title: Transcriptomic analysis of small intestinal mucosa from porcine epidemic diarrhea virus infected piglets

text: Abstract Caused by porcine epidemic diarrhea virus (PEDV), porcine epidemic diarrhea (PED) is an acute infectious disease which causes damage to the intestine including intestinal villus atrophy and shedding, leading to serious economic losses to the pig industry worldwide. In order to obtain detailed information about the pathogenesis and host immune response in a PEDV-infected host for first In vivo study we used high-throughput sequencing to analyze the gene expression differences of the small intestinal mucosa after infection with PEDV. Transcripts obtained were over 65,525,000 clean reads after reassembly were 22,605 genes detected, of which 22,248 were known genes and 371 new genes were predicted. Moreover, 3168 genes expression was up-regulated and 3876 genes down-regulated. (Gene Ontology) GO annotation and functional enrichment analysis indicated that all of the DEGs (differentially expressed genes) were annotated into biological process, cellular component and molecular function. Most of these unigenes are annotated in cellular processes, the cell and binding. KEGG analysis of the DEGs showed that a total of 7044 DEGs unigenes were annotated into 323 pathways classified into 6 main categories. Most of these unigenes are annotated were related to immune system response to the infectious diseases pathways. In addition, 20 DEGs were verified by quantitative real-time PCR. As the first, in vivo, RNAseq analysis of piglets and PEDV infection, our study provides knowledge about the transcriptomics of intestinal mucosa in PEDV-infected piglets, from which a complex molecular pathways and pathogenesis-related biological processes are involved in PEDV interaction with piglet intestinal mucosa.


title: Uganda public health fellowship program’s contribution to building a resilient and sustainable public health system in Uganda

text: Background: Low-income countries with relatively weak-health systems are highly vulnerable to public health threats. Effective public health system with a workforce to investigate outbreaks can reduce disease impact on livelihoods and economic development. Building effective public health partnerships is critical for sustainability of such a system. Uganda has made significant progress in responding to emergencies during the past quarter century, but its public health workforce is still inadequate in number and competency. Objectives: To reinforce implementation of priority public health programs in Uganda and cultivate core capacities for compliance with International Health Regulations. Methods: To develop a competent workforce to manage epidemics and improve disease surveillance, Uganda Ministry of Health (MoH) established an advanced-level Field Epidemiology Training Program, called Public Health Fellowship Program (PHFP); closely modelled after the US CDC’s Epidemic Intelligence Service. PHFP is a 2-year, full-time, non-degree granting program targeting mid-career public health professionals. Fellows spend 85% of their field time in MoH placements learning through service delivery and gaining competencies in major domains. Results: During 2015–2018, PHFP enrolled 41 fellows, and graduated 30. Fellows were placed in 19 priority areas at MoH and completed 235 projects (91 outbreaks, 12 refugee assessments, 50 surveillance, and 60 epidemiologic studies, 3 cost analysis and 18 quality improvement); made 194 conference presentations; prepared 63 manuscripts for peer-reviewed publications (27 published as of December 2018); produced MoH bulletins, and developed three case studies. Projects have resulted in public health interventions with improvements in surveillance systems and disease control. Conclusion: During the 4 years of existence, PHFP has contributed greatly to improving real-time disease surveillance and outbreak response core capacities. Enhanced focus on evidence-based targeted approaches has increased effectiveness in outbreak response and control, and integration of PHFP within MoH has contributed to building a resilient and sustainable health system in Uganda.


title: Molecular detection of respiratory pathogens among children aged younger than 5 years hospitalized with febrile acute respiratory infections: A prospective hospital‐based observational study in Niamey, Niger

text: BACKGROUND AND AIMS: In Niger, acute respiratory infections (ARIs) are the second most common cause of death in children aged younger than 5 years. However, the etiology of ARI is poorly understood in the country. This study aims to describe viral and bacterial infections among children aged younger than 5 years hospitalized with febrile ARI at two hospitals in Niamey, Niger's capital city, and the reported clinical procedures. METHODS: We conducted a prospective study among children aged younger than 5 years hospitalized with febrile ARI at two national hospitals in Niamey between January and December 2015. Clinical presentation and procedures during admission were documented using a standardized case investigation form. Nasopharyngeal specimens collected from each patient were tested for a panel of respiratory viruses and bacteria using the Fast Track Diagnostic 21 Plus kit. RESULTS: We enrolled and tested 638 children aged younger than 5 years, of whom 411 (64.4%) were aged younger than 1 year, and 15 (2.4%) died during the study period. Overall, 496/638 (77.7%) specimens tested positive for at least one respiratory virus or bacterium; of these, 195 (39.3%) tested positive for respiratory viruses, 126 (25.4%) tested positive for respiratory bacteria, and 175 (35.3%) tested positive for both respiratory viruses and bacteria. The predominant viruses detected were respiratory syncytial virus (RSV) (149/638; 23.3%), human parainfluenza virus (HPIV) types 1 to 4 (78/638; 12.2%), human rhinovirus (HRV) (62/638; 9.4%), human adenovirus (HAV) (60/638; 9.4%), and influenza virus (INF) (52/638; 8.1%). Streptococcus pneumoniae (249/638; 39.0%) was the most frequently detected bacterium, followed by Staphylococcus aureus (112/638; 12.2%) and Haemophilus influenzae type B (16/638; 2.5%). Chest X‐rays were performed at the discretion of the attending physician on 301 (47.2%) case patients. Of these patients, 231 (76.7%) had abnormal radiological findings. A total of 135/638 (21.2%) and 572/638 (89.7%) children received antibiotic treatment prior to admission and during admission, respectively. CONCLUSION: A high proportion of respiratory viruses was detected among children aged younger than 5 years with febrile ARI, raising concerns about excessive use of antibiotics in Niger.


title: Important mammalian veterinary viral immunodiseases and their control

text: This paper offers an overview of important veterinary viral diseases of mammals stemming from aberrant immune response. Diseases reviewed comprise those due to lentiviruses of equine infectious anaemia, visna/maedi and caprine arthritis encephalitis and feline immunodeficiency. Diseases caused by viruses of feline infectious peritonitis, feline leukaemia, canine distemper and aquatic counterparts, Aleutian disease and malignant catarrhal fever. We also consider prospects of immunoprophylaxis for the diseases and briefly other control measures. It should be realised that the outlook for effective vaccines for many of the diseases is remote. This paper describes the current status of vaccine research and the difficulties encountered during their development.


title: RNA Viruses: RNA Roles in Pathogenesis, Coreplication and Viral Load

text: The review intends to present and recapitulate the current knowledge on the roles and importance of regulatory RNAs, such as microRNAs and small interfering RNAs, RNA binding proteins and enzymes processing RNAs or activated by RNAs, in cells infected by RNA viruses. The review focuses on how non-coding RNAs are involved in RNA virus replication, pathogenesis and host response, especially in retroviruses HIV, with examples of the mechanisms of action, transcriptional regulation, and promotion of increased stability of their targets or their degradation.


title: Public health and economic responses to COVID-19: finding the tipping point

text: Abstract We shed light on an under-reported dimension of the pandemic and its response: namely, the trade-off between early deaths from the virus and potential deaths arising from the economic fallout. Our previous research has shown that recessions and austerity as an economic response to a recession are associated with rises in cancer mortality and all-cause mortality, respectively. We believe it is important to highlight the considerations in this tradeoff.


Building Knowledge in a Time of Physical Distancing


title: Elevated adipogenesis of marrow mesenchymal stem cells during early steroid-associated osteonecrosis development

text: BACKGROUND: Increased bone marrow lipid deposition in steroid-associated osteonecrosis (ON) implies that abnormalities in fat metabolism play an important role in ON development. The increase in lipid deposition might be explained by elevated adipogenesis of marrow mesenchymal stem cells (MSCs). However, it remains unclear whether there is a close association between elevated adipogenesis and steroid-associated ON development. OBJECTIVE: The present study was designed to test the hypothesis that there might be a close association between elevated adipogenesis and steroid-associated ON development. METHODS: ON rabbit model was induced based on our established protocol. Dynamic-MRI was employed for local intra-osseous perfusion evaluation in bilateral femora. Two weeks after induction, bone marrow was harvested for evaluating the ability of adipogenic differentiation of marrow MSCs at both cellular and mRNA level involving adipogenesis-related gene peroxisome proliferator-activated receptor gamma2 (PPARγ2). The bilateral femora were dissected for examining marrow lipid deposition by quantifying fat cell number, fat cell size, lipid deposition area and ON lesions. For investigating association among adipogenesis, lipid deposition and perfusion function with regard to ON occurrence, the rabbits were divided into ON(+ )(with at least one ON lesion) group and ON(- )(without ON lesion) group. For investigating association among adipogenesis, lipid deposition and perfusion function with regard to ON extension, the ON(+ )rabbits were further divided into sub-single-lesion group (SON group: with one ON lesion) and sub-multiple-lesion group (MON group: with more than one ON lesion). RESULTS: Local intra-osseous perfusion index was found lower in either ON(+ )or MON group when compared to either ON(- )or SON group, whereas the marrow fat cells number and area were much larger in either ON(+ )or MON group as compared with ON(- )and SON group. The adipogenic differentiation ability of MSCs and PPARγ2 expression in either ON(+ )or MON group were elevated significantly as compared with either ON(- )or SON group. CONCLUSION: These findings support our hypothesis that there is a close association between elevated adipogenesis and steroid-associated osteonecrosis development.


title: PCR array profiling of antiviral genes in human embryonic kidney cells expressing human coronavirus OC43 structural and accessory proteins

text: Human coronavirus OC43 (HCoV-OC43) is a respiratory virus that usually causes a common cold. However, it has the potential to cause severe infection in young children and immunocompromised adults. Both SARS-CoV and MERS-CoV were shown to express proteins with the potential to evade early innate immune responses. However, the ability of HCoV-OC43 to antagonise the intracellular antiviral defences has not yet been investigated. The potential role of the HCoV-OC43 structural (M and N) and accessory proteins (ns2a and ns5a) in the alteration of antiviral gene expression was investigated in this study. HCoV-OC43M, N, ns2a and ns5a proteins were expressed in human embryonic kidney 293 (HEK-293) cells before challenge with Sendai virus. The Human Antiviral Response PCR array was used to profile the antiviral gene expression in HEK-293 cells. Over 30 genes were downregulated in the presence of one of the HCoV-OC43 proteins, e.g. genes representing mitogen-activated protein kinases, toll-like receptors, interferons, interleukins, and signaling transduction proteins. Our findings suggest that similarly to SARS-CoV and MERS-CoV, HCoV-OC43 has the ability to downregulate the transcription of genes critical for the activation of different antiviral signaling pathways. Further studies are needed to confirm the role of HCoV-OC43 structural and accessory proteins in antagonising antiviral gene expression.


title: Recruitability and effect of PEEP in SARS-Cov-2-associated acute respiratory distress syndrome

text: BACKGROUND: A large proportion of patients with a SARS-Cov-2-associated respiratory failure develop an acute respiratory distress syndrome (ARDS). It has been recently suggested that SARS-Cov-2-associated ARDS may differ from usual non-SARS-Cov-2-associated ARDS by higher respiratory system compliance (C(RS)), lower potential for recruitment with positive end-expiratory pressure (PEEP) contrasting with severe shunt fraction. The purpose of the study was to systematically assess respiratory mechanics and recruitability in SARS-Cov-2-associated ARDS. METHODS: Gas exchanges, C(RS) and hemodynamics were assessed at 2 levels of PEEP (15 cmH(2)O and 5 cmH(2)O) within 36 h (day1) and from 4 to 6 days (day 5) after intubation. The recruited volume was computed as the difference between the volume expired from PEEP 15 to 5 cmH(2)O and the volume predicted by compliance at PEEP 5 cmH(2)O (or above airway opening pressure). The recruitment-to-inflation (R/I) ratio (i.e. the ratio between the recruited lung compliance and C(RS) at PEEP 5 cmH(2)O) was used to assess lung recruitability. A R/I ratio value higher than or equal to 0.5 was used to define highly recruitable patients. RESULTS: The R/I ratio was calculated in 25 of the 26 enrolled patients at day 1 and in 15 patients at day 5. At day 1, 16 (64%) were considered as highly recruitable (R/I ratio median [interquartile range] 0.7 [0.55–0.94]) and 9 (36%) were considered as poorly recruitable (R/I ratio 0.41 [0.31–0.48]). The PaO(2)/FiO(2) ratio at PEEP 15 cmH(2)O was higher compared to PEEP 5 cmH(2)O only in highly recruitable patients (173 [139–236] vs 135 [89–167] mmHg; p < 0.01). Neither PaO(2)/FiO(2) or C(RS) measured at PEEP 15 cmH(2)O or at PEEP 5 cmH(2)O nor changes in PaO(2)/FiO(2) or C(RS) in response to PEEP changes allowed to identify highly or poorly recruitable patients. CONCLUSION: In this series of 25 patients with SARS-Cov-2 associated ARDS, 64% were considered as highly recruitable and only 36% as poorly recruitable based on the R/I ratio performed on the day of intubation. This observation suggests that a systematic R/I ratio assessment may help to guide initial PEEP titration to limit harmful effect of unnecessary high PEEP in the context of Covid-19 crisis.


title: Comment on “Cutaneous manifestations in COVID‐19: a first perspective ” by Recalcati S

text: Since the coronavirus disease 2019 (COVID 19) outbreak was first reported in the Chinese city of Wuhan on December 31, 2019, it has stricken more than 1,000,000 persons worldwide, of whom over 50,000 have died (1). Having been infected by severe acute respiratory syndrome coronavirus 2 (SARS‐COV‐2), patients with COVID‐19 mainly present with fever and respiratory symptoms (2). Isolated sudden onset anosmia has also frequently been reported (3). Less frequently, rhinorrhea, diarrhoea and dysgeusia may be associated. While only a few reports have evoked cutaneous manifestations (4), we read with interest an initial study on the topic entitled “Cutaneous manifestations in COVID‐19: a first perspective ” by Recalcati S. (5).


title: Highly dynamic animal contact network and implications on disease transmission

text: Contact patterns among hosts are considered as one of the most critical factors contributing to unequal pathogen transmission. Consequently, networks have been widely applied in infectious disease modeling. However most studies assume static network structure due to lack of accurate observation and appropriate analytic tools. In this study we used high temporal and spatial resolution animal position data to construct a high-resolution contact network relevant to infectious disease transmission. The animal contact network aggregated at hourly level was highly variable and dynamic within and between days, for both network structure (network degree distribution) and individual rank of degree distribution in the network (degree order). We integrated network degree distribution and degree order heterogeneities with a commonly used contact-based, directly transmitted disease model to quantify the effect of these two sources of heterogeneity on the infectious disease dynamics. Four conditions were simulated based on the combination of these two heterogeneities. Simulation results indicated that disease dynamics and individual contribution to new infections varied substantially among these four conditions under both parameter settings. Changes in the contact network had a greater effect on disease dynamics for pathogens with smaller basic reproduction number (i.e. R(0) < 2).


title: Early phylogenetic estimate of the effective reproduction number of SARS‐CoV‐2

text: To reconstruct the evolutionary dynamics of the 2019 novel‐coronavirus recently causing an outbreak in Wuhan, China, 52 SARS‐CoV‐2 genomes available on 4 February 2020 at Global Initiative on Sharing All Influenza Data were analyzed. The two models used to estimate the reproduction number (coalescent‐based exponential growth and a birth‐death skyline method) indicated an estimated mean evolutionary rate of 7.8 × 10(−4) subs/site/year (range, 1.1 × 10(−4)‐15 × 10(−4)) and a mean tMRCA of the tree root of 73 days. The estimated R value was 2.6 (range, 2.1‐5.1), and increased from 0.8 to 2.4 in December 2019. The estimated mean doubling time of the epidemic was between 3.6 and 4.1 days. This study proves the usefulness of phylogeny in supporting the surveillance of emerging new infections even as the epidemic is growing.


title: China's position in negotiating the Framework Convention on Tobacco Control and the revised International Health Regulations

text: Abstract This paper examines China's position in the negotiations of the Framework Convention on Tobacco Control and the revised International Health Regulations. In particular, it explores three sets of factors shaping China's attitudes and actions in the negotiations: the aspiration to be a responsible power; concerns about sovereignty; and domestic political economy. In both cases, China demonstrated strong incentives to participate in the negotiation of legally binding international rules. Still, the sovereignty issue was a major, if not the biggest, concern for China when engaging in global health rule making. The two cases also reveal domestic political economy as an important factor in shaping China's position in international health negotiations.


Letter from Korea


title: A N7-guanine RNA cap methyltransferase signature-sequence as a genetic marker of large genome, non-mammalian Tobaniviridae

text: The order Nidovirales is a diverse group of (+)RNA viruses, classified together based on their common genome organisation and conserved replicative enzymes, despite drastic differences in size and complexity. One such difference pertains to the mechanisms and enzymes responsible for generation of the proposed viral 5′ RNA cap. Within the Coronaviridae family, two separate methytransferases (MTase), nsp14 and nsp16, perform the RNA-cap N7-guanine and 2′-OH methylation respectively for generation of the proposed m7GpppNm type I cap structure. For the majority of other families within the Nidovirales order, the presence, structure and key enzymes involved in 5′ capping are far less clear. These viruses either lack completely an RNA MTase signature sequence, or lack an N7-guanine methyltransferase signature sequence, obscuring our understanding about how RNA-caps are N7-methylated for these families. Here, we report the discovery of a putative Rossmann fold RNA methyltransferase in 10 Tobaniviridae members in Orf1a, an unusual genome locus for this gene. Multiple sequence alignments and structural analyses lead us to propose this novel gene as a typical RNA-cap N7-guanine MTase with substrate specificity and active-site organization similar to the canonical eukaryotic RNA-cap N7-guanine MTase.


title: Oleoylethanolamide, A Bioactive Lipid Amide, as A Promising Treatment Strategy for Coronavirus/COVID-19

text: Abstract The current outbreak of COVID-19 (coronavirus) has been identified by World Health Organization (WHO) as a global pandemic. With the emergence of the COVID-19 virus and considering the lack of effective pharmaceutical treatment for it, there is an urgent need to identify safe and effective drugs or potential adjuvant therapy in this regard. Bioactive lipids with an array of known health-promoting properties can be suggested as effective agents in alleviating acute respiratory stress induced by virus. The bioactive lipid amide, oleoylethanolamide (OEA), due to several distinctive homeostatic properties, including anti-inflammatory activities, modulation of immune response, and anti-oxidant effects can be considered as a novel potential pharmacological alternative for the management of COVID-19.


title: Severe air pollution links to higher mortality in COVID-19 patients: the “double-hit” hypothesis.

text: OBJECTIVES: In areas of SARS-CoV-2 outbreak worldwide mean air pollutants concentrations vastly exceed the maximum limits. Chronic exposure to air pollutants have been associated with lung ACE-2 over-expression which is known to be the main receptor for SARS-coV2. The aim of this study was to analyse the relationship between air pollutants concentration (PM 2.5 and NO2) and COVID-19 outbreak, in terms of transmission, number of patients, severity of presentation and number of deaths. METHODS: COVID-19 cases, ICU admissions and mortality rate were correlated with severity of air pollution in the Italian regions. RESULTS: The highest number of COVID-19 cases were recorded in the most polluted regions with patients presenting with more severe forms of the disease requiring ICU admission. In these regions, mortality was two-fold higher than the other regions. CONCLUSIONS: From the data available we propose a “double-hit hypothesis”: chronic exposure to PM 2.5 causes alveolar ACE-2 receptor overexpression. This may increase viral load in patients exposed to pollutants in turn depleting ACE-2 receptors and impairing host defences. High atmospheric NO2 may provide a second hit causing a severe form of SARS-CoV-19 in ACE-2 depleted lungs resulting in a worse outcome.


title: Survey data of COVID-19-related Knowledge, Attitude, and Practices among Indonesian Undergraduate Students

text: The dataset presented in this paper is an examination of COVID-19-related knowledge, attitude, and practice among Indonesian undergraduate students. The data were collected during first month of college or university closure due to COVID-19 through a survey distributed via an online questionnaire, assessing sociodemographic information (6 items), knowledge (18 items), attitude (6 item), and practice (12 items), from 27(th) April and 2(nd) May, 2020, gathering a total of 6,249 responses. A combination of purposive and snowball techniques helped to select the respondents via Whatsapp from more than ten universities in Indonesia. The survey data were analyzed using descriptive and inferential statistics. The data will assist in preventing and curbing the spread of COVID-19 in the university and can assist with planning for educational interventions for students’ awareness.


Reply to 'Delirium, sleep, COVID-19 and melatonin'


title: Improved detection of bovine coronavirus N gene in faeces of calves infected naturally by a semi-nested PCR assay and an internal control

text: Abstract Bovine coronavirus (BCoV), a positive sense single-stranded RNA virus, is an important causative agent of neonatal diarrhoea in calves from beef and dairy cattle worldwide. The routine detection and diagnosis of BCoV have been mainly dependent on assays with low sensitivity. The aim of the present study was to develop and evaluate a semi-nested PCR (SN-PCR) to amplify a 251bp fragment of BCoV N gene from fresh (n =25) and frozen (n =25) diarrhoeic faecal samples of naturally infected calves. To improve detection of BCoV in faecal samples by the SN-PCR an internal control was developed, and the results were compared with a conventional RT-PCR assay. The rates of positive samples by SN-PCR and RT-PCR were 24% (12/50) and 8% (4/50), respectively (K =0.43). Only fresh samples were positive in RT-PCR while the SN-PCR detected BCoV in both fresh and frozen faecal samples. The sensitivity of SN-PCR was determined by 10-fold serial dilutions of the BCoV Kakegawa strain (HA titre: 256) that was detected until 10−7 dilution. The specificity of the amplicons was assessed by restriction fragment length polymorphism and sequence analysis. The inclusion of an internal control provides a way to detect assay inhibition in faecal samples and failure of nucleic acid extraction that allow reduction of the number of false-negative results.


title: Time-series modelling and forecasting of hand, foot and mouth disease cases in China from 2008 to 2018

text: Seasonal autoregressive-integrated moving average (SARIMA) has been widely used to model and forecast incidence of infectious diseases in time-series analysis. This study aimed to model and forecast monthly cases of hand, foot and mouth disease (HFMD) in China. Monthly incidence HFMD cases in China from May 2008 to August 2018 were analysed with the SARIMA model. A seasonal variation of HFMD incidence was found from May 2008 to August 2018 in China, with a predominant peak from April to July and a trough from January to March. In addition, the annual peak occurred periodically with a large annual peak followed by a relatively small annual peak. A SARIMA model of SARIMA (1, 1, 2) (0, 1, 1)(12) was identified, and the mean error rate and determination coefficient were 16.86% and 94.27%, respectively. There was an annual periodicity and seasonal variation of HFMD incidence in China, which could be predicted well by a SARIMA (1, 1, 2) (0, 1, 1)(12) model.


title: Increasing the translation of mouse models of MERS coronavirus pathogenesis through kinetic hematological analysis

text: Newly emerging viral pathogens pose a constant and unpredictable threat to human and animal health. Coronaviruses (CoVs) have a penchant for sudden emergence, as evidenced by severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV) and most recently, swine acute diarrhea syndrome coronavirus (SADS-CoV). Small animal models of emerging viral pathogenesis are crucial to better understand the virus and host factors driving disease progression. However, rodent models are often criticized for their limited translatability to humans. The complete blood count is the most ordered clinical test in the United States serving as the cornerstone of clinical medicine and differential diagnosis. We recently generated a mouse model for MERS-CoV pathogenesis through the humanization of the orthologous entry receptor dipeptidyl peptidase 4 (DPP4). To increase the translatability of this model, we validated and established the use of an automated veterinary hematology analyzer (VetScan HM5) at biosafety level 3 for analysis of peripheral blood. MERS-CoV lung titer peaked 2 days post infection concurrent with lymphopenia and neutrophilia in peripheral blood, two phenomena also observed in MERS-CoV infection of humans. The fluctuations in leukocyte populations measured by Vetscan HM5 were corroborated by standard flow cytometry, thus confirming the utility of this approach. Comparing a sublethal and lethal dose of MERS-CoV in mice, analysis of daily blood draws demonstrates a dose dependent modulation of leukocytes. Major leukocyte populations were modulated before weight loss was observed. Importantly, neutrophil counts on 1dpi were predictive of disease severity with a lethal dose of MERS-CoV highlighting the predictive value of hematology in this model. Taken together, the inclusion of hematological measures in mouse models of emerging viral pathogenesis increases their translatability and should elevate the preclinical evaluation of MERS-CoV therapeutics and vaccines to better mirror the complexity of the human condition.


Donors' roles in building of global public goods in health


Multiscale Genome Organization: Dazzling Subject and Inventive Methods


title: Viral and atypical bacterial aetiologies of infection in hospitalised patients admitted with clinical suspicion of influenza in Thailand, Vietnam and Indonesia

text: BACKGROUND: Influenza constitutes a leading cause of morbidity and mortality worldwide. There is limited information about the aetiology of infection presenting clinically as influenza in hospitalised adults and children in South-East Asia. Such data are important for future management of respiratory infections. OBJECTIVES: To describe the aetiology of infection presenting clinically as influenza in those hospitalised in South-East Asia. METHODS: Respiratory specimens archived from July 2008 to June 2009 from patients hospitalised with suspected influenza from Indonesia, Thailand and Vietnam were tested for respiratory viruses and atypical bacteria by polymerase chain reaction. RESULTS: A total of 1222 patients’ samples were tested. Of 1222, 776 patients (63·5%) were under the age of 5. Viruses detected included rhinoviruses in 229 of 1222 patients (18·7%), bocaviruses in 200 (16·4%), respiratory syncytial viruses in 144 (11·8%), parainfluenza viruses in 140 (11·5%; PIV1: 32; PIV2: 12; PIV3: 71; PIV4: 25), adenovirus in 102 (8·4%), influenza viruses in 93 (7·6%; influenza A: 77; influenza B: 16) and coronaviruses in 23 (1·8%; OC43: 14; E229: 9). Bacterial pathogens were Mycoplasma pneumoniae (n = 33, 2·7%), Chlamydophila psittaci (n = 2), C. pneumoniae (n = 1), Bordetella pertussis (n = 1) and Legionella pneumophila (n = 2). Overall, in-hospital case fatality rate was 29 of 1222 (2·4%). CONCLUSION: Respiratory viruses were the most commonly detected pathogens in patients hospitalised with a clinical suspicion of influenza. Rhinovirus was the most frequently detected virus, and M. pneumoniae, the most common atypical bacterium. The low number of detected influenza viruses demonstrates a low benefit for empirical oseltamivir therapy, unless during an influenza outbreak.


COVID-19: Analogues and lessons for tackling the extinction and climate crises


docid: xvnxkcxq

title: Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012

text: OBJECTIVE: To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008. DESIGN: A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. RESULTS: Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7–9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a Pao (2)/Fio (2) ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a Pao (2)/Fi o (2) <150 mm Hg (2C); a protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are >180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5–10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven “absolute”’ adrenal insufficiency (2C). CONCLUSIONS: Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00134-012-2769-8) contains supplementary material, which is available to authorized users.


title: Protection of Newborn Animals through Maternal Immunization

text: Summary Providing protective immunity to neonatal animals in early life is associated with numerous challenges regarding vaccine safety and efficacy. A much simpler approach is maternal vaccination, either before or during pregnancy, to provide the neonate with passively transferred immunity. In humans, the medical, societal and legal risks of immunizing pregnant women are important considerations in undertaking this approach. By contrast, maternal vaccination has been successfully employed in the animal health industry for decades. These veterinary vaccines have proven to be safe and efficient. Although only passively transferred antibodies have been extensively studied, other immunological mechanisms may be equally important in providing maternally derived immunity.


title: Acute kidney injury in critically ill patients with COVID-19

text: Acute kidney injury (AKI) has been reported in up to 25% of critically-ill patients with SARS-CoV-2 infection, especially in those with underlying comorbidities. AKI is associated with high mortality rates in this setting, especially when renal replacement therapy is required. Several studies have highlighted changes in urinary sediment, including proteinuria and hematuria, and evidence of urinary SARS-CoV-2 excretion, suggesting the presence of a renal reservoir for the virus. The pathophysiology of COVID-19 associated AKI could be related to unspecific mechanisms but also to COVID-specific mechanisms such as direct cellular injury resulting from viral entry through the receptor (ACE2) which is highly expressed in the kidney, an imbalanced renin–angotensin–aldosteron system, pro-inflammatory cytokines elicited by the viral infection and thrombotic events. Non-specific mechanisms include haemodynamic alterations, right heart failure, high levels of PEEP in patients requiring mechanical ventilation, hypovolemia, administration of nephrotoxic drugs and nosocomial sepsis. To date, there is no specific treatment for COVID-19 induced AKI. A number of investigational agents are being explored for antiviral/immunomodulatory treatment of COVID-19 and their impact on AKI is still unknown. Indications, timing and modalities of renal replacement therapy currently rely on non-specific data focusing on patients with sepsis. Further studies focusing on AKI in COVID-19 patients are urgently warranted in order to predict the risk of AKI, to identify the exact mechanisms of renal injury and to suggest targeted interventions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06153-9) contains supplementary material, which is available to authorized users.


title: Infections of the airway

text: Infections of the airway in children may present to the anesthetist as an emergency in several locations: the Emergency Department, the Operating Department or on Intensive Care. In all of these locations, relevant and up to date knowledge of presentations, diagnoses, potential complications and clinical management will help the anesthetist and the surgical team, not only with the performance of their interventions, but also in buying time before these are undertaken, avoiding complications and altering the eventual outcome for the child. Diseases such as epiglottitis and diphtheria may show diminished incidence but they have not gone away and their clinical features and essential management remain unchanged. Paradoxically, perhaps, some conditions such as Lemierre’s syndrome appear to be making a comeback. In these instances, clinicians need to be alert to these less common conditions, not only in regard to the disease itself but also to potentially serious complications. This article describes those infections of the airway that are most likely to present to the anesthetist, their attendant complications and recommendations for treatment.


title: A snapshot of the Covid-19 pandemic among pregnant women in France

text: OBJECTIVE: To describe the course over time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in French women from the beginning of the pandemic until mid-April, the risk profile of women with respiratory complications, and short-term pregnancy outcomes. METHODS: We collected a case series of pregnant women with COVID-19 in a research network of 33 French maternity units between March 1 and April 14, 2020. All cases of SARS-CoV-2 infection confirmed by a positive result on real-time reverse transcriptase polymerase chain reaction tests of a nasal sample and/or diagnosed by a computed tomography chest scan were included and analyzed. The primary outcome measures were COVID-19 requiring oxygen (oxygen therapy or noninvasive ventilation) and critical COVID-19 (requiring invasive mechanical ventilation or extracorporeal membrane oxygenation, ECMO). Demographic data, baseline comorbidities, and pregnancy outcomes were also collected. RESULTS: Active cases of COVID-19 increased exponentially during March 1-31, 2020; the numbers fell during April 1-14, after lockdown was imposed on March 17. The shape of the curve of active critical COVID-19 mirrored that of all active cases. By April 14, among the 617 pregnant women with COVID-19, 93 women (15.1%; 95%CI 12.3-18.1) had required oxygen therapy and 35 others (5.7%; 95%CI 4.0-7.8) had had a critical form of COVID-19. The severity of the disease was associated with age older than 35 years and obesity, as well as preexisting diabetes, previous preeclampsia, and gestational hypertension or preeclampsia. One woman with critical COVID-19 died (0.2%; 95%CI 0-0.9). Among the women who gave birth, rates of preterm birth in women with non-severe, oxygen-requiring, and critical COVID-19 were 13/123 (10.6%), 14/29 (48.3%), and 23/29 (79.3%) before 37 weeks and 3/123 (2.4%), 4/29 (13.8%), and 14/29 (48.3%) before 32 weeks, respectively. One neonate in the critical group died from prematurity. CONCLUSION: COVID-19 can be responsible for significant rates of severe acute, potentially deadly, respiratory distress syndromes. The most vulnerable pregnant women, those with comorbidities, may benefit particularly from prevention measures such as a lockdown.


title: Is safeguard compromised? Surgical mouth mask harboring hazardous microorganisms in dental practice

text: CONTEXT: Dental personals are more prone to acquire infections through saliva and aerosols. Surgical masks (SMs) are used by dental professionals to reduce microorganism shedding from the mouth, nose, and face of the patient. AIMS: This aim of the study is to assess the bacterial and fungal presence and their prevalence over the contaminated surgical mask in dental practice. SETTINGS AND DESIGN: This study was conducted with sample size 240 used surgical masks collected from 130 dental personnel. SUBJECTS AND METHODS: A cross-sectional questionnaire survey was conducted with analysis involved inoculation of external and internal surfaces in an enrichment media for isolation of bacteria and fungi. Group of isolated bacteria and fungi were preliminarily identified by morphology and using Gram's stain and lacto-phenol cotton blue mediums. Data were analyzed using paired t-test; the significant level of P < 0.050. RESULTS: Microbiological analysis of samples revealed bacteria Staphylococci 26.35% as a predominant species followed by Pseudomonas 17.82% and Streptococci 15.50%. Aspergillus fungal species was also present in 6.97%. Mean ± SD of bacterial and fungal contamination on inside/outside area of the used masks was 48 ± 26 and 180 ± 110 cfu/ml/piece and 14 ± 6 and 32 ± 13 cfu/ml/piece, respectively, P < 0.001. The used surgical masks from dental department personnel working outpatient dental department had relatively higher bacterial and fungal contamination than the other dental departments. CONCLUSIONS: To reduce a load of microorganism contamination in the clinical environment, more awareness campaigns should be implemented in daily routine and air quality of dental departments should be improved with necessary protective measures.


Thrombosis management in times of COVID-19 epidemy; a Dutch perspective


title: Detection methods for influenza A H1N1 virus with special reference to biosensors: a review

text: H1N1 (Swine flu) is caused by influenza A virus, which is a member of Orthomyxoviridae family. Transmission of H1N1 occurs from human to human through air or sometimes from pigs to humans. The influenza virus has different RNA segments, which can reassert to make new virus strain with the possibility to create an outbreak in unimmunized people. Gene reassortment is a process through which new strains are emerging in pigs, as it has specific receptors for both human influenza and avian influenza viruses. H1N1 binds specifically with an α-2,6 glycosidic bond, which is present in human respiratory tract cells as well as in pigs. Considering the fact of fast multiplication of viruses inside the living cells, rapid detection methods need an hour. Currently, WHO recommended methods for the detection of swine flu include real-time PCR in specific testing centres that take 3–4 h. More recently, a number of methods such as Antigen–Antibody or RT-LAMP and DNA biosensors have also been developed that are rapid and more sensitive. This review describes the various challenges in the diagnosis of H1N1, and merits and demerits of conventional vis-à-vis latest methods with special emphasis on biosensors.


title: Antiviral RNAi in Insects and Mammals: Parallels and Differences

text: The RNA interference (RNAi) pathway is a potent antiviral defense mechanism in plants and invertebrates, in response to which viruses evolved suppressors of RNAi. In mammals, the first line of defense is mediated by the type I interferon system (IFN); however, the degree to which RNAi contributes to antiviral defense is still not completely understood. Recent work suggests that antiviral RNAi is active in undifferentiated stem cells and that antiviral RNAi can be uncovered in differentiated cells in which the IFN system is inactive or in infections with viruses lacking putative viral suppressors of RNAi. In this review, we describe the mechanism of RNAi and its antiviral functions in insects and mammals. We draw parallels and highlight differences between (antiviral) RNAi in these classes of animals and discuss open questions for future research.


title: Coronavirus Genome Structure and Replication

text: In addition to the SARS coronavirus (treated separately elsewhere in this volume), the complete genome sequences of six species in the coronavirus genus of the coronavirus family [avian infectious bronchitis virus-Beaudette strain (IBV-Beaudette), bovine coronavirus-ENT strain (BCoV-ENT), human coronavirus-229E strain (HCoV-229E), murine hepatitis virus-A59 strain (MHV-A59), porcine transmissible gastroenteritis-Purdue 115 strain (TGEV-Purdue 115), and porcine epidemic diarrhea virus-CV777 strain (PEDV-CV777)] have now been reported. Their lengths range from 27,317 nt for HCoV-229E to 31,357 nt for the murine hepatitis virus-A59, establishing the coronavirus genome as the largest known among RNA viruses. The basic organization of the coronavirus genome is shared with other members of the Nidovirus order (the torovirus genus, also in the family Coronaviridae, and members of the family Arteriviridae) in that the nonstructural proteins involved in proteolytic processing, genome replication, and subgenomic mRNA synthesis (transcription) (an estimated 14–16 end products for coronaviruses) are encoded within the 5′-proximal two-thirds of the genome on gene 1 and the (mostly) structural proteins are encoded within the 3′-proximal one-third of the genome (8–9 genes for coronaviruses). Genes for the major structural proteins in all coronaviruses occur in the 5′ to 3′ order as S, E, M, and N. The precise strategy used by coronaviruses for genome replication is not yet known, but many features have been established. This chapter focuses on some of the known features and presents some current questions regarding genome replication strategy, the cis-acting elements necessary for genome replication [as inferred from defective interfering (DI) RNA molecules], the minimum sequence requirements for autonomous replication of an RNA replicon, and the importance of gene order in genome replication.


Infarto agudo de miocardio con elevación del segmento ST en tiempos de COVID-19: ¿regreso al siglo pasado? Una llamada de atención


title: Fièvre au retour de voyage chez l’enfant

text: Résumé Les enfants voyageurs sont des millions dans le monde et sont exposés à de nombreux risques, infectieux ou non, dont les praticiens n’ont pas toujours l’expérience. La consultation d’un enfant fébrile après un voyage est de plus en plus fréquente. Ainsi, la notion d’antécédent de voyage doit être recherchée devant tout enfant fébrile. La démarche diagnostique prend en compte prioritairement des pathologies intertropicales potentiellement graves, comme le paludisme, qui exigent d’être recherchées et traitées efficacement sans délai. Rapidement sont recherchées des infections contagieuses à risque épidémique qui nécessitent la mise en place de mesures d’hygiène et de santé publique. L’interrogatoire évalue les caractéristiques de la fièvre, les vaccinations réalisées, les antécédents médico-chirurgicaux et les risques d’exposition aux infections lors du voyage d’après les données géographiques, saisonnières, environnementales, socioculturelles et épidémiologiques. Il oriente avec les données cliniques et paracliniques élémentaires certains examens complémentaires qui permettent un diagnostic étiologique et un traitement optimal dans près de 75 % des cas. La majorité des causes de fièvre des enfants au retour de voyage sont des infections cosmopolites. En cas de paludisme, le traitement antipaludique est une urgence. Cet article décrit la démarche diagnostique et la prise en charge recommandée en France devant un enfant fébrile de retour de voyage. Abstract Child travelers are numerous, exposed to the risk of diseases, both infectious and noninfectious, for which practitioners often lack experience. The assessment of febrile returning child travelers is becoming more frequent and challenging. The question of previous travel should be foremost in the checklist of the interview of any febrile child traveler, because this implies a possible tropical disease such as malaria that may be life-threatening. These need to be investigated and treated effectively and rapidly. There are highly contagious infections that could pose public health risks requiring implementation of hygienic and public health measures. A detailed immunization, medical, and travel history for exposure to infectious risks using geographic, seasonal, environmental, sociocultural, and epidemiological data are needed. Along with clinical examination and elementary first-line investigations, the history should guide second-line exams, which will provide the etiology and optimal treatment in approximately 75 % of cases. The majority of children will have a cosmopolitan infection that resolves spontaneously or is simple to treat. Malaria will need urgent and specific treatment. This article describes guidance on first-line evaluation and management of febrile child travelers as recommended in France.


title: Efficacy of ethanol against viruses in hand disinfection

text: Summary Ethanol is used worldwide in healthcare facilities for hand rubbing. It has been reported to have a stronger and broader virucidal activity compared with propanols. The aim of this review was to describe the spectrum of virucidal activity of ethanol in solution or as commercially available products. A systematic search was conducted. Studies were selected when they contained original data on reduction of viral infectivity from suspension tests (49 studies) and contaminated hands (17 studies). Ethanol at 80% was highly effective against all 21 tested, enveloped viruses within 30 s. Murine norovirus and adenovirus type 5 are usually inactivated by ethanol between 70% and 90% in 30 s whereas poliovirus type 1 was often found to be too resistant except for ethanol at 95% (all test viruses of EN 14476). Ethanol at 80% is unlikely to be sufficiently effective against poliovirus, calicivirus (FCV), polyomavirus, hepatitis A virus (HAV) and foot-and-mouth disease virus (FMDV). The spectrum of virucidal activity of ethanol at 95%, however, covers the majority of clinically relevant viruses. Additional acids can substantially improve the virucidal activity of ethanol at lower concentrations against, e.g. poliovirus, FCV, polyomavirus and FMDV although selected viruses such as HAV may still be too resistant. The selection of a suitable virucidal hand rub should be based on the viruses most prevalent in a unit and on the user acceptability of the product under frequent-use conditions.


title: Inflammasome activation and regulation: toward a better understanding of complex mechanisms

text: Inflammasomes are cytoplasmic multiprotein complexes comprising a sensor protein, inflammatory caspases, and in some but not all cases an adapter protein connecting the two. They can be activated by a repertoire of endogenous and exogenous stimuli, leading to enzymatic activation of canonical caspase-1, noncanonical caspase-11 (or the equivalent caspase-4 and caspase-5 in humans) or caspase-8, resulting in secretion of IL-1β and IL-18, as well as apoptotic and pyroptotic cell death. Appropriate inflammasome activation is vital for the host to cope with foreign pathogens or tissue damage, while aberrant inflammasome activation can cause uncontrolled tissue responses that may contribute to various diseases, including autoinflammatory disorders, cardiometabolic diseases, cancer and neurodegenerative diseases. Therefore, it is imperative to maintain a fine balance between inflammasome activation and inhibition, which requires a fine-tuned regulation of inflammasome assembly and effector function. Recently, a growing body of studies have been focusing on delineating the structural and molecular mechanisms underlying the regulation of inflammasome signaling. In the present review, we summarize the most recent advances and remaining challenges in understanding the ordered inflammasome assembly and activation upon sensing of diverse stimuli, as well as the tight regulations of these processes. Furthermore, we review recent progress and challenges in translating inflammasome research into therapeutic tools, aimed at modifying inflammasome-regulated human diseases.


docid: vctvcyim

title: The hypothesis that SARS-CoV-2 affects male reproductive ability by regulating autophagy

text: The outbreak of CoronaVirus Disease19 (COVID19) in December 2019 posed a serious threat to public safety, and its rapid spread caused a global health emergency. Clinical data show that in addition to respiratory system damage, some male patients with COVID-19 are also accompanied by abnormal renal function and even renal damage. As the main receptor of syndrome coronavirus 2 (SARS-CoV-2), angiotensin converting enzyme 2 (ACE2) is also found to be highly expressed not only in respiratory mucosa and alveolar epithelial cells, but also in renal tubule cells, testicular Leydig cells and seminiferous tubule cells. This suggests that SARS-CoV-2 has the possibility of infecting the male reproductive system, and the recent detection of SARS-CoV-2 in the patient's semen further confirms this theory. In previous studies, it has been found that ACE2 has the ability to regulate autophagy. Not only that, recent studies have also found that SARS-CoV-2 infection can also lead to a reduction in autophagy. All of these associate SARS-CoV-2 with autophagy. Furthermore, autophagy has been shown to have an effect on male reproduction in many studies. Based on these, we propose the hypothesis that SARS-CoV-2 affects male reproductive function by regulating autophagy. This hypothesis may provide a new idea for future treatment of COVID-19 male patients with reproductive function injury, and it can also prompt medical staff and patients to consciously check their reproductive function.


Autoantibodies Exacerbate the Severity of MHV-Induced Encephalitis


title: Structure of the Nucleocapsid Protein of Porcine Reproductive and Respiratory Syndrome Virus

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped RNA virus of the Arteriviridae family, genomically related to the coronaviruses. PRRSV is the causative agent of both severe and persistent respiratory disease and reproductive failure in pigs worldwide. The PRRSV virion contains a core made of the 123 amino acid nucleocapsid (N) protein, a product of the ORF7 gene. We have determined the crystal structure of the capsid-forming domain of N. The structure was solved to 2.6 Å resolution by SAD methods using the anomalous signal from sulfur. The N protein exists in the crystal as a tight dimer forming a four-stranded β sheet floor superposed by two long α helices and flanked by two N- and two C-terminal α helices. The structure of N represents a new class of viral capsid-forming domains, distinctly different from those of other known enveloped viruses, but reminiscent of the coat protein of bacteriophage MS2.


title: Characteristics and Outcomes in Patients Presenting with COVID-19 and ST-Segment Elevation Myocardial Infarction

text: There is limited information regarding clinical characteristics and outcomes of patients with SARS-CoV-2 (COVID-19) disease presenting with ST-segment elevation myocardial infarction (STEMI). In this multicenter retrospective study, we reviewed charts of patients admitted with symptomatic COVID-19 infection and STEMI to a total of 4 hospitals spanning Italy, Lithuania, Spain and Iraq from February 1, 2020 to April 15, 2020. A total of 78 patients were included in this study, 49 (63%) of whom were men, with a median age of 65 [58, 71] years, and high comorbidity burden. During hospitalization, 8 (10%) developed acute respiratory distress syndrome, and 14 (18%) required mechanical ventilation. 19 (24%) patients were treated with primary PCI and 59 (76%) were treated with fibrinolytic therapy. 13 (17%) patients required cardiac resuscitation, and 9 (11%) died. For the 19 patients treated with primary PCI, 8 (42%) required intubation and 8 (42%) required cardiac resuscitation; stent thrombosis occurred in 4 patients (21%). A total of 5 patients (26%) died during hospitalization. 50 (85%) of the 59 patients initially treated with fibrinolytic therapy had successful fibrinolysis. The median time to reperfusion was 27 minutes [20, 34]. Hemorrhagic stroke occurred in 5 patients (9%). Six patients (10%) required invasive mechanical ventilation; 5 (9%) required cardiac resuscitation, and 4 (7%) died. In conclusion, this is the largest case series to-date of COVID-19 positive patients presenting with STEMI and spans 4 countries. We found a high rate of stent thrombosis, indicating a possible need to adapt STEMI management for COVID-19 patients.


title: [(18)F]Atorvastatin: synthesis of a potential molecular imaging tool for the assessment of statin-related mechanisms of action

text: BACKGROUND: Statins are lipid-lowering agents that inhibit cholesterol synthesis and are clinically used in the primary and secondary prevention of cardiovascular diseases. However, a considerable group of patients does not respond to statin treatment, and the reason for this is still not completely understood. [(18)F]Atorvastatin, the (18)F-labeled version of one of the most widely prescribed statins, may be a useful tool for statin-related research. RESULTS: [(18)F]Atorvastatin was synthesized via an optimized ruthenium-mediated late-stage (18)F-deoxyfluorination. The defluoro-hydroxy precursor was produced via Paal-Knorr pyrrole synthesis and was followed by coordination of the phenol to a ruthenium complex, affording the labeling precursor in approximately 10% overall yield. Optimization and automation of the labeling procedure reliably yielded an injectable solution of [(18)F]atorvastatin in 19% ± 6% (d.c.) with a molar activity of 65 ± 32 GBq·μmol(−1). Incubation of [(18)F]atorvastatin in human serum did not lead to decomposition. Furthermore, we have shown the ability of [(18)F]atorvastatin to cross the hepatic cell membrane to the cytosolic and microsomal fractions where HMG-CoA reductase is known to be highly expressed. Blocking assays using rat liver sections confirmed the specific binding to HMG-CoA reductase. Autoradiography on rat aorta stimulated to develop atherosclerotic plaques revealed that [(18)F]atorvastatin significantly accumulates in this tissue when compared to the healthy model. CONCLUSIONS: The improved ruthenium-mediated (18)F-deoxyfluorination procedure overcomes previous hurdles such as the addition of salt additives, the drying steps, or the use of different solvent mixtures at different phases of the process, which increases its practical use, and may allow faster translation to clinical settings. Based on tissue uptake evaluations, [(18)F]atorvastatin showed the potential to be used as a tool for the understanding of the mechanism of action of statins. Further knowledge of the in vivo biodistribution of [(18)F]atorvastatin may help to better understand the origin of off-target effects and potentially allow to distinguish between statin-resistant and non-resistant patients.


title: Chapter Three Negative Regulation of Cytosolic Sensing of DNA

text: Abstract In mammals, cytosolic detection of nucleic acids is critical in initiating innate antiviral responses against invading pathogens (like bacteria, viruses, fungi and parasites). These programs are mediated by multiple cytosolic and endosomal sensors and adaptor molecules (c-GAS/STING axis and TLR9/MyD88 axis, respectively) and lead to the production of type I interferons (IFNs), pro-inflammatory cytokines, and chemokines. While the identity and role of multiple pattern recognition receptors (PRRs) have been elucidated, such immune surveillance systems must be tightly regulated to limit collateral damage and prevent aberrant responses to self- and non-self-nucleic acids. In this review, we discuss recent advances in our understanding of how cytosolic sensing of DNA is controlled during inflammatory immune responses.


title: Metabolic host response and therapeutic approaches to influenza infection

text: Based on available metabolomic studies, influenza infection affects a variety of cellular metabolic pathways to ensure an optimal environment for its replication and production of viral particles. Following infection, glucose uptake and aerobic glycolysis increase in infected cells continually, which results in higher glucose consumption. The pentose phosphate shunt, as another glucose-consuming pathway, is enhanced by influenza infection to help produce more nucleotides, especially ATP. Regarding lipid species, following infection, levels of triglycerides, phospholipids, and several lipid derivatives undergo perturbations, some of which are associated with inflammatory responses. Also, mitochondrial fatty acid β-oxidation decreases significantly simultaneously with an increase in biosynthesis of fatty acids and membrane lipids. Moreover, essential amino acids are demonstrated to decline in infected tissues due to the production of large amounts of viral and cellular proteins. Immune responses against influenza infection, on the other hand, could significantly affect metabolic pathways. Mainly, interferon (IFN) production following viral infection affects cell function via alteration in amino acid synthesis, membrane composition, and lipid metabolism. Understanding metabolic alterations required for influenza virus replication has revealed novel therapeutic methods based on targeted inhibition of these cellular metabolic pathways.


title: Inducible Bronchus-Associated Lymphoid Tissue: Taming Inflammation in the Lung

text: Following pulmonary inflammation, leukocytes that infiltrate the lung often assemble into structures known as inducible Bronchus-Associated Lymphoid Tissue (iBALT). Like conventional lymphoid organs, areas of iBALT have segregated B and T cell areas, specialized stromal cells, high endothelial venules, and lymphatic vessels. After inflammation is resolved, iBALT is maintained for months, independently of inflammation. Once iBALT is formed, it participates in immune responses to pulmonary antigens, including those that are unrelated to the iBALT-initiating antigen, and often alters the clinical course of disease. However, the mechanisms that govern immune responses in iBALT and determine how iBALT impacts local and systemic immunity are poorly understood. Here, we review our current understanding of iBALT formation and discuss how iBALT participates in pulmonary immunity.


Insights into the June 2020 issue of the JOE


title: SARS-CoV-2 strategically mimics proteolytic activation of human ENaC

text: Molecular mimicry is an evolutionary strategy adopted by viruses to exploit the host cellular machinery. We report that SARS-CoV-2 has evolved a unique S1/S2 cleavage site, absent in any previous coronavirus sequenced, resulting in the striking mimicry of an identical FURIN-cleavable peptide on the human epithelial sodium channel α-subunit (ENaC-α). Genetic alteration of ENaC-α causes aldosterone dysregulation in patients, highlighting that the FURIN site is critical for activation of ENaC. Single cell RNA-seq from 66 studies shows significant overlap between expression of ENaC-α and the viral receptor ACE2 in cell types linked to the cardiovascular-renal-pulmonary pathophysiology of COVID-19. Triangulating this cellular characterization with cleavage signatures of 178 proteases highlights proteolytic degeneracy wired into the SARS-CoV-2 lifecycle. Evolution of SARS-CoV-2 into a global pandemic may be driven in part by its targeted mimicry of ENaC-α, a protein critical for the homeostasis of airway surface liquid, whose misregulation is associated with respiratory conditions.


title: Extra-intestinal detection of canine kobuvirus in a puppy from Southern Brazil

text: This study presents the pathological, immunohistochemical, and molecular findings associated with the extra-intestinal detection of canine kobuvirus (CaKV) in a 5-month-old Chihuahua puppy, that had a clinical history of bloody-tinged feces. Principal pathological findings were interstitial pneumonia, necrotizing bronchitis, and parvovirus-induced enteritis. Molecular diagnostic methods identified CaKV within the cerebellum, cerebrum, lung, tonsil, and liver. CaKV and rotavirus were not identified within the feces and intestine. Immunohistochemistry (IHC) assays detected antigens of CDV and CAdV-1 in the lungs. These results confirmed the extra-intestinal detection of CaKV in this puppy and represent the first extra-intestinal detection of CaKV in a dog.


title: COVID‐19 and Inequalities

text: This paper brings together evidence from various data sources and the most recent studies to describe what we know so far about the impacts of the COVID‐19 crisis on inequalities across several key domains of life, including employment and ability to earn, family life and health. We show how these new fissures interact with existing inequalities along various key dimensions, including socio‐economic status, education, age, gender, ethnicity and geography. We find that the deep underlying inequalities and policy challenges that we already had are crucial in understanding the complex impacts of the pandemic itself and our response to it, and that the crisis does in itself have the potential to exacerbate some of these pre‐existing inequalities fairly directly. Moreover, it seems likely that the current crisis will leave legacies that will impact inequalities in the long term. These possibilities are not all disequalising, but many are.


title: Phylogenetic and Pathotypic Characterization of Newcastle Disease Viruses Circulating in South China and Transmission in Different Birds

text: Although Newcastle disease virus (NDV) with high pathogenicity has frequently been isolated in poultry in China since 1948, the mode of its transmission among avian species remains largely unknown. Given that various wild bird species have been implicated as sources of transmission, in this study we genotypically and pathotypically characterized 23 NDV isolates collected from chickens, ducks, and pigeons in live bird markets (LBMs) in South China as part of an H7N9 surveillance program during December 2013–February 2014. To simulate the natural transmission of different kinds of animals in LBMs, we selected three representative NDVs—namely, GM, YF18, and GZ289—isolated from different birds to evaluate the pathogenicity and transmission of the indicated viruses in chickens, ducks, and pigeons. Furthermore, to investigate the replication and shedding of NDV in poultry, we inoculated the chickens, ducks, and pigeons with 10(6) EID(50) of each virus via intraocular and intranasal routes. Eight hour after infection, the naïve contact groups were housed with those inoculated with each of the viruses as a means to monitor contact transmission. Our results indicated that genetically diverse viruses circulate in LBMs in South China's Guangdong Province and that NDV from different birds have different tissue tropisms and host ranges when transmitted in different birds. We therefore propose the continuous epidemiological surveillance of LBMs to support the prevention of the spread of these viruses in different birds, especially chickens, and highlight the need for studies of the virus–host relationship.


title: Highly suspected cases of salmonellosis in two cats fed with a commercial raw meat-based diet: health risks to animals and zoonotic implications

text: BACKGROUND: Feeding raw meat-based diets (RMBD) to companion animals raises public health concerns for both animals and humans. While considerable attention has been paid to bacterial contamination of commercial pet food, few literature studies have investigated foodborne disease in companion animals. Salmonellosis is reported to be infrequent in cats but no known data or studies estimating feline salmonellosis are available or large-scale epidemiological studies assessing Salmonella risk factors. CASE PRESENTATION: Two highly suspected cases of salmonellosis in two cats fed with a commercial frozen poultry RMBD are presented, for the first time from the same household. The clinical presentation, diagnostics, treatment and follow-up are reported and the zoonotic implications are discussed. CONCLUSIONS: This case highlights the health risks posed to both animals and owners by feeding RMBD to pets, and suggests that these risks should be considered by veterinary practitioners.


title: Telemedicine Online Visits in Urology During the COVID-19 Pandemic—Potential, Risk Factors, and Patients’ Perspective

text: Abstract The current coronavirus disease 2019 (COVID-19) pandemic has placed considerable strain on hospital resources. We explored whether telemedicine (defined as a videoconference) might help. We undertook prospective structured phone interviews of urological patients (n = 399). We evaluated their suitability for telemedicine (judged by a panel of four physicians) and their risks from COVID-19 (10 factors for a poor outcome), and collected willingness for telemedicine and demographic data. Risk factors for an adverse outcome from COVID-19 infection were common (94.5% had one or more) and most patients (63.2%) were judged suitable for telemedicine. When asked, 84.7% of patients wished for a telemedical rather than a face-to-face consultation. Those favouring telemedicine were younger (68 [58–75] vs 76 [70–79.2] yr, p < 0.001). There was no difference in preference with oncological (mean 86%) or benign diagnoses (mean 85%), or with COVID-19 risks factors. In subgroup analysis, men with prostate cancer preferred telemedicine (odds ratio: 2.93 [1.07–8.03], p = 0.037). We concluded that many urological patients have risk factors for a poor outcome from COVID-19 and most preferred telemedicine consultations at this time. This appears to be a solution to offer contact-free continuity of care. Patient summary Risk factors for a severe course of coronavirus disease 2019 are common (94.5%) in urology patients. Most patients wished for a telemedical consultation (84.7%). This appears to be a solution to offer contact-free continuity of care.


title: Recombination and Coronavirus Defective Interfering RNAs

text: Abstract Naturally occurring defective interfering RNAs have been found in 4 of 14 coronavirus species. They range in size from 2.2 kb to approximately 25 kb, or 80% of the 30-kb parent virus genome. The large DI RNAs do not in all cases appear to require helper virus for intracellular replication and it has been postulated that they may on their own function as agents of disease. Coronavirus DI RNAs appear to arise by internal deletions (through nonhomologous recombination events) on the virus genome or on DI RNAs of larger size by a polymerase strand-switching (copy-choice) mechanism. In addition to their use in the study of virus RNA replication and virus assembly, coronavirus DI RNAs are being used in a major way to study the mechanism of a high-frequency, site-specific RNA recombination event that leads to leader acquisition during virus replication (i.e., the leader fusion event that occurs during synthesis of subgenomic mRNAs, and the leader-switching event that can occur during DI RNA replication), a distinguishing feature of coronaviruses (and arteriviruses). Coronavirus DI RNAs are also being engineered as vehicles for the generation of targeted recombinants of the parent virus genome.


title: Cell cycle arrest and apoptosis induced by the coronavirus infectious bronchitis virus in the absence of p53

text: Abstract Manipulation of the cell cycle and induction of apoptosis are two common strategies used by many viruses to regulate their infection cycles. In cells infected with coronaviruses, cell cycle perturbation and apoptosis were observed in several reports. However, little is known about how these effects are brought out, and how manipulation of the functions of host cells would influence the replication cycle of coronavirus. In this study, we demonstrate that infection with coronavirus infectious bronchitis virus (IBV) imposed a growth-inhibitory effect on cultured cells by inducing cell cycle arrest at S and G2/M phases in both p53-null cell line H1299 and Vero cells. This cell cycle arrest was catalyzed by the modulation of various cell cycle regulatory genes and the accumulation of hypophosphorylated RB, but was independent of p53. Proteasome inhibitors, such as lactacystin and NLVS, could bypass the IBV-induced S-phase arrest by restoring the expression of corresponding cyclin/Cdk complexes. Our data also showed that cell cycle arrest at both S- and G2/M-phases was manipulated by IBV for the enhancement of viral replication. In addition, apoptosis induced by IBV at late stages of the infection cycle in cultured cells was shown to be p53-independent. This conclusion was drawn based on the observations that apoptosis occurred in both IBV-infected H1299 and Vero cells, and that IBV infection did not affect the expression of p53 in host cells.


title: Protocolo diagnóstico del síndrome febril importado

text: Resumen En este protocolo expondremos los pasos a seguir en la evaluación clínica del paciente con fiebre y antecedente epidemiológico de estancia en zonas tropicales o subtropicales. No pretendemos ser exhaustivos, sino proporcionar una guía al médico que se enfrenta a una primera aproximación diagnóstica, en el Servicio de Urgencias o en la sala de hospitalización, de un enfermo procedente del trópico y que consulta por fiebre. El diagnóstico diferencial debe ir encaminado sobre todo y en primer lugar a excluir la malaria, pero también fiebres hemorrágicas, ricketsiosis, fiebre tifoidea y otras muchas infecciones, algunas solo propias de zonas tropicales y otras cosmopolitas pero de mayor prevalencia en dichas áreas. Abstract In this protocol we shall set out the steps to follow in the clinical assessment of the patient with fever and where there is an epidemiological history of travel to tropical or subtropical areas. This is not intended to be exhaustive, but as a guide to doctors in their initial diagnostic approach to the patient who has come from the tropics consulting with a fever in the Emergency Department or the hospital ward. Differential diagnosis should be approached first and foremost on the basis of excluding malaria, but haemorrhagic fevers, rickettsiosis, typhoid fever and many other infections, some that are unique to tropical areas, and others that are cosmopolitan but more prevalent in such areas should also be taken into account.


title: Development and Application of an ELISA for the Detection of Porcine Deltacoronavirus IgG Antibodies

text: Porcine deltacoronavirus (PDCoV), also known as porcine coronavirus HKU15, was first detected in North America in early 2014 and associated with enteric disease in pigs, resulting in an urgent need to further investigate the ecology of this virus. While assays detecting nucleic acids were implemented quickly, assays to detect anti-PDCoV antibodies have not been available. In this study, an indirect anti-PDCoV IgG enzyme-linked immunosorbent assay (ELISA) based on the putative S1 portion of the spike protein was developed and utilized to determine the prevalence of anti-PDCoV IgG in U.S. pigs. The diagnostic sensitivity of the PDCoV ELISA was 91% with a diagnostic specificity of 95%. A total of 968 serum samples were tested including samples with confirmed infection with PDCoV, porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus or porcine respiratory coronavirus. There was no cross-reactivity with any of the other coronaviruses. Among 355 arbitrarily selected serum samples collected in 2014 and originating from 51 farms across 18 U.S. states, anti-PDCoV IgG antibodies were detected in 8.7% of the samples and in 25.5% of the farms whereas anti-PEDV IgG was detected in 22.8% of the samples and in 54.9% of the farms. In addition, anti-PDCoV IgG antibodies were detected in archived samples collected in 2010, perhaps indicating an earlier undetected introduction into the U.S. pig population. Overall, the obtained data suggest that PDCoV seroprevalence in U.S. pigs is lower compared to PEDV and PDCoV may have been introduced to the U.S. prior to PEDV.


title: Impact of COVID-19 on maxillofacial surgery practice: a worldwide survey

text: Abstract The outbreak of coronavirus disease 2019 (COVID-19) is rapidly changing our habits. To date, April 12, 2020, the virus has reached 209 nations, affecting 1.8 million people and causing more than 110,000 deaths. Maxillofacial surgery represents an example of a specialty that has had to adapt to this outbreak, because of the subspecialties of oncology and traumatology. The aim of this study was to examine the effect of this outbreak on the specialty of maxillofacial surgery and how the current situation is being managed on a worldwide scale. To achieve this goal, the authors developed an anonymous questionnaire which was posted on the internet and also sent to maxillofacial surgeons around the globe using membership lists from various subspecialty associations. The questionnaire asked for information about the COVID-19 situation in the respondent’s country and in their workplace, and what changes they were facing in their practices in light of the outbreak. The objective was not only to collect and analyse data, but also to highlight what the specialty is facing and how it is handling the situation, in the hope that this information will be useful as a reference in the future, not only for this specialty, but also for others, should COVID-19 or a similar global threat arise again.


COVID-19 infection among medical staff in Wuhan: A retrospective study from a single-center


title: Epidemiology and immunoprotection of nephropathogenic avian infectious bronchitis virus in southern China

text: BACKGROUND: In last three years, 96 suspected poultry farms from different provinces in China were diagnosed for avian infectious bronchitis (IB) survey. Finally, 221 IBV strains were confirmed by dwarf embryo test and RT-PCR assay. By virus recovery trials, 187 of the isolates caused the birds died or distressed from nephritis, which was accordant with the clinical record. RESULTS: Based on epidemiology analysis of recent field isolates of nephropathogenic IB in vaccinated farms in China, YL6 strain were used for vaccination and evaluated by antibody titer and challenge tests. The immunoprotection test indicated that the practical application of vaccine based on the recent field strains could finely facilitate controlling the nephropathogenic IB. CONCLUSIONS: Our study was aim at setting a guide for safeguard against nephropathogenic IBV-caused disease in China.


title: Amplification of human β‐glucuronidase gene for appraising the accuracy of negative SARS‐CoV‐2 RT‐PCR results in upper respiratory tract specimens

text: Real-time reverse transcription polymerase-chain reaction (RT-PCR) is the mainstay of Covid-19 diagnosis.1 Up to 30% of patients clinically suspected of Covid-19 may have initial or repeat RT-PCR negative results prior to positive test conversion, most notably when upper respiratory tract (URT) specimens are processed.2-7 This article is protected by copyright. All rights reserved.


title: CD8+ T Lymphocyte Epitopes From The Herpes Simplex Virus Type 2 ICP27, VP22 and VP13/14 Proteins To Facilitate Vaccine Design And Characterization

text: CD8+ T cells have the potential to control HSV-2 infection. However, limited information has been available on CD8+ T cell epitopes or the functionality of antigen specific T cells during infection or following immunization with experimental vaccines. Peptide panels from HSV-2 proteins ICP27, VP22 and VP13/14 were selected from in silico predictions of binding to human HLA-A*0201 and mouse H-2Kd, Ld and Dd molecules. Nine previously uncharacterized CD8+ T cell epitopes were identified from HSV-2 infected BALB/c mice. HSV-2 specific peptide sequences stabilized HLA-A*02 surface expression with intermediate or high affinity binding. Peptide specific CD8+ human T cell lines from peripheral blood lymphocytes were generated from a HLA-A*02+ donor. High frequencies of peptide specific CD8+ T cell responses were elicited in mice by DNA vaccination with ICP27, VP22 and VP13/14, as demonstrated by CD107a mobilization. Vaccine driven T cell responses displayed a more focused immune response than those induced by viral infection. Furthermore, vaccination with ICP27 reduced viral shedding and reduced the clinical impact of disease. In conclusion, this study describes novel HSV-2 epitopes eliciting strong CD8+ T cell responses that may facilitate epitope based vaccine design and aid immunomonitoring of antigen specific T cell frequencies in preclinical and clinical settings.


title: Synthetic peptides coupled to the surface of liposomes effectively induce SARS coronavirus-specific cytotoxic T lymphocytes and viral clearance in HLA-A*0201 transgenic mice

text: We investigated whether the surface-linked liposomal peptide was applicable to a vaccine based on cytotoxic T lymphocytes (CTLs) against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV). We first identified four HLA-A*0201-restricted CTL epitopes derived from SARS-CoV using HLA-A*0201 transgenic mice and recombinant adenovirus expressing predicted epitopes. These peptides were coupled to the surface of liposomes, and inoculated into mice. Two of the liposomal peptides were effective for peptide-specific CTL induction, and one of them was efficient for the clearance of vaccinia virus expressing epitopes of SARS-CoV, suggesting that the surface-linked liposomal peptide might offer an effective CTL-based vaccine against SARS.


title: Chapter 4 Interaction of virus populations with their hosts

text: Abstract Viral population numbers are extremely large compared with those of their host species. Population bottlenecks are frequent during the life cycle of viruses and can reduce viral populations transiently to very few individuals. Viruses have to confront several types of constraints that can be divided into basal, cell-dependent, and organism-dependent constraints. Viruses overcome them exploiting a number of molecular mechanisms, with an important contribution of population numbers and genome variation. The adaptive potential of viruses is reflected in modifications of cell tropism and host range, escape to components of the host immune response, and capacity to alternate among different host species, among other phenotypic changes. Despite a fitness cost of most mutations required to overcome a selective constraint, viruses can find evolutionary pathways that ensure their survival in equilibrium with their hosts.


title: Contact Transmission of COVID-19 in South Korea: Novel Investigation Techniques for Tracing Contacts

text: In the epidemiological investigation of an infectious disease, investigating, classifying, tracking, and managing contacts by identifying the patient’s route are important for preventing further transmission of the disease. However, omissions and errors in previous activities can occur when the investigation is performed through only a proxy interview with the patient. To overcome these limitations, methods that can objectively verify the patient’s claims (medical facility records, Global Positioning System, card transactions, and closed-circuit television) were used for the recent ongoing coronavirus disease 2019 contact investigations in South Korea.


title: Translating old drugs into new treatments: ribosomal frameshifting as a target for antiviral agents

text: Abstract Programmed ribosomal frameshifting is used by many viruses to regulate the production of structural and enzymatic proteins. Altering the frameshifting efficiencies disrupts the virus life cycle and eliminates or reduces virus production. Ribosomal frameshifting therefore provides a unique target on which antiviral agents can function. This article describes a series of rapid assay strategies that have been developed and used to identify potential antiviral agents that target programmed −1 ribosomal frameshifting.


title: Nasal delivery of Protollin-adjuvanted H5N1 vaccine induces enhanced systemic as well as mucosal immunity in mice

text: Abstract Sporadic, yet frequent human infections with avian H5N1 influenza A viruses continue to pose a potential pandemic threat. Poor immunogenicity of unadjuvanted H5N1 vaccines warrants developing novel adjuvants and formulations as well as alternate delivery systems to improve their immunogenicity and efficacy. Here, we show that Protollin, a nasal adjuvant composed of Neisseria meningitides outer membrane proteins non-covalently linked to Shigella flexneri 2a lipopolysaccharide, is a potent nasal adjuvant for an inactivated split virion H5N1 clade 1 A/Viet Nam1203/2004 (A/VN/1203/04) vaccine in a mouse model. Protollin-adjuvanted vaccines elicited enhanced serum protective hemagglutination inhibition titers, mucosal IgA responses, and H5N1-specific cell-mediated immunity that resulted in complete protection against a lethal challenge with a homologous virus as well as a heterologous clade 2 virus A/Indonesia/05/2005 (A/IN/05/05). Detailed analysis of adaptive immunity revealed that Protollin increased the frequency of lymphoid- as well as local tissue-resident antibody-secreting cells, local germinal center reaction of B cells, broad-spectrum of CD4 T cell response. Our findings suggest that nasal delivery of H5N1 vaccine with Protollin adjuvant can overcome the poor immunogenicity of H5N1 vaccines, induce both cellular and humoral immune responses, enhance protection against challenge with clade 1 and clade 2 H5N1 viruses and achieve significant antigen dose-sparing.


title: Influence of plant origin on propagation capacity and alkaloid biosynthesis during long-term in vitro cultivation of Leucojum aestivum L.

text: The investigation deals with in vitro clonal propagation of L. aestivum L. (summer snowflake), a threatened Amaryllidaceae plant species in Bulgaria used in the pharmaceutical industry as raw material for production of galanthamine-based medicines. Plants of known origin and with different alkaloid profile were taken from the living collection of the Institute of Botany, Sofia. Bulbs were used to initiate in vitro cultures and 24 clones were multiplied. The influence of the clone origin on the propagation coefficient, shoot and bulblet morphology, alkaloid profile and content of galanthamine, lycorine, and four related alkaloids was evaluated. Clones kept stable alkaloid profiles and for most of them, high regeneration rates were noted. Galanthamine content of some clones was commensurable with that of Bulgarian populations of L. aestivum of commercial importance. Five clones: four galanthamine-type and one lycorine-type were selected as promising for further investigation.


title: Social network analysis on a topic‐based navigation guidance system in a public health portal

text: We investigated a topic‐based navigation guidance system in the World Health Organization portal, compared the link connection network and the semantic connection network derived from the guidance system, analyzed the characteristics of the 2 networks from the perspective of the node centrality (in_closeness, out_closeness, betweenness, in_degree, and out_degree), and provided the suggestions to optimize and enhance the topic‐based navigation guidance system. A mixed research method that combines the social network analysis method, clustering analysis method, and inferential analysis methods was used. The clustering analysis results of the link connection network were quite different from those of the semantic connection network. There were significant differences between the link connection network and the semantic network in terms of density and centrality. Inferential analysis results show that there were no strong correlations between the centrality of a node and its topic information characteristics. Suggestions for enhancing the navigation guidance system are discussed in detail. Future research directions, such as application of the same research method presented in this study to other similar public health portals, are also included.


title: Témoignage: Expérience d’un étudiant en Masso-Kinésithérapie en renfort dans un EPHAD touché par le COVID-19

text: Abstract As a physiotherapist student, I was asked by the ARS to reinforce the care team of a nursing home welcoming residents affected by Covid-19. I had to acquire the specific hygiene and protection rules for this situation in addition to nursing work. Whenever necessary, I applied my physiotherapist knowledge’s to serve residents and carers. This disease is exhausting for the patients; their respiratory and general condition can fluctuate quickly. Without treatment to cure them, we have to accompany them as comfortably as possible.


title: Availability of COVID-19 Information from National and International Aesthetic Surgery Society Websites

text: BACKGROUND: National and international aesthetic surgery society websites are an important source of information for patients and aesthetic surgeons. The current COVID-19 pandemic represents an unprecedented global health crisis. The aim of this study was to assess the information available on national and international aesthetic surgery society websites on the current pandemic of COVID-19. METHODS: National and international aesthetic surgery society websites were assessed with regard to COVID-19 information. RESULTS: Thirty-one per cent of nations had aesthetic surgery society websites. Twenty-two per cent of national society websites had a specific COVID-19 section. Seventeen per cent of these websites had COVID-19-specific guidelines available; of these websites with guidelines, 77% had a specific COVID-19 section advising to provide only urgent or emergent care and 46% provided their sovereign state’s directives to provide only urgent or emergent care. Two international aesthetic surgery society websites had COVID-19-specific guidelines, and one of the two had significant educational resources. CONCLUSION: The availability of COVID-19 clinical guidelines and patient information sheets on national plastic surgery society websites is sparse. In contrast, one international society website carefully analysed national and international recommendations and guidelines and made general recommendations for its members with regularly updated resources. This study suggests that improvement and increase in COVID-19 information provided by many national aesthetic surgery society websites may be improved by links to the ISAPS website. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.


title: Histopathological characterization of the naturally occurring hepatotropic virus infections of nude mice

text: In the last ten years the mutant athymic nude mouse has been used by many researchers as a model for studying pathological conditions in an immunodeficient host. A major problem with such mice is their susceptibility to viral infections indigenous to murine stocks, such as the hepatotropic mouse coronaviruses. In an effort to define the hepatotropic virus diseases indigenous to nude mice this paper details the pathogenesis and associated comparative histopathology of three common strains of mouse hepatitis virus, reovirus 3 and murine cytomegalovirus in the nude mouse.


title: Structural and molecular basis of mismatch correction and ribavirin excision from coronavirus RNA

text: Coronaviruses (CoVs) stand out among RNA viruses because of their unusually large genomes (∼30 kb) associated with low mutation rates. CoVs code for nsp14, a bifunctional enzyme carrying RNA cap guanine N7-methyltransferase (MTase) and 3′-5′ exoribonuclease (ExoN) activities. ExoN excises nucleotide mismatches at the RNA 3′-end in vitro, and its inactivation in vivo jeopardizes viral genetic stability. Here, we demonstrate for severe acute respiratory syndrome (SARS)-CoV an RNA synthesis and proofreading pathway through association of nsp14 with the low-fidelity nsp12 viral RNA polymerase. Through this pathway, the antiviral compound ribavirin 5′-monophosphate is significantly incorporated but also readily excised from RNA, which may explain its limited efficacy in vivo. The crystal structure at 3.38 Å resolution of SARS-CoV nsp14 in complex with its cofactor nsp10 adds to the uniqueness of CoVs among RNA viruses: The MTase domain presents a new fold that differs sharply from the canonical Rossmann fold.


title: Case Report: Clinical Treatment of the First Critical Patient With Coronavirus Disease (COVID-19) in Liaocheng, Shandong Province

text: This paper reports the clinical characteristics, diagnosis, and treatment of the first critical COVID-19 patient in Liaocheng City, who was admitted to the intensive care unit isolation ward of Liaocheng People's Hospital on February 11, 2020. On admission, the patient had difficulty breathing, the oxygenation index was 135 mmHg, and the blood lactate was 5.6 mmol/L. After comprehensive treatment including high-flow nasal cannula oxygen therapy, plasma exchange, antiviral and anti-infection therapies, immune regulation, liquid volume management, glucocorticoid, enteral nutrition support, analgesia and sedation, blood glucose control, anticoagulation and thrombus prevention, and electrolyte balance maintenance, the patient was finally cured, and discharged. The purpose of this case report is to provide a reference for the clinical diagnosis and treatment of critical COVID-19 patients.