title: Temporal Variability and Social Heterogeneity in Disease Transmission: The Case of SARS in Hong Kong

text: The extent to which self-adopted or intervention-related changes in behaviors affect the course of epidemics remains a key issue for outbreak control. This study attempted to quantify the effect of such changes on the risk of infection in different settings, i.e., the community and hospitals. The 2002–2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong, where 27% of cases were healthcare workers, was used as an example. A stochastic compartmental SEIR (susceptible-exposed-infectious-removed) model was used: the population was split into healthcare workers, hospitalized people and general population. Super spreading events (SSEs) were taken into account in the model. The temporal evolutions of the daily effective contact rates in the community and hospitals were modeled with smooth functions. Data augmentation techniques and Markov chain Monte Carlo (MCMC) methods were applied to estimate SARS epidemiological parameters. In particular, estimates of daily reproduction numbers were provided for each subpopulation. The average duration of the SARS infectious period was estimated to be 9.3 days (±0.3 days). The model was able to disentangle the impact of the two SSEs from background transmission rates. The effective contact rates, which were estimated on a daily basis, decreased with time, reaching zero inside hospitals. This observation suggests that public health measures and possible changes in individual behaviors effectively reduced transmission, especially in hospitals. The temporal patterns of reproduction numbers were similar for healthcare workers and the general population, indicating that on average, an infectious healthcare worker did not infect more people than any other infectious person. We provide a general method to estimate time dependence of parameters in structured epidemic models, which enables investigation of the impact of control measures and behavioral changes in different settings.


title: Chapter 1 Introduction into nanotechnology and microbiology

text: Abstract The current chapter summaries the world of Microbiology and boom of Nanotechnology and how both the exciting fields come together to help men kind with various new applications in water, food, medical biology and immunology. Furthermore synthesis of nano materials utilising the potential of microorganisms also opens a newer avenue for ‘green’ synthesis.


title: Comparative analytical evaluation of the respiratory TaqMan Array Card with real-time PCR and commercial multi-pathogen assays

text: Abstract In this study, a multicenter evaluation of the Life Technologies TaqMan® Array Card (TAC) with 21 custom viral and bacterial respiratory assays was performed on the Applied Biosystems ViiA™ 7 Real-Time PCR System. The goal of the study was to demonstrate the analytical performance of this platform when compared to identical individual pathogen specific laboratory developed tests (LDTs) designed at the Centers for Disease Control and Prevention (CDC), equivalent LDTs provided by state public health laboratories, or to three different commercial multi-respiratory panels. CDC and Association of Public Health Laboratories (APHL) LDTs had similar analytical sensitivities for viral pathogens, while several of the bacterial pathogen APHL LDTs demonstrated sensitivities one log higher than the corresponding CDC LDT. When compared to CDC LDTs, TAC assays were generally one to two logs less sensitive depending on the site performing the analysis. Finally, TAC assays were generally more sensitive than their counterparts in three different commercial multi-respiratory panels. TAC technology allows users to spot customized assays and design TAC layout, simplify assay setup, conserve specimen, dramatically reduce contamination potential, and as demonstrated in this study, analyze multiple samples in parallel with good reproducibility between instruments and operators.


title: Post-traumatic stress disorder among Chinese women survivors of intimate partner violence: A review of the literature

text: Abstract Background Post-traumatic stress disorder is one of the most prevalent mental health sequelae of intimate partner violence, and as a result, it has been extensively documented in Western literature. However, whether abused women from non-Western cultures experience similar post-traumatic responses to intimate partner violence is less documented. Objectives The objectives of this paper were (1) to review the literature for information about post-traumatic stress disorder among Chinese women survivors of intimate partner violence; (2) to provide a synthesis of the literature on post-traumatic stress disorder among abused Chinese women; and (3) to identify implications for practice and to suggest directions for research relating to post-traumatic stress disorder among abused Chinese women. Design A systematic review of the literature. Data Sources Following a systematic search for relevant literature in computerized databases and manual searches of English and Chinese language publications, five papers reporting on four studies conducted in China, Taiwan, Malaysia, and the United States were included in the review. Review Methods Abstracts meeting the inclusion criteria were reviewed independently by two of the authors and any discrepancies were resolved by discussion. Full papers for selected abstracts were then retrieved and assessed independently by the same reviewers. Results The present literature review revealed a paucity of information relating to post-traumatic stress disorder symptoms or diagnoses in abused Chinese women. Nevertheless, a link between post-traumatic stress disorder and intimate partner violence was demonstrated by the reviewed papers. Conclusions Caution should be exercised when making comparison of the findings across the four studies because of the inherent methodological differences. Also, as the assessment tools have not been validated for culture-bound interpretation of trauma and symptom manifestation, comparisons of findings for Chinese women to women in Western literature should be undertaken with due consideration. Implications for practice and recommendations for future research are discussed.


title: Securitizing HIV/AIDS: a game changer in state-societal relations in China?

text: BACKGROUND: China has experienced unprecedented economic growth since the 1980s. Despite this impressive economic development, this growth exists side by side with the human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and severe acute respiratory syndrome (SARS) crises and the persisting deficiencies in public health provision in China. Acknowledging the prevailing health problems, the Chinese government has encouraged the development of health non-governmental organizations (NGOs) to respond to the health challenges and address the gaps in public health provision of the government. HIV/AIDS-focused NGOs have been perceived as the most outstanding civil society group developed in China. Considering the low priority of health policies since the economic reform, the limitation of the “third sector” activity permitted in authoritarian China, together with the political sensitivity of the HIV/AIDS problem in the country, this article aims to explain the proliferation of HIV/AIDS-focused NGOs in China with the usage of the securitization framework in the field of international relations (IR). METHODS: The research that underpins this article is based on a desk-based literature review as well as in-depth field interviews with individuals working in HIV/AIDS-focused NGOs in China. Face-to-face interviews for this research were conducted between January and May in 2011, and between December 2016 and January 2017, in China. Discourse analysis was in particular employed in the study of the security-threat framing process (securitization) of HIV/AIDS in China. RESULTS: This article argues that the proliferation of HIV/AIDS-related NGOs in China is largely attributed to the normative and technical effects of HIV/AIDS securitization ushered in by the United Nations Security Council (UNSC) and supported by the Global Fund to Fight AIDS, Tuberculosis, and Malaria (hereinafter Global Fund) observed in China. Despite depicting a positive scenario, the development of HIV/AIDS-focused NGOs in China generated by the international securitization efforts is largely limited. An internal and external factor was identified to verify the argument, namely (1) the reduction of international financial commitments, as well as (2) the fragmentation of HIV/AIDS-focused NGO community in China. CONCLUSIONS: This article shows that international securitization weakened with the rise of Chinese commitment on HIV/AIDS interventions. In other words, HIV/AIDS-related responses delivered by the national government are no longer checked by the global mechanism of HIV/AIDS; thus it is unclear whether these NGOs would remain of interest as partners for the government. The fragmentation of the HIV/AIDS community would further hinder the development, preventing from NGOs with the same interest forming alliances to call for changes in current political environment. Such restriction on the concerted efforts of HIV/AIDS-related NGOs in China would make achievement of the Sustainable Development Goals (SDGs) to foster stronger partnerships between the government and civil society difficult, which in turn hindering the realization of ending HIV/AIDS in the world by 2030.


title: Action at a Distance: Geriatric Research during a Pandemic

text: BACKGROUND: “Action at a distance” may be the new norm for clinical researchers in the context of the COVID‐19 pandemic that may require social distancing for the next 18 months. We must minimize face‐to‐face contact with vulnerable populations. But we must also persist, adapt, and help our older patients and study participants during the pandemic. METHODS: Clinical researchers have an obligation to help, and we can. Recommendations for clinical researchers working with older adults during the COVID‐19 pandemic are discussed. RESULTS: Implement technology now: Minimize face‐to‐face contact with participants by utilizing digital tools, such as shifting to electronic informed consent and digital HIPAA‐compliant tools such as e‐mailed surveys or telehealth assessments. Assess the psychological and social impact of COVID‐19: How are participants coping? What health or social behaviors have changed? How are they keeping up with current events? What are they doing to stay connected to their families, friends, and communities? Are their healthcare needs being met? Current studies should be adapted immediately to these ends. Mobilize research platforms for patient needs: Leverage our relationships with participants and rapidly deploy novel clinical engagement techniques such as digital tools to intervene remotely and reduce the negative effects of social isolation on our participants. Equip research staff with tangible resources, and provide timely population‐specific health information to support patients and healthcare providers. CONCLUSIONS: We have an opportunity to make an impact on our older adult patients now as this pandemic continues to unfold. Above all, clinical researchers need to continue working, to help as many people as possible through the crisis.


title: Preweaned heifer management on US dairy operations: Part V. Factors associated with morbidity and mortality in preweaned dairy heifer calves

text: ABSTRACT The objective of this study was to evaluate morbidity and mortality in preweaned dairy heifer calves based on different health, feeding, and management practices, as well as environmental factors. This study was conducted as part of the calf component of the National Animal Health Monitoring System's Dairy 2014 study, which included 104 dairy operations in 13 states. The calf component was an 18-mo longitudinal study focused on dairy heifer calves from birth to weaning; data were collected on 2,545 calves. The percentage morbidity for all calves enrolled in the study was 33.9%. Backward elimination model selection was used after univariate screening to determine which management practices and environmental factors significantly affected morbidity and mortality. The final morbidity model included birth weight, serum IgG concentration, ventilation type, and average temperature-humidity index (THI) during the preweaning period. After controlling for other independent variables in the model, calves born at a higher birth weight had a lower predicted risk of morbidity than calves with a lower birth weight. An increase in serum IgG concentration was associated with decreased morbidity. Calves housed in positive- or cross-ventilated systems had a 2.2 times higher odds of developing disease compared with calves housed in natural ventilation systems. Average THI during the preweaning period was inversely correlated with morbidity; as THI increased, the predicted morbidity risk decreased. The percent mortality for all calves enrolled in the study was 5.0%. The final mortality model included birth weight, serum IgG concentration, amount of fat/day in the liquid diet, and morbidity. After controlling for other independent variables in the model, calves born at a higher birth weight had a lower risk of mortality. An increase in serum IgG concentration decreased the risk of mortality. The odds of mortality were 3.1 times higher in calves fed ≤0.15 kg of fat/d in the liquid diet compared with calves fed ≥0.22 kg of fat/d. The odds of mortality were 4.7 times higher in calves that experienced any disease throughout the preweaning period than in calves with no disease. In summary, morbidity and mortality were both associated with birth weight and serum IgG concentration. Additionally, morbidity was associated with ventilation type and average monthly THI, and mortality was associated with amount of fat per day in the liquid diet and morbidity.


Dermatologic treatments in the era of COVID‐19 pandemic—Data and Hypothesis


title: Evolutionary relatedness of the predicted gene product of RNA segment 2 of the Tick-Borne Dhori virus and the PB1 polymerase gene of influenza viruses

text: Abstract The complete nucleotide sequence of the second largest RNA segment of Dhori/India/1313/61 virus was determined and the deduced amino acid sequence was compared with the polymerase (P) proteins of influenza A, B, and C viruses. RNA segment 2 (2224 nucleotides) of Dhori virus contains a single long open reading frame that can encode a 716-amino amid polypeptide (81.3 kDa). The predicted polypeptide shares between 27 and 31% sequence identities with the PB1 polypeptides of influenza A, B, and C viruses. Among the regions most highly conserved are the sequences around the Asp-Asp motif common to many RNA polymerases. In spite of the high level of sequence identity between the Dhori RNA segment 2 gene product and the influenza A, B, and C virus PB1 proteins the amino acid composition of the Dhori protein indicates an acidic charge feature at pH 7.0 in contrast to the basic nature of the PB1 proteins of the influenza viruses. We suggest that the Dhori PB1-like protein be designated the Pα protein of this virus.


title: Preparation and characterization of the anti-virus and anti-bacteria composite air filter materials

text: The anti-virus and anti-bacteria active components were extracted from some Chinese medicine, such as the honeysuckle, forsythia and the licorice. Using a w/o/w emulsion method, the active components were fabricated to uniform particulate microcapsule with sustained-release properties. The polypropylene punched felt was finished with the finishing agent of microcapsule, nano ZnO and TiO(2) and polymer adhesive, and the composite air filter with anti-virus and anti-bacteria properties were formed, staphylococcus aureus, colibacillus and candida albicans were applied to antibacterial experiments. The results indicate that the anti-bacteria rate are all 100%, and the virus inactivation rate also reaches 100% to pandemic influenza A virus.


title: RT‐LAMP for rapid diagnosis of coronavirus SARS‐CoV‐2

text: The pandemic coronavirus SARS‐CoV‐2 in the world has caused a large infected population suffering from COVID‐19. To curb the spreading of the virus, WHO urgently demanded an extension of screening and testing; thus, a rapid and simple diagnostic method is needed. We applied a reverse transcription‐loop‐mediated isothermal amplification (RT‐LAMP) to achieve the detection of SARS‐CoV‐2 in 30 min. We designed four sets of LAMP primers (6 primers in each set), targeting the viral RNA of SARS‐CoV‐2 in the regions of orf1ab, S gene and N gene. A colorimetric change was used to report the results, which enables the outcome of viral RNA amplification to be read by the naked eye without the need of expensive or dedicated instrument. The sensitivity can be 80 copies of viral RNA per ml in a sample. We validated the RT‐LAMP method in a hospital in China, employing 16 clinic samples with 8 positives and 8 negatives. The testing results are consistent with the conventional RT‐qPCR. In addition, we also show that one‐step process without RNA extraction is feasible to achieve RNA amplification directly from a sample. This rapid, simple and sensitive RT‐LAMP method paves a way for a large screening at public domain and hospitals, particularly regional hospitals and medical centres in rural areas.


title: Horses and the risk of zoonotic infections

text: Infectious agents are insidious, often changing to adapt to host defenses or treatment advances. Because these challenges will continue, the need to apply standard and transmission-based precautions is important not only in the human hospital setting but in the veterinary clinic setting. In addition, to prevent human infection and potential liability, clinics need to establish program algorithms to prevent disease spread for specific agents or planned procedures to respond to potential nosocomial and zoonotic disease events. These need to be done proactively. Furthermore, more money needs to be dedicated to establish infection control programs and to improve the science of infection control in the veterinary setting.


title: An Improved Barcoded Oligonucleotide Primers-based Next-generation Sequencing Approach for Direct Identification of Viral Pathogens in Clinical Specimens

text: Abstract Objective To provide a feasible and cost-effective next-generation sequencing (NGS) method for accurate identification of viral pathogens in clinical specimens, because enormous limitations impede the clinical use of common NGS, such as high cost, complicated procedures, tremendous data analysis, and high background noise in clinical samples. Methods Viruses from cell culture materials or clinical specimens were identified following an improved NGS procedure: reduction of background noise by sample preprocessing, viral enrichment by barcoded oligonucleotide (random hexamer or non-ribosomal hexanucleotide) primer-based amplification, fragmentation-free library construction and sequencing of one-tube mixtures, as well as rapid data analysis using an in-house pipeline. Results NGS data demonstrated that both barcoded primer sets were useful to simultaneously capture multiple viral pathogens in cell culture materials or clinical specimens and verified that hexanucleotide primers captured as many viral sequences as hexamers did. Moreover, direct testing of clinical specimens using this improved hexanucleotide primer-based NGS approach provided further detailed genotypes of enteroviruses causing hand, foot, and mouth disease (HFMD) and identified other potential viruses or differentiated misdiagnosis events. Conclusion The improved barcoded oligonucleotide primer-based NGS approach is simplified, time saving, cost effective, and appropriate for direct identification of viral pathogens in clinical practice.


title: The prospect of pandemic influenza: Why should the optometrist be concerned about a public health problem?

text: Abstract Background Optometrists are uniquely placed in the health care field because they provide both services as well as goods to patients. In the event of an influenza pandemic, optometrists may be challenged with a host of issues, including impediments to clinical patient care, manufacture and delivery of ophthalmic devices, and maintaining business continuity and infection control. Overview This report reviews pandemic influenza, the effect of a pandemic event on business survival, and response measures for the primary eye care provider. The ethical and legal issues surrounding control of a pandemic influenza and the prospect of telemedicine as a form of social distancing are also discussed. Conclusions Knowledge of the pharmacologic and nonpharmacologic measures to control a pandemic influenza will help prepare the eye care provider for addressing challenges to patient care and business continuity in the face of a highly contagious disease. Understanding the legal and ethical issues that arise during a pandemic event will help optometrists make informed choices as health care professionals and as citizens.


Challenges to paediatric services during COVID-19 Pandemic: a London, UK perspective


title: COVID-19 virus outbreak lockdown: What impacts on household food wastage?

text: The 2019–2020 coronavirus disease (COVID-19) is a public health issue. Lockdown is among options suggested to reduce spread of the virus. This study aimed to determining the impact of COVID-19 lockdown on Tunisian consumer awareness, attitudes and behaviors related to food wastage. An online survey was conducted during the first 2 weeks of COVID-19 lockdown. The survey collected information on demographic data, awareness and attitudes toward food waste, food purchase behavior and household food expenditure estimation; extent of household food waste; willingness and information needs to reduce food waste. This study included 284 respondents. About 89% of respondents claimed to be aware of food waste, and the COVID-19 lockdown would impact for 93% of respondents, their waste levels, and for 80%, their grocery shopping habits. Interestingly, the COVID-19 lockdown improved food shopping performances and pushed toward a positive behavioral change regarding food wastage: 85% respondents declared nothing of what they bought would be discarded, and most of the respondents have set up a strategy of saving, storing and eating leftovers. The most cited reasons given for discarding food were overcooking, inappropriate storage and overbuying. Consumers’ changes in food waste prevention might be probably driven more by the socioeconomical context of the COVID-19 lockdown (i.e. food availability, restricted movements, loss of income), than by a pro-environmental concern. Finally, our study pointed out the consumers’ needs of information for taking further action. In conclusion, our study can constitute a basis to further promote household food waste prevention behavior, outlasting the COVID-19 crisis.


CSI Microbiology: Emerging Pathogens and a Staged Strategy for Detection and Discovery


title: Hematopoietic stem cell transplantation for Shwachman-Diamond syndrome: experience of the French neutropenia registry

text: Our objective was to study the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) for Shwachman-Diamond Syndrome (SDS). Among 71 SDS patients included in the French Severe Chronic Neutropenia Registry, 10 received HSCT between 1987 and 2004 in five institutions. The indications were bone marrow failure in five cases, and myelodysplastic syndrome (MDS) or leukemia in five cases. The median follow-up of patients who survived without relapse is 6.9 years (3.1–16.8 years). The conditioning regimen consisted of a busulfan–cyclophosphamide combination (n=6) or total body irradiation plus chemotherapy (n=4). Six patients received stem cells from unrelated donors and four from identical siblings. Engraftment was complete in eight patients and unassessable in two patients. These latter two patients died of infections 32 and 36 days after HSCT, with grade IV graft-versus-host disease and multiorgan dysfunction. A third patient died from an acute respiratory distress syndrome 17 months after HSCT with progressive granulocytic sarcoma. One patient had an MDS relapse 4 months after HSCT and died 10 months later. The overall 5-year event-free survival rate is 60±15%. We conclude that HSCT is feasible for patients with SDS who develop bone marrow failure or malignant transformation.


title: Characteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan, China

text: Abstract Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is continuously and rapidly circulating at present. Asymptomatic patients have been proven to be contagious and thus pose a significant infection control challenge. Here we describe the characteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan, Shandong province, China. A total of 47 patients with confirmed COVID-19 were recruited. Among them, 11 patients were categorized as asymptomatic cases. We found that the asymptomatic patients in Jinan were relatively young and were mainly clustered cases. The laboratory indicators and lung lesion on chest CT were mild. No special factors were found accounting for the presence or absence of symptoms. The presence of asymptomatic patients increased the difficulty of screening. It is necessary to strengthen the identification of such patients in the future.


title: Prevalence of viral, bacterial and parasitological diseases in rats and mice used in research environments in Australasia over a 5-y period

text: Viral, bacterial and parasitological infections in rats and mice used in biomedical research continue to occur despite improved housing and biosurveillance. The presence of disease in laboratory animals can lead to spurious results for research undertaken in universities, research institutes and the pharmaceutical industry. Here the authors report the results of serological, microbiological, parasitological and molecular tests done on mice and rats from Australasia submitted to a rodent health monitoring laboratory (Cerberus Sciences) from 2004 to 2009. In tested mice, norovirus was the most prevalent virus and ectromelia virus was the least prevalent virus. In tested rats, pneumonia virus of mice was the most prevalent virus and adenoviruses 1 and 2 were the least prevalent viruses. In mice, Helicobacter hepaticus was the most prevalent bacterium, and in rats, Proteus spp. were the most prevalent bacteria. The most common positive helminthological finding in mice and rats was the presence of all pinworms (including Aspicularis spp. and Syphacia spp.). The most common positive protozoan findings in mice and rats were Chilomastix spp. and Trichomonads.


title: Weighted multifractal cross-correlation analysis based on Shannon entropy

text: Abstract In this paper, we propose a modification of multifractal cross-correlation analysis based on statistical moments (MFSMXA) method, called weighted MFSMXA method based on Shannon entropy (W-MFSMXA), to investigate cross-correlations and cross-multifractality between time series. Robustness of this method is verified by numerical experiments with both artificial and stock returns series. Results show that the proposed W-MFSMXA method not only keep the multifractal structure unchanged, but contains more significant information of series compared to the previous MFSMXA method. Furthermore, analytic formulas of the binomial multifractal model are generated for W-MFSMXA. Theoretical analysis and finite-size effect test demonstrate that W-MFSMXA slightly outperforms MFSMXA for relatively shorter series. We further generate the scaling exponent ratio to describe the relation of two methods, whose profile is found approximating a centrosymmetric hyperbola. Cross-multifractality is found in returns series but then destroyed after being shuffled as a consequence of the removed long memory in separate series.


title: Key data for outbreak evaluation: building on the Ebola experience

text: Following the detection of an infectious disease outbreak, rapid epidemiological assessment is critical for guiding an effective public health response. To understand the transmission dynamics and potential impact of an outbreak, several types of data are necessary. Here we build on experience gained in the West African Ebola epidemic and prior emerging infectious disease outbreaks to set out a checklist of data needed to: (1) quantify severity and transmissibility; (2) characterize heterogeneities in transmission and their determinants; and (3) assess the effectiveness of different interventions. We differentiate data needs into individual-level data (e.g. a detailed list of reported cases), exposure data (e.g. identifying where/how cases may have been infected) and population-level data (e.g. size/demographics of the population(s) affected and when/where interventions were implemented). A remarkable amount of individual-level and exposure data was collected during the West African Ebola epidemic, which allowed the assessment of (1) and (2). However, gaps in population-level data (particularly around which interventions were applied when and where) posed challenges to the assessment of (3). Here we highlight recurrent data issues, give practical suggestions for addressing these issues and discuss priorities for improvements in data collection in future outbreaks. This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.


title: Middle East respiratory syndrome coronavirus (MERS-CoV): Impact on Saudi Arabia, 2015

text: Middle East respiratory syndrome is the acute respiratory syndrome caused by betacoronavirus MERS-CoV. The first case of this disease was reported from Saudi Arabia in 2012. This virus is lethal and is a close relative of a severe acute respiratory syndrome (SARS), which is responsible for more than 3000 deaths in 2002–2003. According to Ministry of Health, Saudi Arabia. The number of new cases is 457 in 2015. Riyadh has the highest number of reports in comparison to the other cities. According to this report, males are more susceptible than female, especially after the age of 40. Because of the awareness and early diagnosis the incidence is falling gradually. The pre-existence of another disease like cancer or diabetic etc. boosts the infection. MERS is a zoonotic disease and human to human transmission is low. The MERS-CoV is a RNA virus with protein envelope. On the outer surface, virus has spike like glycoprotein which is responsible for the attachment and entrance inside host cells. There is no specific treatment for the MERS-CoV till now, but drugs are in pipeline which bind with the spike glycoprotein and inhibit its entrance host cells. MERS-CoV and SAR-CoV are from the same genus, so it was thought that the drugs which inhibit the growth of SARS-CoV can also inhibit the growth of MERS-CoV but those drugs are not completely inhibiting virus activity. Until we don’t have proper structure and the treatment of MERS-CoV, We should take precautions, especially the health care workers, Camel owners and Pilgrims during Hajj and Umrah, because they are at a higher risk of getting infected.


title: The profile of peripheral blood lymphocyte subsets and serum cytokines in children with 2019 novel coronavirus pneumonia

text: Abstract Objectives The study was aimed at investigating the characteristics of peripheral blood lymphocyte subsets and serum cytokines in children with 2019 novel coronavirus (2019-nCoV) pneumonia. Methods Children with 2019-nCoV pneumonia or with respiratory syncytial virus (RSV) pneumonia were included. Data including lymphocyte subsets and serum cytokines were collected and analyzed. Results : 56 patients were included in the study, 40 children with 2019-nCoV pneumonia and 16 children with RSV pneumonia. Compared with children with RSV pneumonia, patients with 2019-nCoV pneumonia had higher count of CD3+8+ lymphocyte, higher percentages of CD3+, CD3+8+ lymphocytes and a lower percentage of CD19+ lymphocyte. The serum IL-10 level was significantly higher in children with RSV pneumonia. One 2019-nCoV pneumonia child who was with an obvious increase of IL-10 developed severe pneumonia. Conclusions Immune response played a very important role in the development of 2019-nCoV pneumonia. The effective CD8+ T cell response might influence the severity of 2019-nCoV pneumonia. The adaptable change in IL-10 level might contribute to the relatively mild pneumonia symptoms in children with 2019-nCoV pneumonia and bacterial co-infection might be a risk factor of severe 2019-nCoV pneumonia.


title: Detection of HHV-6B in post-mortem central nervous system tissue of a post-bone marrow transplant recipient: a multi-virus array analysis

text: Abstract Background HHV-6 has been implicated in a number of neurological disorders. Recent evidence has suggested high incidence of HHV-6 infection in patients (46%) undergoing allogeneic bone marrow transplant (BMT). Objective To investigate whether HHV-6 plays a role in the development of fatal encephalopathy in an allogeneic post-BMT patient using an unbiased approach. Results Detection of HHV-6 viral DNA sequence and RNA expression were demonstrated in fresh frozen post-mortem autopsy material derived from the insular cortex using a multi-virus array platform. In addition, PCR analysis by real-time quantitative TaqMan demonstrated high viral burden in multiple brain regions tested. Sequencing analysis of PCR product confirmed the virus to be HHV-6 variant B. Conclusions Active infection as demonstrated by expression of viral RNA and high viral load in the CNS suggest a possible pathogenic role of HHV-6 in development neurologic complications post-BMT.


title: “The Most Dangerous Strain”

text: Socioeconomic inequities have direct implications in COVID presentation, severity of illness and prognosis. From practice of prophylactic measures to availability of personal protective equipment, from access to diagnostic tests to treatment resources, there are many facets and distinct disease processes of a virus that, among many things, serves to expose and highlight our global disparities.


title: Placebo: Its action and place in health research today* — Summary and conclusions

text: The material presented at this conference pointed to a new dimension in the prosecution of activities that seek to relieve people of disease. While the simple instrument of the placebo may show those interested in the efficacy of physiologically active chemicals the extent to which the chemical of interest is actually active, the surprising outcome of such studies is that the placebo per se is worthy of more general study. This, when taken further, points to the ways in which mind can influence the matter of the body. Of course, mind itself is an activity of matter, so we may retain the experimental approach that has told us about the world outside ourselves to examine the world that is inside our brains. New techniques and approaches to these once intractable problems are now in train. Where they will lead us we cannot predict, but as with the emergence of all new tools, we have to adopt those ethics that will carry us forward with the expectation that we will maximise benefits and minimise harms.


title: A Novel Bacterium-Like Particle Vaccine Displaying the MERS-CoV Receptor-Binding Domain Induces Specific Mucosal and Systemic Immune Responses in Mice

text: Middle East respiratory syndrome coronavirus (MERS-CoV), a new coronavirus that has been causing severe and fatal acute respiratory illnesses in humans since its outbreak in 2012, has raised public fear worldwide. The development of prophylactics and therapeutics is urgently needed to prevent and control MERS-CoV infections. In this study, a bacterium (Lactococcus lactis)-like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). The designs included different numbers of lysin motif (LysM) repeats in the PAs linked by linkers (RBD-linker-PA2 (RLP(2)), RBD-linker-PA3 (RLP(3)) and RBD-PA3 (RP(3))), and three LysM repeats and a linker in the fusion proteins increased the binding activity to the RBD. The specific immune responses were tested by intranasally immunizing mice with RLP(3)-GEM with or without the adjuvant GEL01. The results showed that GEL01-adjuvanted RLP(3)-GEM increased the systemic humoral, cellular and local mucosal immune responses in the mouse model, especially in the intestinal tract. The above results indicate that the MERS-CoV BLP product has the potential to be developed into a promising mucosal candidate vaccine to protect against MERS-CoV infections.


title: In the fight against the new coronavirus outbreak, we must also struggle with human bias

text: A compounding factor of the outbreak is the potential for the general public to misunderstand the facts and design conspiracy theories.


title: In silico disease model: from simple networks to complex diseases

text: In this chapter we consider in silico modeling of diseases starting from some simple to some complex (and mathematical) concepts. Examples and applications of in silico modeling for some important categories of diseases (such as for cancers, infectious diseases, and neuronal diseases) are also given.


Covid-19 Pandemic and Comments From Miami, Florida


title: Virtual screening and dynamics of potential inhibitors targeting RNA binding domain of nucleocapsid phosphoprotein from SARS-CoV-2

text: The emergence of the coronavirus disease-2019 pandemic has led to an outbreak in the world. The SARS-CoV-2 is seventh and latest in coronavirus family with unique exonucleases for repairing any mismatches in newly transcribed genetic material. Therefore, drugs with novel additional mechanisms are required to simultaneously target and eliminate the virus. Thus, a newly deciphered N protein is taken as a target that belongs to SARS-CoV-2. They play a vital role in RNA transcription, viral replication and new virion formation. This study used virtual screening, molecular modeling and docking of the 8987 ligands from Asinex and PubChem databases against this novel target protein. Three hotspot sites having DScore ≥1 (Site 1, Site 2 and Site 3) for ligand binding were selected. Subsequently, high throughput screening, standard precision and extra precision docking process and molecular dynamics concluded three best drugs from two libraries. Two antiviral moieties from Asinex databases (5817 and 6799) have docking scores of −10.29 and −10.156; along with their respective free binding energies (ΔG bind) of −51.96 and −64.36 on Site 3. The third drug, Zidovudine, is from PubChem database with docking scores of −9.75 with its binding free energies (ΔG bind) of −59.43 on Site 3. The RMSD and RMSF were calculated for all the three drugs through molecular dynamics simulation studies for 50 ns. Zidovudine shows a very stable interaction with fluctuation starting at 2.4 Å on 2 ns and remained stable at 3 Å from 13 to 50 ns. Thus, paving the way for further biological validation as a potential treatment. Communicated by Ramaswamy H. Sarma


Hypofractionation in COVID-19 Radiotherapy: A Mix of Evidence Based Medicine and of Opportunities


title: Can indoor sports centers be allowed to re-open during the COVID-19 pandemic based on a certificate of equivalence?

text: Within a time span of only a few months, the SARS-CoV-2 virus has managed to spread across the world. This virus can spread by close contact, which includes large droplet spray and inhalation of microscopic droplets, and by indirect contact via contaminated objects. While in most countries, supermarkets have remained open, due to the COVID-19 pandemic, authorities have ordered many other shops, restaurants, bars, music theaters and indoor sports centers to be closed. As part of COVID-19 (semi)lock-down exit strategies, many government authorities are now (May 2020) allowing a gradual re-opening, where sometimes indoor sport centers are last in line to be permitted to re-open. This technical note discusses the challenges in re-opening these facilities and the measures already suggested by some to tackle these challenges. It also elaborates three potential additional measures and based on these additional measures, it suggests the concept of a certificate of equivalence that could allow indoor sports centers with such a certificate to re-open more rapidly. It also attempts to stimulate increased preparedness of indoor sports centers for potential next waves of SARS-CoV-2 as well as future pandemics. It is concluded that fighting situations such as the COVID-19 pandemic and limiting economic damage requires increased collaboration and research by virologists, epidemiologists, microbiologists, aerosol scientists, building physicists, building services engineers and sports scientists.


title: The S proteins of human coronavirus NL63 and severe acute respiratory syndrome coronavirus bind overlapping regions of ACE2

text: The cellular receptor for human coronavirus NL63 (HCoV-NL63), a group I coronavirus, is angiotensin-converting enzyme2 (ACE2). ACE2 is also the receptor for the SARS coronavirus (SARS-CoV), a group II coronavirus. Here we describe the ability of HCoV-NL63 to utilize a number of ACE2 variants previously characterized as SARS-CoV receptors. Several ACE2 variants that reduced SARS-CoV S-protein association similarly reduced that of HCoV-NL63, whereas alteration of a number of solvent-exposed ACE2 residues did not interfere with binding by either S protein. One notable exception is ACE2 residue 354, at the boundary of the SARS-CoV binding site, whose alteration markedly inhibited utilization by the HCoV-NL63 but not SARS-CoV S proteins. In addition, the SARS-CoV S-protein receptor-binding domain inhibited entry mediated by the HCoV-NL63 S protein. These studies indicate that HCoV-NL63, like SARS-CoV, associates region of human ACE2 that includes a key loop formed by β-strands 4 and 5.


title: Non-invasive bioluminescence imaging of HCoV-OC43 infection and therapy in the central nervous system of live mice

text: Abstract Human coronaviruses (HCoVs) are important pathogens that cause upper respiratory tract infections and have neuroinvasive abilities; however, little is known about the dynamic infection process of CoVs in vivo, and there are currently no specific antiviral drugs to prevent or treat HCoV infection. Here, we verified the replication ability and pathogenicity of a reporter HCoV-OC43 strain expressing Renilla luciferase (Rluc; rOC43-ns2DelRluc) in mice with different genetic backgrounds (C57BL/6 and BALB/c). Additionally, we monitored the spatial and temporal progression of HCoV-OC43 through the central nervous system (CNS) of live BALB/c mice after intranasal or intracerebral inoculation with rOC43-ns2DelRluc. We found that rOC43-ns2DelRluc was fatal to suckling mice after intranasal inoculation, and that viral titers and Rluc expression were detected in the brains and spinal cords of mice infected with rOC43-ns2DelRluc. Moreover, viral replication was initially observed in the brain by non-invasive bioluminescence imaging before the infection spread to the spinal cord of BALB/c mice, consistent with its tropism in the CNS. Furthermore, the Rluc readout correlated with the HCoV replication ability and protein expression, which allowed quantification of antiviral activity in live mice. Additionally, we validated that chloroquine strongly inhibited rOC43-ns2DelRluc replication in vivo. These results provide new insights into the temporal and spatial dissemination of HCoV-OC43 in the CNS, and our methods provide an extremely sensitive platform for evaluating the efficacy of antiviral therapies to treat neuroinvasive HCoVs in live mice.


title: The intestinal microbiome in dogs and cats with diarrhoea as detected by a faecal polymerase chain reaction‐based panel in Perth, Western Australia

text: This study reports the prevalence of potential faecal pathogens in the microbiome detected in a cohort of cats and dogs with diarrhoea in Perth, Western Australia. Records from a commercial diagnostic laboratory using faecal PCR testing between July 2014 and August 2015 were reviewed.Of 289 feline faecal samples reviewed, Salmonella spp. (1.7%), Campylobacter spp. (47.6%), Clostridium perfringens (81.3%), Giardia spp. (11.1%), Toxoplasma gondii (1.2%), Tritrichomonas foetus (4.8%), panleukopenia virus (6.5%) and coronavirus (39.5%) were detected. In dogs, Salmonella spp. (5.4%), Campylobacter spp. (36.3%), C. perfringens (85.4%), Giardia spp. (6.2%), parvovirus (9.4%), coronavirus (4.7%) and distemper virus (1.5%) were detected.


Dysgeusia in COVID-19: possible mechanisms and implications


A Brewing Storm: The Neuropsychological Sequelae of Hyperinflammation due to COVID-19


title: MERS coronavirus: diagnostics, epidemiology and transmission

text: The first known cases of Middle East respiratory syndrome (MERS), associated with infection by a novel coronavirus (CoV), occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia (KSA). Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels (DC). MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. In humans, MERS is mostly known as a lower respiratory tract (LRT) disease involving fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20 % to 40 % of those infected. However, MERS-CoV has also been detected in mild and influenza-like illnesses and in those with no signs or symptoms. Older males most obviously suffer severe disease and MERS patients often have comorbidities. Compared to severe acute respiratory syndrome (SARS), another sometimes- fatal zoonotic coronavirus disease that has since disappeared, MERS progresses more rapidly to respiratory failure and acute kidney injury (it also has an affinity for growth in kidney cells under laboratory conditions), is more frequently reported in patients with underlying disease and is more often fatal. Most human cases of MERS have been linked to lapses in infection prevention and control (IPC) in healthcare settings, with approximately 20 % of all virus detections reported among healthcare workers (HCWs) and higher exposures in those with occupations that bring them into close contact with camels. Sero-surveys have found widespread evidence of past infection in adult camels and limited past exposure among humans. Sensitive, validated reverse transcriptase real-time polymerase chain reaction (RT-rtPCR)-based diagnostics have been available almost from the start of the emergence of MERS. While the basic virology of MERS-CoV has advanced over the past three years, understanding of the interplay between camel, environment, and human remains limited. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0439-5) contains supplementary material, which is available to authorized users.


title: Cellular Proteins Associated with the Interior and Exterior of Vesicular Stomatitis Virus Virions

text: Virus particles (virions) often contain not only virus-encoded but also host-encoded proteins. Some of these host proteins are enclosed within the virion structure, while others, in the case of enveloped viruses, are embedded in the host-derived membrane. While many of these host protein incorporations are likely accidental, some may play a role in virus infectivity, replication and/or immunoreactivity in the next host. Host protein incorporations may be especially important in therapeutic applications where large numbers of virus particles are administered. Vesicular stomatitis virus (VSV) is the prototypic rhabdovirus and a candidate vaccine, gene therapy and oncolytic vector. Using mass spectrometry, we previously examined cell type dependent host protein content of VSV virions using intact (“whole”) virions purified from three cell lines originating from different species. Here we aimed to determine the localization of host proteins within the VSV virions by analyzing: i) whole VSV virions; and ii) whole VSV virions treated with Proteinase K to remove all proteins outside the viral envelope. A total of 257 proteins were identified, with 181 identified in whole virions and 183 identified in Proteinase K treated virions. Most of these proteins have not been previously shown to be associated with VSV. Functional enrichment analysis indicated the most overrepresented categories were proteins associated with vesicles, vesicle-mediated transport and protein localization. Using western blotting, the presence of several host proteins, including some not previously shown in association with VSV (such as Yes1, Prl1 and Ddx3y), was confirmed and their relative quantities in various virion fractions determined. Our study provides a valuable inventory of virion-associated host proteins for further investigation of their roles in the replication cycle, pathogenesis and immunoreactivity of VSV.


title: Find the right sample: A study on the versatility of saliva and urine samples for the diagnosis of emerging viruses

text: BACKGROUND: The emergence of different viral infections during the last decades like dengue, West Nile, SARS, chikungunya, MERS-CoV, Ebola, Zika and Yellow Fever raised some questions on quickness and reliability of laboratory diagnostic tests for verification of suspected cases. Since sampling of blood requires medically trained personal and comprises some risks for the patient as well as for the health care personal, the sampling by non-invasive methods (e.g. saliva and/ or urine) might be a very valuable alternative for investigating a diseased patient. MAIN BODY: To analyse the usefulness of alternative noninvasive samples for the diagnosis of emerging infectious viral diseases, a literature search was performed on PubMed for alternative sampling for these viral infections. In total, 711 papers of potential relevance were found, of which we have included 128 in this review. CONCLUSIONS: Considering the experience using non-invasive sampling for the diagnostic of emerging viral diseases, it seems important to perform an investigation using alternative samples for routine diagnostics. Moreover, during an outbreak situation, evaluation of appropriate sampling and further processing for laboratory analysis on various diagnostic platforms are very crucial. This will help to achieve optimal diagnostic results for a good and reliable case identification. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3611-x) contains supplementary material, which is available to authorized users.


One lung ventilation during COVID-19 pandemic


title: Diagnostic Accuracy of FebriDx: A Rapid Test to Detect Immune Responses to Viral and Bacterial Upper Respiratory Infections

text: C-reactive protein (CRP) and myxovirus resistance protein A (MxA) are associated with bacterial and viral infections, respectively. We conducted a prospective, multicenter, cross-sectional study of adults and children with febrile upper respiratory tract infections (URIs) to evaluate the diagnostic accuracy of a rapid CRP/MxA immunoassay to identify clinically significant bacterial infection with host response and acute pathogenic viral infection. The reference standard for classifying URI etiology was an algorithm that included throat bacterial culture, upper respiratory PCR for viral and atypical pathogens, procalcitonin, white blood cell count, and bandemia. The algorithm also allowed for physician override. Among 205 patients, 25 (12.2%) were classified as bacterial, 53 (25.9%) as viral, and 127 (62.0%) negative by the reference standard. For bacterial detection, agreement between FebriDx and the reference standard was 91.7%, with FebriDx having a sensitivity of 80% (95% CI: 59–93%), specificity of 93% (89–97%), positive predictive value (PPV) of 63% (45–79%), and a negative predictive value (NPV) of 97% (94–99%). For viral detection, agreement was 84%, with a sensitivity of 87% (75–95%), specificity of 83% (76–89%), PPV of 64% (63–75%), and NPV of 95% (90–98%). FebriDx may help to identify clinically significant immune responses associated with bacterial and viral URIs that are more likely to require clinical management or therapeutic intervention, and has potential to assist with antibiotic stewardship.


title: 25 Host Defenses to Viruses

text: Abstract Virus infections continue to pose a substantial threat to human health. Unravelling the intricacies of immune defenses against viruses should lead to improved control of infections through the design of new vaccines and therapies. Our understanding of the fundamental cellular and molecular mechanisms involved in the immune systems response to virus infection has improved substantially in recent years. This wealth of new information and the promise of new insight from systems biology approaches continue to drive research in this field. Such knowledge has revealed why viruses sometimes induce immune dysfunction or trigger disastrous pathology and has paved the way for new therapies being tested against chronic and emerging infections. In this chapter, we briefly summarize the general concepts in immunity to virus infections and highlight some of the key challenges remaining for the future. Virus infections continue to pose a substantial threat to human health.


title: Quantitative and qualitative flow cytometric analysis of nanosized cell-derived membrane vesicles

text: Abstract Nanosized cell-derived membrane vesicles are increasingly recognized as therapeutic vehicles and high-potential biomarkers for several diseases. Currently available methods allow bulk analysis of vesicles but are not suited for accurate quantification and fail to reveal phenotypic heterogeneity in membrane vesicle populations. For such analyses, single vesicle-based, multiparameter, high-throughput methods are needed. We developed a fluorescence-based, high-resolution flow cytometric method for quantitative and qualitative analysis of nanosized membrane vesicles. Proof of principle was obtained by single-particle analysis of virions and liposomes. Further validation was obtained by quantification of cell-derived nanosized membrane vesicles from cell cultures and body fluids. An important aspect was that the technology was extended to detect specific proteins on individual vesicles. This allowed identification of exosome subsets and phenotyping of individual exosomes produced by dendritic cells (DCs) undergoing different modes of activation. The described technology allows quantitative, multiparameter, and high-throughput analysis of a wide variety of nanosized particles and has broad applications. From the Clinical Editor The authors developed a fluorescence-based, high-resolution flow cytometric method for quantitative and qualitative analysis of nanosized cell-derived membrane vesicles that are increasingly recognized both as therapeutic vehicles and high-potential biomarkers for several diseases. A high throughput, easily available, and sensitive detection method such as the one discussed here is a critically important prerequisite for further refinements of this technology.


title: Less expression of CD4(+) and CD8(+) T cells might reflect the severity of infection and predict worse prognosis in patients with COVID-19: evidence from a pooled analysis

text: This study mainly focused on the very serious COVID-19 epidemic situation at present and provided a new insight for the treatment and monitor of patients with COVID-19. Through this meta-analysis, we could draw a conclusion that less expression of blood CD4(+) and CD8(+) T cells count might reflect the severity of infection and often accompanied by a poor prognosis. Hence, we inferred blood CD4+ and CD8+ T cells count could be a promising biomarker for disease assessment and monitor of patients with COVID-19.


title: Susceptibility of human and rat neural cell lines to infection by SARS-coronavirus

text: Abstract Pathological characterization of autopsied tissues from patients with SARS revealed severe damage in restricted tissues, such as lung, with no apparent cell damage in other tissues, such as intestine and brain. Here, we examined the susceptibility of neural cell lines of human (OL) and rat (C6) origins to SARS-associated coronavirus. Both of the neural cell lines showed no apparent cytopathic effects (CPE) by infection but produced virus with infectivity of 102–5 per ml, in sharp contrast to the production by infected Vero E6 cells of >109 per ml that showed a lytic infection with characteristic rounding CPE. Interestingly, the infection of intestinal cell line CaCo-2 also induced no apparent CPE, with production of the virus at a slightly lower level as that of the Vero E6 cell culture. Notably, the cellular receptor for the virus, angiotensin-converting enzyme 2 was expressed at similar levels on Vero E6 and CaCo-2 cells, but at undetectable levels on OL and C6 cells.


SIMILARITIES OF IMMUNE REACTIONS BETWEEN HEPATITIS C AND SEVERE ACUTE RESPIRATORY SYNDROME‐ASSOCIATED CORONAVIRUS INFECTIONS


title: Challenges, Learning Curve, and Safety of Endoscopic Endonasal Surgery of Sellar-Suprasellar Lesions in a Community Hospital

text: Background and Objective Endoscopic endonasal surgery (EES) for the management of sellar, suprasellar, and anterior skull base lesions is gaining popularity. Our aim was to analyze and present the clinical outcomes of EES for the management of these lesions in a community hospital setting. Methods We retrospectively reviewed the charts of 56 patients with sellar, suprasellar, and anterior skull base lesions who underwent EES between 2010 and 2018. Results There was male predominance (53.6%) with a mean age of 54.9 ± 13.7 years. Lesions were 45 pituitary adenomas, 5 meningiomas, 3 metastatic, 1 craniopharyngioma, 1 Rathke cyst, and 1 mucocele. Gross total excision was achieved in 57.1%, subtotal excision occurred in 37.5%, and decompression and biopsy were achieved in 5.4% patients. Postoperative vision normalized or improved in 27 patients (86.1%) and was stable in 4 patients (13.9%). Recovery of a preexisting hormonal deficit occurred in 13 (23.2%) patients, and a new hormonal deficit occurred in 9 patients (16.1%). The mean hospital stay was 6.1 ± 4.9 days. Postoperative complications included cerebrospinal fluid leak in 8 patients (14.3%). Four patients (7.1%) had meningitis. Diabetes insipidus was present in 19 patients (33.9%), and postoperative intracranial hematoma requiring evacuation was necessary in 2 patients (3.6%). The mean follow-up duration was 47.5 ± 25.8 months. Lesion progression or recurrence requiring redo surgery occurred in 5 patients (8.9%). Regarding the learning curve, the postoperative cerebrospinal fluid leak, meningitis, new hormonal deficits, and diabetes insipidus decreased in the second half of the patients. Conclusions EES provides an effective and safe surgical option with low morbidity and mortality for the treatment of sellar, suprasellar, and anterior skull base lesions in a community hospital setting.


title: The association between laryngopharyngeal reflux and COVID‐19 is still not demonstrated

text: We read with interest the paper entitled «The impact of laryngopharyngeal reflux disease on 95 hospitalized patients with COVID-19 in Wuhan, China: A retrospective study.»1 The authors retrospectively reported that hospitalized patients with laryngopharyngeal reflux (LPR) had poorer clinical outcomes compared with those without LPR according to Reflux Symptom Index (RSI). The LPR diagnosis was based on RSI>13, which is the threshold used by Belafsky et al. to suspect LPR.2 This article is protected by copyright. All rights reserved.


title: COVID-19 response in northwest Syria: innovation and community engagement in a complex conflict

text: Despite lacking capacity and resources, the health system in the northwest Syria is using innovative approaches for the containment of COVID-19. Lessons drawn from previous outbreaks in the region, such as the polio outbreak in 2013 and the annual seasonal influenza, have enabled the Early Warning and Response Network, a surveillance system to develop mechanisms of predicting risk and strengthening surveillance for the new pandemic. Social media tools such as WhatsApp are effectively collecting health information and communicating health messaging about COVID-19. Community engagement has also been scaled up, mobilizing local resources and encouraging thousands of volunteers to join the ‘Volunteers against Corona’ campaign. Bottom-up local governance technical entities, such as Idleb Health Directorate and the White Helmets, have played key leadership role in the response. These efforts need to be scaled up to prevent the transmission of COVID-19 in a region chronically affected by a complex armed conflict.


title: Construction and characterization of recombinant human adenovirus type 5 expressing foot-and-mouth disease virus capsid proteins of Indian vaccine strain, O/IND/R2/75

text: AIM: Generation of recombinant human adenovirus type 5 expressing foot-and-mouth disease virus (FMDV) capsid protein genes along with full-length 2B, 3B and 3C(pro) and its characterization. MATERIALS AND METHODS: FMD viral RNA isolation, cDNA synthesis, and polymerase chain reaction were performed to synthesize expression cassettes (P1-2AB3BC(wt) and P1-2AB3BC(m)) followed by cloning in pShuttle-CMV vector. Chemically competent BJ5183-AD-1 cells were transformed with the recombinant pShuttle-CMV to produce recombinant adenoviral plasmids. HEK-293 cells were transfected with the recombinant adenoviral plasmids to generate recombinant adenoviruses (hAd5/P1-2AB3BC(wt) and hAd5/P1-2AB3BC(m)). Expression of the target proteins was analyzed by sandwich ELISA and indirect immunofluorescence assay. The recombinant adenoviruses were purified and concentrated by CsCl density gradient ultracentrifugation. Growth kinetics and thermostability of the recombinant adenoviruses were compared with that of non-recombinant replication-defective adenovirus (dAd5). RESULTS: The recombinant adenoviruses containing capsid protein genes of the FMDV O/IND/R2/75 were generated and amplified in HEK-293 cells. The titer of the recombinant adenoviruses was approximately 10(8), 10(9.5) and 10(11) TCID(50)/ml in supernatant media, cell lysate and CsCl purified preparation, respectively. Expression of the FMDV capsid protein was detectable in sandwich ELISA and confirmed by immunofluorescence assay. Growth kinetics of the recombinant adenoviruses did not reveal a significant difference when compared with that of dAd5. A decrement of up to 10-fold at 4°C and 21-fold at 37°C was recorded in the virus titers during 60 h incubation period and found to be statistically significant (p<0.01). CONCLUSION: Recombinant adenoviruses expressing capsid proteins of the FMDV O/IND/R2/75 were constructed and produced in high titers. In vitro expression of the target proteins in the adenovirus vector system was detected by sandwich ELISA and immunofluorescence assay.


Managing ophthalmic practices in a referral emergency COVID‐19 hospital in north‐east Italy


title: 2,6-Bis-arylmethyloxy-5-hydroxychromones with antiviral activity against both hepatitis C virus (HCV) and SARS-associated coronavirus (SCV)

text: In this study, as a bioisosteric alternative scaffold of the antiviral aryl diketoacids (ADKs), we used 5-hydroxychromone on which two arylmethyloxy substituents were installed. The 5-hydroxychromones (5b–5g) thus prepared showed anti-HCV activity and, depending on the aromatic substituents on the 2-arylmethyloxy moiety, some of the derivatives (5b–5f) were also active against SCV. In addition, unlike the ADKs which showed selective inhibition against the helicase activity of the SCV NTPase/helicase, the 5-hydroxychromones (5b–5f) were active against both NTPase and helicase activities of the target enzyme. Among those, 3-iodobenzyloxy-substituted derivative 5e showed the most potent activity against HCV (EC(50) = 4 μM) as well as SCV (IC(50) = 4 μM for ATPase activity, 11 μM for helicase activity) and this might be used as a platform structure for future development of the multi-target or broad-spectrum antivirals.


title: Public Health Crisis Preparedness and Response in Korea

text: Since the 2006 Pandemic Influenza Preparedness and Response Plan according to the World Health Organization’s recommendation, the Republic of Korea has prepared and periodically evaluated the plan to respond to various public health crises including pandemic influenza. Korea has stockpiled 13,000,000 doses of antiviral drugs covering 26% of the Korean population and runs 519 isolated beds in 16 medical institutions. The division of public health crisis response in Korea Centers for Disease Control and Prevention are in charge of responding to public health crises caused by emerging infectious diseases including severe acute respiratory syndrome, avian influenza human infection, and pandemic influenza. Its job description includes preparing for emerging infectious diseases, securing medical resources during a crisis, activating the emergency response during the crisis, and fortification of capabilities of public health personnel. It could evolve into a comprehensive national agency to deal with public health crisis based on the experience of previous national emerging infectious diseases.


“Pandemic fear” and COVID-19: mental health burden and strategies


title: Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy

text: Abstract Background Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19. Methods We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020–10.04.2020). The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI). Secondary outcome was overt disseminated intravascular coagulation (DIC). Results We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]). Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward. Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%–11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward). Half of the thromboembolic events were diagnosed within 24 h of hospital admission. Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%). Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA). The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively. Overt DIC was present in 8 (2.2%) patients. Conclusions The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.


title: Plasma therapy against infectious pathogens, as of yesterday, today and tomorrow

text: Abstract Plasma therapy consists in bringing to a patient in need – in general suffering a severe, resistant to current therapy, and even lethal infection – plasma or specific, fractioned, antibodies, along with other immunoglobulins and possibly healing factors that can be obtained from immunized blood donors; donors (voluntary and benevolent) can be either actively immunized individuals or convalescent persons. Plasma therapy has been used since the Spanish flu in 1917–1918, and regularly then when viral epidemics threatened vulnerable populations, the last reported occurrence being the 2013–2015 Ebola virus outbreak in West Africa. The precise action mechanism of plasma therapy is not fully delineated as it may function beyond purified, neutralizing antibodies.


title: COVID-19 and Individual Genetic Susceptibility/Receptivity: Role of ACE1/ACE2 Genes, Immunity, Inflammation and Coagulation. Might the Double X-Chromosome in Females Be Protective against SARS-CoV-2 Compared to the Single X-Chromosome in Males?

text: In December 2019, a novel severe acute respiratory syndrome (SARS) from a new coronavirus (SARS-CoV-2) was recognized in the city of Wuhan, China. Rapidly, it became an epidemic in China and has now spread throughout the world reaching pandemic proportions. High mortality rates characterize SARS-CoV-2 disease (COVID-19), which mainly affects the elderly, causing unrestrained cytokines-storm and subsequent pulmonary shutdown, also suspected micro thromboembolism events. At the present time, no specific and dedicated treatments, nor approved vaccines, are available, though very promising data come from the use of anti-inflammatory, anti-malaria, and anti-coagulant drugs. In addition, it seems that males are more susceptible to SARS-CoV-2 than females, with males 65% more likely to die from the infection than females. Data from the World Health Organization (WHO) and Chinese scientists show that of all cases about 1.7% of women who contract the virus will die compared with 2.8% of men, and data from Hong Kong hospitals state that 32% of male and 15% of female COVID-19 patients required intensive care or died. On the other hand, the long-term fallout of coronavirus may be worse for women than for men due to social and psychosocial reasons. Regardless of sex- or gender-biased data obtained from WHO and those gathered from sometimes controversial scientific journals, some central points should be considered. Firstly, SARS-CoV-2 has a strong interaction with the human ACE2 receptor, which plays an essential role in cell entry together with transmembrane serine protease 2 (TMPRSS2); it is interesting to note that the ACE2 gene lays on the X-chromosome, thus allowing females to be potentially heterozygous and differently assorted compared to men who are definitely hemizygous. Secondly, the higher ACE2 expression rate in females, though controversial, might ascribe them the worst prognosis, in contrast with worldwide epidemiological data. Finally, several genes involved in inflammation are located on the X-chromosome, which also contains high number of immune-related genes responsible for innate and adaptive immune responses to infection. Other genes, out from the RAS-pathway, might directly or indirectly impact on the ACE1/ACE2 balance by influencing its main actors (e.g., ABO locus, SRY, SOX3, ADAM17). Unexpectedly, the higher levels of ACE2 or ACE1/ACE2 rebalancing might improve the outcome of COVID-19 in both sexes by reducing inflammation, thrombosis, and death. Moreover, X-heterozygous females might also activate a mosaic advantage and show more pronounced sex-related differences resulting in a sex dimorphism, further favoring them in counteracting the progression of the SARS-CoV-2 infection.


title: Occurrence of SARS‐CoV‐2 during mycophenolate mofetil treatment for pemphigus

text: we read with great interest the article entitled “Should SARS‐CoV‐2 influence immunosuppressive therapy for autoimmune blistering diseases?” published by Di Altobrando A. et al. in the JEADV. This is the first report of COronaVIrus DIsease 2019 (COVID‐19) in a patient affected by autoimmune blistering disease (ABD) during immunosuppressive treatment (i.e. azathioprine). The authors conclude that it is crucial to learn of more cases of ABD patients under immunosuppressive treatment who have developed COVID‐19, in order to better quantify the risk of infection under immunosuppressive therapy.


COVID-19 and Individuals with Mental Illness in Psychiatric Facilities


title: Molecular Diagnostics for Detection of Bacterial and Viral Pathogens in Community-Acquired Pneumonia

text: Traditional microbiological methods for detection of respiratory tract pathogens can be slow, are often not sensitive, may not distinguish infection from colonization, and are influenced by previous antibiotic therapy. Molecular diagnostic tests for common and atypical causative pathogens of community-acquired pneumonia have the potential to dramatically increase the diagnostic yield and decrease the time required to render results. Unfortunately, these tests often lack standardization and are not widely available. Consideration should be given to the development and evaluation of companion molecular diagnostic tests for detection of respiratory pathogens in future clinical trials of antimicrobials intended to treat community-acquired pneumonia.


Keep “time is brain,” even in the crisis of COVID-19


title: Detection of hepatitis C virus in the nasal secretions of an intranasal drug-user

text: BACKGROUND: One controversial source of infection for hepatitis C virus (HCV) involves the sharing of contaminated implements, such as straws or spoons, used to nasally inhale cocaine and other powdered drugs. An essential precondition for this mode of transmission is the presence of HCV in the nasal secretions of intranasal drug users. METHODS: Blood and nasal secretion samples were collected from five plasma-positive chronic intranasal drug users and tested for HCV RNA using RT-PCR. RESULTS: HCV was detected in all five blood samples and in the nasal secretions of the subject with the highest serum viral load. CONCLUSIONS: This study is the first to demonstrate the presence of HCV in nasal secretions. This finding has implications for potential transmission of HCV through contact with contaminated nasal secretions.


title: CT manifestations of the coronavirus disease 2019 of imported infection versus second-generation infection in patients outside the original district (Wuhan, China) of this disease: An observational study

text: To explore the discrepancy in computed tomography (CT) manifestations of the coronavirus disease 2019 (COVID-19) in patients outside the original district (Wuhan, China) between cases with imported infection and second-generation infection, 22 patients with COVID-19 from 2 hospitals in Nanchong, China, 938 km away from the original district (Wuhan, China) of this disease were enrolled. All patients underwent initial and follow-up CT after admission during the treatment, and were divided into 2 groups. Group A and B were composed of 15 patients with a history of exposure to the original district (Wuhan, China) in short-term (i.e., imported infection), and 7 with a close contact with the patients with confirmed COVID-19 or with the healthy individuals from the original district (i.e., second-generation infection), respectively. Initial CT features including extent score and density score between groups were statistically compared. We found that all patients in group A and 3 of 7 patients in group B had abnormal CT findings while 4 of 7 patients in group B had not. Patients with abnormal CT findings were more frequent in group A than in group B (P < .05). On initial CT, pure ground glass opacity (GGO), and GGO with consolidation and/or other abnormalities were found in 20% (3/15) and 80% (12/15) patients in group A, respectively, while 1 (14.3%), 2 (28.6%), and 4 (57.1%) had pure GGOs, GGO with focal consolidation, and normal CT appearances in Group B, respectively. Patients with extent and density scores of ≥5 were more frequent in group A than in group B (all P-values < .01). Additionally, 3 of 4 (75%) patients with normal initial CT findings had focal pure GGO lesions on follow-up. In conclusion, COVID-19 in patients with a history of exposure to the original district can be severer than with the second-generation infection on CT.


title: Quasispecies and its impact on viral hepatitis

text: Abstract Quasispecies dynamics mediates adaptability of RNA viruses through a number of mechanisms reviewed in the present article, with emphasis on the medical implications for the hepatitis viruses. We discuss replicative and non-replicative molecular mechanisms of genome variation, modulating effects of mutant spectra, and several modes of viral evolution that can affect viral pathogenesis. Relevant evolutionary events include the generation of minority virus variants with altered functional properties, and alterations of mutant spectrum complexity that can affect disease progression or response to treatment. The widespread occurrence of resistance to antiviral drugs encourages new strategies to control hepatic viral disease such as combination therapies and lethal mutagenesis. In particular, ribavirin may be exerting in some cases its antiviral activity with participation of its mutagenic action. Despite many unanswered questions, here we document that quasispecies dynamics has provided an interpretation of the adaptability of the hepatitis viruses, with features conceptually similar to those observed with other RNA viruses, a reflection of the common underlying Darwinian principles.


title: Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection

text: The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no approved prophylactic and therapeutic interventions are currently available. The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4). Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S). Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice. In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA). Passive transfer of immune sera to naïve hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge. Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein. These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans.


title: Chapter 28 Experimental Infections of the Common Marmoset (Callithrix jacchus)

text: Abstract Interest in the use of marmosets for experimental infectious disease has dramatically increased in the last decade. These animals are native to the Atlantic coastal forests in northeastern Brazil. The majority of experimental animals come from the National Primate Research Centers and other breeding facilities. They are advantageous because of their relative small size, weighting 350–400g as adults, their life span is compact compared with other nonhuman primate (NHP), and they produce offspring by 3years of age. They are free of Herpes B virus and, it is believed, to date, other dangerous human pathogens (Abbot et al., 2003) [1]. We describe here the experimental infections of marmosets to human pathogens. While it is always interesting to compare various NHPs with each other, the importance of an animal model is always in comparing its similarities to human infections.


title: COVID-19 STEMI 2020: It’s Not What You Know, It’s How You Think

text: [Figure: see text]


title: Ion channel activity of the CSFV p7 viroporin in surrogates of the ER lipid bilayer

text: [Figure: see text]


title: Single dose of an adenovirus vectored mouse interferon-α protects mice from lethal EV71 challenge

text: Abstract Enterovirus 71 (EV71) causes hand-foot-and-mouth diseases as well as neurological complications in young children. Interferon (IFN) can inhibit the replication of many viruses with low cytotoxic effects. Previously, an adenovirus vectored mouse interferon-α (DEF201), subtype 5, was generated by Wu et al, 2007. In this study, the antiviral effects of DEF201 against EV71 were evaluated in a murine model. 6–day-old BALB/c mice were administered a single dose of DEF201 before or after infection with lethal dose of EV71. The survival rate, clinical symptoms, tissue viral loads and histology pathogenesis were evaluated. IFN gene expression following a single dose of DEF201 maintained high concentrations of 100–9000 pg/mL for more than 7 days in mice serum. Pre-infection administration of a single dose of 106 PFU of DEF201 offered full protection of the mice against EV71 infection compared with the empty Ad5 vector control. In addition, virus load in DEF201-treated mice muscle tissue was significantly decreased as compared with empty vector control. Histopathology analysis revealed that DEF201 significantly prevented the development of severe tissue damage with reduction of viral antigen in the murine muscle tissue. Post-infection treatment at 6 h offered full protection and partial protection at 12 h, indicating that DEF201 could be used as an anti-EV71 therapeutic agent in early stage of EV71 infection. In addition, our study showed that DEF201 enhanced the neutralization ability of serum in EV71-vaccinated mice, implying that DEF201 could promote the production of specific anti-EV71 antibodies. In conclusion, single dose of DEF201 is highly efficacious as a prophylactic agent against EV71 infection in vivo.


title: Validating a Widely Implemented Deterioration Index Model Among Hospitalized COVID-19 Patients

text: Introduction: The coronavirus disease 2019 (COVID-19) pandemic is straining the capacity of U.S. healthcare systems. Accurately identifying subgroups of hospitalized COVID-19 patients at high- and low-risk for complications would assist in directing resources. Objective: To validate the Epic Deterioration Index (EDI), a predictive model implemented in over 100 U.S. hospitals that has been recently promoted for use in COVID-19 patients. Methods: We studied adult patients admitted with COVID-19 to non-ICU level care at a large academic medical center from March 9 through April 7, 2020. We used the EDI, calculated at 15-minute intervals, to predict a composite adverse outcome of ICU-level care, mechanical ventilation, or death during the hospitalization. In a subset of patients hospitalized for at least 48 hours, we also evaluated the ability of the EDI (range 0-100) to identify patients at low risk of experiencing this composite outcome during their remaining hospitalization. We evaluated model discrimination and calibration using both raw EDI scores and their slopes. Results: Among 174 COVID-19 patients meeting inclusion criteria, 61 (35%) experienced the composite outcome. Area under the receiver-operating-characteristic curve (AUC) of the EDI was 0.76 (95% CI 0.68-0.84). Patients who met or exceeded an EDI of 64.8 made up 17% of the study cohort and had an 80% probability of experiencing the outcome during their hospitalization with a median lead time of 28 hours from when the threshold was first exceeded to the outcome. Employing the EDI slope lowered the AUCs to 0.68 (95% CI 0.60-0.77) and 0.67 (95% CI 0.59-0.75) for slopes calculated over 4 and 8 hours, respectively. In a subset of 109 patients hospitalized for at least 48 hours and who had not experienced the composite outcome, 14 (13%) patients who never exceeded an EDI of 37.9 had a 93% probability of not experiencing the outcome throughout the rest of their hospitalization, suggesting low risk. Conclusion: In this validation study, we found the EDI identifies small subsets of high- and low-risk patients with fair discrimination. These findings highlight the need for hospitals to carefully evaluate prediction models before widespread operational use among COVID-19 patients.


title: The coming plague

text: A killer pandemic is now more likely than ever. Where will it come from and how can we beat it, asks Debora MacKenzie


title: Temporal trends in the incidence and demographics of cancers, communicable diseases, and non-communicable diseases in Saudi Arabia over the last decade

text: OBJECTIVES: To describe the trends in the incidence rates of 5 most common cancers, communicable diseases, and non-communicable diseases in Saudi Arabia over the last decade. METHODS: The incidence rates of cancers (2001-2014), communicable diseases (2003-2016), and non-communicable diseases (1990-2017) were retrieved, classified, and analyzed retrospectively during November 2017, based on data available with the Ministry of Health and were analyzed at the Imam Abdulrahman Bin Faisal University in Dammam, Kingdom of Saudi Arabia. RESULTS: Age-standardized incidence rate (ASR) (per 100,000 population) of breast cancer among women increased dramatically from 11.8 in 2001 to 22.7 in 2014, indicating a 92.4% increase over the decade. Colorectal cancer incidence was the highest among men, and its ASR per 100,000 population increased from 5.0 to 10.6 in men and from 5.0 to 8.2 in women. Among communicable diseases, incidences of hepatitis B, measles, chickenpox, and brucellosis decreased while dengue fever increased. An alarming increase was observed in the incidence rate of non-communicable diseases namely, obesity, diabetes, and hypertension. CONCLUSION: The incidence rate of non-communicable diseases increased over the decade and was associated with increased mortality and disability, reduced quality of life, and increased health-care costs, indicating an urgent need to establish prevention and control programs. The rising trend in the incidence of cancers may also become a health care issue in Saudi Arabia in the coming years.


title: Integrated urban services: Experience from four cities on different continents

text: Abstract Rapid urbanization combined with climate change necessitates new types of urban services that make best use of science and technology. The Integrated Urban Hydro-Meteorological, Climate and Environmental Services and systems are a new initiative from the World Meteorological Organization (WMO) that seeks to provide science-based integrated urban services supporting safe, healthy and resilient cities. Various cities have already started development and implementation of such Integrated Urban Services and successfully test and use them following specific requirements of local stakeholders. This paper demonstrates the novel concept and approach of Integrated Urban Hydro-Meteorological, Climate and Environmental Services (IUS) from a set of four case study cities: Hong Kong, Toronto, Mexico City and Paris, that use different IUS configurations with good existing practice. These cities represent a range of countries, climates and geophysical settings. The aggregate main joint similarities of the IUS in these cities and synergy of the cities' experience, achievements and research findings are presented, as well as identification of existing gaps in knowledge and further research needs. A list of potential criteria for identifying and classifying IUS demonstration cities is proposed. It will aid future, more detailed analysis of the IUS experience, and selection of additional demonstration cities.


title: Charged PVDF multilayer nanofiber filter in filtering simulated airborne novel coronavirus (COVID-19) using ambient nano-aerosols

text: Abstract The novel coronavirus (COVID-19), average size 100 nm, can be aerosolized by cough, sneeze, speech and breath of infected persons. The airborne carrier for the COVID-19 can be tiny droplets and particulates from infected person, fine suspended mists (humidity) in air, or ambient aerosols in air. To-date, unfortunately there are no test standards for nano-aerosols (≤100 nm). A goal in our study is to develop air filters (e.g. respirator, facemask, ventilator, medical breathing filter/system) with 90% capture on 100-nm airborne COVID-19 with pressure drop of less than 30 Pa (3.1 mm water). There are two challenges. First, this airborne bio-nanoaerosol (combined virus and carrier) is amorphous unlike cubic NaCl crystals. Second, unlike standard laboratory tests on NaCl and test oil (DOP) droplets, these polydispersed aerosols all challenge the filter simultaneously and they are of different sizes and can interact among themselves complicating the filtration process. For the first time, we have studied these two effects using ambient aerosols (simulating the bio-nanoaerosols of coronavirus plus carrier of different shapes and sizes) to challenge electrostatically charged multilayer/multimodule nanofiber filters. This problem is fundamentally complicated due to mechanical and electrostatic interactions among aerosols of different sizes with induced charges of different magnitudes. The test filters were arranged in 2, 4, and 6 multiple-modules stack-up with each module having 0.765 g/m2 of charged PVDF nanofibers (mean diameter 525 ± 191 nm). This configuration minimized electrical interference among neighboring charged nanofibers and reduced flow resistance in the filter. For ambient aerosol size>80 nm (applicable to the smallest COVID-19), the electrostatic effect contributes 100–180% more efficiency to the existing mechanical efficiency (due to diffusion and interception) depending on the number of modules in the filter. By stacking-up modules to increase fiber basis weight in the filter, a 6-layer charged nanofiber filter achieved 88%, 88% and 96% filtration efficiency for, respectively, 55-nm, 100-nm and 300-nm ambient aerosol. This is very close to attaining our set goal of 90%-efficiency on the 100-nm ambient aerosol. The pressure drop for the 6-layer nanofiber filter was only 26 Pa (2.65 mm water column) which was below our limit of 30 Pa (3.1 mm water). For the test multi-module filters, a high ‘quality factor’ (efficiency-to-pressure-drop ratio) of about 0.1 to 0.13 Pa−1 can be consistently maintained, which was far better than conventional filters. Using the same PVDF 6-layer charged nanofiber filter, laboratory tests results using monodispersed NaCl aerosols of 50, 100, and 300 nm yielded filtration efficiency, respectively, 92%, 94% and 98% (qualified for 'N98 standard') with same pressure drop of 26 Pa. The 2–6% discrepancy in efficiency for the NaCl aerosols was primarily attributed to the absence of interaction among aerosols of different sizes using monodispersed NaCl aerosols in the laboratory. This discrepancy can be further reduced with increasing number of modules in the filter and for larger 300-nm aerosol. The 6-layer charged nanofiber filter was qualified as a 'N98 respirator' (98% capture efficiency for 300-nm NaCl aerosols) but with pressure drop of only 2.65-mm water which was 1/10 below conventional N95 with 25-mm (exhaling) to 35-mm (inhaling) water column! The 6-layer charged PVDF nanofiber filter provides good personal protection against airborne COVID-19 virus and nano-aerosols from pollution based on the N98 standard, yet it is at least 10X more breathable than a conventional N95 respirator.


Fetal Interventions in the Setting of COVID-19 Pandemic: Statement from the North American Fetal Therapy Network (NAFTNet)


The story of the pandemic: navigating our way between optimism and pessimism


title: COVID-19 pandemic in sub-Saharan Africa: preparedness, response, and hidden potentials

text: After the detection of coronavirus disease 2019 (COVID-19) first reported case in Nigeria, the virus has spread to all sub-Saharan Africa (SSA). Through different initiatives, SSA countries came together to create goal-driven taskforces to improve their responses against the virus. As COVID-19 raises major concerns over the scarcity of medical supplies, numbers of SSA countries adopted innovative solutions to fill in their shortage. This health crisis may come as an opportunity for SSA to demonstrate its pandemic readiness, responses, and reveal unknown potential.


title: Fear and Stigma: The Epidemic within the SARS Outbreak

text: Because of their evolving nature and inherent scientific uncertainties, outbreaks of emerging infectious diseases can be associated with considerable fear in the general public or in specific communities, especially when illness and deaths are substantial. Mitigating fear and discrimination directed toward persons infected with, and affected by, infectious disease can be important in controlling transmission. Persons who are feared and stigmatized may delay seeking care and remain in the community undetected. This article outlines efforts to rapidly assess, monitor, and address fears associated with the 2003 severe acute respiratory syndrome (SARS) epidemic in the United States. Although fear, stigmatization, and discrimination were not widespread in the general public, Asian-American communities were particularly affected.


title: Fine Tuning the Cytokine Storm by IFN and IL-10 Following Neurotropic Coronavirus Encephalomyelitis

text: The central nervous system (CNS) is vulnerable to several viral infections including herpes viruses, arboviruses and HIV to name a few. While a rapid and effective immune response is essential to limit viral spread and mortality, this anti-viral response needs to be tightly regulated in order to limit immune mediated tissue damage. This balance between effective virus control with limited pathology is especially important due to the highly specialized functions and limited regenerative capacity of neurons, which can be targets of direct virus cytolysis or bystander damage. CNS infection with the neurotropic strain of mouse hepatitis virus (MHV) induces an acute encephalomyelitis associated with focal areas of demyelination, which is sustained during viral persistence. Both innate and adaptive immune cells work in coordination to control virus replication. While type I interferons are essential to limit virus spread associated with early mortality, perforin, and interferon-γ promote further virus clearance in astrocytes/microglia and oligodendrocytes, respectively. Effective control of virus replication is nonetheless associated with tissue damage, characterized by demyelinating lesions. Interestingly, the anti-inflammatory cytokine IL-10 limits expansion of tissue lesions during chronic infection without affecting viral persistence. Thus, effective coordination of pro- and anti-inflammatory cytokines is essential during MHV induced encephalomyelitis in order to protect the host against viral infection at a limited cost.


Colorectal cancer surgery during the COVID‐19 pandemic


title: COVID-19: beta-thalassemia subjects immunised?

text: The novel coronavirus pneumonia (COVID-19) is a contagious acute respiratory infectious disease whose causative agent has been demonstrated to be a novel virus of the coronavirus family, SARSCoV-2. A recent PRE-print study has showed a heme attack on the 1-beta chain of hemoglobin by COVID19. Beta-thalassemia results of a default in the hemoglobin beta- chain synthesis. 1,5% global population are heterozygotes for this disease. In this study, by a multiple linear regression, we have analyzed the evolution of COVID-19 infection in three Italian regions (Puglia, Sardinia, Sicilia) with different beta-thalassemic prevalences, in order to search a link. The results have showed that betathalassemic heterozygote population prevalence is correlated to immunity against COVID-19, by a regression. This paper is only for academic discussion, the hypotheses and conclusions needs to be confirmed by further research .


Leptomeningeal involvement in a patient with systemic lupus erythematosus infecting by COVID-19


title: Involvement of caveolin-1 in the Jak–Stat signaling pathway and infectious spleen and kidney necrosis virus infection in mandarin fish (Siniperca chuatsi)

text: Abstract Caveolae, the major source of caveolin-1 protein, are specialized invaginated microdomains of the plasma membrane that act as organizing centers for signaling molecules in the immune system. In the present study, we report the cloning and characterization of caveolin-1 (mCav-1) from mandarin fish (Siniperca chuatsi) and study on the roles of mCav-1 in the fish Jak–Stat signaling pathway and in virus infection. The cDNA sequence of mCav-1 was 707bp in size, encoding a protein of 181 amino acids, which was different from the mammalian protein (178 amino acids). The deduced amino acid sequence of mCav-1 shared similar architecture with vertebrate caveolin-1 proteins, but mCav-1 lacked a phosphorylation site (y14). The major subcellular location of mCav-1 was in the caveolae, where the protein appeared to have major functions. Real-time PCR revealed that the expression of the mandarin fish Mx, IRF-1, SOCS1, and SOCS3 genes involved in the poly(I:C)-induced Jak–Stat signaling pathway was impaired by the mCav-1 scaffolding domain peptide (mSDP). In mandarin fish fry (MFF-1) cells, the protein levels of mCav-1 were markedly up-regulated at 12 and 24h post-infection with ISKNV (infectious spleen and kidney necrosis virus). In addition, ISKNV entry into MFF-1 cells was significantly inhibited by mSDP, and the inhibition was dose-dependent. Thus, ISKNV infection was apparently associated with mCav-1 protein and may utilize the caveolae-related endocytosis pathway. The findings reported here further our understanding of the function of caveolin-1 in the complex signal transduction network in fish immune systems and in the cellular entry mechanism of iridoviruses.