docid: nxfgoyhg

title: Common viral illnesses in intensive care: presentation, diagnosis, and management


title: Impact of intervention methods on COVID-19 transmission in Shenzhen

text: By March 31, 2020, COVID-19 had spread to more than 200 countries. Over 750,000 confirmed cases were reported, leading to more than 36,000 deaths. In this study, we analysed the efficiency of various intervention strategies to prevent infection by the virus, SARS-CoV-2, using an agent-based SEIIR model, in the fully urbanised city of Shenzhen, Guangdong Province, China. Shortening the duration from symptom onset to hospital admission, quarantining recent arrivals from Hubei Province, and letting symptomatic individuals stay at home were found to be the three most important interventions to reduce the risk of infection in Shenzhen. The ideal time window for a mandatory quarantine of arrivals from Hubei Province was between 10 January and January 17, 2020, while the ideal time window for local intervention strategies was between 15 and 22 January. The risk of infection could have been reduced by 50% if all symptomatic individuals had immediately gone to hospital for isolation, and by 35% if a 14-day quarantine for arrivals from Hubei Province had been introduced one week earlier. Intervention strategies implemented in Shenzhen were effective, and the spread of infection would be controlled even if the initial basic reproduction number had doubled. Our results may be useful for other cities when choosing their intervention strategies to prevent outbreaks of COVID-19.


docid: nhlflscn

title: Genetic diversity of Hungarian canine distemper virus strains

text: Abstract To achieve proper diagnosis of dogs based on acute clinical symptoms and poorly preserved field samples taken from animals that died due to canine distemper (CD), a new differential diagnostic test has been developed based on polymerase chain reaction (PCR). In this study, more than 150 samples collected from dogs showing respiratory, gastrointestinal and neurological signs suggesting canine distemper virus (CDV) infection were examined. The samples consisted of urine, blood and nasal swabs collected from clinically ill patients, sent to our laboratory by clinicians from various veterinary clinics throughout Hungary. Various organs collected during the necropsy of dogs with pathological changes that suggested CDV infection were also included. Three distinct PCRs were designed. For diagnostic purposes, a primer pair specific to a 409 bases-long segment within the conservative part of the large polymerase region (L) of the CDV genome was designed. Using this test, out of the 150 analyzed samples, 46 (30.66%) proved to be positive for CDV, indicating that CDV still represents a high risk to the canine population in Hungary. For the phylogenetical analysis, a primer pair that completely encompasses the hemagglutinin (H) gene of the CDV genome was designed. The amplicons of this region were sequenced in both directions using the appropriate primers. Our results indicate that several different CDV genotypes are currently present in Hungary. Nine of the analyzed Hungarian strains turned out to belong to the so-called Arctic group of CDVs, and were most closely related to non-European strains from North America, China and Greenland, as well as to the phocine distemper virus 2 (PDV-2) isolated from Baikal seals (Phoca sibirica). One of the Hungarian strains showed high similarity to other European isolates from Denmark, Germany, Italy and Turkey, as well as to other isolates from geographically more distant regions, such as the USA. Three Hungarian strains seem to join a new cluster that is formed by only a couple of strains, one isolated from a mink in Denmark, and another from a dog in North America. Using a third set of primers, a restriction fragment length polymorphism (RFLP) assay has also been designed for the fast and reliable differentiation of the wild-type CDVs from the vaccine strains.


The pivotal role of TMPRSS2 in coronavirus disease 2019 and prostate cancer


title: Incidence, risk factors, and outcome of pulmonary invasive fungal disease after respiratory virus infection in allogeneic hematopoietic stem cell transplantation recipients

text: BACKGROUND: There is growing evidence that community‐acquired respiratory virus (CARV) increases the risk of pulmonary invasive fungal disease (IFD) in the allogeneic hematopoietic stem cell transplantation (allo‐HSCT) setting. To date, there is a lack of knowledge regarding the risk factors (RFs), as well as the most critical period for subsequent onset of IFD after CARV infections in allo‐HSCT recipients. METHODS: In this prospective longitudinal observational CARV survey, we analyzed the effect of CARV on subsequent IFD development in 287 adult allo‐HSCT recipients diagnosed with 597 CARV episodes from December 2013 to December 2018. Multiplex PCR panel assays were used to test CARVs in respiratory specimens. FINDINGS: Twenty‐nine out of 287 allo‐HSCT recipients (10%) developed IFD after a CARV episode. The median time of IFD onset was 21 days (range, 0‐158 days) from day of the first CARV detection. Generalized estimating equation model identified 4 risk factors for IFD: ATG‐based conditioning regimen [odds ratio (OR) 2.34, 95% confidence interval (CI) 1.05‐5.2, P = .038], CARV lower respiratory tract disease (OR 10.6, 95% CI 3.7‐30.8, P < .0001), CARV infection during the first year after transplant (OR 5.34, 95% CI 1.3‐21.8, P = .014), and corticosteroids during CARV (OR 2.6, 95% CI 1.1‐6.3, P = .03). CONCLUSION: Allo‐HSCT recipients conditioned with ATG and under corticosteroid therapy at the time of CARV LRTD during the first year after transplant may require close monitoring for subsequent IFD.


title: Geographic variation in the eukaryotic virome of human diarrhea

text: Abstract Little is known about the population of eukaryotic viruses in the human gut (“virome”) or the potential role it may play in disease. We used a metagenomic approach to define and compare the eukaryotic viromes in pediatric diarrhea cohorts from two locations (Melbourne and Northern Territory, Australia). We detected viruses known to cause diarrhea, non-pathogenic enteric viruses, viruses not associated with an enteric reservoir, viruses of plants, and novel viruses. Viromes from Northern Territory children contained more viral families per sample than viromes from Melbourne, which could be attributed largely to an increased number of sequences from the families Adenoviridae and Picornaviridae (genus enterovirus). qRT-PCR/PCR confirmed the increased prevalence of adenoviruses and enteroviruses. Testing of additional diarrhea cohorts by qRT-PCR/PCR demonstrated statistically different prevalences in different geographic sites. These findings raise the question of whether the virome plays a role in enteric diseases and conditions that vary with geography.


title: Viral Hepatitis

text: While …


title: Cardiovascular Safety of Potential Drugs for the Treatment of Coronavirus Disease 2019

text: Coronavirus disease 2019 (COVID-19) has become a global pandemic. It is still uncontrolled in most countries and no therapies are currently available. Various drugs are under investigation for its treatment. The disease is known to have worse outcomes in patients who have underlying cardiovascular disease. Chloroquine/hydroxychloroquine, azithromycin, remdesivir and lopinavir/ritonavir are currently being studied in trials and show some promise. Conduction disorders, heart failure and mortality have been reported with the use of these drugs. It is important to have a knowledge of potential cardiotoxic effects of these drugs before using them for COVID-19 patients for better allocation of healthcare resources and improvement in clinical outcomes.


title: Hemagglutinating encephalomyelitis virus attaches to N-acetyl-9-O-acetylneuraminic acid-containing receptors on erythrocytes: comparison with bovine coronavirus and influenza C virus

text: Abstract The receptors for the hemagglutinating encephalomyelitis virus (HEV, a porcine coronavirus) on chicken erythrocytes were analyzed and compared to the receptors for bovine coronavirus (BCV) and influenza C virus. Evidence was obtained that HEV requires the presence of N-acetyl-9-O-acetylneuraminic acid (Neu5,9Ac2) on the cell surface for agglutination of erythrocytes as has been previously shown for BCV and influenza C virus: (i) Incubation of red blood cells with sialate 9-O-acetylesterase, the receptor-destroying enzyme of influenza C virus, rendered the erythrocytes resistant against agglutination by each of the three viruses; (ii) Human erythrocytes which are resistant to agglutination by HEV acquire receptors for HEV after resialylation with Neu5,9Ac2. Sialylation of red blood cells with limiting amounts of sialic acid indicated that strain JHB/1/66 of influenza C virus requires less Neu5,9Ac2 for agglutination of erythrocytes than the two coronaviruses, both of which were found to be similar in their reactivity with Neu5,9Ac2-containing receptors.


title: Visualization of protein sequence space with force-directed graphs, and their application to the choice of target-template pairs for homology modelling

text: Abstract The protein sequence-structure gap results from the contrast between rapid, low-cost deep sequencing, and slow, expensive experimental structure determination techniques. Comparative homology modelling may have the potential to close this gap by predicting protein structure in target sequences using existing experimentally solved structures as templates. This paper presents the first use of force-directed graphs for the visualization of sequence space in two dimensions, and applies them to the choice of suitable RNA-dependent RNA polymerase (RdRP) target-template pairs within human-infective RNA virus genera. Measures of centrality in protein sequence space for each genus were also derived and used to identify centroid nearest-neighbour sequences (CNNs) potentially useful for production of homology models most representative of their genera. Homology modelling was then carried out for target-template pairs in different species, different genera and different families, and model quality assessed using several metrics. Reconstructed ancestral RdRP sequences for individual genera were also used as templates for the production of ancestral RdRP homology models. High quality ancestral RdRP models were consistently produced, as were good quality models for target-template pairs in the same genus. Homology modelling between genera in the same family produced mixed results and inter-family modelling was unreliable. We present a protocol for the production of optimal RdRP homology models for use in further experiments, e.g. docking to discover novel anti-viral compounds. (219 words)


UpToDate: Using clinicians’ searches to track outbreaks


title: Molecular dynamics simulation revealed binding of nucleotide inhibitors to ZIKV polymerase over 444 nanoseconds

text: In the year 2015, new Zika virus (ZIKV) broke out in Brazil and spread away in more than 80 countries. Scientists directed their efforts toward viral polymerase in attempt to find inhibitors that might interfere with its function. In this study, molecular dynamics simulation (MDS) was performed over 444 ns for a ZIKV polymerase model. Molecular docking (MD) was then performed every 10 ns during the MDS course to ensure the binding of small molecules to the polymerase over the entire time of the simulation. MD revealed the binding ability of four suggested guanosine inhibitors (GIs); (Guanosine substituted with OH and SH (phenyl) oxidanyl in the 2′ carbon of the ribose ring). The GIs were compared to guanosine triphosphate (GTP) and five anti‐hepatitis C virus drugs (either approved or under clinical trials). The mode of binding and the binding performance of GIs to ZIKV polymerase were found to be the same as GTP. Hence, these compounds were capable of competing GTP for the active site. Moreover, GIs bound to ZIKV active site more tightly compared to ribavirin, the wide‐range antiviral drug.


title: Biologie moléculaire et microbiologie clinique en 2007 Généralités - Partie 1

text: Résumé La biologie moléculaire est omniprésente en biologie médicale et plus particulièrement en microbiologie. De nombreux articles démontrent son importance tant dans le domaine du diagnostic que du pronostic, de l'évaluation thérapeutique, de l'épidémiologie ou des risques biologiques naturels ou non. La quantité considérable d'articles sur ce sujet, n'apporte pas toujours une réponse évidente sur le rôle de la biologie moléculaire dans un laboratoire de microbiologie qu'il soit hospitalier ou non. Cette revue constitue une synthèse des apports de cette discipline en microbiologie. À partir de cet état des lieux, certaines questions se posent, par exemple: la biologie moléculaire constitue-t-elle un réel apport en microbiologie? Dans quelles indications prescrire un examen de biologie moléculaire? Les réponses ne sont pas toujours simples. Dans cet article composé de deux parties, la première partie aborde les généralités de biologie moléculaire et plus particulièrement les principales techniques utilisées dans le domaine de la microbiologie et la seconde partie à venir traitera des applications. Abstract Molecular biology is omnipresent in medical biology especially in microbiology. Many papers report studies on its importance in diagnosis, prognosis, therapeutic field, epidemiology, natural (or not) biological risks alike. The important sum of reports on this subject does not always bring an obvious answer to the part that molecular biology could play in a microbiology laboratory either public or private. This article summarizes the contributions of this specialized field in microbiology and brings some questions on its contribution. Is molecular biology a real progress in microbiology? What are the main indications of molecular biology today in this field? According to the infectious particle, the answers are not always simple. They can be obvious in some cases (for instance, hepatitis C) or less obvious in other cases (tuberculosis for instance). In this article divided in two parts, the first one report an introduction to molecular biology in microbiology and the following second part will deal with the main applications in microbiology.


title: Tourism and COVID-19: impacts and implications for advancing and resetting industry and research

text: The paper aims to critically review past and emerging literature to help professionals and researchers alike to better understand, manage and valorize both the tourism impacts and transformational affordance of COVID-19. To achieve this, first, the paper discusses why and how the COVID-19 can be a transformational opportunity by discussing the circumstances and the questions raised by the pandemic. By doing this, the paper identifies the fundamental values, institutions and pre-assumptions that the tourism industry and academia should challenge and break through to advance and reset the research and practice frontiers. The paper continues by discussing the major impacts, behaviours and experiences that three major tourism stakeholders (namely tourism demand, supply and destination management organisations and policy makers) are experiencing during three COVID-19 stages (response, recovery and reset). This provides an overview of the type and scale of the COVID-19 tourism impacts and implications for tourism research.


title: Lactogenic immunity following vaccination of cattle with bovine coronavirus

text: Abstract In order to investigate the ability of an oil adjuvanted vaccine containing bovine coronavirus antigen to enhance lactogenic immunity in the calf, pregnant cows and heifers were vaccinated and specific virus neutralising antibody levels determined in serum, colostrum and milk. Pre-existing antibody titres (as a result of natural infection) in the serum of these animals were found to be significantly increased as a result of a single shot vaccination carried out between 2 and 12 weeks before calving. This was reflected in a similar increase in the titre and duration of specific antibody in milk and colostrum that was passed on to the calves. The overall response observed was highly dependent on an adequate antigen payload being incorporated within the single dose vaccine. No abnormal local or systemic reactions were observed as a result of vaccination. It is hoped that this approach will lead to the production of a superior commercial vaccine for the protection of neonatal calves against enteric coronavirus infection.


title: The SARS-Coronavirus PLnc domain of nsp3 as a replication/transcription scaffolding protein

text: Abstract Many genetic and mechanistic features distinguish the coronavirus replication machinery from that encoded by most other RNA viruses. The coronavirus replication/transcription complex is an assembly of viral and, most probably, cellular proteins that mediate the synthesis of both the unusually large (∼30kb) RNA genome and an extensive set of subgenomic mRNAs. The viral components of the complex are encoded by the giant replicase gene, which is expressed in the form of two polyproteins (pp1a and pp1ab) that are processed into 16 cleavage products (nonstructural proteins 1–16). Using the combination of yeast two-hybrid screening and GST pull-down assays, we have now analyzed all potential interactions between SARS-Coronavirus nonstructural proteins, which may contribute to the structure and/or function of the viral replication/transcription complex. We demonstrate the existence of a complex network of interactions involving all 16 nonstructural proteins. Our results both confirmed previously described associations and identified novel heterodimerizations. The interaction map thus provides a sum of the interactions that may occur at some point during coronavirus RNA synthesis and provides a framework for future research.


title: Establishing a genetic recombination map for murine coronavirus strain A59 complementation groups

text: Abstract MHV-A59 temperature-sensitive mutants, representing one RNA+ and five RNA− complementation groups, were isolated and characterized by genetic recombination techniques. Maximum recombination frequencies occurred under multiplicities of infection greater than 10 each in which 99.99% of the cells were co-infected. Recombination frequencies between different is mutants increased steadily during infection and peaked late in the virus growth cycle. These data suggest that recombination is a late event in the virus replication cycle. Recombination frequencies were also found to range from 63 to 20,000 times higher than the sum of the spontaneous reversion frequencies of each is mutant used in the cross. Utilizing standard genetic recombination techniques, the five RNA− complementation groups of MHV-A59 were arranged into an additive, linear, genetic map located at the 5′ end of the genome in the 23-kb polymerase region. These data indicate that at least five distinct functions are encoded in the MHV polymerase region which function in virus transcription. Moreover, using well-characterized is mutants the recombination frequency for the entire 32-kb MHV genome was found to approach 25% or more. This is the highest recombination frequency described for a nonsegmented, linear, plus-polarity RNA virus.


title: Respiratory Viruses and Bacteria among Pilgrims during the 2013 Hajj

text: Pilgrims returning from the Hajj might contribute to international spreading of respiratory pathogens. Nasal and throat swab specimens were obtained from 129 pilgrims in 2013 before they departed from France and before they left Saudi Arabia, and tested by PCR for respiratory viruses and bacteria. Overall, 21.5% and 38.8% of pre-Hajj and post-Hajj specimens, respectively, were positive for ≥1 virus (p = 0.003). One third (29.8%) of the participants acquired ≥1 virus, particularly rhinovirus (14.0%), coronavirus E229 (12.4%), and influenza A(H3N2) virus (6.2%) while in Saudi Arabia. None of the participants were positive for the Middle East respiratory syndrome coronavirus. In addition, 50.0% and 62.0% of pre-Hajj and post-Hajj specimens, respectively, were positive for Streptococcus pneumoniae (p = 0.053). One third (36.3%) of the participants had acquired S. pneumoniae during their stay. Our results confirm high acquisition rates of rhinovirus and S. pneumoniae in pilgrims and highlight the acquisition of coronavirus E229.


Corona-associated suicide – Observations made in the autopsy room


MHC Antigen Expression on Glial Cells


title: Human endogenous retroviruses and multiple sclerosis: Innocent bystanders or disease determinants?

text: Abstract Human endogenous retroviruses (HERVs) constitute 5–8% of human genomic DNA and are replication incompetent despite expression of individual HERV genes from different chromosomal loci depending on the specific tissue. Several HERV genes have been detected as transcripts and proteins in the central nervous system, frequently in the context of neuroinflammation. The HERV-W family has received substantial attention in large part because of associations with diverse syndromes including multiple sclerosis (MS) and several psychiatric disorders. A HERV-W-related retroelement, multiple sclerosis retrovirus (MSRV), has been reported in MS patients to be both a biomarker as well as an effector of aberrant immune responses. HERV-H and HERV-K have also been implicated in MS and other neurological diseases but await delineation of their contributions to disease. The HERV-W envelope-encoded glycosylated protein, syncytin-1, is encoded by chromosome 7q21 and exhibits increased glial expression within MS lesions. Overexpression of syncytin-1 in glia induces endoplasmic reticulum stress leading to neuroinflammation and the induction of free radicals, which damage proximate cells. Syncytin-1's receptor, ASCT1 is a neutral amino acid transporter expressed on glia and is suppressed in white matter of MS patients. Of interest, antioxidants ameliorate syncytin-1's neuropathogenic effects raising the possibility of using these agents as therapeutics for neuroinflammatory diseases. Given the multiple insertion sites of HERV genes as complete and incomplete open reading frames, together with their differing capacity to be expressed and the complexities of individual HERVs as both disease markers and bioactive effectors, HERV biology is a compelling area for understanding neuropathogenic mechanisms and developing new therapeutic strategies.


title: Nursing and the novel coronavirus: Risks and responsibilities in a global outbreak

text: In December of 2019, reports emerged of pneumonia clusters of unknown cause at health facilities in Wuhan, China. These cases were linked to a wet animal wholesale market in the region and, after extensive epidemiologic investigation, led to identification of a novel coronavirus (COVID-19). COVID-19 is among a family of viruses-called coronaviruses-that can affect both humans and animals (Zhu et al., 2020).


title: Novel screening systems for HIV-1 fusion mediated by two extra-virion heptad repeats of gp41

text: Abstract Entry of human immunodeficiency virus type 1 (HIV-1) into target cells is mediated by its envelope protein gp41 through membrane fusion. Interaction of two extra-virion heptad repeats (HRs) in the gp41 plays a pivotal role in the fusion, and its inhibitor, enfuvirtide (T-20), blocks HIV-1 entry. To identify agents that block HIV-1 fusion, two screening methods based on detection and quantification by the enzyme-linked immunosorbent assay (ELISA) principle have been established. One method uses an alkaline phosphatase (ALP)-conjugated antibody (Ab-ELISA) and the other uses an ALP-fused HR (F-ELISA) to detect and quantify the interaction of the two HRs. The F-ELISA was more simple and rapid, since no ALP-conjugated antibody reaction was required. Both ELISAs detected all the fusion inhibitors tested except for T-20. Interaction of the two HRs was observed in both ELISAs, even in the presence of 10% dimethyl sulfoxide. Ab-ELISA performed best in a pH ranging from 6 to 8, while F-ELISA performed best at a pH ranging from 7 to 8. These results indicate that both established ELISAs are suitable for the identification of HIV-1 fusion inhibitors.


The use of simulation to prepare for changes in emergent airway management in the early days of the Covid-19 outbreak


title: Nanobioimaging and sensing of infectious diseases

text: Abstract New methods to identify trace amount of infectious pathogens rapidly, accurately and with high sensitivity are in constant demand to prevent epidemics and loss of lives. Early detection of these pathogens to prevent, treat and contain the spread of infections is crucial. Therefore, there is a need and urgency for sensitive, specific, accurate, easy-to-use diagnostic tests. Versatile biofunctionalized engineered nanomaterials are proving to be promising in meeting these needs in diagnosing the pathogens in food, blood and clinical samples. The unique optical and magnetic properties of the nanoscale materials have been put to use for the diagnostics. In this review, we focus on the developments of the fluorescent nanoparticles, metallic nanostructures and superparamagnetic nanoparticles for bioimaging and detection of infectious microorganisms. The various nanodiagnostic assays developed to image, detect and capture infectious virus and bacteria in solutions, food or biological samples in vitro and in vivo are presented and their relevance to developing countries is discussed.


title: Evaluation of sex‐related hormones and semen characteristics in reproductive‐aged male COVID‐19 patients

text: In the past several months, the outbreak of SARS‐CoV‐2‐associated infection (coronavirus disease 2019, COVID‐19) developed rapidly and has turned into a global pandemic. Although SARS‐CoV‐2 mainly attacks respiratory systems, manifestations of multiple organs have been observed. Great concern was raised about whether COVID‐19 may affect male reproductive functions. In this study, we collected semen specimens from twelve male COVID‐19 patients for virus detection and semen characteristics analysis. No SARS‐CoV‐2 was found in semen specimens. 8 out of 12 patients had normal semen quality. We also compared the sex‐related hormone levels between 119 reproductive‐aged men with SARS‐CoV‐2 infection and 273 age‐matched control men. A higher serum luteinizing hormone (LH) and a lower ratio of testosterone (T) to LH were observed in the COVID‐19 group. Multiple regression analysis indicated that serum T:LH ratio was negatively associated with white blood cell counts (WBC) and c‐reactive protein (CRP) level in COVID‐19 patients. It's the first report about semen assessment and sex‐hormone evaluation in reproductive‐aged male COVID‐19 patients. Although further study is needed to clarify the reasons and underlying mechanisms, our study presents an abnormal sex hormone secretion among COVID‐19 patients, suggesting that attention should be paid to reproductive function evaluation in the follow‐up. This article is protected by copyright. All rights reserved.


title: Surveillance of diarrhea‐causing pathogens in dairy and beef cows in Yamagata Prefecture, Japan from 2002 to 2011

text: The economic consequences of bovine diarrhea are serious. Few long‐term epidemiological data are available concerning the causative pathogens of bovine diarrhea in Japan. From 2002 to 2011, surveillance of enteric pathogens was performed in cows of various breed and age from 302 farms in which diarrhea had occurred in Yamagata Prefecture, Japan. Differences between dairy and beef cows in the number of cases of diarrhea and rates of infection by Salmonella spp. and Eimeria spp. were found. Clinical symptoms (duration of epidemic, hematochezia and complications) caused by bovine rotavirus infection were milder than those caused by bovine coronavirus infection.


title: eEF1A Interacts with the NS5A Protein and Inhibits the Growth of Classical Swine Fever Virus

text: The NS5A protein of classical swine fever virus (CSFV) is involved in the RNA synthesis and viral replication. However, the NS5A-interacting cellular proteins engaged in the CSFV replication are poorly defined. Using yeast two-hybrid screen, the eukaryotic elongation factor 1A (eEF1A) was identified to be an NS5A-binding partner. The NS5A–eEF1A interaction was confirmed by coimmunoprecipitation, glutathione S-transferase (GST) pulldown and laser confocal microscopy assays. The domain I of eEF1A was shown to be critical for the NS5A–eEF1A interaction. Overexpression of eEF1A suppressed the CSFV growth markedly, and conversely, knockdown of eEF1A enhanced the CSFV replication significantly. Furthermore, eEF1A, as well as NS5A, was found to reduce the translation efficiency of the internal ribosome entry site (IRES) of CSFV in a dose-dependent manner, as demonstrated by luciferase reporter assay. Streptavidin pulldown assay revealed that eEF1A could bind to the CSFV IRES. Collectively, our results suggest that eEF1A interacts with NS5A and negatively regulates the growth of CSFV.


title: The standard of care of patients with ARDS: ventilatory settings and rescue therapies for refractory hypoxemia

text: PURPOSE: Severe ARDS is often associated with refractory hypoxemia, and early identification and treatment of hypoxemia is mandatory. For the management of severe ARDS ventilator settings, positioning therapy, infection control, and supportive measures are essential to improve survival. METHODS AND RESULTS: A precise definition of life-threating hypoxemia is not identified. Typical clinical determinations are: arterial partial pressure of oxygen < 60 mmHg and/or arterial oxygenation < 88 % and/or the ratio of PaO(2)/FIO(2) < 100. For mechanical ventilation specific settings are recommended: limitation of tidal volume (6 ml/kg predicted body weight), adequate high PEEP (>12 cmH(2)O), a recruitment manoeuvre in special situations, and a ‘balanced’ respiratory rate (20-30/min). Individual bedside methods to guide PEEP/recruitment (e.g., transpulmonary pressure) are not (yet) available. Prone positioning [early (≤ 48 hrs after onset of severe ARDS) and prolonged (repetition of 16-hr-sessions)] improves survival. An advanced infection management/control includes early diagnosis of bacterial, atypical, viral and fungal specimen (blood culture, bronchoalveolar lavage), and of infection sources by CT scan, followed by administration of broad-spectrum anti-infectives. Neuromuscular blockage (Cisatracurium ≤ 48 hrs after onset of ARDS), as well as an adequate sedation strategy (score guided) is an important supportive therapy. A negative fluid balance is associated with improved lung function and the use of hemofiltration might be indicated for specific indications. CONCLUSIONS: A specific standard of care is required for the management of severe ARDS with refractory hypoxemia.


title: Impact of Comorbidity on Fatality Rate of Patients with Middle East Respiratory Syndrome

text: To date, 1841 cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection have been reported worldwide, with 652 deaths. We used a publically available case line list to explore the effect of relevant factors, notably underlying comorbidities, on fatal outcome of Middle East respiratory syndrome (MERS) cases up to the end of October 2016. A Bayesian Weibull proportional hazards regression model was used to assess the effect of comorbidity, age, epidemic period and sex on the fatality rate of MERS cases and its variation across countries. The crude fatality rate of MERS cases was 32.1% (95% credibility interval (CI): 29.9%, 34.3%). Notably, the incremental change of daily death rate was most prominent during the first week since disease onset with an average increase of 13%, but then stabilized in the remaining two weeks when it only increased 3% on average. Neither sex, nor country of infection were found to have a significant impact on fatality rates after taking into account the age and comorbidity status of patients. After adjusting for age, epidemic period, MERS patients with comorbidity had around 4 times the risk for fatal infection than those without (adjusted hazard ratio of 3.74 (95% CI: 2.57, 5.67)).


Life in Times of COVID‐19


title: TLR3 Regulated Poly I:C-Induced Neutrophil Extracellular Traps and Acute Lung Injury Partly Through p38 MAP Kinase

text: Acute lung injury (ALI) is the leading cause of morbidity and mortality in critically ill patients. Neutrophil extracellular traps (NETs) have been well documented in the ALI model of bacterial infection. In the present study, we demonstrated that poly I:C could induce pulmonary NETs. Upon poly I:C intratracheal inoculation, neutrophil infiltration in the bronchoalveolar lavage fluid (BALF) was significantly increased. Furthermore, the inflammatory cytokines IL-1β, IL-6, and TNF-α in the lung were also significantly elevated. Neutrophil depletion abolished NETs and decreased both neutrophil infiltration and IL-1β in the lung. As expected, DNase I, an inhibitor of MPO and NADPH, decreased pulmonary inflammation and NETs. Blocking of the poly I:C receptor TLR3 reduced lung inflammation and NETs. The MAPK kinase inhibitor p38 diminished the formation of NETs and restored the expression of the tight junction protein claudin-5 in the mouse lung when challenged with poly I:C. In summary, poly I:C induced the formation of pulmonary NETs and ALI, which may be associated with the activation of p38 MAPK and the decreased expression of claudin-5.


title: Rhinitis in the first 18 months of life: Exploring the role of respiratory viruses

text: BACKGROUND: Rhinitis is common in early childhood, but allergic rhinitis is considered a later manifestation of the atopic march. This study aimed to evaluate rhinitis (allergic and non‐allergic) in the first 18 months of life, its link with other atopic manifestations and the role of respiratory viruses. METHODS: Subjects (n = 1237) of the Singapore GUSTO birth cohort were followed up quarterly until 18 months of age with questionnaires to screen for rhinitis symptoms lasting at least 2 wk and with monthly calls to positive subjects to detect prolonged/recurrent rhinitis symptoms (total duration ≥4 wk). Anterior nasal swabbing for molecular‐based virus detection was conducted during these visits and near (within a month) rhinitis episodes. Skin prick testing to common environmental and food allergens was conducted at the 18 month visit. RESULTS: Prolonged/recurrent rhinitis was significantly associated with history of parental atopy (mother: aOR = 2.17; father: aOR = 1.82) and atopic comorbidities of eczema (aOR = 2.53) and wheeze (aOR = 4.63) (p < 0.05), though not with allergen sensitization. Although the frequency of nasal respiratory virus detection during scheduled quarterly visits did not differ between prolonged/recurrent rhinitis and matched controls (p > 0.05), virus detection was higher in swabs obtained within a month following rhinitis episodes in prolonged/recurrent rhinitis subjects compared with scheduled visits (adjusted p = 0.04). CONCLUSIONS: Based on the duration of rhinitis symptoms, this study defined a subset of early childhood rhinitis which was associated with atopic predisposition and comorbidities. Persistent respiratory viral shedding may contribute to the symptomatology. Whether this entity is a precursor of subsequent childhood allergic rhinitis will require longer follow‐up.


title: Brassiparin, an antifungal peptide from Brassica parachinensis seeds

text: Aims: To isolate and characterize an antifungal peptide from the seeds of Brassica parachinensis L.H.Bailey. Methods and Results: An antifungal peptide designated as brassiparin was isolated. It exhibited a molecular mass of 5716 Da. It potently inhibited mycelial growth in a number of fungal species including Fusarium oxysporum, Helminthosporium maydis, Mycosphaerella arachidicola and Valsa mali. The antifungal activity of brassiparin toward M. arachidicola exhibited pronounced thermostability and pH stability. It inhibited proliferation of hepatoma (HepG2) and breast cancer (MCF7) cells and the activity of HIV‐1 reverse transcriptase. Its N‐terminal sequence differed from those of antifungal proteins which have been reported to date. Conclusions: Brassiparin can be purified by using a protocol involving ion exchange chromatography, affinity chromatography and gel filtration. It manifests potent, thermostable and pH‐stable antifungal activity. It demonstrates antiproliferative activity toward tumour cells, and inhibitory activity toward HIV‐1 reverse transcriptase. Thus, brassiparin is a defense protein. Significance and Impact of the Study: Brassiparin represents one of the few antifungal proteins reported to date from Brassica species. Its antifungal activity has pronounced pH stability and thermostability. Brassiparin exhibits other exploitable activities such as antiproliferative activity toward hepatoma and breast cancer cells and inhibitory activity toward HIV‐reverse transcriptase.


title: Can Masks Be Reused After Hot Water Decontamination During the COVID-19 Pandemic?

text: Masks have become one of the most indispensable pieces of personal protective equipment and are important strategic products during the coronavirus disease 2019 (COVID-19) pandemic. Due to the huge mask demand–supply gap all over the world, the development of user-friendly technologies and methods is urgently needed to effectively extend the service time of masks. In this article, we report a very simple approach for the decontamination of masks for multiple reuse during the COVID-19 pandemic. Used masks were soaked in hot water at a temperature greater than 56 °C for 30 min, based on a recommended method to kill COVID-19 virus by the National Health Commission of the People’s Republic of China. The masks were then dried using an ordinary household hair dryer to recharge the masks with electrostatic charge to recover their filtration function (the so-called “hot water decontamination + charge regeneration” method). Three kinds of typical masks (disposable medical masks, surgical masks, and KN95-grade masks) were treated and tested. The filtration efficiencies of the regenerated masks were almost maintained and met the requirements of the respective standards. These findings should have important implications for the reuse of polypropylene masks during the COVID-19 pandemic. The performance evolution of masks during human wear was further studied, and a company (Zhejiang Runtu Co., Ltd.) applied this method to enable their workers to extend the use of masks. Mask use at the company was reduced from one mask per day per person to one mask every three days per person, and 122 500 masks were saved during the period from 20 February to 30 March 2020. Furthermore, a new method for detection of faulty masks based on the penetrant inspection of fluorescent nanoparticles was established, which may provide scientific guidance and technical methods for the future development of reusable masks, structural optimization, and the formulation of comprehensive performance evaluation standards.


title: In vivo toxicity study of quatro stimuli nanocontainers in pregnant rats: Gestation, parturition and offspring evaluation

text: The aim of the present study was to investigate the impact of intravenous administration of newly fabricated nanocontainers (NCs) on the last third of pregnancy in rats. Fifteen pregnant 3-month-old Wistar rats were separated into 3 groups. On the 15th and 17th day of pregnancy all animals received an intravenous administration of 1 ml of 15 mg of NCs (Group A), 1 ml of 5 mg NCs (Group B) while Control group received 1 ml of 0.9% NaCl. On the 14th and 17th of pregnancy ultrasonography was performed and the parameters evaluated were the width of placenta, the length and width of the embryonic sac, the foetus length and the heart rate. On parturition the number of pups per dam was evaluated. Half of the pups were euthanised the day after parturition and their liver and kidney was histologically evaluated and for the rest of the pups the body growth curve was evaluated until the age of 14 week. At the end of the 14th week the remaining pups were euthanised and their liver and kidney was histologically evaluated. At weaning the dams were euthanised and their liver and kidney was histologically evaluated. Ultrasonography: Baseline measurements of the width of placenta, the length and width of embryonic sac, the foetus length and the heart rate on the 14th day of pregnancy, revealed no statistical significant differences between groups. Comparison of the same values on the 17th day of pregnancy after 2 intravenous administrations of NCs showed no statistical significant effect on the respective parameters. The administration of NCs had no impact on the mean number of pups per dam. Additionally, no impact of the NCs on the body weights of the pups was observed on the 1st day after parturition. Moreover, comparisons between groups, for both sexes showed no difference on growth rate. During the histological evaluation no inflammatory, degenerative or neoplastic lesions were observed as far as the newborn, adult offspring and dams were concerned. According to our results no toxic impact of the low and high doses of the NCs was observed on the parameters selected to be evaluated.


title: Sloths host Anhanga virus‐related phleboviruses across large distances in time and space

text: Sloths are genetically and physiologically divergent mammals. Phleboviruses are major arthropod‐borne viruses (arboviruses) causing disease in humans and other animals globally. Sloths host arboviruses, but virus detections are scarce. A phlebovirus termed Anhanga virus (ANHV) was isolated from a Brazilian Linnaeus's two‐toed sloth (Choloepus didactylus) in 1962. Here, we investigated the presence of phleboviruses in sera sampled in 2014 from 74 Hoffmann's two‐toed (Choloepus hoffmanni, n = 65) and three‐toed (Bradypus variegatus, n = 9) sloths in Costa Rica by broadly reactive RT‐PCR. A clinically healthy adult Hoffmann's two‐toed sloth was infected with a phlebovirus. Viral load in this animal was high at 8.5 × 10(7) RNA copies/ml. The full coding sequence of the virus was determined by deep sequencing. Phylogenetic analyses and sequence distance comparisons revealed that the new sloth virus, likely representing a new phlebovirus species, provisionally named Penshurt virus (PEHV), was most closely related to ANHV, with amino acid identities of 93.1%, 84.6%, 94.7% and 89.0% in the translated L, M, N and NSs genes, respectively. Significantly more non‐synonymous mutations relative to ANHV occurred in the M gene encoding the viral glycoproteins and in the NSs gene encoding a putative interferon antagonist compared to L and N genes. This was compatible with viral adaptation to different sloth species and with micro‐evolutionary processes associated with immune evasion during the genealogy of sloth‐associated phleboviruses. However, gene‐wide mean dN/dS ratios were low at 0.02–0.15 and no sites showed significant evidence for positive selection, pointing to comparable selection pressures within sloth‐associated viruses and genetically related phleboviruses infecting hosts other than sloths. The detection of a new phlebovirus closely‐related to ANHV, in sloths from Costa Rica fifty years after and more than 3,000 km away from the isolation of ANHV confirmed the host associations of ANHV‐related phleboviruses with the two extant species of two‐toed sloths.


SARS‐CoV‐2 Viral Inactivation Using Low Dose Povidone‐Iodine Oral Rinse—Immediate Application for the Prosthodontic Practice


docid: wrlmyfxf

title: Molecular point-of-care testing for respiratory viruses versus routine clinical care in adults with acute respiratory illness presenting to secondary care: a pragmatic randomised controlled trial protocol (ResPOC)

text: BACKGROUND: Respiratory viruses are associated with a huge socio-economic burden and are responsible for a large proportion of acute respiratory illness in hospitalised adults. Laboratory PCR is accurate but takes at least 24 h to generate a result to clinicians and antigen-based point-of-care tests (POCT) lack sensitivity. Rapid molecular platforms, such as the FilmArray Respiratory Panel, have equivalent diagnostic accuracy to laboratory PCR and can generate a result in 1 h making them deployable as POCT. Molecular point-of-care testing for respiratory viruses in hospital has the potential to improve the detection rate of respiratory viruses, improve the use of influenza antivirals and reduce unnecessary antibiotic use, but high quality randomised trials with clinically relevant endpoints are needed. METHODS: The ResPOC study is a pragmatic randomised controlled trial of molecular point-of-care testing for respiratory viruses in adults with acute respiratory illness presenting to a large teaching hospital in the United Kingdom. Eligible participants are adults presenting with acute respiratory illness to the emergency department or the acute medicine unit. Participants are allocated 1:1 by internet-based randomisation service to either the intervention of a nose and throat swab analysed immediately on the FilmArray Respiratory Panel as a POCT or receive routine clinical care. The primary outcome is the proportion of patients treated with antibiotics. Secondary outcomes include turnaround time, virus detection, neuraminidase inhibitor use, length of hospital stay and side room use. Analysis of the primary outcome will be by intention-to-treat and all enrolled participants will be included in safety analysis. DISCUSSION: Multiple novel molecular POCT platforms for infections including respiratory viruses have been developed and licensed in the last few years and many more are in development but the evidence base for clinical benefit above standard practice is minimal. This randomised controlled trial aims to close this evidence gap by generating high quality evidence for the clinical impact of molecular POCT for respiratory viruses in secondary care and to act as an exemplar for future studies of molecular POCT for infections. This study has the potential to change practice and improve patient care for patients presenting to hospital with acute respiratory illness. TRIAL REGISTRATION: This study was registered with ISRCTN, number ISRCTN90211642, on 14th January 2015.


title: Molecular pathology of emerging coronavirus infections

text: Respiratory viruses can cause a wide spectrum of pulmonary diseases, ranging from mild, upper respiratory tract infections to severe and life-threatening lower respiratory tract infections, including the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Viral clearance and subsequent recovery from infection require activation of an effective host immune response; however, many immune effector cells may also cause injury to host tissues. Severe acute respiratory syndrome (SARS) coronavirus and Middle East respiratory syndrome (MERS) coronavirus cause severe infection of the lower respiratory tract, with 10% and 35% overall mortality rates, respectively; however, >50% mortality rates are seen in the aged and immunosuppressed populations. While these viruses are susceptible to interferon treatment in vitro, they both encode numerous genes that allow for successful evasion of the host immune system until after high virus titres have been achieved. In this review, we discuss the importance of the innate immune response and the development of lung pathology following human coronavirus infection.


title: Neurologic Alterations Due to Respiratory Virus Infections

text: Central Nervous System (CNS) infections are one of the most critical problems in public health, as frequently patients exhibit neurologic sequelae. Usually, CNS pathologies are caused by known neurotropic viruses such as measles virus (MV), herpes virus and human immunodeficiency virus (HIV), among others. However, nowadays respiratory viruses have placed themselves as relevant agents responsible for CNS pathologies. Among these neuropathological viruses are the human respiratory syncytial virus (hRSV), the influenza virus (IV), the coronavirus (CoV) and the human metapneumovirus (hMPV). These viral agents are leading causes of acute respiratory infections every year affecting mainly children under 5 years old and also the elderly. Up to date, several reports have described the association between respiratory viral infections with neurological symptoms. The most frequent clinical manifestations described in these patients are febrile or afebrile seizures, status epilepticus, encephalopathies and encephalitis. All these viruses have been found in cerebrospinal fluid (CSF), which suggests that all these pathogens, once in the lungs, can spread throughout the body and eventually reach the CNS. The current knowledge about the mechanisms and routes used by these neuro-invasive viruses remains scarce. In this review article, we describe the most recent findings associated to neurologic complications, along with data about the possible invasion routes of these viruses in humans and their various effects on the CNS, as studied in animal models.


COVID-19-associated invasive pulmonary aspergillosis


Luftverschmutzung wird zur "Pandemie"


Is SARSCoV-2 nasopharyngeal swab still a gold standard in children?


Comment on “COVID‐19 and psoriasis: Is it time to limit treatment with immunosuppressants? A call for action”


Loneliness and belonging: Exploring experiences with the COVID‐19 pandemic in psycho‐oncology


title: Biological characters of bats in relation to natural reservoir of emerging viruses

text: Abstract Many investigators focused on bats (Chiroptera) for their specific character, i.e. echolocation system, phylogenic tree, food practice and unique reproduction. However, most of basic information about the vital functions related to anti-viral activity has been unclear. For evaluating some animals as a natural reservoir or host of infectious pathogens, it is necessary that not only their immune system but also their biology, the environment of their living, food habits and physiological features should be clarified and they should be analyzed from these multi-view points. The majority of current studies on infectious diseases have been conducted for the elucidation of viral virulence using experimental animals or viral gene function in vitro, but in a few case, researchers focused on wild animal itself. In this paper, we described basic information about bats as follows; genetic background, character of the immunological factors, histological character of immune organs, the physiological function and sensitivity of bat cells to viral infection.


title: Identification of IFITM1 and IFITM3 in Goose: Gene Structure, Expression Patterns, and Immune Reponses against Tembusu Virus Infection

text: As interferon-stimulated genes (ISGs), interferon-inducible transmembrane proteins 1 and 3 (IFITM1 and IFITM3) can effectively inhibit the replication of multiple viruses. Here, goose IFITM1 and IFITM3 were cloned and identified for the first time. The two proteins share the same topological structure and several important sites critical for the antiviral functions in other species are conserved in the goose. Goose IFITM1 and IFITM3 are most closely related to their respective orthologs in ducks; these proteins exhibited high mRNA transcript levels in immune-related tissues, including the thymus, bursa of Fabricius, and Harderian gland, compared to other tissues. Moreover, goose IFITM1 was highly constitutively expressed in gastrointestinal tract tissues, while goose IFITM3 was expressed in respiratory organs. Furthermore, goose IFITM3 was activated in goose peripheral blood mononuclear cells (PBMCs) infected with Tembusu virus (TMUV) or treated with Toll-like receptors (TLRs) agonists, while only the R848 and Poly (I:C) agonists induced significant upregulation of goose IFITM1. Furthermore, goose IFITM1 and IFITM3 were upregulated in the sampled tissues, to some extent, after TMUV infection. Notably, significant upregulation of goose IFITM1 and IFITM3 was detected in the cecum and cecal tonsil, where TMUV was primarily distributed. These data provide new insights into the immune effectors in geese and promote our understanding of the role of IFITM1 and IFITM3 in the defense against TMUV.


title: Isolation of a variant infectious bronchitis virus in Australia that further illustrates diversity among emerging strains

text: Australian infectious bronchitis viruses (IBV) have undergone a separate evolution due to geographic isolation. Consequently, changes occurring in Australian IBV illustrate, independently from other countries, types of variability that could occur in emerging IBV strains. Previously, we have identified two distinct genetic groups of IBV, designated subgroups 1 and 2. IBV strains of subgroup 1 have S1 and N proteins that share a high degree of amino acid identity, 81 to 98% in S1 and 91 to 99% in N. Subgroup 2 strains possess S1 and N proteins that share a low level of identity with subgroup 1 strains: 54 to 62% in S1 and 60 to 62% in N. This paper describes the isolation and characterisation of a third, previously undetected genetic group of IBV in Australia. The subgroup 3 strains, represented by isolate chicken/Australia/N2/04, had an S1 protein that shared a low level of identity with both subgroups 1 and 2: 61 to 63% and 56 to 59%, respectively. However, the N protein and the 3′ untranslated region were similar to subgroup 1: 90 to 97% identical with the N protein of subgroup 1 strains. This N4/02 subgroup 3 of IBV is reminiscent of two other strains, D1466 and DE072, isolated in the Netherlands and in the USA, respectively. The emergence of the subgroup 3 viruses in Australia, as well as the emergence of subgroup 2 in 1988, could not be explained by any of the mechanisms that are currently considered to be involved in generation of IBV variants.


title: Structural and Functional Properties of the Hepatitis C Virus p7 Viroporin

text: The high prevalence of hepatitis C virus (HCV) infection in the human population has triggered intensive research efforts that have led to the development of curative antiviral therapy. Moreover, HCV has become a role model to study fundamental principles that govern the replication cycle of a positive strand RNA virus. In fact, for most HCV proteins high-resolution X-ray and NMR (Nuclear Magnetic Resonance)-based structures have been established and profound insights into their biochemical and biological properties have been gained. One example is p7, a small hydrophobic protein that is dispensable for RNA replication, but crucial for the production and release of infectious HCV particles from infected cells. Owing to its ability to insert into membranes and assemble into homo-oligomeric complexes that function as minimalistic ion channels, HCV p7 is a member of the viroporin family. This review compiles the most recent findings related to the structure and dual pore/ion channel activity of p7 of different HCV genotypes. The alternative conformations and topologies proposed for HCV p7 in its monomeric and oligomeric state are described and discussed in detail. We also summarize the different roles p7 might play in the HCV replication cycle and highlight both the ion channel/pore-like function and the additional roles of p7 unrelated to its channel activity. Finally, we discuss possibilities to utilize viroporin inhibitors for antagonizing p7 ion channel/pore-like activity.


Faut-il une surveillance ophtalmologique en cas de traitement de courte durée par hydroxychloroquine en cette période d’épidémie au COVID-19?1


title: Diagnostic cerebrospinal fluid biomarkers for Parkinson's disease: A pathogenetically based approach

text: Abstract The inaccuracy of the early diagnosis of Parkinson's disease (PD) has been a major incentive for studies aimed at the identification of biomarkers. Brain-derived cerebrospinal fluid (CSF) proteins are potential biomarkers considering the major role that proteins play in PD pathogenesis. In this review, we discuss the current hypotheses about the pathogenesis of PD and identify the most promising candidate biomarkers among the CSF proteins studied so far. The list of potential markers includes proteins involved in various pathogenetic processes, such as oxidative stress and protein aggregation. This list will undoubtedly grow in the near future by application of CSF proteomics and subsequent validation of identified proteins. Probably a single biomarker will not suffice to reach high sensitivity and specificity, because PD is pathogenetically heterogeneous and shares etiological factors with other neurodegenerative diseases. Furthermore, identified candidate biomarkers will have to be thoroughly validated before they can be implemented as diagnostic aids.


title: Acute Respiratory Infection in Human Dipeptidyl Peptidase 4-Transgenic Mice Infected with Middle East Respiratory Syndrome Coronavirus

text: Middle East respiratory syndrome coronavirus (MERS-CoV) infection can manifest as a mild illness, acute respiratory distress, organ failure, or death. Several animal models have been established to study disease pathogenesis and to develop vaccines and therapeutic agents. Here, we developed transgenic (Tg) mice on a C57BL/6 background; these mice expressed human CD26/dipeptidyl peptidase 4 (hDPP4), a functional receptor for MERS-CoV, under the control of an endogenous hDPP4 promoter. We then characterized this mouse model of MERS-CoV. The expression profile of hDPP4 in these mice was almost equivalent to that in human tissues, including kidney and lung; however, hDPP4 was overexpressed in murine CD3-positive cells within peripheral blood and lymphoid tissues. Intranasal inoculation of young and adult Tg mice with MERS-CoV led to infection of the lower respiratory tract and pathological evidence of acute multifocal interstitial pneumonia within 7 days, with only transient loss of body weight. However, the immunopathology in young and adult Tg mice was different. On day 5 or 7 postinoculation, lungs of adult Tg mice contained higher levels of proinflammatory cytokines and chemokines associated with migration of macrophages. These results suggest that the immunopathology of MERS-CoV infection in the Tg mouse is age dependent. The mouse model described here will increase our understanding of disease pathogenesis and host mediators that protect against MERS-CoV infection. IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) infections are endemic in the Middle East and a threat to public health worldwide. Rodents are not susceptible to the virus because they do not express functional receptors; therefore, we generated a new animal model of MERS-CoV infection based on transgenic mice expressing human DPP4 (hDPP4). The pattern of hDPP4 expression in this model was similar to that in human tissues (except lymphoid tissue). In addition, MERS-CoV was limited to the respiratory tract. Here, we focused on host factors involved in immunopathology in MERS-CoV infection and clarified differences in antiviral immune responses between young and adult transgenic mice. This new small-animal model could contribute to more in-depth study of the pathology of MERS-CoV infection and aid development of suitable treatments.


title: Enhancing ergosterol production in Pichia pastoris GS115 by overexpressing squalene synthase gene from Glycyrrhiza uralensis

text: Abstract The present study was designed to determine the effects of copy number variations (CNVs) of squalene synthase 1(SQS1) gene on the mevalonate (MVA) pathway. SQS1 gene from G. uralensis (GuSQS1) was cloned and over-expressed in Pichia pastoris GS115. Six recombinant P. pastoris strains containing different copy number of GuSQS1 were constructed. HPLC was used to assay the level of ergosterol in all transgenic P. pastoris strains containing GuSQS1. HPLC analysis showed that the contents of ergosterol in all of the transgenic P. pastoris containing GuSQS1 were higher than that in the negative control. And with the increase of copy number of GuSQS1, the content of ergosterol showed an increasing-decreasing-increasing pattern. The contents of ergosterol in 10-copy-GuSQS1 P. pastoris and 47-copy-GuSQS1 P. pastoris were significantly higher than that in the rest recombinant P. pastoris strains. In conclusion, the CNVs of GuSQS1 influence the content of secondary metabolites in the MVA pathway. The present study provides a basis for over-expressing GuSQS1 and increasing the content of glycyrrhizin in G. uralensis cultivars.


Lessons already learnt from the Covid-19 pandemic


title: Analysis of the SARS-CoV-2 spike protein glycan shield: implications for immune recognition

text: Here we have generated 3D structures of glycoforms of the spike (S) glycoprotein from SARS-CoV-2, based on reported 3D structures and glycomics data for the protein produced in HEK293 cells. We also analyze structures for glycoforms representing those present in the nascent glycoproteins (prior to enzymatic modifications in the Golgi), as well as those that are commonly observed on antigens present in other viruses. These models were subjected to molecular dynamics (MD) simulation to determine the extent to which glycan microheterogeneity impacts the antigenicity of the S glycoprotein. Lastly, we have identified peptides in the S glycoprotein that are likely to be presented in human leukocyte antigen (HLA) complexes, and discuss the role of S protein glycosylation in potentially modulating the adaptive immune response to the SARS-CoV-2 virus or to a related vaccine. The 3D structures show that the protein surface is extensively shielded from antibody recognition by glycans, with the exception of the ACE2 receptor binding domain, and also that the degree of shielding is largely insensitive to the specific glycoform. Despite the relatively modest contribution of the glycans to the total molecular weight (17% for the HEK293 glycoform) the level of surface shielding is disproportionately high at 42%.


title: Comparison of Patients Hospitalized With Influenza A Subtypes H7N9, H5N1, and 2009 Pandemic H1N1

text: Background. Influenza A(H7N9) viruses isolated from humans show features suggesting partial adaptation to mammals. To provide insights into the pathogenesis of H7N9 virus infection, we compared risk factors, clinical presentation, and progression of patients hospitalized with H7N9, H5N1, and 2009 pandemic H1N1 (pH1N1) virus infections. Methods. We compared individual-level data from patients hospitalized with infection by H7N9 (n = 123), H5N1 (n = 119; 43 China, 76 Vietnam), and pH1N1 (n = 3486) viruses. We assessed risk factors for hospitalization after adjustment for age- and sex-specific prevalence of risk factors in the general Chinese population. Results. The median age of patients with H7N9 virus infection was older than other patient groups (63 years; P < .001) and a higher proportion was male (71%; P < .02). After adjustment for age and sex, chronic heart disease was associated with an increased risk of hospitalization with H7N9 (relative risk, 9.68; 95% confidence interval, 5.24–17.9). H7N9 patients had similar patterns of leukopenia, thrombocytopenia, and elevated alanine aminotransferase, creatinine kinase, C-reactive protein, and lactate dehydrogenase to those seen in H5N1 patients, which were all significantly different from pH1N1 patients (P < .005). H7N9 patients had a longer duration of hospitalization than either H5N1 or pH1N1 patients (P < .001), and the median time from onset to death was 18 days for H7N9 (P = .002) vs 11 days for H5N1 and 15 days for pH1N1 (P = .154). Conclusions. The identification of known risk factors for severe seasonal influenza and the more protracted clinical course compared with that of H5N1 suggests that host factors are an important contributor to H7N9 severity.


title: Direct-acting antivirals and host-targeting strategies to combat enterovirus infections

text: Enteroviruses (e.g., poliovirus, enterovirus-A71, coxsackievirus, enterovirus-D68, rhinovirus) include many human pathogens causative of various mild and more severe diseases, especially in young children. Unfortunately, antiviral drugs to treat enterovirus infections have not been approved yet. Over the past decades, several direct-acting inhibitors have been developed, including capsid binders, which block virus entry, and inhibitors of viral enzymes required for genome replication. Capsid binders and protease inhibitors have been clinically evaluated, but failed due to limited efficacy or toxicity issues. As an alternative approach, host-targeting inhibitors with potential broad-spectrum activity have been identified. Furthermore, drug repurposing screens have recently uncovered promising new inhibitors with disparate viral and host targets. Together, these findings raise hope for the development of (broad-range) anti-enteroviral drugs.


title: Zoonotic parasites of dromedary camels: so important, so ignored

text: With a global population of about 35 million in 47 countries, dromedary camels play a crucial role in the economy of many marginal, desert areas of the world where they survive under harsh conditions. Nonetheless, there is scarce knowledge regarding camelsʼ parasite fauna which can reduce their milk and meat productions. In addition, only scattered information is available about zoonotic parasites transmitted to humans via contamination (e.g. Cryptosporidium spp., Giardia duodenalis, Balantidium coli, Blastocystis spp. and Enterocytozoon bieneusi), as foodborne infections (e.g. Toxoplasma gondii, Trichinella spp. and Linguatula serrata) or by arthropod vectors (Trypanosoma spp.). Herein, we draw attention of the scientific community and health policy-making organizations to the role camels play in the epidemiology of parasitic zoonotic diseases also in the view of an increase in their farming in desert areas worldwide. [Image: see text]


title: How Modelling Can Enhance the Analysis of Imperfect Epidemic Data

text: Mathematical models play an increasingly important role in our understanding of the transmission and control of infectious diseases. Here, we present concrete examples illustrating how mathematical models, paired with rigorous statistical methods, are used to parse data of different levels of detail and breadth and estimate key epidemiological parameters (e.g., transmission and its determinants, severity, impact of interventions, drivers of epidemic dynamics) even when these parameters are not directly measurable, when data are limited, and when the epidemic process is only partially observed. Finally, we assess the hurdles to be taken to increase availability and applicability of these approaches in an effort to ultimately enhance their public health impact.


Situación clínica de infección por SARS-CoV-2 en pacientes con carcinoma broncogénico: contexto actual


title: Free and perfectly safe but only partially effective vaccines can harm everyone

text: Abstract Risk compensation can undermine the ability of partially-effective vaccines to curb epidemics: Vaccinated agents may optimally choose to engage in more risky interactions and, as a result, may increase everyone's infection probability. We show that—in contrast to the prediction of standard models—things can be worse than that: Free and perfectly safe but only partially effective vaccines can reduce everyone's welfare, and hence fail to satisfy—in a strong sense—the fundamental principle of “first, do no harm.” Our main departure from standard economic epidemiological models is that we allow agents to strategically choose their partners, which we show creates strategic complementarities in risky interactions. As a result, the introduction of a partially-effective vaccine can lead to a much denser interaction structure—whose negative welfare effects overwhelm the beneficial direct welfare effects of this intervention.


title: The role of growth factor receptors in viral infections: An opportunity for drug repurposing against emerging viral diseases such as COVID‐19?

text: Growth factor receptors are known to be involved in the process of viral infection. Many viruses not only use growth factor receptors to physically attach to the cell surface and internalize, but also divert receptor tyrosine kinase signaling in order to replicate. Thus, repurposing drugs that have initially been developed to target growth factor receptors and their signaling in cancer may prove to be a fast track to effective therapies against emerging new viral infections, including the coronavirus disease 19 (COVID‐19).


Educación médica en tiempo de Pandemia: el caso de la Enfermedad por Coronavirus 2019 (COVID-19)


title: Zika virus inhibits eIF2α-dependent stress granule assembly

text: Zika virus (ZIKV), a member of the Flaviviridae family, is the most recent emerging arbovirus with pandemic potential. During infection, viruses trigger the host cell stress response, leading to changes in RNA translation and the assembly of large aggregates of stalled translation preinitiation complexes, termed stress granules (SGs). Several reports demonstrate that flaviviruses modulate the assembly of stress granules (SG). As an emerging pathogen, little is known however about how ZIKV modulates the host cell stress response. In this work, we investigate how ZIKV modulates SG assembly. We demonstrate that ZIKV negatively impacts SG assembly under oxidative stress conditions induced by sodium arsenite (Ars), a treatment that leads to the phosphorylation of eIF2α. By contrast, no measurable difference in SG assembly was observed between mock and ZIKV-infected cells treated with sodium selenite (Se) or Pateamine A (PatA), compounds that trigger eIF2α-independent SG assembly. Interestingly, ZIKV infection markedly impaired the phosphorylation of eIF2α triggered in Ars-treated infected cells, and the abrogation of SG assembly in ZIKV-infected cells is, at least in part, dependent on eIF2α dephosphorylation. These data demonstrate that ZIKV elicits mechanisms to counteract host anti-viral stress responses to promote a cellular environment propitious for viral replication.


title: Mouse hepatitis virus (MHV-4, JHM) blocks γ-interferon-induced major histocompatibility complex class II antigen expression on murine cerebral endothelial cells

text: Abstract The regulation of γ-interferon-induced major histocompatibility complex (MHC) class II antigen expression on mouse cerebral endothelial cells by the neurotropic mouse hepatitis virus (MHV-4, JHM) was studied in vitro. The results presented demonstrate that MHV-4 can selectively block γ-interferon-induced class II antigen expression on cerebral endothelial cells. The blocking effect of class II expression occurs in a strain-dependent manner, and is limited to virus-susceptible mouse strains. Virus replication is not required to obtain the blocking effect since UV-inactivated MHV-4 produces the same result. MHV-4 blocking of γ-interferon-induced class II antigen expression is observed at both the cell surface (flow cytometry) and transcriptional level (Norhtern analysis).


Illness in Intensive Care Staff after Brief Exposure to Severe Acute Respiratory Syndrome


title: MagaZorb: A simple tool for rapid isolation of viral nucleic acids

text: Effective isolation of nucleic acids from samples containing viral materials is an essential step for accurate diagnosis of viral infections. The necessity of this critical step before analytical identification and diagnosis of viral infections is paramount to screening programs and to identifying and monitoring epidemics and pandemics. With molecular assays rapidly evolving into routine practice, clinical laboratories face several challenges, including presence of small amounts of viral nucleic acids in abundant levels of genomic DNA and total RNA, processing of various sample types, and carry-over of polymerase chain reaction inhibitors, which could significantly affect polymerase chain reaction and microarray results. MagaZorb nucleic acid isolation technology overcomes these challenges and offers a simple and reliable method for isolation of highquality and high-yield nucleic acids. Although the MagaZorb technology is readily adaptable to automated platforms, it is also well suited to laboratories in remote areas of resource-poor countries, because a simple magnet is the only device required to perform the procedure manually. Performance characteristics and clinical application of the MagaZorb technology are briefly described here.


title: Preventive and therapeutic strategies in critically ill patients with highly resistant bacteria

text: The antibiotic pipeline continues to diminish and the majority of the public remains unaware of this critical situation. The cause of the decline of antibiotic development is multifactorial and currently most ICUs are confronted with the challenge of multidrug-resistant organisms. Antimicrobial multidrug resistance is expanding all over the world, with extreme and pandrug resistance being increasingly encountered, especially in healthcare-associated infections in large highly specialized hospitals. Antibiotic stewardship for critically ill patients translated into the implementation of specific guidelines, largely promoted by the Surviving Sepsis Campaign, targeted at education to optimize choice, dosage, and duration of antibiotics in order to improve outcomes and reduce the development of resistance. Inappropriate antimicrobial therapy, meaning the selection of an antibiotic to which the causative pathogen is resistant, is a consistent predictor of poor outcomes in septic patients. Therefore, pharmacokinetically/pharmacodynamically optimized dosing regimens should be given to all patients empirically and, once the pathogen and susceptibility are known, local stewardship practices may be employed on the basis of clinical response to redefine an appropriate regimen for the patient. This review will focus on the most severely ill patients, for whom substantial progress in organ support along with diagnostic and therapeutic strategies markedly increased the risk of nosocomial infections. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00134-015-3719-z) contains supplementary material, which is available to authorized users.


title: Considerations in the evaluation and management of oral potentially malignant disorders during the COVID‐19 pandemic

text: AIM: The COVID‐19 pandemic has resulted in society experiencing unprecedented challenges for health care practitioners and facilities serving at the frontlines of this pandemic. With regard to oral cancer, there is a complete absence of literature regarding the long‐term impact of pandemics on patients with oral potentially malignant disorders (OPMDs). The objective of this article is to put forth an institutional multidisciplinary approach for the evaluation and management of OPMDs. METHODS: A multidisciplinary approach was put formalized within our institution to risk stratify patients based on need for in‐person assessment vs telehealth assessment during the COVID‐19 pandemic. RESULTS: With judicious risk stratification of patients based on clinical features of their OPMD and with consideration of ongoing mitigation efforts and regional pandemic impact, providers are able to safely care for their patients. CONCLUSIONS: The COVID‐19 pandemic has required health care practitioners to make novel decisions that are new to us with development of creative pathways of care that focused on patient safety, mitigation efforts, and clinical management of disease processes. The care of patients with OPMDs requires special considerations especially as patients at high risk for severe COVID‐19 illness are also higher risk for the development of OPMDs.


title: Bubble in, bubble out: lessons for the COVID-19 recovery and future crises from the Pacific

text: This note presents three important facts on the COVID-19 pandemic and 22 developing countries, namely those in the Pacific. First, social protection systems are less common in the Pacific than in the rest of the world, meaning the region is not particularly well equipped to deal with the sharp decline in economic activity associated with the disease and standard policy responses (e.g., lockdowns) without plunging a large share of the population into poverty. Second, aggressive travel restrictions and effective domestic policy responses have spared many Pacific countries from the worst impacts of COVID-19. Ten countries have not had a single confirmed case. The experience of the region thus offers helpful lessons for other developing countries in keeping the crisis at bay. Third, the relative success of Australia and New Zealand in managing the virus provides an opportunity to pilot and test in the region what a carefully managed pathway to allow the tourism, migration, and remittances, that many countries depend on, to begin flowing again. Against its relative success, the Pacific has a unique opportunity to show the world how to safely emerge from the current crisis and address underlying vulnerabilities before the next one.


title: Ribosomal frameshifting, jumping and readthrough

text: Abstract New examples of high-level ribosomal frameshift and readthrough events have been described over the past year and a half. These include −1 frameshifiting at tandem codons and + 1 frameshifiting at neighboring slow codons. Several bizarre examples of ribosome jumping and multiple stop-codon readthrough continue to perplex investigators in this field.


title: The importance of hypertension as a risk factor for severe illness and mortality in COVID‐19

text: The virus responsible for COVID-19 binds to the angiotensin converting enzyme-2 (ACE-2) receptor [1]. Several articles have noted that hypertension is a risk factor for COVID-19 [2-7]. It is currently difficult to distinguish between hypertension as an independent risk factor in COVID-19 from one that co-varies with other patient factors such as age and cardiovascular disease. It is difficult from individual reports to determine whether hypertension is a risk factor for development of symptomatic disease or hospitalisation or for more severe disease. Reviewing the literature that reports rates of hypertension amongst included patients indicates a consistent association with more severe disease and increased mortality.


title: COVID-19 pandemic and environmental pollution: A blessing in disguise?

text: Abstract In late 2019, a novel infectious disease with human to human transmission (COVID-19) was identified in Wuhan China, which now has turned into a global pandemic. Countries all over the world have implemented some sort of lockdown to slow down its infection and mitigate it. Lockdown due to COVID-19 has drastic effects on social and economic fronts. However, this lockdown also have some positive effect on natural environment. Recent data released by NASA (National Aeronautics and Space Administration) and ESA (European Space Agency) indicates that pollution in some of the epicenters of COVID-19 such as Wuhan, Italy, Spain and USA etc. has reduced up to 30%. This study compiled the environmental data released by NASA and ESA before and after the coronavirus pandemic and discusses its impact on environmental quality.


title: Limiting respiratory viral infection by targeting antiviral and immunological functions of BST-2/Tetherin: Knowledge and gaps

text: Recent findings regarding the cellular biology and immunology of BST-2 (also known as tetherin) indicate that its function could be exploited as a universal replication inhibitor of enveloped respiratory viruses (e.g., influenza, respiratory syncytial virus, etc.). BST-2 inhibits viral replication by preventing virus budding from the plasma membrane and by inducing an antiviral state in cells adjacent to infection via unique inflammatory signaling mechanisms. This review presents the first comprehensive summary of what is currently known about BST-2 antiviral function against respiratory viruses, how these viruses construct countermeasures to antagonize BST-2, and how BST-2 function might be targeted to develop therapies to treat respiratory virus infections. We address the current gaps in knowledge, including the need for mechanistic understanding of BST-2 antagonism by respiratory viruses, that should be bridged to achieve that goal.


title: Absence of antibody-dependent, complement-mediated lysis of feline infectious peritonitis virus-infected cells

text: Abstract Cats infected with virulent feline coronavirus which causes feline infectious peritonitis (FIP) usually succumb to disease despite high antibody concentrations. One of the mechanisms that can help resolving infection is antibody-dependent, complement-mediated lysis (ADCML) of infected cells. ADCML consists of virus-specific antibodies that bind to cell surface expressed viral proteins which result in complement activation and cell lysis. The objective of this study was to determine the sensitivity of FIP-virus (FIPV) infected cells towards ADCML and to examine the role of the accessory proteins 3abc and 7ab in this process. ADCML assays, using FIPV strain 79-1146 and its deletion mutant strain Δ3abc/Δ7ab, were performed on: (i) CrFK cells that show surface-expressed viral antigens, (ii) monocytes without surface-expressed viral proteins due to retention and (iii) monocytes with surface-expressed viral proteins since the antibody-mediated internalization of these proteins was blocked. As expected, no ADCML was detected of the monocytes without surface-expressed viral antigens. Surprisingly, no lysis was observed in the CrFK cells and the monocytes that do show surface-expressed viral proteins, while controls showed that the ADCML assay was functional. These experiments proof that FIPV can employ another immune evasion strategy against ADCML (besides preventing surface expression): the inhibition of complement-mediated lysis. This new evasion strategy is not attributed to the group-specific proteins since lysis of cells infected with FIPV Δ3abc/Δ7ab was not detected.


title: Chilblain acral lesions in the COVID ‐19 era. Are they marker of infection in asymptomatic patients?

text: During these months in which the COVID‐19 emergency is waning, the activity of dermatologists has changes substantially. Since the beginning of March 2020, in the Dermatology Clinic at the University Hospital in Turin (Italy) the outpatient access has been significantly reduced and telemedicine has been useful whenever possible, by putting the patient in contact directly with dermatologists or mediated by the general practitioners.


title: Phytoconstituents and therapeutic uses of Rheum emodi wall. ex Meissn

text: Abstract Rhubarb (Rheum emodi, family Polygonaceae) has been traditionally used as diuretic, liver stimulant, purgative/cathartic, stomachic, anticholesterolaemic, antitumour, antiseptic and tonic. A number of anthraquinone derivatives including emodin, aloe-emodin, physcion, chrysophanol, rhein, emodin glycoside and chrysophanol glycoside occur as the main chemical constituents. In the past few years, new components such as sulfemodin 8-O-β-d-glucoside, revandchinone-1, revandchinone-2, revandchinone-3, revandchinone-4, 6-methyl-rhein and 6-methyl aloe-emodin have been reported from the same species. Anthraquinone derivatives show evidence of antifungal, anti-microbial, anti-Parkinson’s, anti-proliferative, immuno-enhancing, antiviral and antioxidant activities. This review covers published work on botany, chemistry and therapeutic uses of different components from rhubarb.


title: Roles of peroxiredoxins in cancer, neurodegenerative diseases and inflammatory diseases

text: Abstract Peroxiredoxins (PRDXs) are antioxidant enzymes, known to catalyze peroxide reduction to balance cellular hydrogen peroxide (H2O2) levels, which are essential for cell signaling and metabolism and act as a regulator of redox signaling. Redox signaling is a critical component of cell signaling pathways that are involved in the regulation of cell growth, metabolism, hormone signaling, immune regulation and variety of other physiological functions. Early studies demonstrated that PRDXs regulates cell growth, metabolism and immune regulation and therefore involved in the pathologic regulator or protectant of several cancers, neurodegenerative diseases and inflammatory diseases. Oxidative stress and antioxidant systems are important regulators of redox signaling regulated diseases. In addition, thiol-based redox systems through peroxiredoxins have been demonstrated to regulate several redox-dependent process related diseases. In this review article, we will discuss recent findings regarding PRDXs in the development of diseases and further discuss therapeutic approaches targeting PRDXs. Moreover, we will suggest that PRDXs could be targets of several diseases and the therapeutic agents for targeting PRDXs may have potential beneficial effects for the treatment of cancers, neurodegenerative diseases and inflammatory diseases. Future research should open new avenues for the design of novel therapeutic approaches targeting PRDXs.


title: Recommendations of the Working Groups from the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) for the management of adult critically ill patients in the coronavirus disease (COVID-19)

text: Abstract On March 11, 2020, the Director-General of the World Health Organization (WHO) declared the disease caused by SARS-CoV-2 (COVID-19) as a pandemic. The spread and evolution of the pandemic is overwhelming the healthcare systems of dozens of countries and has led to a myriad of opinion papers, contingency plans, case series and emerging trials. Covering all this literature is complex. Briefly and synthetically, in line with the previous recommendations of the Working Groups, the Spanish Society of Intensive, Critical Medicine and Coronary Units (SEMICYUC) has prepared this series of basic recommendations for patient care in the context of the pandemic.


title: A comprehensive microbiological safety approach for agarose encapsulated porcine islets intended for clinical trials

text: BACKGROUND: The use of porcine islets to replace insulin‐producing islet β‐cells, destroyed during the diabetogenic disease process, presents distinct challenges if this option is to become a therapeutic reality for the treatment of type 1 diabetes. These challenges include a thorough evaluation of the microbiological safety of the islets. In this study, we describe a robust porcine islet‐screening program that provides a high level of confidence in the microbiological safety of porcine islets suitable for clinical trials. METHODS: A four‐checkpoint program systematically screens the donor herd (Large White – Yorkshire × Landrace F1 hybrid animals), individual sentinel and pancreas donor animals and, critically, the islet macrobeads themselves. Molecular assays screen for more than 30 known viruses, while electron microscopy and in vitro studies are employed to screen for potential new or divergent (emergent) viruses. RESULTS: Of 1207 monthly samples taken from random animals over a 2‐year period, only a single positive result for Transmissible gastroenteritis virus was observed, demonstrating the high level of biosecurity maintained in the source herd. Given the lack of clinical signs, positive antibody titers for Porcine reproductive and respiratory syndrome virus, Porcine parvovirus, and Influenza A confirm the efficacy of the herd vaccination program. Porcine respiratory coronavirus was found to be present in the herd, as expected for domestic swine. Tissue homogenate samples from six sentinel and 11 donor animals, over the same 2‐year period, were negative for the presence of viruses when co‐cultured with six different cell lines from four species. The absence of adventitious viruses in separate islet macrobead preparations produced from 12 individual pancreas donor animals was confirmed using validated molecular (n = 32 viruses), in vitro culture (cells from four species), and transmission electron microscopy assays (200 cell profiles per donor animal) over the same 2‐year period. There has been no evidence of viral transmission following the implantation of these same encapsulated and functional porcine islets into non‐immunosuppressed diabetic cynomolgus macaques for up to 4 years. Isolated peripheral blood mononuclear cells from all time points were negative for PCV (Type 2), PLHV, PRRSV, PCMV, and PERV‐A, PERV‐B, and PERV‐C by PCR analysis in all six recipient animals. CONCLUSION: The four‐checkpoint program is a robust and reliable method for characterization of the microbiological safety of encapsulated porcine islets intended for clinical trials.


title: Clinical Presentation and Birth Outcomes Associated with Respiratory Syncytial Virus Infection in Pregnancy

text: BACKGROUND: Respiratory syncytial virus (RSV) is the most important cause of viral pneumonia in children worldwide. A maternal vaccine may protect both the mother and infant from RSV illness. The epidemiology and clinical presentation of RSV in pregnant and postpartum women is not well-described. METHODS: Data were collected from a prospective, randomized trial of influenza immunization in pregnant women in rural southern Nepal. Women were enrolled in their second trimester of pregnancy and followed until six months postpartum. Active weekly home-based surveillance for febrile respiratory illness was performed. Mid-nasal swabs collected with episodes of respiratory illness were tested for RSV by real-time polymerase chain reaction. RESULTS: RSV was detected in 14 (0.4%) illness episodes in 3693 women over 3554 person-years of surveillance from 2011–2014. RSV incidence was 3.9/1000 person-years overall, and 11.8/1000 person-years between September and December. Seven (50%) women sought care for RSV illness; none died. Of the 7 (50%) illness episodes during pregnancy, all had live births with 2 (29%) preterm births and a median birthweight of 3060 grams. This compares to 469 (13%) preterm births and a median birthweight of 2790 grams in women without RSV during pregnancy. Of the 7 mothers with postpartum RSV infection, RSV was detected in 4 (57%) of their infants. CONCLUSIONS: RSV was an uncommon cause of febrile respiratory illness in mothers during pregnancy in Nepal. These data will inform prevention and therapeutic strategies against RSV in resource-limited settings.


title: Frequent detection of cytomegalovirus (CMV) DNA in the lower respiratory tract in CMV‐seropositive pediatric patients with underlying chronic bronchopulmonary diseases lacking canonical immunosuppression

text: Cytomegalovirus (CMV) may be a relevant cause of morbidity in patients displaying various inflammatory diseases. In this study, it was investigated whether CMV DNA is detected in the lower respiratory tract and the systemic compartment in pediatric patients with chronic or recurrent bronchopulmonary diseases. A total of 42 lower respiratory tract specimens and 11 paired plasma samples from 42 patients were analyzed for the presence of CMV DNA by real‐time PCR. The respiratory specimens were also screened for the presence of respiratory viruses and human herpesvirus 6 (HHV‐6) and 7 (HHV‐7) by PCR methods. Quantitative bacterial and fungal cultures were performed. IL‐6 levels in the respiratory specimens were quantified using ELISA. CMV DNA was detected either in the lower respiratory airways, in plasma, or both in 54.5% of CMV‐seropositive patients. The levels of IL‐6 were significantly higher in these patients than in those with no detectable levels of CMV DNA. HHV‐6 and HHV‐7 DNA were detected in three and one patients, respectively. Respiratory viruses were detected in 13 of the 42 patients. Significant growth of one or more bacterial species was observed in 17 patients. No significant association was found between the presence of CMV DNA and the detection of other microorganisms. The data indicated that the presence of CMV DNA in the lower respiratory tract is a frequent finding in children with chronic or recurrent bronchopulmonary diseases. Further, prospective observational studies are needed to assess the impact of this phenomenon, if any, on the clinical course of these patients. J. Med. Virol. 85:888–892, 2013. © 2013 Wiley Periodicals, Inc.


title: Viruses and the nucleolus: The fatal attraction

text: Abstract Viruses are small obligatory parasites and as a consequence, they have developed sophisticated strategies to exploit the host cell's functions to create an environment that favors their own replication. A common feature of most – if not all – families of human and non-human viruses concerns their interaction with the nucleolus. The nucleolus is a multifunctional nuclear domain, which, in addition to its well-known role in ribosome biogenesis, plays several crucial other functions. Viral infection induces important nucleolar alterations. Indeed, during viral infection numerous viral components localize in nucleoli, while various host nucleolar proteins are redistributed in other cell compartments or are modified, and non-nucleolar cellular proteins reach the nucleolus. This review highlights the interactions reported between the nucleolus and some human or animal viral families able to establish a latent or productive infection, selected on the basis of their known interactions with the nucleolus and the nucleolar activities, and their links with virus replication and/or pathogenesis. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease.


title: Epidemiology of rotavirus diarrhoea in Iranian children

text: Human rotavirus is the most important cause of severe diarrhoea in infants and young children worldwide. We describe the aetiology of viral diarrhoea and the characteristics of rotavirus infection in Shahrekord, Iran. Two hundred and fifty nine children <5 years old admitted to Hajar Hospital, 245 children with acute diarrhoea attending primary health centres in Shahrekord, and 114 children hospitalised for elective surgery were selected from October 2001 to August 2002. Stool samples were screened for enteric viruses using EM. Rotaviruses were characterised using ELISA, reverse transcription‐polymerase chain reaction (RT‐PCR), and electropherotyping. One hundred and eighty six viruses were identified, of which 146 (78%) were rotavirus. The second most frequent virus was coronavirus, followed by calicivirus. Rotaviruses exhibited a marked seasonal variation, being most frequently isolated from November to February (50% of rotavirus recovered) and affected mostly children <2 years old. The RT‐PCR successfully typed 139 of the 146 (95%) rotavirus G types and 124 (85%) P types. The most frequent P type was, P[8] in 108 (74%), P[4] in 16 (11%), and was P non‐typeable in 22 (15%). Among the G types, G1 was identified in 120 (82%), G2 in 19 (13%), and was G‐non‐typeable in 7 (5%). Our results are the first report of rotavirus genotypes affecting Iranian children. The most frequent G and P types (G1, G2, P[8], and P[4]) are similar to those reported from around the world and will be covered by existing rotavirus vaccines targeting G types G1–G4. J. Med. Virol. 73:309–312, 2004. © 2004 Wiley‐Liss, Inc.


title: Adjuvant effects of mannose-binding lectin ligands on the immune response to infectious bronchitis vaccine in chickens with high or low serum mannose-binding lectin concentrations

text: Abstract Mannose-binding lectin (MBL) plays a major role in the immune response as a soluble pattern-recognition receptor. MBL deficiency and susceptibility to different types of infections have been subject to extensive studies over the last decades. In humans and chickens, several studies have shown that MBL participates in the protection of hosts against virus infections. Infectious bronchitis (IB) is a highly contagious disease of economic importance in the poultry industry caused by the coronavirus infectious bronchitis virus (IBV). MBL has earlier been described to play a potential role in the pathogenesis of IBV infection and the production of IBV-specific antibodies, which may be exploited in optimising IBV vaccine strategies. The present study shows that MBL has the capability to bind to IBV in vitro. Chickens from two inbred lines (L10H and L10L) selected for high or low MBL serum concentrations, respectively, were vaccinated against IBV with or without the addition of the MBL ligands mannan, chitosan and fructooligosaccharide (FOS). The addition of MBL ligands to the IBV vaccine, especially FOS, enhanced the production of IBV-specific IgG antibody production in L10H chickens, but not L10L chickens after the second vaccination. The addition of FOS to the vaccine also increased the number of circulating CD4+ cells in L10H chickens compared to L10L chickens. The L10H chickens as well as the L10L chickens also showed an increased number of CD4−CD8α−γδ T-cells when an MBL ligand was added to the vaccine, most pronouncedly after the first vaccination. As MBL ligands co-administered with IBV vaccine induced differences between the two chicken lines, these results indirectly suggest that MBL is involved in the immune response to IBV vaccination. Furthermore, the higher antibody response in L10H chickens receiving vaccine and FOS makes FOS a potential adjuvant candidate in an IBV vaccine.


title: The outbreak of Novel Coronavirus disease (COVID‐19) caused a worrying delay in the diagnosis of oral cancer in north‐west Italy: The Turin Metropolitan Area experience

text: Recently, the epidemic of Novel Coronavirus disease 2019 (COVID-19) has become a chief public health challenge for many countries around the world. In Italy, it started in January the 31st with the first 2 cases reported; on Monday the 13th of April, the total confirmed cases were 156.363 with 19.901 total deaths (www.who.int). Turin is the fourth Italian city, with roughly 862.000 inhabitants, and the capital of Piedmont region, one of the most affected by COVID-19.