title: Porcine Circovirus type 2 – Systemic disease on pig farms and associated knowledge of key players in the pig industry in Central Uganda

text: Porcine Circovirus type 2 (PCV2) infections and associated diseases have been rarely studied in Africa. There is no report of PCV2 infection-associated morbidity and the level of awareness of stakeholders has never been investigated in Uganda. This cross sectional survey investigated the occurrence of Porcine Circovirus type 2 – systemic disease (PCV2-SD) among pigs and the associated level of awareness of stakeholders in Central Uganda. Data were collected using questionnaires, Focus Group Discussions (FGDs), key informant interviews and laboratory investigations. All respondents (n = 131) and farmers attending FGDs (n = 31) had never heard of PCV2-SD and only 16.7% (n = 2) of the interviewed animal health workers (n = 12) knew about the disease. Among the farms, 20 piglets presenting with a chronic wasting and a persistent diarrhea were detected and sampled for laboratory investigations. Severe lymphoid depletion with histiocytic and macrophage infiltration in lymphoid organs (n = 8), shortening of intestinal villi (n = 9), abscesses in various organs (n = 15) and granulomatous pneumonia (n = 2) were the major histopathological lesions described. Immunohistochemistry and PCR assays on organs with implicating lesions confirmed PCV2 infection in 25% (n = 5) of the 20 pigs. The study confirmed the occurrence of PCV2 infections among piglets with persistent diarrhea on pig farms in central Uganda and revealed a low level of associated knowledge among farmers and veterinary practitioners. The study arouses the need for systematic studies on prevalence of PCV2 infections and sensitization of stakeholders on occurrence of PCV2 infections in Uganda.


title: Dynamics of scientific publications on the MERS-CoV outbreaks in Saudi Arabia

text: Abstract Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an emerging disease with a relatively high case fatality rate. Most cases have been reported from Saudi Arabia, and the disease epidemic potential is considered to be limited. However, human–human transmission has occurred, usually in the context of healthcare facility-associated outbreaks. The scientific and medical community depends on timely publication of epidemiological information on emerging diseases during outbreaks to appropriately target public health responses. In this review, we considered the academic response to four MERS CoV outbreaks that occurred in Al-Hasa in 2013, Jeddah in 2014 and Riyadh in 2014 and 2015. We analysed 68 relevant epidemiology articles. For articles for which submission dates were available, six articles were submitted during the course of an outbreak. One article was published within a month of the Al-Hasa outbreak, and one each was accepted during the Jeddah and Riyadh outbreaks. MERS-CoV epidemiology articles were cited more frequently than articles on other subjects in the same journal issues. Thus, most epidemiology articles on MERS-CoV were published with no preferential advantage over other articles. Collaboration of the research community and the scientific publishing industry is needed to facilitate timely publication of emerging infectious diseases.


title: Child Victim Services in the Time of COVID-19: New Challenges and Innovative Solutions

text: The impact of COVID-19 has been felt by all facets of the criminal justice system and victim services agencies. The ability to monitor and report maltreatment has been severely limited for organizations that work with children of abuse and neglect; this is particularly troubling given that abuse and neglect are likely to rise during times of distress and turmoil. The purpose of this paper is to discuss the importance of organizations that work with children exposed to maltreatment, highlight the novel approach of Child Advocacy Services, SEGA, Inc. (CASSEGA), the sponsoring agency for Court Appointed Special Advocates (CASA) and the Ogeechee Visitation Centers, in rural southeast Georgia and how the COVID-19 pandemic has challenged this work, and develop strategies that can be put into place to alleviate these challenges for other child-serving organizations.


title: Deep Learning-Based Method of Diagnosing Hyperlipidemia and Providing Diagnostic Markers Automatically

text: INTRODUCTION: The research of auxiliary diagnosis has always been one of the hotspots in the world. The implementation of auxiliary diagnosis support algorithm for medical text data faces challenges with interpretability and creditability. The improvement of clinical diagnostic techniques means not only the improvement of diagnostic accuracy but also the further study of diagnostic basis. Traditional research methods for diagnostic markers often require a large amount of time and economic costs. Research objects are often dozens of samples, and it is, therefore, difficult to synthesize large amounts of data. Therefore, the comprehensiveness and reliability of traditional methods have yet to be improved. Therefore, the establishment of a model that can automatically diagnose diseases and automatically provide a diagnostic basis at the same time has a positive effect on the improvement of medical diagnostic techniques. METHODS: Here, we established an auxiliary diagnostic tool based on attention deep learning algorithm to diagnostic hyperlipemia and automatically predict the corresponding diagnostic markers using hematological parameters. In this paper, we not only demonstrated the ability of the proposed model to automatically diagnose diseases using text-based medical data, such as physiological parameters, but also demonstrated its ability to forecast disease diagnostic markers. Human physiological parameters are used as input to the model, and the doctor’s diagnosis results as an output. Through the attention layer, the degree of attention of the model to different physiological parameters can be obtained, that is, the model provides a diagnostic basis. RESULTS: It achieved 94% ACC, 97.48% AUC, 96% sensitivity and 92% specificity with the test dataset. All the above samples are drawn from clinical practice. Moreover, the model predicted the diagnostic markers of hyperlipidemia by the attention mechanism, and the results were fully agreeable to the golden criteria. DISCUSSION: The auxiliary diagnosis system proposed in this paper not only achieves the accurate and robust performance, and can be used for the preliminary diagnosis of patients, but also showing its great potential to discover new diagnostic markers. Therefore, it not only can improve the efficiency of clinical diagnosis but also shorten the research period of researching a diagnosis basis to an extent. It has a positive significance to the development of the medical diagnosis level.


Severe Acute Respiratory Syndrome, Avian Influenza, the World Health Organization, and the Internet


title: Seasonal Variation of Newly Notified Pulmonary Tuberculosis Cases from 2004 to 2013 in Wuhan, China

text: BACKGROUND: Although there was a report about the seasonal variation in Wuhan city, it only analyzed the prevalence data of pulmonary tuberculosis (TB) cases, and just studied the seasonality by subgroup of smear positive and negative from 2006 to 2010 by spectral analysis. In this study, we investigated the seasonality of the total newly notified pulmonary TB cases by subgroups such as time period, sex, age, occupation, district, and sputum smear result from 2004 to 2013 in Wuhan by a popular seasonal adjustment model (TRAMO-SEATS). METHODS: Monthly pulmonary TB cases from 2004 to 2013 in Wuhan were analyzed by the TRAMO-SEATS seasonal adjustment program. Seasonal amplitude was calculated and compared within the subgroups. RESULTS: From 2004 to 2013, there were 77.76 thousand newly notified pulmonary TB cases in Wuhan, China. There was a dominant peak spring peak (March) with seasonal amplitude of 56.81% and a second summer peak (September) of 43.40%, compared with the trough month (December). The spring seasonal amplitude in 2004–2008 was higher than that of 2009–2013(P<0.05). There were no statistical differences for spring seasonal amplitude within subgroups of gender, age, district, and sputum smear result (P>0.05). However, there were significant differences in spring seasonal amplitude by occupation, with amplitude ranging from 59.37% to 113.22% (P<0.05). The summer seasonal amplitude in 2004–2008 was higher than that of 2009–2013(P<0.05). There were no statistical differences in summer seasonal amplitude within subgroups of gender, district, sputum smear result(P>0.05). There were significant differences in summer seasonal amplitude by age, with amplitude ranging from 36.05% to 100.09% (P<0.05). Also, there were significant differences in summer seasonal amplitude by occupation, with amplitude ranging from 43.40% to 109.88% (P<0.05). CONCLUSIONS: There was an apparent seasonal variation in pulmonary TB cases in Wuhan. We speculated that spring peak in our study was most likely caused by the increased reactivation of the latent TB due to vitamin D deficiency and high PM2.5 concentration, while the summer peak was mainly resulted from the enhanced winter transmission due to indoor crowding in winter, overcrowding of public transportation over the period of the Spring Festival and health care seeking delay in winter.


title: Anti-inflammatory properties of Type I interferons

text: Abstract The notion that Type I interferons (interferon-α and -β) possess anti-inflammatory potential is supported by data from clinical application in multiple sclerosis, by studies on cultured immune-competent cells and by investigation of experimental diseases in whole animals. These observations deserve the attention of virologists for their potential role in the pathogenesis and clinical management of virus infections.


title: Laboratory capacity building for the International Health Regulations (IHR[2005]) in resource-poor countries: the experience of the African Field Epidemiology Network (AFENET)

text: Laboratory is one of the core capacities that countries must develop for the implementation of the International Health Regulations (IHR[2005]) since laboratory services play a major role in all the key processes of detection, assessment, response, notification, and monitoring of events. While developed countries easily adapt their well-organized routine laboratory services, resource-limited countries need considerable capacity building as many gaps still exist. In this paper, we discuss some of the efforts made by the African Field Epidemiology Network (AFENET) in supporting laboratory capacity development in the Africa region. The efforts range from promoting graduate level training programs to building advanced technical, managerial and leadership skills to in-service short course training for peripheral laboratory staff. A number of specific projects focus on external quality assurance, basic laboratory information systems, strengthening laboratory management towards accreditation, equipment calibration, harmonization of training materials, networking and provision of pre-packaged laboratory kits to support outbreak investigation. Available evidence indicates a positive effect of these efforts on laboratory capacity in the region. However, many opportunities exist, especially to support the roll-out of these projects as well as attending to some additional critical areas such as biosafety and biosecuity. We conclude that AFENET’s approach of strengthening national and sub-national systems provide a model that could be adopted in resource-limited settings such as sub-Saharan Africa.


title: 18S rRNA is a reliable normalisation gene for real time PCR based on influenza virus infected cells

text: BACKGROUND: One requisite of quantitative reverse transcription PCR (qRT-PCR) is to normalise the data with an internal reference gene that is invariant regardless of treatment, such as virus infection. Several studies have found variability in the expression of commonly used housekeeping genes, such as beta-actin (ACTB) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), under different experimental settings. However, ACTB and GAPDH remain widely used in the studies of host gene response to virus infections, including influenza viruses. To date no detailed study has been described that compares the suitability of commonly used housekeeping genes in influenza virus infections. The present study evaluated several commonly used housekeeping genes [ACTB, GAPDH, 18S ribosomal RNA (18S rRNA), ATP synthase, H+ transporting, mitochondrial F1 complex, beta polypeptide (ATP5B) and ATP synthase, H+ transporting, mitochondrial Fo complex, subunit C1 (subunit 9) (ATP5G1)] to identify the most stably expressed gene in human, pig, chicken and duck cells infected with a range of influenza A virus subtypes. RESULTS: The relative expression stability of commonly used housekeeping genes were determined in primary human bronchial epithelial cells (HBECs), pig tracheal epithelial cells (PTECs), and chicken and duck primary lung-derived cells infected with five influenza A virus subtypes. Analysis of qRT-PCR data from virus and mock infected cells using NormFinder and BestKeeper software programmes found that 18S rRNA was the most stable gene in HBECs, PTECs and avian lung cells. CONCLUSIONS: Based on the presented data from cell culture models (HBECs, PTECs, chicken and duck lung cells) infected with a range of influenza viruses, we found that 18S rRNA is the most stable reference gene for normalising qRT-PCR data. Expression levels of the other housekeeping genes evaluated in this study (including ACTB and GPADH) were highly affected by influenza virus infection and hence are not reliable as reference genes for RNA normalisation.


title: A Pancoronavirus RT-PCR Assay for Detection of All Known Coronaviruses

text: The recent discoveries of novel human coronaviruses, including the coronavirus causing SARS, and the previously unrecognized human coronaviruses HCoV-NL63 and HCoV-HKU1, indicate that the family Coronaviridae harbors more members than was previously assumed. All human coronaviruses characterized at present are associated with respiratory illnesses, ranging from mild common colds to more severe lower respiratory tract infections. Since the etiology of a relatively large percentage of respiratory tract diseases remains unidentified, it is possible that for a certain number of these illnesses, a yet unknown viral causative agent may be found. Screening for the presence of novel coronaviruses requires the use of a method that can detect all coronaviruses known at present. In this chapter, we describe a pancoronavirus degenerate primer-based method that allows the detection of all known and possibly unknown coronaviruses by RT-PCR amplification and sequencing of a 251-bp fragment of the coronavirus polymerase gene.


title: Acute and chronic infections of the ear, nose and throat

text: Abstract The article focuses on infections that present with external signs, require surgery and carry the risk of life-threatening complications. This contribution looks at the infections of the ear, nose, oral cavity and neck.


title: Prevalence of avian respiratory viruses in broiler flocks in Egypt

text: In this study, respiratory viral pathogens were screened using real-time RT-PCR in 86 broiler chicken flocks suffering from respiratory diseases problems in 4 Egyptian governorates between January 2012 and February 2014. The mortality rates in the investigated flocks ranged from 1 to 47%. Results showed that mixed infection represented 66.3% of the examined flocks. Mixed infectious bronchitis (IBV) and avian influenza (AI)-H9N2 viruses were the most common infection (41.7%). Lack of AI-H9N2 vaccination and high rates of mixed infections in which AI-H9N2 is involved indicate an early AI-H9N2 infection with a potential immunosuppressive effect that predisposes for other viral infections. High pathogenic AI-H5N1 and virulent Newcastle disease virus (vNDV) infections were also detected (26.7% and 8.1%, respectively). Interestingly, co-infection of AI-H9N2 with either AIV-H5N1 or vNDV rarely resulted in high mortality. Partial cell-mediated immunity against similar internal AI genes, as well as virus interference between AI and vNDV, could be an explanation for this. Highly prevalent IBV and AI-H9N2 were isolated and were molecularly characterized based on S1 gene hypervariable region 3 (HVR3) and hemagglutinin gene (HA) sequences, respectively. IBV strains were related to the variant group of IBV with multiple mutations in HVR3. Though AI-H9N2 viruses showed low rate of evolution in comparison to recent strains, few amino acid substitutions indicative of antibody selection pressure were observed in the HA gene. In conclusion, mixed viral infections, especially with IBV and AI-H9N2 viruses, are the predominant etiology of respiratory disease problems in broiler chickens in Egypt. Further investigations of the role of AI, IBV, and ND viruses’ co-infections and interference in terms of altering the severity of clinical signs and lesions and/or generating novel reassortants within each virus are needed.


Transmission of Avian Influenza Viruses to and between Humans


title: Association of specific viral infections with childhood asthma exacerbations

text: INTRODUCTION: Asthma exacerbations may occur due to a variety of triggers including respiratory viruses. The aim of this study was to determine the role of particular viral infections in asthma exacerbations in children. MATERIALS AND METHODS: The study was performed at Dr. Daneshvari Hospital Pediatric Emergency Department, Shahid Beheshti University of Medical Sciences, Tehran, Iran between 2014 and 2015. A nasopharyngeal aspirate or swab was obtained from each patient during admission. All samples were maintained at 4 °C until submission to the virology laboratory and were tested for respiratory viruses by nucleic acid testing. RESULTS: A total of 60 patients with asthma exacerbations were recruited for this study. Of the 60 samples collected from the patients with acute asthma exacerbations, rhinovirus was detected in 12 patients (20%), respiratory syncytial virus in 5 (8%), adenovirus in 5 (8%), and influenza virus in 1 (1.6%). Respiratory pathogens were not detected in 37 (61%) samples. All the samples investigated showed single viral infection. CONCLUSIONS: To conclude, the most common viruses detected were rhinovirus followed by respiratory syncytial virus (RSV) and adenovirus. RSV was more commonly associated with more severe attacks. Both the study design (e.g., time of sampling, age of the patients, etc.) and also the method used for viral detection influence the frequency of detection of the respiratory viruses.


title: Antiviral lectins: Selective inhibitors of viral entry

text: Abstract Many natural lectins have been reported to have antiviral activity. As some of these have been put forward as potential development candidates for preventing or treating viral infections, we have set out in this review to survey the literature on antiviral lectins. The review groups lectins by structural class and class of source organism we also detail their carbohydrate specificity and their reported antiviral activities. The review concludes with a brief discussion of several of the pertinent hurdles that heterologous proteins must clear to be useful clinical candidates and cites examples where such studies have been reported for antiviral lectins. Though the clearest path currently being followed is the use of antiviral lectins as anti-HIV microbicides via topical mucosal administration, some investigators have also found systemic efficacy against acute infections following subcutaneous administration.


title: The perils of premature phenotyping in COVID: a call for caution

text: By prematurely phenotyping patients with COVID-19, we expose ourselves and our patients to considerable and preventable risk. If we do not insist on data-driven phenotypes, our cognitive biases guarantee that we'll end up with phenotype-driven data.


title: Detection of COPD Exacerbations and Compliance With Patient-Reported Daily Symptom Diaries Using a Smartphone-Based Information System

text: Background Paper-based diaries and self-report of symptom worsening in COPD may lead to underdetection of exacerbations. Epidemiologically, COPD exacerbations exhibit seasonal patterns peaking at year-end. We examined whether the use of a BlackBerry-based daily symptom diary would detect 95% or more of exacerbations and enable characterization of seasonal differences among them. Methods Fifty participants with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage I to IV COPD began a community-based study in December 2007. Another 30 began in December 2008. Participants transmitted daily symptom diaries using a BlackBerry. Alerts were triggered when symptom changes, missed diary transmissions, or medical care for a respiratory problem occurred. Participant encounters were initiated if COPD exacerbations were suspected. Participants used their BlackBerrys to report returns to normal breathing. Results Participants transmitted 99.9% of 28,514 possible daily diaries. All 191 (2.5/participant-year) COPD exacerbations meeting Anthonisen criteria were detected. During 148 of the 191 exacerbations (78%, 1.97/participant-year), patients were hospitalized and/or ordered prednisone, an antibiotic, or both. Respiratory viruses were detected in 78 of the 191 exacerbations (41%). Those coinciding with a respiratory viral infection averaged 12.0 days, and those without averaged 8.9 days (P < .04), with no difference in Anthonisen score. Respiratory symptom scores before exacerbations and after normal breathing return showed no differences. Exacerbations were more frequent during the Christmas period than the rest of the year but were not more frequent than in the rest of winter alone. Conclusions Smartphone-based collection of COPD symptom diaries enables near-complete identification of exacerbations at inception. Exacerbation rates in the Christmas season do not reach levels that necessitate changes in disease management.


title: Current progress in the development of a prophylactic vaccine for HIV-1

text: Since its discovery and characterization in the early 1980s as a virus that attacks the immune system, there has been some success for the treatment of human immunodeficiency virus-1 (HIV-1) infection. However, due to the overwhelming public health impact of this virus, a vaccine is needed urgently. Despite the tireless efforts of scientist and clinicians, there is still no safe and effective vaccine that provides sterilizing immunity. A vaccine that provides sterilizing immunity against HIV infection remains elusive in part due to the following reasons: 1) degree of diversity of the virus, 2) ability of the virus to evade the hosts’ immunity, and 3) lack of appropriate animal models in which to test vaccine candidates. There have been several attempts to stimulate the immune system to provide protection against HIV-infection. Here, we will discuss attempts that have been made to induce sterilizing immunity, including traditional vaccination attempts, induction of broadly neutralizing antibody production, DNA vaccines, and use of viral vectors. Some of these attempts show promise pending continued research efforts.


title: Human Metapneumovirus and Other Respiratory Viral Infections during Pregnancy and Birth, Nepal

text: Human metapneumovirus (HMPV) is a respiratory virus that can cause severe lower respiratory tract disease and even death, primarily in young children. The incidence and characteristics of HMPV have not been well described in pregnant women. As part of a trial of maternal influenza immunization in rural southern Nepal, we conducted prospective, longitudinal, home-based active surveillance for febrile respiratory illness during pregnancy through 6 months postpartum. During 2011–2014, HMPV was detected in 55 of 3,693 women (16.4 cases/1,000 person-years). Twenty-five women were infected with HMPV during pregnancy, compared with 98 pregnant women who contracted rhinovirus and 7 who contracted respiratory syncytial virus. Women with HMPV during pregnancy had an increased risk of giving birth to infants who were small for gestational age. An intervention to reduce HMPV febrile respiratory illness in pregnant women may have the potential to decrease risk of adverse birth outcomes in developing countries.


title: Teledermatologic monitoring for chronic cutaneous autoimmune diseases with smartworking during Covid‐19 emergency in a tertiary center in Italy

text: Because of the COVID‐19 emergency, on March 9, 2020 Italy went in lock‐down imposing the closure of non‐urgent outpatient clinics devoted to care of chronic, severe, inflammatory skin diseases that require periodic follow‐up. In this emergency situation, due to the lack of a teledermatology platform and in order not to leave our vulnerable high‐need patients without proper follow‐up, we started a teledermatologic service in smartworking using phone calls and emails. The total number of patients scheduled was 195; in 12 cases we were not able to talk to the patients. Remote monitoring was performed in 183 patients (126 moderate to severe psoriasis, 10 severe acne, 11 severe atopic dermatitis, 11 hidradenitis suppurativa, 9 blistering autoimmune diseases, 16 other autoimmune skin diseases). During remote‐visits several interventions were conducted: triage for COVID‐19 suspected symptoms, email check of clinical pictures and of laboratory examinations, advices for topical and systemic therapy continuation or discontinuation/switch and re‐schedule of next appointment. Only 5 patients required personal office visit (2.6%), reducing consistently the number of face‐to face visits. Our real‐life experience shows that remote monitoring was effective in preventing unnecessary worsening of severe chronic skin diseases and poor outcomes due to withdrawal of current therapy. This article is protected by copyright. All rights reserved.


title: Ensuring Safety and Sustainability of Radiotherapy Services during the COVID-19 Pandemic in Resources Constrain Country: An Indonesian Experience

text: The global COVID-19 pandemic has placed a significant burden on the healthcare sector, overwhelming health services in affected countries worldwide. As healthcare facilities reorganize their services to adapt to this challenging problem, it is important that the sustainability of essential oncology services, including radiotherapy, is maintained. This article describes the Indonesian experience in ensuring sustainability of radiotherapy services during the pandemic, highlighting various important adjustments which were made to allow radiotherapy centers nationwide to continue operating while protecting staff and patients from the risk of disease transmission. As the backlog of patients waiting to start treatment will inevitably grow, some insight on how to proactively manage this issue will also be described.


title: The operational readiness capacities of the grassroots health system in responses to epidemics: Implications for COVID-19 control in Vietnam

text: BACKGROUND: There is a paucity of data on the operational readiness capacities of the grassroots health system in Vietnam while it plays a vital role as a first-line defense against health emergencies, including the coronavirus disease (COVID-19). This study, therefore, aims to assess the operational readiness capacities of the grassroots health system in response to epidemics and provides implications for controlling COVID-19 in Vietnam. METHODS: An online cross-sectional study using the respondent-driven sampling technique was conducted with 6029 health professionals and medical students in Vietnam from December 2019 to February 2020. The operational readiness capacities of the health system were assessed by the sufficiency of health professionals, administrative and logistics staffs, equipment and facilities, and general capacity of health professionals. Kruskal-Wallis test, Fisher exact test and χ(2) test were employed to identify the differences among variables. Tobit and censored regression models were operated to determine associated factors. RESULTS: The operational readiness capacities of the grassroots health system for four assessed criteria were at moderate levels, ranging from 6.3 to 6.8 over 10. In Vietnam, the grassroots health system in rural areas, in the South, and at the district level were more likely to be vulnerable compared to their counterparts. CONCLUSIONS: According to empirical data, this study reveals the vulnerability of the grassroots health system in Vietnam and provides the rationality of prompt and vigorous actions of the Vietnamese Government against COVID-19. Findings also offer useful insights for effective strategies to strengthen the grassroots health system in the long term. In the short term, practicing precautionary measures and mobilizing human resources, as well as medical equipment, are needed to successfully contain COVID-19 in Vietnam.


title: Neutralization of feline infectious peritonitis virus: preparation of monoclonal antibody that shows cell tropism in neutralizing activity after viral absorption into the cells

text: Feline infectious peritonitis virus (FIPV) infection of feline macro-phages is enhanced by mouse anti-FIPV monoclonal antibody (MAb). This anti-body-dependent enhancement (ADE) of FIPV infection is dependent on mouse MAb subclass, and MAb of IgG2a subclass has a strong ADE activity. Furthermore, MAb showing strong neutralizing activity in Felis catus whole fetus (fcwf-4) cells and Crandell feline kidney (CrFK) cells shows strong enhancing activity in feline macrophages, indicating that the neutralizing epitope and the enhancing epitope are closely related. In this study, we prepared MAb FK50-4 that showed a strong neutralizing activity in feline macrophages, despite the fact that the MAb belonged to the IgG2a subclass. However, MAb FK50-4 did not exhibit neutralizing activity in CrFK cells or fcwf-4 cells, thus showing a very unusual property. MAb FK50-4 recognized FIPV small integral membrane glycoprotein (M protein). Even when feline macrophages were pretreated with MAb FK50-4 prior to FIPV inoculation, this antibody prevented FIPV infection. This reaction disappeared after treatment of FK50-4 with protein A. The neutralizing activity of FK50-4 was also effective on feline macrophages after the cells were inoculated with FIPV. These findings indicated that the FIPV replication mechanism differs between feline macrophages and CrFK/fcwf-4 cells and that a neutralizing epitope that can prevent FIPV infection of feline macrophages after viral absorption is present on M protein.


title: Participants’ Experiences of the 2018–2019 Government Shutdown and Subsequent Supplemental Nutrition Assistance Program (SNAP) Benefit Disruption Can Inform Future Policy

text: The federal government shutdown from 22 December 2018 to 25 January 2019 created an unprecedented disruption in Supplemental Nutrition Assistance Program (SNAP) benefits. We conducted a cross-sectional qualitative study to begin to capture how the disruption affected food security and wellbeing among a small sample of California SNAP participants. We collected data from 26 low-income adults in four focus groups in four diverse California counties. We found that participants routinely struggle to secure an adequate and healthy diet in the context of high costs of living, the shutdown and benefit disruption added to participants’ stress and uncertainty and exacerbated food insecurity, and it diminished some participants’ faith in government. Participants reported that, while having additional benefits in January felt like a relief from typical end-of-month deprivation, the subsequent extended gap between benefit distributions and a lack of clarity about future benefits caused cascading effects as participants later had to divert money from other expenses to buy food and faced added uncertainty about future economic stability. Additionally, the shutdown highlighted challenges related to the availability, timing, and tone of communications between participants and SNAP agencies. Participants recommended that SNAP adjust benefit and eligibility levels to better address costs of living, improve customer service, and avoid future disruptions.


title: Cutaneous manifestations of COVID-19: Report of three cases and a review of literature

text: ABSTRACT Background Various cutaneous manifestations have been observed in patients with COVID-19 infection. However, overall similarities in the clinical presentation of these dermatological manifestations have not yet been summarized. Objective This review aims to provide an overview of various cutaneous manifestations in patients with COVID-19 through three case reports and a literature review. Methods A literature search was conducted using PubMed, OVID, and Google search engines for original and review articles. Studies written in the English language that mentioned cutaneous symptoms and COVID-19 were included. Results Eighteen articles and three additional cases reported in this paper were included in this review. Of these studies, 6 are case series and 12 are case report studies. The most common cutaneous manifestation of COVID-19 was found to be maculopapular exanthem (morbilliform), presenting in 36.1% (26/72) patients. The other cutaneous manifestations included: a papulovesicular rash (34.7%, 25/72), urticaria (9.7%, 7/72), painful acral red purple papules (15.3%, 11/72) of patients, livedo reticularis lesions (2.8%, 2/72) and petechiae (1.4%, 1/72). Majority of lesions were localized on the trunk (66.7%, 50/72), however, 19.4% (14/72) of patients experienced cutaneous manifestations in the hands and feet. Skin lesion development occurred after the onset of respiratory symptoms or before COVID-19 diagnosis in 12.5% (9/72) of the patients, and lesions spontaneously healed in all patients within 10 days. Majority of the studies reported no correlation between COVID-19 severity and skin lesions. Conclusion Infection with COVID-19 may result in dermatological manifestations with various clinical presentations, which may aid in the timely diagnosis of this infection.


title: Characterization of germline antibody libraries from human umbilical cord blood and selection of monoclonal antibodies to viral envelope glycoproteins: implications for mechanisms of immune evasion and design of vaccine immunogens

text: We have previously observed that all known HIV-1 broadly neutralizing antibodies (bnAbs) are highly divergent from germline antibodies in contrast to bnAbs against Hendra virus, Nipah virus and SARS coronavirus (SARS CoV). We have hypothesized that because the germline antibodies are so different from the mature HIV-1-specific bnAbs they may not bind the epitopes of the mature antibodies and provided the first evidence to support this hypothesis by using individual putative germline-like predecessor antibodies. To further validate the hypothesis and understand initial immune responses to different viruses, two phage-displayed human cord blood-derived IgM libraries were constructed which contained mostly germline antibodies or antibodies with very low level of somatic hypermutations. They were panned against different HIV-1 envelope glycoproteins (Envs), SARS CoV protein receptor-binding domain (RBD), and soluble Hendra virus G protein (sG). Despite a high sequence and combinatorial diversity observed in the cord blood-derived IgM antibody repertoire, no enrichment for binders of Envs was observed in contrast to considerable specific enrichments produced with panning against RBD and sG; one of the selected monoclonal antibodies (against the RBD) was of high (nM) affinity with only few somatic mutations. These results further support and expand our initial hypothesis for fundamental differences in immune responses leading to elicitation of bnAbs against HIV-1 compared to SARS CoV and Hendra virus. HIV-1 uses a strategy to minimize or eliminate strong binding of germline antibodies to its Env; in contrast, SARS CoV and Hendra virus, and perhaps other viruses causing acute infections, can bind germline antibody or minimally somatically mutated antibodies with relatively high affinity which could be one of the reasons for the success of sG and RBD as vaccine immunogens.


title: Bystander CD4 T cells do not mediate demyelination in mice infected with a neurotropic coronavirus

text: Abstract Demyelination following infection of mice with the neurotropic coronavirus mouse hepatitis virus strain JHM (MHV) is immune-mediated. It has been demonstrated that MHV-specific CD4 and CD8 T cells are capable of causing demyelination independent of the other T cell subset. Recent work has also demonstrated that activated bystander CD8 T cells mediate significant demyelination. The ability of bystander CD4 T cells to mediate demyelination was investigated using CD4 T cell transgenic mice. The results indicated that bystander CD4 T cells were unable to cause demyelination in MHV-infected mice, despite being recruited into the central nervous system (CNS) and irrespective of activation status. These results suggest that CD4 T cells must recognize antigen in the CNS in order to cause demyelination.


title: Comparison of Prevalence and Associated Factors of Anxiety and Depression Among People Affected by versus People Unaffected by Quarantine During the COVID-19 Epidemic in Southwestern China

text: BACKGROUND: At the end of 2019, the COVID-19 outbreak began in Wuhan, Hubei, China, and spread rapidly to the whole country within 1 month. This new epidemic caused a great mental reaction among the public. This study aimed to assess and compare the prevalence and associated factors of anxiety and depression among the public affected by quarantine and those unaffected during the COVID-19 outbreak in southwestern China in early Feb. 2020. MATERIAL/METHODS: Data were collected using the self-rating anxiety scale (SAS) and the self-rating depression scale (SDS) administered to 1593 respondents aged 18 years and above. The respondents were grouped as ‘affected group’ and ‘unaffected group’ on the basis of whether they or their families/colleagues/classmates/neighbors had been quarantined. RESULTS: Among 1593 participants, the prevalence of anxiety and depression was approximately 8.3% and 14.6%, respectively, and the prevalence in the affected group (12.9%, 22.4%) was significantly higher than that in the unaffected group (6.7%, 11.9%). Lower average household income, lower education level, having a higher self-evaluated level of knowledge, being more worried about being infected, having no psychological support, greater property damage, and lower self-perceived health condition were significant associated with higher scores on the SAS and SDS. People living in Chongqing had higher SAS and SDS scores than those living in Yunnan Province. CONCLUSIONS: The prevalence of anxiety and depression of the affected group are higher than in the unaffected group during the COVID-19 outbreak in southwestern China in early Feb. 2020. The government should focus more on providing economic and medical support to improve the general population’s mental state.


title: A Rare Deletion in SARS-CoV-2 ORF6 Dramatically Alters the Predicted Three-Dimensional Structure of the Resultant Protein

text: The function of the SARS-CoV-2 accessory protein p6, encoded by ORF6, is not fully known. Based upon its similarity to p6 from SARS-CoV, it may play a similar role, namely as an antagonist of type I interferon (IFN) signaling. Here we report the sequencing of a SARS-CoV-2 strain passaged six times after original isolation from a clinical patient in Hong Kong. The genome sequence shows a 27 nt in-frame deletion (Δ27,264-27,290) within ORF6, predicted to result in a 9 aa deletion (ΔFKVSIWNLD) from the central portion of p6. This deletion is predicted to result in a dramatic alteration in the three-dimensional structure of the resultant protein (p6Δ22-30), possibly with significant functional implications. Analysis of the original clinical sample indicates that the deletion was not present, while sequencing of subsequent passages of the strain identifies the deletion as a majority variant. This suggests that the deletion originated ab initio during passaging and subsequently propagated into the majority, possibly due to the removal of selective pressure through the IFN-deficient Vero E6 cell line. The specific function of the SARS-CoV-2 p6 N-terminus, if any, has not yet been determined. However, this deletion is predicted to cause a shift from N-endo to N-ecto in the transmembrane localization of the SARS-CoV-2 p6Δ22-30 N-terminus, possibly leading to the ablation of its native function.


title: Extremely high canine C-reactive protein concentrations > 100 mg/l – prevalence, etiology and prognostic significance

text: BACKGROUND: In human medicine, extremely high CRP (C-reactive protein) concentrations > 100 mg/l are indicators of bacterial infection and the need of antibiotic treatment. Similar decision limits for septic pneumonia are recommended for dogs but have not yet been evaluated for other organ systems. The aim of the retrospective study was to investigate the prevalence and evaluate dogs with CRP concentrations > 100 mg/l regarding the underlying etiology, the affected organ system and the prognostic significance. RESULTS: Prevalence of CRP > 100 mg/l was investigated in dogs presented between 2014 and 2015 and was 12%. For evaluation of etiology and organ systems, dogs with CRP > 100 mg/l presented between 2014 and 2016 were enrolled. Dogs were classified into 4 main disease categories, i.e. inflammatory, neoplastic, tissue damage or “diverse”. Diseases were assigned to the affected organ system. If an organ classification was not possible, dogs were classified as “multiple”. 147 dogs with CRP 101–368 mg/l were included and classified into disease categories: 86/147 (59%) with inflammatory etiology (among these, 23/86 non-infectious, 44/86 infectious (33/44 bacterial), 19/86 inflammation non-classifiable), 31/147 (21%) tissue damage, 17/147 (12%) neoplastic (all malignant) and 13/147 (9%) diverse diseases. The affected organ systems included 57/147 (39%) multiple, 30/147 (20%) trauma, 21/147 (14%) gastrointestinal tract, 10/147 (7%) musculoskeletal system, 8/147 (5%) respiratory tract, 7/147 (5%) urinary/reproductive tract, 6/147 (4%) skin/subcutis/ear, 6/147 (4%) central/peripheral nervous system and 2/147 (1%) heart. The disease group (p = 0.081) or organ system (p = 0.17) did not have an impact on CRP. Based on CRP, a detection of bacterial infection was not possible. The prognostic significance was investigated by determining the 3-months survival and hospitalization rate in a subgroup with known outcome. The 3-months survival rate was 46/73 (63%) while the majority 66/73 (90%) of patients was hospitalized. CONCLUSIONS: CRP concentrations > 100 mg/l are occasionally seen in a clinic population. They indicate a severe systemic disease of various etiologies with guarded prognosis. Extremely high CRP concentrations do not allow a conclusion of the underlying etiology or an identification of bacterial inflammation.


title: JNK and PI3k/Akt signaling pathways are required for establishing persistent SARS-CoV infection in Vero E6 cells

text: Abstract Persistence was established after most of the SARS-CoV-infected Vero E6 cells died. RNA of the defective interfering virus was not observed in the persistently infected cells by Northern blot analysis. SARS-CoV diluted to 2 PFU failed to establish persistence, suggesting that some particular viruses in the seed virus did not induce persistent infection. Interestingly, a viral receptor, angiotensin converting enzyme (ACE)-2, was down-regulated in persistently infected cells. G418-selected clones established from parent Vero E6 cells, which were transfected with a plasmid containing the neomycin resistance gene, were infected with SARS-CoV, resulting in a potential cell population capable of persistence in Vero E6 cells. Our previous studies demonstrated that signaling pathways of extracellular signal-related kinase (ERK1/2), c-Jun N-terminal protein kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3′-kinase (PI3K)/Akt were activated in SARS-CoV-infected Vero E6 cells. Previous studies also showed that the activation of p38 MAPK by viral infection-induced apoptosis, and a weak activation of Akt was not sufficient to protect from apoptosis. In the present study, we showed that the inhibitors of JNK and PI3K/Akt inhibited the establishment of persistence, but those of MAPK/ERK kinase (MEK; as an inhibitor for ERK1/2) and p38 MAPK did not. These results indicated that two signaling pathways of JNK and PI3K/Akt were important for the establishment of persistence in Vero E6 cells.


title: Synthesis of 4-hydroxy-1-methylindole and benzo[b]thiophen-4-ol based unnatural flavonoids as new class of antimicrobial agents

text: Abstract Synthesis of nitrogen and sulfur heterocyclic mimics of furanoflavonoids have been achieved for the first time. Synthesized flavonoid alkaloids and thiophenyl flavonoids have been screened for antifungal and antibacterial activities. All the test compounds barring 25 exhibited antifungal activity. The compound 19 was the best and showed comparable MICs to the known compound karanjin. Compounds 5, 12, 14 and 22 also showed comparable MIC to karanjin.


title: Control of virus-induced cell fusion by host cell lipid composition

text: Abstract Virus-induced cell fusion has been examined in a series of stable cell lines which were originally selected for resistance to the fusogenic effects of polyethylene glycol (PEG). For a wide variety of viruses, including murine hepatitis virus (a coronavirus), vesicular stomatitis virus (a rhabdovirus), and two paramyxoviruses (Sendai virus and SV5), susceptibility to virus-induced fusion was found to be inversely correlated with susceptibility to PEG-induced fusion. This phenomenon was observed both for cell fusion occurring in the course of viral infection and for fusion induced “from without” by the addition of high titers of noninfectious or inactivated virus. The fusion-altered cell lines (fusible by virus but not by PEG) are characterized by their unusual lipid composition, including marked elevation of saturated fatty acids and the presence of an unusual ether-linked neutral lipid. To test the association between lipid composition and fusion, acyl chain saturation was manipulated by supplementing the culture medium with exogenous fatty acids. In such experiments, it was possible to control the responses of these cells to both viral and chemical fusogens. Increasing the cellular content of saturated fatty acyl chains increased the susceptibility of cells to viral fusion and decreased susceptibility to PEG-induced fusion, whereas lowering fatty acid saturation had the opposite effect. Thus, parallel cultures of cells can be either driven toward the PEG-fusible/virus-fusion-resistant phenotype of the parental cells or rendered susceptible to viral fusion but resistant to PEG-induced fusion, solely by the alteration of cellular lipids. The ability of cellular lipid composition to regulate virus-induced membrane fusion suggests a possible role for lipids in viral infection and pathogenesis


title: Characterisation and Mutational Analysis of an ORF 1a-Encoding Proteinase Domain Responsible for Proteolytic Processing of the Infectious Bronchitis Virus 1a/1b Polyprotein

text: Abstract Coronavirus gene expression involves proteolytic processing of the mRNA 1-encoded polyproteins by viral and cellular proteinases. Recently, we have demonstrated that an ORF 1b-encoded 100-kDa protein is proteolytically cleaved from the 1a/1b fusion polyprotein by a viral-specific proteinase of the picornavirus 3C proteinase group (3C-like proteinase). In this report, the 3C-like proteinase has been further analysed by internal deletion of a 2.3-kb fragment between the 3C-like proteinase-encoding region and ORF 1b and by substitution mutations of its catalytic centre as well as the two predicted cleavage sites flanking the 100-kDa protein. The results show that internal deletion of ORF 1a sequences from nucleotide 9911 to 12227 does not influence the catalytic activity of the proteinase in processing of the 1a/1b polyprotein to the 100-kDa protein species. Site-directed mutagenesis studies have confirmed that the predicted nucleophilic cysteine residue (Cys2922) and a histidine residue encoded by ORF 1a from nucleotide 8985 to 8987 (His2820) are essential for the catalytic activity of the proteinase, and that the QS(G) dipeptide bonds are its target cleavage sites. Substitution mutations of the third component of the putative catalytic triad, the glutamic acid 2843 (Glu2843) residue, however, do not affect the processing to the 100-kDa protein. In addition, cotransfection experiment shows that the 3C-like proteinase is capable of trans-cleavage of the 1a/1b polyprotein. These studies have confirmed the involvement of the 3C-like proteinase domain in processing of the 1a/1b polyprotein, the predicted catalytic centre of the proteinase, and its cleavage sites.


ESTABLISHMENT OF A SAFETY PROTOCOL FOR THE ADMINISTRATION OF TREATMENTS IN MULTIPLE SCLEROSIS DURING THE SARS-CoV-2 PANDEMIC


title: Type 1 Interferons and NK Cells Limit Murine Cytomegalovirus Escape from the Lymph Node Subcapsular Sinus

text: Cytomegaloviruses (CMVs) establish chronic, systemic infections. Peripheral infection spreads via lymph nodes, which are also a focus of host defence. Thus, this is a point at which systemic infection spread might be restricted. Subcapsular sinus macrophages (SSM) captured murine CMV (MCMV) from the afferent lymph and poorly supported its replication. Blocking the type I interferon (IFN-I) receptor (IFNAR) increased MCMV infection of SSM and of the fibroblastic reticular cells (FRC) lining the subcapsular sinus, and accelerated viral spread to the spleen. Little splenic virus derived from SSM, arguing that they mainly induce an anti-viral state in the otherwise susceptible FRC. NK cells also limited infection, killing infected FRC and causing tissue damage. They acted independently of IFN-I, as IFNAR blockade increased NK cell recruitment, and NK cell depletion increased infection in IFNAR-blocked mice. Thus SSM restricted MCMV infection primarily though IFN-I, with NK cells providing a second line of defence. The capacity of innate immunity to restrict MCMV escape from the subcapsular sinus suggested that enhancing its recruitment might improve infection control.


title: Prognostic value of NT-proBNP in patients with severe COVID-19

text: BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China has been declared a public health emergency of international concern. The cardiac injury is a common condition among the hospitalized patients with COVID-19. However, whether N terminal pro B type natriuretic peptide (NT-proBNP) predicted outcome of severe COVID-19 patients was unknown. METHODS: The study initially enrolled 102 patients with severe COVID-19 from a continuous sample. After screening out the ineligible cases, 54 patients were analyzed in this study. The primary outcome was in-hospital death defined as the case fatality rate. Research information and following-up data were obtained from their medical records. RESULTS: The best cut-off value of NT-proBNP for predicting in-hospital death was 88.64 pg/mL with the sensitivity for 100% and the specificity for 66.67%. Patients with high NT-proBNP values (> 88.64 pg/mL) had a significantly increased risk of death during the days of following-up compared with those with low values (≤88.64 pg/mL). After adjustment for potential risk factors, NT-proBNP was independently correlated with in-hospital death. CONCLUSION: NT-proBNP might be an independent risk factor for in-hospital death in patients with severe COVID-19. TRIAL REGISTRATION: ClinicalTrials, NCT04292964. Registered 03 March 2020,


title: COVID-19 and preeclampsia with severe features at 34-weeks gestation

text: The evolving coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a rapid expansion of knowledge on the disease's clinical manifestations, laboratory and radiographic abnormalities, and patient trajectories. One area of particular focus is the effect that this illness may have on pregnancy and maternal-fetal disease. As of April 24, 2020, we identified 55 English language reports in the scientific literature summarizing data for 339 women and 258 fetuses and neonates. The majority of these data have focused on maternal-fetal transmission and neonatal outcomes. One systematic review and meta-analysis including the spectrum of coronaviruses [Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and COVID-19] in pregnancy noted increased rates of adverse outcomes associated with this group of infections. Here, we report the case of a COVID-19 positive woman presenting to our emergency department (ED) at 34 weeks gestation with preeclampsia. This case highlights the unique diagnostic and therapeutic challenges associated with treating patients with these concomitant diseases.


docid: rgvvqgvm

title: Management of surgery in the era of COVID‐19: preliminary data from 11 medical centres in Beijing


Can the 2019 novel coronavirus cause Parkinson's disease?


title: Impact of the COVID-19 epidemic on the provision of pharmaceutical care in community pharmacies

text: BACKGROUND: Community pharmacists and their teams are easy accessible healthcare providers with an important role in primary care. As a consequence of the COVID-19 epidemic, (pharmaceutical) care and specifically communication between patients and healthcare providers is compromised. OBJECTIVE: To describe the impact of the COVID-19 epidemic on the provision of pharmaceutical care in the Netherlands. METHODS: A cross-sectional study with an online questionnaire was sent to community pharmacies in the Netherlands. The questionnaire covered the following main topics: changes in pharmacy setting and logistic procedures, communication about medication and baseline characteristics. RESULTS: Pharmacies implemented hygiene measures and minimized direct patient-provider contact, e.g. by delivering medication at home to a wider range of patients (47.0%), temporarily not conducting medication reviews (55.8%) and only performing inhalation instructions via telephone (22.3%). Only a small number of pharmacies used telepharmacy, such as video calling during patient education and counseling. A total of 76.7% of the participants expressed concerns towards the pharmaceutical care for vulnerable patients. CONCLUSIONS: Our results show considerable impact of the COVID-19 epidemic on both logistic procedures and services regarding patient education and counseling. Pharmacies should be stimulated to implement telepharmacy or remote service to optimally support patients during the COVID-19 epidemic.


title: Review of methods for space–time disease surveillance

text: Abstract A review of some methods for analysis of space–time disease surveillance data is presented. Increasingly, surveillance systems are capturing spatial and temporal data on disease and health outcomes in a variety of public health contexts. A vast and growing suite of methods exists for detection of outbreaks and trends in surveillance data and the selection of appropriate methods in a given surveillance context is not always clear. While most reviews of methods focus on algorithm performance, in practice, a variety of factors determine what methods are appropriate for surveillance. In this review, we focus on the role of contextual factors such as scale, scope, surveillance objective, disease characteristics, and technical issues in relation to commonly used approaches to surveillance. Methods are classified as testing-based or model-based approaches. Reviewing methods in the context of factors other than algorithm performance highlights important aspects of implementing and selecting appropriate disease surveillance methods.


title: Chlamydia Pneumoniae and Atherosclerosis: From Koch Postulates to Clinical Trials

text: Atherosclerosis is increasingly viewed as an inflammatory process. A number of infectious agents have been implicated in the pathogenesis of coronary artery disease. Chlamydia pneumoniae has been the most popular and well-studied of these pathogens. It is difficult to prove a causal relationship which requires the fulfillment of Koch's postulates, first developed in the late 1800s, to establish an infectious agent as the cause of a disease process. This paper reviews the evidence for and against Chlamydia pneumoniae infection as a contributing factor to atherosclerosis disease. It examines seroepidemiologic and histopathologic studies as well as animal models using Koch's postulates and then provides an analysis of current clinical trial data.


title: Risk factors associated with seropositivity to porcine respiratory coronavirus in Danish swine herds

text: Abstract Serological screening of swine herds in 1984 indicated that porcine respiratory coronavirus (PRCV) had been introduced into Denmark. To determine risk factors associated with the introduction of PRCV, a cross-sectional study of 408 Danish swine herds was carried out between May 1985 and June 1986. The association between herd-PRCV serological status and possible risk factors, obtained from a field questionnaire, was assessed by unconditional maximum likelihood logistic regression. An increasing herd size, location in the Jutland peninsula (compared with location on the island of Funen) (OR = 7.9 in a multivariable logistic regression model not including interaction terms), the presence of a slurry system (i.e. pigs living on a slatted floor) (OR = 4.6) and purchase of pigs (OR= 1.7) were significantly (P < 0.05) associated with seropositivity. Two significant interactions, both involving herd size, were subsequently identified. The PRCV serological status of neighbouring herds was found to be related, and closeness of a seropositive herd was associated with an increased risk of a herd being serologically positive. The results of this study indicate that herd size may be an important determinant of airborne transmission of PRCV infection, and that herd size may modify the effect of other risk factors.


title: Progress in the Therapeutic Applications of siRNAs Against HIV-1

text: Therapeutic options against the human immunodeficiency virus type 1 (HIV-1) continue to expand with the development of new drugs and new therapeutic strategies. Nevertheless, management of HIV-1 infected individuals has become increasingly complex. The emergence of drug-resistant variants, the growing recognition of the long-term toxicity of antiretroviral therapies and the persistence of viral reservoirs justify the continued efforts to develop new anti-HIV-1 strategies. Recent advances regarding the utility of RNA-mediated interference (RNAi) to specifically inhibit HIV-1 replication have opened new possibilities for the development of gene-based therapies against HIV-1 infection. Here, the recent advances in siRNA-based therapies are reviewed.


title: Utility of Digital Respondent Driven Sampling to Recruit Community-Dwelling Emerging Adults for Assessment of Drinking and Related Risks

text: INTRODUCTION: Emerging adulthood often entails heightened risk-taking, including risky drinking, and research is needed to guide intervention development and delivery. This study adapted Respondent Driven Sampling, a peer-driven recruitment method, to a digital platform (d-RDS) and evaluated its utility to recruit community-dwelling emerging adult (EA) risky drinkers, who are under-served and more difficult to reach for assessment and intervention than their college student peers. MATERIALS AND METHODS: Community-dwelling EA risky drinkers (N = 357) were recruited using d-RDS (M age = 23.6 years, 64.0% women). Peers recruited peers in an iterative fashion. Participants completed a web-based cross-sectional survey of drinking practices and problems and associated risk and protective factors. RESULTS: d-RDS successfully recruited EA risky drinkers. On average, the sample reported recent drinking exceeding low-risk drinking guidelines and 8.80 negative consequences in the past three months. Compared to age-matched respondents from the representative U.S. National Survey on Drug Use and Health, the sample reported more past month drinking days and more drinks consumed per drinking day (ps < .001). At higher consumption levels, predicted positive associations were found with lower education and receipt of public assistance. CONCLUSIONS: Results supported the utility of d-RDS as a sampling method and grassroots platform for research and intervention with community-dwelling EA drinkers who are harder to reach than traditional college students. The study provides a method and lays an empirical foundation for extending efficacious alcohol brief interventions with college drinkers to this underserved population.


title: Explaining rapid reinfections in multiple-wave influenza outbreaks: Tristan da Cunha 1971 epidemic as a case study

text: Influenza usually spreads through the human population in multiple-wave outbreaks. Successive reinfection of individuals over a short time interval has been explicitly reported during past pandemics. However, the causes of rapid reinfection and the role of reinfection in driving multiple-wave outbreaks remain poorly understood. To investigate these issues, we focus on a two-wave influenza A/H3N2 epidemic that occurred on the remote island of Tristan da Cunha in 1971. Over 59 days, 273 (96%) of 284 islanders experienced at least one attack and 92 (32%) experienced two attacks. We formulate six mathematical models invoking a variety of antigenic and immunological reinfection mechanisms. Using a maximum-likelihood analysis to confront model predictions with the reported incidence time series, we demonstrate that only two mechanisms can be retained: some hosts with either a delayed or deficient humoral immune response to the primary influenza infection were reinfected by the same strain, thus initiating the second epidemic wave. Both mechanisms are supported by previous empirical studies and may arise from a combination of genetic and ecological causes. We advocate that a better understanding and account of heterogeneity in the human immune response are essential to analysis of multiple-wave influenza outbreaks and pandemic planning.


title: Viral and host determinants of RNA virus vector replication and expression

text: Positive-strand RNA viruses have proven to be valuable vectors for delivery and expression of antigens for direct vaccination of animals and vaccine production in plants. However, optimal use of these viruses as vectors for vaccine and other purposes is limited by incomplete understanding of their replication pathways and associated constraints on inserted foreign genes. Further insights into RNA virus vector design and optimization are emerging from recent advances on the function of viral RNA replication factors, the nature of the viral RNA replication complex as a membrane-bounded compartment sequestering replication components from competing processes and host defenses, and identification of surprisingly diverse host genes contributing to many virus replication steps.


title: Real-time RT-PCR assays for discriminating influenza B virus Yamagata and Victoria lineages

text: Abstract Since the late 1980s, two genetically and antigenically distinct lineages of influenza B virus, namely, B/Victoria/2/87-like (B/Victoria) and B/Yamagata/16/88-like (B/Yamagata), have co-circulated. In this study, one-step real-time reverse transcription-PCR (rRT-PCR) assays were developed to differentiate B/Victoria and B/Yamagata lineages. The assays were evaluated using in vitro transcribed control RNA, isolated viruses, and other respiratory pathogenic viruses, and were shown to have high sensitivity, good linearity (R 2 =0.99), and high specificity. Using the developed rRT-PCR assays, 169 clinical specimens collected between 2010 and 2013 were then tested, resulting in the identification of 20 clinical specimens as positive for influenza B virus. Of these, 14 and 6 samples were identified as positive for the B/Victoria and B/Yamagata lineages, respectively, whereas 149 samples were negative for the influenza B virus. The rRT-PCR assays were also examined using 20 clinical isolates from 20 influenza B virus-positive specimens, revealing that there was no discrepancy between the results from the rRT-PCR assays and the hemagglutination inhibition (HI) test, with the exception that one clinical isolate with different antigenicity could not be discriminated by the HI test. The present results suggest that these highly sensitive and specific assays are useful not only for diagnosing influenza viruses but also for their surveillance.


title: nSynergistic antiviral effect of hydroxychloroquine and azithromycin in combination against SARS-CoV-2: what molecular dynamics studies of virus-host interactions reveal

text: The emergence of SARS-coronavirus-2 (SARS-CoV-2) is responsible for a global pandemic disease referred to as coronavirus disease 19 (Covid-19). Hydroxychloroquine/azithromycin combination therapy is currently tested for curing Covid-19, with promising results. However, the molecular mechanism of action of this combination is not established yet. Using molecular dynamics (MD) simulations we show that both drugs act in synergy to prevent any close contact between the virus and the plasma membrane of host cells. We reveal unexpected molecular similarity between azithromycin and the sugar moiety of GM1, a lipid raft ganglioside acting as a host attachment cofactor for respiratory viruses. Due to this mimicry, azithromycin interacts with the ganglioside-binding domain of SARS-CoV-2 spike protein. This binding site shared by azithromycin and GM1 displays a conserved amino acid triad Q-134/F-135/N-137 located at the tip of the spike protein. We also show that hydroxychloroquine molecules can saturate virus attachment sites on gangliosides in the vicinity of the primary coronavirus receptor ACE-2. Taken together, these data show that azithromycin is directed against the virus, whereas hydroxychloroquine is directed against cellular attachment cofactors. We conclude that both drugs act as competitive inhibitors of SARS-CoV-2 attachment to the host cell membrane. This is consistent with a synergistic antiviral mechanism at the plasma membrane level, where the most efficient therapeutic intervention probably stands. This molecular mechanism may explain the beneficial effects of hydroxychloroquine/azithromycin combination therapy in patients with Covid-19. Incidentally, our data suggest that the conserved Q-134/F-135/N-137 triad could be considered as a target for vaccine strategies.


title: Transmission of communicable respiratory infections and facemasks

text: BACKGROUND: Respiratory protection efficiency of facemasks is critically important in the battle against communicable respiratory infections such as influenza and severe acute respiratory syndrome (SARS). We studied the spatial distributions of simulated virus-laden respiratory droplets when human subjects wore facemasks and were exposed to regulatory viral droplets by conducting in vivo experiments in facemask use. METHODS: Transmission pathway of aerosols of Fluorescein-KCl solution through facemasks and protective efficiency of facemasks were examined by using normal surgical facemasks and two facemasks with exhaust valves (Facemask A) and exhaust holes (Facemask B) covered with the same surgical filters situated at the back of the facemasks. Fluorescein-KCl solution was sprayed onto the faces of participants wearing the facemasks and performing intermittent exercises on a treadmill in a climatic chamber. RESULTS: Experimental results showed that when droplets spread onto a person face-to-face over short distances, 92.3% to 99.5% of droplets were blocked by the front surface of the facemask, whereas only 0.5% to 7.7% of droplets reached the back of the facemask. Both facemasks A and B had near or over 99% protection efficiency, compared with that of 95.5% to 97% of surgical facemasks. Using the same filters as normal surgical masks, facemasks A and B provided more effective respiratory protection against communicable respiratory infections such as influenza and SARS by the location of the breathing pathway to the back of the facemasks. CONCLUSIONS: Separating the breathing pathway from the virus-contaminated area in facemasks can provide more effective protection against communicable respiratory infections such as influenza and SARS.


docid: kwzsdhrr

title: Oral saliva and CVID-19

text: Outbreak pneumonia announced in Wuhan, China, in December 2019, had its causative factor classified as a new coronavirus (SARS-CoV-2). Since saliva can host several viruses including SARS-CoV-2, the transmission chance of viruses through saliva, particularly those causing respiratory infections, is unavoidable. COVID-19 can be detected through salivary diagnostic testing which has lots of advantages for medical care professionals and patients. It should be noted that not only does saliva offer an ecological niche for the colonization and development of oral microorganisms, but it also prevents the overgrowth of particular pathogens such as viral factors. The aim of this study is to gather all the information about saliva and its association with COVID-19 for the whole health care professionals across the world.


title: G2/M cell cycle arrest in the life cycle of viruses

text: Abstract There is increasing evidence that viral infection, expression of viral protein or the presence of viral DNA causes the host cell cycle to arrest during G2/M. The mechanisms used by viruses to cause arrest vary widely; some involve the activation of the cellular pathways that induce arrest in response to DNA damage, while others use completely novel means. The analysis of virus-mediated arrest has not been proven easy, and in most cases the consequences of arrest for the virus life cycle are not well defined. However, a number of effects of arrest are being investigated and it will be interesting to see to what extent perturbation of the G2/M transition is involved in viral infections.


title: Daily medical education for confined students during COVID‐19 pandemic: A simple videoconference solution

text: The outbreak of coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 infection has recently spread globally and is now a pandemic. As a result, university hospitals have had to take unprecedented measures of containment, including asking nonessential staff to stay at home. Medical students practicing in the surgical departments find themselves idle, as nonurgent surgical activity has been canceled, until further notice. Likewise, universities are closed and medical training for students is likely to suffer if teachers do not implement urgent measures to provide continuing education. Thus, we sought to set up a daily medical education procedure for surgical students confined to their homes. We report a simple and free teaching method intended to compensate for the disappearance of daily lessons performed in the surgery department using the Google Hangouts application. This video conference method can be applied to clinical as well as anatomy lessons.


title: Irreversible inactivation of ISG15 by a viral leader protease enables alternative infection detection strategies

text: In response to viral infection, cells mount a potent inflammatory response that relies on ISG15 and ubiquitin posttranslational modifications. Many viruses use deubiquitinases and deISGylases that reverse these modifications and antagonize host signaling processes. We here reveal that the leader protease, Lb(pro), from foot-and-mouth disease virus (FMDV) targets ISG15 and to a lesser extent, ubiquitin in an unprecedented manner. Unlike canonical deISGylases that hydrolyze the isopeptide linkage after the C-terminal GlyGly motif, Lb(pro) cleaves the peptide bond preceding the GlyGly motif. Consequently, the GlyGly dipeptide remains attached to the substrate Lys, and cleaved ISG15 is rendered incompetent for reconjugation. A crystal structure of Lb(pro) bound to an engineered ISG15 suicide probe revealed the molecular basis for ISG15 proteolysis. Importantly, anti-GlyGly antibodies, developed for ubiquitin proteomics, are able to detect Lb(pro) cleavage products during viral infection. This opens avenues for infection detection of FMDV based on an immutable, host-derived epitope.


title: ‘What is Inconvenient for You is Life-saving for Me’: How Health Inequities are playing out during the COVID-19 Pandemic

text: The COVID-19 pandemic has had a significant impact globally. Most affected, however, are those individuals and groups routinely disadvantaged by the social injustice created by the misdistribution of power, money, and resources. Simple measures that prevent the spread of COVID-19, such as frequent hand washing and social distancing, are unavailable to millions of people in the wealthiest of nations and in the poorest of nations. Disadvantaged groups are impacted more directly and in disproportionately higher numbers due to existing poor health, and the disruption of services central to securing an income and an education will have lasting consequences for their futures. The unintended effect of exclusionary government policies is that privileged citizens and healthcare systems are also at greater risk. This paper seeks to highlight the impact of COVID-19 on those already suffering health inequities through consideration of some of the social determinants of health on groups in affluent and poorer nations. It also highlights some of the factors that may assist in tackling health inequities as we emerge from this pandemic.


title: Evaluation of an octahydroisochromene scaffold used as a novel SARS 3CL protease inhibitor

text: Abstract An octahydroisochromene scaffold has been introduced into a known SARS 3CL protease inhibitor as a novel hydrophobic core to interact with the S2 pocket of the protease. An alkyl or aryl substituent was also introduced at the 1-position of the octahydroisochromene scaffold and expected to introduce additional interactions with the protease. Sharpless–Katsuki asymmetric epoxidation and Sharpless asymmetric dihydroxylation were employed to construct the octahydroisochromene scaffold. The introductions of the P1 site His-al and the substituent at 1-position was achieved using successive reductive amination reactions. Our initial evaluations of the diastereo-isomeric mixtures (16a–d) revealed that the octahydroisochromene moiety functions as a core hydrophobic scaffold for the S2 pocket of the protease and the substituent at the 1-position may form additional interactions with the protease. The inhibitory activities of the diastereoisomerically-pure inhibitors (3a–d) strongly suggest that a specific stereo-isomer of the octahydroisochromene scaffold, (1S, 3S) 3b, directs the P1 site imidazole, the warhead aldehyde, and substituent at the 1-position of the fused ring to their appropriate pockets in the protease.


title: Characterization of neutralizing antibodies from a SARS-CoV-2 infected individual

text: B cells specific for the SARS-CoV-2 S envelope glycoprotein spike were isolated from a COVID-19-infected subject using a stabilized spike-derived ectodomain (S2P) twenty-one days post-infection. Forty-four S2P-specific monoclonal antibodies were generated, three of which bound to the receptor binding domain (RBD). The antibodies were minimally mutated from germline and were derived from different B cell lineages. Only two antibodies displayed neutralizing activity against SARS-CoV-2 pseudo-virus. The most potent antibody bound the RBD in a manner that prevented binding to the ACE2 receptor, while the other bound outside the RBD. Our study indicates that the majority of antibodies against the viral envelope spike that were generated during the first weeks of COVID-19 infection are non-neutralizing and target epitopes outside the RBD. Antibodies that disrupt the SARS-CoV-2 spike-ACE2 interaction can potently neutralize the virus without undergoing extensive maturation. Such antibodies have potential preventive/therapeutic potential and can serve as templates for vaccine-design. IN BRIEF SARS-CoV-2 infection leads to expansion of diverse B cells clones against the viral spike glycoprotein (S). The antibodies bind S with high affinity despite being minimally mutated. Thus, the development of neutralizing antibody responses by vaccination will require the activation of certain naïve B cells without requiring extensive somatic mutation. Highlights Analysis of early B cell response to SARS-CoV-2 spike protein Most antibodies target non-neutralizing epitopes Potent neutralizing mAb blocks the interaction of the S protein with ACE2 Neutralizing antibodies are minimally mutated


title: Deep throat saliva as an alternative diagnostic specimen type for the detection of SARS‐CoV‐2

text: Nasopharyngeal swabs (NPS) are widely accepted as specimens for the detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in the current pandemic of coronavirus disease 2019. However, the collection procedures for NPS specimens causes sneezing and coughing in most patients, which generate droplets or aerosol particles that are hazardous to the healthcare workers collecting these specimens. In this study, 95 patient‐matched paired deep throat saliva (DTS) and NPS specimens from 62 patients were analyzed. Samples were tested for SARS‐CoV‐2 by reverse‐transcription polymerase chain reaction (RT‐PCR). The rates of detection for DTS (53.7%) and NPS (47.4%) samples were comparable (P = .13). It is important to note that the patients should be clearly instructed or supervised during DTS collection. In conclusion, SARS‐CoV‐2 detection by RT‐PCR was equivalent in DTS and NPS specimens.


title: VOLATILITY SPILLOVER AROUND PRICE LIMITS IN AN EMERGING MARKET

text: Abstract The intraday volatility effects of price-limit hits for stocks in the BIST-50 index during a volatile period are examined. Our evidence supports the volatility no-effect, dampening and spillover hypotheses depending on whether the lower or upper price limit is hit and on when the hit begins and ends. Post-hit volatilities tend to be lower for limit hits near the beginning of the first trading session, unchanged for those that transcend a trading session and for upper price-limit hits near the end of either trading session, and higher for lower price-limit hits near the end of either trading session. These results are robust using samples differentiated by cross-listed status, same-day news, equi-distant and trade-by-trade returns and volatility measures accounting for return-series autocorrelations. Our findings have implications for emerging markets planning to impose price-limit bands or to increase their efficacy.


title: Management of patients with magnetically controlled growth rods amidst the global COVID-19 pandemic

text: INTRODUCTION: At the time of writing, we are all coping with the global COVID-19 pandemic. Amongst other things, this has had a significant impact on postponing virtually all routine clinic visits and elective surgeries. Concurrently, the Magnetic Expansion Control (MAGEC) rod has been issued with a number of field safety notices and UK regulator medical device alerts. METHODS: This document serves to provide an overview of the current situation regarding the use of MAGEC rods, primarily in the UK, and the impact that the pandemic has had on the management of patients with these rods. RESULTS AND CONCLUSION: The care of each patient must of course be determined on an individual basis; however, the experience of the authors is that a short delay in scheduled distractions and clinic visits will not adversely impact patient treatment. The authors caution against a gap in distractions of longer than 6 months and emphasise the importance of continued remote patient monitoring to identify those who may need to be seen more urgently.


Is it possible to achieve 100 percent hand hygiene compliance during the COVID-19 pandemic?


title: Asymptomatic carriage and transmission of SARS-CoV-2: What do we know?

text: PURPOSE: Risk to healthcare workers treating asymptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the operating room depends on multiple factors. This review examines the evidence for asymptomatic or pre-symptomatic carriage of SARS-CoV-2, the risk of transmission from asymptomatic patients, and the specific risks associated with aerosol-generating procedures. Protective measures, such as minimization of aerosols and use of personal protective equipment in the setting of treating asymptomatic patients, are also reviewed. SOURCE: We examined the published literature as well as Societal guidelines. PRINCIPAL FINDINGS: There is evidence that a proportion of those infected with SARS-CoV-2 have detectable viral loads prior to exhibiting symptoms, or without ever developing symptoms. The degree of risk of transmission from asymptomatic patients to healthcare providers will depend on the prevalence of disease in the population, which is difficult to assess without widespread population screening. Aerosol-generating procedures increase the odds of viral transmission from infected symptomatic patients to healthcare providers, but transmission from asymptomatic patients has not been reported. Techniques to minimize aerosolization and appropriate personal protective equipment may help reduce the risk to healthcare workers in the operating room. Some societal guidelines recommend the use of airborne precautions during aerosol-generating procedures on asymptomatic patients during the coronavirus disease pandemic, although evidence supporting this practice is limited. CONCLUSION: Viral transmission from patients exhibiting no symptoms in the operating room is plausible and efforts to reduce risk to healthcare providers include reducing aerosolization and wearing appropriate personal protective equipment, the feasibility of which will vary based on geographic risk and equipment availability.


title: Rationale for targeting Complement in COVID‐19

text: A novel coronavirus, SARS‐CoV‐2, has recently emerged in China and spread internationally, posing a health emergency to the global community. COVID‐19 caused by SARS‐CoV‐2 is associated with an acute respiratory illness that varies from mild to the life‐threatening acute respiratory distress syndrome (ARDS). The complement system is part of the innate immune arsenal against pathogens, which many viruses can evade or employ to mediate cell entry. The immunopathology and acute lung injury orchestrated through the influx of pro‐inflammatory macrophages and neutrophils can be directly activated by complement components to prime an overzealous cytokine storm. The manifestations of severe COVID‐19 such as the ARDS, sepsis and multiorgan failure have an established relationship with activation of the complement cascade. We have collected evidence from all the current studies we are aware of on SARS‐CoV‐2 immunopathogenesis and the preceding literature on SARS‐CoV‐1 and MERS‐CoV infection linking severe COVID‐19 disease directly with dysfunction of the complement pathways. This information lends support for a therapeutic anti‐inflammatory strategy against complement, where a number of clinically ready potential therapeutic agents are available.


title: Peering into the future: long-run economic and social consequences of automation; with an epilogue on COVID-19

text: This final chapter reviews and considers speculations on economic and social development in the context of further automation and progress in artificial intelligence (AI). First, it discusses two possible extreme sets of economic consequences: one being a dystopian scenario with high inequality and deprivation among large swaths of society and the other being “The Happy Leisure Society,” in which most people benefit from the new technologies. We move on to elaborate on the potential effects of automation and AI on living arrangements and the design of cities. Finally, we discuss the possibility of human augmentation to stay competitive with robots in the age of automation and where these trends could possibly lead. This chapter aims mainly to create awareness of these possibilities and to stimulate corresponding discussion—not to sketch a future we think will unfold.


title: Chapter 1 Introduction to the Immune Response

text: Abstract In this chapter we provide an overview of the immune system and its vital role maintaining human health. Immune responses require the coordinated action of leukocytes that travel the body to eliminate threats posed by trauma, infection, toxins, and cancer. Leukocytes communicate via direct contact and via production and receipt of soluble proteins and intercellular messenger proteins called cytokines. Complete clearance of unwanted entities may involve both innate and adaptive leukocyte responses, which influence each other. Some innate mechanisms require no induction and are completely non-specific, whereas others are inducible and involve broad receptor-mediated recognition of a limited number of pathogen-associated or damage-associated molecular patterns (PAMPs/DAMPs). Adaptive responses involve the selective activation of lymphocytes via engagement of their antigen receptors by a specific foreign antigen. The three major subsets of lymphocytes are T helper cells (Th), cytotoxic T cells (Tc) and B cells, which use distinct mechanisms to recognize antigen and carry out different effector functions. Immune system malfunction can contribute to many clinical illnesses including autoimmune disorders, allergies, immunodeficiencies, chronic inflammation and cancer.


SARS-like virus reignites ownership feuds


title: Impact of COVID-19 Outbreak on Healthcare Workers in Italy: Results from a National E-Survey

text: Italy has been the first-hit European country to face the outbreak of coronavirus disease 2019 (COVID-19). Aim of this survey was to assess in depth the impact of the outbreak on healthcare workers (HCW). A 40-item online survey was disseminated via social media inviting Italian HCW, with questions exploring demographics, health status and work environment of respondents. A total of 527 were invited to take part in March 2020, of whom 74% (n = 388) responded to the survey. Of these, 235 (61%) were women. HCW were mostly physicians (74%), from high-prevalence regions (52%). 25% experienced typical symptoms during the last 14 days prior to survey completion, with only 45% of them being tested for COVID-19. Among the tested population, 18 (18%) resulted positive for COVID-19, with 33% being asymptomatic. Only 22% of HCW considered personal protective equipment adequate for quality and quantity. Females and respondents working in high-risk sectors were more likely to rate psychological support as useful (OR, 1.78 [CI 95% 1.14–2.78] P = 0.012, and 2.02 [1.12–3.65] P = 0.020, respectively) and workload as increased (mean increase, 0.38 [0.06–0.69] P = 0.018; and 0.54 [0.16–0.92] P = 0.005, respectively). The insights from this survey may help authorities in countries where COVID-19 epidemic has not yet broken out. Management strategies should be promptly undertaken in order to enhance safety and optimise resource allocation.


title: Optimal and sub-optimal quarantine and isolation control in SARS epidemics

text: Abstract This paper discusses the application of optimal and sub-optimal controls to a SEQIJR SARS model via the Pontryagin’s Maximum Principle. To this end, two control variables representing the quarantine and isolation strategies are considered in the model. The numerical optimal control laws are implemented in an iterative method, and the sub-optimal solution is computed using a genetic algorithm. The simulation results demonstrate that the maximal applications of quarantining and isolation strategies in the early stage of the epidemic are of very critical impacts in both cases of optimal and sub-optimal control. Otherwise, the control effect will be much worse. This gives a theoretical interpretation to the practical experiences that the early quarantine and isolation strategies are critically important to control the outbreaks of epidemics. Furthermore, our results also show that the proposed sub-optimal control can lead to performances close to the optimal control, but with much simpler strategies for long periods of time in practical use.


COVID-19 in persons with multiple sclerosis treated with ocrelizumab – a pharmacovigilance case series


title: The Proteolytic Regulation of Virus Cell Entry by Furin and Other Proprotein Convertases

text: A wide variety of viruses exploit furin and other proprotein convertases (PCs) of the constitutive protein secretion pathway in order to regulate their cell entry mechanism and infectivity. Surface proteins of enveloped, as well as non-enveloped, viruses become processed by these proteases intracellularly during morphogenesis or extracellularly after egress and during entry in order to produce mature virions activated for infection. Although viruses also take advantage of other proteases, it is when some viruses become reactive with PCs that they may develop high pathogenicity. Besides reacting with furin, some viruses may also react with the PCs of the other specificity group constituted by PC4/PC5/PACE4/PC7. The targeting of PCs for inhibition may result in a useful strategy to treat infections with some highly pathogenic viruses. A wide variety of PC inhibitors have been developed and tested for their antiviral activity in cell-based assays.


title: What Does Plant-Based Vaccine Technology Offer to the Fight against COVID-19?

text: The emergence of new pathogenic viral strains is a constant threat to global health, with the new coronavirus strain COVID-19 as the latest example. COVID-19, caused by the SARS-CoV-2 virus has quickly spread around the globe. This pandemic demands rapid development of drugs and vaccines. Plant-based vaccines are a technology with proven viability, which have led to promising results for candidates evaluated at the clinical level, meaning this technology could contribute towards the fight against COVID-19. Herein, a perspective in how plant-based vaccines can be developed against COVID-19 is presented. Injectable vaccines could be generated by using transient expression systems, which offer the highest protein yields and are already adopted at the industrial level to produce VLPs-vaccines and other biopharmaceuticals under GMPC-processes. Stably-transformed plants are another option, but this approach requires more time for the development of antigen-producing lines. Nonetheless, this approach offers the possibility of developing oral vaccines in which the plant cell could act as the antigen delivery agent. Therefore, this is the most attractive approach in terms of cost, easy delivery, and mucosal immunity induction. The development of multiepitope, rationally-designed vaccines is also discussed regarding the experience gained in expression of chimeric immunogenic proteins in plant systems.


docid: smkglves

title: Crisis and disaster management in the light of the Islamic approach: COVID‐19 pandemic crisis as a model (a qualitative study using the grounded theory)

text: The current study sought to generate a theory from the data on crisis management in Islam, and also aimed to identify the strategies used by leaders in the crisis management process. The grounded theory approach was applied, which is one of the qualitative designs. The content of the verses of the Noble Qur'an and the hadiths of the Prophet Muhammad that dealt with the issue of crises were analyzed. The results of the qualitative analysis of the verses of the Qur'an and the hadiths of the Prophet's noble Sunnah have resulted in four concepts that constitute a broad conceptual theory of crisis management according to the Islamic approach. These concepts are: Crisis management strategies in Islam, the stages of crisis management, the characteristics of a leader who manages crises, and the roles of a leader during the crisis management process. A number of assumptions have been made of this generated theory about Islamic crisis management model. In light of the results of this study, recommendations were formulated that indicate the necessity of training leaders in the Islamic approach to crisis management, its strategies and its scientific steps in crisis management. These results have wide applications in the field of training leaders, and also recommend future studies to verify the assumptions of the theory that emerged from the data in this study on crisis management in Islam (COVID‐19 pandemic crisis as a model).


title: Study of ARIMA and Least Square Support Vector Machine (LS-SVM) Models for the Prediction of SARS-CoV-2 Confirmed Cases in the Most Affected Countries

text: Discussions about the recently identified deadly coronavirus disease (COVID-19) which originated in Wuhan, China in December 2019 are common around the globe now. This is an infectious and even life-threatening disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has rapidly spread to other countries from its originating place infecting millions of people globally. To understand future phenomena, strong mathematical models are required with the least prediction errors. In the present study, autoregressive integrated moving average (ARIMA) and least square support vector machine (LS-SVM) models are applied to the data consisting of daily confirmed cases of SARS-CoV-2 in the most affected five countries of the world for modeling and predicting one-month confirmed cases of this disease. To validate these models, the prediction results were tested by comparing it with testing data. The results revealed better accuracy of the LS-SVM model over the ARIMA model and also suggested a rapid rise of SARS-CoV-2 confirmed cases in all the countries under study. This analysis would help governments to take necessary actions in advance associated with the preparation of isolation wards, availability of medicines and medical staff, a decision on lockdown, training of volunteers, and economic plans.


title: Delmarva (DMV/1639) Infectious Bronchitis Virus (IBV) Variants Isolated in Eastern Canada Show Evidence of Recombination

text: Infectious bronchitis virus (IBV) infection in chickens can lead to an economically important disease, namely, infectious bronchitis (IB). New IBV variants are continuously emerging, which complicates vaccination-based IB control. In this study, five IBVs were isolated from clinical samples submitted to a diagnostic laboratory in Ontario, Canada, and subjected to detailed molecular characterization. Analysis of the spike (S)1 gene showed that these five IBVs were highly related to the Delmarva (DMV/1639) strain (~97.0% nucleotide sequence similarity) that was firstly isolated from an IB outbreak in the Delmarva peninsula, United States of America (USA), in 2011. However, the complete genomic sequence analysis showed a 93.5–93.7% similarity with the Connecticut (Conn) vaccine strain, suggesting that Conn-like viruses contributed to the evolution of the five Canadian IBV/DMV isolates. A SimPlot analysis of the complete genomic sequence showed evidence of recombination for at least three different IBV strains, including a Conn vaccine-like strain, a 4/91 vaccine-like strain, and one strain that is yet-unidentified. The unidentified strain may have contributed the genomic regions of the S, 3, and membrane (M) genes of the five Canadian IBV/DMV isolates. The study outcomes add to the existing knowledge about involvement of recombination in IBV evolution.


title: Ethnic Disparities in Hospitalisation for COVID-19 in England: The Role of Socioeconomic Factors, Mental Health, and Inflammatory and Pro-inflammatory Factors in a Community-based Cohort Study

text: BACKGROUND: Differentials in COVID-19 hospitalisations and mortality according to ethnicity have been reported but their origin is uncertain. We examined the role of socioeconomic, mental health, and pro-inflammatory factors in a community-based sample. METHODS: We used data on 340,966 men and women (mean age 56.2 years) from the UK Biobank study, a prospective cohort study with linkage to hospitalisation for COVID-19. Logistic regression models were used to estimate associations between ethnicity and hospitalisation for COVID-19. RESULTS: There were 640 COVID-19 cases (571/324,306 White, 31/4,485 Black, 21/5,732 Asian, 17/5,803 Other). Compared to the White study members and after adjusting for age and sex, Black individuals had over a 4-fold increased risk of COVID-19 infection (odds ratio; 95% confidence interval: 4.32; 3.00-6.23), and there was a doubling of risk in the Asian group (2.12; 1.37, 3.28) and the ‘other’ non-white group (1.84; 1.13, 2.99). After controlling for potential explanatory factors which included neighbourhood deprivation, household crowding, smoking, body size, inflammation, glycated haemoglobin, and mental illness, these effect estimates were attenuated by 33% for Blacks, 52% for Asians and 43% for Other, but remained raised for Blacks (2.66; 1.82, 3.91), Asian (1.43; 0.91, 2.26) and other non-white groups (1.41; 0.87, 2.31). CONCLUSIONS: There were clear ethnic differences in risk of COVID-19 hospitalisation and these do not appear to be fully explained by measured factors. If replicated, our results have implications for health policy, including the targeting of prevention advice and vaccination coverage.