title: A Probiotic-Based Sanitation System for the Reduction of Healthcare Associated Infections and Antimicrobial Resistances: A Budget Impact Analysis

text: Healthcare associated infections (HAIs) and antibiotic resistance have high social and economic burdens. Healthcare environments play an important role in the transmission of HAIs. The Probiotic Cleaning Hygiene System (PCHS) has been shown to decrease hospital surface pathogens up to 90% vs. conventional chemical cleaning (CCC). This study compares PCHS to CCC as to reduction of HAIs and their severity, related antibiotic resistances, and costs. Incidence rates of HAIs/antibiotic resistances were estimated from a previously conducted multicenter pre-post (6 months CCC + 6 months PCHS) intervention study, after applying the propensity score matching technique. A budget impact analysis compared the current scenario of use of CCC with future scenarios considering increasing utilization of PCHS, from 5% to 50% in the next five years, from a hospital perspective in Italy. The cumulative incidence of HAI was 4.6% and 2.4% (p < 0.0001) for CCC (N = 4160) and PCHS (N = 4160) (OR = 0.47, CI 95% 0.37–0.60), with severe HAIs of 1.57% vs. 1% and antibiotic resistances of 1.13% vs. 0.53%, respectively. Increased use of PCHS over CCC in Italian internal medicine/geriatrics and neurology departments in the next 5 years is expected to avert at least about 31,000 HAIs and 8500 antibiotic resistances, and save at least 14 million euros, of which 11.6 for the treatment of resistant HAIs. Innovative, environmentally sustainable sanitation systems, like PCHS, might substantially reduce antibiotic resistance and increase protection of health worldwide.


MERS-CoV Infection of Alpaca in a Region Where MERS-CoV is Endemic


title: Functional Interplay between RNA Viruses and Non-Coding RNA in Mammals

text: Exploring virus–host interactions is key to understand mechanisms regulating the viral replicative cycle and any pathological outcomes associated with infection. Whereas interactions at the protein level are well explored, RNA interactions are less so. Novel sequencing methodologies have helped uncover the importance of RNA–protein and RNA–RNA interactions during infection. In addition to messenger RNAs (mRNAs), mammalian cells express a great number of regulatory non-coding RNAs, some of which are crucial for regulation of the immune system whereas others are utilized by viruses. It is thus becoming increasingly clear that RNA interactions play important roles for both sides in the arms race between virus and host. With the emerging field of RNA therapeutics, such interactions are promising antiviral targets. In this review, we discuss direct and indirect RNA interactions occurring between RNA viruses or retroviruses and host non-coding transcripts upon infection. In addition, we review RNA virus derived non-coding RNAs affecting immunological and metabolic pathways of the host cell typically to provide an advantage to the virus. The relatively few known examples of virus–host RNA interactions suggest that many more await discovery.


title: Development and verification of real-time PCR assay for identification of viral agents causing acute respiratory infections in human beings

text: A multiplex polymerase chain reaction (PCR) for identification of four viruses causing acute respiratory diseases in human beings was developed. The analytical sensitivity of developed RT-PCR for identification of adenovirus, respiratory-syncytial virus, flu viruses types A and B, and actual subtypes of type A flu virus (seasonal and pandemic variants H1N1, seasonal H3N2, and viruses of bird flu that are pathogenic to human beings H5 and H7) was 1 × 10(3) genome equivalents per milliliter. Diagnostic sensitivity for flu virus type A and B, and also subtypes H1 (seasonal H1N1, pandemic variant of H1N1 of year 2009), H3, H5 was 1 × 10(3)–10(4) viral particles per milliliter. The method developed has high specificity and does not have positive signal in experiments with DNA/cDNA of human beings and viral DNA. We have studied 50 samples using the developed set. Etiology was defined in 33 samples.


title: Online health information – what the newspapers tell their readers: a systematic content analysis

text: BACKGROUND: This study investigated the nature of newspaper reporting about online health information in the UK and US. Internet users frequently search for health information online, although the accuracy of the information retrieved varies greatly and can be misleading. Newspapers have the potential to influence public health behaviours, but information has been lacking in relation to how newspapers portray online health information to their readers. METHODS: The newspaper database Nexis(®)UK was searched for articles published from 2003 – 2012 relating to online health information. Systematic content analysis of articles published in the highest circulation newspapers in the UK and US was performed. A second researcher coded a 10% sample to establish inter-rater reliability of coding. RESULTS: In total, 161 newspaper articles were included in the analysis. Publication was most frequent in 2003, 2008 and 2009, which coincided with global threats to public health. UK broadsheet newspapers were significantly more likely to cover online health information than UK tabloid newspapers (p = 0.04) and only one article was identified in US tabloid newspapers. Articles most frequently appeared in health sections. Among the 79 articles that linked online health information to specific diseases or health topics, diabetes was the most frequently mentioned disease, cancer the commonest group of diseases and sexual health the most frequent health topic. Articles portrayed benefits of obtaining online health information more frequently than risks. Quotations from health professionals portrayed mixed opinions regarding public access to online health information. 108 (67.1%) articles directed readers to specific health-related web sites. 135 (83.9%) articles were rated as having balanced judgement and 76 (47.2%) were judged as having excellent quality reporting. No difference was found in the quality of reporting between UK and US articles. CONCLUSIONS: Newspaper coverage of online health information was low during the 10-year period 2003 to 2012. Journalists tended to emphasise the benefits and understate the risks of online health information and the quality of reporting varied considerably. Newspapers directed readers to sources of online health information during global epidemics although, as most articles appeared in the health sections of broadsheet newspapers, coverage was limited to a relatively small readership. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2458-14-1316) contains supplementary material, which is available to authorized users.


title: Re-Engineering Academic Departments of Obstetrics and Gynecology to Operate in a Pandemic World and Beyond – A Joint AGOS/CUCOG Statement

text: Abstract The COVID-19 pandemic has significantly disrupted operations in academic Departments of Obstetrics and Gynecology throughout the U.S. and will continue to impact them for the foreseeable future. It has also created an environment conducive to innovation and the accelerated implementation of new ideas. These departments will need to adapt their operations to accomodate COVID-19 and to continue to meet their tripartite mission of clinical excellence, medical education, and women’s health research. This “Call to Action” paper from leaders of AGOS and CUCOG provides a framework to help leaders of Departments of Obstetrics and Gynecology re-imagine and re-engineer their operations in light of the current COVID-19 crisis and future pandemics.


title: Current smoking, former smoking, and adverse outcome among hospitalized COVID-19 patients: a systematic review and meta-analysis

text: BACKGROUND: The purpose of this study was to examine the prevalence and effects of current smoking on adverse outcomes among hospitalized COVID-19 patients. METHODS: A systematic review of the literature (PubMed) identified 18 (from a total of 1398) relevant studies. Pooled current smoking prevalence was compared with the gender-adjusted and gender and age-adjusted, population-based expected prevalence by calculating prevalence odds ratio (POR). The association between current, compared with non-current and former, smoking and adverse outcome was examined. A secondary analysis was performed by including 12 pre-publications (30 studies in total). All analyses were performed using random-effects meta-analysis. RESULTS: Among 6515 patients, the pooled prevalence of current smoking was 6.8% [95% confidence interval (CI): 4.8–9.1%]. The gender-adjusted POR was 0.20 (95% CI: 0.16–0.25, p < 0.001), and the gender and age-adjusted POR was 0.24 (95% CI: 0.19–0.30, p < 0.001). Current smokers were more likely to have an adverse outcome compared with non-current smokers [odds ratio (OR): 1.53, 95%CI: 1.06–2.20, p = 0.022] but less likely compared with former smokers (OR: 0.42, 95% CI: 0.27–0.74, p = 0.003). When pre-publications were added (n = 10,631), the gender-adjusted POR was 0.27 (95% CI: 0.19–0.38, p < 0.001) and the gender and age-adjusted POR was 0.34 (95% CI: 0.24–0.48, p < 0.001). CONCLUSION: This meta-analysis of retrospective observational case series found an unexpectedly low prevalence of current smoking among hospitalized patients with COVID-19. Hospitalized current smokers had higher odds compared with non-current smokers but lower odds compared with former smokers for an adverse outcome. Smoking cannot be considered a protective measure for COVID-19. However, the hypothesis that nicotine may have a protective effect in COVID-19 that is partially masked by smoking-related toxicity and by the abrupt cessation of nicotine intake when smokers are hospitalized should be explored in laboratory studies and clinical trials using pharmaceutical nicotine products.


title: PD-1 Dynamically Regulates Inflammation and Development of Brain-Resident Memory CD8 T Cells During Persistent Viral Encephalitis

text: Programmed cell death-1 (PD-1) receptor signaling dampens the functionality of T cells faced with repetitive antigenic stimulation from chronic infections or tumors. Using intracerebral (i.c.) inoculation with mouse polyomavirus (MuPyV), we have shown that CD8 T cells establish a PD-1(hi), tissue-resident memory population in the brains (bT(RM)) of mice with a low-level persistent infection. In MuPyV encephalitis, PD-L1 was expressed on infiltrating myeloid cells, microglia and astrocytes, but not on oligodendrocytes. Engagement of PD-1 on anti-MuPyV CD8 T cells limited their effector activity. NanoString gene expression analysis showed that neuroinflammation was higher in PD-L1(−/−) than wild type mice at day 8 post-infection, the peak of the MuPyV-specific CD8 response. During the persistent phase of infection, however, the absence of PD-1 signaling was found to be associated with a lower inflammatory response than in wild type mice. Genetic disruption and intracerebroventricular blockade of PD-1 signaling resulted in an increase in number of MuPyV-specific CD8 bT(RM) and the fraction of these cells expressing CD103, the αE integrin commonly used to define tissue-resident T cells. However, PD-L1(−/−) mice persistently infected with MuPyV showed impaired virus control upon i.c. re-infection with MuPyV. Collectively, these data reveal a temporal duality in PD-1-mediated regulation of MuPyV-associated neuroinflammation. PD-1 signaling limited the severity of neuroinflammation during acute infection but sustained a level of inflammation during persistent infection for maintaining control of virus re-infection.


title: Monarch butterfly migration and parasite transmission in eastern North America

text: Seasonal migration occurs in many animal systems and is likely to influence interactions between animals and their parasites. Here, we focus on monarch butterflies (Danaus plexippus) and a protozoan parasite (Ophryocystis elektroscirrha) to investigate how host migration affects infectious disease processes. Previous work showed that parasite prevalence was lower among migratory than nonmigratory monarch populations; two explanations for this pattern are that (1) migration allows animals to periodically escape contaminated habitats (i.e., migratory escape), and (2) long‐distance migration weeds out infected animals (i.e., migratory culling). We combined field‐sampling and analysis of citizen science data to examine spatiotemporal trends of parasite prevalence and evaluate evidence for these two mechanisms. Analysis of within‐breeding‐season variation in eastern North America showed that parasite prevalence increased from early to late in the breeding season, consistent with the hypothesis of migratory escape. Prevalence was also positively related to monarch breeding activity, as indexed by larval density. Among adult monarchs captured at different points along the east coast fall migratory flyway, parasite prevalence declined as monarchs progressed southward, consistent with the hypothesis of migratory culling. Parasite prevalence was also lower among monarchs sampled at two overwintering sites in Mexico than among monarchs sampled during the summer breeding period. Collectively, these results indicate that seasonal migration can affect parasite transmission in wild animal populations, with implications for predicting disease risks for species with threatened migrations.


title: Laboratory Tests for Diagnosis of Gastrointestinal and Pancreatic Diseases

text: The panel of laboratory tests available for diagnosis of gastrointestinal (GI) diseases in dogs and cats is wide, and, recently, several new tests have been developed. This article will focus on advances in laboratory tests that are available for the general practitioner for diagnosis of GI diseases. Laboratory tests for diagnosis of gastric and intestinal infectious diseases include fecal parasite screening tests, enzyme-linked immunosorbent assays for parvoviral enteritis, and some specific bacterial tests like fluorescent in situ hybridization for identification of specific bacteria attached to the intestinal epithelial cells. Serum concentrations of folate and cobalamin are markers of intestinal absorption, but are also changed in exocrine pancreatic insufficiency and intestinal bacterial overgrowth. Hypocobalaminemia is common in GI and pancreatic disease. Decreased serum trypsin-like immunoreactivity is a very sensitive and specific test for the diagnosis of exocrine pancreatic insufficiency in dogs and cats. Serum pancreatic lipase is currently the most sensitive and specific test to identify pancreatic cell damage and acute pancreatitis. However, serum canine pancreas-specific lipase is less sensitive in canine chronic pancreatitis. Increased serum trypsin-like immunoreactivity is also specific for pancreatic damage but is less sensitive. It is very likely that further studies will help to better specify the role of these new tests in the diagnosis of canine and feline pancreatic diseases.


title: Hemagglutination by Murine Hepatitis Viruses

text: Erythrocytes from twelve mammalian and avian sources in ten different buffers at three incubation temperatures could not be hemagglutinated with murine hepatitis virus (MHV) strains 3, A59, or S grown on DBT cells. Viral antigen preparation in the absence of fetal calf serum, partial virus purification, or various concentrations of red blood cells still failed to yield detectable hemagglutinating activity. Thus, the newly described MHV-DVIM remains the only hemagglutinating strain of murine coronavirus.


When a global pandemic complicates cancer care: Although oncologists and their patients are accustomed to fighting tough battles against a lethal disease, Coronavirus Disease 2019 (COVID‐19) has posed an unprecedented challenge


docid: cvuuoqed

title: The 2019-nCoV pandemic in the global south: A Tsunami ahead


title: Retroauricular dermatitis with vehement use of ear loop face masks during COVID19 pandemic

text: The COVID‐19 pandemic forged theexponential use of masks of various kinds, not just by health workers but also by general population as a personal protective equipment (PPE). Although contact dermatitis due to PPE is well reported, mask induced dermatitis is a relatively unexplored phenomenon. In this article, we report a preliminary data of patients experiencing retroauricaular dermatitis due to ear loop face masks.


docid: mknutfmk

title: Characterization of a novel coronavirus responsible for severe acute respiratory syndrome

text: Abstract In February, a new avian H5N1/03 virus took two persons' lives in Hong Kong. After this incidence, a newly emerged disease has been identified, associated with pneumonia in infected patients. Here we report that a newly discovered coronoavirus (Cov) is responsible for this disease. In addition, the basic features, diagnosis and possible animal sources of Severe Acute Respiratory Syndrome (SARS) Cov are also discussed.


title: Pneumopathies dites atypiques à coronavirus

text: Résumé La nouvelle pneumopathie, appelée pneumonie atypique, revêt dans 20 % de cas l’aspect d’une forme grave (severe acute respiratory syndrome, SARS). C’est parmi ces cas que l’on trouve surtout les 5 % de mortalité. C’est le diagnostic et le traitement tardif qui entraînent ces formes sévères. Il faut donc traiter tôt en se fondant sur le tableau clinique, la notion de contage, l’identification du virus. ribavirine et corticoïdes en sont les éléments principaux. Abstract A new respiratory illness, designated as atypical pneumonia, produces in 20% of the cases a much more serious disease termed severe acute respiratory syndrome (SARS), which can be fatal in 5% of the cases. Delayed diagnosis and treatment are the underlying causes for the development of SARS. Measures for the management of the disease should be taken swiftly, based on clinical symptoms, definite contact and isolation of the virus. Current treatment of SARS involves antiviral agents, such as ribavirin, and corticosteroids.


title: Some simple rules for estimating reproduction numbers in the presence of reservoir exposure or imported cases

text: Abstract For many diseases, the basic reproduction number ( R 0 ) is a threshold parameter for disease extinction or survival in isolated populations. However no human population is fully isolated from other human or animal populations. We use compartmental models to derive simple rules for the basic reproduction number in populations where an endemic disease is sustained by a combination of local transmission within the population and exposure from some other source: either a reservoir exposure or imported cases. We introduce the idea of a reservoir-driven or importation-driven disease: diseases that would become extinct in the population of interest without reservoir exposure or imported cases (since R 0 < 1 ), but nevertheless may be sufficiently transmissible that many or most infections are acquired from humans in that population. We show that in the simplest case, R 0 < 1 if and only if the proportion of infections acquired from the external source exceeds the disease prevalence and explore how population heterogeneity and the interactions of multiple strains affect this rule. We apply these rules in two case studies of Clostridium difficile infection and colonisation: C. difficile in the hospital setting accounting for imported cases, and C. difficile in the general human population accounting for exposure to animal reservoirs. We demonstrate that even the hospital-adapted, highly-transmissible NAP1/RT027 strain of C. difficile had a reproduction number <1 in a landmark study of hospitalised patients and therefore was sustained by colonised and infected admissions to the study hospital. We argue that C. difficile should be considered reservoir-driven if as little as 13.0% of transmission can be attributed to animal reservoirs.


title: The European Commission’s Task Force on Bioterrorism

text: In response to the increased threat of bioterrorism, a task force on health security was established in the European Commission. Task force members address a broad range of issues related to preparedness for and response to bioterrorist events and seek to bring about a greater collaboration between the European Union member states.


title: Actin- and clathrin-dependent mechanisms regulate interferon gamma release after stimulation of human immune cells with respiratory syncytial virus

text: BACKGROUND: Respiratory syncytial virus (RSV) can cause recurrent and severe respiratory tract infections. Cytoskeletal proteins are often involved during viral infections, either for cell entry or the initiation of the immune response. The importance of actin and clathrin dynamics for cell entry and the initiation of the cellular immune response against RSV in human immune cells is not known yet. The aim of this study was to investigate the role of actin and clathrin on cell entry of RSV and the subsequent effect on T cell activation and interferon gamma release in human immune cells. METHODS: Peripheral blood mononuclear cells and purified monocytes were isolated from healthy adults and stimulated in vitro with RSV. Actin and clathrin dynamics were inhibited with respectively cytochalasin D and chlorpromazine. T cell receptor signaling was inhibited with cyclosporin A. Flow cytometry was used to determine the role of actin and clathrin on cell entry and T cell activation by RSV. Enzyme-linked immunosorbent assays were used to investigate the contribution of actin and clathrin on the release of interferon gamma. RESULTS: Cell entry, virus gene transcription and interferon gamma release are actin-dependent. Post-endocytic processes like the increased expression of major histocompatibility complex II on monocytes , T cell activation and the release of interferon gamma are clathrin-dependent. Finally, T cell receptor signaling affects T cell activation, whereas soluble interleukin 18 is dispensable. CONCLUSION: Analysis of cell entry and interferon gamma release after infection with RSV reveals the importance of actin- and clathrin-dependent signaling in human immune cells. Insights into the cellular biology of the human immune response against respiratory syncytial virus will provide a better understanding of disease pathogenesis and may prove useful in the development of preventive strategies.


title: Mechanisms of Coronavirus Cell Entry Mediated by the Viral Spike Protein

text: Coronaviruses are enveloped positive-stranded RNA viruses that replicate in the cytoplasm. To deliver their nucleocapsid into the host cell, they rely on the fusion of their envelope with the host cell membrane. The spike glycoprotein (S) mediates virus entry and is a primary determinant of cell tropism and pathogenesis. It is classified as a class I fusion protein, and is responsible for binding to the receptor on the host cell as well as mediating the fusion of host and viral membranes—A process driven by major conformational changes of the S protein. This review discusses coronavirus entry mechanisms focusing on the different triggers used by coronaviruses to initiate the conformational change of the S protein: receptor binding, low pH exposure and proteolytic activation. We also highlight commonalities between coronavirus S proteins and other class I viral fusion proteins, as well as distinctive features that confer distinct tropism, pathogenicity and host interspecies transmission characteristics to coronaviruses.


docid: sxbyxnxn

title: MANAGEMENT OF PERSISTENT PNEUMOTHORAX WITH THORACOSCOPY AND BLEBS RESECTION IN COVID-19 PATIENTS

text: Abstract Several studies have been published describing the clinical and radiographic findings on the novel coronavirus (COVID-19) pneumonia. Therefore, there is currently a lack of pathologic data about its effects in intubated patients. Pneumothorax may occur rarely and results from a combination of fibrotic parenchyma with prolonged high-pressure ventilation. Chest drain represent the first line treatment. However, in case of persistent pneumothorax, thoracoscopy and bleb resection may be a feasible option to reduce air leak and improve ventilation. We report the cases of two COVID-19 patients successfully treated with thoracoscopy, bleb resection, and pleurectomy for persistent pneumothorax.


title: Chest X-ray in new Coronavirus Disease 2019 (COVID-19) infection: findings and correlation with clinical outcome

text: AIM: The purpose of this study is to describe the main chest radiological features (CXR) of COVID-19 and correlate them with clinical outcome. MATERIALS AND METHODS: This is a retrospective study involving patients with clinical-epidemiological suspect of COVID-19 infection, who performed CXRs at the emergency department (ED) of our University Hospital from March 1 to March 31, 2020. All patients performed RT-PCR nasopharyngeal and throat swab, CXR at the ED and clinical-epidemiological data. RT-PCR results were considered the reference standard. The final outcome was expressed as discharged or hospitalized patients into a medicine department or intensive care unit (ICU). RESULTS: Patients that had a RT-PCR positive for COVID-19 infection were 234 in total: 153 males (65.4%) and 81 females (34.6%), with a mean age of 66.04 years (range 18–97 years). Thirteen CXRs were negative for radiological thoracic involvement (5.6%). The following alterations were more commonly observed: 135 patients with lung consolidations (57.7%), 147 (62.8%) with GGO, 55 (23.5%) with nodules and 156 (66.6%) with reticular–nodular opacities. Patients with consolidations and GGO coexistent in the same radiography were 35.5% of total. Peripheral (57.7%) and lower zone distribution (58.5%) were the most common predominance. Moreover, bilateral involvement (69.2%) was most frequent than unilateral one. Baseline CXR sensitivity in our experience is about 67.1%. The most affected patients were especially males in the age group 60–79 years old (45.95%, of which 71.57% males). RALE score was slightly higher in male than in female patients. ANOVA with Games-Howell post hoc showed significant differences of RALE scores for group 1 vs 3 (p < 0.001) and 2 vs 3 (p = 0.001). Inter-reader agreement in assigning RALE score was very good (ICC: 0.92—with 95% confidence interval 0.88–0.95). CONCLUSION: In COVID-19, CXR shows patchy or diffuse reticular–nodular opacities and consolidation, with basal, peripheral and bilateral predominance. In our experience, baseline CXR had a sensitivity of 68.1%. The RALE score can be used in the emergency setting as a quantitative method of the extent of SARS-CoV-2 pneumonia, correlating with an increased risk of ICU admission.


title: Fecal virome analysis of three carnivores reveals a novel nodavirus and multiple gemycircularviruses

text: BACKGROUND: More knowledge about viral populations in wild animals is needed in order to better understand and assess the risk of zoonotic diseases. In this study we performed viral metagenomic analysis of fecal samples from three healthy carnivores: a badger (Meles meles), a mongoose (Herpestes ichneumon) and an otter (Lutra lutra) from Portugal. RESULTS: We detected the presence of novel highly divergent viruses in the fecal material of the carnivores analyzed, such as five gemycircularviruses. Four of these gemycircularviruses were found in the mongoose and one in the badger. In addition we also identified an RNA-dependent RNA polymerase gene from a putative novel member of the Nodaviridae family in the fecal material of the otter. CONCLUSIONS: Together these results underline that many novel viruses are yet to be discovered and that fecal associated viruses are not always related to disease. Our study expands the knowledge of viral species present in the gut, although the interpretation of the true host species of such novel viruses needs to be reviewed with great caution.


Assessing Immune Response to SARS-CoV-2 Infection


Surgeons' response to COVID‐19 – Preparing from the sideline


title: Multisystem Inflammatory Syndrome in Children (MIS‐C) Related to COVID‐19: A New York City Experience

text: In December 2019, the 2019 novel coronavirus disease (COVID‐19) caused by Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) first emerged in Wuhan, China. This has now spread worldwide and was declared a pandemic by March 2020. Initially, the pediatric population was described as low risk for severe COVID‐19. However, reports have emerged recently of cases of COVID‐19 in children with a systemic inflammatory disease, with features that overlap with Kawasaki Disease (KD). We describe the first 15 cases with multi‐system inflammatory syndrome in children (MIS‐C), temporally related to COVID‐19, who presented for care to a tertiary pediatric referral center in New York City. We discuss the disproportionate burden of disease among Hispanic/Latino and black/African‐American ancestry, the distinct cytokine signature across the disease spectrum (IL‐1/IL‐6), and the potential role and pathogenesis of SARS‐CoV‐2 in this new clinical entity. This article is protected by copyright. All rights reserved.


title: The alphabet of intrinsic disorder: II. Various roles of glutamic acid in ordered and intrinsically disordered proteins

text: The ability of a protein to fold into unique functional state or to stay intrinsically disordered is encoded in its amino acid sequence. Both ordered and intrinsically disordered proteins (IDPs) are natural polypeptides that use the same arsenal of 20 proteinogenic amino acid residues as their major building blocks. The exceptional structural plasticity of IDPs, their capability to exist as heterogeneous structural ensembles and their wide array of important disorder-based biological functions that complements functional repertoire of ordered proteins are all rooted within the peculiar differential usage of these building blocks by ordered proteins and IDPs. In fact, some residues (so-called disorder-promoting residues) are noticeably more common in IDPs than in sequences of ordered proteins, which, in their turn, are enriched in several order-promoting residues. Furthermore, residues can be arranged according to their “disorder promoting potencies,” which are evaluated based on the relative abundances of various amino acids in ordered and disordered proteins. This review continues a series of publications on the roles of different amino acids in defining the phenomenon of protein intrinsic disorder and concerns glutamic acid, which is the second most disorder-promoting residue.


title: Icariin promotes osteogenic differentiation of BMSCs by upregulating BMAL1 expression via BMP signaling

text: Increasing research has demonstrated that expression of brain and muscle ARNT-like 1 (BMAL1) and other circadian clock genes can be regulated by drugs and toxicants. We previously demonstrated that icariin, extracted from Herba Epimedii, sromotes osteogenic differentiation. However, the mechanism underlying the association between icariin and BMAL1 in osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) remains unclear. The present study was designed with an aim to clarify the association between icariin and BMAL1 in osteogenic differentiation of BMSCs. The Cell Counting Kit-8 assay was used to evaluate cell proliferation. The expression of bone morphogenetic protein 2 (BMP2), RUNX family transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OC) and BMAL1 in BMSCs was evaluated by reverse transcription-quantitative PCR and western blotting. ALP and Alizarin red S (ARS) staining were also performed. Icariin promoted BMSC proliferation, and upregulated expression of osteogenic genes and BMAL1. In addition, expression of the osteogenic genes BMP2, RUNX2, ALP and OC were upregulated by BMAL1 overexpression. Furthermore, we confirmed that BMAL1 deficiency suppressed osteogenic differentiation in BMSCs. Finally, ARS staining of BMAL1(−/−) BMSCs revealed that BMAL1 was an essential intermediary in matrix mineralization during osteogenic differentiation. In conclusion, these results demonstrated that icariin promoted osteogenic differentiation through BMAL1-BMP2 signaling in BMSCs. The present study thus described a novel target of icariin that has potential applications in the treatment of osteogenic disorders.


Independent validation of experimental results requires timely and unrestricted access to animal models and reagents


title: Adeno-Associated Viruses Serotype 2-Mediated RNA Interference Efficiently Inhibits Rabies Virus Replication In Vitro and In Vivo

text: To investigate the potential of adeno-associated viruses serotype 2 (AAV2)-mediated RNA interference (RNAi) as an antiviral agent against rabies, recombinant AAV2 vectors expressing siRNA targeting the nucleoprotein (N) gene of rabies virus (RABV) (rAAV-N796) were constructed and evaluated. When NA cells pretreated with rAAV-N796 were challenged with RABV, there was a 37.8 ± 3.4% to 55.1 ± 5.3% reduction in RABV virus titer. When cells pre-challenged with RABV were treated with rAAV-N796, there was a 4.4 ± 1.4 to 28.8 ± 3.2% reduction in RABV virus titer. Relative quantification of RABV transcripts using real-time PCR and Western blot revealed that the knockdown of RABV-N gene transcripts was based on the rAAV-N796 inoculation titer. When any NA cells were treated with rAAV-N796 before or after challenged with RABV, significant reduction in virus titer was observed in both administrations. Mice treated intracerebrally with rAAV-N796 exhibited 50 ± 5.3 and 62.5 ± 4.7% protection when challenged intracerebrally or intramuscally, respectively, with lethal RABV. When mice treated intramuscularly with rAAV-N796 were challenged intramuscularly with lethal RABV, they exhibited 37.5 ± 3.7% protection. When mice were intracerebrally and intramuscularly with rAAV-N796 24 hr after exposure to RABV infection, they exhibited 25 ± 4.1% protection The N gene mRNA levels in the brains of challenged mice with three different administrations were reduced (55, 68, 32 and 25%, respectively). These results indicated that AAV2 vector-mediated siRNA delivery in vitro in NA cells inhibited RABV multiplication, inhibited RABV multiplication in vivo in the mice brain and imparted partial protection against lethal rabies. So, it may have a potential to be used as an alternative antiviral approach against rabies.


title: Diagnóstico microbiológico de las infecciones virales respiratorias

text: Acute respiratory infection is the most common disease occurring over a person's lifetime, with etiological variations determined mainly by age, environmental circumstances, the healthcare setting, and the underlying pathology. More than 200 different viruses distributed in six viral families have been implicated in the pathogenesis of respiratory tract infection. These facts are generating an increasing diagnostic demand that should be incorporated into the healthcare setting without delay. To meet this demand, the Spanish Society of Infectious Diseases and Clinical Microbiology has updated its Standard Procedure for the microbiological diagnosis of viral respiratory infection. This document contains an update primarily of infections caused by influenza viruses, and secondarily, infections due to other conventional and emerging respiratory viruses. In all cases, the methods for direct virological diagnosis (cell culture, and detection of antigens and nucleic acid) are reviewed, with special reference to techniques for molecular detection and genetic characterization.


title: Exposure to disease agents in the endangered Iberian lynx (Lynx pardinus)

text: The Iberian lynx (Lynx pardinus) is the most endangered felid species in the world. Lynx populations have decreased dramatically in size and distribution in the last four decades, thus becoming increasingly vulnerable to catastrophic events such as epizooties. From 1989 to 2000, serum samples were obtained from 48 free-ranging lynx captured in the Doñana National Park (DNP, n = 31) and mountains of Sierra Morena (SM, n = 17) in southern Spain. Samples were tested for antibodies against Toxoplasma gondii, feline herpesvirus 1 (FHV-1), feline calicivirus (FCV), feline/canine parvovirus (FPV/CPV), feline coronavirus, feline immunodeficiency virus (FIV), feline leukaemia virus and canine distemper virus (CDV) and for FeLV p27 antigen, to document baseline exposure levels. Antibodies against T. gondii were detected in 44% of lynx, with a significantly greater prevalence in DNP (61%) than in SM (12%). In DNP, prevalence was significantly higher in adult (81%) than in juvenile and sub-adult (41%) lynx, but no such difference was observed in SM. Low prevalences (≤11%) of minimally positive titres were found for FHV-1, FCV and FPV/CPV. This, combined with the lack of evidence for exposure to CDV, FIV and FeLV, suggests that these lynx populations are naïve and might be vulnerable to a disease outbreak in the future. Because of the reduced size of lynx populations, the documented low level of genetic variation (particularly in the DNP population) coupled with the recently documented state of immune depletion in a majority of necropsied lynx, it is important to better understand the threat and potential impact that disease agents might pose for the conservation of this endangered species. Future surveillance programs must include possible disease reservoir hosts such as domestic cats and dogs and other wild carnivores.


Corona Virus Disease-19 (COVID-19) Presenting as Conjunctivitis: Atypically High-risk During a Pandemic


title: The viral etiology of an influenza‐like illness during the 2009 pandemic

text: Many viruses are known to cause influenza‐like illness (ILI); however, in nearly 50% of patients, the etiologic agent remains unknown. The distribution of viruses in patients with ILI was investigated during the 2009 A/H1N1 influenza pandemic (A/H1N1p). From June 2009 to January 2010, 660 patients with suspected influenza were questioned and examined, and nasal swabs were collected. All patient samples were tested for influenza virus, and 286 negative nasal swabs were tested further for 18 other respiratory viruses using real‐time RT‐PCR. Two waves of ILI were observed in the epidemic curve (weeks 35–42 and 42–49). At least eight viruses co‐circulated during this period: human rhinovirus (HRV) (58), parainfluenza 1–4 viruses (PIV) (9), human Coronavirus (hCoV) OC43 (9), enterovirus (5), adenovirus (AdV) (4), and human metapneumovirus (hMPV) (2); however, 204 samples remained negative for all viruses tested. ILI symptoms, according to the Centers for Disease Control and Prevention criteria for ILI definition, were reported in 75% of cases. These patients had positive swabs for A/H1N1p, HRV, hCoV‐OC43, PIV, AdV, and hMPV without significant difference with non‐ILI patients. This study found that many respiratory viruses circulated during this period and that the A/H1N1p did not impact on the kinetics of other respiratory viruses. The proportion of non‐documented cases remains high. ILI could not distinguish A/H1N1p infection from that due to other respiratory viruses. However, in multivariate anlaysis, cough, chills, hyperemia, and dyspnea were associated significantly with influenza virus versus other respiratory viruses. J. Med. Virol. 84: 1071–1079, 2012. © 2012 Wiley Periodicals, Inc.


title: The impact of protein characterization in structural proteomics

text: Protein characterization plays a role in two key aspects of structural proteomics. The first is the quality assessment of the produced protein preparations. Obtaining well diffracting crystals is one of the major bottlenecks in the structure‐determination pipeline. Often, this is caused by the poor quality of the protein preparation used for crystallization trials. Hence, it is essential to perform an extensive quality assessment of the protein preparations prior to crystallization and to use the results in the evaluation of the process. Here, a protein‐production and crystallization strategy is proposed with threshold values for protein purity (95%) and monodispersity (85%) below which a further optimization of the protein‐production process is strongly recommended. The second aspect is the determination of protein characteristics such as domains, oligomeric state, post‐translational modifications and protein–protein and protein–ligand interactions. In this paper, applications and new developments of protein‐characterization methods using MS, fluorescence spectroscopy, static light scattering, analytical ultracentrifugation and small‐angle X‐ray scattering within the EC Structural Proteomics in Europe contract are described. Examples of the application of the various methods are given.


title: Update on Bronchiolitis Obliterans Syndrome in Lung Transplantation

text: Lung transplantation has become an important therapeutic option for patients with end-stage organ dysfunction; however, its clinical usefulness has been limited by the relatively early onset of chronic allograft dysfunction and progressive clinical decline. Obliterative bronchiolitis is characterized histologically by luminal fibrosis of the respiratory bronchioles and clinically by bronchiolitis obliterans syndrome (BOS) which is defined by a measured decline in lung function based on forced expiratory volume (FEV(1)). Since its earliest description, a number of risk factors have been associated with the development of BOS, including acute rejection, lymphocytic bronchiolitis, primary graft dysfunction, infection, donor specific antibodies, and gastroesophageal reflux disease. However, despite this broadened understanding, the pathogenesis underlying BOS remains poorly understood and once begun, there are relatively few treatment options to battle the progressive deterioration in lung function.


docid: yfwauksi

title: BCG Vaccination in Humans Elicits Trained Immunity via the Hematopoietic Progenitor Compartment

text: Induction of trained immunity by Bacille-Calmette-Guérin (BCG) vaccination mediates beneficial heterologous effects, but the mechanisms underlying its persistence and magnitude remain elusive. In this study, we show that BCG vaccination in healthy human volunteers induces a persistent transcriptional program connected to myeloid cell development and function within the hematopoietic stem and progenitor cell (HSPC) compartment in the bone marrow. We identify hepatic nuclear factor (HNF) family members 1a and b as crucial regulators of this transcriptional shift. These findings are corroborated by higher granulocyte numbers in BCG-vaccinated infants, HNF1 SNP variants that correlate with trained immunity, and elevated serum concentrations of the HNF1 target alpha-1 antitrypsin. Additionally, transcriptomic HSPC remodeling was epigenetically conveyed to peripheral CD14(+) monocytes, displaying an activated transcriptional signature three months after BCG vaccination. Taken together, transcriptomic, epigenomic, and functional reprogramming of HSPCs and peripheral monocytes is a hallmark of BCG-induced trained immunity in humans.


title: Glycan-Protein Interactions in Viral Pathogenesis

text: The surfaces of host cells and viruses are decorated by complex glycans, which play multifaceted roles in the dynamic interplay between the virus and the host including viral entry into host cell, modulation of proteolytic cleavage of viral proteins, recognition and neutralization of virus by host immune system. These roles are mediated by specific multivalent interactions of glycans with their cognate proteins (generally termed as glycan-binding proteins or GBPs or lectins). The advances in tools and technologies to chemically synthesize and structurally characterize glycans and glycan-GBP interactions have offered several insights into the role of glycan-GBP interactions in viral pathogenesis and have presented opportunities to target these interactions for novel antiviral therapeutic or vaccine strategies. This review covers aspects of role of host cell surface glycan receptors and viral surface glycans in viral pathogenesis and offers perspectives on how to employ various analytical tools to target glycan-GBP interactions.


title: COVID‐19: psychological issues for people with diabetes and health care staff

text: COVID‐19 has frightened us all. Not only are we at risk of a potentially fatal infection, but our governments’ efforts to protect us have separated us from our families and disrupted our lives. People with diabetes are especially vulnerable. Dr Rowan Hillson looks at lessons from past disasters and pandemics to highlight the emotional effects of this pandemic on people with diabetes and health care professionals.


title: The effect of latitude and PM(2.5) on spreading of SARS-CoV-2 in tropical and temperate zone countries()

text: The present work describes spreading of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) at the tropical and temperate zones which are explained based on insolation energy, Particulate Matter (PM(2.5)), latitude, temperature, humidity, Population Density (PD), Human Development Index (HDI) and Global Health Security Index (GHSI) parameters. In order to analyze the spreading of SARS-CoV-2 by statistical data based on the confirmed positive cases which are collected between December 31, 2019 to April 25, 2020. The present analysis reveals that the outbreak of SARS-CoV-2 in the major countries lie on the Equator is 78,509 cases, the countries lie on the Tropic of Cancer is 62,930 cases (excluding China) and the countries lie on the Tropic of Capricorn is 22,842 cases. The tropical countries, which comes between the Tropic of Cancer and Tropic of Capricorn is reported to be 1,77,877 cases. The temperate zone countries, which are above and below the tropical countries are reported to be 25, 66,171 cases so, the pandemic analysis describes the correlation between latitude, temperate zones, PM(2.5) and local environmental factors. Hence, the temperature plays a pivotal role in the spreading of coronavirus at below 20 °C. The spreading of SARS-CoV-2 cases in Northern and Southern Hemispheres has inverse order against absorption of insolated energy. In temperate zone countries, the concentration of PM(2.5) at below 20 μg/m(3) has higher spreading rate of SARS-CoV-2 cases. The effect of insolation energy and PM(2.5), it is confirmed that the spreading of SARS-CoV-2 is explained by dumb-bell model and solid/liquid interface formation mechanism. The present meta-analysis also focuses on the impact of GHSI, HDI, PD and PM(2.5) on spreading of SARS-CoV-2 cases.


title: Development of ultrahigh‐performance liquid chromatography‐ mass spectrometry and ultrahigh‐performance supercritical fluid chromatography‐mass spectrometry assays to determine the concentration of Bitrex™ and sodium saccharin in homemade facemask fit testing solutions

text: RATIONALE: Fast and easily transferable chromatography‐mass spectrometry assays were required to detect and quantify the amount of Bitrex™ and sodium saccharin in homemade facemask fit testing solutions. METHODS: Bitrex™ solutions were analysed using reversed phase ultrahigh‐performance liquid chromatography coupled with positive ion electrospray ionisation mass spectrometry (UHPLC/MS). Separation was achieved using a mobile phase gradient with an Acquity BEH C18 packed column. Sodium saccharin solutions were analysed using ultrahigh‐performance supercritical fluid chromatography coupled with negative ion electrospray ionisation (UHPSFC/MS). Separation was achieved using isocratic elution with an Acquity UPC(2) Torus Diol packed column and a methanol (25 mM ammonium acetate) co‐solvent. RESULTS: The calibration curves obtained using the ratio of the active compound an internal standard generated linear regression values (R(2)) > 0.99. Samples analysed prior to and after an autoclave sterilisation process and bottling give repeatable measurements within 10% of the expected concentration. CONCLUSIONS: The two assays afford a fast robust and quantitative analytical method for the detection of the active components used to test the efficacy of the homemade facemask testing solutions.


title: The pandemic characteristics of 2019-nCoV: case-control study for severity and geographic locations for 2019-nCoV epidemics worldwide

text: Using available official data we found 248 epidemics curves caused worldwide by the 2019-nCoV in the period December 2019–March 31st 2020. The analysis of this material allowed two main observations: 1) it is possible to describe the main geographical pathway of the diffusion of the virus in different directions. This strongly suggests a unique point of origin of the pandemics in Wuhan, China, from where it spread in many different directions. 2) of the 74 epidemics which were characterized by at least 1000 cases, 65 (90%) were located in the geographic region of the world delimitated by 52–30 degrees latitude North. Viceversa 110 (60%) of the 176 epidemics with less than 1000 cases were located outside the cited geographical world region. These results suggest considerations on the pandemic characteristics of 2019-nCoV.


Hyperammonemic encephalopathy in a pediatric patient with Salmonella enteritis and after Roux‐en‐Y surgery


title: Temporal rise in the proportion of younger adults and older adolescents among coronavirus disease (COVID-19) cases following the introduction of physical distancing measures, Germany, March to April 2020

text: Using data on coronavirus disease (COVID-19) cases in Germany from the Robert Koch Institute, we found a relative increase with time in the prevalence in 15–34 year-olds (particularly 20–24-year-olds) compared with 35–49- and 10–14-year-olds (we excluded older and younger ages because of different healthcare seeking behaviour). This suggests an elevated role for that age group in propagating the epidemic following the introduction of physical distancing measures.


title: Biopolymeric nano/microspheres for selective and reversible adsorption of coronaviruses

text: Abstract A novel biopolymeric material in the form of nano/microspheres was developed which was capable of adsorbing coronaviruses. The biopolymer was obtained by crosslinking of chitosan (CHIT) with genipin, a nontoxic compound of plant origin, in inverted emulsion and reacting the chitosan nano/microspheres obtained (CHIT-NS/MS) with glycidyltrimethyl-ammonium chloride (GTMAC). As a result the nano/microspheres of N-(2-hydroxypropyl)-3-trimethyl chitosan (HTCC-NS/MS) were obtained. HTCC-NS/MS were studied as the adsorbents of human coronavirus NL63 (HCoV-NL63), mouse hepatitis virus (MHV), and human coronavirus HCoV-OC43 particles in aqueous virus suspensions. By studying cytopathic effect (CPE) caused by these viruses and performing PCR analyses it was found HTCC-NS/MS strongly adsorb the particles of HCoV-NL63 virus, moderately adsorb mouse hepatitis virus (MHV) particles, but do not adsorb HCoV-OC43 coronavirus. The adsorption capacity of HTCC-NS/MS well correlated with the antiviral activity of soluble HTCC against a given virus. Importantly, it was shown that HCoV-NL63 particles could be desorbed from the HTCC-NS/MS surface with a salt solution of high ionic strength with retention of virus virulence. The obtained material may be applied for the removal of coronaviruses, purification and concentration of virus samples obtained from biological matrices and for purification of water from pathogenic coronaviruses.


docid: namrrffp

title: A Quick “Can I Donate Blood” Self-assessment Tool amid the COVID-19 Outbreak

text: Abstract When presenting with flu-like illnesses, the existing eligibility criteria set within the guidelines, bar such individuals from donating blood. All the same, when healthy-looking ‘asymptomatic’ rather 'innocent blood donors' [IBDs] come forward to donate blood, they’ll pose a serious threat to the health of the blood community. These IBDs may be completely unaware of their viral status at the time of donation. We, therefore, created a "Can I Donate?" self-estimation tool [SAT] within the context of the outbreak of COVID-19, to facilitate an estimation of the seriousness of the present pandemic, its implications for blood safety and to encourage self-deferral by these IBDs if they found themselves to be unsuitable for blood donation.


title: Genetics-Based Classification of Filoviruses Calls for Expanded Sampling of Genomic Sequences

text: We have recently developed a computational approach for hierarchical, genome-based classification of viruses of a family (DEmARC). In DEmARC, virus clusters are delimited objectively by devising a universal family-wide threshold on intra-cluster genetic divergence of viruses that is specific for each level of the classification. Here, we apply DEmARC to a set of 56 filoviruses with complete genome sequences and compare the resulting classification to the ICTV taxonomy of the family Filoviridae. We find in total six candidate taxon levels two of which correspond to the species and genus ranks of the family. At these two levels, the six filovirus species and two genera officially recognized by ICTV, as well as a seventh tentative species for Lloviu virus and prototyping a third genus, are reproduced. DEmARC lends the highest possible support for these two as well as the four other levels, implying that the actual number of valid taxon levels remains uncertain and the choice of levels for filovirus species and genera is arbitrary. Based on our experience with other virus families, we conclude that the current sampling of filovirus genomic sequences needs to be considerably expanded in order to resolve these uncertainties in the framework of genetics-based classification.


Child and adolescent mental health service provision and research during the Covid-19 pandemic: challenges, opportunities, and a call for submissions


title: A COVID-19 case report from asymptomatic contact: implication for contact isolation and incubation management

text: BACKGROUND: As of 2 March, 2020, at least 80 151 coronavirus disease 2019 (COVID-19) cases were reported in China. Most of the patients had a history of visiting Hubei Province or contacting with people who had ever stayed in or passed by Hubei Province or were exposed to symptoms. Some patients got infected through only asymptomatic contact. This study aimed to report the epidemic features and lab identification of a patient confirmed with COVID-19 infection through only asymptomatic contact. CASE PRESENTATION: A 44-year-old man, who lived in Nanchang, Jiangxi Province, China until 6 March 2020, suffered from cough on 27 January 2020. Fever symptoms appeared on 28 January, with a maximum temperature of 38.8 °C, accompanied by cough, sore throat, headache, fatigue, muscle ache, joint ache, and other symptoms. The symptoms continued until he was hospitalized on 30 January. Coronavirus conventional polymerase chain reaction assay was positive for the throat swab sample. The patient, along with his wife and son, drove from Nanchang to back to Honghu City, Hubei Province, on 23 January 2020. After staying with his parents and brother’s family for 3 days, the patient drove back to Nanchang and arrived on 25 January. On the way back home, they stopped by Tongshan service area, Hubei Province, without any close contact with other people. After arriving home in Nanchang City, Jiangxi Province, none of them left their residence. In addition, his parents stayed at home for 20 days with his younger brother’s family before they got back. His younger brother and one of his brother’s children visited Wuhan on 5 January and came home on 6 January 2020. CONCLUSIONS: This report suggested that, in the early phase of COVID-19 pneumonia, routine screening could miss patients who were virus carriers. Highlighting travel history is of paramount importance for the early detection and isolation of severe acute respiratory syndrome coronavirus 2 cases.


title: Virtual screening, ADME/Tox predictions and the drug repurposing concept for future use of old drugs against the COVID-19

text: The new Coronavirus (SARS-CoV-2) is the cause of a serious infection in the respiratory tract called COVID-19. Structures of the main protease of SARS-CoV-2 (M(pro)), responsible for the replication of the virus, have been solved and quickly made available, thus allowing the design of compounds that could interact with this protease and thus to prevent the progression of the disease by avoiding the viral peptide to be cleaved, so that smaller viral proteins can be released into the host's plasma. These structural data are extremely important for in silico design and development of compounds as well, being possible to quick and effectively identify potential inhibitors addressed to such enzyme's structure. Therefore, in order to identify potential inhibitors for M(pro), we used virtual screening approaches based with the structure of the enzyme and two compounds libraries, targeted to SARS-CoV-2, containing compounds with predicted activity against M(pro). In this way, we selected, through docking studies, the 100 top-ranked compounds, which followed for subsequent studies of pharmacokinetic and toxicity predictions. After all the simulations and predictions here performed, we obtained 10 top-ranked compounds that were again in silico analyzed inside the M(pro) catalytic site, together some drugs that are being currently investigated for treatment of COVID-19. After proposing and analyzing the interaction modes of these compounds, we submitted one molecule then selected as template to a 2D similarity study in a database containing drugs approved by FDA and we have found and indicated Apixaban as a potential drug for future treatment of COVID-19.


title: Using the contact network model and Metropolis-Hastings sampling to reconstruct the COVID-19 spread on the “Diamond Princess”

text: Abstract Traditional compartmental models such as SIR (susceptible, infected, recovered) assume that the epidemic transmits in a homogeneous population, but the real contact patterns in epidemics are heterogeneous. Employing a more realistic model that considers heterogeneous contact is consequently necessary. Here, we use a contact network to reconstruct unprotected, protected contact, and airborne spread to simulate the two-stages outbreak of COVID-19 (coronavirus disease 2019) on the “Diamond Princess” cruise ship. We employ Bayesian inference and Metropolis-Hastings sampling to estimate the model parameters and quantify the uncertainties by the ensemble simulation technique. During the early epidemic with intensive social contacts, the results reveal that the average transmissibility t was 0.026 and the basic reproductive number R 0 was 6.94, triple that in the WHO report, indicating that all people would be infected in one month. The t and R 0 decreased to 0.0007 and 0.2 when quarantine was implemented. The reconstruction suggests that diluting the airborne virus concentration in closed settings is useful in addition to isolation, and high-risk susceptible should follow rigorous prevention measures in case exposed. This study can provide useful implications for control and prevention measures for the other cruise ships and closed settings.


title: Diffuse Alveolar Damage: A Common Phenomenon in Progressive Interstitial Lung Disorders

text: It has become obvious that several interstitial lung diseases, and even viral lung infections, can progress rapidly, and exhibit similar features in their lung morphology. The final histopathological feature, common in these lung disorders, is diffuse alveolar damage (DAD). The histopathology of DAD is considered to represent end stage phenomenon in acutely behaving interstitial pneumonias, such as acute interstitial pneumonia (AIP) and acute exacerbations of idiopathic pulmonary fibrosis (IPF). Acute worsening and DAD may occur also in patients with nonspecific interstitial pneumonias (NSIPs), and even in severe viral lung infections where there is DAD histopathology in the lung. A better understanding of the mechanisms underlying the DAD reaction is needed to clarify the treatment for these serious lung diseases. There is an urgent need for international efforts for studying DAD-associated lung diseases, since the prognosis of these patients has been and is still dismal.


title: Covid-19 spreads in US

text: Multiple outbreaks worldwide have led to countries stepping up their responses. By Debora MacKenzie and Press Association


title: RANTES, Macrophage-Inhibitory Protein 1α, and the Eosinophil Product Major Basic Protein Are Released into Upper Respiratory Secretions during Virus-Induced Asthma Exacerbations in Children

text: The presence of cytokines and the toxic eosinophil granule product major basic protein (MBP) was investigated in nasal aspirates from children with naturally occurring virus-induced asthma exacerbations and compared with levels in nasal aspirates taken from the same children when asymptomatic. Increased levels of MBP accompanied by increased levels of the chemokines RANTES and macrophage-inhibitory protein 1α were observed in nasal aspirates from children during the virus-induced exacerbations. Granulocyte-macrophage colony-stimulating factor was mostly undetectable in samples obtained during both symptomatic and asymptomatic periods. Interleukin-5 levels were low, but tended to increase in samples from symptomatic children. These data confirm that the eosinophil product MBP and the eosinophil chemoattractant chemokines RANTES and macrophage-inhibitory protein 1α are increased in upper respiratory viral infections associated with asthma exacerbations and suggest an important role for these chemokines in regulating eosinophil influx and activation. These chemokines may represent targets for therapeutic intervention in virus-induced asthma exacerbations.


title: Infecciones virales de vías respiratorias en los primeros seis meses de vida

text: Resumen Antecedentes El virus respiratorio sincitial (VRS) y otros virus son causas conocidas de hospitalización en lactantes. Menos conocido es el patrón de virus en infecciones extrahospitalarias en menores de 6 meses. Objetivo El objetivo de este estudio es describir las características clínicas y los factores epidemiológicos asociados con las infecciones respiratorias virales de ámbito extrahospitalario en menores de 6 meses. Pacientes y métodos Estudio prospectivo en cohorte de niños de las áreas 8 y 9 de Madrid controlados desde el nacimiento mediante llamadas telefónicas quincenales durante una temporada invernal. Se registraron datos clínicos y epidemiológicos en cuestionarios prediseñados. Se exploró y recogió el aspirado nasofaríngeo (ANF) cuando el paciente presentó sintomatología compatible con una infección respiratoria. El diagnóstico de los virus más comunes se realizó con inmunofluorescencia directa (IFD) y amplificación genómica (PCR). Resultados Fueron seleccionados 316 recién nacidos. Se realizaron 1.865 llamadas telefónicas (mediana 4), y 106 visitas, en 89 de las cuales se confirmó la enfermedad. Los síntomas más frecuentes fueron rinitis (91 %) y tos (69 %). El diagnóstico clínico principal fue infección respiratoria de vías altas (82 %); 17 de 72 ANF realizados (23,2 %) fueron positivos. Se detectaron rinovirus (41,1 %) y VRS (35,2 %). Ingresaron un 16 % (17/106) de los niños atendidos por enfermedad (el 5,3% de la cohorte), diagnosticados de síndrome febril y de bronquiolitis. No encontramos ningún factor epidemiológico asociado con la infección respiratoria viral en los casos positivos. Conclusiones En nuestro medio las infecciones respiratorias de los lactantes son en su mayoría banales y no precisan atención hospitalaria. El rinovirus y el VRS son los principales agentes etiológicos. No se encontraron factores epidemiológicos relacionados con la infección respiratoria asociada a virus. Abstract Background Respiratory syncytial virus and Influenza virus infections are known causes of hospital admission in infants. It is less well known the pattern of virus infections in infants under 6 months of age in the outpatient setting. Objective To describe the clinical and epidemiological pattern of community-acquired viral respiratory infections in infants under 6 months. Patients and methods A cohort of infants from the 8 and 9 Madrid Health Districts was followed by telephone calls every two weeks since birth during the epidemic winter season. Clinical and epidemiological data were collected in pre-designed questionnaires. Nasopharyngeal aspirate was obtained in every patient with symptoms compatible with respiratory infection. Diagnosis of the more common virus was made with direct immunofluorescence and nucleic acid amplification test (PCR). Results Were recruited 316 newborns. The 1,865 phone calls made (median 4 for every child), produced 106 visits, and the illness confirmed in 89 illness. Rhinitis (91 %) and cough (69 %) were the most common symptoms. Upper respiratory infection was the principal clinical diagnosis (84.5 %), and 17 of the 72 samples (23.2 %) were positive. Most common viruses were RSV (41.1 %) and rhinovirus (35.2 %). Of the children visited, 17 out of 106 (16 %) (5.3% of the cohort) were admitted to hospital. Diagnoses were febrile syndrome and bronchiolitis. We did not find any epidemiological factor associated with viral respiratory infection in positive cases. Conclusions In our population most of the respiratory infections in infants are minor and do not need hospital assistance. Rhinovirus and RSV are the major pathogens. We did not find any epidemiological factor associated with viral respiratory infection.


title: New targets for treatment against HCV infection

text: Owing to the tremendous effort from both academia and industry, drug development for hepatitis C virus (HCV) infection has been flourishing, with a range of pipeline compounds at various stages of development. Although combination of the recently launched serine protease inhibitors will further improve the response rate of current interferon-based therapy, some intrinsic limitations of these compounds and the tendency of resistance development by the virus, urge the development of alternative or additional therapeutic strategies. In this article we provide an overview of different host and viral factors which have emerged as new potential targets for therapeutic intervention using state-of-the-art technologies.


SENEGAL: Force‐Covid‐19


title: Sequence Comparison of Avian Infectious Bronchitis Virus S1 Glycoproteins of the Florida Serotype and Five Variant Isolates from Georgia and California

text: The infectious bronchitis virus (IBV) spike glycoprotein S1 subunit is required to initiate infection and contains virus-neutralizing and serotype-specific epitope(s). Reported are the S1 gene nucleotide and predicted amino acid sequences for the Florida 18288 strain and isolates GA-92, CV-56b, CV-9437, CV-1686, and 1013. These sequences were compared with previously published gene sequences of IBV strains, and phylogenetic relationships are reported. The S1 amino acid sequence of Florida 18288 was 94.9% similar to the Connecticut strain, and GA-92 was 92.8% similar to the Arkansas 99 strain. S1 amino acid sequences of the California variants, CV-56b, CV-9437, and CV-1686, were 97.6–99.3% similar to one another and only 76.6%–76.8% similar to the Arkansas-type strains. Isolate 1013, also from California, was 84.0% similar to Ark DPI and 77.9% similar to CV-56b. When comparing 19 viruses isolated from the United States, sequence variations were observed between amino acids 55–96, 115–149, 255–309, and 378–395. Similar regions are reported to be involved in virus-neutralizing and/or serotype-specific epitopes. These data demonstrate that variant IBV strains continue to emerge, and unique variants may circulate among poultry in geographically isolated areas.


title: An approximation-based approach for periodic estimation of effective reproduction number: a tool for decision-making in the context of Covid-19 outbreak

text: Abstract Objectives The effective reproduction number (R) is a more practical epidemiological parameter than basic reproduction number (R 0 ) for characterization of infectious disease epidemics as it takes into account presence of immune individuals in the population which R 0 does not. Periodic assessment of R can inform public health strategies during long-standing epidemics like the current Covid-19 situation. This is especially relevant for large and resource-poor countries like India, which may require differential intervention strategies in different regions. However, the complexity of the calculation involved often proves to be a barrier for calculation of R. This communication proposes a simpler data collection and analytical method – involving a combination approach instead of full-fledged primary data collection - to estimate R for public-health decision-making. Study design Review of literature. Methods Data from available sources (time series data of new cases at population level) can be combined with some primary data (time interval between infection of index and secondary cases in family clusters) that can be collected with little resources. These data can then be fed into an approximation-based method (Wallinga and Lipsitch) for R calculation at the state/regional levels. The calculations can be repeated every fortnight using newly available data. Results The value of R, estimated using the proposed method, from subsequent periods can be used for assessing the status of the epidemic and values from subsequent periods can be compared for decision-making regarding implementation/modification of control measures. Conclusions The approximate R may be a little inaccurate but can still prove useful for rough estimation of epidemic evolution and for comparison between different periods, as the extent of error in R values across different periods is likely to be similar. Thus, the approximate R may not only be utilized to estimate the epidemic change in smaller geographies such as states/regions but also used for making appropriate changes to public health measures for managing a pandemic like Covid-19.


title: Prolonged presence of SARS-CoV-2 in a COVID-19 case with rheumatoid arthritis taking iguratimod treated with ciclesonide

text: Abstract We report a coronavirus disease 2019 (COVID-19) case with rheumatoid arthritis taking iguratimod. The patient who continued iguratimod therapy without dose reduction was treated with ciclesonide had an uneventful clinical course, but prolonged detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was observed after resolution of symptoms. The effects of disease-modifying antirheumatic drugs (DMARDs) and ciclesonide on clinical course and viral shedding remain unknown and warrant further investigation.


title: Recurrent positive nucleic acid detection in a recovered COVID-19 patient: a case report and literature review

text: OBJECTIVE: To describe a case of recurrent positive nucleic acid detection in a recovered coronavirus disease 2019 (COVID-19) patient and to provide clinical data for the further study of COVID-19. METHODS: A case of COVID-19 was retrospectively analyzed, and the relevant literature was reviewed. RESULTS: Based on the 6th edition of the COVID-19 treatment plan, the patient met the discharge standards after treatment and was discharged after consultation with the expert panel. Two weeks after discharge, nucleic acid testing of a sputum sample for severe acute respiratory coronavirus 2 (SARS-CoV-2) was positive again. There may be various reasons. CONCLUSION: Recurring positive SARS-CoV-2 nucleic acid tests pose a formidable challenge, and more stringent discharge standards should be considered. When considering recurrent positive nucleic acid results in COVID-19 patients, the clinicians should have a rational judgment.


title: Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

text: The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we determined a 3.5-angstrom-resolution cryo–electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophysical and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.


title: Reassortant Group A Rotavirus from Straw-colored Fruit Bat (Eidolon helvum)

text: Bats are known reservoirs of viral zoonoses. We report genetic characterization of a bat rotavirus (Bat/KE4852/07) detected in the feces of a straw-colored fruit bat (Eidolon helvum). Six bat rotavirus genes (viral protein [VP] 2, VP6, VP7, nonstructural protein [NSP] 2, NSP3, and NSP5) shared ancestry with other mammalian rotaviruses but were distantly related. The VP4 gene was nearly identical to that of human P[6] rotavirus strains, and the NSP4 gene was closely related to those of previously described mammalian rotaviruses, including human strains. Analysis of partial sequence of the VP1 gene indicated that it was distinct from cognate genes of other rotaviruses. No sequences were obtained for the VP3 and NSP1 genes of the bat rotavirus. This rotavirus was designated G25-P[6]-I15-R8(provisional)-C8-Mx-Ax-N8-T11-E2-H10. Results suggest that several reassortment events have occurred between human, animal, and bat rotaviruses. Several additional rotavirus strains were detected in bats.


title: Demographic and Socioeconomic Disparities Among Cancer Survivors in Clinical Trials Participation, USA, 2016–2018

text: The established findings of lower representation of minority population in clinical trials are skewed by the national representation of the US population by race where they account only for 30%, making it difficult to compare the participation rate by race. We report the direct age-adjusted demographic and socioeconomic disparities in clinical trial participation among cancer survivors using the most recent national survey data. In 2018, 7.1% of cancer survivors reported participating in the clinical trial as a part of their cancer treatment. The participation rate was significantly higher among younger adults (age 18–24, 19.1%), male (8.5%), black (19.8%), and Hispanic (14.4%) cancer survivors, while rate was lower among female (4.2%), and white (5.4%). By marital status, 8.5% of unmarried and 3.5% of married cancer survivors reported clinical trial participation. These results help explain the demographic disparities in cancer survivors and drawing attention to targeted education and awareness intervention for ideal cancer care.


Spontaneous breathing, transpulmonary pressure and mathematical trickery


title: Comorbid Chronic Diseases are Strongly Correlated with Disease Severity among COVID-19 Patients: A Systematic Review and Meta-Analysis

text: Coronavirus disease 2019 (COVID-19) has resulted in considerable morbidity and mortality worldwide since December 2019. In order to explore the effects of comorbid chronic diseases on clinical outcomes of COVID-19, a search was conducted in PubMed, Ovid MEDLINE, EMBASE, CDC, and NIH databases to April 25, 2020. A total of 24 peer-reviewed articles, including 10948 COVID-19 cases were selected. We found diabetes was present in 10.0%, coronary artery disease/cardiovascular disease (CAD/CVD) was in 8.0%, and hypertension was in 20.0%, which were much higher than that of chronic pulmonary disease (3.0%). Specifically, preexisting chronic conditions are strongly correlated with disease severity [Odds ratio (OR) 3.50, 95% CI 1.78 to 6.90], and being admitted to intensive care unit (ICU) (OR 3.36, 95% CI 1.67 to 6.76); in addition, compared to COVID-19 patients with no preexisting chronic diseases, COVID-19 patients who present with either diabetes, hypertension, CAD/CVD, or chronic pulmonary disease have a higher risk of developing severe disease, with an OR of 2.61 (95% CI 1.93 to 3.52), 2.84 (95% CI 2.22 to 3.63), 4.18 (95% CI 2.87 to 6.09) and 3.83 (95% CI 2.15 to 6.80), respectively. Surprisingly, we found no correlation between chronic conditions and increased risk of mortality (OR 2.09, 95% CI 0.26 to16.67). Taken together, cardio-metabolic diseases, such as diabetes, hypertension and CAD/CVD were more common than chronic pulmonary disease in COVID-19 patients, however, each comorbid disease was correlated with increased disease severity. After active treatment, increased risk of mortality in patients with preexisting chronic diseases may reduce.


title: Interactions of Pathogens with the Host

text: Abstract Infection occurs when a microbe enters a normally nonsterile tissue and may cause an infectious disease with signs and symptoms or a subclinical infection. Infections that are not cleared by the host are characterized as persistent. The agent in nonreplicating or latent infection may begin to grow again or to reactivate. Growth of a microorganism such as normal bacterial flora on a normally nonsterile body surface such as the colonic mucosa in the absence of disease is called colonization. Some infectious agents known as pathogens routinely cause disease; others known as opportunistic cause disease only in persons with altered host defenses, such as acquired immunodeficiency syndrome. The location where a pathogen normally resides is the reservoir, such as naturally infected animals. The mechanism by which the pathogen moves from the reservoir into the patient is known as transmission such as by drinking contaminated water. The portals of entry are mucosal, respiratory, gastrointestinal, genitourinary, and cutaneous. A pathogen may replicate at the portal of entry and cause disease by secreting a toxin or enter the body and spread via the lymphatic or blood vessels, nerves, urinary tract, respiratory tract, cerebrospinal fluid, over mesothelial surfaces, or to the fetus transplacentally. Many infectious agents target a particular organ where they replicate and cause damage, for example, hepatitis, myocarditis, and meningoencephalitis.


title: Thermostable DNA Polymerase from a Viral Metagenome Is a Potent RT-PCR Enzyme

text: Viral metagenomic libraries are a promising but previously untapped source of new reagent enzymes. Deep sequencing and functional screening of viral metagenomic DNA from a near-boiling thermal pool identified clones expressing thermostable DNA polymerase (Pol) activity. Among these, 3173 Pol demonstrated both high thermostability and innate reverse transcriptase (RT) activity. We describe the biochemistry of 3173 Pol and report its use in single-enzyme reverse transcription PCR (RT-PCR). Wild-type 3173 Pol contains a proofreading 3′-5′ exonuclease domain that confers high fidelity in PCR. An easier-to-use exonuclease-deficient derivative was incorporated into a PyroScript RT-PCR master mix and compared to one-enzyme (Tth) and two-enzyme (MMLV RT/Taq) RT-PCR systems for quantitative detection of MS2 RNA, influenza A RNA, and mRNA targets. Specificity and sensitivity of 3173 Pol-based RT-PCR were higher than Tth Pol and comparable to three common two-enzyme systems. The performance and simplified set-up make this enzyme a potential alternative for research and molecular diagnostics.


The critical bedside role in identifying and treating lung injury during the COVID‐19 pandemic


title: How to avoid nosocomial spread during tracheostomy for COVID‐19 patients

text: As the novel coronavirus (Covid-19) globally spreads, the Covid-19 pandemic is straining healthcare workers worldwide. In hospitalized patients with severe Covid-19, endotracheal intubation is one of the most common and indispensable life-saving interventions. For patients in need of long-term endotracheal intubation, tracheostomy may be considered. Some patients with unfavorable neck anatomy, such as short neck, enlarged thyroid, and neck cicatricial contracture, are not suitable for percutaneous tracheostomy, a minimally invasive method.1 In these circumstances, conventional open tracheostomy is the primary option for surgeons. However, it is one of the most hazardous procedures, because the direct airway opening and the coughing of patients causes aerosolization of the virus potentially exposing healthcare workers.2 To prevent healthcare-associated infections, we are willing to share our modified tracheostomy procedures with other surgeons worldwide. This article is protected by copyright. All rights reserved.


title: Highly potent anti-HIV-1 activity isolated from fermented Polygonum tinctorium Aiton

text: Abstract A water-soluble extract of fermented Polygonum tinctorium Aiton (Polygonaceae) called Sukumo, exhibited a potent inhibitory activity against HIV type 1 in vitro. The extract potently suppressed acute HIV-1 (IIIB) infection in MT-4 cells with EC50 values of 0.5μg/ml but exhibited low cytotoxicity to MT-4 cells even at a high concentration (CC50 >1000μg/ml). It also inhibited giant cell formation in co-cultures of HIV-infected cells and uninfected Molt-4 cells. Sukumo extract was found to interact with both the viral envelope glycoprotein and cellular receptors, thus blocking virus-cell binding and virus-induced syncytium formation. There was a good correlation between the extract's anti-HIV-1 activity and its inhibitory effects on HIV-1 binding. It also suppressed replication of herpes simplex virus type 1 in Vero cells with an EC50 of 11.56μg/ml. On the other hand, there was no appreciable activity against influenza A virus, poliovirus or SARS corona virus when tested at concentrations ranging from 3.2–400μg/ml as shown by microscopic image analysis for cytopathic effect (CPE). Physico-chemical studies revealed that the anti-HIV activity in the extract was essentially maintained after boiling at 100°C in 1N HCl or 1N NaOH, and after treatment with 100mM NaIO4. The inhibitory activity of the extract was also not reduced after pronase digestion. The active factor in the extract is likely to be a novel compound(s) having a polyanionic substructure and a molecular weight of 10,000–50,000.


LIST OF CONTENTS, AUTHOR AND SUBJECT INDEX FOR VOLUME 43, 2006


Aspects médico-psychologiques relatifs à l’épidémie de coronavirus (Covid-19) : l’apport de la théorie de la détection du signal et du concept de lieu de contrôle


Covid‐19‐related pancreatic injury


title: Governing Under Pressure: German Policy Making During the Coronavirus Crisis

text: The global threat of the coronavirus pandemic has forced policy makers to react quickly with totally new policy‐making approaches under conditions of uncertainty. This article focuses on such crisis‐driven policy learning, examining how the experiences of China and South Korea as early responder states influenced the subsequent coronavirus crisis management in Germany. The first reaction of the German core executive was the quick concentration of decision‐making power at the top of the political hierarchy. Asserting the prerogatives of the executive included the radical simplification of the relationship between politics, law and science. State actors took emergency measures by recourse to a single piece of legislation—the ‘infection protection law’ (Infektionsschutzgesetz)—overriding other elements of the legal order. They also limited the government’s use of scientific expertise to a small number of advisors, thereby cutting short debates about the appropriateness or otherwise of the government’s crisis measures. Finally, German actors failed to understand that some of the earlier Chinese and Korean responses required a precondition—namely public willingness to sacrifice privacy for public health—that is absent in the German case.


title: Synergistic effects of ATP and RNA binding to human DEAD-box protein DDX1

text: RNA helicases of the DEAD-box protein family form the largest group of helicases. The human DEAD-box protein 1 (DDX1) plays an important role in tRNA and mRNA processing, is involved in tumor progression and is also hijacked by several virus families such as HIV-1 for replication and nuclear export. Although important in many cellular processes, the mechanism of DDX1′s enzymatic function is unknown. We have performed equilibrium titrations and transient kinetics to determine affinities for nucleotides and RNA. We find an exceptional tight binding of DDX1 to adenosine diphosphate (ADP), one of the strongest affinities observed for DEAD-box helicases. ADP binds tighter by three orders of magnitude when compared to adenosine triphosphate (ATP), arresting the enzyme in a potential dead-end ADP conformation under physiological conditions. We thus suggest that a nucleotide exchange factor leads to DDX1 recycling. Furthermore, we find a strong cooperativity in binding of RNA and ATP to DDX1 that is also reflected in ATP hydrolysis. We present a model in which either ATP or RNA binding alone can partially shift the equilibrium from an ‘open’ to a ‘closed’-state; this shift appears to be not further pronounced substantially even in the presence of both RNA and ATP as the low rate of ATP hydrolysis does not change.


title: Renal hypouricemia is an ominous sign in patients with severe acute respiratory syndrome

text: Background: The purpose of this study is to determine the incidence and significance of hypouricemia in patients with severe acute respiratory syndrome (SARS). Pulmonary lesions in patients with SARS are thought to result from proinflammatory cytokine dysregulation. Acute renal failure has been reported in patients with SARS, but whether cytokines can injure renal tubules is unknown. Methods: Sixty patients diagnosed with SARS in Taiwan in April 2003 were studied. Patients were identified as hypouricemic when their serum uric acid (UA) level was less than 2.5 mg/dL (<149 μmol/L) within 15 days after fever onset. Urine UA and creatinine levels were available for 43 patients; the serum cytokines interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α (TNF-α) were measured in 16 patients. Results: Sixteen patients (26.7%) had hypouricemia (UA, 1.68 ± 0.52 mg/dL [100 ± 31 μmol/L]). No differences in age, sex, symptoms, vital signs, hemogram, or other biochemistry data existed between the hypouricemic and normouricemic groups. Fractional excretion (FE) of UA (FEUA) in 12 hypouricemic patients was 39.6% ± 23.4%, significantly greater than that of 31 normouricemic patients (16.4% ± 11.4%; P < 0.0001). After adjustments for age and sex, high FEUA was significantly associated with the lowest blood oxygenation (P = 0.001; r = −0.624). The number of catastrophic outcomes (endotracheal intubation and/or death) adjusted for older age and sex showed that hypouremic patients had an odds ratio of 10.57 (confidence interval, 2.33 to 47.98; P = 0.002). Kaplan-Meier curves for catastrophic outcome–free results showed significant differences between patients with normouricemia or hypouricemia (P = 0.01). Serum IL-8 levels correlated significantly with FEUA (P < 0.001; r = 0.785) and inversely with serum UA level (P = 0.044; r = −0.509); neither IL-6 nor TNF-α level showed such correlations. Conclusion: One fourth of patients with SARS developed hypouricemia, which might result from a defect in renal UA handling and was associated with a high serum IL-8 level. Renal hypouricemia is an ominous sign in patients with SARS.


title: Public health education for parents during the outbreak of COVID-19: A rapid review

text: Background: It is well-known that public health education plays a crucial role in the prevention and control of emerging infectious diseases, but how health providers should advise families and parents to obtain health education information is a challenging question. With coronavirus disease 2019 (COVID-19) spreading around the world, this rapid review aims to answer that question and thus to promote evidence-based decision making in health education policy and practice. Methods: We systematically searched the literature on health education during COVID-19, severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS) epidemics in Medline (via PubMed), Cochrane Library, EMBASE, Web of Science, China Biology Medicine disc (CBM), China National Knowledge Infrastructure (CNKI), and Wanfang Data from their inception until March 31, 2020. The potential bias of the studies was assessed by Joanna Briggs Institute Prevalence Critical Appraisal Tool. Results: Of 1,067 papers found, 24 cross-sectional studies with a total of 35,967 participants were included in this review. The general public lacked good knowledge of SARS and MERS at the early stage of epidemics. Some people's knowledge, attitude and practice (KAP) of COVID-19 had been improved, but the health behaviors of some special groups including children and their parents need to be strengthened. Negative emotions including fear and stigmatization occurred during the outbreaks. Reliable health information was needed to improve public awareness and mental health for infectious diseases. Health information from nonprofit, government and academic websites was more accurate than privately owned commercial websites and media websites. Conclusions: For educating and cultivating children, parents should obtain information from the official websites of authorities such as the World Health Organization (WHO) and national Centers for Disease Control, or from other sources endorsed by these authorities, rather than from a general search of the internet or social media.


title: Healthcare worker exposure to Middle East respiratory syndrome coronavirus (MERS-CoV): Revision of screening strategies urgently needed

text: Abstract Objectives Middle East respiratory syndrome coronavirus (MERS-CoV) continues to cause frequent hospital outbreaks in Saudi Arabia, with emergency departments as the initial site of the spread of this virus. Methods The risk of transmission of MERS-CoV infection to healthcare workers (HCWs) was assessed in an outbreak in Riyadh. All HCWs with unprotected exposure to confirmed cases were tested after 24h of exposure. Two negative results for MERS-CoV obtained 3days apart and being free of any suggestive signs and symptoms were used to end the isolation of the HCWs and allow their return to duty. Results Overall 17 out of 879 HCWS with different levels of exposure tested positive for MERS-CoV. Of the 15 positive HCWS with adequate follow-up, 40% (6/15 HCWs) tested positive on the first sampling and 53% (8/15) tested positive on the second sampling. The time to negative results among the 15 positive HCWs ranged between 4 and 47days (average 14.5 days) and the infected HCWs needed on average two samples for clearance. All positive HCWs were either asymptomatic or had mild disease. Conclusions The data obtained in this study support the widespread testing of all close contacts of MERS-CoV cases, regardless of the significance of the contact or presence or absence of symptoms. In addition, urgent careful review of guidance regarding the return of asymptomatic MERS-CoV-positive HCWs under investigation to active duty is needed.


title: Extensive Viable Middle East Respiratory Syndrome (MERS) Coronavirus Contamination in Air and Surrounding Environment in MERS Isolation Wards

text: Background. The largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) outside the Middle East occurred in South Korea in 2015 and resulted in 186 laboratory-confirmed infections, including 36 (19%) deaths. Some hospitals were considered epicenters of infection and voluntarily shut down most of their operations after nearly half of all transmissions occurred in hospital settings. However, the ways that MERS-CoV is transmitted in healthcare settings are not well defined. Methods. We explored the possible contribution of contaminated hospital air and surfaces to MERS transmission by collecting air and swabbing environmental surfaces in 2 hospitals treating MERS-CoV patients. The samples were tested by viral culture with reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence assay (IFA) using MERS-CoV Spike antibody, and electron microscopy (EM). Results. The presence of MERS-CoV was confirmed by RT-PCR of viral cultures of 4 of 7 air samples from 2 patients' rooms, 1 patient's restroom, and 1 common corridor. In addition, MERS-CoV was detected in 15 of 68 surface swabs by viral cultures. IFA on the cultures of the air and swab samples revealed the presence of MERS-CoV. EM images also revealed intact particles of MERS-CoV in viral cultures of the air and swab samples. Conclusions. These data provide experimental evidence for extensive viable MERS-CoV contamination of the air and surrounding materials in MERS outbreak units. Thus, our findings call for epidemiologic investigation of the possible scenarios for contact and airborne transmission, and raise concern regarding the adequacy of current infection control procedures.


title: Medical molecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants

text: The use of plants for medicinal purposes dates back thousands of years but genetic engineering of plants to produce desired biopharmaceuticals is much more recent. As the demand for biopharmaceuticals is expected to increase, it would be wise to ensure that they will be available in significantly larger amounts, on a cost-effective basis. Currently, the cost of biopharmaceuticals limits their availability. Plant-derived biopharmaceuticals are cheap to produce and store, easy to scale up for mass production, and safer than those derived from animals. Here, we discuss recent developments in this field and possible environmental concerns.


title: Viral respiratory infections in a nursing home: a six-month prospective study

text: BACKGROUND: The knowledge on viral respiratory infections in nursing home (NH) residents and their caregivers is limited. The purpose of the present study was to assess and compare the incidence of acute respiratory infections (ARI) in nursing home (NH) residents and staff, to identify viruses involved in ARI and to correlate viral etiology with clinical manifestations of ARI. METHODS: The prospective surveillance study was accomplished in a medium-sized NH in Slovenia (central Europe). Ninety NH residents and 42 NH staff were included. Nasopharyngeal swabs were collected from all participants at enrollment (December 5th, 2011) and at the end of the study (May 31st, 2012), and from each participant that developed ARI within this timeframe. Molecular detection of 15 respiratory viruses in nasopharyngeal swab samples was performed. RESULTS: The weekly incidence rate of ARI in NH residents and NH staff correlated; however, it was higher in staff members than in residents (5.9 versus 3.8/1,000 person-days, P = 0.03), and was 2.5 (95 % CI: 1.36–4.72) times greater in residents without dementia than in residents with dementia. Staff members typically presented with upper respiratory tract involvement, whereas in residents lower respiratory tract infections predominated. Respiratory viruses were detected in 55/100 ARI episodes. In residents, influenza A virus, respiratory syncytial virus, and human metapneumovirus were detected most commonly, whereas in NH staff rhinovirus and influenza A virus prevailed. 38/100 ARI episodes (30/56 in residents, 8/44 in staff) belonged to one of three outbreaks (caused by human metapneumovirus, influenza A virus and respiratory syncytial virus, respectively). NH residents had higher chances for virus positivity within outbreak than HN staff (OR = 7.4, 95 % CI: 1.73–31.48, P < 0.01). CONCLUSIONS: ARI are common among NH residents and staff, and viruses were detected in a majority of the episodes of ARI. Many ARI episodes among NH residents were outbreak cases and could be considered preventable. TRIAL REGISTRATION: The study was registered on the 1(th) of December 2011 at ClinicalTrials (NCT01486160).


Enfermedad por Coronavirus 2019 (COVID-19) en América Latina: Papel de la atención primaria en la preparación y respuesta


title: Evaluation of a field-deployable reverse transcription-insulated isothermal PCR for rapid and sensitive on-site detection of Zika virus

text: BACKGROUND: The recent emergence of Zika virus (ZIKV) in Brazil and its precipitous expansion throughout the Americas has highlighted the urgent need for a rapid and reliable on-site diagnostic assay suitable for viral detection. Such point-of-need (PON), low-cost diagnostics are essential for ZIKV control in vulnerable areas with limited resources. METHODS: We developed and evaluated a ZIKV-specific field-deployable RT-iiPCR reagent set targeting the E gene for rapid detection of ZIKV in ZIKV-spiked human and mosquito specimens, and compared its performance to the Center for Disease Control and Prevention (CDC) and Pan American Health Organization (PAHO) RT-qPCR assays targeting the E and NS2B genes, respectively. RESULTS: These assays demonstrated exclusive specificity for ZIKV (African and Asian lineages), had limits of detection ranging from 10 to 100 in vitro transcribed RNA copies/μl and detection endpoints at 10 plaque forming units/ml of infectious tissue culture fluid. Analysis of human whole blood, plasma, serum, semen, urine, and mosquito pool samples spiked with ZIKV showed an agreement of 90% (k = 0.80), 92% (k = 0.82), 95% (k = 0.86), 92% (k = 0.81), 90% (k = 0.79), and 100% (k = 1), respectively, between the RT-iiPCR assay and composite results from the reference RT-qPCR assays. Overall, the concurrence between the ZIKV RT-iiPCR and the reference RT-qPCR assays was 92% (k = 0.83). CONCLUSIONS: The ZIKV RT-iiPCR has a performance comparable to the reference CDC and PAHO RT-qPCR assays but provides much faster results (~1.5 h) with a field-deployable system that can be utilized as a PON diagnostic with the potential to significantly improve the quality of the health care system in vulnerable areas. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-017-2852-4) contains supplementary material, which is available to authorized users.