title: Inhibitory effect of anti-aminopeptidase N/CD13 antibodies on fibroblast migration

text: Aminopeptidase N (APN)/CD13 is a widely expressed transmembrane ectoenzyme and has been implicated in a myriad of physiological processes that are specific to cell type and tissue origin, including cancer cell metastasis, angiogenesis, cholesterol uptake, apoptosis, and cell migration. Skin cells, in particular fibroblasts have a relatively high level of APN/CD13 expression. The migratory capacity of skin cells is critical for the outcome of wound repair, as successful wound healing requires timely re-epithelialization which involves reformation of epithelium over wound surface by migrating keratinocytes. While failure of keratinocytes to undergo proper migration leads to chronic non-healing wounds, the presence of excess fibroblasts may contribute to formation of hypertrophic scars and keloids. The aim of this study was to investigate the role of APN/CD13 in skin cell migration and explore its potential as a therapeutic target in wound healing. Our results show an elevated expression of APN/CD13 in fibroblasts on the edge of the wound compared to unwounded cells. The presence of anti-APN/CD13 antibodies WM15, 3D8, and H300 reduces the migratory activity of human dermal fibroblasts in a dose-dependent manner by 42, 21, and 28%, respectively. However, the antibodies have no effect on keratinocyte migration. Further, none of the anti-APN/CD13 antibodies used in this study has any antiproliferative and cytotoxic effect on primary human keratinocytes or fibroblasts when used at 10 μg/ml in vitro. The differential inhibition on the migratory capacity of fibroblasts and keratinocytes presents an opportunity for anti-APN/CD13 antibodies to be used as a therapeutic agent for high fibroblast cellularity seen in fibroproliferative disorders.


When do you say it's SARS‐CoV‐2‐associated diarrhea?


Could patients taking isotretinoin therapy be immune against SARS‐CoV‐2?


title: Recent advances in influenza vaccines

text: Seasonal influenza remains a major public health problem, responsible for hundreds of thousands of deaths every year, mostly of elderly people. Despite the wide availability of vaccines, there are multiple problems decreasing the effectiveness of vaccination programs. These include viral variability and hence the requirement to match strains by estimating which will become prevalent each season, problems associated with vaccine and adjuvant production, and the route of administration as well as the perceived lower vaccine efficiency in older adults. Clinical protection is still suboptimal for all of these reasons, and vaccine uptake remains too low in most countries. Efforts to improve the effectiveness of influenza vaccines include developing universal vaccines independent of the circulating strains in any particular season and stimulating cellular as well as humoral responses, especially in the elderly. This commentary assesses progress over the last 3 years towards achieving these aims. Since the beginning of 2020, an unprecedented international academic and industrial effort to develop effective vaccines against the new coronavirus SARS-CoV-2 has diverted attention away from influenza, but many of the lessons learned for the one will synergize with the other to mutual advantage. And, unlike the SARS-1 epidemic and, we hope, the SARS-CoV-2 pandemic, influenza will not be eliminated and thus efforts to improve influenza vaccines will remain of crucial importance.


title: Early Self‐Proning in Awake, Non‐intubated Patients in the Emergency Department: A Single ED’s Experience During the COVID‐19 Pandemic

text: OBJECTIVE: Prolonged and unaddressed hypoxia can lead to poor patient outcomes. Proning has become a standard treatment in the management of patients with ARDS who have difficulty achieving adequate oxygen saturation. The purpose of this study was to describe the use of early proning of awake, non‐intubated patients in the emergency department (ED) during the COVID‐19 pandemic. METHODS: This pilot study was carried out in a single urban ED in New York City. We included patients suspected of having COVID‐19 with hypoxia on arrival. A standard pulse oximeter was used to measure SpO(2). SpO(2) measurements were recorded at triage and after 5 minutes of proning. Supplemental oxygenation methods included non‐rebreather mask (NRB) and nasal cannula. We also characterized post‐proning failure rates of intubation within the first 24 hours of arrival to the ED. RESULTS: Fifty patients were included. Overall, the median SpO(2) at triage was 80% (IQR 69 to 85). After application of supplemental oxygen was given to patients on room air it was 84% (IQR 75 to 90). After 5 minutes of proning was added SpO(2) improved to 94% (IQR 90 to 95). Comparison of the pre‐ to post‐median by the Wilcoxon Rank‐sum test yielded P = 0.001. Thirteen patients (24%) failed to improve or maintain their oxygen saturations and required endotracheal intubation within 24 hours of arrival to the ED. CONCLUSION: Awake early self‐proning in the emergency department demonstrated improved oxygen saturation in our COVID‐19 positive patients. Further studies are needed to support causality and determine the effect of proning on disease severity and mortality.


title: Predictors of symptoms of posttraumatic stress in Chinese university students during the 2009 H1N1 influenza pandemic

text: BACKGROUND: The university environment poses a high risk of spreading infectious diseases, particularly the 2009 pandemic influenza H1N1, as it is a mass gathering place for youth. This study aimed to evaluate the predictors of stress symptoms among Chinese university students during the 2009 H1N1 influenza pandemic. MATERIAL/METHODS: We used a self-reported questionnaire, the PTSD (posttraumatic stress disorder) Checklist-Civilian Version (PCL-C) to evaluate the stress symptoms among Chinese university students from Heilongjiang (n=455), Beijing (n=106), Shanghai (n=419) and Sichuan (n=102). We then analyzed the predictors of stress symptoms. RESULTS: The proportion of university students enrolled in this study who met symptomatic criteria for PTSD was 2% (22 students). The mean PCL-C total score in the sample was 22.09±8.01. The correlational analyses revealed a significant positive relationship between the PCL-C total score and area, and university grade (P<0.01). Moreover, a negative relationship was found between the PCL-C total score and gender, having H1N1 influenza, having family members, friends or acquaintances having H1N1 influenza, and being afraid of H1N1 influenza (P<0.01). The regression analyses showed that in North China, female gender, having H1N1 influenza, having family members or acquaintances with H1N1 influenza, and being afraid of H1N1 influenza were significant predictors of the stress symptoms. CONCLUSIONS: In North China, female gender, having H1N1 influenza, having family members, friends, or acquaintances with H1N1 influenza, and being afraid of H1N1 influenza were significant predictors of the stress symptoms.


title: Efficiency of Airborne Sample Analysis Platform (ASAP) bioaerosol sampler for pathogen detection

text: The threat of bioterrorism and pandemics has highlighted the urgency for rapid and reliable bioaerosol detection in different environments. Safeguarding against such threats requires continuous sampling of the ambient air for pathogen detection. In this study we investigated the efficacy of the Airborne Sample Analysis Platform (ASAP) 2800 bioaerosol sampler to collect representative samples of air and identify specific viruses suspended as bioaerosols. To test this concept, we aerosolized an innocuous replication-defective bovine adenovirus serotype 3 (BAdV3) in a controlled laboratory environment. The ASAP efficiently trapped the surrogate virus at 5 × 10(3) plaque-forming units (p.f.u.) [2 × 10(5) genome copy equivalent] concentrations or more resulting in the successful detection of the virus using quantitative PCR. These results support the further development of ASAP for bioaerosol pathogen detection.


title: RETRACTED ARTICLE: Interferon-mediated antiviral activities of Angelica tenuissima Nakai and its active components

text: Angelica tenuissima Nakai is a widely used commodity in traditional medicine. Nevertheless, no study has been conducted on the antiviral and immune-modulatory properties of an aqueous extract of Angelica tenuissima Nakai. In the present study, we evaluated the antiviral activities and the mechanism of action of an aqueous extract of Angelica tenuissima Nakai both in vitro and in vivo. In vitro, an effective dose of Angelica tenuissima Nakai markedly inhibited the replication of Influenza A virus (PR8), Vesicular stomatitis virus (VSV), Herpes simplex virus (HSV), Coxsackie virus, and Enterovirus (EV-71) on epithelial (HEK293T/HeLa) and immune (RAW264.7) cells. Such inhibition can be described by the induction of the antiviral state in cells by antiviral, IFNrelated gene induction and secretion of IFNs and pro-inflammatory cytokines. In vivo, Angelica tenuissima Nakai treated BALB/c mice displayed higher survivability and lower lung viral titers when challenged with lethal doses of highly pathogenic influenza A subtypes (H1N1, H5N2, H7N3, and H9N2). We also found that Angelica tenuissima Nakai can induce the secretion of IL-6, IFN-λ, and local IgA in bronchoalveolar lavage fluid (BALF) of Angelica tenuissima Nakai treated mice, which correlating with the observed prophylactic effects. In HPLC analysis, we found the presence of several compounds in the aqueous fraction and among them; we evaluated antiviral properties of ferulic acid. Therefore, an extract of Angelica tenuissima Nakai and its components, including ferulic acid, play roles as immunomodulators and may be potential candidates for novel anti-viral/anti-influenza agents.


title: Advances Towards Painless Vaccination and Newer Modes of Vaccine Delivery

text: Vaccines have been successful in reducing the mortality and morbidity, but most of them are delivered by intramuscular or intravenous route. They are associated with pain to the baby and bring lot of anxiety for the parents. There has been a marked increase in the number of injections required in first two years of life for completing the vaccination schedule. Hence, there is a need to have a painless vaccine delivery system. Numerous new routes of vaccination like, oral, nasal and transdermal routes are being tried. Oral polio and intranasal influenza have already been a success. Other newer approaches like edible vaccines, nasal sprays, dry powder preparations, jet injectors, microneedles and nanopatches are promising in delivering painless vaccines. Many of them are under clinical trials. These vaccine delivery systems will not only be painless but also cost effective, safe and easy to administer in mass population. They may be devoid of the need of cold chain. Painless delivery system will ensure better compliance to vaccination schedule.


title: MERS-CoV geography and ecology in the Middle East: analyses of reported camel exposures and a preliminary risk map

text: BACKGROUND: Middle Eastern respiratory syndrome coronavirus (MERS-CoV) has spread rapidly across much of the Middle East, but no quantitative mapping of transmission risk has been developed to date. Moreover, details of the transmission cycle of the virus remain unclear, particularly regarding the role of camels as a reservoir host for human infections. METHODS: We present a first analysis of the environmental circumstances under which MERS-CoV cases have occurred in the Middle East, covering all case occurrences through May 2015, using ecological niche modeling approaches to map transmission risk. We compare the environmental breadth of conditions under which cases have reported camel contacts with that of the broader population of all cases, to assess whether camel-associated cases occur under a more restricted set of environmental circumstances. RESULTS: We documented geographic and environmental distributions of MERS-CoV cases across the Middle East, and offer preliminary mapping of transmission risk. We confirm the idea that climatic dimensions of camel-associated cases are more constrained and less variable than the broader suite of case occurrences; hence, camel exposure may be a key limiting element in MERS-CoV transmission. CONCLUSION: This study offers a first detailed geographic and environmental analysis of MERS-CoV distributions across the Middle East. Results indicated that camel-exposed cases occur under a narrower suite of environmental conditions than non-camel-exposed cases, suggesting perhaps a key role for camels in the transmission of the disease, and perhaps a narrower area of risk for ‘primary,’ camel-derived cases of MERS.


title: The Globalization of Healthcare: Implications of Medical Tourism for the Infectious Disease Clinician

text: Travel abroad for healthcare has increased rapidly; interventions include organ transplant; cardiac surgery; reproductive care; and joint, cosmetic, and dental procedures. Individuals who receive medical care abroad are a vulnerable, sentinel population, who sample the local environment and can carry home unusual and resistant infections, documented in many reports. Medical tourists are at risk for hospital-associated and procedure-related infections as well as for locally endemic infections. Patients may not volunteer details about care abroad, so clinicians must inquire about medical procedures abroad as well as recent travel. Special infection control measures may be warranted. Healthcare abroad is associated with diverse financial, legal, ethical, and health-related issues. We focus on problems the infectious disease clinician may encounter and provide a framework for evaluating returned medical tourists with suspected infections. A better system is needed to ensure broad access to high-quality health services, continuity of care, and surveillance for complications.


Fulminant Necrotizing Fasciitis and Nonsteroidal Anti-Inflammatory Drugs


title: Nocardia polymerase chain reaction (PCR)-based assay performed on bronchoalveolar lavage fluid after lung transplantation: A prospective pilot study

text: BACKGROUND: Transplant recipients are at risk of pulmonary nocardiosis, a life-threatening opportunistic infection caused by Nocardia species. Given the limitations of conventional diagnostic techniques (i.e., microscopy and culture), a polymerase chain reaction (PCR)-based assay was developed to detect Nocardia spp. on clinical samples. While this test is increasingly being used by transplant physicians, its performance characteristics are not well documented. We evaluated the performance characteristics of this test on bronchoalveolar lavage (BAL) fluid samples from lung transplant recipients (LTRs). METHODS: We prospectively included all BAL samples from LTRs undergoing bronchoscopy at our institution between December 2016 and June 2017 (either surveillance or clinically-indicated bronchoscopies). Presence of microbial pathogens was assessed using techniques available locally (including microscopy and 10-day culture for Nocardia). BAL samples were also sent to the French Nocardiosis Observatory (Lyon, France) for the Nocardia PCR-based assay. Transplant physicians and patients were blinded to the Nocardia PCR results. RESULTS: We included 29 BAL samples from 21 patients (18 surveillance and 11 clinically-indicated bronchoscopies). Nocardiosis was not diagnosed in any of these patients by conventional techniques. However, Nocardia PCR was positive in five BAL samples from five of the patients (24%, 95% confidence interval: 11–45%); four were asymptomatic and undergoing surveillance bronchoscopy, and one was symptomatic and was later diagnosed with influenza virus infection. None of the five PCR-positive patients died or were diagnosed with nocardiosis during the median follow-up of 21 months after the index bronchoscopy (range: 20–23 months). CONCLUSIONS: In this prospective study, Nocardia PCR was positive on BAL fluid from one fourth of the LTRs. Nocardia PCR-based assays should be used with caution on respiratory samples from LTRs because of the possible detection of airway colonization using this technique. Larger studies are required to determine the usefulness of the Nocardia PCR-based assay in transplant recipients.


title: Functional movement disorders in a patient with COVID-19

text: The infectious diseases (ID) specialty continues to be in crisis due to a lack of interest by residents in the recruitment pool It is possible that enhancing and innovating how microbiology is taught in medical school could increase the interest in ID We need to improve teaching of preclinical medical microbiology and immunology by incorporating advancements in education and learning technologies to reignite the interest in the field The shortage of ID specialists has important implications in our fight against ID threats such as the current COVID-19 global pandemic In order to address this problem, we need to perform extensive research to identify the issues that medical learners and trainees are facing as they progress through their medical education towards the ID specialty


Caution and clarity required in the use of chloroquine for COVID-19


African Primates: Likely Victims, Not Reservoirs, of Ebolaviruses


title: Investigation into the Role of Potentially Contaminated Feed as a Source of the First-Detected Outbreaks of Porcine Epidemic Diarrhea in Canada

text: SUMMARY: In January 2014, approximately 9 months following the initial detection of porcine epidemic diarrhea (PED) in the USA, the first case of PED was confirmed in a swine herd in south-western Ontario. A follow-up epidemiological investigation carried out on the initial and 10 subsequent Ontario PED cases pointed to feed as a common risk factor. As a result, several lots of feed and spray-dried porcine plasma (SDPP) used as a feed supplement were tested for the presence of PEDV genome by real-time RT-PCR assay. Several of these tested positive, supporting the notion that contaminated feed may have been responsible for the introduction of PEDV into Canada. These findings led us to conduct a bioassay experiment in which three PEDV-positive SDPP samples (from a single lot) and two PEDV-positive feed samples supplemented with this SDPP were used to orally inoculate 3-week-old piglets. Although the feed-inoculated piglets did not show any significant excretion of PEDV, the SDPP-inoculated piglets shed PEDV at a relatively high level for ≥9 days. Despite the fact that the tested PEDV genome positive feed did not result in obvious piglet infection in our bioassay experiment, contaminated feed cannot be ruled out as a likely source of this introduction in the field where many other variables may play a contributing role.


title: Nasal swab bacteriology by PCR during the first 24‐months of life: A prospective birth cohort study

text: BACKGROUND: Most respiratory bacterial carriage studies in children are based on cross‐sectional samples or longitudinal studies with infrequent sampling points. The prospective Observational Research in Childhood Infectious Diseases birth cohort study intensively evaluated the community‐based epidemiology of respiratory viruses and bacteria during the first 2‐years of life. Here we report the bacteriologic findings. METHODS: Pregnant women in Brisbane, Australia were recruited between September 2010 and October 2012, and their healthy newborn children were followed for the first 2‐years of life. Parents kept a daily symptom diary for the study child, collected a weekly anterior nose swab and completed an illness burden diary when their child met pre‐defined illness criteria. Specimens were tested for respiratory bacteria by real‐time polymerase chain reaction (PCR) assays and those containing human genomic DNA, deemed as high‐quality, were analyzed. RESULTS: Altogether 8100 high‐quality nasal swab specimens from 158 enrolled children were analyzed. Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae were detected in 42.4%, 38.9%, and 14.8% of these samples, respectively. Concomitant detection of bacteria was common. In contrast, Bordetella pertussis, B. parapertussis, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Simkania negevensis were rarely identified. The prevalence of the three major bacteria was higher with increasing age and in the winter and spring months. Siblings and childcare attendance were the other risk factors identified. CONCLUSIONS: We confirmed the feasibility of frequent nasal swabbing by parents for studying bacterial colonization. PCR detected the major respiratory tract bacteria with expected high frequencies, but atypical bacteria were found rarely in this cohort.


COVID-19 con afectación pulmonar. Una enfermedad autoinmune de causa conocida


COVID-19 Outbreak and Inflammatory Bowel Disease Management: A Questionnaire Survey From Realistic Practice


title: A Compact Immunoassay Platform Based on a Multicapillary Glass Plate

text: A highly sensitive, rapid immunoassay performed in the multi-channels of a micro-well array consisting of a multicapillary glass plate (MCP) and a polydimethylsiloxane (PDMS) slide is described. The micro-dimensions and large surface area of the MCP permitted the diffusion distance to be decreased and the reaction efficiency to be increased. To confirm the concept of the method, human immunoglobulin A (h-IgA) was measured using both the proposed immunoassay system and the traditional 96-well plate method. The proposed method resulted in a 1/5-fold decrease of immunoassay time, and a 1/56-fold cut in reagent consumption with a 0.05 ng/mL of limit of detection (LOD) for IgA. The method was also applied to saliva samples obtained from healthy volunteers. The results correlated well to those obtained by the 96-well plate method. The method has the potential for use in disease diagnostic or on-site immunoassays.


title: Strengths, Weaknesses, Opportunities and Threats (SWOT) Analysis of China’s Prevention and Control Strategy for the COVID-19 Epidemic

text: This study used the Strengths (S), Weaknesses (W), Opportunities (O) and Threats (T) (SWOT) analysis method, drawing on our experience of the response to the 2003 SARS epidemic, the 2019 China Health Statistics Yearbook data, and changes in China’s policy environment for the pneumonia epidemic response relating to the novel coronavirus (COVID-19) infection, to perform a systematic analysis of the COVID-19 epidemic prevention and control strategy S, W, O, and T, with a further analysis of a strategic foundation and to determine a significant and relative strategy. We assessed and formulated strength-opportunity (SO), weakness-opportunity (WO), strength-threat (ST), and weakness-threat (WT) strategies for the prevention and control of the COVID-19 epidemic. We conducted an in-depth analysis and identified the highest-priority policies. These are: reshaping the emergency system (SO1); adding health emergency departments to universities and other institutions (WO2); adjusting the economic structure and strengthening international and domestic linkages (ST2); and strengthening public intervention in responding to public health emergencies (WT1).


title: Dengue virus infection induces autophagy: an in vivo study

text: BACKGROUND: We and others have reported that autophagy is induced by dengue viruses (DVs) in various cell lines, and that it plays a supportive role in DV replication. This study intended to clarify whether DV infection could induce autophagy in vivo. Furthermore, the effect of DV induced autophagy on viral replication and DV-related pathogenesis was investigated. RESULTS AND CONCLUSIONS: The physiopathological parameters were evaluated after DV2 was intracranially injected into 6-day-old ICR suckling mice. Autophagy-related markers were monitored by immunohistochemical/immunofluorescent staining and Western blotting. Double-membrane autophagic vesicles were investigated by transmission-electron-microscopy. DV non-structural-protein-1 (NS1) expression (indicating DV infection) was detected in the cerebrum, medulla and midbrain of the infected mice. In these infected tissues, increased LC3 puncta formation, LC3-II expression, double-membrane autophagosome-like vesicles (autophagosome), amphisome, and decreased p62 accumulation were observed, indicating that DV2 induces the autophagic progression in vivo. Amphisome formation was demonstrated by colocalization of DV2-NS1 protein or LC3 puncta and mannose-6-phosphate receptor (MPR, endosome marker) in DV2-infected brain tissues. We further manipulated DV-induced autophagy by the inducer rapamycin and the inhibitor 3-methyladenine (3MA), which accordingly promoted or suppressed the disease symptoms and virus load in the brain of the infected mice. We demonstrated that DV2 infection of the suckling mice induces autophagy, which plays a promoting role in DV replication and pathogenesis.


title: The effects of COVID-19 induced lockdown measures on maritime settings of a coastal region

text: Abstract The spread of coronavirus (COVID-19) caused an unprecedented implementation of lockdown measures across world's nations. Veneto Region, located in the North-Eastern Italy was one of the first maritime regions in Italy and Europe subjected to progressive lockdown restrictions. We systematically analyse the effects of national lockdown policies on maritime settings of the region using Automated Identification System (AIS) data from fishing vessels, passenger ships, tanker and cargo vessels collected through the Aqua Alta Oceanographic Tower (AAOT). We derive consequences on vessel activities during the March–April 2020 lockdown, by using a data-driven, comparative spatio-temporal analysis for vessel trajectories. Results show that compared to the same period of 2017, we found that vessel activity were reduced by 69% during the lockdown, fishing activities reduced by 84% and passenger traffic by 78%. We register a restart of fishing activity in the third week of April 2020. We suggest that the presented conceptual and spatial assessment protocol can guide future research on environmental and socio-economic effects of COVID-19 on marine realms and contribute to further interdisciplinary research with other marine scientific fields.


title: Complete Genome Sequences of Two Genetically Distinct Variants of Porcine Epidemic Diarrhea Virus in the Eastern Region of Thailand

text: Porcine epidemic diarrhea virus (PEDV) has continued to cause sporadic outbreaks in Thailand since 2007. Previously, PEDV in Thailand was a new variant containing an insertion and deletion in the spike gene. Herein, full-length genome sequences are reported for two variants of PEDV isolates from pigs displaying diarrhea in Thailand.


Editorial note for manuscripts from the Second International Congress of the Asia Pacific Society of Infection Control (Singapore, March 14-17, 2004) submitted for publication in the American Journal of Infection Control


title: In vitro and in vivo evaluation of small interference RNA‐mediated gynaecophoral canal protein silencing in Schistosoma japonicum

text: BACKGROUND: Schistosomiasis causes liver and intestinal damage and can be very debilitating. The pairing of a male worm with a female worm residing in the gynaecophoral canal of male plays a critical role in the development of female parasite. Because the male specific gynaecophoral canal protein of Schistosoma japonicum (SjGCP) is found in significant quantities in the adult female worm after pairing, it could play an important role in parasite pairing. METHODS: In the present study, three small interfering (si)RNA duplexes targeting the SjGCP gene were designed, synthesized and the silencing effects were evaluated in vitro as well as in mice infected with S. japonicum in vivo. RESULTS: In vitro studies using semi‐quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR) and real‐time RT‐PCR revealed the reduction of SjGCP at the transcript level. Similarly, western blotting and immunofluorescence studies showed its reduction at the protein level after treatment of parasites with siRNAs. At a concentration of 200 nm, two siRNAs totally abolished the parasite pairing. To evaluate such a pairing inhibitory effect in vivo, mice infected with S. japonicum were treated with siRNA and both parasite pairing and burden were evaluated. In vivo tests confirmed the in vitro silencing effect of SjGCP siRNA and revealed that the systemic delivery of siRNA significantly inhibited early parasite pairing and the associated burden. CONCLUSIONS: Our preliminary results demonstrated that the SjGCP plays an important role in pairing and subsequent development in S. japonicum, and its silencing might have potential as a therapeutic approach for controlling schistosomiasis. Copyright © 2009 John Wiley & Sons, Ltd.


title: Viroporins: structure and biological functions

text: Viroporins are small, hydrophobic proteins that are encoded by a wide range of clinically relevant animal viruses. When these proteins oligomerize in host cell membranes, they form hydrophilic pores that disrupt a number of physiological properties of the cell. Viroporins are crucial for viral pathogenicity owing to their involvement in several diverse steps of the viral life cycle. Thus, these viral proteins, which include influenza A virus matrix protein 2 (M2), HIV-1 viral protein U (Vpu) and hepatitis C virus p7, represent ideal targets for therapeutic intervention, and several compounds that block their pore-forming activity have been identified. Here, we review recent studies in the field that have advanced our knowledge of the structure and function of this expanding family of viral proteins.


title: Evaluation of Low versus High Volume per Minute Displacement CO(2) Methods of Euthanasia in the Induction and Duration of Panic-Associated Behavior and Physiology

text: SIMPLE SUMMARY: Current recommendations for the use of CO(2) as a euthanasia agent for rats require the use of gradual fill methods in order to render the animal insensible prior to their experience of pain. However, there is concern that the use of these gradual fill methods may increase the distress experienced by these animals. We evaluated social and anxiety behavior of rats that had been exposed to concentrations of CO(2) that did not cause a loss of consciousness. We also evaluated the physiologic changes of rats that were euthanized with gradual fill protocols as compared to rapid fill methods. We found that rats exposed to concentrations of CO(2) that did not cause a loss of consciousness did exhibit increased anxiety and decreased social behavior. We also found that the use of a 10% volume per minute displacement rate of CO(2) resulted in physiologic and behavioral changes suggestive of distress. ABSTRACT: Current recommendations for the use of CO(2) as a euthanasia agent for rats require the use of gradual fill protocols (such as 10% to 30% volume displacement per minute) in order to render the animal insensible prior to exposure to levels of CO(2) that are associated with pain. However, exposing rats to CO(2), concentrations as low as 7% CO(2) are reported to cause distress and 10%–20% CO(2) induces panic-associated behavior and physiology, but loss of consciousness does not occur until CO(2) concentrations are at least 40%. This suggests that the use of the currently recommended low flow volume per minute displacement rates create a situation where rats are exposed to concentrations of CO(2) that induce anxiety, panic, and distress for prolonged periods of time. This study first characterized the response of male rats exposed to normoxic 20% CO(2) for a prolonged period of time as compared to room air controls. It demonstrated that rats exposed to this experimental condition displayed clinical signs consistent with significantly increased panic-associated behavior and physiology during CO(2) exposure. When atmospheric air was then again delivered, there was a robust increase in respiration rate that coincided with rats moving to the air intake. The rats exposed to CO(2) also displayed behaviors consistent with increased anxiety in the behavioral testing that followed the exposure. Next, this study assessed the behavioral and physiologic responses of rats that were euthanized with 100% CO(2) infused at 10%, 30%, or 100% volume per minute displacement rates. Analysis of the concentrations of CO(2) and oxygen in the euthanasia chamber and the behavioral responses of the rats suggest that the use of the very low flow volume per minute displacement rate (10%) may prolong the duration of panicogenic ranges of ambient CO(2), while the use of the higher flow volume per minute displacement rate (100%) increases agitation. Therefore, of the volume displacement per minute rates evaluated, this study suggests that 30% minimizes the potential pain and distress experienced by the animal.


title: Sensitive Diagnostics Confirm That Influenza C is an Uncommon Cause of Medically Attended Respiratory Illness in Adults

text: Among 4200 adults who presented with acute respiratory symptoms at a variety of medical practice settings (November 2006 through May 2012), only 13 (0.3%) nasal/throat swabs were positive for influenza C. Influenza C was rarely associated with medical care visits in adults.


title: Relationships between A(H1N1)pdm09 influenza infection and infections with other respiratory viruses

text: BACKGROUND: A(H1N1)pdm09, a new influenza pandemic virus emerged in 2009. The A(H1N1)pdm09 infection had several unique characteristics which included rapid transmissibility and high morbidity in obese individuals, pregnant women and individuals suffering from chronic diseases. OBJECTIVES: To study the relationships between A(H1N1)pdm09 influenza infection and infections with other respiratory viruses such as respiratory syncytial virus (RSV), human metapneumo virus (hMPV), adenovirus and seasonal influenza. METHODS: Samples (nasopharyngeal swabs or aspirates) collected between 2007 until 2012 from patients of various ages that were hospitalized due to respiratory virus infections were analyzed for the presence of various respiratory viruses, using qRT‐PCR. RESULTS: In 2009–2010, when the pandemic influenza A(H1N1)pdm09 first appeared, two major infection peaks were noted and individuals of various ages were infected. Following the decline of the A(H1N1)pdm09 virus infection, the percentages of patients infected with adenovirus and hMPV increased, while infection frequency with RSV B and with seasonal influenza virus decreased. Furthermore, RSV infections were delayed and very few percentages of patients were co‐infected with more than one virus. Interestingly, the A(H1N1)pdm09 virus lost its dominancy when it reappeared in the winter of 2010–2011, and at this time, only the incidence of RSV infections was affected by the A(H1N1)pdm09 virus. CONCLUSIONS: The A(H1N1)pdm09 virus had distinct effects on other respiratory viruses when it first appeared versus later, when it evolved from being a pandemic to a seasonal virus.


title: ONLINE FORECASTING OF COVID-19 CASES IN NIGERIA USING LIMITED DATA

text: Abstract The novel Coronavirus disease (COVID-19) was first identified in Wuhan, China in December 2019 but later spread to other parts of the world. The disease as at the point of writing this paper has been declared a pandemic by the World Health Organization (WHO). The application of mathematical models, artificial intelligence, big data, and similar methodologies are potential tools to predict the extent of the spread and effectiveness of containment strategies to stem the transmission of this disease. In societies with constrained data infrastructures, modeling and forecasting COVID-19 becomes an extremely difficult endeavor. Nonetheless, we propose an online forecasting mechanism that streams data from the Nigeria Center for Disease Control to update the parameters of an ensemble model which in turn provides updated COVID-19 forecasts every 24 hours. The ensemble combines an Auto-Regressive Integrated Moving Average model (ARIMA), Prophet - an additive regression model developed by Facebook, and a Holt-Winters Exponential Smoothing model combined with Generalized Autoregressive Conditional Heteroscedasticity (GARCH). The outcomes of these efforts are expected to provide academic thrust in guiding the policymakers in the deployment of containment strategies and/or assessment of containment interventions in stemming the spread of the disease in Nigeria


title: Proposal for Coronavirus Disease 2019 Management

text: SETTING: The coronavirus disease 2019 pandemic has raised fear throughout the nation. Current news and social media predictions of ventilator, medication, and personnel shortages are rampant. PATIENTS: Patients with coronavirus disease 2019 are presenting with early respiratory distress and hypoxemia, but not hypercapnia. INTERVENTIONS: Patients who maintain adequate alveolar ventilation, normocapnia, and adequate oxygenation may avoid the need for tracheal intubation. Facemask continuous positive airway pressure has been used to treat patients with respiratory distress for decades, including those with severe acute respiratory syndrome. Of importance, protocols were successful in protecting caregivers from contracting the virus, obviating the need for tracheal intubation just to limit the spread of potentially infectious particles. CONCLUSIONS: During a pandemic, with limited resources, we should provide the safest and most effective care, while protecting caregivers. Continuous positive airway pressure titrated to an effective level and applied early with a facemask may spare ventilator usage. Allowing spontaneous ventilation will decrease the need for sedative and paralytic drugs and may decrease the need for highly skilled nurses and respiratory therapists. These goals can be accomplished with devices that are readily available and easier to obtain than mechanical ventilators, which then can be reserved for the sickest patients.


title: Rapid reconstruction of SARS-CoV-2 using a synthetic genomics platform

text: Reverse genetics has been an indispensable tool revolutionising our insights into viral pathogenesis and vaccine development. Large RNA virus genomes, such as from Coronaviruses, are cumbersome to clone and to manipulate in E. coli hosts due to size and occasional instability1-3. Therefore, an alternative rapid and robust reverse genetics platform for RNA viruses would benefit the research community. Here we show the full functionality of a yeast-based synthetic genomics platform for the genetic reconstruction of diverse RNA viruses, including members of the Coronaviridae, Flaviviridae and Paramyxoviridae families. Viral subgenomic fragments were generated using viral isolates, cloned viral DNA, clinical samples, or synthetic DNA, and reassembled in one step in Saccharomyces cerevisiae using transformation associated recombination (TAR) cloning to maintain the genome as a yeast artificial chromosome (YAC). T7-RNA polymerase has been used to generate infectious RNA, which was then used to rescue viable virus. Based on this platform we have been able to engineer and resurrect chemically-synthetized clones of the recent epidemic SARS-CoV-24 in only a week after receipt of the synthetic DNA fragments. The technical advance we describe here allows to rapidly responding to emerging viruses as it enables the generation and functional characterization of evolving RNA virus variants - in real-time - during an outbreak.


title: Developing clinical practice guidelines for the integration of Chinese medicine and biomedicine: A new process

text: Abstract Introduction Despite the integration of Chinese medicine and biomedicine which has emerged in clinical practice worldwide, a comprehensive development process for clinical practice guidelines (CPG) has up to now been missing. A valid method for the rational use of predictions for herb-drug interaction is a biggest challenge in guideline development process. Methods This article summarises the development process by reviewing key literature from CPG developers. It focuseson key methods and challenges specific to CPGs for integration by using text mining and bioinformatics to provide a powerful adjunct to CPG development. Results The guideline development process identified, together with new approaches, incorporates evidence-based methodology and provides better decisions through analysis of uncertain herb-drug interaction. Conclusions This new process used three basic phases (preparation, development, and finalization) and seven steps providing a set of methodological principles for CPG development intergrating Chinese medicine and biomedicine.


title: Detection of the Middle East respiratory syndrome coronavirus in dromedary camel’s seminal plasma in Saudi Arabia 2015–2017

text: The Middle East respiratory syndrome coronavirus (MERS‐CoV) is an emergent respiratory virus. Dromedary camels are currently the only known reservoir of MERS‐CoV and are capable of transmitting the virus within a herd. The role of semen in the transmission of MERS‐CoV has never been investigated as yet, to the best of our knowledge. Our goal was to test semen collected from dromedary camels for MERS‐CoV. A total of 67 seminal plasma samples from infertile and 13 from fertile dromedary camels were collected. The RNA was extracted from the samples and tested using commercial real‐time PCR. Nine out of sixty‐seven infertile animals (13.4%) were positive. The obtained PCR products were sequenced using the conserved MERS‐CoV‐N gene primers. MERS‐CoV‐RNA detected in seminal plasma was closely related to the lineage B. To the best of our knowledge, this is the first report about the detection of MERS‐CoV‐RNA in camel's seminal plasma. Regular testing of semen of common male camels' used for insemination should be considered to avoid a possible spread of the virus through semen.


title: Epimedium koreanum Nakai Displays Broad Spectrum of Antiviral Activity in Vitro and in Vivo by Inducing Cellular Antiviral State

text: Epimedium koreanum Nakai has been extensively used in traditional Korean and Chinese medicine to treat a variety of diseases. Despite the plant’s known immune modulatory potential and chemical make-up, scientific information on its antiviral properties and mode of action have not been completely investigated. In this study, the broad antiviral spectrum and mode of action of an aqueous extract from Epimedium koreanum Nakai was evaluated in vitro, and moreover, the protective effect against divergent influenza A subtypes was determined in BALB/c mice. An effective dose of Epimedium koreanum Nakaimarkedly reduced the replication of Influenza A Virus (PR8), Vesicular Stomatitis Virus (VSV), Herpes Simplex Virus (HSV) and Newcastle Disease Virus (NDV) in RAW264.7 and HEK293T cells. Mechanically, we found that an aqueous extract from Epimedium koreanum Nakai induced the secretion of type I IFN and pro-inflammatory cytokines and the subsequent stimulation of the antiviral state in cells. Among various components present in the extract, quercetin was confirmed to have striking antiviral properties. The oral administration of Epimedium koreanum Nakai exhibited preventive effects on BALB/c mice against lethal doses of highly pathogenic influenza A subtypes (H1N1, H5N2, H7N3 and H9N2). Therefore, an extract of Epimedium koreanum Nakai and its components play roles as immunomodulators in the innate immune response, and may be potential candidates for prophylactic or therapeutic treatments against diverse viruses in animal and humans.


title: Angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas axis prevents lipopolysaccharide–induced apoptosis of pulmonary microvascular endothelial cells by inhibiting JNK/NF–κB pathways

text: ACE2 and Ang–(1–7) have important roles in preventing acute lung injury. However, it is not clear whether upregulation of the ACE2/Ang–(1–7)/Mas axis prevents LPS–induced injury in pulmonary microvascular endothelial cells (PMVECs) by inhibiting the MAPKs/NF–κB pathways. Primary cultured rat PMVECs were transduced with lentiviral–borne Ace2 or shRNA–Ace2, and then treated or not with Mas receptor blocker (A779) before exposure to LPS. LPS stimulation resulted in the higher levels of AngII, Ang–(1–7), cytokine secretion, and apoptosis rates, and the lower ACE2/ACE ratio. Ace2 reversed the ACE2/ACE imbalance and increased Ang–(1–7) levels, thus reducing LPS–induced apoptosis and inflammation, while inhibition of Ace2 reversed all these effects. A779 abolished these protective effects of Ace2. LPS treatment was associated with activation of the ERK, p38, JNK, and NF–κB pathways, which were aggravated by A779. Pretreatment with A779 prevented the Ace2–induced blockade of p38, JNK, and NF–κB phosphorylation. However, only JNK inhibitor markedly reduced apoptosis and cytokine secretion in PMVECs with Ace2 deletion and A779 pretreatment. These results suggest that the ACE2/Ang–(1–7)/Mas axis has a crucial role in preventing LPS–induced apoptosis and inflammation of PMVECs, by inhibiting the JNK/NF–κB pathways.


title: Evolution of information-driven HIV/AIDS policies in China

text: Background As China continues to commit to universal access to HIV/AIDS prevention, treatment and care services, its HIV/AIDS policies have become increasingly information driven. We review China’s key national-level HIV/AIDS policies and discuss policy gaps and challenges ahead. Methods We conducted a desk review of key national-level policies that have had a major impact on China’s HIV/AIDS epidemic, and examined recent epidemiological data relevant to China’s HIV response. Results National-level policies that have had a major impact on China’s HIV/AIDS response include: ‘Four Frees and One Care’; 5-year action plans; and HIV/AIDS regulation. These landmark policies have facilitated massive scaling up of services over the past decade. For example, the number of drug users provided with methadone maintenance treatment significantly increased from 8116 in 2005 to 241 975 in 2009; almost a 30-fold increase. The ‘Four Frees and One Care’ policy has increased the number of people living with AIDS on anti-retroviral treatment from some 100 patients in 2003 to over 80 000 in 2009. However, stigma and discrimination remains major obstacles for people living with HIV/AIDS trying to access services. Conclusions China’s current national policies are increasingly information driven and responsive to changes in the epidemic. However, gaps remain in policy implementation, and new policies are needed to meet emerging challenges.


Tracing SARS-Coronavirus Variant with Large Genomic Deletion


title: The DEAD-Box RNA Helicase DDX1 Interacts with the Viral Protein 3D and Inhibits Foot-and-Mouth Disease Virus Replication

text: Foot-and-mouth disease virus (FMDV) can infect domestic and wild cloven-hoofed animals. The non-structural protein 3D plays an important role in FMDV replication and pathogenesis. However, the interaction partners of 3D, and the effects of those interactions on FMDV replication, remain incompletely elucidated. In the present study, using the yeast two-hybrid system, we identified a porcine cell protein, DEAD-box RNA helicase 1 (DDX1), which interacted with FMDV 3D. The DDX1-3D interaction was further confirmed by co-immunoprecipitation experiments and an indirect immunofluorescence assay (IFA) in porcine kidney 15 (PK-15) cells. DDX1 was reported to either inhibit or facilitate viral replication and regulate host innate immune responses. However, the roles of DDX1 during FMDV infection remain unclear. Our results revealed that DDX1 inhibited FMDV replication in an ATPase/helicase activity-dependent manner. In addition, DDX1 stimulated IFN-β activation in FMDV-infected cells. Together, our results expand the body of knowledge regarding the role of DDX1 in FMDV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-019-00148-7) contains supplementary material, which is available to authorized users.


title: Human metapneumovirus and human coronavirus infection and pathogenicity in Saudi children hospitalized with acute respiratory illness

text: BACKGROUND AND OBJECTIVES: Human metapneumovirus (hMPV) and the Netherlands human coronavirus (HCoV-NL63) have been isolated from children with respiratory tract infection. The prevalence of these viruses has not been reported from Saudi Arabia. We sought to determine whether hMPV and HCoV-NL63 are responsible for acute respiratory illness and also to determine clinical features and severity of illness in the hospitalized pediatric patient population. DESIGN AND SETTING: Prospective hospital-based study from July 2007 to November 2008. PATIENTS AND METHODS: Nasopharyngeal specimens from children less than 16 years old who were suffering from acute respiratory diseases were tested for hMPV and HCoV-NL63 by reverse transcriptase–polymerase chain reaction. Samples were collected from July 2007 to November 2008. RESULTS: Both viruses were found among Saudi children with upper and lower respiratory tract diseases during the autumn and winter of 2007 and 2008, contributing to 11.1% of all viral diagnoses, with individual incidences of 8.3% (hMPV) and 2.8% (HCoV-NL63) among 489 specimens. Initial symptoms included fever, cough, and nasal congestion. Lower respiratory tract disease occurs in immunocompromised individuals and those with underlying conditions. Clinical findings of respiratory failure and culture-negative shock were established in 7 children infected with hMPV and having hematologic malignancies, myelofibrosis, Gaucher disease, and congenital immunodeficiency; 2 of the 7 patients died with acute respiratory failure. All children infected with HCoV-NL63 had underlying conditions; 1 of the 4 patients developed respiratory failure. CONCLUSION: hMPV and HCoV-NL63 are important causes of acute respiratory illness among hospitalized Saudi children. hMPV infection in the lower respiratory tract is associated with morbidity and mortality in immunocompromised children. HCoV-NL63 may cause severe lower respiratory disease with underlying conditions.


COVID-19 mortality and health-care resources: organization


title: Isolation of a Novel Swine Influenza Virus from Oklahoma in 2011 Which Is Distantly Related to Human Influenza C Viruses

text: Of the Orthomyxoviridae family of viruses, only influenza A viruses are thought to exist as multiple subtypes and has non-human maintenance hosts. In April 2011, nasal swabs were collected for virus isolation from pigs exhibiting influenza-like illness. Subsequent electron microscopic, biochemical, and genetic studies identified an orthomyxovirus with seven RNA segments exhibiting approximately 50% overall amino acid identity to human influenza C virus. Based on its genetic organizational similarities to influenza C viruses this virus has been provisionally designated C/Oklahoma/1334/2011 (C/OK). Phylogenetic analysis of the predicted viral proteins found that the divergence between C/OK and human influenza C viruses was similar to that observed between influenza A and B viruses. No cross reactivity was observed between C/OK and human influenza C viruses using hemagglutination inhibition (HI) assays. Additionally, screening of pig and human serum samples found that 9.5% and 1.3%, respectively, of individuals had measurable HI antibody titers to C/OK virus. C/OK virus was able to infect both ferrets and pigs and transmit to naive animals by direct contact. Cell culture studies showed that C/OK virus displayed a broader cellular tropism than a human influenza C virus. The observed difference in cellular tropism was further supported by structural analysis showing that hemagglutinin esterase (HE) proteins between two viruses have conserved enzymatic but divergent receptor-binding sites. These results suggest that C/OK virus represents a new subtype of influenza C viruses that currently circulates in pigs that has not been recognized previously. The presence of multiple subtypes of co-circulating influenza C viruses raises the possibility of reassortment and antigenic shift as mechanisms of influenza C virus evolution.


title: Q&A: What are pathogens, and what have they done to and for us?

text: Microbes are found on us, within us and around us. They inhabit virtually every environment on the planet and the bacteria carried by an average human, mostly in their gut, outnumber human cells. The vast majority of microbes are harmless to us, and many play essential roles in plant, animal and human health. Others, however, are either obligate or facultative pathogens exerting a spectrum of deleterious effects on their hosts. Infectious diseases have historically represented the most common cause of death in humans until recently, exceeding by far the toll taken by wars or famines. From the dawn of humanity and throughout history, infectious diseases have shaped human evolution, demography, migrations and history.


title: Hypothesized and found mechanisms for potentiation of bradykinin actions

text: Potentiation of hormone actions can occur by different mechanisms, including inhibition of degrading enzymes, interaction with the hormone receptor leading to stabilization of bioactive conformation or leading to receptor homo‐ and hetero‐oligomerization, receptor phosphorylation and dephosphorylation or can occur by directly influencing the signal transduction and ion channels. In this review the potentiation of bradykinin actions in different systems by certain compounds will be reviewed. Despite many long years of experimental research and investigation the mechanisms of potentiating action remain not fully understood. One of the most contradictory findings are the distinct differences between the inhibition of the angiotensin I‐converting enzyme and the potentiation of the bradykinin induced smooth muscle reaction. Contradictory findings and hypothesized mechanisms in the literature are discussed in this review and in some cases compared to own results. Investigation of potentiating actions was extended from hypotension, smooth muscle reaction and cellular actions to activation of immunocompetent cells. In our opinion the potentiation of bradykinin action can occur by different mechanisms, depending on the system and the applied potentiating factor used.


title: Coronavirus: Stehen wir am Beginn einer neuen Pandemie?

text: Beunruhigende Nachrichten aus China, erste Erkrankungsfälle in Europa. Das Coronoavirus breitet sich aus. MMW-Schriftleiter Prof. Johannes Bogner, München, berichtet aus infektiologischer Sicht über den derzeitigen Kenntnisstand und macht Sie zugleich fit für Fragen Ihrer Patienten.


title: Surveillance of travel-associated diseases at two referral centres in Marseille, France: a 12-year survey

text: BACKGROUND: With increasing international travel and historically high numbers of residents visiting friends and relatives overseas, travel-associated illnesses are frequent in Marseille, France. We report the changing epidemiology of travel-related illnesses over a 12-year period. METHODS: A single site GeoSentinel surveillance analysis was undertaken for 3460 ill returned travellers presenting to two public hospitals in Marseille, France from March 2003 to October 2015, with travel-related illnesses. Demographic characteristics, travel history, presenting symptoms and information on pre-travel consultations were collected. RESULTS: There was a predominance of travel to sub-Saharan Africa, in particular to Comoros archipelago. Tourism was the main reason for travel (1591/3460, 46%), followed by visiting friends or relatives (VFR) (895/3460, 26%), with a mean duration of 29 days; 35% (1212/3460) of travellers reported a pre-travel health consultation. The most common syndromic diagnoses were febrile systemic illness (1343, 39%), dermatologic (716, 21%), gastrointestinal (340, 10%) and respiratory/ear–nose–throat (331, ENT) (10%). Hospitalization rates were highest amongst travellers from sub-Saharan Africa (858/ 1632, 53%), and VFR (573/ 895, 64%, P < 0.001). Frequent diagnoses included malaria (797, 23%), dengue (96, 2.77%) and chikungunya (75, 2.17%), reflecting global trends. Comparison of two periods (2003–10 to 2011–15) demonstrated an increase in chikungunya and decrease in malaria and influenza-like illness. We report an increase in ill travellers from the Caribbean, Middle East and South-East Asia. CONCLUSION: Surveillance of travellers provides relevant sentinel information on the changing epidemiology of infectious diseases across the globe, most notably for malaria, dengue and chikungunya. We demonstrate the use of travel surveillance in improving pre-travel consultation needs and to address autochthonous vector-borne viral risks.


title: Roadmap to developing a recombinant coronavirus S protein receptor-binding domain vaccine for severe acute respiratory syndrome

text: A subunit vaccine, RBD-S, is under development to prevent severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV), which is classified by the US NIH as a category C pathogen. This vaccine is comprised of a recombinant receptor-binding domain (RBD) of the SARS-CoV spike (S) protein and formulated on alum, together with a synthetic glucopyranosyl lipid A. The vaccine would induce neutralizing antibodies without causing Th2-type immunopathology. Vaccine development is being led by the nonprofit product development partnership; Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development in collaboration with two academic partners (the New York Blood Center and University of Texas Medical Branch); an industrial partner (Immune Design Corporation); and Walter Reed Army Institute of Research. A roadmap for the product development of the RBD-S SARS vaccine is outlined with a goal to manufacture the vaccine for clinical testing within the next 5 years.


title: COVID‐19 in Lung Transplant Recipients

text: Solid organ transplant recipients are considered at a high risk for severe COVID‐19 disease due to chronic immunosuppression, though their risk compared to that of the general population remains unclear. Management of lung transplant recipients can be particularly challenging given high levels of maintenance immunosuppression, high incidence of rejection, constant exposure of the graft to the external environment, and diagnostic uncertainty in patients with respiratory symptoms. There is currently limited data on manifestations, management, and outcomes in lung transplant recipients who develop this novel infection (1).


title: Further evidence that far‐UVC for disinfection is unlikely to cause erythema or pre‐mutagenic DNA lesions in skin

text: It is well understood that ultraviolet‐C (UVC) radiation is effective for the destruction of micro‐organisms and drug‐resistant bacteria and is being investigated for its effectiveness at destroying the virus responsible for the current Covid‐19 global pandemic. Far‐UVC (200 ‐ 220 nm) has been proposed as an effective disinfection radiation that is safe to humans. In 2014, Woods et al. undertook a first‐in‐person study to assess the effect on skin of a 222 nm UVC emitting device (Sterilray disinfectant wand, Healthy Environment Innovations, Dover, NH, USA).


title: Identification of 2019-nCoV related coronaviruses in Malayan pangolins in southern China

text: The ongoing outbreak of viral pneumonia in China and beyond is associated with a novel coronavirus, provisionally termed 2019-nCoV. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection. Although bats are likely reservoir hosts for 2019-nCoV, the identity of any intermediate host facilitating transfer to humans is unknown. Here, we report the identification of 2019-nCoV related coronaviruses in pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin associated CoVs that belong to two sub-lineages of 2019-nCoV related coronaviruses, including one very closely related to 2019-nCoV in the receptor-binding domain. The discovery of multiple lineages of pangolin coronavirus and their similarity to 2019-nCoV suggests that pangolins should be considered as possible intermediate hosts for this novel human virus and should be removed from wet markets to prevent zoonotic transmission.


title: Emerging strategies for the noninvasive diagnosis of nosocomial pneumonia

text: Introduction: Hospital-acquired pneumonia is a common and therapeutically challenging diagnosis that can lead to severe sepsis, critical illness, and respiratory failure. In this review, we focus on efforts to enhance microbiological diagnosis of hospital-acquired pneumonia, including ventilator-associated pneumonia. Areas covered: A systematic literature review was conducted by searching Medline from inception to December 2018, including hand-searching of the reference lists for additional studies. The search strategy comprised the following common search terms: hospital pneumonia OR nosocomial pneumonia OR noninvasive OR molecular diagnostic tests (OR point-of-care systems OR VOC [i.e. volatile organic compounds]) OR rapid (or simple or quick test), including brand names for the most common commercial tests. Expert opinion: In recent years, the microbiological diagnosis of respiratory pathogens has improved significantly by the development and implementation of molecular diagnostic tests for pneumonia. Real-time polymerase chain reaction, hybridization, and mass spectrometry-based platforms dominate the scene, with microarray-based assays, multiplex polymerase chain reaction, and MALDI-TOF mass spectrometry capable of detecting the determinants of antimicrobial resistance (mainly β-lactamase genes). Introducing these assays into routine clinical practice for rapid identification of the causative microbes and their resistance patterns could transform the care of pneumonia, improving antimicrobial selection, de-escalation, and stewardship.


title: On a Statistical Transmission Model in Analysis of the Early Phase of COVID-19 Outbreak

text: Since December 2019, a disease caused by a novel strain of coronavirus (COVID-19) had infected many people and the cumulative confirmed cases have reached almost 180,000 as of 17, March 2020. The COVID-19 outbreak was believed to have emerged from a seafood market in Wuhan, a metropolis city of more than 11 million population in Hubei province, China. We introduced a statistical disease transmission model using case symptom onset data to estimate the transmissibility of the early-phase outbreak in China, and provided sensitivity analyses with various assumptions of disease natural history of the COVID-19. We fitted the transmission model to several publicly available sources of the outbreak data until 11, February 2020, and estimated lock down intervention efficacy of Wuhan city. The estimated [Formula: see text] was between 2.7 and 4.2 from plausible distribution assumptions of the incubation period and relative infectivity over the infectious period. 95% confidence interval of [Formula: see text] were also reported. Potential issues such as data quality concerns and comparison of different modelling approaches were discussed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12561-020-09277-0) contains supplementary material, which is available to authorized users.


Akute Exazerbation bei COPD


Mouse Hepatitis Virus Infection Activates the IRE1/XBP1 Pathway of the Unfolded Protein Response


title: Epidemiologic data and pathogen genome sequences: a powerful synergy for public health

text: Epidemiologists aim to inform the design of public health interventions with evidence on the evolution, emergence and spread of infectious diseases. Sequencing of pathogen genomes, together with date, location, clinical manifestation and other relevant data about sample origins, can contribute to describing nearly every aspect of transmission dynamics, including local transmission and global spread. The analyses of these data have implications for all levels of clinical and public health practice, from institutional infection control to policies for surveillance, prevention and treatment. This review highlights the range of epidemiological questions that can be addressed from the combination of genome sequence and traditional ‘line lists’ (tables of epidemiological data where each line includes demographic and clinical features of infected individuals). We identify opportunities for these data to inform interventions that reduce disease incidence and prevalence. By considering current limitations of, and challenges to, interpreting these data, we aim to outline a research agenda to accelerate the genomics-driven transformation in public health microbiology.


title: Integration of transcriptomic profile of SARS-CoV-2 infected normal human bronchial epi-thelial cells with metabolic and protein-protein interaction networks

text: A novel coronavirus (SARS-CoV-2, formerly known as nCoV-2019) that causes an acute respiratory disease has emerged in Wuhan, China and spread globally in early 2020. On January the 30th, the World Health Organization (WHO) declared spread of this virus as an epidemic and a public health emergency. With its highly contagious characteristic and long incubation time, confinement of SARS-CoV-2 requires drastic lock-down measures to be taken and therefore early diagnosis is crucial. We analysed transcriptome of SARS-CoV-2 infected human lung epithelial cells, compared it with mock-infected cells, used network-based reporter metabolite approach and integrated the transcriptome data with protein-protein interaction network to elucidate the early cellular response. Significantly affected metabolites have the potential to be used in diagnostics while pathways of protein clusters have the potential to be used as targets for supportive or novel therapeutic approaches. Our results are in accordance with the literature on response of IL6 family of cytokines and their importance, in addition, we find that matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) with keratan sulfate synthesis pathway may play a key role in the infection. We hypothesize that MMP9 inhibitors have potential to prevent "cytokine storm" in severely affected patients.


title: Nuclear localization signal in TRIM22 is essential for inhibition of type 2 porcine reproductive and respiratory syndrome virus replication in MARC-145 cells

text: Porcine reproductive and respiratory syndrome virus (PRRSV) infection causes one of the most economically important swine diseases worldwide. Tripartite motif-containing 22 (TRIM22), a TRIM family protein, has been identified as a crucial restriction factor that inhibits a group of human viruses. Currently, the role of cellular TRIM22 in PRRSV infection remains unclear. In the present study, we analyzed the effect of TRIM22 on PRRSV replication in vitro and explored the underlying mechanism. Ectopic expression of TRIM22 impaired the viral replication, while TRIM22-RNAi favored the replication of PRRSV in MARC-145 cells. Additionally, we observed that TRIM22 deletion SPRY domain or Nuclear localization signal (NLS) losses the ability to inhibit PRRSV replication. Finally, Co-IP analysis identified that TRIM22 interacts with PRRSV nucleocapsid (N) protein through the SPRY domain, while the NLS2 motif of N protein is involved in interaction with TRIM22. Although the concentration of PRRSV N protein was not altered in the presence of TRIM22, the abundance of N proteins from simian hemorrhagic fever virus (SHFV), equine arteritis virus (EAV), and murine lactate dehydrogenase-elevating virus (LDV) diminished considerably with increasing TRIM22 expression. Together, our findings uncover a previously unrecognized role for TRIM22 and extend the antiviral effects of TRIM22 to arteriviruses.


title: Remdesivir in Treatment of COVID-19: A Systematic Benefit–Risk Assessment

text: INTRODUCTION: There is a need to identify effective, safe treatments for COVID-19 (coronavirus disease) rapidly, given the current, ongoing pandemic. A systematic benefit–risk assessment was designed and conducted to examine the benefit–risk profile of remdesivir in COVID-19 patients compared with standard of care, placebo or other treatments. A key objective of this study was to provide a platform for a dynamic systematic benefit–risk evaluation, which starts with inevitably limited information (to meet the urgent unmet public health need worldwide), then update the benefit–risk evaluation as more data become available. METHODS: The Benefit–Risk Action Team (BRAT) framework was used to assess the overall benefit–risk of the use of remdesivir as a treatment for COVID-19 compared with standard of care, placebo or other treatments. We searched PubMed, Google Scholar and government agency websites to identify literature reporting clinical outcomes in patients taking remdesivir for COVID-19. A value tree was constructed and key benefits and risks were ranked by two clinicians in order of considered importance. RESULTS: Using the BRAT method, several key benefits and risks for use of remdesivir in COVID-19 compared with placebo have been identified. In one trial, the benefit of time to clinical improvement was not statistically significant (21 vs 23 days, HR 1.23, 95% CI 0.87–1.75), although the study was underpowered. In another trial, a shorter time to recovery in patients treated with remdesivir was observed (11 vs 15 days), with non-significant reduced mortality risk (8% vs 12%). Risk data were only available from one trial. This trial reported fewer serious adverse events in patients taking remdesivir (18%) compared with the placebo group (26%); however, more patients in the remdesivir group discontinued treatment as a result of an adverse event compared with those patients receiving placebo (12% vs 5%). CONCLUSIONS: Preliminary clinical trial results suggest that there may be a favourable benefit–risk profile for remdesivir compared with placebo in severe COVID-19 infection and further data on benefits would strengthen this evaluation. There is limited safety data for remdesivir, which should be obtained in further studies. The current framework summarises the key anticipated benefits and risks for which further data are needed. Ongoing clinical trial data can be incorporated into the framework when available to provide an updated benefit–risk assessment.


title: Amplicon competition enables end-point quantitation of nucleic acids following isothermal amplification

text: It is inherently difficult to quantitate nucleic acid analytes with most isothermal amplification assays. We have now developed loop-mediated isothermal amplification (LAMP) reactions in which competition between defined numbers of ‘false’ and ‘true’ amplicons leads to order of magnitude quantitation via a single end-point determination. These thresholded LAMP reactions were successfully used to directly and quantitatively estimate the numbers of nucleic acids in complex biospecimens, including directly from cells and in sewage, with the values obtained closely correlating with qPCR quantitations. Thresholded LAMP reactions are amenable to endpoint readout via cell phone, unlike other methods that require continuous monitoring, and should therefore prove extremely useful in developing one-pot reactions for point-of-care diagnostics determinations without any sophisticated material or informatics infrastructure.


title: Prospective surveillance study of acute respiratory infections, influenza-like illness and seasonal influenza vaccine in a cohort of juvenile idiopathic arthritis patients

text: BACKGROUND: Acute respiratory infections (ARI) are frequent in children and complications can occur in patients with chronic diseases. We evaluated the frequency and impact of ARI and influenza-like illness (ILI) episodes on disease activity, and the immunogenicity and safety of influenza vaccine in a cohort of juvenile idiopathic arthritis (JIA) patients. METHODS: Surveillance of respiratory viruses was conducted in JIA patients during ARI season (March to August) in two consecutive years: 2007 (61 patients) and 2008 (63 patients). Patients with ARI or ILI had respiratory samples collected for virus detection by real time PCR. In 2008, 44 patients were immunized with influenza vaccine. JIA activity index (ACRPed30) was assessed during both surveillance periods. Influenza hemagglutination inhibition antibody titers were measured before and 30-40 days after vaccination. RESULTS: During the study period 105 ARI episodes were reported and 26.6% of them were ILI. Of 33 samples collected, 60% were positive for at least one virus. Influenza and rhinovirus were the most frequently detected, in 30% of the samples. Of the 50 JIA flares observed, 20% were temporally associated to ARI. Influenza seroprotection rates were higher than 70% (91-100%) for all strains, and seroconversion rates exceeded 40% (74-93%). In general, response to influenza vaccine was not influenced by therapy or disease activity, but patients using anti-TNF alpha drugs presented lower seroconversion to H1N1 strain. No significant differences were found in ACRPed30 after vaccination and no patient reported ILI for 6 months after vaccination. CONCLUSION: ARI episodes are relatively frequent in JIA patients and may have a role triggering JIA flares. Trivalent split influenza vaccine seems to be immunogenic and safe in JIA patients.


title: COVID-19: review on latest available drugs and therapies against SARS-CoV-2. Coagulation and inflammation cross-talking

text: SARS-CoV-2 is the agent responsible for COVID-19. The infection can be dived into three phases: mild infection, the pulmonary phase and the inflammatory phase. Treatment options for the pulmonary phase include: Hydroxychloroquine, Remdesivir, Lopinavir/Ritonavir. The inflammatory phase includes therapeutic options like Tocilizumab, Anakinra, Baricitinib, Eculizumab, Emapalumab and Heparin. Human clinical trials are starting to show some results, in some cases like that of Remdesivir these are controversial. Coagulopathy is a common complication in severe cases, inflammation and coagulation are intertwined and cross-talking between these two responses is known to happen. A possible amplification of this cross-talking is suggested to be implicated in the severe cases that show both a cytokine storm and coagulopathy.


title: How 3D Printing and Social Media Tackles the PPE Shortage during Covid – 19 Pandemic

text: During the recent Covid-19 pandemic, additive Technology and Social Media were used to tackle the shortage of Personal Protective Equipment. A literature review and a social media listening software were employed to explore the number of the users referring to specific keywords related to 3D printing and PPE. Additionally, the QALY model was recruited to highlight the importance of the PPE usage. More than 7 billion users used the keyword covid or similar in the web while mainly Twitter and Facebook were used as a world platform for PPE designs distribution through individuals and more than 100 different 3D printable PPE designs were developed.


title: Cellular unfolded protein response against viruses used in gene therapy

text: Viruses are excellent vehicles for gene therapy due to their natural ability to infect and deliver the cargo to specific tissues with high efficiency. Although such vectors are usually “gutted” and are replication defective, they are subjected to clearance by the host cells by immune recognition and destruction. Unfolded protein response (UPR) is a naturally evolved cyto-protective signaling pathway which is triggered due to endoplasmic reticulum (ER) stress caused by accumulation of unfolded/misfolded proteins in its lumen. The UPR signaling consists of three signaling pathways, namely PKR-like ER kinase, activating transcription factor 6, and inositol-requiring protein-1. Once activated, UPR triggers the production of ER molecular chaperones and stress response proteins to help reduce the protein load within the ER. This occurs by degradation of the misfolded proteins and ensues in the arrest of protein translation machinery. If the burden of protein load in ER is beyond its processing capacity, UPR can activate pro-apoptotic pathways or autophagy leading to cell death. Viruses are naturally evolved in hijacking the host cellular translation machinery to generate a large amount of proteins. This phenomenon disrupts ER homeostasis and leads to ER stress. Alternatively, in the case of gutted vectors used in gene therapy, the excess load of recombinant vectors administered and encountered by the cell can trigger UPR. Thus, in the context of gene therapy, UPR becomes a major roadblock that can potentially trigger inflammatory responses against the vectors and reduce the efficiency of gene transfer.


Neumoperitoneo espontáneo no quirúrgico en paciente COVID-19 positivo con neumonía bilateral severa


title: On the different sources of cooperativity in pH titrating sites of a membrane protein channel

text: ABSTRACT. Cooperative interactions play a central role in the regulation of protein functions. Here we show that in multi-site systems like ion channels the application of the Hill formalism could require a combination of different experiments, even involving site-directed mutagenesis, to identify the different sources of cooperativity and to discriminate between genuine and apparent cooperativity. We discuss the implications for the channel function in the bacterial porins PorA (N. meningitidis) and OmpF (E. coli) and the viroporin SARS-CoV E. GRAPHICAL ABSTRACT: [Image: see text]


title: Structural similarity between HIV-1 gp41 and SARS-CoV S2 proteins suggests an analogous membrane fusion mechanism

text: Abstract SARS-associated coronavirus (SARS-CoV) has been identified as the causal agent of a new emerging disease: severe acute respiratory syndrome (SARS). Its spike protein S2 is responsible for mediating fusion of viral and cellular membrane. In this study, we modeled the 3D structure of S2 subunit and compared this model with the core structure of gp41 from HIV-1. We found that SARS-CoV S2 and gp41 share the same two α helices, suggesting that the two viruses could follow an analogous membrane fusion mechanism. Further ligand-binding analysis showed that two inhibitors GGL and D-peptide from HIV-1 gp41 may serve as inhibitors for SARS-CoV entry.


title: Rhinovirus and Coronavirus Infection-Associated Hospitalizations among Older Adults

text: Rhinoviruses and coronaviruses are recognized as the major causes of the common cold syndrome. The role of these viruses in more serious respiratory illnesses resulting in hospitalization is less well defined. During a winter when influenza A infection was prevalent, 100 elderly adults hospitalized because of cardiopulmonary illnesses were evaluated for rhinovirus and coronavirus infection. Patients who tested negative for influenza or respiratory syncytial virus had nasal swab samples tested for rhinovirus, coronavirus OC43, and coronavirus 229E by reverse-transcription polymerase chain reaction and for coronaviruses by serologic testing. Twelve percent of patients had rhinovirus or coronavirus identified (rhinovirus, 4 patients; coronavirus 229E, 4 patients; coronavirus OC43, 3 patients; and mixed rhinovirus/coronavirus 229E infection, 1 patient). All patients had significant underlying diseases. Although all patients recovered, the mean length of stay was 8 days; 4 persons had pneumonia, and 1 required ventilator support. These data suggest that rhinoviruses and coronaviruses may be associated with serious respiratory illnesses in frail older adults.


title: Adverse effects of Influenza A(H1N1)pdm09 virus infection on growth performance of Norwegian pigs - a longitudinal study at a boar testing station

text: BACKGROUND: Influenza A(H1N1)pdm09 virus infection in Norwegian pigs was largely subclinical. This study tested the hypothesis that the infection causes negligible impact on pigs’ growth performance in terms of feed conversion efficiency, daily feed intake, daily growth, age on reaching 100 kg bodyweight and overall feed intake. A sample of 1955 pigs originating from 43 breeding herds was classified into five infection status groups; seronegative pigs (n = 887); seropositive pigs (n = 874); pigs positive for virus at bodyweight between 33 kg and 60 kg (n = 123); pigs positive for virus at bodyweight between 61 kg and 80 kg (n = 34) and pigs positive for virus at bodyweight between 81 kg and 100 kg (n = 37). Each pig had daily recordings of feed intake and bodyweight from 33 kg to 100 kg. Marginal effects of the virus infection on the outcomes were estimated by multi-level linear regression, which accounted for known fixed effects (breed, birthdate, average daily feed intake and growth phase) and random effects (cluster effects of pig and herd). RESULTS: The seropositive and virus positive pigs had decreased (P value<0.05) growth performance compared to seronegative pigs even though feed intake was not decreased. Reduced feed conversion efficiency led to lower average daily growth, additional feed requirement and longer time needed to reach the 100 kg bodyweight. The effects were more marked (P value<0.03) in pigs infected at a younger age and lasted a longer period. Despite increased feed intake observed, their growth rates were lower and they took more time to reach 100 kg bodyweight compared to the seronegative pigs. CONCLUSION: Our study rejected the null hypothesis that the virus infection had negligible adverse effects on growth performance of Norwegian pigs.


title: Association between genetic polymorphisms of MMP8 and the risk of steroid-induced osteonecrosis of the femoral head in the population of northern China

text: BACKGROUND: Steroid-induced osteonecrosis of the femoral head (ONFH) is the most common clinical nontraumatic ONFH. Once ONFH occurs, it seriously reduces patients’ quality of life. The matrix metalloproteinase/tissue inhibitor of metalloproteinase (MMP/TIMP) system was found to play a significant role in the development of ONFH. The aim of this study was to identify the associations between 7 genes selected from the MMP/TIMP system and steroid-induced ONFH. METHODS: We genotyped 34 single-nucleotide polymorphisms (SNPs) of 7 genes selected from the MMP/TIMP system in a case–control study with 285 cases of steroid-induced ONFH and 308 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using the chi-squared test, genetic model analysis, haplotype analysis, and stratification analysis. RESULTS: We found that the minor alleles of rs1940475 and rs11225395 in MMP8 were associated with a 1.32-fold increased risk of steroid-induced ONFH in the allelic model analysis (P = 0.021 and 0.022, respectively). In the genetic model analysis, we found that rs3740938, rs2012390, rs1940475, and rs11225395 were associated with an increased risk of steroid-induced ONFH. In further stratification analysis, rs3740938 and rs2012390 displayed a significantly increased risk of steroid-induced ONFH in females under the dominant (rs3740938, OR = 2.69, 95% CI: 1.50–4.83, P = 0.001; rs2012390, OR = 2.30, 95% CI: 1.31–4.03, P = 0.012) and additive (rs3740938, OR = 2.02, 95% CI: 1.24–3.29, P = 0.010; rs2012390, OR = 1.77, 95% CI: 1.12–2.80, P = 0.047) models. In addition, haplotype “AGTCA” of MMP8 was found to be associated with a 1.40-fold increased risk of steroid-induced ONFH (95% CI: 1.04–1.88, P = 0.025). CONCLUSION: Our results verify that genetic variants of MMP8 contribute to steroid-induced ONFH susceptibility in the population of northern China. In addition, we found that gender differences might interact with MMP8 polymorphisms to contribute to the overall susceptibility to steroid-induced ONFH.


Pre‐procedural COVID‐19 Screening: Do Rhinologic Patients Carry a Unique Risk Burden for False Negative Results?


title: Evaluating the diagnostic accuracy of the WHO Severe Acute Respiratory Infection (SARI) criteria in Middle Eastern children under two years over three respiratory seasons

text: OBJECTIVE: The World Health Organization created the Severe Acute Respiratory Infection (SARI) criteria in 2011 to monitor influenza (flu)-related hospitalization. Many studies have since used the SARI case definition as inclusion criteria for surveillance studies. We sought to determine the sensitivity, specificity, positive predictive value, and negative predictive value of the SARI criteria for detecting ten different respiratory viruses in a Middle Eastern pediatric cohort. MATERIALS AND METHODS: The data for this study comes from a prospective acute respiratory surveillance study of hospitalized children <2 years in Amman, Jordan from March 16, 2010 to March 31, 2013. Participants were recruited if they had a fever and/or respiratory symptoms. Nasal and throat swabs were obtained and tested by real-time RT-PCR for eleven viruses. Subjects meeting SARI criteria were determined post-hoc. Sensitivity, specificity, positive predictive value, and negative predictive value of the SARI case definition for detecting ten different viruses were calculated and results were stratified by age. RESULTS: Of the 3,175 patients enrolled, 3,164 were eligible for this study, with a median age of 3.5 months, 60.4% male, and 82% virus-positive (44% RSV and 3.8% flu). The sensitivity and specificity of the SARI criteria for detecting virus-positive patients were 44% and 77.9%, respectively. Sensitivity of SARI criteria for any virus was lowest in children <3 months at 22.4%. Removing fever as a criterion improved the sensitivity by 65.3% for detecting RSV in children <3 months; whereas when cough was removed, the sensitivity improved by 45.5% for detecting flu in same age group. CONCLUSIONS: The SARI criteria have poor sensitivity for detecting RSV, flu, and other respiratory viruses—particularly in children <3 months. Researchers and policy makers should use caution if using the criteria to estimate burden of disease in children.


title: Cordyceps industry in China

text: Cordyceps, as a general term, describes a group of ascomycetous fungi growing on arthropods and other related fungi. Some cordyceps have been used in traditional Chinese medicine for centuries and cordyceps-derived products are currently a big industry in China. A number of medicinal and health products have been developed and extensively commercialized from natural Chinese cordyceps, its anamorphic fungus (Hirsutella sinensis), and other fungi known as Chinese cordyceps. The lack of a defined classification system for medicinal cordyceps fungi is a source of confusion in the industry and the public, and even among pharmaceutical scientists. This review summarizes the cordyceps fungi currently used in the industry in China with a special reference to clarify Chinese cordyceps and associated fungi. Cordyceps militaris, Cordyceps guangdongensis and Isaria cicadae are well recognized and commercialized cordyceps fungi in China. Except the natural Chinese cordyceps and its anamorphic fungus, Paecilomyces hepiali, Mortierella hepiali, Cephalosporium sinensis and Clonostachys rosea isolated from natural Chinese cordyceps are classified as Chinese cordyceps–associated fungi. P. hepiali is a cordyceps fungus based on current phylogenetic analysis of Hypocreales, while M. hepiali is a fungus in the Zygomycetes and should only be treated as associated fungus of Chinese cordyceps. C. sinensis and C. rosea belong to the Hypocreales and their relationship to cordyceps fungi should be further studied. The exploitation of the resources of cordyceps fungi and their quality control in the industry should be major topics for future studies. Cooperation between the industry and the research community will enhance the whole cordyceps industry.


title: Competing endogenous RNA network profiling reveals novel host dependency factors required for MERS-CoV propagation

text: Circular RNAs (circRNAs) are an integral component of the host competitive endogenous RNA (ceRNA) network. These noncoding RNAs are characterized by their unique splicing reactions to form covalently closed loop structures and play important RNA regulatory roles in cells. Recent studies showed that circRNA expressions were perturbed in viral infections and circRNAs might serve as potential antiviral targets. We investigated the host ceRNA network changes and biological relevance of circRNAs in human lung adenocarcinoma epithelial (Calu-3) cells infected with the highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV). A total of ≥49337 putative circRNAs were predicted. Among the 7845 genes which generated putative circRNAs, 147 (1.9%) of them each generated ≥30 putative circRNAs and were involved in various biological, cellular, and metabolic processes, including viral infections. Differential expression (DE) analysis showed that the proportion of DE circRNAs significantly (P < 0.001) increased at 24 h-post infection. These DE circRNAs were clustered into 4 groups according to their time-course expression patterns and demonstrated inter-cluster and intra-cluster variations in the predicted functions of their host genes. Our comprehensive circRNA-miRNA-mRNA network identified 7 key DE circRNAs involved in various biological processes upon MERS-CoV infection. Specific siRNA knockdown of two selected DE circRNAs (circFNDC3B and circCNOT1) significantly reduced MERS-CoV load and their target mRNA expression which modulates various biological pathways, including the mitogen-activated protein kinase (MAPK) and ubiquitination pathways. These results provided novel insights into the ceRNA network perturbations, biological relevance of circRNAs, and potential host-targeting antiviral strategies for MERS-CoV infection.


title: Cutaneous manifestations of COVID‐19: A review of the published literature

text: COVID‐19 is a highly contagious respiratory tract infection caused by severe acute respiratory syndrome coronavirus 2 (SARS‐Cov‐2). COVID‐19 outbreak, which caused thousands of deaths, has been declared a pandemic by the World Health Organization in March 2020. The infection has been reported to demonstrate different types of cutaneous manifestations including urticarial, maculopapular, papulovesicular, purpuric, livedoid, and thromboticischemic lesions. Given the high mortality rate of the infection, timely and accurate identification of relevant cutaneous manifestations may play a key role in the early diagnosis and management. In this study, we provide a review with a focus on the reported cutaneous manifestations of COVID‐19. This article is protected by copyright. All rights reserved.


Genetic epilepsies and COVID‐19 pandemic: Lessons from the caregiver perspective


title: Chest computed tomography findings of coronavirus disease 2019 (COVID-19) pneumonia

text: OBJECTIVE: To retrospectively analyze the chest computed tomography (CT) features in patients with coronavirus disease 2019 (COVID-19) pneumonia. METHODS: From January 9, 2020, to February 26, 2020, totally 56 laboratory-confirmed patients with COVID-19 underwent chest CT. For 40 patients, follow-up CT scans were obtained. The CT images were evaluated for the number, type and distribution of the opacity, and the affected lung lobes. Furthermore, the initial CT scan and the follow-up CT scans were compared. RESULTS: Forty patients (83.6%) had two or more opacities in the lung. Eighteen (32.7%) patients had only ground-glass opacities; twenty-nine patients (52.7%) had ground-glass and consolidative opacities; and eight patients (14.5%) had only consolidation. A total of 43 patients (78.2%) showed two or more lobes involved. The opacities tended to be both in peripheral and central (30/55, 54.5%) or purely peripheral distribution (25/55, 45.5%). Fifty patients (90.9%) had the lower lobe involved. The first follow-up CT scans showed that twelve patients (30%) had improvement, 26 (65%) patients had mild-moderate progression, and two patients (5%) had severe progression with “white lungs.” The second follow-up CT showed that 22 patients (71%) showed improvement compared with the first follow-up CT, four patients (12.9%) had aggravated progression, and five patients (16.1%) showed unchanged radiographic appearance. CONCLUSIONS: The common CT features of COVID-19 pneumonia are multiple lung opacities, multiple types of the opacity (ground-glass, ground-glass and consolidation, and consolidation alone), and multiple lobes especially the lower lobe involved. Follow-up CT could demonstrate the rapid progression of COVID-19 pneumonia (either in aggravation or absorption). KEY POINTS: • The predominant CT features of COVID-19 pneumonia are multiple ground-glass opacities with or without consolidation and, with both lungs, multiple lobes and especially the lower lobe affected. • CT plays a crucial role in early diagnosis and assessment of COVID-19 pneumonia progression. • CT findings of COVID-19 pneumonia may not be consistent with the clinical symptoms or the initial RT-PCR test results.


title: High fractional exhaled nitric oxide and sputum eosinophils are associated with an increased risk of future virus‐induced exacerbations: A prospective cohort study

text: BACKGROUND: The major trigger of asthma exacerbations is infection with a respiratory virus, most commonly rhinovirus. Type 2 inflammation is known to be associated with an increased risk of exacerbations in general. Whether type 2 inflammation at baseline increases the risk of future virus‐induced exacerbations is unknown. OBJECTIVE: To assess whether type 2 inflammation is associated with an increased risk of virus‐induced exacerbations of asthma. METHODS: Stable asthmatics had spirometry, skin prick test, measurement of FeNO and sputum induced for differential cell counts. Patients were followed up for 18 months, during which they were assessed at the research unit when they had symptoms of an exacerbation. Nasal swabs collected at these assessments underwent viral detection by PCR. RESULTS: A total of 81 asthma patients were recruited, of which 22 (27%) experienced an exacerbation during the follow‐up period. Of these, 15 (68%) had a respiratory virus detected at exacerbation. Sputum eosinophils >1% at baseline increased the risk of having a subsequent virus‐induced exacerbation (HR 7.6 95% CI: 1.6‐35.2, P=.010) as did having FeNO >25 ppb (HR 3.4 95% CI: 1.1‐10.4, P=.033). CONCLUSION AND CLINICAL RELEVANCE: Established type 2 inflammation during stable disease is a risk factor for virus‐induced exacerbations in a real‐life setting. Measures of type 2 inflammation, such as sputum eosinophils and FeNO, could be included in the risk assessment of patients with asthma in future studies.


title: Chapter 11 Laboratory Biosafety and Good Laboratory Practices

text: Abstract In order to ensure biosafety, comprehensive guidelines have been prepared by the National Institutes of Health (NIH) and the World Health Organization (WHO). Both the NIH and the WHO guidelines recommend classification of biological agents based on their potential to cause harm to humans, animals, and the environment. Four Biosafety Levels are recommended to handle organisms of increasing risk potential. Recommended for each level are standard microbiological practices as well as facilities for physical and biological containment of genetically modified organisms (microbes, plants, or animals). In order to harmonize toxicity testing and generation of mutually acceptable preclinical data that may be used for decisions regarding regulation including commercialization, several countries have adopted the principles of Good Laboratory Practices. These principles establish a framework and a minimum standard for the conduct of tests and documentation and analysis of data.


Spinoza: thoughts on hope in our political present


title: Death rate mystery

text: Knowing the true rate of death from covid-19 will help us fight the pandemic, but for the moment it eludes us, reports Michael Le Page


title: Therapeutic ISCOMATRIX™ adjuvant vaccine elicits effective anti-tumor immunity in the TRAMP-C1 mouse model of prostate cancer

text: Cancer vaccine development has proven challenging with the exception of some virally induced cancers for which prophylactic vaccines exist. Currently, there is only one FDA approved vaccine for the treatment of prostate cancer and as such prostate cancer continues to present a significant unmet medical need. In this study, we examine the effectiveness of a therapeutic cancer vaccine that combines the ISCOMATRIX™ adjuvant (ISCOMATRIX) with the Toll-like receptor 3 agonist, polyinosinic–polycytidylic acid (Poly I:C), and Flt3L, FMS-like tyrosine kinase 3 ligand. We employed the TRAMP-C1 (transgenic adenocarcinoma of the mouse prostate) model of prostate cancer and the self-protein mPAP (prostatic acid phosphatase) as the tumor antigen. ISCOMATRIX™–mPAP–Poly I:C–Flt3L was delivered in a therapeutic prime-boost regime that was consistently able to achieve complete tumor regression in 60% of animals treated and these tumor-free animals were protected upon rechallenge. Investigations into the underlying immunological mechanisms contributing to the effectiveness of this vaccine identified that both innate and adaptive responses are elicited and required. NK cells, CD4(+) T cells and interferon-γ were all found to be critical for tumor control while tumor infiltrating CD8(+) T cells became disabled by an immunosuppressive microenvironment. There is potential for broader application of this cancer vaccine, as we have been able to demonstrate effectiveness in two additional cancer models; melanoma (B16-OVA) and a model of B cell lymphoma (Eµ-myc-GFP-OVA). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00262-020-02597-6) contains supplementary material, which is available to authorized users.


The importance of PHC-based measures in controlling COVID-19 outbreak: implications for global health system