no further significant change at 4 days. Conclusions: Conventional treatment for severe AECOPD is associated with rapid reduction of neutrophilic inflammation and improvement in anti‐protease defences.


title: Murine monoclonal antibody which can distinguish cystatins SA1 and SA2

text: Abstract To develop a diagnostic trial enabling the selective examination for a target cystatin in human body fluids, we attempted to prepare monoclonal antibodies against human cystatin SA1 (originally cystatin SA) and its variant form (cystatin SA2). BALB/c mice were immunized with recombinant (r-) cystatins SA1 and SA2. Two monoclonal antibodies designated Cys3F11 and Cys2E5 were selected. By ELISA analyses, the Cys2E5 was shown to react with r-cystatin SA2 but also somewhat with r-cystatin SA1 (22% cross-reactivity) and with plasma cystatin C (18% cross-reactivity), indicating a high specificity for cystatin SA2. The Cys3F11 reacted not only with r-cystatin SA1 but also with r-cystatin SA2 (89% cross-reactivity) and plasma cystatin C (47% cross-reactivity). This finding was further emphasized by immunoblotting of human submandibular–sublingual saliva samples. ELISA additivity test suggests that the two monoclonal antibodies bind to distinct epitopes. In conclusion, we have succeeded in producing two antibodies that discriminate the structural differences between salivary cystatins S and SN, which share more than 90% identity in amino acid sequence with cystatin SA.


title: A New Penicillin?

text: The spectre of antimicrobial resistance looms very large indeed in the 21st century; the supply of efficacious conventional drugs is short and not guaranteed, for various reasons. It is time to look elsewhere for answers and for protocols which might be used in tandem with our diminishing arsenal in order to protect vital drugs. This could bridge the gap before new development in conventional antimicrobial therapy occurs, or might be a longer-term solution, particularly in the area of infectious disease prophylaxis (conventional-sensitive or -resistant). Reliable and safe protocols have been developed for the use of photoantimicrobials in this respect, offering much greater coverage, in terms of the microbial target, than Fleming ever imagined.


title: Comparison of Risk Factors for Human Metapneumovirus and Respiratory Syncytial Virus Disease Severity in Young Children

text: Background. Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are leading pediatric pathogens. However, risk factors for severe hMPV disease remain unknown. We comparatively assessed environmental, host, and viral determinants for severe hMPV and RSV infections. Methods. We studied a prospective cohort of >1000 children aged <3 years hospitalized in or presenting to a pediatric clinic for acute respiratory infection. We collected clinical data at enrollment and 1-month follow-up and tested nasopharyngeal secretions for respiratory viruses. Disease severity was defined as hospitalization and was also assessed with a severity score (1 point/variable) calculated on the basis of fraction of inhaled O(2) ≥ 30%, hospitalization >5 days, and pediatric intensive care unit admission. Results. hMPV was identified in 58 of 305 outpatient children (19.0%) and 69 of 734 hospitalized children (9.4%), second only to RSV (48.2% and 63.6%, respectively). In multivariate regression analysis of hMPV cases, age <6 months and household crowding were associated with hospitalization. Among hospitalized patients, risk factors for severe hMPV disease were female sex, prematurity, and genotype B infection. Age <6 months, comorbidities, and household crowding were risk factors for RSV hospitalization; breast-feeding and viral coinfection were protective. Age <6 months and prematurity were associated with severe RSV cases among hospitalized children. Conclusions. hMPV and RSV severity risk factors may differ slightly. These findings will inform hMPV prevention strategies.


title: Time Series Forecasting of COVID-19 transmission in Canada Using LSTM Networks

text: Abstract On March 11 th 2020, World Health Organization (WHO) declared the 2019 novel corona virus as global pandemic. Corona virus, also known as COVID-19 was first originated in Wuhan, Hubei province in China around December 2019 and spread out all over the world within few weeks. Based on the public datasets provided by John Hopkins university and Canadian health authority, we have developed a forecasting model of COVID-19 outbreak in Canada using state-of-the-art Deep Learning (DL) models. In this novel research, we evaluated the key features to predict the trends and possible stopping time of the current COVID-19 outbreak in Canada and around the world. In this paper we presented the Long short-term memory (LSTM) networks, a deep learning approach to forecast the future COVID-19 cases. Based on the results of our Long short-term memory (LSTM) network, we predicted the possible ending point of this outbreak will be around June 2020. In addition to that, we compared transmission rates of Canada with Italy and USA. Here we also presented the 2, 4, 6, 8, 10, 12 and 14 th day predictions for 2 successive days. Our forecasts in this paper is based on the available data until March 31, 2020. To the best of our knowledge, this of the few studies to use LSTM networks to forecast the infectious diseases.


title: Pharmacovigilance in Patients with Diabetes: A Data-Driven Analysis Identifying Specific RAS Antagonists with Adverse Pulmonary Safety Profiles That Have Implications for COVID-19 Morbidity and Mortality

text: ABSTRACT OBJECTIVES Current demographic information from China reports that 10-19% of patients hospitalized with COVID-19 were diabetic. Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin-II receptor blockers (ARBs) are considered first-line agents in diabetics due to their nephroprotective effects but administration of these drugs leads to upregulation of angiotensin-converting-enzyme-2 (ACE2), responsible for viral entry of severe-acute-respiratory-distress-syndrome, coronavirus-2 (SARS-CoV-2). Data is lacking to determine what pulmonary effects ACEIs/ARBs may have in patients with diabetes, which could be relevant in the management of patients infected with SARS-CoV-2. In this study, the aim was to assess the prevalence of pulmonary adverse drug effects (ADEs) in diabetic patients taking ACEI or ARBs to help provide guidance as to how these medications could affect outcomes in acute respiratory illness, such as SARS-CoV-2 infection. METHODS 1DATA, a unique data platform resulting from collaboration across veterinary and human healthcare, utilized an intelligent medicine recommender system (1DrugAssist) developed using several national and international databases, to evaluate all ADEs reported to the FDA for patients with diabetes taking ACEIs or ARBs. RESULTS Mining of this data elucidated the proportion of a cluster of pulmonary ADEs associated with specific medications in these classes, which may aid healthcare professionals in understanding how these medications could worsen or predispose patients with diabetes to infections affecting the respiratory system specifically, COVID-19. Based on this data mining, Captopril was found to have a statistically significantly higher incidence of pulmonary ADEs compared to other ACEIs (P = 0.005) as well as ARBs (P = 0.012), though other specific drugs also had important pulmonary ADEs associated with their use. CONCLUSION These analyses suggest that pharmacists and clinicians will need to consider specific medication’s adverse event profile, particularly captopril, and how this profile may affect infections and other acute disease states that alter pulmonary function, such as COVID-19.


title: Update: Severe Respiratory Illness Associated with a Novel Coronavirus — Worldwide, 2012–2013

text: CDC continues to work closely with the World Health Organization (WHO) and other partners to better understand the public health risk posed by a novel coronavirus that was first reported to cause human infection in September 2012. Genetic sequence analyses have shown that this new virus is different from any other known human coronaviruses, including the one that caused severe acute respiratory syndrome (SARS). As of March 7, 2013, a total of 14 confirmed cases of novel coronavirus infection have been reported to WHO, with eight deaths. Illness onsets have occurred from April 2012 through February 2013. To date, no cases have been reported in the United States.


title: Monitoring for airborne respiratory viruses in a general pediatric ward in Singapore

text: There is an increasing body of evidence suggesting that transmission of respiratory viruses occurs through the inhalation of virus-laden particles. Our study describes the use of an aerosol sampling system to monitor the prevalence of airborne viruses in a hospital setting. Using SKC AirCheck Touch pumps, with National Institute for Occupational Safety and Health (NIOSH) bioaerosol samplers and SKC filter cassette blanks, 28 aerosol samples were collected in a hospital ward in Singapore. Following DNA/RNA extraction, real-time RT-PCR/PCR was used for the detection of influenza A, B and D viruses, coronaviruses, enteroviruses, and adenoviruses. Airborne virus was detected in nine (32%) of 28 samples. Among the nine positive samples, eight were PCR-positive for adenovirus and one for influenza A virus. Our data suggest that bioaerosol sampling could be valuable in monitoring for airborne respiratory viruses in clinical environments to better understand the risk of infection during a hospital visit.


title: Induction of protective immunity against coronavirus‐induced encephalomyelitis: Evidence for an important role of CD8(+) T cells in vivo

text: Coronavirus MHV‐JHM infections of rats provide useful models to study the pathogenesis of virus‐induced central nervous system disease. To analyze the role of the immune response against defined MHV‐JHM antigens, we tested the protective efficacy of vaccinia virus (VV) recombinants expressing either the nucleocapsid (N) or the spike (S) protein. A strong protection was mediated in animals by immunization with recombinant VV encoding a wild‐type S protein (VV‐S(Wildtype)), whereas VV recombinant expressing a mutant S(354CR) protein (VV‐S(354CR)) had no protective effect. Recombinant VV encoding N protein (VV‐N) induces a humoral and a CD4(+) T cell response, but did not prevent acute disease regardless of the immunization protocol. In these experiments, challenge with an otherwise lethal dose of MHV‐JHM was performed prior to the induction of virus‐neutralizing antibodies and studies with the anti‐CD8(+) monoclonal antibody, MRC OX8 showed that elimination of the CD8(+) subset of T cells abrogates the protective effect. This result indicates that CD8(+) T cells primed by recombinant VV expressing wild‐type S protein are a primary mechanism of immunological defense against MHV‐JHM infection in rats.