title: Clinical features of three avian influenza H7N9 virus‐infected patients in Shanghai

text: INTRODUCTION: Since February 2013, a novel reassortant H7N9 virus associated with human deaths, but no apparent outbreaks in poultry and wild birds has emerged in eastern China. OBJECTIVES: The potential reemergence of H7N9 during next year's influenza season demand a further understanding of this important disease. METHODS: Between March 1 and April 30, 2013, we obtained and analyzed clinical, epidemiologic and radiologic features, and virologic data from three laboratory‐confirmed patients of A H7N9 infection admitted in Shanghai Ruijin Hospital. RESULTS: All patients were middle to old aged (mean age 62 years) and overweight (mean body mass index 31) patients. Two patients were exposed to poultry directly or indirectly in food market. They presented with fever and rapidly progressive pneumonia that did not respond to antibiotics. Time between onset of symptoms and onset of respiratory failure (days) were 7–11 days. Two patients presented secondary invasive bacterial infections. All patients died on day 7 to day 86 after the onset of symptoms. CONCLUSIONS: Cross species poultry‐to‐person transmission of this new reassortant avian influenza H7N9 virus can result in severe and fatal respiratory disease like acute respiratory distress syndrome (ARDS) in humans. Reduplicate chest imaging examination is suggested for risky patients with fever and dyspnea. Secondary invasive bacterial infections and pneumothorax can cause severe and fatal consequence. Old age, obesity and presence of comorbidity may be associated with increased mortality. Pulmonary fibrosis can be seen at late stage of the disease.


Is susceptibility to severe COVID‐19 disease an inborn error of metabolism?


Severity of cardiovascular diseases during the COVID-19 pandemic: A letter in response to the article entitled “One train may hide another: Acute cardiovascular diseases could be neglected because of the COVID-19 pandemic.” by Huet et al


title: Non-autophagic roles of autophagy-related proteins

text: Autophagy and autophagy-related processes are fundamentally important in human health and disease. These processes are viewed primarily as cellular degradative pathways that recycle macromolecules and dysfunctional or redundant organelles into amino acids, sugars and lipids, especially during starvation. However, the ubiquitin-like autophagy proteins and other components of the autophagic machinery additionally participate in cellular reprogramming. We highlight these non-autophagic roles of autophagy proteins with the aim of drawing attention to this growing, but unexplored, research topic. We focus on the non-autophagic functions of autophagy proteins in cell survival and apoptosis, modulation of cellular traffic, protein secretion, cell signalling, transcription, translation and membrane reorganization.


title: 2009 H1N1 influenza infection in Korean healthcare personnel

text: Healthcare personnel (HCP) can acquire influenza and transmit it to patients and other hospital staff. The aim of this study was to evaluate the attack rate of HCP by the 2009 H1N1 influenza virus during the 2009 pandemic influenza season in Korea. HCP infected with H1N1 virus were asked to fill out a questionnaire, which included job type, method of diagnosis, facility type, history of contact with patients infected by H1N1 virus, vaccination status, and use of personal protective equipment. A total of 328 HCP (female 68.6%, 225/328) were infected with H1N1 virus at the nine study centers. The highest attack rate was in physicians, followed by nurses and nurses’ aides. Transmission occurred primarily after contact with outpatients (27.8%), followed by contact with inpatients (21.6%). Most (77.3%) of the infected HCP never used an N95 mask during contact with patients. Surgical masks were always used by 29.4% of the subjects and usually or intermittent used by 46.9%. The peak incidence of the H1N1 infection among HCP preceded that among the general population. Among HCPs, physicians, nurses, and nurses’ aides were at the greatest risk of H1N1 infection. HCP should be more vigilant and protect themselves with appropriate personal protective equipment during the influenza season.


title: The impact of asymptomatic individuals on the strength of public health interventions to prevent the second outbreak of COVID-19

text: The pandemic of coronavirus disease 2019 (COVID-19) has threatened the social and economic structure all around the world. Generally, COVID-19 has three possible transmission routes, including pre-symptomatic, symptomatic and asymptomatic transmission, among which the last one has brought a severe challenge for the containment of the disease. One core scientific question is to understand the influence of asymptomatic individuals and of the strength of control measures on the evolution of the disease, particularly on a second outbreak of the disease. To explore these issues, we proposed a novel compartmental model that takes the infection of asymptomatic individuals into account. We get the relationship between asymptomatic individuals and critical strength of control measures theoretically. Furthermore, we verify the reliability of our model and the accuracy of the theoretical analysis by using the real confirmed cases of COVID-19 contamination. Our results, showing the importance of the asymptomatic population on the control measures, would provide useful theoretical reference to the policymakers and fuel future studies of COVID-19.


title: Biomedical Research in Times of Emergency: Lessons From History

text: Coronavirus disease 2019 has disrupted the lives of billions of persons worldwide. Emergencies can stimulate substantial investment of resources that catalyze impressive scientific accomplishments but can also lead to false promises and ethical breaches. The authors discuss how history shows the importance of treating early results with caution, because we are only beginning to understand severe acute respiratory syndrome coronavirus 2.


title: Comparative proteomic analysis reveals different responses in porcine lymph nodes to virulent and attenuated homologous African swine fever virus strains

text: African swine fever (ASF) is a pathology of pigs against which there is no treatment or vaccine. Understanding the equilibrium between innate and adaptive protective responses and immune pathology might contribute to the development of strategies against ASFV. Here we compare, using a proteomic approach, the course of the in vivo infection caused by two homologous strains: the virulent E75 and the attenuated E75CV1. Our results show a progressive loss of proteins by day 7 post-infection (pi) with E75, reflecting tissue destruction. Many signal pathways were affected by both infections but in different ways and extensions. Cytoskeletal remodelling and clathrin-endocytosis were affected by both isolates, while a greater number of proteins involved on inflammatory and immunological pathways were altered by E75CV1. 14-3-3 mediated signalling, related to immunity and apoptosis, was inhibited by both isolates. The implication of the Rho GTPases by E75CV1 throughout infection is also evident. Early events reflected the lack of E75 recognition by the immune system, an evasion strategy acquired by the virulent strains, and significant changes at 7 days post-infection (dpi), coinciding with the peak of infection and the time of death. The protein signature at day 31 pi with E75CV1 seems to reflect events observed at 1 dpi, including the upregulation of proteosomal subunits and molecules described as autoantigens (vimentin, HSPB1, enolase and lymphocyte cytosolic protein 1), which allow the speculation that auto-antibodies could contribute to chronic ASFV infections. Therefore, the use of proteomics could help understand ASFV pathogenesis and immune protection, opening new avenues for future research. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13567-018-0585-z) contains supplementary material, which is available to authorized users.


title: Envelope glycoprotein interactions in coronavirus assembly

text: Coronaviruses are assembled by budding into smooth membranes of the intermediate ER-to-Golgi compartment. We have studied the association of the viral membrane glycoproteins M and S in the formation of the virion envelope. Using coimmunoprecipitation analysis we demonstrated that the M and S proteins of mouse hepatitis virus (MHV) interact specifically forming heteromultimeric complexes in infected cells. These could be detected only when the detergents used for their solubilization from cells or virions were carefully chosen: a combination of nonionic (NP-40) and ionic (deoxycholic acid) detergents proved to be optimal. Pulse-chase experiments revealed that newly made M and S proteins engaged in complex formation with different kinetics. Whereas the M protein appeared in complexes immediately after its synthesis, newly synthesized S protein did so only after a lag phase of > 20 min. Newly made M was incorporated into virus particles faster than S, which suggests that it associates with preexisting S molecules. Using the vaccinia virus T7-driven coexpression of M and S we also demonstrate formation of M/S complexes in the absence of other coronaviral proteins. Pulse-chase labelings and coimmunoprecipitation analyses revealed that M and S associate in pre-Golgi membranes because the unglycosylated form of M appeared in M/S complexes rapidly. Since no association of M and S was detected when protein export from the ER was blocked by brefeldin A, stable complexes most likely arise in the ER-to-Golgi intermediate compartment. Sucrose velocity gradient analysis showed the M/S complexes to be heterogeneous and of higher order, suggesting that they are maintained by homo- and heterotypic interactions. M/S complexes colocalized with alpha-mannosidase II, a resident Golgi protein. They acquired Golgi-specific oligosaccharide modifications but were not detected at the cell surface. Thus, the S protein, which on itself was transported to the plasma membrane, was retained in the Golgi complex by its association with the M protein. Because coronaviruses bud at pre-Golgi membranes, this result implies that the envelope glycoprotein complexes do not determine the site of budding. Yet, the self-association of the MHV envelope glycoproteins into higher order complexes is indicative of its role in the sorting of the viral membrane proteins and in driving the formation of the viral lipoprotein coat in virus assembly.


title: Cloning, expression, and antiviral activity of interferon β from the Chinese microbat, Myotis davidii

text: Bats are natural reservoir hosts for many viruses that produce no clinical symptoms in bats. Therefore, bats may have evolved effective mechanisms to control viral replication. However, little information is available on bat immune responses to viral infection. Type I interferon (IFN) plays a key role in controlling viral infections. In this study, we report the cloning, expression, and biological activity of interferon β (IFNβ) from the Chinese microbat species, Myotis davidii. We demonstrated the upregulation of IFNB and IFN-stimulated genes in a kidney cell line derived from M. davidii after treatment with polyI:C or infection with Sendai virus. Furthermore, the recombinant IFNβ inhibited vesicular stomatitis virus and bat adenovirus replication in cell lines from two bat species, M. davidii and Rhinolophus sinicus. We provide the first in vitro evidence of IFNβ antiviral activity in microbats, which has important implications for virus interactions with these hosts. [Image: see text]


title: Chapter 4 Social Media and Health Crisis Communication During Epidemics

text: Abstract Reacting to public health threats as early as possible is crucial in preventing harm from large population groups. Surveillance systems support the management and early detection of disease activity. Besides traditional systems that rely on reported diagnoses from laboratories, electronic media and discussion groups are increasingly recognized as valuable sources of public health alerts. Beyond, crisis communication increasingly relies upon online communication for exchanging information and opinions on a crisis and for supporting the coordination of resources including equipment, personnel, and information during a crisis situation. This chapter gives an overview on social media tools and data sources and their content with respect to a use in disease surveillance and health crisis management. We further provide an overview on approaches to disease surveillance using the Web and analyze their strengths and weaknesses. Ethical and legal aspects to be considered during implementation of web-based disease surveillance will be presented.


title: Interferon-induced transmembrane protein-3 genetic variant rs12252-C is associated with disease severity in COVID-19

text: A major unanswered question in the current global COVID-19 outbreak is why a small minority of infected individuals develop severe disease. Here we report that homozygosity for the C allele of rs12252 in the interferon-induced transmembrane protein 3 (IFITM3) gene is associated with more severe disease in an age dependent manner. This supports a role for IFITM3 in disease pathogenesis and the opportunity for early targeted intervention in at risk individuals.


title: Internal quality assurance in diagnostic microbiology: A simple approach for insightful data

text: Given the importance of microbiology results on patient care, high quality standards are expected. Internal quality assurance (IQA) could mitigate the limitations of internal quality control, competency assessment and external quality assurance, adding a longitudinal insight, including pre- and post-analytical steps. Here, we implemented an IQA program in our clinical microbiology facilities with blind resubmission of routine samples during 22 months. One-hundred-and-twenty-one out of 123 (98.4%) serological analyses and 112 out of 122 (91.8%) molecular analyses were concordant. Among the discordances in molecular biology analyses, 6 results were low positive samples that turned out negative, likely due to stochastic repartition of nucleic acids. Moreover, one identified retranscription error led us to implement automated results transmission from the Applied Biosystems instruments to the laboratory information system (LIS). Regarding Gram stain microscopy, 560 out of 745 (75.2%) of compared parameters were concordant. As many as 67 out of 84 (79.8%) pairs of culture results were similar, including 16 sterile pairs, 27 having identical identification or description and semi-quantification and 24 only showing variations in semi-quantification with identical description or identification of colonies. Seventeen pairs had diverging identification or description of colonies. Culture was twice only done for one member of the pairs. Regarding antibiotic susceptibility testing, a major discrepancy was observed in 5 out of 48 results (10.4%). In conclusion, serological tests were highly reproducible. Molecular diagnosis also revealed to be robust except when the amounts of nucleic acids present in the sample were close to the limits of detection. Conventional microbiology was less robust with major discrepancies reaching 39.5% of the samples for microscopy. Similarly, culture and antibiotic susceptibility testing were prone to discrepancies. This work was ground for reconsidering multiples aspects of our practices and demonstrates the importance of IQA to complete the other quality management procedures.


title: The nucleolus – a gateway to viral infection?

text: A number of viruses and viral proteins interact with a dynamic sub-nuclear structure called the nucleolus. The nucleolus is present during interphase in mammalian cells and is the site of ribosome biogenesis, and has been implicated in controlling regulatory processes such as the cell cycle. Viruses interact with the nucleolus and its antigens; viral proteins co-localise with factors such as nucleolin, B23 and fibrillarin, and can cause their redistribution during infection. Viruses can use these components as part of their replication process, and also use the nucleolus as a site of replication itself. Many of these properties are not restricted to any particular type of virus or replication mechanism, and examples of these processes can be found in DNA, RNA and retroviruses. Evidence suggests that viruses may target the nucleolus and its components to favour viral transcription, translation and perhaps alter the cell cycle in order to promote virus replication. Autoimmunity to nucleolin and fibrillarin have been associated with a number of diseases, and by targeting the nucleolus and displacing nucleolar antigens, virus infection might play a role in the initiation of these conditions.


title: Bats in urban areas of Brazil: roosts, food resources and parasites in disturbed environments

text: Urbanization is a widespread intense land use that generally results in biodiversity decline. Among the taxa capable to adapt to urban landscapes, bats are particularly ubiquitous. Brazil has one of the world’s largest diversity of bat species and one of the highest urbanization rates of the world. Yet, few studies have synthesized the biology of bats in urban environments, especially in Brazil. To fill this gap, we systematically reviewed the published scientific literature on the bat fauna found in urban areas of Brazil. The knowledge of urban bats is still incipient and heterogeneously spatially distributed, mostly concentrated in the southeastern region of the country. The assembled list of 84 urban species, of which nineteen are new species records for urban areas (including one new family), represents 47% of the bat richness registered in the country. Thirty-one bat species (37%) were captured exclusively inside forest fragments. Moreover, we provide information on the resources used within the urban matrix by summarizing the roosting sites for 38 bat species, as well as 31 plants consumed by at least twelve bat species. Regarding parasitological aspects, we listed eleven zoonotic parasites hosted by 27 bat species and discussed their potential to become a public health threat. Likewise, we considered the different features linked to urbanization, including impacts on immunity, body condition and susceptibility to acquiring parasites, as possible bat conservation issues. Finally, we defined an agenda for bat studies in urban areas of Brazil. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11252-016-0632-3) contains supplementary material, which is available to authorized users.


4 General Systemic States


title: Trigger factor assisted soluble expression of recombinant spike protein of porcine epidemic diarrhea virus in Escherichia coli

text: BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric pathogen of swine. The spike glycoprotein (S) of PEDV is the major immunogenic determinant that plays a pivotal role in the induction of neutralizing antibodies against PEDV, which therefore is an ideal target for the development of subunit vaccine. In an attempt to develop a subunit vaccine for PEDV, we cloned two different fragments of S protein and expressed as glutathione S-transferase (GST)-tagged fusion proteins, namely rGST-COE and rGST-S1D, in E.coli. However, the expression of these recombinant protein antigens using a variety of expression vectors, strains, and induction conditions invariably resulted in inclusion bodies. To achieve the soluble expression of recombinant proteins, several chaperone co-expression systems were tested in this study. RESULTS: We firstly tested various chaperone co-expression systems and found that co-expression of trigger factor (TF) with recombinant proteins at 15 °C was most useful in soluble production of rGST-COE and rGST-S1D compared to GroEL-ES and DnaK-DnaJ-GrpE/GroEL-ES systems. The soluble rGST-COE and rGST-S1D were purified using glutathione Sepharose 4B with a yield of 7.5 mg/l and 5 mg/l, respectively. Purified proteins were detected by western blot using mouse anti-GST mAb and pig anti-PEDV immune sera. In an indirect ELISA, purified proteins showed immune reactivity with pig anti-PEDV immune sera. Finally, immunization of mice with 10 μg of purified proteins elicited highly potent serum IgG and serum neutralizing antibody titers. CONCLUSIONS: In this study, soluble production of recombinant spike protein of PEDV, rGST-COE and rGST-S1D, were achieved by using TF chaperone co-expression system. Our results suggest that soluble rGST-COE and rGST-S1D produced by co-expressing chaperones may have the potential to be used as subunit vaccine antigens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12896-016-0268-7) contains supplementary material, which is available to authorized users.


title: Cryptic transmission of SARS-CoV-2 in Washington State

text: Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread throughout the world. On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Genome sequencing of SARS-CoV-2 strains allows for the reconstruction of transmission history connecting these infections. Here, we analyze 346 SARS-CoV-2 genomes from samples collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We found that the large majority of SARS-CoV-2 infections sampled during this time frame appeared to have derived from a single introduction event into the state in late January or early February 2020 and subsequent local spread, strongly suggesting cryptic spread of COVID-19 during the months of January and February 2020, before active community surveillance was implemented. We estimate a common ancestor of this outbreak clade as occurring between 18 January and 9 February 2020. From genomic data, we estimate an exponential doubling between 2.4 and 5.1 days. These results highlight the need for large-scale community surveillance for SARS-CoV-2 introductions and spread and the power of pathogen genomics to inform epidemiological understanding.


title: Hepatic sinusoidal-obstruction syndrome and busulfan-induced lung injury in a post-autologous stem cell transplant recipient

text: Veno-occlusive disease of the liver is mostly encountered as a complication of hematopoietic stem cell transplantation with myeloablative regimens with an incidence estimated to be 13.7%. It is clinically characterized by tender hepatomegaly, jaundice, weight gain and ascites. Strong clinical suspicion and an early recognition of clinical signs are essential to establish the diagnosis and institute effective regimen. Another complication of cytotoxic drugs given for cancers, is development of busulfan-induced lung injury. A strong index of suspicion is needed for its diagnosis, especially in setting where opportunistic fungal and viral infections manifest similarly. We illustrate the clinical and autopsy finings in a 2½-year-old boy who received autologous stem-cell transplantation following resection of stage IV neuroblastoma. He subsequently developed both hepatic veno-occlusive disease and busulfan-induced lung injury. The autopsy findings are remarkable for their rarity.


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title: A multi-faceted approach of a nursing led education in response to MERS-CoV infection

text: Abstract Background The emergence of the Middle East respiratory syndrome-coronavirus (MERS-CoV) resulted in multiple healthcare associated outbreaks. In response, we developed a nurse-led program to screen and triage patients with MERS-CoV infection. Methods A formal educational program was implemented to ensure a standardized approach to care planning and delivery. The essential skills that were included were the use of Personal Protective Equipment (PPE) including gown, gloves, head cover and N95 mask, hand hygiene, the practice of donning and doffing and the collection of MERS-CoV nasopharyngeal specimens. Results A core group of nurses were identified from high-risk units. The education program consisted of four skill-days. Nurses were assigned a pre-course work from Mosby’s Nursing Skills, an online skill module, donning and doffing of PPE, and the process for obtaining a nasopharyngeal swab. The skill lab incorporated multiple methods such group discussion, watching an on-line video, and a simulated demonstration and practice on a mannequin. In total, 450 nurses attended the Nasopharyngeal Skills Day and 1000 nurses received training. Donning and doffing PPE and N95 mask fit testing has become an annual mandatory competency requirement for staff in nursing and clinical services. Conclusion The application of specified protocols minimizes the risks of cross infection, placing emphasis on patient and staff safety as well as expediting the patient to definitive treatment. Nurse educators have an instrumental role in training nurses and other healthcare providers on the specifics needed to identify, contain and manage patient presenting with MERS-CoV.


title: Risk estimation of infectious diseases determines the effectiveness of the control strategy

text: Abstract Usually, whether to take vaccination or not is a voluntary decision, which is determined by many factors, from societal factors (such as religious belief and human rights) to individual preferences (including psychology and altruism). Facing the outbreaks of infectious diseases, different people often have different estimations on the risk of infectious diseases. So, some persons are willing to vaccinate, but other persons are willing to take risks. In this paper, we establish two different risk assessment systems using the technique of dynamic programming, and then compare the effects of the two different systems on the prevention of diseases on complex networks. One is that the perceived probability of being infected for each individual is the same (uniform case). The other is that the perceived probability of being infected is positively correlated to individual degrees (preferential case). We show that these two risk assessment systems can yield completely different results, such as, the effectiveness of controlling diseases, the time evolution of the number of infections, and so on.


title: Antimalarial Activity of 4-Metoxychalcones: Docking Studies as Falcipain/Plasmepsin Inhibitors, ADMET and Lipophilic Efficiency Analysis to Identify a Putative Oral Lead Candidate

text: Herein, we report the antimalarial activity of nine 4-methoxychalcone derivatives 1a–i and an initial analysis of their ADMET properties. All compounds showed potent activity against the P. falciparum chloroquine-resistant clone W2, with IC(50) values ranging from 1.96 µM to 10.99 µM, with moderate or low cytotoxicity against the HeLa cell line. The compound 1a (IC(50) = 2.06 µM) had the best selectivity index (9.0). All the sulfonamide 4-metychalcone derivatives synthesized had cLogP values between 2 and 5 (mean value 3.79) and molecular weights (MWs) below 500. The substitution of the pyrrolidine group in 1i by a morpholine group in 1a reduced the cLogP value from 3.05 in compound 1i to 2.34 in compound 1a. Indeed, compound 1a had the highest LipE value. The binding free energy of compound 1a showed it to be the most optimal chalcone derivative for plasmepsin-2 (−7.3 Kcal/mol). The physicochemical properties and LipE analysis of the dataset allowed us to establish that compound 1a is the highest quality compound of the series and a potential oral lead candidate.


title: C-type lectin receptors and RIG-I-like receptors: new points on the oncogenomics map

text: The group of pattern recognition receptors includes families of Toll-like receptors, NOD-like receptors, C-type lectin receptors, and RIG-I-like receptors. They are key sensors for a number of infectious agents, some of which are oncogenic, and they launch an immune response against them, normally promoting their eradication. Inherited variations in genes encoding these receptors and proteins and their signaling pathways may affect their function, possibly modulating cancer risk and features of cancer progression. There are numerous studies investigating the association of single nucleotide polymorphisms within or near genes encoding Toll-like receptors and NOD-like receptors, cancer risk, and features of cancer progression. However, there is an almost total absence of articles analyzing the correlation between polymorphisms of genes encoding C-type lectin receptors and RIG-I-like receptors and cancer risk or progression. Nevertheless, there is some evidence supporting the hypothesis that inherited C-type lectin receptor and RIG-I-like receptor variants can be associated with increased cancer risk. Certain C-type lectin receptors and RIG-I-like receptors recognize pathogen-associated molecular patterns of potentially oncogenic infectious agents, and certain polymorphisms of genes encoding C-type lectin receptors and RIG-I-like receptors may have functional consequences at the molecular level that can lead to association of such single nucleotide polymorphisms with risk or progression of some diseases that may modulate cancer risk, so these gene polymorphisms may affect cancer risk indirectly. Polymorphisms of genes encoding C-type lectin receptors and RIG-I-like receptors thereby may be correlated with a risk of lung, oral, esophageal, gastric, colorectal, and liver cancer, as well as nasopharyngeal carcinoma, glioblastoma, multiple myeloma, and lymphoma. The list of the most promising polymorphisms for oncogenomic investigations may include rs1926736, rs2478577, rs2437257, rs691005, rs2287886, rs735239, rs4804803, rs16910526, rs36055726, rs11795404, and rs10813831.


title: Why are vaccines against many human viral diseases still unavailable; an historic perspective?

text: The number of new and improved human viral vaccines licensed in recent years contrasts sharply with what could be termed the golden era (1955‐1990) when vaccines against polio‐, measles, mumps, rubella, and hepatitis B viruses first became available. Here, we attempt to explain why vaccines, mainly against viruses other than human immunodeficiency virus and hepatitis C virus, are still unavailable. They include human herpesviruses other than varicella‐zoster virus, respiratory syncytial and most other respiratory, enteric and arthropod‐borne viruses. Improved oral poliovirus vaccines are also urgently required. Their unavailability is attributable to regulatory/economic factors and the properties of individual viruses, but also to an absence of relevant animal models and ethical problems for the conduct of clinical of trials in pediatric and other critical populations. All are portents of likely difficulties for the licensing of effective vaccines against emerging pathogens, such as avian influenza, Ebola, and Zika viruses.


title: Efficacy of slit lamp breath shields

text: PURPOSE: To evaluate the efficacy of slit lamp breath shields to prevent droplet spray from a simulated sneeze. DESIGN: Experimental study to test effectiveness of personal protective equipment. METHODS: The nozzle of a spray gun was adjusted to angularly disperse a mist of colored dye that approximated a patient sneezing on a dimensionally accurate cardboard slit lamp model. We tested the designs of six commercially available breath shields, and one breath shield repurposed from a plastic container lid. Each breath shield was sprayed in a standardized fashion three times and the amount of overspray compared with no shield was quantified. The surface area that was sprayed was calculated using Adobe Photoshop’s color range function. The average percentage of overspray of each breath shield was computed in comparison to the control. RESULTS: The breath shields ranged in surface area from 116-1254 cm(2) and the amount of overspray varied from 54% to virtually none. Larger breath shields offered better protection than smaller ones. Breath shields attached to the objective lens arm were a better barrier than those hung by the oculars of comparable size. A repurposed plastic lid breath shield was 513cm(2), was slightly curved toward the examiner’s face, and allowed only 2% overspray. The largest breath shield (1254 cm(2)) hung near the oculars and prevented essentially all the overspray. CONCLUSION: The performance of different designs of breath shields is variable. Even high functioning shields should be used in conjunction with personal protective equipment including masks, goggles and gloves, and handwashing. Ideally patients should also wear a cloth mask during all slit lamp exams.


title: Should we expect neurological symptoms in the SARS-CoV-2 epidemic?

text: Abstract Introduction There is growing evidence that SARS-CoV-2 can gain access to the central nervous system (CNS). We revise the literature on coronavirus infection of the CNS associated with neurological diseases. Development Neurological symptoms were rarely reported in the SARS-CoV and MERS-CoV epidemics, although isolated cases were described. There are also reports of cases of neurological symptoms associated with CoV-OC43 and CoV-229E infection. The presence of neurological lesions, especially demyelinating lesions in the mouse hepatitis virus model, may explain the mechanisms by which coronaviruses enter the CNS, particularly those related with the immune response. This may explain the presence of coronavirus in patients with multiple sclerosis. We review the specific characteristics of SARS-CoV-2 and address the question of whether the high number of cases may be associated with greater CNS involvement. Conclusion Although neurological symptoms are not frequent in coronavirus epidemics, the high number of patients with SARS-CoV-2 infection may explain the presence of the virus in the CNS and increase the likelihood of early- or delayed-onset neurological symptoms. Follow-up of patients affected by the SARS-CoV-2 epidemic should include careful assessment of the CNS.


title: High incidence of rhinovirus infection in children with community‐acquired pneumonia from a city in the Brazilian pre‐Amazon region

text: Community‐acquired pneumonia (CAP) is the leading cause of child death worldwide. Viruses are the most common pathogens associated with CAP in children, but their incidence varies greatly. This study investigated the presence of respiratory syncytial virus (RSV), adenovirus, human rhinovirus (HRV), human metapneumovirus (HMPV), human coronavirus (HCoV‐OC43 and HCoV‐NL63), and influenza A virus (FluA) in children with CAP and the contributing risk factors. Here, children with acute respiratory infections were screened by pediatrics; and a total of 150 radiographically‐confirmed CAP patients (aged 3 months to 10 years) from two clinical centers in Sao Luis, Brazil were recruited. Patient's clinical and epidemiological data were recorded. Nasopharyngeal swab and tracheal aspirate samples were collected to extract viral nucleic acid. RSV, adenovirus, rhinovirus, FluA, HMPV, HCoV‐OC43, and HCoV‐NL63 were detected by real‐time polymerase chain reaction. The severe CAP was associated with ages between 3 and 12 months. Viruses were detected in 43% of CAP patients. Rhinovirus infections were the most frequently identified (68%). RSV, adenovirus, FluA, and coinfections were identified in 14%, 14%, 5%, and 15% of children with viral infection, respectively. Rhinovirus was associated with nonsevere CAP (P = .014); RSV, FluA, and coinfections were associated with severe CAP (P < .05). New strategies for prevention and treatment of viral respiratory infections, mainly rhinovirus and RSV infections, are necessary.


title: Biochip sensors for the rapid and sensitive detection of viral disease

text: Recent advances in DNA and protein microarray methodology and the emerging technology of cell-based sensors have massively increased the speed and sensitivity with which we can detect viral infections. The advantages of the multi-parameter microarray technologies could be combined with the speed and sensitivity of cell-based systems to give 'cell-omic' sensors.


title: Recommandations de la SOFFCO-MM en vue de la reprise de l’activité de chirurgie bariatrique et métabolique pendant et après la pandémie covid-19

text: Resumen Face à l’émergence de la pandémie à COVID 19, l’activité de chirurgie bariatrique/métabolique a été arrêtée. Le confinement et l’arrêt de cette chirurgie ont eu un impact sous-estimé sur la population obèse avec prise de poids, et aggravation des comorbidités. Un certain nombre de candidats à cette chirurgie sont exposés à un risque important de mortalité liée à la pandémie. En effet, l’obésité et le diabète sont deux facteurs de risque majeurs de forme grave d’infection à COVID-19. Le seul traitement efficace actuel de l’obésité est la chirurgie métabolique avec un bénéfice rapide et durable. Il parait donc nécessaire de reprendre une activité de chirurgie métabolique Le but de ce travail est de hiérarchiser la reprise chirurgicale afin qu’elle soit progressive et cohérente. Les organigrammes proposés aideront les centres à déterminer les patients prioritaires selon la balance bénéfice-risque. Le diabète a une place centrale dans l’arbre décisionnel. Les modalités de reprise seront variables d’un centre à l’autre selon les ressources humaines, matérielles et médicamenteuses, et seront à adapter à l’évolution épidémique. Un consentement éclairé spécifique sera nécessaire. Un dépistage chez les patients obèses est à envisager dont les modalités de dépistage sont élaborées sur la base des connaissances disponibles. En cas de suspicion de COVID, la chirurgie doit être différée. Il faut insister sur les mesures et gestes barrières afin de protéger le patient et le personnel soignant. Un confinement est fortement suggéré pour le patient durant le premier mois postopératoire. Le suivi des patients sera effectué de préférence par téléconsultation. Abstract Bariatric/metabolic surgery was paused during the Covid-19 pandemic. The impact of social confinement and the interruption of this surgery on the population with obesity has been underestimated, with weight gain and worsened comorbidities. Some candidates for this surgery are exposed to a high risk of mortality linked to the pandemic. Obesity and diabetes are two major risk factors for severe forms of Covid-19. The only currently effective treatment for obesity is metabolic surgery, which confers prompt, lasting benefits. It is thus necessary to resume such surgery. To ensure that this resumption is both gradual and well-founded, we have devised a priority ranking plan. The flow charts we propose will help centres to identify priority patients according to a benefit/risk assessment. Diabetes holds a central place in the decision tree. Resumption patterns will vary from one centre to another according to human, physical and medical resources, and will need adjustment as the epidemic unfolds. Specific informed consent will be required. Screening of patients with obesity should be considered, based on available knowledge. If Covid-19 is suspected, surgery must be postponed. Emphasis must be placed on infection control measures to protect patients and healthcare professionals. Confinement is strongly advocated for patients for the first month post-operatively. Patient follow-up should preferably be by teleconsultation.


title: Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2

text: BACKGROUND: The pneumonia caused by the 2019 novel coronavirus (SARS-CoV-2, also called 2019-nCoV) recently break out in Wuhan, China, and was named as COVID-19. With the spread of the disease, similar cases have also been confirmed in other regions of China. We aimed to report the imaging and clinical characteristics of these patients infected with SARS-CoV-2 in Guangzhou, China. METHODS: All patients with laboratory-identified SARS-CoV-2 infection by real-time polymerase chain reaction (PCR) were collected between January 23, 2020, and February 4, 2020, in a designated hospital (Guangzhou Eighth People’s Hospital). This analysis included 90 patients (39 men and 51 women; median age, 50 years (age range, 18–86 years). All the included SARS-CoV-2-infected patients underwent non-contrast enhanced chest computed tomography (CT). We analyzed the clinical characteristics of the patients, as well as the distribution characteristics, pattern, morphology, and accompanying manifestations of lung lesions. In addition, after 1–6 days (mean 3.5 days), follow-up chest CT images were evaluated to assess radiological evolution. FINDINGS: The majority of infected patients had a history of exposure in Wuhan or to infected patients and mostly presented with fever and cough. More than half of the patients presented bilateral, multifocal lung lesions, with peripheral distribution, and 53 (59%) patients had more than two lobes involved. Of all included patients, COVID-19 pneumonia presented with ground glass opacities in 65 (72%), consolidation in 12 (13%), crazy paving pattern in 11 (12%), interlobular thickening in 33 (37%), adjacent pleura thickening in 50 (56%), and linear opacities combined in 55 (61%). Pleural effusion, pericardial effusion, and lymphadenopathy were uncommon findings. In addition, baseline chest CT did not show any abnormalities in 21 patients (23%), but 3 patients presented bilateral ground glass opacities on the second CT after 3–4 days. CONCLUSION: SARS-CoV-2 infection can be confirmed based on the patient’s history, clinical manifestations, imaging characteristics, and laboratory tests. Chest CT examination plays an important role in the initial diagnosis of the novel coronavirus pneumonia. Multiple patchy ground glass opacities in bilateral multiple lobular with periphery distribution are typical chest CT imaging features of the COVID-19 pneumonia.


title: Extracorporeal membrane oxygenation for severe Middle East respiratory syndrome coronavirus

text: BACKGROUND: Middle East respiratory syndrome (MERS) is caused by a coronavirus (MERS‐CoV) and is characterized by hypoxemic respiratory failure. The objective of this study is to compare the outcomes of MERS-CoV patients before and after the availability of extracorporeal membrane oxygenation (ECMO) as a rescue therapy in severely hypoxemic patients who failed conventional strategies. METHODS: We collected data retrospectively on MERS-CoV patients with refractory respiratory failure from April 2014 to December 2015 in 5 intensive care units (ICUs) in Saudi Arabia. Patients were classified into two groups: ECMO versus conventional therapy. Our primary outcome was in-hospital mortality; secondary outcomes included ICU and hospital length of stay. RESULTS: Thirty-five patients were included; 17 received ECMO and 18 received conventional therapy. Both groups had similar baseline characteristics. The ECMO group had lower in-hospital mortality (65 vs. 100%, P = 0.02), longer ICU stay (median 25 vs. 8 days, respectively, P < 0.01), and similar hospital stay (median 41 vs. 31 days, P = 0.421). In addition, patients in the ECMO group had better PaO2/FiO2 at days 7 and 14 of admission to the ICU (124 vs. 63, and 138 vs. 36, P < 0.05), and less use of norepinephrine at days 1 and 14 (29 vs. 80%; and 36 vs. 93%, P < 0.05). CONCLUSIONS: ECMO use, as a rescue therapy, was associated with lower mortality in MERS patients with refractory hypoxemia. The results of this, largest to date, support the use of ECMO as a rescue therapy in patients with severe MERS-CoV.


docid: ugrgmuds

title: Starting a Biologic Therapy in IBD Patients Amid COVID-19: Hold, Careful Monitoring, or Testing?


title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory

text: Introduction. Middle East respiratory syndrome coronavirus was first recognized in September 2012 in Saudi Arabia. The clinical presentations of MERS and non-MERS SARI are often similar. Therefore, the identification of suspected cases that may have higher chances of being diagnosed as cases of MERS-CoV is essential. However, the real challenge is to flag these patients through some demographic markers. The nature of these markers has not previously been investigated in Saudi Arabia, and hence, this study aims to identify them. METHODS: It was a surveillance system-based study, for which data from a total of 23,646 suspected patients in Riyadh and Al Qassim regions were analyzed from January 2017 until December 2017 to estimate the prevalence of MERS-CoV among suspected cases and to determine potential demographic risk factors related to the confirmation of the diagnosis. RESULTS: Of 23,646 suspected cases, 119 (0.5%) were confirmed by laboratory results. These confirmed cases (67.2% of which were males) had a mean age of 43.23 years (SD ± 22.8). Around 42.2% of the confirmed cases were aged between 41 and 60 years and about 47% of confirmed cases had their suspected specimen tested in the summer. The study identified three significant and independent predictors for confirmation of the disease: an age between 41 and 60 years, male gender, and summer season admission. CONCLUSION: The study provides evidence that the MERS-CoV epidemic in the subject regions has specific characteristics that might help future plans for the prevention and management of such a contagious disease. Future studies should aim to confirm such findings in other regions of Saudi Arabia as well and explore potential preventable risk factors.


title: Descriptive epidemiology of morbidity and mortality in Minnesota dairy heifer calves

text: Abstract A prospective study was carried out on 845 heifer calves born during 1991 on 30 Holstein dairy farms in southeast Minnesota. The objectives of the study were to describe the epidemiology of morbidity and mortality in dairy calves from birth to 16 weeks of age (with an emphasis on respiratory disease), to examine individual calf and herd management practices as risk factors for calf morbidity and mortality, and to validate producer diagnosis of mortality. Incidence rates for all morbidity, enteritis, and pneumonia were 0.20, 0.15, and 0.10 cases per 100 calf-days at risk for the period of the study. Risk of enteritis was highest in the first 3 weeks of life, with pneumonia risk highest at 10 weeks of age. Case fatality rates averaged 11.8%, 17.9%, and 9.4% for all diagnoses, enteritis, and pneumonia, respectively. Average daily rates of gain from birth to 16 weeks of age differed between farms that had inadequate calf housing (0.8 kg day−1) versus those with adequate calf housing (1.0 kg day−1). Approximately half of the calves in the cohort (418) had blood samples taken monthly from birth until 16 weeks of age. Of the calves sampled, only 19 calves showed a four-fold rise in serum titers to respiratory viruses. Sixteen calves seroconverted to BVDV, two calves to IBRV, and one calf to PI3 virus. Of 98 calves less than 10 days of age tested for adequacy of passive transfer, 35 (35.7%) had serum immunoglobulin levels of less than 800 mg dl−1. There were no significant differences in mortality or morbidity between calves that had adequate passive transfer and those that did not. The incidence of mortality was 0.08 deaths per 100 calf-days at risk; 64 calves died during the 16 months of the study. The risk of death was highest at 2 weeks of age. Enteritis was the most common cause of death (28 deaths, 44% of all deaths) followed by pneumonia (19 deaths, 30% of all deaths). Comparing producer diagnosis of mortality with necropsy results yielded sensitivities of 58.3% and 56% and specificities of 93% and 100% for producer diagnoses of enteritis and pneumonia, respectively. The kappa statistic comparing producer diagnosis with necropsy result was 0.47. The most common pathogens isolated from calves that died of enteritis were rotavirus (five calves), and Escherichia coli (four calves). Pathogens isolated from pneumonic lungs included Pasteurella multocida (three calves), Haemophilus somnus (three calves), and Pasteurella haemolytica (one calf).


title: Challenge-driven design for public housing: The case of Hong Kong

text: Abstract Public housing (PH) has existed in Hong Kong for six decades. Previous and current challenges that have been encountered over time function as a collective driver for design progression. However, such challenges have remained under research to be able to draw useful lessons from them. To understand how this established motif can suit the sustainability-conscious era, this study uses Hong Kong as a representative case for sub-tropical compact cities by critiquing its PH design against multiple constraints. The objective of this study is to trace the historical relationships between challenges and design progress as well as to assess current and future implications of sustainability trends on PH design. By synthesizing data from literature, policy documents, and empirical evidence, this research develops an evolution map for PH design in Hong Kong that is driven by seven major challenges. Based on this map, a conceptual framework for intersecting considerations that envisages five main future prospects toward future PH design is also established.


docid: bozgrzvf

title: Exposure to novel coronavirus in patients on renal replacement therapy during the exponential phase of COVID-19 pandemic: survey of the Italian Society of Nephrology

text: BACKGROUND: Between February and April 2020, Italy experienced an overwhelming growth of the COVID-19 pandemic. Little is known, at the country level, where and how patients on renal replacement therapy (RRT) have been mostly affected. METHODS: Survey of the network of Nephrology centers using a simplified 17 items electronic questionnaire designed by Italian Society of Nephrology COVID-19 Research Group. We used spatial epidemiology and geographical information systems to map SARS-CoV-2 spread among RRT patients in Italy. RESULTS: On April 9th 2020, all nephrology centers (n = 454) listed in the DialMap database were invited to complete the electronic questionnaire. Within 11 days on average, 365 centers responded (80.4% response rate; 2.3% margin of error) totaling 60,441 RRT patients. The surveyed RRT population included 30,821 hemodialysis (HD), 4139 peritoneal dialysis (PD), and 25,481 transplanted (Tx) patients respectively. The proportion of SARS-CoV-2 positive RRT patients in Italy was 2.26% (95% CI 2.14–2.39) with significant differences according to treatment modality (p < 0.001). The proportion of patients positive for SARS-CoV-2 was significantly higher in HD (3.55% [95% CI 3.34–3.76]) than PD (1.38% [95% CI 1.04–1.78] and Tx (0.86% [95% CI 0.75–0.98]) (p < 0.001), with substantial heterogeneity across regions and along the latitude gradient (p < 0.001). In RRT patients the highest rate was in the north-west (4.39% [95% CI 4.11–4.68], followed by the north-east (IR 2.06% [1.79–2.36]), the center (0.91% [0.75–1.09]), the main islands (0.67% [0.47–0.93]), and the south (0.59% [0.45–0.75]. During the COVID-19 pandemic, among SARS-Cov-2 positive RRT patients the fatality rate was 32.8%, as compared to 13.3% observed in the Italian population as of April 23rd. CONCLUSIONS: A substantial proportion of the 60,441 surveyed RRT patients in Italy were SARS-Cov-2 positive and subsequently died during the exponential phase of COVID-19 pandemic. Infection risk and rates seems to differ substantially across regions, along geographical latitude, and by treatment modality. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40620-020-00794-1) contains supplementary material, which is available to authorized users.


title: Synthesis of hybrid carbon nanotube structures coated with Sophora flavescens nanoparticles and their application to antimicrobial air filtration

text: Abstract Controlling airborne microorganisms has become increasingly important with increase in human indoor activities, epidemic disease outbreaks, and airborne pathogen transmission. Treatments using antimicrobial nanoparticles have shown promise because of the high surface-to-volume ratio of nanoparticles compared to their bulk counterparts, and their unique physical and chemical properties. In this study, hybrid nanostructures of multi-walled carbon nanotubes (MWCNTs) coated with antimicrobial, natural product (NP) nanoparticles were synthesized using a twin-head electrospray system (THES). The coated nanoparticles were then used in antimicrobial air filters to increase their antimicrobial efficiency. Electrosprayed droplets were converted to NP nanoparticles and MWCNTs through ethanol evaporation. Oppositely charged NP nanoparticles and MWCNTs were coagulated via Coulombic collisions to form hybrid nanoparticles that were deposited continuously onto an air filter medium. The size distribution and composition of the hybrid NP/MWCNT particles were characterized using a wide-range particle spectrometer (WPS) and transmission electron microscope (TEM). The concentration of hybrid NP/MWCNT nanoparticles was lower than that of NP nanoparticles but higher than that of MWCNTs and showed a bimodal size distribution with peak diameters of 21.1 and 49nm. TEM analyses confirmed that the NP nanoparticles were attached to the MWCNT surface with a density of ~4–9 particles/MWCNT. When deposited onto the filter medium, NP/MWCNT particles formed dendrites on the filter׳s fiber surface. The filtration efficiency and pressure drop of the NP/MWCNT-coated filters were higher than those of pristine, NP nanoparticles-coated or MWCNTs-coated filters. The hybrid filter also exhibited stronger antimicrobial activity than those of NP or MWCNT-coated filters at identical deposited volumes (1.1×10–2 cm3/cm2 filter). Ninety-five percent of the tested bacterial aerosols were inactivated on the NP/MWCNTs filter while only <70% were inactivated on NP- or MWCNT-coated filters.


Drop in urban air pollution from COVID-19 pandemic: Policy implications for the megacity of São Paulo()


title: The role of palliative medicine in ICU bed allocation in COVID-19: a joint position statement of the Singapore Hospice Council and the Chapter of Palliative Medicine Physicians

text: Facing the possibility of a surge of COVID-19-infected patients requiring ventilatory support in Intensive Care Units (ICU), the Singapore Hospice Council and the Chapter of Palliative Medicine Physicians forward its position on the guiding principles that ought to drive the allocation of ICU beds and its role in care of these patients and their families.


title: Upper airway inflammatory diseases and bronchial hyperresponsiveness

text: Abstract Inflammatory processes of the upper airway may alter the responsiveness of the lower airway. For example, bronchial hyperresponsiveness may be seen in patients with allergic rhinitis. This could represent coexistent but unrecognized asthma, but also suggests that IgE-dependent inflammation may occur in the lower airway that can increase bronchial hyperresponsiveness without at the same time precipitating obvious obstruction. Clearly, allergic rhinitis is a risk factor for asthma. A second example of the interaction of upper airway inflammation and bronchial hyperreactivity are reports that viral upper respiratory tract infections may cause otherwise healthy persons to respond abnormally to inhaled histamine or irritants for several months after the infections. These same viruses usually precipitate attacks in patients with asthma, who already have hyperresponsive airways. Both of these examples suggest that inflammatory processes occurring totally or primarily in the upper airway may participate in the pathogenesis of lower respiratory tract hyperresponsiveness and asthma.


docid: iclruwmx

title: Infection-mediated asthma: etiology, mechanisms and treatment options, with focus on Chlamydia pneumoniae and macrolides

text: Asthma is a chronic respiratory disease characterized by reversible airway obstruction and airway hyperresponsiveness to non-specific bronchoconstriction agonists as the primary underlying pathophysiology. The worldwide incidence of asthma has increased dramatically in the last 40 years. According to World Health Organization (WHO) estimates, over 300 million children and adults worldwide currently suffer from this incurable disease and 255,000 die from the disease each year. It is now well accepted that asthma is a heterogeneous syndrome and many clinical subtypes have been described. Viral infections such as respiratory syncytial virus (RSV) and human rhinovirus (hRV) have been implicated in asthma exacerbation in children because of their ability to cause severe airway inflammation and wheezing. Infections with atypical bacteria also appear to play a role in the induction and exacerbation of asthma in both children and adults. Recent studies confirm the existence of an infectious asthma etiology mediated by Chlamydia pneumoniae (CP) and possibly by other viral, bacterial and fungal microbes. It is also likely that early-life infections with microbes such as CP could lead to alterations in the lung microbiome that significantly affect asthma risk and treatment outcomes. These infectious microbes may exacerbate the symptoms of established chronic asthma and may even contribute to the initial development of the clinical onset of the disease. It is now becoming more widely accepted that patterns of airway inflammation differ based on the trigger responsible for asthma initiation and exacerbation. Therefore, a better understanding of asthma subtypes is now being explored more aggressively, not only to decipher pathophysiologic mechanisms but also to select treatment and guide prognoses. This review will explore infection-mediated asthma with special emphasis on the protean manifestations of CP lung infection, clinical characteristics of infection-mediated asthma, mechanisms involved and antibiotic treatment outcomes.


docid: kuysgfju

title: Chapter 19 Nanodiagnostics in microbiology and dentistry

text: Abstract Nanotechnology is the engineering of functional systems at the molecular scale. The term “nanotechnology” is now commonly used to refer to the creation of new objects with nanoscale dimensions between 1 and 100nm. Functionalities can be added to nanomaterials by interfacing them with biological molecules or structures. The integration of nanomaterials with biology has led to the development of diagnostic devices, contrast agents, analytical tools, and drug-delivery vehicles. Many diseases that do not have a cure today may be cured by nanotechnology in the future. Nanoscience does have an impact on several areas of microbiology. It allows for the study and visualization at the molecular assembly level of a biological process. More studies are needed to determine the environmental and health risks associated with nanomaterials. The current crossdisciplinary inclinations of dental research groups to the nanotechnological field, altogether with the major investments aimed toward developing the methods to grow tooth structures artificially by soft chemical approaches and to understand the mechanism for remineralization of dental defects at various scales in vivo, certainly present a promising trend. Nevertheless, the pace of application of nanotechnology to dentistry has been less than revolutionary. Scientists believe that nanotechnology could give man a better quality of life, power to prevent diseases, speed up tissue reconstruction, and alter his genetic sequence in the future. “There is plenty of room at the bottom.”


title: Social isolation during the COVID-19 pandemic can increase physical inactivity and the global burden of cardiovascular disease

text: Emerging data indicate a substantial decrease in global physical activity levels during the period of social isolation adopted worldwide to contain the spread of the coronavirus disease 2019 (COVID-19). Confinement-induced decreases in physical activity levels and increases in sedentary behavior may provoke a rapid deterioration of cardiovascular health and premature deaths among populations with increased cardiovascular risk. Even short-term (1–4 wk) inactivity has been linked with detrimental effects in cardiovascular function and structure and increased cardiovascular risk factors. In this unprecedented and critical scenario, home-based physical activity programs arise as a clinically relevant intervention to promote health benefits to cardiac patients. Many studies have demonstrated the feasibility, safety, and efficacy of different models of home-based exercise programs in the primary and secondary prevention of cardiovascular diseases and major cardiovascular events among different populations. This body of knowledge can inform evidence-based policies to be urgently implemented to counteract the impact of increased physical inactivity and sedentary behavior during the COVID-19 outbreak, thereby alleviating the global burden of cardiovascular disease.


title: Modern veterinary vaccines and the Shaman's apprentice

text: Abstract This paper is an overview and assessment of new, commercially available veterinary vaccines placed in a historical context. The authors critically evaluate the current state of the field of veterinary vaccines in both food and companion animals and the promises for future vaccine development. The authors maintain that there is considerable variability in safety and sustained efficacy among veterinary vaccines, especially those developed for companion animals. It is proposed that establishment of an international vaccine advisory committee be supported which would function to apprise the veterinary profession of the current status of vaccines and their use.


title: COVID-19 Public Sentiment Insights and Machine Learning for Tweets Classification

text: Along with the Coronavirus pandemic, another crisis has manifested itself in the form of mass fear and panic phenomena, fueled by incomplete and often inaccurate information. There is therefore a tremendous need to address and better understand COVID-19's informational crisis and gauge public sentiment, so that appropriate messaging and policy decisions can be implemented. In this research article, we identify public sentiment associated with the pandemic using Coronavirus specific Tweets and R statistical software, along with its sentiment analysis packages. We demonstrate insights into the progress of fear-sentiment over time as COVID-19 approached peak levels in the United States, using descriptive textual analytics supported by necessary textual data visualizations. Furthermore, we provide a methodological overview of two essential machine learning (ML) classification methods, in the context of textual analytics, and compare their effectiveness in classifying Coronavirus Tweets of varying lengths. We observe a strong classification accuracy of 91% for short Tweets, with the Naive Bayes method. We also observe that the logistic regression classification method provides a reasonable accuracy of 74% with shorter Tweets, and both methods showed relatively weaker performance for longer Tweets. This research provides insights into Coronavirus fear sentiment progression, and outlines associated methods, implications, limitations and opportunities.


ECMO as an emergency medical countermeasure


title: Inappropriate modeling of chronic and complex disorders: How to reconsider the approach in the context of predictive, preventive and personalized medicine, and translational medicine

text: Preclinical investigations such as animal modeling make the basis of clinical investigations and subsequently patient care. Predictive, preventive, and personalized medicine (PPPM) not only highlights a patient-tailored approach by choosing the right medication, the right dose at the right time point but it as well essentially requires early identification, by the means of complex and state-of-the-art technologies of unmanifested pathological processes in an individual, in order to deliver targeted prevention early enough to reverse manifestation of a pathology. Such an approach can be achieved by taking into account clinical, pathological, environmental, and psychosocial characteristics of the patients or an individual who has a suboptimal health condition. Inappropriate modeling of chronic and complex disorders, in this context, may diminish the predictive potential and slow down the development of PPPM and consequently modern healthcare. Therefore, it is the common goal of PPPM and translational medicine to find the solution for the problem we present in our review. Both, translational medicine and PPPM in parallel, essentially need accurate surrogates for misleading animal models. This study was therefore undertaken to provide shreds of evidence against the validity of animal models. Limitations of current animal models and drug development strategies based on animal modeling have been systematically discussed. Finally, a variety of potential surrogates have been suggested to change the unfavorable situation in medical research and consequently in healthcare.


title: The immune vulnerability landscape of the 2019 Novel Coronavirus, SARS-CoV-2

text: The outbreak of the 2019 Novel Coronavirus (SARS-CoV-2) rapidly spread from Wuhan, China to more than 150 countries, areas or territories, causing staggering number of infections and deaths. A systematic profiling of the immune vulnerability landscape of SARS-CoV-2, which can bring critical insights into the immune clearance mechanism, peptide vaccine development, and antiviral antibody development, is lacking. In this study, we investigated the potential of the SARS-CoV-2 viral proteins to induce class I and II MHC presentation and to form linear antibody epitopes. We created an online database to broadly share the predictions as a resource for the research community. Using this resource, we showed that genetic variations in SARS- CoV-2, though still few for the moment, already follow the pattern of mutations in related coronaviruses, and could alter the immune vulnerability landscape of this virus. Importantly, we discovered evidence that SARS-CoV-2, along with related coronaviruses, used mutations to evade attack from the human immune system. Overall, we present an immunological resource for SARS-CoV-2 that could promote both therapeutic development and mechanistic research.


title: Targeted Nutrition in Chronic Disease

text: Today, chronic disease is a major public health problem around the world that is rapidly increasing with a growing and aging population [...].


title: X-ray structure and activities of an essential Mononegavirales L-protein domain

text: The L protein of mononegaviruses harbours all catalytic activities for genome replication and transcription. It contains six conserved domains (CR-I to -VI; Fig. 1a). CR-III has been linked to polymerase and polyadenylation activity, CR-V to mRNA capping and CR-VI to cap methylation. However, how these activities are choreographed is poorly understood. Here we present the 2.2-Å X-ray structure and activities of CR-VI+, a portion of human Metapneumovirus L consisting of CR-VI and the poorly conserved region at its C terminus, the +domain. The CR-VI domain has a methyltransferase fold, which besides the typical S-adenosylmethionine-binding site ((SAM)P) also contains a novel pocket ((NS)P) that can accommodate a nucleoside. CR-VI lacks an obvious cap-binding site, and the (SAM)P-adjoining site holding the nucleotides undergoing methylation ((SUB)P) is unusually narrow because of the overhanging +domain. CR-VI+ sequentially methylates caps at their 2′O and N7 positions, and also displays nucleotide triphosphatase activity.


KI and WU Polyomaviruses in Children, France


title: Congenital Malaria in China

text: ABSTRACT: BACKGROUND: Congenital malaria, in which infants are directly infected with malaria parasites from their mother prior to or during birth, is a potentially life-threatening condition that occurs at relatively low rates in malaria-endemic regions. It is recognized as a serious problem in Plasmodium falciparum–endemic sub-Saharan Africa, where recent data suggests that it is more common than previously believed. In such regions where malaria transmission is high, neonates may be protected from disease caused by congenital malaria through the transfer of maternal antibodies against the parasite. However, in low P. vivax–endemic regions, immunity to vivax malaria is low; thus, there is the likelihood that congenital vivax malaria poses a more significant threat to newborn health. Malaria had previously been a major parasitic disease in China, and congenital malaria case reports in Chinese offer valuable information for understanding the risks posed by congenital malaria to neonatal health. As most of the literature documenting congenital malaria cases in China are written in Chinese and therefore are not easily accessible to the global malaria research community, we have undertaken an extensive review of the Chinese literature on this subject. METHODS/PRINCIPAL FINDINGS: Here, we reviewed congenital malaria cases from three major searchable Chinese journal databases, concentrating on data from 1915 through 2011. Following extensive screening, a total of 104 cases of congenital malaria were identified. These cases were distributed mainly in the eastern, central, and southern regions of China, as well as in the low-lying region of southwest China. The dominant species was P. vivax (92.50%), reflecting the malaria parasite species distribution in China. The leading clinical presentation was fever, and other clinical presentations were anaemia, jaundice, paleness, diarrhoea, vomiting, and general weakness. With the exception of two cases, all patients were cured with antimalarial drugs such as chloroquine, quinine, artemether, and artesunate. CONCLUSIONS: The symptoms of congenital malaria vary significantly between cases, so clear and early diagnosis is difficult. We suggest that active surveillance might be necessary for neonates born to mothers with a history of malaria.


Correction for Li et al., “Discovery of Bat Coronaviruses through Surveillance and Probe Capture-Based Next-Generation Sequencing”


title: Are official confirmed cases and fatalities counts good enough to study the COVID-19 pandemic dynamics? A critical assessment through the case of Italy

text: As the COVID-19 outbreak is developing the two most frequently reported statistics seem to be the raw confirmed case and case fatalities counts. Focusing on Italy, one of the hardest hit countries, we look at how these two values could be put in perspective to reflect the dynamics of the virus spread. In particular, we find that merely considering the confirmed case counts would be very misleading. The number of daily tests grows, while the daily fraction of confirmed cases to total tests has a change point. It (depending on region) generally increases with strong fluctuations till (around, depending on region) 15–22 March and then decreases linearly after. Combined with the increasing trend of daily performed tests, the raw confirmed case counts are not representative of the situation and are confounded with the sampling effort. This we observe when regressing on time the logged fraction of positive tests and for comparison the logged raw confirmed count. Hence, calibrating model parameters for this virus’s dynamics should not be done based only on confirmed case counts (without rescaling by the number of tests), but take also fatalities and hospitalization count under consideration as variables not prone to be distorted by testing efforts. Furthermore, reporting statistics on the national level does not say much about the dynamics of the disease, which are taking place at the regional level. These findings are based on the official data of total death counts up to 15 April 2020 released by ISTAT and up to 10 May 2020 for the number of cases. In this work, we do not fit models but we rather investigate whether this task is possible at all. This work also informs about a new tool to collect and harmonize official statistics coming from different sources in the form of a package for the R statistical environment and presents the “COVID-19 Data Hub.”


title: Mechanism of Fulminant Pulmonary Edema Caused by Enterovirus 71

text: Pulmonary edema (PE) may occur with enterovirus 71 (EV71) infection. We monitored arterial pressure (AP) and heart rate (HR) in patients with EV71 infection and analyzed the variability of AP and HR. Sympathetic activity, AP, and HR increased with respiratory stress. Thereafter, parasympathetic activity increased with decreases in AP and HR. The lungs showed edema with inducible nitric oxide synthase (iNOS) expression. Destruction of the medial, ventral, and caudal medulla may lead to sympathetic overactivation, causing blood to shift to the lungs. The pathogenesis of PE may also involve iNOS and nitric oxide.


title: A review of the 2019 Novel Coronavirus (COVID-19) based on current evidence

text: Abstract The pneumonia caused by novel coronavirus (SARS-CoV-2) in Wuhan, China in December 2019 is a highly contagious disease. The World Health Organization (WHO) has declared the ongoing outbreak as a global public health emergency. Currently, the research on novel coronavirus is still in the primary stage. Based on the current published evidence, we systematically summarizes the epidemiology, clinical characteristics, diagnosis, treatment and prevention of knowledge surrounding COVID-19. This review in the hope of helping the public effectively recognize and deal with the 2019 novel coronavirus (SARS-CoV-2), and providing a reference for future studies.


title: The Impacts on Health, Society, and Economy of SARS and H7N9 Outbreaks in China: A Case Comparison Study

text: BACKGROUND: Epidemics such as SARS and H7N9 have caused huge negative impacts on population health and the economy in China. AIMS: This article discusses the impacts of SARS in 2003 and H7N9 in 2013 in China, in order to provide a better understanding to government and practitioners of why improving management of response to infectious disease outbreaks is so critical for a country's economy, its society, and its place in the global community. METHODS: To provide the results of an analysis of impacts of SARS and H7N9 based on feedback from documents, informants, and focus groups on events during the SARS and H7N9 outbreaks. RESULTS: Both outbreaks of SARS and H7N9 have had an impact on China, causing significant negative impacts on health, the economy, and even national and even international security. CONCLUSIONS: Both SARS coronavirus and H7N9 viruses presented a global epidemic threat, but the social and economic impacts of H7N9 were not as serious as in the case of SARS because the response to H7N9 was more effective.


title: Reduced plasma ACE2 activity in dialysis patients: another piece in the conundrum of factors involved in hypertension and cardiovascular morbidity?

text: the reduction in plasma ACE2 activity reported in ESRD patients treated by dialysis, particularly in female subjects, could limit Ang II degradation leading to increased levels of this peptide, which could contribute to the high prevalence of hypertension and cardiovascular morbidity that afflicts the dialysis population


title: Psychometric Evaluation of the Arabic Version of the Fear of COVID-19 Scale

text: Fear is a central emotional response to imminent threats such as the coronavirus-19 disease (COVID-19). The Fear of COVID-19 Scale (FCV-19S) assesses the severity of fear towards COVID-19. The present study examined the psychometric properties of the Arabic version of the FCV-19S. Using a forward-backward translation, the FCV-19S was translated into Arabic. An online survey using the Arabic versions of FCV-19S and the Hospital Anxiety and Depression Scale (HADS) was administered. Reliability and concurrent and confirmatory validity were examined. The dataset consisted of 693 Saudi participants. The internal consistency of the Arabic FCV-19S was satisfactory (α = .88), with sound concurrent validity indicated by significant and positive correlations with HADS (r = .66). The unidimensional structure of the FCV-19S was confirmed. The Arabic version of the FCV-19S is psychometrically robust and can be used in research assessing the psychological impact of COVID-19 among a Saudi adult population.


title: Racial disparities in knowledge, attitudes and practices related to COVID-19 in the USA

text: BACKGROUND: Recent reports indicate racial disparities in the rates of infection and mortality from the 2019 novel coronavirus (coronavirus disease 2019 [COVID-19]). The aim of this study was to determine whether disparities exist in the levels of knowledge, attitudes and practices (KAPs) related to COVID-19. METHODS: We analyzed data from 1216 adults in the March 2020 Kaiser Family Foundation ‘Coronavirus Poll’, to determine levels of KAPs across different groups. Univariate and multivariate regression analysis was used to identify predictors of KAPs. RESULTS: In contrast to White respondents, Non-White respondents were more likely to have low knowledge (58% versus 30%; P < 0.001) and low attitude scores (52% versus 27%; P < 0.001), but high practice scores (81% versus 59%; P < 0.001). By multivariate regression, White race (odds ratio [OR] 3.06; 95% confidence interval [CI]: 1.70–5.50), higher level of education (OR 1.80; 95% CI: 1.46–2.23) and higher income (OR 2.06; 95% CI: 1.58–2.70) were associated with high knowledge of COVID-19. Race, sex, education, income, health insurance status and political views were all associated with KAPs. CONCLUSIONS: Racial and socioeconomic disparity exists in the levels of KAPs related to COVID-19. More work is needed to identify educational tools that tailor to specific racial and socioeconomic groups.


Utilization of Pediatric Nurse Practitioners as Adult Critical Care Providers During the COVID-19 Pandemic: A Novel Approach


title: The cardiovascular burden of coronavirus disease 2019 (COVID-19) with a focus on congenital heart disease

text: Abstract Coronavirus disease 2019 (COVID-19), caused by a novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first described in a cluster of patients presenting with pneumonia symptoms in Wuhan, China, in December of 2019. Over the past few months, COVID-19 has developed into a worldwide pandemic, with over 400,000 documented cases globally as of March 24, 2020. The SARS-CoV-2 virus is most likely of zoonotic origin, but has been shown to have effective human-to-human transmission. COVID-19 results in mild symptoms in the majority of infected patients, but can cause severe lung injury, cardiac injury, and death. Given the novel nature of COVID-19, no established treatment beyond supportive care exists currently, but extensive public-health measures to reduce person-to-person transmission of COVID-19 have been implemented globally to curb the spread of disease, reduce the burden on healthcare systems, and protect vulnerable populations, including the elderly and those with underlying medical comorbidities. Since this is an emerging infectious disease, there is, as of yet, limited data on the effects of this infection on patients with cardiovascular disease, particularly so for those with congenital heart disease. We summarize herewith the early experience with COVID-19 and consider the potential applicability to and implications for patients with cardiovascular disease in general and congenital heart disease in particular.


The dilemmas of the classification of SARS-CoV-2 infection without clinical manifestations: asymptomatic or presymptomatic


title: IFITM Proteins Restrict Viral Membrane Hemifusion

text: The interferon-inducible transmembrane (IFITM) protein family represents a new class of cellular restriction factors that block early stages of viral replication; the underlying mechanism is currently not known. Here we provide evidence that IFITM proteins restrict membrane fusion induced by representatives of all three classes of viral membrane fusion proteins. IFITM1 profoundly suppressed syncytia formation and cell-cell fusion induced by almost all viral fusion proteins examined; IFITM2 and IFITM3 also strongly inhibited their fusion, with efficiency somewhat dependent on cell types. Furthermore, treatment of cells with IFN also markedly inhibited viral membrane fusion and entry. By using the Jaagsiekte sheep retrovirus envelope and influenza A virus hemagglutinin as models for study, we showed that IFITM-mediated restriction on membrane fusion is not at the steps of receptor- and/or low pH-mediated triggering; instead, the creation of hemifusion was essentially blocked by IFITMs. Chlorpromazine (CPZ), a chemical known to promote the transition from hemifusion to full fusion, was unable to rescue the IFITM-mediated restriction on fusion. In contrast, oleic acid (OA), a lipid analog that generates negative spontaneous curvature and thereby promotes hemifusion, virtually overcame the restriction. To explore the possible effect of IFITM proteins on membrane molecular order and fluidity, we performed fluorescence labeling with Laurdan, in conjunction with two-photon laser scanning and fluorescence-lifetime imaging microscopy (FLIM). We observed that the generalized polarizations (GPs) and fluorescence lifetimes of cell membranes expressing IFITM proteins were greatly enhanced, indicating higher molecularly ordered and less fluidized membranes. Collectively, our data demonstrated that IFITM proteins suppress viral membrane fusion before the creation of hemifusion, and suggested that they may do so by reducing membrane fluidity and conferring a positive spontaneous curvature in the outer leaflets of cell membranes. Our study provides novel insight into the understanding of how IFITM protein family restricts viral membrane fusion and infection.


title: Pearls of experience for safe and efficient hospital practices in otorhinolaryngology—head and neck surgery in Hong Kong during the 2019 novel coronavirus disease (COVID-19) pandemic

text: The 2019 novel coronavirus disease (COVID-19) epidemic originated in Wuhan, China and spread rapidly worldwide, leading the World Health Organization to declare an official global COVID-19 pandemic in March 2020. In Hong Kong, clinicians and other healthcare personnel collaborated closely to combat the outbreak of COVID-19 and minimize the cross-transmission of disease among hospital staff members. In the field of otorhinolaryngology—head and neck surgery (OHNS) and its various subspecialties, contingency plans were required for patient bookings in outpatient clinics, surgeries in operating rooms, protocols in wards and other services. Infected patients may shed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) particles into their environments via body secretions. Therefore, otolaryngologists and other healthcare personnel in this specialty face a high risk of contracting COVID-19 and must remain vigilant when performing examinations and procedures involving the nose and throat. In this article, we share our experiences of the planning and logistics undertaken to provide safe and efficient OHNS practices over the last 2 months, during the COVID-19 pandemic. We hope that our experiences will serve as pearls for otolaryngologists and other healthcare personnel working in institutes that serve large numbers of patients every day, particularly with regard to the sharing of clinical and administrative tasks during the COVID-19 pandemic.


title: Behavioral immune system linked to responses to the threat of COVID-19

text: People possess psychological processes that help them avoid pathogens, which is particularly important when novel infectious diseases (e.g., COVID-19) spread through the population. Across two studies we examined whether trait pathogen avoidance (operationalized as perceived vulnerability to disease; PVD) was linked with responses to COVID-19 and preventative behaviors. In Study 1, PVD was positively associated with stronger reactions to the threat of COVID-19, including increased anxiety, perceptions that people should alter their typical behavior, as well as reported importance of engaging in proactive and social distancing behaviors. In Study 2, PVD was again associated with increased anxiety, as well as more vigilant behavior when grocery shopping, fewer trips to the store, and fewer face-to-face interactions. These associations remained significant when controlling for the Big-5 personality traits. Although the two subscales of PVD (germ aversion and perceived infectability) were often parallel predictors, several differences between the subscales emerged. Germ aversion may be more associated with behaviors whereas perceived infectability with vigilance.


title: Pre-infection of pigs with Mycoplasma hyopneumoniae modifies outcomes of infection with European swine influenza virus of H1N1, but not H1N2, subtype

text: Abstract Swine influenza virus (SIV) and Mycoplasma hyopneumoniae (Mhp) are widespread in farms and are major pathogens involved in the porcine respiratory disease complex (PRDC). The aim of this experiment was to compare the pathogenicity of European avian-like swine H1N1 and European human-like reassortant swine H1N2 viruses in naïve pigs and in pigs previously infected with Mhp. Six groups of SPF pigs were inoculated intra-tracheally with either Mhp, or H1N1, or H1N2 or Mhp+H1N1 or Mhp+H1N2, both pathogens being inoculated at 21 days intervals in these two last groups. A mock-infected group was included. Although both SIV strains induced clinical signs when singly inoculated, results indicated that the H1N2 SIV was more pathogenic than the H1N1 virus, with an earlier shedding and a greater spread in lungs. Initial infection with Mhp before SIV inoculation increased flu clinical signs and pathogenesis (hyperthermia, loss of appetite, pneumonia lesions) due to the H1N1 virus but did not modify significantly outcomes of H1N2 infection. Thus, Mhp and SIV H1N1 appeared to act synergistically, whereas Mhp and SIV H1N2 would compete, as H1N2 infection led to the elimination of Mhp in lung diaphragmatic lobes. In conclusion, SIV would be a risk factor for the severity of respiratory disorders when associated with Mhp, depending on the viral subtype involved. This experimental model of coinfection with Mhp and avian-like swine H1N1 is a relevant tool for studying the pathogenesis of SIV-associated PRDC and testing intervention strategies for the control of the disease.


title: Dermatologic manifestations and complications of COVID-19

text: The novel coronavirus disease of 2019 (COVID-19) is associated with significant morbidity and mortality. While much of the focus has been on the cardiac and pulmonary complications, there are several important dermatologic components that clinicians must be aware of. OBJECTIVE: This brief report summarizes the dermatologic manifestations and complications associated with COVID-19 with an emphasis on Emergency Medicine clinicians. DISCUSSION: Dermatologic manifestations of COVID-19 are increasingly recognized within the literature. The primary etiologies include vasculitis versus direct viral involvement. There are several types of skin findings described in association with COVID-19. These include maculopapular rashes, urticaria, vesicles, petechiae, purpura, chilblains, livedo racemosa, and distal limb ischemia. While most of these dermatologic findings are self-resolving, they can help increase one's suspicion for COVID-19. CONCLUSION: It is important to be aware of the dermatologic manifestations and complications of COVID-19. Knowledge of the components is important to help identify potential COVID-19 patients and properly treat complications.


title: Quantification of human bocavirus in lower respiratory tract infections in China

text: A quantitative PCR method was established to quantify human bocavirus (HBoV) genomic copies in clinical specimens from children with lower respiratory tract infections (LRTI) in China. A total of 257 respiratory tract specimens were tested, and 7 (2.7%) of these (all sputum samples) were positive, with genomic copies that ranged from 8.0 × 10(3 )to 8.0 × 10(9 )in the samples. The main clinical symptom of patients who were positive for HBoV DNA was a pneumonia-like syndrome represented by high fever and cough. Our results suggest that HBoV may be an important etiological agent of LRTI in children in China.


docid: rnuslepe

title: Chapter 5 Political and Administrative Systems

text: China’s political and administrative systems are mysteries to many Westerners. At one level, China is a one-party state that has been ruled by the Chinese Communist Party since 1949. In the late 1950s, the same authoritarian regime was waging a massive campaign under the name of the ‘Great Leap Forward’, which resulted in the loss of a large number of lives. From 1966 to 1976, the same regime was launching a so-called ‘Great Cultural Revolution’, causing serious cultural and economic damages to this nation. Furthermore, influential theories of the political economy of the former socialist systems emphasize that unless the one-party monopoly is abolished, reforms are doomed to fail. Obviously, the achievements of China’s modernization defy conventional explanations. Consequently, this will lead to the asking of questions such as: How has the Chinese political system worked during the past decades? Can it be sustained in the long run? Keywords Political system, Chinese Communist Party (CCP), Chinese characteristics, authoritarianism, governance, administrative efficiency, legal system, corruption control


title: COVID‐19 will accelerate the decline in international student enrollment

text: ‘Dates of destiny are always on time.’ — Anonymous ‘I hate quotations. Tell me what you know.’ — Ralph Waldo Emerson


title: Zero Transmission of Middle East Respiratory Syndrome: Lessons Learned From Thailand

text: New emerging pathogens can quickly become a global health threat in this era. A number of Middle East respiratory syndrome (MERS) outbreaks have been linked to healthcare facilities. The healthcare-associated transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) has been attributed to overcrowding, delayed diagnosis, and the breakdown of infection control systems. Strict infection control precautions and a well-prepared hospital system may have contributed to no nosocomial transmission occurring during the treatment of MERS-CoV infections imported to Thailand. The recent outbreaks of MERS and previous emerging infections provide valuable lessons to be learned. Continuous vigilance and strengthening of infection control systems will shape the capacity to prevent and control MERS-CoV or new emerging disease transmission.


title: Detection of collagen triple helix repeat containing-1 and nuclear factor (erythroid-derived 2)-like 3 in colorectal cancer

text: BACKGROUND: Collagen Triple Helix Repeat Containing-1 (CTHRC1) and Nuclear factor (erythroid-derived 2)-like 3 (NFE2L3) may be useful biomarker candidates for the diagnosis of colorectal cancer (CRC) since they have shown an increase messenger RNA transcripts (mRNA) expression level in adenomas and colorectal tumours when compared to normal tissues. METHODS: To evaluate CTHRC1 and NFE2L3 as cancer biomarkers, it was generated and characterised several novel specific polyclonal antibodies (PAb), monoclonal antibodies (MAbs) and soluble Fab fragments (sFabs) against recombinant CTHRC1 and NFE2L3 proteins, which were obtained from different sources, including a human antibody library and immunised animals. The antibodies and Fab fragments were tested for recognition of native CTHRC1 and NFE2L3 proteins by immunoblotting analysis and enzyme-linked immunosorbent assay (ELISA) in colorectal cell lines derived from tumour and cancer tissues. RESULTS: Both, antibodies and a Fab fragment showed high specificity since they recognised only their corresponding recombinant antigens, but not a panel of different unrelated- and related proteins. In Western blot analysis of CTHRC1, a monoclonal antibody designated CH21D7 was able to detect a band of the apparent molecular weight of a full-length CTHRC1 in the human colon adenocarcinoma cell line HT29. This result was confirmed by a double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) with the monoclonal antibodies CH21D7 and CH24G2, detecting CTHRC1 in HT29 and in the colon adenocarcinoma cell line SW620. Similar experiments were performed with PAb, MAbs, and sFab against NFE2L3. The immunoblot analysis showed that the monoclonal antibody 41HF8 recognised NFE2L3 in HT29, and leukocytes. These results were verified by DAS-ELISA assay using the pairs PAb/sFab E5 and MAb 41HF8/sFab E5. Furthermore, an immunoassay for simultaneous detection of the two cancer biomarkers was developed using a Dissociation-Enhanced Lanthanide Fluorescent Immunoassay technology (DELFIA). CONCLUSIONS: In conclusion, the antibodies obtained in this study are specific for CTHRC1 and NFE2L3 since they do not cross-react with unrelated- and related proteins and are useful for specific measurement of native CTHRC1 and NFE2L3 proteins. The antibodies and immunoassays may be useful for the analysis of CTHRC1 and NFE2L3 in clinical samples and for screening of therapeutic compounds in CRC.


title: Storm, typhoon, cyclone or hurricane in patients with COVID-19? Beware of the same storm that has a different origin

text: Some of the articles being published during the severe acute respiratory syndrome–coronavirus (SARS-CoV)-2 pandemic highlight a link between severe forms of coronavirus disease 2019 (COVID-19) and the so-called cytokine storm, also with increased ferritin levels. However, this scenario is more complex than initially thought due to the heterogeneity of hyperinflammation. Some patients with coronavirus 2019 disease (COVID-19) develop a fully blown secondary haemophagocytic lymphohistiocytosis (sHLH), whereas others, despite a consistent release of pro-inflammatory cytokines, do not fulfil sHLH criteria but still show some features resembling the phenotype of the hyperferritinemic syndrome. Despite the final event (the cytokine storm) is shared by various conditions leading to sHLH, the aetiology, either infectious, autoimmune or neoplastic, accounts for the differences in the various phases of this process. Moreover, the evidence of a hyperinflammatory microenvironment provided the rationale to employ immunomodulating agents for therapeutic purposes in severe COVID-19. This viewpoint aims at discussing the pitfalls and issues to be considered with regard to the use of immunomodulating agents in COVID-19, such as timing of treatment based on the viral load and the extent of cytokine/ferritin overexpression. Furthermore, it encompasses recent findings in the paediatric field about a novel multisystem inflammatory disease resembling toxic shock syndrome and atypical Kawasaki disease observed in children with proven SARS-CoV2 infection. Finally, it includes arguments in favour of adding COVID-19 to the spectrum of the recently defined ‘hyperferritinemic syndrome’, which already includes adult-onset Still’s disease, macrophage activation syndrome, septic shock and catastrophic anti-phospholipid syndrome.


title: Bluetongue Serotype 3 in Israel 2013–2018: Clinical Manifestations of the Disease and Molecular Characterization of Israeli Strains

text: In this paper, the results of the diagnostic activities on Bluetongue virus serotype 3 (BTV-3) conducted at Kimron Veterinary Institute (Beit Dagan, Israel) between 2013 and 2018 are reported. Bluetongue virus is the causative agent of bluetongue (BT), a disease of ruminants, mostly transmitted by competent Culicoides species. In Israel, BTV-3 circulation was first detected in 2013 from a sheep showing classical BT clinical signs. It was also evidenced in 2016, and, since then, it has been regularly detected in Israeli livestock. Between 2013 and 2017, BTV-3 outbreaks were limited in sheep flocks located in the southern area only. In 2018, BTV-3 was instead found in the Israeli coastal area being one of the dominant BTV serotypes isolated from symptomatic sheep, cattle and goats. In Israeli sheep, BTV-3 was able to cause BT classical clinical manifestations and fatalities, while in cattle and goats infection ranged from asymptomatic forms to death cases, depending on either general welfare of the herds or on the occurrence of viral and bacterial co-infections. Three different BTV-3 strains were identified in Israel between 2013 and 2018: ISR-2019/13 isolated in 2013, ISR-2153/16 and ISR-2262/2/16 isolated in 2016. Sequencing and phylogenetic analysis of these strains showed more than 99% identity by segment (Seg) 2, 5, 6, 7, and 8 sequences. In contrast, a wide range of diversity among these strains was exhibited in other viral gene segments, implying the occurrence of genome reassortment between these local circulating strains and those originating from Africa. The genome sequences of the BTV-3 isolated in 2017 and 2018 were most closely related to those of the ISR-2153/16 strain suggesting their common ancestor. Comparison of BTV-3 Israeli strains with those recently detected in the Mediterranean region uncovered high percentage identity (98.19–98.28%) only between Seg-2 of all Israeli strains and the BTV-3 Zarzis/TUN2016 strain. A 98.93% identity was also observed between Seg-4 sequences of ISR-2019/13 and the BTV-3 Zarzis/TUN2016 strain. This study demonstrated that BTV-3 has been circulating in the Mediterranean region at least since 2013, but, unlike the other Mediterranean strains, Israeli BTV-3 were able to cause clinical signs also in cattle.