title: Novel system for detecting SARS coronavirus nucleocapsid protein using an ssDNA aptamer

text: Abstract The outbreak of severe acute respiratory syndrome (SARS) in 2002 affected thousands of people and an efficient diagnostic system is needed for accurate detection of SARS coronavirus (SARS CoV) to prevent or limit future outbreaks. Of the several SARS CoV structural proteins, the nucleocapsid protein has been shown to be a good diagnostic marker. In this study, an ssDNA aptamer that specifically binds to SARS CoV nucleocapsid protein was isolated from a DNA library containing 45-nuceotide random sequences in the middle of an 88mer single-stranded DNA. After twelve cycles of systematic evolution of ligands by exponential enrichment (SELEX) procedure, 15 ssDNA aptamers were identified. Enzyme-linked immunosorbent assay (ELISA) analysis was then used to identify the aptamer with the highest binding affinity to the SARS CoV nucleocapsid protein. Using this approach, an ssDNA aptamer that binds to the nucleocapsid protein with a K d of 4.93±0.30nM was identified. Western blot analysis further demonstrated that this ssDNA aptamer could be used to efficiently detect the SARS CoV nucleocapsid protein when compared with a nucleocapsid antibody. Therefore, we believe that the selected ssDNA aptamer may be a good alternative detection probe for the rapid and sensitive detection of SARS.


title: Comparison of Thermal and Non-Thermal Processing of Swine Feed and the Use of Selected Feed Additives on Inactivation of Porcine Epidemic Diarrhea Virus (PEDV)

text: Infection with porcine epidemic diarrhea virus (PEDV) causes diarrhea, vomiting, and high mortality in suckling pigs. Contaminated feed has been suggested as a vehicle of transmission for PEDV. The objective of this study was to compare thermal and electron beam processing, and the inclusion of feed additives on the inactivation of PEDV in feed. Feed samples were spiked with PEDV and then heated to 120–145°C for up to 30 min or irradiated at 0–50 kGy. Another set of feed samples spiked with PEDV and mixed with Ultracid P (Nutriad), Activate DA (Novus International), KEM-GEST (Kemin Agrifood), Acid Booster (Agri-Nutrition), sugar or salt was incubated at room temperature (~25°C) for up to 21 days. At the end of incubation, the virus titers were determined by inoculation of Vero-81 cells and the virus inactivation kinetics were modeled using the Weibull distribution model. The Weibull kinetic parameter delta represented the time or eBeam dose required to reduce virus concentration by 1 log. For thermal processing, delta values ranged from 16.52 min at 120°C to 1.30 min at 145°C. For eBeam processing, a target dose of 50 kGy reduced PEDV concentration by 3 log. All additives tested were effective in reducing the survival of PEDV when compared with the control sample (delta = 17.23 days). Activate DA (0.81) and KEM-GEST (3.28) produced the fastest inactivation. In conclusion, heating swine feed at temperatures over 130°C or eBeam processing of feed with a dose over 50 kGy are effective processing steps to reduce PEDV survival. Additionally, the inclusion of selected additives can decrease PEDV survivability.


title: Viral interference induced by live attenuated virus vaccine (OPV) can prevent otitis media

text: Abstract Background The goal of this study was to evaluate whether a live attenuated poliovirus vaccine (OPV) has clinically relevant interfering effect with non-polio infections causing otitis media in young children. Methods Open trial in which the intervention group (64 children) received OPV at the age of 2, 3, 6 and 12months. The control group (250 children) received IPV (inactivated polio vaccine) at the age of 6 and 12months. Clinical symptoms were recorded by a questionnaire at the age of 3, 6, 12, 18 and 24months. Results Otitis media episodes were less frequent in the OPV than in the control group. A significant difference was seen at the age of 6–18months (IRR=0.76 [95% CI 0.59–0.94], P =0.011) and was particularly clear among children, who attended daycare (IRR 0.37 [95% CI 0.19–0.71], P =0.003). Conclusions OPV provides some protection against otitis media. This effect may be mediated by viral interference with non-polio viruses.


title: Health systems planning for an influenza pandemic

text: Abstract District planning, in general, and influenza pandemic planning, in particular, are necessary to sustain health care organizations and systems. An extensive stakeholder process used by Capital District Health Authority (CDHA) and the Izaak Walton Killam (IWK) Health Centre involved more than 25 teams. This work resulted in a joint CDHA/IWK pandemic influenza contingency plan for public health, primary care, acute care and tertiary care services. In addition, district and business continuity planning has been enhanced.


title: Proactive Identification of Palliative Care Needs Among Patients with COVID-19 in the ICU

text: In the setting of the COVID-19 pandemic, new strategies are needed to address the unique and significant palliative care (PC) needs of patients with COVID-19 and their families, particularly when health systems are stressed by patient surges. Many PC teams rely on referral-based consultation methods that can result in needs going unidentified and/or unmet. Here we describe a novel system to proactively identify and meet the PC needs of all patients with COVID-19 being cared for in our hospital’s ICUs. Patients were screened through a combination of chart review and brief provider interview, and PC consultations were provided via telemedicine for those with unmet needs identified. In the first six weeks of operation, our pilot program of proactive screening and outreach resulted in PC consultation for 12 of the 29 (41%) adult patients admitted to the ICU with COVID-19 at our institution. Consultations were most commonly for patient and family support as well as for goals of care and advance care planning, consistent with identified PC needs within this unique patient population.


title: Potential for evolution of complex defense strategies in a multi-scale model of virus-host coevolution

text: BACKGROUND: Host resistance and viral pathogenicity are determined by molecular interactions that are part of the evolutionary arms race between viruses and their hosts. Viruses are obligate intracellular parasites and entry to the host cell is the first step of any virus infection. Commonly, viruses enter host cells by binding cell surface receptors. We adopt a computational modeling approach to study the evolution of the first infection step, where we consider two possible levels of resistance mechanism: at the level of the binding interaction between the host receptor and a virus binding protein, and at the level of receptor protein expression where we use a standard gene regulatory network model. At the population level we adopted the Susceptible-Infected-Susceptible (SIS) model. We used our multi-scale model to understand what conditions might determine the balance between use of resistance mechanisms at the two different levels. RESULTS: We explored a range of different conditions (model parameters) that affect host evolutionary dynamics and, in particular, the balance between the use of different resistance mechanisms. These conditions include the complexity of the receptor binding protein-protein interaction, selection pressure on the host population (pathogenicity), and the number of expressed cell-surface receptors. In particular, we found that as the receptor binding complexity (understood as the number of amino acids involved in the interaction between the virus entry protein and the host receptor) increases, viruses tend to become specialists and target one specific receptor. At the same time, on the host side, the potential for resistance shifts from the changes at the level of receptor binding (protein-protein) interaction towards changes at the level of gene regulation, suggesting a mechanism for increased biological complexity. CONCLUSIONS: Host resistance and viral pathogenicity depend on quite different evolutionary conditions. Viruses may evolve cell entry strategies that use small receptor binding regions, represented by low complexity binding in our model. Our modeling results suggest that if the virus adopts a strategy based on binding to low complexity sites on the host receptor, the host will select a defense strategy at the protein (receptor) level, rather than at the level of the regulatory network - a virus-host strategy that appears to have been selected most often in nature. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12862-016-0804-z) contains supplementary material, which is available to authorized users.


title: Pharmacological (or Synthetic) and Nutritional Agonists of PPAR-γ as Candidates for Cytokine Storm Modulation in COVID-19 Disease

text: The cytokine storm is an abnormal production of inflammatory cytokines, due to the over-activation of the innate immune response. This mechanism has been recognized as a critical mediator of influenza-induced lung disease, and it could be pivotal for COVID-19 infections. Thus, an immunomodulatory approach targeting the over-production of cytokines could be proposed for viral aggressive pulmonary disease treatment. In this regard, the peroxisome proliferator-activated receptor (PPAR)-γ, a member of the PPAR transcription factor family, could represent a potential target. Beside the well-known regulatory role on lipid and glucose metabolism, PPAR-γ also represses the inflammatory process. Similarly, the PPAR-γ agonist thiazolidinediones (TZDs), like pioglitazone, are anti-inflammatory drugs with ameliorating effects on severe viral pneumonia. In addition to the pharmacological agonists, also nutritional ligands of PPAR-γ, like curcuma, lemongrass, and pomegranate, possess anti-inflammatory properties through PPAR-γ activation. Here, we review the main synthetic and nutritional PPAR-γ ligands, proposing a dual approach based on the strengthening of the immune system using pharmacological and dietary strategies as an attempt to prevent/treat cytokine storm in the case of coronavirus infection.


title: Passive immunity to control Bovine coronavirus diarrhea in a dairy herd in Argentina

text: Abstract Bovine coronavirus (BCoV) is a viral enteric pathogen associated with calf diarrhea worldwide being, in Argentina, mostly detected in dairy husbandry systems. The aim of the present work was to study if maternal IgG1 antibodies (Abs) to BCoV acquired by colostrum intake modulate the development of BCoV infection in calves reared in a dairy farm in Argentina. Thirty Holstein calves were monitored during their first 60 days of age. Animals were classified into two groups depending on their initial BCoV IgG1 Ab titers. The “failure of passive transfer” (FPT) group had significantly lower IgG1 Abs to BCoV than the “acceptable passive transfer” (APT) group of calves (log10 1.98 vs. 3.38 respectively) (p <0.0001). These differences were also observed when the total protein levels in both groups were compared (p =0.0081). Moreover, 71% (5/7) of calves from the FPT group showed IgG1 seroconversion to BCoV compared to 29.4% (5/17) of animals from the APT group. Regarding viral circulation, BCoV was detected in 10% (3/30) of all calves and BCoV IgG1 Ab seroconversion was detected in 42% of the total animals showing that almost half of the calves were infected with BCoV. In conclusion, calves with high titers of specific BCoV IgG1 (≥1024) were mostly protected against viral infection, while animals with low titers of IgG1 (<1024) were mostly infected with BCoV. IgG1 Abs from colostrum origin are critical for prevention of BCoV infection.


title: Coinfection of Chlamydiae and other Bacteria in Reactive Arthritis and Spondyloarthritis: Need for Future Research

text: Reactive (inflammatory) arthritis has been known for many years to follow genital infection with the intracellular bacterial pathogen Chlamydia trachomatis in some individuals. Recent studies from several groups have demonstrated that a related bacterium, the respiratory pathogen Chlamydia pneumoniae, can elicit a similar arthritis. Studies of these organisms, and of a set of gastrointestinal pathogens also associated with engendering inflammatory arthritis, have been relatively extensive. However, reports focusing on coinfections with these and/or other organisms, and the effects of such coinfections on the host immune and other systems, have been rare. In this article, we review the extant data regarding infections by multiple pathogens in the joint as they relate to engendering arthritis, and we suggest a number of research areas that must be given a high priority if we are to understand, and therefore to treat in an effective manner, such arthritides.


title: Comparing the analytical performance of three SARS-CoV-2 molecular diagnostic assays

text: Abstract In December 2019, a novel coronavirus (SARS-CoV-2) was first isolated from Wuhan city, China and within three months, the global community was challenged with a devastating pandemic. The rapid spread of the virus challenged diagnostic laboratories to rapidly develop molecular diagnostic methods. As SARS CoV-2 assays became available for testing on existing molecular platforms, laboratories devoted unprecedented energy and resources into evaluating the analytical performance of the new tests and in some cases developed their own diagnostic assays under FDA-EUA guidance. This study compares the validation of three different molecular assays at the Johns Hopkins Molecular Virology laboratory: the RealStar® SARS-CoV-2 RT-PCR, ePlex® SARS-CoV-2, and the CDC COVID-19 RT-PCR tests. Overall, our studies indicate a comparable analytical performance of the three assays for the detection of SARS-CoV-2.


title: Individual and common inhibitors of coronavirus and picornavirus main proteases

text: Picornaviruses (PV) and coronaviruses (CoV) are positive-stranded RNA viruses which infect millions of people worldwide each year, resulting in a wide range of clinical outcomes. As reported in this study, using high throughput screening against ∼6800 small molecules, we have identified several novel inhibitors of SARS-CoV 3CL(pro) with IC(50) of low μM. Interestingly, one of them equally inhibited both 3C(pro) and 3CL(pro) from PV and CoV, respectively. Using computer modeling, the structural features of these compounds as individual and common protease inhibitors were elucidated to enhance our knowledge for developing anti-viral agents against PV and CoV.


docid: hmwsumqg

title: Addressing the concerns about smallpox


title: Anxiety Regarding Contracting COVID-19 Related to Interoceptive Anxiety Sensations: The Moderating Role of Disgust Propensity and Sensitivity

text: Abstract The COVID-19 public health crisis has led to extensive recommendations by officials to contain its spread. Anxiety regarding contracting the virus is prominent in the public. Specific routes to anxiety over disease contraction are under studied. It is expected that a contributory feature of fear of contracting COVID-19 involve disgust propensity and sensitivity, emotional reactions that are part of a broader behavioral immune system (BIS). A total of N = 908 Chinese adults (mean age = 40.37 years, SD = 9.27; n = 752 female) participated in a survey distributed between February 24 and March 15, 2020. Participants completed measures of anxiety sensitivity, disgust propensity and sensitivity, and fear of contracting COVID-19. Results support a moderating relationship between both disgust propensity and sensitivity in the relationship between physical concerns associated with anxiety sensitivity and fear of contracting COVID-19. These results lend support for individual variation in the activation of the BIS. Recommendations for public education to target individuals who may experience mental health consequences from pandemics are provided.


title: The use of the temporal scan statistic to detect methicillin-resistant Staphylococcus aureus clusters in a community hospital

text: BACKGROUND: In healthcare facilities, conventional surveillance techniques using rule-based guidelines may result in under- or over-reporting of methicillin-resistant Staphylococcus aureus (MRSA) outbreaks, as these guidelines are generally unvalidated. The objectives of this study were to investigate the utility of the temporal scan statistic for detecting MRSA clusters, validate clusters using molecular techniques and hospital records, and determine significant differences in the rate of MRSA cases using regression models. METHODS: Patients admitted to a community hospital between August 2006 and February 2011, and identified with MRSA > 48 hours following hospital admission, were included in this study. Between March 2010 and February 2011, MRSA specimens were obtained for spa typing. MRSA clusters were investigated using a retrospective temporal scan statistic. Tests were conducted on a monthly scale and significant clusters were compared to MRSA outbreaks identified by hospital personnel. Associations between the rate of MRSA cases and the variables year, month, and season were investigated using a negative binomial regression model. RESULTS: During the study period, 735 MRSA cases were identified and 167 MRSA isolates were spa typed. Nine different spa types were identified with spa type 2/t002 (88.6%) the most prevalent. The temporal scan statistic identified significant MRSA clusters at the hospital (n = 2), service (n = 16), and ward (n = 10) levels (P ≤ 0.05). Seven clusters were concordant with nine MRSA outbreaks identified by hospital staff. For the remaining clusters, seven events may have been equivalent to true outbreaks and six clusters demonstrated possible transmission events. The regression analysis indicated years 2009–2011, compared to 2006, and months March and April, compared to January, were associated with an increase in the rate of MRSA cases (P ≤ 0.05). CONCLUSIONS: The application of the temporal scan statistic identified several MRSA clusters that were not detected by hospital personnel. The identification of specific years and months with increased MRSA rates may be attributable to several hospital level factors including the presence of other pathogens. Within hospitals, the incorporation of the temporal scan statistic to standard surveillance techniques is a valuable tool for healthcare workers to evaluate surveillance strategies and aid in the identification of MRSA clusters.


title: Heterogeneity in reporting venous thromboembolic phenotypes in COVID‐19: Methodological issues and clinical implications

text: COVID‐19 is associated with increased risk of venous thromboembolic events (VTE). However, there is significant heterogeneity in the thromboembolic phenotypes of COVID‐19 patients (deep vein thrombosis, pulmonary embolism/thrombosis). The latter might be partly attributed to the variation in VTE risk factors in COVID‐19 patients including: (i) patients’ characteristics; (ii) hospitalization conditions and interventions; (iii) SARS‐Cov‐2 specific factors (coagulopathy, endothelial injury/microthrombosis). Furthermore, there is methodological heterogeneity in relation to the assessment of VTE (indications for screening, diagnostic methodology, etc). Physicians should be aware of the increased VTE risk, strongly consider VTE screening, and use thromboprophylaxis in all hospitalized patients.


title: Adjuvants and adjuvanticity

text: Adjuvants are added to vaccines to increase their potency. In general they do this by stimulating innate immune responses. They can be classified into damage-associated molecular patterns-type adjuvants that act by killing cells so that their released products trigger inflammation. Pathogen-associated molecular patterns-type adjuvants contain microbial molecules that trigger inflammation and dendritic cell maturation through pattern recognition receptors. A third type of adjuvant consists of nanoparticles or emulsions optimized to deliver antigen efficiently to dendritic cells or alternatively to prolong the release of antigen into the body. Different types of adjuvants may be combined to maximize their effect.


title: Complete Genome Sequence of Human Coronavirus Strain 229E Isolated from Plasma Collected from a Haitian Child in 2016

text: Human coronavirus strain 229E (HCoV-229E) and human alphaherpesvirus 1 were isolated from the plasma of a Haitian child in 2016 with suspected arbovirus diseases. To our knowledge, this is the first description of HCoV-229E in human plasma, which is the focus of this article.


title: The chronology of the 2002–2003 SARS mini pandemic

text: Summary Severe acute respiratory syndrome (SARS) was a new human disease in the autumn of 2002. It first occurred in Southern China in November 2002 and was transported to Hong Kong on February 21, 2003 by an infected and ill patient. Ten secondary cases spread the infection to two hospitals in Hong Kong and to Singapore, Toronto and Hanoi. In March 2003 a novel coronavirus (SARS-CoV) was found to be the causative agent. Within 11 weeks from the first SARS case in Hong Kong it had spread to an additional 27 countries or special administrative regions. The mini pandemic peaked during the last week of May 2003 and the last new probable case was on July 13, 2003. There were a total of 8096 probable cases and 774 deaths. Sixty-six per cent of the cases occurred in China, 22% in Hong Kong, 4% in Taiwan and 3% in both Singapore and Canada. Twenty-one per cent of all cases occurred in healthcare workers.


docid: nxolyakn

title: Cells of human aminopeptidase N (CD13) transgenic mice are infected by human coronavirus-229E in vitro, but not in vivo

text: Abstract Aminopeptidase N, or CD13, is a receptor for serologically related coronaviruses of humans, pigs, and cats. A mouse line transgenic for the receptor of human coronavirus-229E (HCoV-229E) was created using human APN (hAPN) cDNA driven by a hAPN promoter. hAPN-transgenic mice expressed hAPN mRNA in the kidney, small intestine, liver, and lung. hAPN protein was specifically expressed on epithelial cells of the proximal convoluted renal tubules, bronchi, alveolar sacs, and intestinal villi. The hAPN expression pattern within transgenic mouse tissues matched that of mouse APN and was similar in mice heterozygous or homozygous for the transgene. Primary embryonic cells and bone marrow dendritic cells derived from hAPN-transgenic mice also expressed hAPN protein. Although hAPN-transgenic mice were resistant to HCoV-229E in vivo, primary embryonic cells and bone marrow dendritic cells were infected in vitro. hAPN-transgenic mice are valuable as a source of primary mouse cells expressing hAPN. This hAPN-transgenic line will also be used for crossbreeding experiments with other knockout, immune deficient, or transgenic mice to identify factors, in addition to hAPN, that are required for HCoV-229E infection.


title: Label-free localized surface plasmon resonance biosensor composed of multi-functional DNA 3 way junction on hollow Au spike-like nanoparticles (HAuSN) for avian influenza virus detection

text: Abstract In the present study, we fabricated a label-free avian influenza (AIV H5N1) detection biosensor composed of a multi-functional DNA 3 way-Junction (3 W J) on a hollow Au spike-like nanoparticle (hAuSN) using a localized surface plasmon resonance (LSPR) method. To construct the multi-functional DNA (MF-DNA) as a bioprobe, the 3 W J was introduced. The proposed AIV detection bioprobe should contain three functionalities: target recognition, signal amplification, and connection to substrate. To achieve this goal, each piece of the DNA 3 W J was tailored to a hemagglutinin (HA) binding aptamer, FAM dye and thiol group, respectively. The assembly of each DNA 3 W J functional fragment was then confirmed by TBM-Native PAGE. Moreover, the hAuSN was immobilized on the indium-tin-oxide (ITO) substrate for LSPR measurement. The DNA 3 W J was immobilized onto the hAuSN electrode through the thiol-group of DNA 3 W J. The fabricated DNA 3 W J/hAuSN heterolayer on the ITO substrate was investigated by field emission scanning electron microscopy (FE-SEM) and atomic force microscopy (AFM). LSPR experiments were conducted to confirm HA protein binding to the DNA 3 W J/ hAuSN -modified electrode. The proposed biosensor can detected the HA protein in PBS buffer (LOD: 1 pM) as well as in the diluted chicken serum (LOD: 1 pM). The present study details a label-free, simple fabrication method consisted of DNA 3 W J/ hAuSN heterolayer that uses easy-to-tailor elements to detect not only AIV but also various viruses detection platform easily.


title: Middle East respiratory syndrome coronavirus-encoded ORF8b strongly antagonizes IFN-β promoter activation: its implication for vaccine design

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a causative agent of severe-to-fatal pneumonia especially in patients with pre-existing conditions, such as smoking and chronic obstructive pulmonary disease (COPD). MERS-CoV transmission continues to be reported in the Saudi Arabian Peninsula since its discovery in 2012. However, it has rarely been epidemic outside the area except one large outbreak in South Korea in May 2015. The genome of the epidemic MERS-CoV isolated from a Korean patient revealed its homology to previously reported strains. MERS-CoV encodes 5 accessory proteins and generally, they do not participate in the genome transcription and replication but rather are involved in viral evasion of the host innate immune responses. Here we report that ORF8b, an accessory protein of MERS-CoV, strongly inhibits both MDA5- and RIG-I-mediated activation of interferon beta promoter activity while downstream signaling molecules were left largely unaffected. Of note, MDA5 protein levels were significantly down-regulated by ORF8b and co-expression of ORF4a and ORF4b. These novel findings will facilitate elucidation of mechanisms of virus-encoded evasion strategies, thus helping design rationale antiviral countermeasures against deadly MERS-CoV infection.


title: Using GPS collars to investigate the frequency and behavioural outcomes of intraspecific interactions among carnivores: A case study of male cheetahs in the Maasai Mara, Kenya

text: Intraspecific interactions between individuals or groups of individuals of the same species are an important component of population dynamics. Interactions can be static, such as spatial overlap, or dynamic based on the interactions of movements, and can be mediated through communication, such as the deployment of scent marks. Interactions and their behavioural outcomes can be difficult to determine, especially for species that live at low densities. With the use of GPS collars we quantify both static and dynamic interactions between male cheetahs (Acinonyx jubatus) and the behavioural outcomes. The 99% home-ranges of males overlapped significantly while there was little overlap of the 50% home-ranges. Despite this overlap, male cheetahs rarely came into close proximity of one another, possibly because presence was communicated through frequent visits to marking posts. The minimum distance between individuals in a dyad ranged from 89m to 196m but the average proximity between individuals ranged from 17,145 ± 6,865m to 26,367 ± 11,288m. Possible interactions took place more frequently at night than by day and occurred mostly in the 50% home-range of one individual of a dyad or where cores of both individuals overlapped. After a possible encounter male cheetahs stayed in close proximity to each other for up to 6 hours, which could be the result of a territory defence strategy or the presence of a receptive female. We believe that one of the encounters between a singleton and a 5-male coalition resulted in the death of the singleton. Our results give new insights into cheetah interactions, which could help our understanding of ecological processes such as disease transmission.


title: Viruses and atypical bacteria in the respiratory tract of immunocompromised and immunocompetent patients with airway infection

text: Respiratory tract infections (RTI) can take a serious course under immunosuppression. Data on the impact of the underlying pathogens are still controversial. Samples from the upper (n = 322) and lower RT (n = 169) were collected from 136 children and 355 adults; 225 among them have been immunocompromised patients. Exclusion criteria were presence of relevant cultivable microorganisms, C-reactive protein > 20 mg/dl, or procalcitonin > 2.0 ng/ml. Samples were tested by PCR for the presence of herpesviruses (HSV-1/-2; VZV; CMV; HHV6; EBV), adenoviruses, bocaviruses, entero-/rhinoviruses (HRV), parechoviruses, coronaviruses, influenza viruses (IV), parainfluenza viruses as well as for pneumoviruses (HMPV and RSV), and atypical bacteria (Mycoplasma pneumoniae, M.p.; Chlamydia pneumoniae, C.p.). Viral/bacterial genome equivalents were detected in more than two-thirds of specimens. Under immunosuppression, herpesviruses (EBV 30.9%/14.6%, p < 0.001; CMV 19.6%/7.9%, p < 0.001; HSV-1: 14.2%/7.1%, p = 0.012) were frequently observed, mainly through their reactivation in adults. Immunocompromised adults tended to present a higher RSV prevalence (6.4%/2.4%, p = 0.078). Immunocompetent patients were more frequently tested positive for IV (15.0%/5.8%, p = 0.001) and M.p. (6.4%/0.4%, p < 0.001), probably biased due to the influenza pandemic of 2009 and an M.p. epidemic in 2011. About 41.8% of samples were positive for a single pathogen, and among them EBV (19.9%) was most prevalent followed by HRV (18.2%) and IV (16.6%). HSV-2 and C.p. were not found. Marked seasonal effects were observed for HRV, IV, and RSV. Differences in pathogen prevalence were demonstrated between immunocompetent and immunocompromised patients. The exact contribution of some herpesviruses to the development of RTI remains unclear. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-020-03878-9) contains supplementary material, which is available to authorized users.


title: Intranasal immunization with plasmid DNA encoding spike protein of SARS-coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses

text: BACKGROUND: Immunization with the spike protein (S) of severe acute respiratory syndrome (SARS)-coronavirus (CoV) in mice is known to produce neutralizing antibodies and to prevent the infection caused by SARS-CoV. Polyethylenimine 25K (PEI) is a cationic polymer which effectively delivers the plasmid DNA. RESULTS: In the present study, the immune responses of BALB/c mice immunized via intranasal (i.n.) route with SARS DNA vaccine (pci-S) in a PEI/pci-S complex form have been examined. The size of the PEI/pci-S nanoparticles appeared to be around 194.7 ± 99.3 nm, and the expression of the S mRNA and protein was confirmed in vitro. The mice immunized with i.n. PEI/pci-S nanoparticles produced significantly (P < 0.05) higher S-specific IgG1 in the sera and mucosal secretory IgA in the lung wash than those in mice treated with pci-S alone. Compared to those in mice challenged with pci-S alone, the number of B220(+ )cells found in PEI/pci-S vaccinated mice was elevated. Co-stimulatory molecules (CD80 and CD86) and class II major histocompatibility complex molecules (I-A(d)) were increased on CD11c(+ )dendritic cells in cervical lymph node from the mice after PEI/pci-S vaccination. The percentage of IFN-γ-, TNF-α- and IL-2-producing cells were higher in PEI/pci-S vaccinated mice than in control mice. CONCLUSION: These results showed that intranasal immunization with PEI/pci-S nanoparticles induce antigen specific humoral and cellular immune responses.


title: Characterization of turkey coronavirus from turkey poults with acute enteritis

text: Abstract The present study was to characterize turkey coronavirus associated with turkey poult enteritis and mortality. Intestinal contents or intestines from affected turkey poults and inoculated turkey embryos contained coronaviruses as revealed by electron microscopy or were positive for turkey coronavirus by immunofluorescent antibody assay. Sucrose density gradient ultracentrifugation of the virus-containing intestinal homogenate yielded two opalescent bands corresponding to the buoyant densities of 1.14–1.15 and 1.18–1.20g/ml, respectively. Coronaviral particles from intestinal contents or the sucrose density gradient preparation were mainly spherical in shape and had envelope and central depression. They were surrounded by a fringe of regularly spaced petal-shaped projections attached to the particles by a short stalk. Purified viruses hemagglutinated rabbit erythrocytes with a titer of 16. Major protein bands of purified viruses analyzed by SDS-PAGE were located at 200, 100–110, 50–60, and 30–35kDa. The patterns of protein bands were consistent with those of Minnesota or Quebec turkey coronavirus isolates. A 568bp nucleotide fragment of turkey coronavirus spike protein gene was amplified from RNA of inoculated turkey embryo intestine or purified virus. Sequence analysis of the 568bp PCR product revealed high degree of identity with the corresponding spike protein gene sequence of human and bovine coronaviruses. The results indicated that turkey coronavirus was associated with turkey poults with acute enteritis.


title: NS5B induces up-regulation of the BH3-only protein, BIK, essential for the hepatitis C virus RNA replication and viral release

text: Abstract Hepatitis C virus (HCV) induces cytopathic effects in the form of hepatocytes apoptosis thought to be resulted from the interaction between viral proteins and host factors. Using pathway specific PCR array, we identified 9 apoptosis-related genes that are dysregulated during HCV infection, of which the BH3-only pro-apoptotic Bcl-2 family protein, BIK, was consistently up-regulated at the mRNA and protein levels. Depletion of BIK protected host cells from HCV-induced caspase-3/7 activation but not the inhibitory effect of HCV on cell viability. Furthermore, viral RNA replication and release were significantly suppressed in BIK-depleted cells and over-expression of the RNA-dependent RNA polymerase, NS5B, was able to induce BIK expression. Immunofluorescence and co-immunoprecipitation assays showed co-localization and interaction of BIK and NS5B, suggesting that BIK may be interacting with the HCV replication complex through NS5B. These results imply that BIK is essential for HCV replication and that NS5B is able to induce BIK expression.


title: Changes of several acute phase factors in broiler chickens in response to infectious bronchitis virus infection

text: ABSTRACT This study was performed to clarify the acute phase response following infectious bronchitis virus inoculation. Ninety clinically healthy 1-d-old Ross chicks were randomly assigned into 2 groups: control (n = 20) and infected group (n = 70). At the age of 20 d, all birds in the infected group were challenged intranasally with allantoic fluid containing 105 embryo lethal dose (ELD50)/0.1 mL of the infectious bronchitis virus. Blood samples were collected from 20 clinically healthy and 70 infected chicks at prior and 1, 2, 3, 5, 7, 11, 13, 15, and 20 d postinoculation. On d 1, 7, and 11 postinoculation 4 chickens from the experimental group and 2 chickens from the control group were randomly selected. Their trachea, lungs, and cecal tonsil were collected for virus detection and quantitation by real-time reverse-transcription PCR assay. In the serum the acute phase proteins (haptoglobin and serum amyloid A), pro-inflammatory cytokines (interferon-γ and tumor necrosis factor-α), and serum sialic acid (total, TSA; lipid-bound, LBSA; and protein-bound, PBSA) concentrations were measured using validated standard procedures. All variables were significantly higher in the infected birds after virus inoculation compared with the healthy group (P < 0.05). There were positive correlations between all variables in the infected group. Correlation coefficients were significantly positive between haptoglobin and interferon-γ, LBSA and TSA, and TSA and LBSA (P < 0.05). There were positive correlations among viral RNA and all studied variables; however, these correlations were not statistically significant (P > 0.05).


COVID-19 pneumonia and the reversed halo sign.


docid: vtxzlqcc

title: COVID-19 and Nigeria: Putting the realities in context

text: Abstract Background The Coronavirus Disease 2019 (COVID-19) which was previously known as 2019-novel Coronavirus (2019-nCoV) was first reported in Wuhan,China in December, 2019. As at today the disease has evolved into a serious global emergency leading to its declaration as a pandemic recently. Body On the African continent, Nigeria is just experiencing the direct effects of this pandemic having recorded her index case in February, 2020 with an increasing number of cases by the day and current case fatality ratio of 0.03 as at 13 April, 2020. Although the recorded cases may albeit seem low, it has been forecasted that Africa will have a fair share of the worst effects of this disease by the end of the pandemic. Generally, African countries have fragile health systems and this remains a source of concern especially in the event of increased outbreaks. Nigeria's current national health systems cannot effectively respond to the growing needs of already infected patients requiring admission into Intensive care units (ICUs) for Acute Respiratory Diseases (ARDs) and SARS COV-2 pnuemonia. This has grim implications for Nigeria especially as increased cases that may require critical care looms. The provision of quarantine or isolation facilities can also be a challenge in Africa and availability of rapid diagnostic kits for fast and reliable testing and diagnosis of the disease. Conclusion There is an urgent need to put in perspective the realities peculiar to Nigeria, and explore available collective measures and interventions to address the Coronavirus pandemic.


title: Social isolation and loneliness among older adults in the context of COVID-19: a global challenge

text: We are experiencing a historical moment with an unprecedented challenge of the COVID-19 global pandemic. The outbreak of COVID-19 will have a long-term and profound impact on older adults’ health and well-being. Social isolation and loneliness are likely to be one of the most affected health outcomes. Social isolation and loneliness are major risk factors that have been linked with poor physical and mental health status. This paper discusses several approaches that may address the issues of social isolation and loneliness. These approaches include promoting social connection as public health messaging, mobilizing the resources from family members, community-based networks and resources, developing innovative technology-based interventions to improve social connections, and engaging the health care system to begin the process of developing methods to identify social isolation and loneliness in health care settings.


title: Differential expression of miR-195-5p in collapse of steroid-induced osteonecrosis of the femoral head

text: BACKGROUND: Femoral head collapse is a key reference point for determining a treatment regimen of femoral head osteonecrosis. However, there are no effective preventive measures and the efficacy of hip-preserving surgery is unsatisfactory due to the unclear mechanism of collapse. This study aimed to identify and validate miRNAs differentially expressed in collapse and non-collapse areas of the osteonecrotic femoral head, and to predict the target genes and pathways of these miRNAs. RESULTS: Nine samples passed the quality control test. A total of 2085 differentially expressed miRNAs were detected, among which 433 miRNAs showed differential expression in the T1 group compared to the W1 group; 344 miRNAs showed differential expression in the T2 group compared to the W2 group; 107 miRNAs showed differential expression in the T3 group compared to the W3 group. After combining data from all three patients, 10 miRNAs showed differential expression in the collapse area (T1+T2+T3) compared to the non-collapse area (W1+W2+W3). Compared to the normal area, has-miR-195-5p showed the most significant downregulation. Expression results from RT-PCR revealed that the expression of hsa-miR-195-5p in the collapse area (T1+T2+T3) was significantly lower than that in the non-collapse area (W1+W2+W3) and normal area (Z1+Z2+Z3). 157 genes were perdicted as the target gene of hsa-miR-195-5p. MATERIALS AND METHODS: Femoral heads of three patients (2 males and 1 female) treated by total hip arthroplasty surgery for steroid-induced femoral head osteonecrosis were selected based on inclusion and exclusion criteria. Bone tissue samples were obtained from the collapse area (T), non-collapse area (W), and normal area (Z) according to the anatomical structure of osteonecrotic femoral heads. Total RNA was extracted from the samples and the microarray chip was scanned. miRNAs showing differential expressions of more than 1.5-fold were selected and was validated by RT-PCR. TargetScan, mirBase and miRanda bioinformatics software was used to predict target genes and identify possible pathways involving these genes. CONCLUSIONS: miR-195-5p showed the most significant difference in the collapse area of osteonecrotic femoral heads, suggesting that collapse may be related to the downregulation of miR-195-5p.


title: Addressing the corona virus outbreak: will a novel filtered eye mask help?

text: Abstract Objective Non-hermetically sealed eye protection does not fully protect the eyes from airborne particles. Hermetically sealed eye protection fully protects the eyes from particles, but tend to fog up rendering unusable. The purpose of this study was build and test a filtered eye mask (FEM) to protect the eyes from airborne particles while being usable without excessive fog build up. Methods The steps performed to build the FEM were described. A hermetically-sealed standard eye mask (SEM) and a FEM were examined at 1minute, 5minutes and 60minute period for performance metrics relating to fog. Results The SEM showed minimal fog at 1-minute, very foggy at 5-minutes and dripping with condensation at 60minutes. The FEM was clear at 1-minute, 5-minutes and showed minimal fog at 60minutes. Conclusion The FEM may play an important role in preventing novel coronavirus (COVID-19) exposure by protecting the eyes from airborne particles and preventing fog, rendering it usable. Further research is strongly recommended.


title: Zoonotic Infection With Pigeon Paramyxovirus Type 1 Linked to Fatal Pneumonia

text: The characteristics and risk factors of pigeon paramyxovirus type 1 (PPMV-1) infection in humans are poorly known. We performed virological, pathological, and epidemiological analyses of a Dutch case, and compared the results with those of a US case. Both infections occurred in transplant patients under immunosuppressive therapy and caused fatal respiratory failure. Both virus isolates clustered with PPMV-1, which has pigeons and doves as reservoir. Experimentally inoculated pigeons became infected and transmitted the virus to naive pigeons. Both patients were likely infected by contact with infected pigeons or doves. Given the large populations of feral pigeons with PPMV-1 infection in cities, increasing urbanization, and a higher proportion of immunocompromised individuals, the risk of severe human PPMV-1 infections may increase. We recommend testing for avian paramyxovirus type 1, including PPMV-1, in respiratory disease cases where common respiratory pathogens cannot be identified.


title: Neutrophil activation and arteritis induced by C. albicans water-soluble mannoprotein-β-glucan complex (CAWS)

text: Abstract We have established a mouse model which shows the symptoms of coronary arteritis after consecutive injections of CAWS, which is released from Candida albicans. In this study, we examined neutrophil activation in the initial period after CAWS injection intraperitoneally. During 10 min to 16 h after the injection, blood profiles and neutrophil functions were determined. At the same time, levels of inflammatory cytokines and chemokines in plasma were measured. Furthermore, level of ICAM-1 as a marker of lesion in arterial endothelial cells was measured. Counts of the peripheral leukocytes increased immediately after CAWS injection, especially involving neutrophil. In vitro sensitivity of neutrophils to stimuli was enhanced. Moreover, proinflammatory cytokines (IL-1β, IL-12 and IL-6) increased in plasma initially followed by an increase in IL-10, G-CSF, MIP-2 and soluble ICAM-1. Locally, ICAM-1 message in arterial walls was significantly increased 16 h after CAWS injection. A decrease in C3 levels was observed in plasma, suggesting complement activation and consumption. In summary, neutrophil activation occurred after CAWS injection, followed by complement activation, and production of proinflammatory cytokines chemokines and G-CSF which may be involved in development of coronary arteritis.


title: What happens next?

text: The novel coronavirus that emerged in Wuhan has exploded worldwide. What happens if it goes pandemic? Debora MacKenzie reports


title: Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)

text: Publisher Summary Severe acute respiratory syndrome (SARS) is caused by a coronavirus (CoV), SARSCoV. SARS-CoV belongs to the family Coronaviridae, which are enveloped RNA viruses in the order Nidovirales. Global research efforts are continuing to increase the understanding of the virus, the pathogenesis of the disease it causes (SARS), and the “heterogeneity of individual infectiousness” as well as shedding light on how to prepare for other emerging viral diseases. Promising drugs and vaccines have been identified. The milestones achieved have resulted from a truly international effort. Molecular studies dissected the adaptation of this virus as it jumped from an intermediary animal, the civet, to humans, thus providing valuable insights into processes of molecular emergence.


title: Ocular Surface Disease in Rodents (Guinea Pigs, Mice, Rats, Chinchillas)

text: This article discusses the clinical appearance, differential diagnoses, and treatment considerations of corneal disease in the most common domesticated species of rodent: mouse, rat, chinchilla, and guinea pig. Many corneal diseases are related to inbred strains of either research or pet rodents. Diseases are complicated by husbandry and treatment-related challenges in this small, social species. This article is broken down by species, first discussing normal anatomy, then discussing commonly encountered diseases, and concluding with treatment considerations.


title: Partial sequence of the spike glycoprotein gene of transmissible gastroenteritis viruses isolated in Korea

text: Abstract The spike (S) glycoprotein of transmissible gastroenteritis virus (TGEV) is the predominant inducer of neutralizing antibodies and has been implicated in virulence and host cell tropism. In this study, the nucleotide and deduced amino acid sequences of the amino terminal half of the S glycoprotein gene of one Korean field TGEV strain (133) isolated in 1997 and three Korean field TGEV strains (KT2, KT3 and KT4) isolated in 2000 and HKT2 strain, KT2 passaged 104 times in ST cells, were determined. The amino terminal half of the S glycoprotein gene including antigenic sites A, B, C and D, were amplified by reverse transcriptase-polymerase chain reaction (RT-PCR). Amplified PCR products were cloned, sequenced, and compared with published sequences for non-Korean TGEV strains. Korea TGEV field strains had 98.5–99.5% nucleotide sequence and 97.2–99.0% amino acid sequence similarity with each other. They had 96.5–99.0% nucleotide sequence similarity and 94.9–97.6% amino acid sequence similarity compared to non-Korean TGEV strains. Korean TGEV strains had several specific nucleotide and amino acid sequences which were not found in foreign TGEV or PRCV strains. HKT2 strain differed by 0.89% in nucleotide and 2.03% amino acid sequences compared to original KT2 strain although the regions forming four antigenic sites were not changed. By phylogenetic tree analysis, Korean field TGEV strains were branched into different groups from non-Korean TGEV or PRCV strains. Korean TGEV field strains KT2 and 133 were branched in separate groups that were differentiated from the other Korean TGEV strains. The Korean TGEV strains seemed to be evolved from a separate lineage of TGEV strain.


title: Bacterial and Parasitic Diseases of Columbiformes

text: Bacterial and parasitic diseases are not uncommon in domestic doves and pigeons. Many of the bacteria and parasites found in columbids do not cause disease unless the birds are immunocompromised. Often there are underlying viral infections that contribute to illness. This article focuses on some of the more common infections from a practical clinical point of view. Recent updates from the literature are included.


docid: ryjxbqno

title: Bronchial hyperresponsiveness and cytokines in virus‐induced asthma exacerbations


title: Acute myocarditis and multisystem inflammatory emerging disease following SARS-CoV-2 infection in critically ill children

text: BACKGROUND: A recent increase in children admitted with hypotensive shock and fever in the context of the COVID-19 outbreak requires an urgent characterization and assessment of the involvement of SARS-CoV-2 infection. This is a case series performed at 4 academic tertiary care centers in Paris of all the children admitted to the pediatric intensive care unit (PICU) with shock, fever and suspected SARS-CoV-2 infection between April 15th and April 27th, 2020. RESULTS: 20 critically ill children admitted for shock had an acute myocarditis (left ventricular ejection fraction, 35% (25–55); troponin, 269 ng/mL (31–4607)), and arterial hypotension with mainly vasoplegic clinical presentation. The first symptoms before PICU admission were intense abdominal pain and fever for 6 days (1–10). All children had highly elevated C-reactive protein (> 94 mg/L) and procalcitonin (> 1.6 ng/mL) without microbial cause. At least one feature of Kawasaki disease was found in all children (fever, n = 20, skin rash, n = 10; conjunctivitis, n = 6; cheilitis, n = 5; adenitis, n = 2), but none had the typical form. SARS-CoV-2 PCR and serology were positive for 10 and 15 children, respectively. One child had both negative SARS-CoV-2 PCR and serology, but had a typical SARS-CoV-2 chest tomography scan. All children but one needed an inotropic/vasoactive drug support (epinephrine, n = 12; milrinone, n = 10; dobutamine, n = 6, norepinephrine, n = 4) and 8 were intubated. All children received intravenous immunoglobulin (2 g per kilogram) with adjuvant corticosteroids (n = 2), IL 1 receptor antagonist (n = 1) or a monoclonal antibody against IL-6 receptor (n = 1). All children survived and were afebrile with a full left ventricular function recovery at PICU discharge. CONCLUSIONS: Acute myocarditis with intense systemic inflammation and atypical Kawasaki disease is an emerging severe pediatric disease following SARS-CoV-2 infection. Early recognition of this disease is needed and referral to an expert center is recommended. A delayed and inappropriate host immunological response is suspected. While underlying mechanisms remain unclear, further investigations are required to target an optimal treatment.


title: Clinico-epidemiological characteristics of acute respiratory infections by coronavirus OC43, NL63 and 229E

text: Abstract Background and objectives Acute respiratory infection is a very common condition in the general population. The majority of these infections are due to viruses. This study attempted to determine the clinical and epidemiological characteristics of adult patients with respiratory infection by the coronavirus OC43, NL63 and 229E. Patients and methods Between January 2013 and February 2014, we prospectively studied all patients with suspected clinical respiratory infection by taking throat swabs and performing a reverse transcription polymerase chain reaction in search of coronavirus. Results In 48 cases (7.0% of the 686 enrolled patients; 12.6% of the 381 in whom a virus was detected) the presence of a coronavirus demonstrated. In 24 cases, the virus was OC43 (50%); in 14 cases, the virus was NL63 (29%); and in 10 cases, the virus was 229E (21%). The mean age was 54.5 years, with a slight predominance of men. The most common clinical presentations were nonspecific influenza symptoms (43.7%), pneumonia (29.2%) and chronic obstructive pulmonary disease exacerbation (8.3%). Fifty-two percent of the patients required hospitalization, and 2 patients required intensive care. There were no deaths. Conclusion Acute respiratory infections caused by coronavirus mainly affect middle-aged male smokers, who are often affected by previous diseases. The most common clinical picture has been nonspecific influenza symptoms.


title: Anatomy and Neurophysiology of Cough: CHEST Guideline and Expert Panel Report

text: Bronchopulmonary C-fibers and a subset of mechanically sensitive, acid-sensitive myelinated sensory nerves play essential roles in regulating cough. These vagal sensory nerves terminate primarily in the larynx, trachea, carina, and large intrapulmonary bronchi. Other bronchopulmonary sensory nerves, sensory nerves innervating other viscera, as well as somatosensory nerves innervating the chest wall, diaphragm, and abdominal musculature regulate cough patterning and cough sensitivity. The responsiveness and morphology of the airway vagal sensory nerve subtypes and the extrapulmonary sensory nerves that regulate coughing are described. The brainstem and higher brain control systems that process this sensory information are complex, but our current understanding of them is considerable and increasing. The relevance of these neural systems to clinical phenomena, such as urge to cough and psychologic methods for treatment of dystussia, is high, and modern imaging methods have revealed potential neural substrates for some features of cough in the human.


Severe acute respiratory syndrome in haemodialysis patients: a report of two cases


title: Middle East respiratory syndrome coronavirus (MERS-CoV) entry inhibitors targeting spike protein

text: Abstract The recent outbreak of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) infection has led to more than 800 laboratory-confirmed MERS cases with a high case fatality rate (∼35%), posing a serious threat to global public health and calling for the development of effective and safe therapeutic and prophylactic strategies to treat and prevent MERS-CoV infection. Here we discuss the most recent studies on the structure of the MERS-CoV spike protein and its role in virus binding and entry, and the development of MERS-CoV entry/fusion inhibitors targeting the S1 subunit, particularly the receptor-binding domain (RBD), and the S2 subunit, especially the HR1 region, of the MERS-CoV spike protein. We then look ahead to future applications of these viral entry/fusion inhibitors, either alone or in combination with specific and nonspecific MERS-CoV replication inhibitors, for the treatment and prevention of MERS-CoV infection.


title: Navigating the impact of COVID‐19 on palliative care for head and neck cancer

text: Health care services are being confronted by a daily dilemma of who can receive critical care and who cannot. In a palliative care clinic, this apprehension gets exemplified, as these patients have limited life expectancy. The head and neck region further makes things critical, as it comprises of all the sites through which the SARS‐CoV‐2 can be transmitted. This document strives to define the ways in which the head and neck cancer services can contribute to better patient care in a triage context. Practical steps suggested are protective equipment use, ensuring access to critical drugs (such as opioids), greater use of telemedicine consultations, discussing advance care plans, and embracing the role of a wider community support.


title: Emerging viral infections

text: "Emerging infections" have been defined as infections that have newly appeared, that have appeared previously but are expanding in incidence and geographic range, or that threaten to increase in the near future. This article focuses on nine emerging viral infectious agents. These viruses illustrate how such agents emerge: by encroaching on previously unvisited habitats (eg, hantaviruses), by air travel (eg, SARS), and by accidental importation (eg, monkeypox). Additionally, the example of SARS demonstrates not only how quickly emerging viral infections can spread but also how quickly they can be identified and contained with motivated cooperation.


title: Delayed Suspicion, Treatment and Isolation of Tuberculosis Patients in Pulmonology/Infectious Diseases and Non-Pulmonology/Infectious Diseases Wards

text: Background/Purpose Delayed diagnosis and isolation increases the risk of nosocomial transmission of tuberculosis (TB). To assess the risk of delayed management of TB, we analyzed the risk factors of prolonged delay in isolation of smear-positive TB patients in pulmonology/infectious diseases and other wards in a tertiary teaching hospital. Methods We enrolled smear-positive TB patients aged > 16 years with delayed respiratory isolation following hospitalization. Medical records were reviewed retrospectively. Time intervals between admission, order of sputum acid-fast staining, initiation of anti-tuberculous treatment and isolation were compared between pulmonology/infectious diseases wards (PIWs) and other wards. Risk factors were analyzed in patients with prolonged isolation delay of > 7 days in individual groups. Results Isolation was delayed in 191 (73.7%) of 259 hospitalized smear-positive TB patients. Median suspicion, treatment and isolation delays were 0, 3 and 4 days in PIWs and 1, 5 and 7 days in other wards. For patients admitted to non-PIWs, atypical chest radiographs, symptoms without dyspnea or not being admitted from the emergency department (ED) were risk factors for prolonged isolation delay exceeding 7 days. The only risk factor for delayed isolation in patients admitted to PIWs was age ≥ 70 years. Conclusion Delays in suspicion, treatment and isolation of TB patients were longer in non-PIWs. Clinicians should be alert to those admitted to non-PIWs with atypical chest radiographs, atypical symptoms, or not admitted from the ED.


title: Revisión sistemática sobre la utilidad pronóstica del dímero-D, coagulación intravascular diseminada y tratamiento anticoagulante en pacientes graves con COVID-19

text: Resumen Durante la nueva pandemia causada por SARS-CoV-2, existe poca evidencia en relación a varios aspectos de la enfermedad, como es el caso de la coagulopatía e interpretación de los niveles de dímero D, su asociación con coagulación intravascular diseminada (CID) y controversia en cuanto al beneficio de la anticoagulación. Por ello, se ha realizado una revisión sistemática para definir el rol del dímero D en la enfermedad, la prevalencia y valor pronóstico de la CID y la utilidad del tratamiento anticoagulante en dichos pacientes. Se realizó una búsqueda bibliográfica y análisis de la literatura sobre pacientes con COVID-19. Se elaboraron cuatro recomendaciones basadas en la opinión de expertos y en el conocimiento científico, según el sistema Grading of Recommendations Assesment, Development and Evaluation (GRADE). La presente revisión en pacientes con COVID-19 sugiere la presencia de mayores niveles de dímero D en aquellos con peor pronóstico, que puede haber un sobrediagnóstico de CID en el curso de la enfermedad y que no existe evidencia sobre el beneficio de iniciar tratamiento anticoagulante basándose únicamente en datos aislados de laboratorio. Abstract During the new pandemic caused by SARS-CoV-2, there is short knowledge regarding the management of different disease areas, such as coagulopathy and interpretation of D-dimer levels, its association with disseminated intravascular coagulation (DIC) and controversy about the benefit of anticoagulation. Thus, a systematic review has been performed to define the role of D-dimer in the disease, the prevalence of DIC and the usefulness of anticoagulant treatment in these patients. A literature search was performed to analyze the studies of COVID-19 patients. Four recommendations were drawn based on expert opinion and scientific knowledge, according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The present review suggests the presence of higher levels of D-dimer in those with worse prognosis, there may be an overdiagnosis of DIC in the course of the disease and there is no evidence on the benefit of starting anticoagulant treatment based only on isolated laboratory data.


docid: qdxqnwee

title: Coronavirus Infection and Hospitalizations for Acute Respiratory Illness in Young Children

text: PROBLEM: There is only limited knowledge on the burden of disease due to both new (HCoV-NL63 and HKU-1) and previously discovered coronaviruses (OC43 and 229E) in children. METHOD OF STUDY: Respiratory specimens and clinical data were prospectively collected in an active, population-based surveillance study over a two-year period from children aged <5 years hospitalized with acute respiratory symptoms or fever. These samples were retrospectively tested by real-time RT-PCR for HCoV-NL63, HKU1, OC43 and 229E. RESULTS: Human coronaviruses (HCoVs) were identified in 2.2% of study children <2 years of age. Rates of HCoV-associated hospitalization per 10,000 were 10.2 (95% CI 4.3, 17.6), 4.2 (95% CI 1.9, 6.9), and 0 (95% CI 0, 3.7) in children aged <6 months, 6-23 months, and 24-59 months, respectively. CONCLUSION: Coronaviruses were identified in a modest number of hospitalized children.


docid: woyexnsh

title: Overview of rapid mitigating strategies in Singapore during COVID-19 pandemic

text: Abstract This article describes the rapid mitigation strategies in addressing the rising numbers of coronavirus disease 2019 (COVID-19) cases in Singapore. Learning from the severe acute respiratory syndrome (SARS) experience in 2003, early preparation started in January 2020 when Wuhan was declared as the epicentre of the epidemic. The government had constructed a three-pronged approach which includes travel, healthcare, and community measures to curb the spread of COVID-19.


Reconstruction of the most recent common ancestor sequences of SARS-Cov S gene and detection of adaptive evolution in the spike protein


title: COVID 19 associated encephalopathy: Neurological manifestation of COVID-19

text: Covid-19 is a viral disease, also known as SARS-Cov-2, was first reported in Wuhan China, December 2019. Respiratory manifestations from the induced acute lung injury were the most common reported findings. Few cases showed extrapulmonary manifestations. Covid-19 associated neurological manifestations have not been widely reported. In this report, we describe a case of encephalopathy in a patient with Covid-19 infection. Abbreviations: SARS-Cov-2, severe acute respiratory syndrome coronavirus 2; COVID-19, coronavirus disease 2019;; RT-PCR, Reverse transcription polymerase chain reaction; ED, emergency department; ICU, intensive care unit; GCS, Glasgow Coma Scale; HRCT, high resolution computed tomography; CT, computed tomography; MRI, magnetic resonance imaging; FLAIR, fluid attenuated inversion recovery; ADC, apparent diffusion coefficient; DWI: diffusion weighted imaging; CNS, central nervous system.


title: Pros and cons for use of statins in people with coronavirus disease-19 (COVID-19)

text: BACKGROUND AND AIMS: Morbidity and mortality from coronavirus disease 2019 (COVID-19) is higher among people with diabetes mellitus (DM), hypertension, and cardiovascular disease (CVD). Statins are used in the majority of people with DM and CVD. This mini-review discusses the current understanding of benefit-risk ratio of use of statins in COVID-19. METHODS: We searched PubMed database using specific keywords related to our aims till June 12, 2020. Full text of relevant articles published in English language were retrieved and reviewed. RESULTS: Statins, with their immunomodulatory, anti-inflammatory, anti-thrombotic, and anti-oxidant properties, have the potential to reduce severity of lung injury in, and mortality from, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) infections. Statin-induced upregulation of angiotensin-converting enzyme-2 (ACE2) has the potential to reduce lung injury from excess angiotensin II. By disrupting lipid rafts, statins have the potential to reduce viral entry into cells. However, benefit-risk ratio of its complex interaction with MYD88 gene expression on outcomes in COVID-19, and the putative role of low serum LDL cholesterol in increasing severity of SARS-CoV2 infection need further clarification. CONCLUSIONS: People with COVID-19, who are already on statins for an underlying co-morbid condition, should continue on it unless there are specific contraindications. De-novo use of statins in people with COVID-19 with no underlying co-morbidity might be beneficial but awaits substantiation in clinical trials; till that time, de novo use of statins in COVID 19 should be limited to a clinical trial setting.


title: Amiodarone impairs trafficking through late endosomes inducing a Niemann-Pick C-like phenotype

text: Abstract Patients treated with amiodarone accumulate lysobisphosphatidic acid (LBPA), also known as bis(monoacylglycero)phosphate, in airway secretions and develop in different tissues vacuoles and inclusion bodies thought to originate from endosomes. To clarify the origin of these changes, we studied in vitro the effects of amiodarone on endosomal activities like transferrin recycling, Shiga toxin processing, ESCRT-dependent lentivirus budding, fluid phase endocytosis, proteolysis and exosome secretion. Furthermore, since the accumulation of LBPA might point to a broader disturbance in lipid homeostasis, we studied the effect of amiodarone on the distribution of LBPA, unesterified cholesterol, sphingomyelin and glycosphyngolipids. Amiodarone analogues were also studied, including the recently developed derivative dronedarone. We found that amiodarone does not affect early endosomal activities, like transferrin recycling, Shiga toxin processing and lentivirus budding. Amiodarone, instead, interferes with late compartments of the endocytic pathway, blocking the progression of fluid phase endocytosis and causing fusion of organelles, collapse of lumenal structures, accumulation of undegraded substrates and amassing of different types of lipids. Not all late endocytic compartments are affected, since exosome secretion is spared. These changes recall the Niemann-Pick type-C phenotype (NPC), but originate by a different mechanism, since, differently from NPC, they are not alleviated by cholesterol removal. Studies with analogues indicate that basic pKa and high water-solubility at acidic pH are crucial requirements for the interference with late endosomes/lysosomes and that, in this respect, dronedarone is at least as potent as amiodarone. These findings may have relevance in fields unrelated to rhythm control.


title: Beyond self-eating: The control of nonautophagic functions and signaling pathways by autophagy-related proteins

text: The identification of conserved autophagy-related proteins (ATGs) that mediate bulk degradation of cytosolic material laid the foundation for breakthroughs linking autophagy to a litany of physiological processes and disease conditions. Recent discoveries are revealing that these same ATGs orchestrate processes that are related to, and yet clearly distinct from, classic autophagy. Autophagy-related functions include secretion, trafficking of phagocytosed material, replication and egress of viral particles, and regulation of inflammatory and immune signaling cascades. Here, we define common processes dependent on ATGs, and discuss the challenges in mechanistically separating autophagy from these related pathways. Elucidating the molecular events that distinguish how individual ATGs function promises to improve our understanding of the origin of diseases ranging from autoimmunity to cancer.


title: Structural basis of mercury- and zinc-conjugated complexes as SARS-CoV 3C-like protease inhibitors

text: Five active metal-conjugated inhibitors (PMA, TDT, EPDTC, JMF1586 and JMF1600) bound with the 3C-like protease of severe acute respiratory syndrome (SARS)-associated coronavirus were analyzed crystallographically. The complex structures reveal two major inhibition modes: Hg(2+)-PMA is coordinated to C(44), M(49) and Y(54) with a square planar geometry at the S3 pocket, whereas each Zn(2+) of the four zinc-inhibitors is tetrahedrally coordinated to the H(41)–C(145) catalytic dyad. For anti-SARS drug design, this Zn(2+)-centered coordination pattern would serve as a starting platform for inhibitor optimization.


title: Seroprevalence of antibodies to the influenza A (H1N1) virus among healthcare workers prior to the 2009 pandemic peak

text: OBJECTIVE: Our aim was to study the proportion of healthcare workers with a positive serology for Influenza A(H1N1)2009 without having flu, in a Spanish hospital at the beginning of the pandemic. METHODS: A survey study carried out during August 2009 (before the peak of the pandemic in Spain) in the Hospital Costa del Sol, a second level hospital with almost 300 beds in the South of Spain. The participants were workers in the following hospital units: Emergencies, Medical Area (Internal Medicine, Chest Diseases), Surgical Area (General Surgery and Anaesthesia) of any professional category. A study was made of the proportion of healthcare workers in our hospital with positive serology for the new influenza A (H1N1)2009 virus, as determined by the haemagglutination inhibition technique (≥1/40). The subjects completed a health status questionnaire, and provided a blood sample for serology testing. RESULTS: A total of 239 workers participated, of whom 25.1% had positive serology. The hospital area in which most individuals had positive serology was the Emergency Department (36.6%), while the professional category in which most individuals with a positive serology worked was that of the orderlies (41.7%). CONCLUSION: Around 25% of healthcare workers in our hospital had positive serology before the peak of the pandemic, none of them had received vaccine for Influenza A (H1N1) 2009 or had been diagnosed of influenza previously.


title: Mutated COVID-19 may foretell a great risk for mankind in the future

text: Coronavirus disease 2019 SARS-CoV-2 (COVID-19) is a zoonotic virus causing a variety of severe respiratory diseases. SARS-CoV-2 is closest to SARS-CoV and MERS-CoV in structure. The high prevalence of COVID-19 is a result of a lack of symptoms at onset. Our study aimed to present an overview of the virus in terms of structure, epidemiology, symptoms, treatment and prevention. Whole genome sequences and some viral proteins were investigated to determine gaps and changes in alternation of nucleotides and amino acid sequences. We evaluate 11 complete genome sequences of different coronaviruses using BAST and MAFFT software. We also selected seven types of structural proteins. We conclude that COVID-19 might produce new mutations, specifically in glycoproteins, so caution and complete preparation by health authorities is required.


title: A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2

text: Neutralizing antibodies could be antivirals against COVID-19 pandemics. Here, we report isolation of four human-origin monoclonal antibodies from a convalescent patient, all of which display neutralization abilities. B38 and H4 block the binding between virus S-protein RBD and cellular receptor ACE2. A competition assay indicates their different epitopes on the RBD, making them a potential virus-targeting MAb-pair to avoid immune escape in future clinical applications. Moreover, a therapeutic study in a mouse model validated that these antibodies can reduce virus titers in infected lungs. The RBD-B38 complex structure revealed that most residues on the epitope overlap with the RBD-ACE2 binding interface, explaining the blocking effect and neutralizing capacity. Our results highlight the promise of antibody-based therapeutics and provide a structural basis for rational vaccine design.


Community health workers reveal COVID-19 disaster in Brazil


title: Evaluation of a protocol to reduce the incidence of neonatal calf diarrhoea on dairy herds

text: Abstract Calf diarrhoea causes substantial economic losses in cattle herds worldwide. Neonatal calves are particularly sensitive to infections with enteropathogens. The present study focused on prevention against the main infectious causes of neonatal calf diarrhoea i.e. Escherichia coli, rota- and coronavirus, and Cryptosporidium parvum. Dairy herds (n =24) with a high percentage of neonatal calves scouring (>10%) were included and calves were sampled for the presence of these four enteropathogens. To decrease diarrhoea problems among neonatal calves, a standard protocol was tested on 13 herds (treatment group) where both C. parvum and either E. coli or rota- or coronavirus were identified as being involved, the other 11 herds served as control group. The protocol consisted of 2 points of action: preventive vaccination of dams against E. coli, rota- and coronavirus, and preventive administration of halofuginone lactate to newborn calves. The average percentage of calves suffering from neonatal diarrhoea (39.7% versus 14.3%, P <0.01) and the average percentage of faecal samples positive for C. parvum (34% versus 11%, P <0.05) differed significantly between control herds and treatment herds after implementation of the protocol. No significant differences between control and treatment group were observed in the percentage of calves excreting E. coli, rotavirus and coronavirus, both before and at the end of the trial. Furthermore, risk factors potentially associated with the development of neonatal calf scours were determined. Non-significant results were obtained for the effect of the protocol on duration of diarrhoea and the effect of the colostral IgG quantity on the risk of diarrhoea. Passive immunity transfer status of the calves, measured both before the onset and at the end of the study, were non-significant between groups.


title: Ultraviolet irradiation of spray-dried porcine plasma does not affect the growth performance of nursery pigs when compared with nonirradiated bovine plasma

text: Ultraviolet light irradiation of spray-dried porcine plasma (SDPP) decreases the risk of disease transmission, but it may decrease the activity of bioactive components in SDPP. Therefore, the objectives of this study were to determine growth performance, morbidity, and mortality responses of nursery pigs fed UV-irradiated SDPP (UV-SDPP) compared with nonirradiated spray-dried bovine plasma (SDBP). Pigs (n = 480; 6.09 ± 2.4 kg initial BW) were blocked by initial BW, and blocks were assigned to pens. the sex ratio was equalized within blocks and pens. Pens were randomly assigned to 1 of 5 dietary treatments (8 pigs/pen and 12 replicates/treatment) in a 3-phase feeding program (phase 1 = d 0 to 13, phase 2 = d 14 to 27, and phase 3 = d 28 to 55). Dietary treatments included a control diet without UV-SDPP or SDBP and diets containing 3% UV-SDPP, 3% SDBP, 6% UV-SDPP, or 6% SDBP during phase 1. Diets were formulated to meet or exceed nutrient requirements and contained the same concentrations of standardized ileal digestible Lys and Lys:ME ratio within phases. Pigs were provided ad libitum access to diets throughout the 55-d experiment. Dietary inclusion rates during phase 2 were reduced to 1.5% UV-SDPP, 1.5% SDBP, 3% UV-SDPP, and 3% SDBP, and all pigs were fed a common diet without UV-SDPP or SDBP during phase 3. Growth performance data were analyzed as a 2 × 2 factorial arrangement of treatments with a control within a completely randomized block design to evaluate the main effects of plasma processing (UV irradiated vs. nonirradiated) and dietary inclusion level, and block, room, and pen were random effects. In phase 1, there were no differences in G:F among treatments, but pigs fed 6% UV-SDPP and 6% SDBP had greater (P < 0.01) ADG (0.11 vs. 0.08 kg/d) and ADFI (0.17 vs. 0.15 kg/d) than pigs fed the control, 3% SDBP, and 3% UV-SDPP diets. After phase 1 (d13), feeding UV-SDPP or SDBP increased (P = 0.02) the BW of pigs. In phases 2 and 3 and the overall feeding period (d 0 to 55), there were no differences in ADG, ADFI, and G:F among dietary treatments. There was a linear decrease (P < 0.01) in mortality of nursery pigs as dietary inclusion rate of SDBP and UV-SDPP increased. In conclusion, feeding SDBP or UV-SDPP diets improved ADG and ADFI during the first 2 wk after weaning due to improved feed consumption, and UV irradiation appeared to have no detrimental effects on the feeding value of SDPP.


docid: ioxljlcu

title: Spike protein assembly into the coronavirion: exploring the limits of its sequence requirements

text: Abstract The coronavirus spike (S) protein, required for receptor binding and membrane fusion, is incorporated into the assembling virion by interactions with the viral membrane (M) protein. Earlier we showed that the ectodomain of the S protein is not involved in this process. Here we further defined the requirements of the S protein for virion incorporation. We show that the cytoplasmic domain, not the transmembrane domain, determines the association with the M protein and suffices to effect the incorporation into viral particles of chimeric spikes as well as of foreign viral glycoproteins. The essential sequence was mapped to the membrane-proximal region of the cytoplasmic domain, which is also known to be of critical importance for the fusion function of the S protein. Consistently, only short C-terminal truncations of the S protein were tolerated when introduced into the virus by targeted recombination. The important role of the about 38-residues cytoplasmic domain in the assembly of and membrane fusion by this approximately 1300 amino acids long protein is discussed.


title: Ethics and Social Value Judgments in Public Health

text: Abstract The exercise of government powers for the health of its population raises ethical issues, such as public welfare, individual autonomy and freedom, privacy and confidentiality, just distribution of benefits and burdens, transparency, and public accountability. Conflicts among these values often arise and how they should be balanced will vary on a case-by-case basis, weighing costs against benefits. This entry discusses justifications for government action in public health, the tension between individual freedom and public health, issues of distributive justice in public health, and ethical guidelines for public health policymaking.


title: Manejo Seguro De La Ropa E Higiene De La Piel En Pacientes Y Profesionales Sanitarios Frente Al Covid-19: Scoping Review

text: Resumen Introducción: En enero de 2020 aparece en China un brote de neumonía causada por un virus zoonótico(SARS-CoV-2). Se considera que la ruta principal de transmisión es por inhalación de grandes gotas respiratorias, por deposición en las mucosas y las manos o los fómites contaminados. El objetivo es identificar las intervenciones a realizar durante la hospitalización para un manejo correcto y seguro de la ropa e higiene de los pacientes y profesionales sanitarios. Método: Scoping review realizada sin delimitación cronológica ni de idioma en las bases de datos PUBMED y Cochrane. Rastreo de normas y recomendaciones de entidades gubernamentales nacionales e internacionales para responder a la pregunta de investigación sobre el manejo seguro de la ropa y la higiene de la piel en pacientes y en profesionales sanitarios para evitar el contagio por Covid-19. El análisis de los datos fue realizado en dos etapas: en la primera, identificación y categorización de los estudios, y en la segunda, análisis de contenido como criterio informativo y clasificatorio. Resultados: Se han seleccionado 14 documentos, principalmente de entidades gubernamentales. Las recomendaciones se estructuran en 5 epígrafes sobre manejo de ropa e higiene de la piel de pacientes infectados y profesionales sanitarios en el ámbito hospitalario. Conclusión: La ropa de los pacientes y del personal sanitario son vehículos transmisores de la enfermedad. Su correcto tratamiento ayuda a mejorar el control de la misma y a una correcta utilización de los recursos disponibles en estos momentos. La adecuada higiene de la piel, en especial la limpieza de las manos, constituye uno de los pilares básicos para la prevención y el control de la infección. Destacamos la semejanza de algunas de las pautas recogidas y proporcionadas por los diferentes organismos consultados Abstract Introduction: In January 2020, an outbreak of pneumonia caused by a zoonotic virus (SARS-CoV-2) appeared in China. The main route of transmission is considered to be the inhalation of large respiratory drops, by deposition in the mucosa and hands or contaminated fomites. The objective is to identify the interventions to be performed during hospitalization for the correct and safe handling of clothing and hygiene of patients and health professionals. Method: Scoping review carried out without chronological or language delimitation in the PUBMED and Cochrane databases. Tracking standards and recommendations of national and international government entities to answer the research question on the safe handling of clothing and skin hygiene in patients and in health professionals to avoid Covid-19 infection. The data analysis was carried out in two stages: in the first, identification and categorization of the studies, and in the second, content analysis as an informative and classifying criterion. Results: 14 documents have been selected, mainly from government entities. The recommendations are structured in 5 sections on the management of clothing and skin hygiene of infected patients and health professionals in the hospital setting. Conclusion: The clothing of patients and healthcare personnel are transmitting vehicles of the disease. Its correct treatment helps to improve the control of the same and the correct use of the resources available at the moment. Proper skin hygiene, especially hand cleansing, is one of the basic pillars for infection prevention and control. We highlight the similarity of some of the guidelines collected and provided by the different agencies consulted.


title: An Expedient Synthesis of Flexible Nucleosides through Enzymatic Glycosylation of Proximal and Distal Fleximer Bases

text: The structurally unique “fleximer” nucleosides were originally designed to investigate how flexibility in a nucleobase could potentially affect receptor–ligand recognition and function. Recently they have been shown to have low‐to‐sub‐micromolar levels of activity against a number of viruses, including coronaviruses, filoviruses, and flaviviruses. However, the synthesis of distal fleximers in particular has thus far been quite tedious and low yielding. As a potential solution to this issue, a series of proximal fleximer bases (flex‐bases) has been successfully coupled to both ribose and 2′‐deoxyribose sugars by using the N‐deoxyribosyltransferase II of Lactobacillus leichmannii (LlNDT) and Escherichia coli purine nucleoside phosphorylase (PNP). To explore the range of this facile approach, transglycosylation experiments on a thieno‐expanded tricyclic heterocyclic base, as well as several distal and proximal flex‐bases were performed to determine whether the corresponding fleximer nucleosides could be obtained in this fashion, thus potentially significantly shortening the route to these biologically significant compounds. The results of those studies are reported herein.


title: SARS in Taiwan: an overview and lessons learned

text: Summary Objectives: This report aims to describe the epidemiology of severe acute respiratory syndrome (SARS) in Taiwan between March and July 2003, and to examine the public health response. Methods: Surveillance for SARS was initiated on 14 March 2003. Response activities are described for the isolation of patients; contact tracing; quarantine of contact persons; fever screening for inbound and outbound passengers at the airport; and hospital infection control as assessed by mobile SARS containment teams. Results: Between 14 March and 30 July 2003 a total of 668 probable cases of SARS were reported. Of the 668 cases, 181 (27%) were fatal. Compared to the survivors, fatal cases were more likely to be older (p <0.001), male (p <0.05), exposed through hospital contact (p <0.001), and have a coexisting medical disorder (p <0.001). Between 28 March and 30 July a total of 151,270 persons were quarantined. Among them, 46 (3.0/10,000) were subsequently classified as being probable SARS cases. At the time of the mobile team assessments, 46 (53%) hospitals had implemented WHO infection control recommendations. Conclusions: In this outbreak, an emergency plan consisted of patient isolation and strict hospital infection control.


This editorial aims to summarize the nine scientific papers that contributed to the Special Issue entitled ‘Nanoparticles to Improve the Efficacy of Vaccines’.


title: Island blues: indigenous knowledge of indigo-yielding plant species used by Hainan Miao and Li dyers on Hainan Island, China

text: BACKGROUND: Historically, indigo-yielding plant species were important cash crops from Central Asia to the southern United States and Central America. Indigo-dyed textiles were widely traded along the legendary Silk Road that linked China to Europe. Today, due to the labor-intensive nature of indigo extraction at the household level, lifestyle changes and the widespread availability of commercially produced indigo paste, traditional indigo extraction methods have declined in villages. Yet Li textile weavers on Hainan Island are internationally recognized as producers of indigo-dyed textile using warp ikat techniques. In contrast, Hainan Miao weavers produce indigo-dyed textiles using batik (wax resist) techniques. The aim of this study was to document the indigenous knowledge on indigo-yielding plant species used by both Hainan Miao and Li people on Hainan Island, China. METHOD: Ethnic uses were documented during three field surveys, through a questionnaire survey of 193 respondents, comprising 144 Hainan Miao and 49 Li traditional dyers. Mention index (QI), Availability index (AI), and Preference ranking (PR) of each indigo-yielding plant species were calculated to screen out plant resources with potential development value. RESULTS: Five indigo-yielding plant species (from four plant families and four genera) were historically used by Hainan Miao and Li dyers. However, just four species are still in use. Strobilanthes cusia was the main indigo source for Hainan Miao dyers. Li dyers also commonly use Indigofera species (I. tinctoria and I. suffruticosa) for indigo extraction. Wrightia laevis is less commonly used as a contemporary indigo source. Indigo extraction by steeping in water to which lime is added to increase the pH is sharing by the five indigo-yielding plant species. Strobilanthes cusia had the highest QI, AI and PR values in Hainan Miao villages. Indigofera tinctoria had the highest QI and AI values, but Indigofera suffruticosa was preferred by Li dyers. CONCLUSION: In the process of modernization and urbanization, some Hainan Miao and Li dyers retain the traditional indigo extraction methods. We found that Strobilanthes cusia and Indigofera tinctoria have the most potential for sustainable indigo production in the future. Furthermore, this study documents the details of extraction method from Wrightia laevis for the first time and the use of Ricinus communis seeds in that process. As one of the last places globally where Wrightia laevis is still used for indigo production, the may also be a nice market among textile collectors and museums that keeps the tradition of Wrightia laevis production and use for indigo extraction alive.


title: Inferring population-level contact heterogeneity from common epidemic data

text: Models of infectious disease spread that incorporate contact heterogeneity through contact networks are an important tool for epidemiologists studying disease dynamics and assessing intervention strategies. One of the challenges of contact network epidemiology has been the difficulty of collecting individual and population-level data needed to develop an accurate representation of the underlying host population's contact structure. In this study, we evaluate the utility of common epidemiological measures (R(0), epidemic peak size, duration and final size) for inferring the degree of heterogeneity in a population's unobserved contact structure through a Bayesian approach. We test the method using ground truth data and find that some of these epidemiological metrics are effective at classifying contact heterogeneity. The classification is also consistent across pathogen transmission probabilities, and so can be applied even when this characteristic is unknown. In particular, the reproductive number, R(0), turns out to be a poor classifier of the degree heterogeneity, while, unexpectedly, final epidemic size is a powerful predictor of network structure across the range of heterogeneity. We also evaluate our framework on empirical epidemiological data from past and recent outbreaks to demonstrate its application in practice and to gather insights about the relevance of particular contact structures for both specific systems and general classes of infectious disease. We thus introduce a simple approach that can shed light on the unobserved connectivity of a host population given epidemic data. Our study has the potential to inform future data-collection efforts and study design by driving our understanding of germane epidemic measures, and highlights a general inferential approach to learning about host contact structure in contemporary or historic populations of humans and animals.


title: The Medicine and Public Health Initiative Ten Years Later

text: Abstract The Medicine and Public Health Initiative (MPHI) was created jointly 10 years ago by the American Medical Association and the American Public Health Association to bridge the nearly century-wide gulf between the respective disciplines. We review the history of MPHI and its growing significance in light of recent terrorism events. We report on current MPHI activities by examining three bellwether states—California, Florida, and Texas—as well as international sites. Upon its inception, MPHI was rapidly embraced and nationally disseminated. Sustainability 10 years later in the post-911 world requires renewed commitment by all collaborators. In order to meet the numerous health challenges facing our nation, from terrorism to chronic disease, and for MPHI to be successful, medicine and public health must work in tandem.


title: Complement and viral pathogenesis

text: Abstract The complement system functions as an immune surveillance system that rapidly responds to infection. Activation of the complement system by specific recognition pathways triggers a protease cascade, generating cleavage products that function to eliminate pathogens, regulate inflammatory responses, and shape adaptive immune responses. However, when dysregulated, these powerful functions can become destructive and the complement system has been implicated as a pathogenic effector in numerous diseases, including infectious diseases. This review highlights recent discoveries that have identified critical roles for the complement system in the pathogenesis of viral infection.


title: Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site

text: Epstein-Barr virus (EBV) represents a major global health problem. Though it is associated with infectious mononucleosis and over 200,000 cancers annually worldwide, a vaccine is not available. The major target of immunity is EBV glycoprotein 350/220 (gp350) that mediates attachment to B cells through complement receptor 2 (CR2/CD21). Here, we created self-assembling nanoparticles that displayed different domains of gp350 in a symmetric array. By focusing presentation of the CR2-binding domain on nanoparticles, potent neutralizing antibodies were elicited in mice and non-human primates. The structurally designed nanoparticle vaccine improved vaccine-induced protection in a mouse model by targeting a functionally conserved site of vulnerability with 10- to 100-fold increased neutralization compared to soluble gp350. This rational approach to EBV vaccine design elicited potent neutralizing antibody responses by focusing on a conserved viral entry domain, a strategy that can be applied to other viruses.


COVID-19, Clinical Trials and QT-Prolonging Prophylactic Therapy in Healthy Subjects: First, Do No Harm


title: Whole-genome characterization of Uruguayan strains of avian infectious bronchitis virus reveals extensive recombination between the two major South American lineages

text: Abstract Infectious bronchitis virus (Gammacoronavirus, Coronaviridae) is a genetically variable RNA virus that causes one of the most persistent respiratory diseases in poultry. The virus is classified in genotypes and lineages with different epidemiological relevance. Two lineages of the GI genotype (11 and 16) have been widely circulating for decades in South America. GI-11 is an exclusive South American lineage while the GI-16 lineage is distributed in Asia, Europe and South America. Here, we obtained the whole genome of two Uruguayan strains of the GI-11 and GI-16 lineages using Illumina high-throughput sequencing. The strains here sequenced are the first obtained in South America for the infectious bronchitis virus and provide new insights into the origin, spreading and evolution of viral variants. The complete genome of the GI-11 and GI-16 strains have 27,621 and 27,638 nucleotides, respectively, and possess the same genomic organization. Phylogenetic incongruence analysis reveals that both strains have a mosaic genome that arose by recombination between Euro Asiatic strains of the GI-16 lineage and ancestral South American GI-11 viruses. The recombination occurred in South America and produced two viral variants that have retained the full-length S1 sequences of the parental lineages but are extremely similar in the rest of their genomes. These recombinant virus have been extraordinary successful, persisting in the continent for several years with a notorious wide geographic distribution. Our findings reveal a singular viral dynamics and emphasize the importance of complete genomic characterization to understand the emergence and evolutionary history of viral variants.


title: How Could This Happen?: Narrowing Down the Contagion of COVID-19 and Preventing Acute Respiratory Distress Syndrome (ARDS)

text: In this rapid commentary, a mini-review is given of the present state-of-knowledge regarding the etiology and epidemiology of the new coronavirus 2019-nCoV and the risks for developing Acute respiratory distress syndrome (ARDS). The available knowledge on the viral genomics, molecular biology and pathogenicity of viruses of the Coronaviridae family and other Nidovirales, forms a helpful template for understanding the present pandemic outbreak. However, important questions remain unanswered about the underlying mechanism causing the very high case fatality ratios (CFR) and mechanisms regarding severe reactions like ARDS, fatal cardiac and renal failures, associated with a number of important comorbidity factors. Immunological reactions to lung alveoles in particular (involving lung macrophages and alveolar epithelial cell damage) in late phase ARDS in SARS-like CoV diseases, so far may not have received enough attention. Finally a shortlist of questions for high priority further research is suggested.


title: Replicable and recombinogenic RNAs

text: Abstract This paper summarizes results of the 40-year studies on replication and recombination of RNA molecules in the cell-free amplification system of bacteriophage Qβ. Special attention is paid to the molecular colony technique that has provided for the discovery of the nature of “spontaneous” RNA synthesis by Qβ replicase and of the ability of RNA molecules to spontaneously rearrange their sequences under physiological conditions. Also discussed is the impact of these data on the concept of RNA World and on the development of new in vitro cloning and diagnostic tools.


title: Effect of genomic drift of influenza PCR tests

text: Abstract Background Nucleic acid amplification assays have become the method of choice for influenza (Flu) testing due to superior accuracy and faster turnaround time. Although assays are designed to detect highly conserved genomic targets, mutations can influence test sensitivity. Most of the circulating viruses in the United States during the 2014–2015 season were associated with significant genetic drift; however, the effect on testing was unknown. Objectives and study design We compared the performance of Prodesse ProFlu+/ProFAST+ (PFlu/PFAST), FilmArray Respiratory Panel (RP), cobas® Influenza A/B test (cIAB), and Xpert® Flu (Xpt) in a retrospective analysis of consecutive nasopharyngeal specimens received for a two-week period during the winter of 2015. Furthermore, limits of detection (LOD) were determined with six isolates of Flu. Results Of the 275 specimens, 63 were positive for FluA by PFAST, 60 were positive by RP, 58 were positive by cIAB and 52 were positive by Xpt. Only a subset of 135 specimens was tested by PFlu, of which 32 were positive. The sensitivity/specificity for PFAST, RP, cIAB, Xpt and PFlu was 100/99.1%, 96.7/99.5%, 91.8/99.1%, 85.2%/100%, and 75.6%/98.9%, respectively. LOD analyses demonstrated assay performance variations were strain associated. Specifically, PFlu’s and cIAB’s LODs were higher with A/Texas/50/2012-like and A/Switzerland/9715293/2013-like strains, while Xpt’s highest LOD was with the Swiss strain. Conclusions Strain-associated assay performance variation is known to occur with other Flu test methods; hence, it is not surprising that such variation would be observed with molecular tests. Careful monitoring and reporting for strain-associated variances are warranted for all test methods.


Conducting Research in Disease Outbreaks


Taxonomy