title: Perceptions of importance and what safety is enough

text: Abstract This research explores perceived importance of safety and security measures from the perspectives of tourists and service providers. Use of face-to-face-semi structured interviews with supply side providers in Thailand results in recognizing safety measures to ask tourists about, other than those found in the literature. Researchers collected questionnaire data from international leisure and business tourists to Thailand on importance of safety and security measures. Analysis of the importance of 23 safety and security measures show a six factor pattern in thinking about measures. However, the most important measure is not in a factor. Therefore, the study considers analysis method issues and raises questions about the value of structured data and merits of the recognition of if-then conditions by research methods such as long interviews. Examination of practical, theoretical and methodological values of findings includes considering research needed and the utility of safety measure information in business decision making.


docid: mauolcsk

title: False-negative detection of respiratory syncytial virus as an example that regular update of RT-PCR is required for reliable molecular detection of respiratory viruses


title: The spectrum of respiratory pathogens among returning Hajj pilgrims: myths and reality

text: Summary Enhanced surveillance systems have been implemented recently in many countries in order to rapidly detect and investigate any possible cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection among travellers returning from the Middle East, including notably Hajj pilgrims. According to the available surveillance data, only a few sporadic travel-associated MERS-CoV cases have been reported outside the Arabian Peninsula so far, mainly in Europe, North Africa, and Asia. These have resulted in no cases, or limited numbers of secondary cases except in Korea. The vast majority of viral respiratory infections in pilgrims returning home have been due to seasonal influenza viruses, rhinoviruses, and other known coronaviruses distinct from the MERS coronavirus. Influenza vaccination should be a priority for all Hajj pilgrims, as recommended by experts.


title: Clinical imaging research of the first Middle East respiratory syndrome in China

text: Abstract Middle East respiratory syndrome is a viral respiratory illness caused by a novel human beta-coronavirus. Based on the first case of Middle East respiratory syndrome found in China, a clinical research in combination with radiological findings was studied. Fever was the main clinical manifestation of this patient, and the primary imaging findings were basically the same as viral pneumonia. Differential imaging diagnosis on the basis of epidemiological and experimental pathogen detection is helpful for clinical diagnosis of MERS, even in distinguishing from SARS and pneumonia caused by H7N9 avian influenza.


title: Potential of Zoonotic Transmission of Non‐Primate Foamy Viruses to Humans

text: The zoonotic introduction of an animal pathogen into the human population and the subsequent extension or alteration of its host range leading to the successful maintenance of the corresponding pathogen by human‐to‐human transmission pose a serious risk for world‐wide health care. Such a scenario occurred for instance by the introduction of simian immunodeficiency viruses into the human population resulting in the human immunodeficiency viruses (HIV) and the subsequent AIDS pandemic or the proposed recent host range switch of the SARS coronavirus from a presently unknown animal species to humans. The occurrence of zoonotic transmissions of animal viruses to humans is a permanent threat to human health and is even increased by changes in the human lifestyle. In this review, the potential of the zoonotic transmission of bovine, feline and equine foamy retroviruses will be discussed in the light of well‐documented cases of zoonotic transmissions of different simian foamy viruses to humans.


title: Evaluation of a multiplex immunoassay for bovine respiratory syncytial virus and bovine coronavirus antibodies in bulk tank milk against two indirect ELISAs using latent class analysis

text: Abstract Bovine respiratory syncytial virus (BRSV) and bovine coronavirus (BCV) are responsible for respiratory disease and diarrhea in cattle worldwide. The Norwegian control program against these infections is based on herd-level diagnosis using a new multiplex immunoassay. The objective of this study was to estimate sensitivity and specificity across different cut-off values for the MVD-Enferplex BCV/BRSV multiplex, by comparing them to a commercially available ELISA, the SVANOVIR® BCV-Ab and SVANOVIR® BRSV-Ab, respectively. We analyzed bulk tank milk samples from 360 herds in a low- and 360 herds in a high-prevalence area. As none of the tests were considered perfect, estimation of test characteristics was performed using Bayesian latent class models. At the manufacturers’ recommended cut-off values, the median sensitivity for the BRSV multiplex and the BRSV ELISA was 94.4 [89.8–98.7 95% Posterior Credibility Interval (PCI)] and 99.8 [98.7–100 95% PCI], respectively. The median specificity for the BRSV multiplex was 90.6 [85.5–94.4 95% PCI], but only 57.4 [50.5–64.4 95% PCI] for the BRSV ELISA. However, increasing the cut-off of the BRSV ELISA increased specificity without compromising sensitivity. For the BCV multiplex we found that by using only one of the three antigens included in the test, the specificity increased, without concurrent loss in sensitivity. At the recommended cut-off this resulted in a sensitivity of 99.9 [99.3–100 95% PCI] and specificity of 93.7 [88.8–97.8 95% PCI] for the multiplex and a sensitivity of 99.5 [98.1–100 95% PCI] and a specificity of 99.6 [97.6–100 95% PCI] for the BCV ELISA.


docid: bnjjtlvw

title: Untersuchungen zur mikrobistatischen, viruziden und antiviralen Wirksamkeit eines antiseptischen Präparates basierend auf Amylmetacresol, 2,4-Dichlorbenzylalkohol und Levomenthol

text: In der vorliegenden Arbeit wurde die viruzide, antivirale und antimikrobielle Wirkung einer Wirkstoffmischung aus 2,4-Dichlorbenzylalkohol, Amylmetacresol und Levomenthol untersucht. Die Prüfung der viruziden Wirkung erfolgte entsprechend der Leitlinie der Deutschen Vereinigung zur Bekämpfung der Viruskrankeiten (DVV) mit Hilfe von Vaccinia-, Adeno- und Poliovirus. Zur Untersuchung der antiviralen Wirkung wurden Interferenztests mit Coronavirus auf PT-Zellen durchgeführt. Zur Prüfung der bakteriostatischen und levurostatischen Wirkung dienten Agardiffusionstests mit Staphylococcus aureus sowie ein multiresistenter Stamm dieses Keims (MRSA), ferner Klebsiella pneumoniae, Streptococcus pyogenes und Candida albicans. Gegenüber Vacciniavirus konnte eine Wirkung gemessen werden, die mit einem Reduktionsfaktor von > 4 log-Stufen die Kriterien eines Desinfektionsmittels für Schleimhautoberflächen erfüllt und so eine umfassende Wirkung gegen andere behüllte Viren nahelegt. Gegenüber unbehüllten Viren erwies sich die Formulierung dagegen als nicht wirksam. Ebenso konnten keine antivirale und damit intrazelluläre Wirkung nachgewiesen werden. Die unverdünnte Wirkstofflösung zeigte gegenüber allen geprüften Bakterienstämmen, insbesondere jedoch gegenüber S. aureus sowie gegenüber dem MRSA-Stamm eine deutliche Wirkung, vor allem jedoch gegenüber C. albicans. Die Ergebnisse legen nahe, dass die Rezepturkomponenten der geprüften Wirkstoffmischung zur Erzielung einer antiseptischen Wirksamkeit in Dosierung wie im Mischungsverhältnis optimal eingestellt sind. Die gemessene Wirkung scheint rein topischer Natur zu sein. Die nicht nachweisbare antivirale Wirkung lässt das Eindringen der Wirkstoffe in Schleimhautzellen als unwahrscheinlich erscheinen.


title: Macrophages from disease resistant B2 haplotype chickens activate T lymphocytes more effectively than macrophages from disease susceptible B19 birds

text: Abstract Resistance to respiratory pathogens, including coronavirus-induced infection and clinical illness in chickens has been correlated with the B (MHC) complex and differential ex vivo macrophage responses. In the current study, in vitro T lymphocyte activation measured by IFNγ release was significantly higher in B2 versus B19 haplotypes. AIV infection of macrophages was required to activate T lymphocytes and prior in vivo exposure of chickens to NP AIV plasmid enhanced responses to infected macrophages. This study suggests that the demonstrated T lymphocyte activation is in part due to antigen presentation by the macrophages as well as cytokine release by the infected macrophages, with B2 haplotypes showing stronger activation. These responses were present both in CD4 and CD8 T lymphocytes. In contrast, T lymphocytes stimulated by ConA showed greater IFNγ release of B19 haplotype cells, further indicating the greater responses in B2 haplotypes to infection is due to macrophages, but not T cells. In summary, resistance of B2 haplotype chickens appears to be directly linked to a more vigorous innate immune response and the role macrophages play in activating adaptive immunity.


title: Renin-angiotensin-system, a potential pharmacological candidate, in acute respiratory distress syndrome during mechanical ventilation

text: Abstract While effective treatments for acute respiratory distress syndrome (ARDS) are lacking, mechanical lung ventilation can sustain adequate gas exchange in critically ill patients with respiratory failure due to ARDS. However, as a result of the phenomenon of ventilator-induced lung injury (VILI), there is an increasing need to seek beneficial pharmacological therapies for ARDS. Recent studies have suggested the renin-angiotensin system (RAS), which consists of the ACE/Ang-II/AT1R axis and ACE2/Ang-(1–7)/MasR axis, plays a dual role in the pathogenesis of ARDS and VILI. This review highlights the deleterious action of ACE/Ang-II/AT1R axis and the beneficial role of ACE2/Ang-(1–7)/MasR axis, as well as AT2R, in VILI and ARDS, and also discusses the possibility of targeting RAS components with pharmacological interventions to improve outcomes in ARDS.


title: Recent synthetic and medicinal perspectives of dihydropyrimidinones: A review

text: Dihydropyrimidines are the most important heterocyclic ring systems which play an important role in the synthesis of DNA and RNA. Synthetically they were synthesized using Multi-component reactions like Biginelli reaction and Hantzschdihydropyridine. In the past decades, such Biginelli type dihydropyrimidones have received a considerable amount of attention due to the interesting pharmacological properties associated with this heterocyclic scaffold. In this review, we highlight recent developments in this area, with a focus on the DHPMs, recently developed as anti-inflammatory, anti-HIV, anti-tubercular, antifungal anticancer, antibacterial, antifilarial, antihyperglycemic, antihypertensive, analgesic, anti-convulsant, antioxidant, anti-TRPA1, anti-SARS, and anti-cancer activity and α(1a) binding affinity.


docid: gibkkpvr

title: Complete Genome Sequence of Avian Coronavirus Strain GA08 (GI-27 Lineage)

text: Avian coronavirus, also known as infectious bronchitis virus, is a highly contagious respiratory pathogen of chickens that is responsible for major economic losses to the poultry industry around the globe. Here, we report the complete genome sequence of strain GA08 of the GI-27 lineage, isolated from a fecal sample from a broiler chicken collected in Georgia in 2015.


title: Drainage of Cells and Soluble Antigen from the CNS to Regional Lymph Nodes

text: Despite the absence of conventional lymphatics, there is efficient drainage of both cerebrospinal fluid (CSF) and interstitial fluid (ISF) from the CNS to regional lymph nodes. CSF drains from the subarachnoid space by channels that pass through the cribriform plate of the ethmoid bone to the nasal mucosa and cervical lymph nodes in animals and in humans; antigen presenting cells (APC) migrate along this pathway to lymph nodes. ISF and solutes drain from the brain parenchyma to cervical lymph nodes by a separate route along 100–150 nm wide basement membranes in the walls of cerebral capillaries and arteries. This pathway is too narrow for the migration of APC so it is unlikely that APC traffic directly from brain parenchyma to lymph nodes by this route. We present a model for the pivotal involvement of regional lymph nodes in immunological reactions of the CNS. The role of regional lymph nodes in immune reactions of the CNS in virus infections, the remote influence of the gut microbiota, multiple sclerosis and stroke are discussed. Evidence is presented for the role of cervical lymph nodes in the induction of tolerance and its influence on neuroimmunological reactions. We look to the future by examining how nanoparticle technology will enhance our understanding of CNS-lymph node connections and by reviewing the implications of lymphatic drainage of the brain for diagnosis and therapy of diseases of the CNS ranging from neuroimmunological disorders to dementias. Finally, we review the challenges and opportunities for progress in CNS-lymph node interactions and their involvement in disease processes.


title: COVID-19 polymerase chain reaction testing before endoscopy: an economic analysis

text: Abstract Background and Aims The COVID-19 pandemic has limited endoscopy utilization, causing significant health and economic losses. We aim to model the impact of PCR testing into resuming endoscopy practice. Methods We performed a retrospective review of endoscopy utilization during the COVID-19 pandemic for a baseline reference. A computer model compared 3 approaches―Strategy 1: endoscopy for urgent indications only; Strategy 2: testing for semi-urgent indications; and Strategy 3: testing all patients. Analysis was made under current COVID-19 prevalence, and projected prevalence of 5% and 10%. Primary outcomes were number of procedures performed/cancelled. Secondary outcomes were direct costs, reimbursement, personal protective equipment used and personnel infected. Disease prevalence, testing accuracy, and costs were obtained from literature. Results During the COVID-19 pandemic, endoscopy volume was 12.7% of expected. Strategy 2 and 3 were safe and effective interventions to resume endoscopy in semi-urgent and elective cases. Investing 22USD and 105USD in testing per patient allowed completing 19.4% and 95.3% of baseline endoscopies respectively. False negative results were seen after testing 4,700 patients (or 3 months applying Strategy 2 in our practice). Implementing PCR testing over 1 week in United States would require 13 and 64 million USD, with a return of 165 and 767 million USD to providers, leaving 65 and 325 health care workers infected. Conclusion PCR testing is an effective strategy to restart endoscopic practice in United States. PCR screening should be implemented during the second phase of the pandemic, once the healthcare system is able to test and isolate all suspected COVID-19 cases.


title: Stochastic persistence and stationary distribution in an SIS epidemic model with media coverage

text: Abstract This paper aims to study an SIS epidemic model with media coverage from a general deterministic model to a stochastic differential equation with environment fluctuation. Mathematically, we use the Markov semigroup theory to prove that the basic reproduction number R 0 s can be used to control the dynamics of stochastic system. Epidemiologically, we show that environment fluctuation can inhibit the occurrence of the disease, namely, in the case of disease persistence for the deterministic model, the disease still dies out with probability one for the stochastic model. So to a great extent the stochastic perturbation under media coverage affects the outbreak of the disease.


Viruses beyond epistemic fallacy


title: The Extent of Transmission of Novel Coronavirus in Wuhan, China, 2020

text: A cluster of pneumonia cases linked to a novel coronavirus (2019-nCoV) was reported by China in late December 2019. Reported case incidence has now reached the hundreds, but this is likely an underestimate. As of 24 January 2020, with reports of thirteen exportation events, we estimate the cumulative incidence in China at 5502 cases (95% confidence interval: 3027, 9057). The most plausible number of infections is in the order of thousands, rather than hundreds, and there is a strong indication that untraced exposures other than the one in the epidemiologically linked seafood market in Wuhan have occurred.


title: Dynamics of virus infections involved in the bovine respiratory disease complex in Swedish dairy herds

text: Abstract The dynamics of bovine respiratory syncytial virus (BRSV), bovine parainfluenza virus 3 (PIV-3), bovine corona virus (BCoV) and bovine viral diarrhoea virus (BVDV) infections were studied in 118 dairy herds in south western Sweden. By using serology on paired samples from three ∼7 vs. ∼15-month-old calves per herd, the propagation of infections was investigated over about a 1-year period. The results implied that at least 74% of calves had experienced one or more of the monitored infections at the age of ∼7 months (Sample 1, Spring); 30%, 48%, 34% and 8% were seropositive to BRSV, PIV-3, BCoV and BVDV, respectively. Seroconversions to BRSV, PIV-3, BCoV and BVDV occurred in 26%, 38%, 50% and 3% of seronegative animals and 63% had antibodies against two or more infections at ∼15 months (Sample 2). In total, 90–97% of animals that were seropositive in Sample 1 remained positive in Sample 2. A significant association was found between BVDV and BCoV (P =0.01). Moreover, a significantly higher proportion of herds in which no calves had a recorded history of respiratory disease (n =15) were classified as negative to all four infections monitored when compared to herds in which disease was observed (P =0.0002). This study showed a high infection burden in young animals and effective spread of BRSV, PIV-3 and BCoV in one area of Sweden. BVDV infections were restricted to a few herds, reflecting the effect of a voluntary control program against BVDV in Sweden.


docid: vbbewppa

title: Secreted Interferon-Inducible Factors Restrict Hepatitis B and C Virus Entry In Vitro

text: Interferon-α (IFN-α) has been used for more than 20 years as the first-line therapy for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, because it has a number of antiviral effects. In this study, we describe a novel mode of its antiviral action. We demonstrate that the supernatant from IFN-α-treated cultured cells restricted HBV and HCV infection by inhibiting viral entry into hepatoma cells. The factors contained in the supernatant competed with the virus for binding to heparan glycosaminoglycans—the nonspecific attachment step shared by HBV and HCV. Secreted factors of high molecular mass that bind to heparin columns elicited the antiviral effect. In conclusion, IFN-α is able to induce soluble factors that can bind to heparan glycosaminoglycans thus leading to the inhibition of viral binding.


title: Complete genome sequence of Nariva virus, a rodent paramyxovirus

text: Nariva virus (NarPV) was isolated from forest rodents (Zygodontomys b. brevicauda) in eastern Trinidad in the early 1960s. Initial classification within the family Paramyxoviridae was based mainly on morphological observations including the structure of nucleocapsids and virion surface projections. Here, we report the characterization of the complete genome sequence of NarPV. The genome is 15,276 nucleotides in length, conforming to the rule-of-six, and has a genome organization typical of most members of the family, with six transcriptional units in the order 3′-N–P-M-F–H-L-5′. The gene junctions contain highly conserved gene start and stop signals and a tri-nucleotide intergenic sequence present in most members of the subfamily Paramyxovirinae. Sequence comparison studies indicate that NarPV is most closely related to Mossman virus, which was isolated from wild rats (Rattus leucopus) in Queensland, Australia, in 1970. This study confirmed the classification of NarPV as a member of the subfamily Paramyxovirinae and established the close genome organization and sequence relationship between the two rodent paramyxoviruses isolated almost a decade apart and from two locations separated by more than 15,000 km.


A snapshot of urgent upper gastrointestinal endoscopy care during the Covid‐19 outbreak in Italy


docid: rgmurgbf

title: SARS-CoV-2: Combating Coronavirus Emergence

text: Summary The emergence and rapid global spread of SARS-CoV-2 mark the third such identification of a novel coronavirus capable of causing severe, potentially fatal disease in humans in the 21st century. As noted by Andersen et al. (Nature Medicine), the sequencing of proximal zoonotic ancestors to SARS-CoV-2 has aided in the identification of alleles that may contribute to the virus’ virulence in humans.


title: Creating Bioethics Distance Learning Through Virtual Reality

text: Abstract Bioethics education is a central element in the biotechnology curriculum. Re-imagining distance learning, virtual reality (VR) is taking student involvement to the next level of interaction, offering a real classroom experience and a new way to gain ethical reasoning skills. We explore a new paradigm for bioethics education that involves VR.


title: Influence of media composition on recombinant monoclonal IgA1 glycosylation analysed by lectin-based protein microarray and MALDI-MS

text: Abstract Glycosylation of therapeutic glycoproteins significantly affects their physico-chemical properties, bioactivity and immunogenicity. The determination of glycan composition is highly important regarding their development and production. Therefore, there is a demand for analytical techniques enabling rapid and reliable glycoprofiling of therapeutic proteins. For the investigation of changes in glycan structures, we have employed two platforms: lectin-based protein microarray, and MALDI-MS. In lectin-based microarray analysis, the samples of IgA were printed on the microarray slide, incubated with the set of lectins with various specificity and evaluation of changes in glycosylation was based on differences in reactivity of samples with lectins. MALDI-MS was used for N-glycan analysis of IgA1 samples. IgAs are effective as therapeutic agents in defense against viruses that use sialic acid as a receptor. Dimeric IgA1 antibodies were produced by stable cell line IgA1/2G9 on the basal medium at different conditions (different supplementation and feeding) and we also evaluated the effect of different conditions on lactate production, which correlates with IgA productivity. Decrease of lactate levels was observed during supplementation with succinic acid, asparagine, or with mannose feeding. We found by lectin-based microarray analysis that the metabolic shift from glutamine to asparagine or feeding with glucose caused increase of high mannose type glycans what was confirmed also by MALDI-MS. Among other changes in IgA glycosylation determined by lectin-based protein microarray were, for example, reduced galactosylation after supplementation with succinic acid and increase of both sialylation and galactosylation after supplementation with glutamine and feeding with mannose. The elucidation of mechanism of determined changes requires further investigation, but the described analytical approach represent effective platform for determination, screening and evaluation of glycosylation of therapeutic proteins.


title: An In Vitro Microneutralization Assay for SARS‐CoV‐2 Serology and Drug Screening

text: The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) emerged in the city of Wuhan, Hubei Province, China, in late 2019. Since then, the virus has spread globally and caused a pandemic. Assays that can measure the antiviral activity of antibodies or antiviral compounds are needed for SARS‐CoV‐2 vaccine and drug development. Here, we describe in detail a microneutralization assay, which can be used to assess in a quantitative manner if antibodies or drugs can block entry and/or replication of SARS‐CoV‐2 in vitro. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Microneutralization assay to test inhibition of virus by antibodies (purified antibodies or serum/plasma) Basic Protocol 2: Screening of anti‐SARS‐CoV‐2 compounds in vitro Support Protocol: SARS‐CoV‐2 propagation


title: A retrospective review of tuberculosis exposure among health care workers in a tertiary hospital

text: BACKGROUND: We evaluated tuberculosis (TB) acquisition rate and risk factors among health care workers (HCWs) exposed to index TB patients. METHODS: We performed a retrospective cohort study on exposed HCWs from August 2016 to January 2018 at a tertiary hospital in Singapore. Demographic factors and TB exposure episodes per HCW were obtained. A modified Poisson regression model was used to identify factors associated with TB infection. RESULTS: A total of 32 TB exposure events occurred during the study period. A total of 881 HCWs with 1,536 exposure episodes were screened with QuantiFERON-TB Gold In-tube assay (QFT-GIT) at baseline and 8 weeks. A total of 129 (14.6%) HCWs had positive QFT-TB at baseline, whereas 22 (2.5%) HCWs had QFT-GIT conversion, with a latent TB infection (LTBI) rate of 1.14 cases per 100 exposure episodes per year. Foreign nationality, non-Chinese ethnicity, and age above 40 years were independently associated with baseline LTBI, whereas having >2 TB exposure episodes and working in internal medicine, medical subspecialties, and psychiatry wards were associated with QFT-GIT conversion. DISCUSSION: The QFT-GIT conversion rate among screened HCWs is low. Foreign HCWs with LTBI likely came from countries with higher TB transmission. Targeted prevention of repeated TB exposures can reduce QFT-GIT conversion. CONCLUSIONS: The study results will guide TB contact tracing protocols in health care institutions.


Pediatric coronavirus disease‐2019: How to assess chest disease?


title: The cost of community-managed viral respiratory illnesses in a cohort of healthy preschool-aged children

text: BACKGROUND: Acute respiratory illnesses (ARIs) during childhood are often caused by respiratory viruses, result in significant morbidity, and have associated costs for families and society. Despite their ubiquity, there is a lack of interdisciplinary epidemiologic and economic research that has collected primary impact data, particularly associated with indirect costs, from families during ARIs in children. METHODS: We conducted a 12-month cohort study in 234 preschool children with impact diary recording and PCR testing of nose-throat swabs for viruses during an ARI. We used applied values to estimate a virus-specific mean cost of ARIs. RESULTS: Impact diaries were available for 72% (523/725) of community-managed illnesses between January 2003 and January 2004. The mean cost of ARIs was AU$309 (95% confidence interval $263 to $354). Influenza illnesses had a mean cost of $904, compared with RSV, $304, the next most expensive single-virus illness, although confidence intervals overlapped. Mean carer time away from usual activity per day was two hours for influenza ARIs and between 30 and 45 minutes for all other ARI categories. CONCLUSION: From a societal perspective, community-managed ARIs are a significant cost burden on families and society. The point estimate of the mean cost of community-managed influenza illnesses in healthy preschool aged children is three times greater than those illnesses caused by RSV and other respiratory viruses. Indirect costs, particularly carer time away from usual activity, are the key cost drivers for ARIs in children. The use of parent-collected specimens may enhance ARI surveillance and reduce any potential Hawthorne effect caused by compliance with study procedures. These findings reinforce the need for further integrated epidemiologic and economic research of ARIs in children to allow for comprehensive cost-effectiveness assessments of preventive and therapeutic options.


title: COVID‐19 vaginal delivery – A case report

text: The novel coronavirus termed SARS‐CoV‐2 (COVID‐19) is a major public health challenge. Many maternity units around the country are currently considering management protocols for these patients. We report a case from a tertiary Australian hospital describing an uncomplicated vaginal birth in a COVID‐19 positive mother. To our knowledge this is also the first case described of a mother with COVID‐19 not separated from her infant. Management provided supports the current Royal College of Obstetricians and Gynaecologists and World Health Organization guidelines suggesting that it is possible to consider rooming in post‐delivery for COVID‐19 positive parents. Encouragement of breastfeeding appears possible and safe when viral precautions are observed.


title: A TRIFfic Perspective on Acute Lung Injury

text: Acute lung injury (ALI) is a leading cause of death in people infected with H5N1 avian influenza virus or the SARS-coronavirus. Imai et al. (2008) now report that ALI is triggered by the signaling of oxidized phospholipids through Toll-like receptor 4 (TLR4) and the adaptor protein TRIF. These findings provide insight into the molecular pathogenesis of ALI, a condition for which treatment options are currently very limited.


title: From plan to market in the health sector? China’s experience

text: Abstract Countries worldwide confront the challenge of defining and achieving appropriate roles for government and market forces in the health sector. China—as both a developing and a transitional economy—represents an important case. This paper uses an international comparative perspective to examine how the health of China’s population and other aspects of health system performance changed during the reform era. We draw on standard public finance and health economics theory, as well as the more recent incomplete-contracting theory of property rights, to summarize the comparative advantages of government and market for financing and delivery of health services, particularly in developing and transitional economies. We then describe and analyze against this theoretical background the transformation of China’s health sector and recent commitment of government funds to move toward universal coverage.


title: P200 family protein IFI204 negatively regulates type I interferon responses by targeting IRF7 in nucleus

text: Interferon-inducible p200 family protein IFI204 was reported to be involved in DNA sensing, and subsequently induces the production of type I interferons and proinflammatory mediators. However, its function in the regulation of antiviral innate immune signaling pathway remains unclear. Here we reported a novel role of IFI204 that specifically inhibits the IRF7-mediated type I interferons response during viral infection. IFI204 and other p200 family proteins are highly expressed in mouse hepatitis coronavirus-infected bone marrow-derived dendritic cells. The abundant IFI204 could significantly interact with IRF7 in nucleus by its HIN domain and prevent the binding of IRF7 with its corresponding promoter. Moreover, other p200 family proteins that possess HIN domain could also inhibit the IRF7-mediated type I interferons. These results reveal that, besides the positive regulation function in type I interferon response at the early stage of DNA virus infection, the interferon-inducible p200 family proteins such as IFI204 could also negatively regulate the IRF7-mediated type I interferon response after RNA virus infection to avoid unnecessary host damage from hyper-inflammatory responses.


title: PIKA provides an adjuvant effect to induce strong mucosal and systemic humoral immunity against SARS-CoV

text: Severe Acute Respiratory Syndrome (SARS) is a deadly infectious disease caused by SARS Coronavirus (SARS-CoV). Inactivated SARS-CoV has been explored as a vaccine against SARS-CoV. However, safe and potent adjuvants, especially with more efficient and economical needle-free vaccination are always needed more urgently in a pandemic. The development of a safe and effective mucosal adjuvant and vaccine for prevention of emergent infectious diseases such as SARS will be an important advancement. PIKA, a stabilized derivative of Poly (I:C), was previously reported to be safe and potent as adjuvant in mouse models. In the present study, we demonstrated that the intraperitoneal and intranasal co-administration of inactivated SARS-CoV vaccine together with this improved Poly (I:C) derivative induced strong anti-SARS-CoV mucosal and systemic humoral immune responses with neutralizing activity against pseudotyped virus. Although intraperitoneal immunization of inactivated SARS-CoV vaccine alone could induce a certain level of neutralizing activity in serum as well as in mucosal sites, co-administration of inactivated SARS-CoV vaccine with PIKA as adjuvant could induce a much higher neutralizing activity. When intranasal immunization was used, PIKA was obligatorily for inducing neutralizing activity in serum as well as in mucosal sites and was correlated with both mucosal IgA and mucosal IgG response. Overall, PIKA could be a good mucosal adjuvant candidate for inactivated SARS-CoV vaccine for use in possible future pandemic.


title: Challenges in teaching human anatomy to students with intellectual disabilities during the Covid‐19 pandemic

text: In the context of the Covid‐19 pandemic and the various subsequent changes and behavioral adjustments necessary in the educational field, two important articles were recently published in Anatomical Sciences Education (Franchi, 2020; Srinivasan, 2020). The first study (Franchi, 2020) reported the impact of the pandemic on human anatomy education in the United Kingdom. This article described from the perspective of a medical student how the lack of practical teaching with cadavers can adversely impact training and lead to losses for students.


title: Rapid differentiation of vaccine strain and Chinese field strains of transmissible gastroenteritis virus by restriction fragment length polymorphism of the N gene

text: A strain of transmissible gastroenteritis virus (TGEV), designated H16, was isolated in PK-15 cells and passaged serially to level 165. Vaccines based on passages 155–165 in cell cultures are available commercially as vaccines for the prevention and control of infections with TGEV in China. Nucleoprotein (N) sequences of the virus at passages 155 and 165 were aligned and compared using a computer software program. The suitability of restriction fragment length polymorphism (RFLP) analysis for differentiation of the vaccine strain from the other TGEVs was investigated. The RFLP analysis identified a change in the cleavage sites of AclI at passages 155 and 165. This RFLP pattern of the N gene differentiated the Chinese vaccine strain from its parental strain, the 11 TGEVs studied and the other reported TGEVs in the GenBank. Using phylogenetic analysis, the Chinese TGEVs were divided into three groups (G1, G2, and G3). The G3 Chinese TGEVs possessed several specific nucleotides and amino acids that were not found in the G1 and G2 Chinese TGEVs or the other reference TGEVs. Analysis of the phylogenetic trees revealed that the G3 TGEVs represent a separate group that is distinct from the non-Chinese TGEVs and from Chinese TGEVs isolated previously. These findings suggest that Chinese strains of TGEV are evolving continuously.


title: Classification of adult cattle infectious diseases: A first step towards prioritization of biosecurity measures

text: An emphasis on biosecurity in the cattle industry was made over the years to improve animal and public health. Nevertheless, the level of implementation of biosecurity measures (BSM) remains largely insufficient due to certain constraints. It is therefore necessary to prioritize the different BSM to be applied in accordance with the individual context and the main infectious diseases affecting cattle. Previous prioritization exercises of infectious diseases were neither specific to Belgium nor based on an exhaustive list of diseases. This study aimed at classifying the most important infectious diseases affecting cattle in Belgium. A list of 74 cattle infectious diseases reported in Europe was compiled based on a literature review. Through an online survey, Belgian rural veterinary practitioners (RVP) were asked to assign a score to each disease according to their frequency (question 1), their trends estimated between 2013‐15 (question 2), and finally to list the five most important diseases for adult cattle (question 3). Respectively, 107 and 93 RVP answered the first two questions and the last one. Results of the survey were used to classify the diseases based on their frequency, trends, and importance through an additional weighting system and a subsequent regression tree analysis. Belgian laboratory databases and previous disease prioritization exercises were also analysed and taken into account as additional data sources. For the most important diseases identified (those ranked as important by the three data sources), a literature review was performed in PubMed to identify their related risk factors and BSM. A total of 48 infectious diseases were classified as important in Belgium with six of them considered as important from the three data sources: bovine respiratory diseases (BRD), bovine respiratory syncytial virus (BRSV), bovine viral diarrhoea (BVD), infectious bovine rhinotracheitis (IBR), Q fever, and salmonellosis. Their related BSM should be prioritized in terms of BSM implementation.


title: Clinical review: Critical care medicine in mainland China

text: Critical care medicine began in mainland China in the early 1980s. After almost 30 years of effort, it has been recognized as a specialty very recently. However, limited data suggest that critical care resources, especially ICU beds, are inadequate compared with those of developed countries. National critical care societies work together to set up good practice standards, and to improve academic levels with scientific meetings, education programs, and training courses. Critical care research in mainland China is beginning to evolve, with great potential for improvement.


title: Advancements in DNA vaccine vectors, non-mechanical delivery methods, and molecular adjuvants to increase immunogenicity

text: A major advantage of DNA vaccination is the ability to induce both humoral and cellular immune responses. DNA vaccines are currently used in veterinary medicine, but have not achieved widespread acceptance for use in humans due to their low immunogenicity in early clinical studies. However, recent clinical data have re-established the value of DNA vaccines, particularly in priming high-level antigen-specific antibody responses. Several approaches have been investigated for improving DNA vaccine efficacy, including advancements in DNA vaccine vector design, the inclusion of genetically engineered cytokine adjuvants, and novel non-mechanical delivery methods. These strategies have shown promise, resulting in augmented adaptive immune responses in not only mice, but also in large animal models. Here, we review advancements in each of these areas that show promise for increasing the immunogenicity of DNA vaccines.


title: Emmprin and KSHV: new partners in viral cancer pathogenesis

text: Emmprin (CD147; basigin) is a multifunctional glycoprotein expressed at higher levels by cancer cells and stromal cells in the tumor microenvironment. Through direct effects within tumor cells and promotion of tumor-stroma interactions, emmprin participates in induction of tumor cell invasiveness, angiogenesis, metastasis and chemoresistance. Although its contribution to cancer progression has been widely studied, the role of emmprin in viral oncogenesis still remains largely unclear, and only a small body of available literature implicates emmprin-associated mechanisms in viral pathogenesis and tumorigenesis. We summarize these data in this review, focusing on the role of emmprin in pathogenesis associated with the Kaposi sarcoma-associated herpesvirus (KSHV), a common etiology for cancers arising in the setting of immune suppression. We also discuss future directions for mechanistic studies exploring roles for emmprin in viral cancer pathogenesis.


docid: cgtmcpaz

title: Characterisation and analysis of indoor tornado for contaminant removal and emergency ventilation

text: Abstract As an essential emergency management strategy, innovative emergency ventilation schemes that can quickly remove infectious and fatal contaminants without further spreading are highly demanded for public and commercial buildings. This study numerically investigated a vortex flow driven ventilation in a model room to explore the dynamic characteristics and 3D visualisation of vortex-driven indoor tornados. Four approaches to identify the core region of the indoor tornado were developed and compared against each other. By successfully capturing the continuously changing centre of the vortex and significant core region size variations at different heights, the swirl vector method was recommended as a quantifiable approach to identify the core region of indoor tornados. The numerical outcomes also revealed a strong connection between the lift angle, vortex intensity, overall size of indoor tornado and maximum size of core region. The best contaminants control and removal was achieved at lift angle of 20° in this study and an optimum lift angle ranging from 10° to 20° was recommended for future study.


title: Overdose and Risk Factors for Severe Acute Respiratory Syndrome

text: Abstract Background There have been significant efforts to respond to the two public health emergencies of COVID-19 and overdose in British Columbia (BC) Canada. The purpose of this study was to quantify the prevalence of known risk factors associated with mortality due to severe acute respiratory syndrome coronavirus 2 (COVID-19) for persons who have had a non-fatal overdose (2015-2017) in comparison to persons who have not had an overdose. Methods Data were extracted from the BC Provincial Overdose Cohort (ODC) which includes a 20% random sample of BC residents and persons who have had a non-fatal overdose in BC from January 2015-December 2017. Chi-square tests and logistic regression were used to compare risk factors by overdose history. Results Persons who had an overdose were significantly more likely to have three (chronic pulmonary disease, diabetes, coronary heart disease) of the four known chronic conditions associated with the development of severe illness due to COVID-19 compared to persons who did not have a previous non-fatal overdose event. Conclusion Persons who had an overdose were more likely to have several chronic conditions associated with the development of severe illness due to COVID-19. The increased likelihood of having these risk factors is reflective of the social and health inequities experienced by persons who have a history of overdose.


title: A review of pathophysiology and neuropsychiatric manifestations of COVID-19

text: INTRODUCTION: The outbreak of coronavirus disease 2019 (COVID-19) has become one of the most serious pandemics of the recent times. Since this pandemic began, there have been numerous reports about the COVID-19 involvement of the nervous system. There have been reports of both direct and indirect involvement of the central and peripheral nervous system by the virus. OBJECTIVE: To review the neuropsychiatric manifestations along with corresponding pathophysiologic mechanisms of nervous system involvement by the COVID-19. BACKGROUND: Since the beginning of the disease in humans in the later part of 2019, the coronavirus disease 2019 (COVID-19) pandemic has rapidly spread across the world with over 2,719,000 reported cases in over 200 countries [World Health Organization. Coronavirus disease 2019 (COVID-19) situation report-96.,]. While patients typically present with fever, shortness of breath, sore throat, and cough, neurologic manifestations have been reported, as well. These include the ones with both direct and indirect involvement of the nervous system. The reported manifestations include anosmia, ageusia, central respiratory failure, stroke, acute inflammatory demyelinating polyneuropathy (AIDP), acute necrotizing hemorrhagic encephalopathy, toxic–metabolic encephalopathy, headache, myalgia, myelitis, ataxia, and various neuropsychiatric manifestations. These data were derived from the published clinical data in various journals and case reports. CONCLUSION: The neurological manifestations of the COVID-19 are varied and the data about this continue to evolve as the pandemic continues to progress.


title: Dissecting antibody-mediated protection against SARS-CoV-2

text: Understanding the properties and mechanisms by which antibodies provide protection is essential to defining immunity. Although neutralizing antibodies have been proposed as a potential key mechanism of protection against many viral pathogens, antibodies mediate additional immune functions that may have both protective and pathological consequences. Dissecting these properties against SARS-CoV-2 is likely necessary for defining metrics of immunity that will inform the design of vaccines and therapeutics and improve clinical management.


title: Methods for Estimating the Case Fatality Ratio for a Novel, Emerging Infectious Disease

text: During the course of an epidemic of a potentially fatal disease, it is important that the case fatality ratio be well estimated. The authors propose a novel method for doing so based on the Kaplan-Meier survival procedure, jointly considering two outcomes (death and recovery), and evaluate its performance by using data from the 2003 epidemic of severe acute respiratory syndrome in Hong Kong, People's Republic of China. They compare this estimate obtained at various points in the epidemic with the case fatality ratio eventually observed; with two commonly quoted, naïve estimates derived from cumulative incidence and mortality statistics at single time points; and with estimates in which a parametric mixture model is used. They demonstrate the importance of patient characteristics regarding outcome by analyzing subgroups defined by age at admission to the hospital.


title: A single center observational study of the clinical characteristics and short-term outcome of 20 kidney transplant patients admitted for SARS-CoV2 pneumonia.

text: Abstract The outcome of SARS-CoV2 infection in patients who have received a kidney allograft and are being treated with immunosuppression is unclear. We describe 20 kidney transplant recipients (median age 59 years [inter quartile range 51-64 years], median age of transplant 13 years [9-20 years], baseline eGFR 36.5 [23-47.5]) with SARS-CoV2 induced pneumonia. At admission, all had immunosuppression withdrawn and were started on methylprednisolone 16 mg/day, all but one was commenced on antiviral therapy and hydroxychloroquine with doses adjusted for kidney function. At baseline, all patients presented fever but only one complained of difficulty in breathing. Half of patients showed chest radiographic evidence of bilateral infiltrates while the other half showed unilateral changes or no infiltrates. During a median follow-up of seven days, 87% experienced a radiological progression and among those 73% required escalation of oxygen therapy. Six patients developed acute kidney injury with one requiring hemodialysis. Six of 12 patients were treated with tocilizumab, a humanized monoclonal antibody to the IL-6 receptor. Overall, five kidney transplant recipients died after a median period of 15 days [15-19] from symptom onset. These preliminary findings describe a rapid clinical deterioration associated with chest radiographic deterioration and escalating oxygen requirement in renal transplant recipients with SARS-Cov2 pneumonia. Thus, in this limited cohort of long-term kidney transplant patients, SARS-CoV-2 induced pneumonia is characterized by high risk of progression and significant mortality.


title: Using routinely collected data to evaluate risk factors for mortality of veal calves

text: Abstract From 2009 to 2012 a gradual increase in on-farm mortality of Dutch veal calves was observed. In 2012, the cattle industry decided that more information was needed on risk factors for mortality in both veal herds and herds of origin to enable implementation of risk mitigating measures. Routinely collected data were available from seven different data sources and contained information from 2.4 million white veal calves that were fattened in the period between 1 January 2011 and 30 June 2014. Survival analysis techniques (Kaplan-Meier), multilevel Poisson and multilevel Logistic regression models were applied to analyse the data. Two different models were assembled in which risk factors for veal calf mortality in respectively veal herds and herds of origin were identified. Univariable and multivariable regression techniques were used to detect risk factors significantly associated with mortality of veal calves during the fattening period. During the study period, the mean mortality was 4.9% per production cycle. The probability to die was highest during the first weeks after arrival in the veal herds and declined thereafter. Important risk factors included a veal herds with a higher use of antimicrobials, hair colour as proxy for breed, certain countries of origin, veal herd management with a limited amount of supplied feed and a not having an all-in / all-out system. A higher body weight at arrival in the veal herd was associated with lower mortality as well as veal calves that were fed an above median amount of milk, roughage and concentrates. From the calves that were fattened during the study period, observations of 1.1 million calves originated from the Netherlands and were available to study risk factors for veal calf mortality associated with the herd of origin. Important risk factors included purchase, herds with high mortality rates in the quarter in which the calf was born, fast growth in herd size, high cattle replacement rates and a higher antibiotic use in the quarter of birth. Calves that originated from herds that were certified BVD-free, Salmonella-unsuspected or Paratuberculosis-unsuspected, had a lower odds to die during the subsequent fattening period in a veal herd. Veal calf mortality was influenced by risk factors at the herd of origin as well as at veal herds. Adequate collaboration between the different industries is necessary to optimize veal calf management leading to a reduction in veal calf mortality during the fattening period.


title: Assess, adapt and act: a paediatric surgery division’s initial approach in a rapidly evolving pandemic

text: PURPOSE: The COVID-19 pandemic has placed an unprecedented test on the delivery and management of healthcare services globally. This study describes the adaptive measures taken and evolving roles of the members of the paediatric surgery division in a developing country during this period. METHODS: We adopted multiple adaptive strategies including changes to stratification of surgeries, out-patient services by urgency and hospital alert status, policy writing involving multidisciplinary teams, and redeployment of manpower. Modifications were made to teaching activities and skills training to observe social distancing and mitigate reduced operative learning opportunities. Roles of academic staff were expanded to include non-surgical duties. RESULTS: The planned strategies and changes to pre COVID-19 practices were successful in ensuring minimal disruption to the delivery of essential paediatric surgical services and training. Despite the lack of established guidelines and literature outlining strategies to address the impact of this pandemic on surgical services, most of the initial measures employed were consistent with that of other surgical centres. CONCLUSION: Changes to delivery of surgical services and surgical training warrant a holistic approach and a constant re-evaluation of practices with emergence of new experiences and guidelines.


title: Comparison of a new transport medium with universal transport medium at a tropical field site

text: Abstract Limited data are available in rural Honduran settings describing the etiology of respiratory infections, partially due to limited specimen transport. A new molecular transport media (MTM) preserves released nucleic acid at ambient temperature for later detection. Prospective surveillance was conducted in a Honduran clinic to identify 233 children less than 5 years of age presenting with respiratory symptoms. We obtained 2 nasopharyngeal samples and stored 1 in PrimeStore® MTM at room temperature and 1 in universal transport media (UTM) at −80 °C. The specimens were then transported to Cincinnati Children's Hospital and tested for 16 respiratory viruses using a multiplex PCR panel. The 2 specimen collection systems were similar for detecting the 4 most common viruses: influenza (Kappa = 0.7676, P < 0.0001), human metapneumovirus (Kappa = 0.8770, P < 0.0001), respiratory syncytial virus (Kappa = 0.6849, P < 0.0001), and parainfluenza (Kappa = 0.8796, P < 0.0001). These results suggest that clinical specimens transported via PrimeStore® MTM and UTM yield similar viral multiplex PCR results.


title: Insulin-Like Growth Factor 1 Regulates Acute Inflammatory Lung Injury Mediated by Influenza Virus Infection

text: The acute inflammatory lung injury is an important cause of death due to influenza A virus (IAV) infection. Insulin-like growth factor 1 (IGF1) played an important role in the regulation of inflammation in the immune system. To investigate the role of IGF1 in IAV-mediated acute inflammatory lung injury, the expression of IGF1 and inflammatory cytokines was tested after IAV A/Puerto Rico/8/1934 (H1N1; abbreviated as PR8) infection in A549 cells. Then, a BALB/c mouse model of PR8 infection was established. On days 3, 5, 7, and 9 post-infection, the mice lung tissue was collected to detect the expression changes in IGF1 mRNA and protein. The mice were divided into four groups: (1) PBS (abbreviation of phosphate buffered saline); (2) PR8 + PBS; (3) PR8 + IGF1; and (4) PR8 + PPP (abbreviation of picropodophyllin, the IGF1 receptor inhibitor). The body weight and survival rate of the mice were monitored daily, and the clinical symptoms of the mice were recorded. On day 5 post-infection, the mice were sacrificed to obtain the serum and lung tissues. The expression of inflammatory cytokines in the serum was detected by enzyme linked immunosorbent assay; lung injury was observed by hematoxylin-eosin staining; the viral proliferation in the lung was detected by real-time quantitative PCR; and the protein expression of the main molecules in the phosphatidylinositol-3-kinases/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) signaling pathways was detected by Western blot. It was found that IGF1 expression is upregulated in A549 cells and BALB/c mice infected with PR8, whereas IGF1 regulated the expression of inflammatory cytokines induced by PR8 infection. Overexpression of IGF1 aggravated the IAV-mediated inflammatory response, whereas the inhibition of IGF1 receptor reduced such inflammatory response. The phosphorylation of IGF1 receptor triggered the PI3K/AKT and MAPK signaling pathways to induce an inflammatory response after IAV infection. Therefore, IGF1 plays an important immune function in IAV-mediated acute inflammatory lung injury. IGF1 may provide a therapeutic target for humans in response to an influenza outbreak, and inhibition of IGF1 or IGF1 receptor may represent a novel approach to influenza treatment.


title: Genetic control of arthritis onset, severity and chronicity in a model for rheumatoid arthritis in rats

text: Rheumatoid arthritis (RA) is a chronic and genetically complex inflammatory disorder that leads to erosive destruction of peripheral joints(1,2,3,4,5). The use of animal models mimicking RA, such as pristane-induced arthritis (PIA) in rats, should facilitate its genetic analysis. Pristane is a non-immunogenic synthetic oil that, after a single subcutaneous injection into DA rats, induces arthritis restricted to peripheral joints with a chronic relapsing disease course(6). To identify genes involved in the control of chronic arthritis, we made crosses between susceptible DA rats and resistant E3 rats and analysed the progeny with microsatellite markers covering the entire rat genome. Our results show that different arthritis phenotypes are associated with different chromosomal loci. Loci on chromosomes 4 and 6 ( Pia2 and Pia3 ) influence arthritis onset, whereas a locus on chromosome 12 ( Pia4 ) is associated with severity and joint erosion. We found that chronicity is associated with a different set of loci, one on chromosome 4 and the other on chromosome 14 ( Pia5, Pia6 ). These findings demonstrate for the first time that different phases of a chronic self-perpetuative disease which mimics RA are associated with distinct sets of genes.


title: Viral hijacking of the host ubiquitin system to evade interferon responses

text: The post-translational attachment of ubiquitin or ubiquitin-like modifiers (ULMs) to proteins regulates many cellular processes including the generation of innate and adaptive immune responses to pathogens. Vice versa, pathogens counteract immune defense by inhibiting or redirecting the ubiquitination machinery of the host. A common immune evasion strategy is for viruses to target host immunoproteins for proteasomal or lysosomal degradation by employing viral or host ubiquitin ligases. By degrading key host adaptor and signaling molecules, viruses thus disable multiple immune response pathways including the production of and response to interferons as well as other innate host defense mechanisms. Recent work further revealed that viruses inhibit the ligation of ubiquitin or ULMs or remove ubiquitin from host cell proteins. Thus, viruses succeed in either stabilizing negative regulators of innate immune signaling or thwart host cell proteins that are activated by ubiquitin or ULM-modification.


title: Expression of an antiviral protein from Lonomia obliqua hemolymph in baculovirus/insect cell system

text: Abstract The control of viral infections, mainly those caused by influenza viruses, is of great interest in Public Health. Several studies have shown the presence of active properties in the hemolymph of arthropods, some of which are of interest for the development of new pharmacological drugs. Recently, we have demonstrated the existence of a potent antiviral property in the hemolymph of Lonomia obliqua caterpillars. The aim of this study was to produce an antiviral protein in a baculovirus/Sf9 cell system. The resulting bacmid contains the sequence coding for the antiviral protein previously described by our group. Total RNA from L. obliqua caterpillars was extracted with Trizol and used in the reverse transcription assay with oligo(d)T primer followed by polymerase chain reactions (RT-PCR) with specific primers for the cDNA coding for the antiviral protein, based on the sequence deposited in the GenBank database. Restriction sites were inserted in the cDNA for ligation in the donor plasmid pFastBac1™. The recombinant plasmid was selected in Escherichia coli DH5α and subsequently used in the transformation of E. coli DH10Bac for the construction of the recombinant bacmid. This bacmid was used for the expression of the antiviral protein in the baculovirus/Sf9 cell system. After identifying the protein by western blot, activity tests were performed, showing that the purified recombinant protein was able to significantly reduce viral replication (about 4 logs). Studies on the optimization of the expression system for the production of this antiviral protein in insect cells are in progress.


title: Diagnostic performances and thresholds: the key to harmonization in serological SARS-CoV-2 assays?

text: BACKGROUND: The evaluation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibody (Ab) assay performances is of the utmost importance in establishing and monitoring virus spread in the community. In this study focusing on IgG antibodies, we compare reliability of three chemiluminescent (CLIA) and two enzyme linked immunosorbent (ELISA) assays. METHODS: Sera from a total of 271 subjects, including 64 reverse transcription-polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 patients were tested for specific Ab using Maglumi (Snibe), Liaison (Diasorin), iFlash (Yhlo), Euroimmun (Medizinische Labordiagnostika AG) and Wantai (Wantai Biological Pharmacy) assays. Diagnostic sensitivity and specificity, positive and negative likelihood ratios were evaluated using manufacturers’ and optimized thresholds. RESULTS: Optimized thresholds (Maglumi 2 kAU/L, Liaison 6.2 kAU/L and iFlash 15.0 kAU/L) allowed us to achieve a negative likelihood ratio and an accuracy of: 0.06 and 93.5% for Maglumi; 0.03 and 93.1% for Liaison; 0.03 and 91% for iFlash. Diagnostic sensitivities and specificities were above 93.8% and 85.9%, respectively for all CLIA assays. Overall agreement was 90.3% (Cohen’s kappa = 0.805 and SE = 0.041) for CLIA, and 98.4% (Cohen’s kappa = 0.962 and SE = 0.126) for ELISA. CONCLUSIONS: The results obtained indicate that, for CLIA assays, it might be possible to define thresholds that improve the negative likelihood ratio. Thus, a negative test result enables the identification of subjects at risk of being infected, who should then be closely monitored over time with a view to preventing further viral spread. Redefined thresholds, in addition, improved the overall inter-assay agreement, paving the way to a better harmonization of serologic tests.


title: IFN-γ expression is up-regulated by peripheral blood mononuclear cells (PBMC) from non-exposed dogs upon Leishmania chagasi promastigote stimulation in vitro

text: Abstract While the response to Leishmania spp. is well characterized in mice and humans, much less is known concerning the canine immune response, particularly soon after exposure to the parasite. Early events are considered to be a determinant of infection outcome. To investigate the dog's early immune response to L. chagasi, an in vitro priming system (PIV) using dog naïve PBMC was established. Until now, dog PIV immune response to L. chagasi has not been assessed. We co-cultivated PBMC primarily stimulated with L. chagasi in vitro with autologous infected macrophages and found that IFN-γ mRNA is up-regulated in these cells compared to control unstimulated cells. IL-4 and IL-10 mRNA expression by L. chagasi-stimulated PBMC was similar to control unstimulated PBMC when incubated with infected macrophages. Surprisingly, correlation studies showed that a lower IFN-γ/IL-4 expression ratio correlated with a lower percentage of infection. We propose that the direct correlation between IFN-γ/IL-4 ratio and parasite load is dependent on the higher correlation of both IFN-γ and IL-4 expression with lower parasite infection. This PIV system was shown to be useful in evaluating the dog immune response to L. chagasi, and results indicate that a balance between IFN-γ and IL-4 is associated with control of parasite infection in vitro.


title: Feline Uveitis: Diagnosis and Treatment

text: Uveitis is the inflammation of any or all parts of the vascular tunic of the eye; the vascular tunic includes the iris, the ciliary body, and choroid. A good knowledge base, up-to-date reference materials, and good instruments will improve the diagnosis of uveitis. Feline uveitis can be caused by numerous infectious agents in addition to neoplasia and less likely trauma. The infectious causes most commonly associated with feline uveitis include feline leukemia virus, feline immunodeficiency virus, feline infectious peritonitis, systemic fungal infections, toxoplasmosis, and bartonellosis. Neoplastic causes of uveitis can be primary or secondary. Iris melanoma is the most common primary uveal neoplasia and trauma-associated sarcoma is the second most common primary uveal neoplasia. Treatment for the clinical signs of anterior uveitis include topical steroidal or non-steroidal anti-inflammatory agents, parasympatholytic agents for ciliary spasm, to keep the pupil dilated, and to prevent posterior synechia. Posterior uveitis should be treated with systemic medications that will address the underlying cause. Enucleation of blind, painful eyes not responsive to medications is a means to alleviate the animal’s discomfort and to further diagnose the underlying cause.


How disparities in gamete maturity influence the nascent conceptus, and beyond


El tratamiento de la pandemia por COVID 19. Ante la expectativa de evitar una oportunidad perdida


COVID-19 Seroconversion in Emergency Professionals at an Urban Academic Emergency Department in New York City


title: Outcomes in patients with severe COVID-19 disease treated with tocilizumab: a case–controlled study

text: BACKGROUND: COVID-19 is an ongoing threat to society. Patients who develop the most severe forms of the disease have high mortality. The interleukin-6 inhibitor tocilizumab has the potential to improve outcomes in these patients by preventing the development of cytokine release storm. AIMS: To evaluate the outcomes of patients with severe COVID-19 disease treated with the interleukin-6 inhibitor tocilizumab. METHODS: We conducted a retrospective, case–control, single-center study in patients with severe to critical COVID-19 disease treated with tocilizumab. Disease severity was defined based on the amount of oxygen supplementation required. The primary endpoint was the overall mortality. Secondary endpoints were mortality in non-intubated patients and mortality in intubated patients. RESULTS: A total of 193 patients were included in the study. Ninety-six patients received tocilizumab, while 97 served as the control group. The mean age was 60 years. Patients over 65 years represented 43% of the population. More patients in the tocilizumab group reported fever, cough and shortness of breath (83%, 80% and 96% vs. 73%, 69% and 71%, respectively). There was a non-statistically significant lower mortality in the treatment group (52% vs. 62.1%, P = 0.09). When excluding intubated patients, there was statistically significant lower mortality in patients treated with tocilizumab (6% vs. 27%, P = 0.024). Bacteremia was more common in the control group (24% vs. 13%, P = 0.43), while fungemia was similar for both (3% vs. 4%, P = 0.72). CONCLUSION: Our study showed a non-statistically significant lower mortality in patients with severe to critical COVID-19 disease who received tocilizumab. When intubated patients were excluded, the use of tocilizumab was associated with lower mortality.


title: Interferon-inducible effector mechanisms in cell-autonomous immunity

text: Interferons (IFNs) induce the expression of hundreds of genes as part of an elaborate antimicrobial programme designed to combat infection in all nucleated cells — a process termed cell-autonomous immunity. As described in this Review, recent genomic and subgenomic analyses have begun to assign functional properties to novel IFN-inducible effector proteins that restrict bacteria, protozoa and viruses in different subcellular compartments and at different stages of the pathogen life cycle. Several newly described host defence factors also participate in canonical oxidative and autophagic pathways by spatially coordinating their activities to enhance microbial killing. Together, these IFN-induced effector networks help to confer vertebrate host resistance to a vast and complex microbial world.


title: COVID-19 research has overall low methodological quality thus far: case in point for chloroquine/hydroxychloroquine

text: What is new? KEY FINDINGS: Clinical decision-makers must be informed by the best, most trustworthy, highest-quality, robust evidence. This translates into how much confidence we can have in the research findings and thus be optimally informed for decision-making. The estimates of effect in clinical research depends on the underlying research methodology. COVID-19 disease is presenting global health systems, clinicians, and patients grave challenges. No treatment or prophylaxis currently exists for COVID-19. The overall body of COVID-19 research is very flawed methodologically. An examination of hydroxychloroquine-azithromycin research findings due to the recent media focus revealed very low-quality methodology underpins the research. Vast amounts of time and resources are being allocated to COVID-19 research, and being potentially squandered. WHAT THIS ADDS TO WHAT WAS KNOWN: Flawed methodology and sub-optimal reporting of research findings could lead to biased estimates of effect. This could lead to treatment decisions that are not optimal based on biased estimates which could harm the patient. This article provides specific suggestions for improving on the COVID-19 methods and reporting with a focus on the issues that researchers must consider in their methodology and reporting if we are to have confidence in the estimates of effect. Failure to consider harms in research could be detrimental to the patient. This article focuses on the potential harms when therapeutic agents such as hydroxychloroquine, are being considered. WHAT IS THE IMPLICATION AND WHAT SHOULD CHANGE NOW: Research thus far on finding an optimal therapeutic agent (s) for COVID-19 could be hampered by methodologically flawed research. COVID-19 researchers must immediately and acutely focus on improving their methodology and reporting.


Isolation


title: A Four-Biomarker Blood Signature Discriminates Systemic Inflammation Due to Viral Infection Versus Other Etiologies

text: The innate immune system of humans and other mammals responds to pathogen-associated molecular patterns (PAMPs) that are conserved across broad classes of infectious agents such as bacteria and viruses. We hypothesized that a blood-based transcriptional signature could be discovered indicating a host systemic response to viral infection. Previous work identified host transcriptional signatures to individual viruses including influenza, respiratory syncytial virus and dengue, but the generality of these signatures across all viral infection types has not been established. Based on 44 publicly available datasets and two clinical studies of our own design, we discovered and validated a four-gene expression signature in whole blood, indicative of a general host systemic response to many types of viral infection. The signature’s genes are: Interferon Stimulated Gene 15 (ISG15), Interleukin 16 (IL16), 2′,5′-Oligoadenylate Synthetase Like (OASL), and Adhesion G Protein Coupled Receptor E5 (ADGRE5). In each of 13 validation datasets encompassing human, macaque, chimpanzee, pig, mouse, rat and all seven Baltimore virus classification groups, the signature provides statistically significant (p < 0.05) discrimination between viral and non-viral conditions. The signature may have clinical utility for differentiating host systemic inflammation (SI) due to viral versus bacterial or non-infectious causes.


title: The effect of a porcine reproductive and respiratory syndrome outbreak on genetic parameters and reaction norms for reproductive performance in pigs

text: The objective of this study was to estimate genetic parameters of antibody response and reproductive traits after exposure to porcine reproductive and respiratory syndrome virus. Blood samples were taken approximately 60 d after the outbreak. Antibody levels were quantified as the sample-to-positive ratio (S/P ratio) using a fluorescent microsphere assay. Reproductive traits included total number born (TNB), number born alive (NBA), number stillborn (NSB), number mummified (NBM), and number born dead (NBD). Mortality traits were log transformed for genetic analyses. Data were split into prior, during, and after the disease outbreak phases using visual appraisal of the estimates of farm-year-week effects for each reproductive trait. For NBA, data from all phases were combined into a reaction norm analysis with regression on estimates of farm-year-week effects for NBA. Heritability for S/P ratio was estimated at 0.17 ± 0.05. Heritability estimates for reproduction traits were all low and were lower during the outbreak for NBA but greater for mortality traits. TNB was not greatly affected during the outbreak, as many sows that farrowed during the outbreak were mated prior to the outbreak. Heritability for TNB decreased from 0.13 (prior) to 0.08 (after). Genetic correlation estimates between prior to and during the outbreak were high for TNB (0.86 ± 0.23) and NBA (0.98 ± 0.38) but lower for mortality traits: 0.65 ± 0.43, −0.42 ± 0.55, and 0.29 ± 1.39 for LNSB, LNBM, and LNBD, respectively. TNB prior to and after the outbreak had a lower genetic correlation (0.32 ± 0.33). In general, genetic correlation estimates of S/P ratio with reproductive performance during the outbreak were below 0.20 in absolute value, except for LNSB (−0.73 ± 0.29). Based on the reaction norm model, estimates of genetic correlations between the intercept and slope terms ranged from 0.24 ± 0.50 to 0.54 ± 0.35 depending on the parameterization used, indicating that selection for the intercept may result in indirect selection for steeper slopes, and thus, less resilient animals. In general, estimates of genetic correlations between farm-year-week effect classes based on the reaction norm model resembled estimates of genetic correlations from the multivariate analysis. Overall, compared to previous studies, antibody S/P ratios showed a lower heritability (0.17 ± 0.05) and low genetic correlations with reproductive performance during a porcine reproductive and respiratory syndrome outbreak, except for the LNSB.


Implementing Telemedicine in Inflammatory Bowel Disease: is COVID-19 the definitive trigger?


title: Comparative analysis of primer-probe sets for the laboratory confirmation of SARS-CoV-2

text: Coronavirus disease 2019 (COVID-19) is newly emerging human infectious diseases, which is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, also previously known as 2019-nCoV). Within two months of the outbreak, more than 80,000 cases of COVID-19 have been confirmed worldwide. Since the human to human transmission occurred easily and the human infection is rapidly increasing, the sensitive and early diagnosis is essential to prevent the global outbreak. Recently, World Health Organization (WHO) announced various primer and probe sets for SARS-CoV-2 previously developed in China, Germany, Hong Kong, Japan, Thailand, and USA. In this study, we compared the ability to detect SARS-CoV-2 RNA among the seven primer-probe sets for N gene and the three primer-probe sets for Orf1 gene. The result of the comparative analysis represented that the ‘2019-nCoV_N2, N3’ of USA and the ‘ORF1ab’ of China are the most sensitive primer-probe sets for N and Orf1 genes, respectively. Therefore, the appropriate combination from ORF1ab (China), 2019-nCoV_N2, N3 (USA), and NIID_2019-nCOV_N (Japan) sets should be selected for the sensitive and reliable laboratory confirmation of SARS-CoV-2.


title: A general insert label for peptide display on chimeric filamentous bacteriophages

text: Abstract The foreign insert intended to be displayed via recombinant phage proteins can have a negative effect on protein expression and phage assembly. A typical example is the case of display of peptides longer than 6 amino acid residues on the major coat protein, protein VIII of the filamentous bacteriophages M13 and fd. A solution to this problem has been the use of “two-gene systems” generating chimeric phages that concomitantly express wild-type protein VIII along with recombinant protein VIII. Although the two-gene systems are much more permissive in regard to insert length and composition, some cases can still adversely affect phage assembly. Although these phages genotypically contain the desired DNA of the insert, they appear to be phenotypically wild type. To avoid false-negative results when using chimeric phages in binding studies, it is necessary to confirm that the observed lack of phage recognition is not due to faulty assembly and display of the intended insert. Here we describe a strategy for generating antibodies that specifically recognize recombinant protein VIII regardless of the nature of its foreign insert. These antibodies can be used as a general monitor of the display of recombinant protein VIII into phage particles.


title: Eosinophils: changing perspectives in health and disease

text: Eosinophils have been traditionally perceived as terminally differentiated cytotoxic effector cells. Recent studies have profoundly altered this simplistic view of eosinophils and their function. New insights into the molecular pathways that control the development, trafficking and degranulation of eosinophils have improved our understanding of the immunomodulatory functions of these cells and their roles in promoting homeostasis. Likewise, recent developments have generated a more sophisticated view of how eosinophils contribute to the pathogenesis of different diseases, including asthma and primary hypereosinophilic syndromes, and have also provided us with a more complete appreciation of the activities of these cells during parasitic infection. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nri3341) contains supplementary material, which is available to authorized users.


title: Antiviral Mechanisms of Human Defensins

text: Defensins are an effector component of the innate immune system with broad antimicrobial activity. Humans express two types of defensins, α- and β-defensins, which have antiviral activity against both enveloped and non-enveloped viruses. The diversity of defensin-sensitive viral species reflects a multitude of antiviral mechanisms. These include direct defensin targeting of viral envelopes, glycoproteins, and capsids in addition to inhibition of viral fusion and post-entry neutralization. Binding and modulation of host cell surface receptors and disruption of intracellular signaling by defensins can also inhibit viral replication. In addition, defensins can function as chemokines to augment and alter adaptive immune responses, revealing an indirect antiviral mechanism. Nonetheless, many questions regarding the antiviral activities of defensins remain. Although significant mechanistic data is known for α-defensins, molecular details for β-defensin inhibition are mostly lacking. Importantly, the role of defensin antiviral activity in vivo has not been addressed due to the lack of a complete defensin knockout model. Overall, the antiviral activity of defensins is well established as are the variety of mechanisms by which defensins achieve this inhibition; however, additional research is needed to fully understand the role of defensins in viral pathogenesis.


title: Chapter 31 Galliformes and Columbiformes

text: Abstract Galliformes and columbifomes are closely associated with humans and some species have been domesticated for well over 5000 years. Both orders remain diverse, ranging from the common domestic poultry species (e.g., chicken, turkey, and squabs) to the more exotic species found in the wild and in zoological collections. While many species have been benefited from human activities and have increased their ranges, others have declined in numbers and some have become threatened (e.g., Trinidad piping-guan and wood quail) or even extinct (e.g., dodo and passenger pigeon). Nondomestic galliformes and columbiformes are susceptible to many of the same diseases that occur in domestic species, yet predisposition may be different. Furthermore, disease prevalence depends on exposure and potential risk factors. Infectious diseases that tend to be more common under intensive commercial production may not pose as great a risk to exotic and free-living species.


title: Swine models, genomic tools and services to enhance our understanding of human health and diseases

text: The pig is becoming increasingly important as a biomedical model. Given the similarities between pigs and humans, a greater understanding of the underlying biology of human health and diseases may come from the pig rather than from classical rodent models. With an increasing need for swine models, it is essential that the genomic tools, models and services be readily available to the scientific community. Many of these are available through the National Swine Resource and Research Center (NSRRC), a facility funded by the US National Institutes of Health at the University of Missouri. The goal of the NSRRC is to provide high-quality biomedical swine models to the scientific community.


docid: jnztspph

title: Coupled effects of local movement and global interaction on contagion

text: Abstract By incorporating segregated spatial domain and individual-based linkage into the SIS (susceptible–infected–susceptible) model, we propose a generalized epidemic model which can change from the territorial epidemic model to the networked epidemic model. The role of the individual-based linkage between different spatial domains is investigated. As we adjust the timescale parameter τ from 0 to unity, which represents the degree of activation of the individual-based linkage, three regions are found. Within the region of 0 < τ < 0.02 , the epidemic is determined by local movement and is sensitive to the timescale τ . Within the region of 0.02 < τ < 0.5 , the epidemic is insensitive to the timescale τ . Within the region of 0.5 < τ < 1 , the outbreak of the epidemic is determined by the structure of the individual-based linkage. As we keep an eye on the first region, the role of activating the individual-based linkage in the present model is similar to the role of the shortcuts in the two-dimensional small world network. Only activating a small number of the individual-based linkage can prompt the outbreak of the epidemic globally. The role of narrowing segregated spatial domain and reducing mobility in epidemic control is checked. These two measures are found to be conducive to curbing the spread of infectious disease only when the global interaction is suppressed. A log–log relation between the change in the number of infected individuals and the timescale τ is found. By calculating the epidemic threshold and the mean first encounter time, we heuristically analyze the microscopic characteristics of the propagation of the epidemic in the present model.


title: Directional and reoccurring sequence change in zoonotic RNA virus genomes visualized by time-series word count

text: Ebolavirus, MERS coronavirus and influenza virus are zoonotic RNA viruses, which mutate very rapidly. Viral growth depends on many host factors, but human cells may not provide the ideal growth conditions for viruses invading from nonhuman hosts. The present time-series analyses of short and long oligonucleotide compositions in these genomes showed directional changes in their composition after invasion from a nonhuman host, which are thought to recur after future invasions. In the recent West Africa Ebola outbreak, directional time-series changes in a wide range of oligonucleotides were observed in common for three geographic areas, and the directional changes were observed also for the recent MERS coronavirus epidemics starting in the Middle East. In addition, common directional changes in human influenza A viruses were observed for three subtypes, whose epidemics started independently. Long oligonucleotides that showed an evident directional change observed in common for the three subtypes corresponded to some of influenza A siRNAs, whose activities have been experimentally proven. Predicting directional and reoccurring changes in oligonucleotide composition should become important for designing diagnostic RT-PCR primers and therapeutic oligonucleotides with long effectiveness.


Re: Novel Coronavirus COVID-19 in late pregnancy: outcomes of first nine cases in an inner city London hospital


title: Characteristics of Febrile Patients with Normal White Blood Cell Counts and High C-Reactive Protein Levels in an Emergency Department

text: Fever is one of the more common chief complaints of patients who visit emergency departments (ED). Many febrile patients have markedly elevated C-reactive protein (CRP) levels and normal white blood cell (WBC) counts. Most of these patients have bacterial infection and no previous underlying disease of impaired WBC functioning. We reviewed patients who visited our ED between November 2003 and July 2004. The WBC count and CRP level of patients over 18 years of age who visited the ED because of or with fever were recorded. Patients who had normal WBC count (4,000–10,000/mL) and high CRP level (> 100 mg/L) were included. The data, including gender, age and length of hospital stay, were reviewed. Underlying diseases, diagnosis of the febrile disease and final condition were recorded according to the chart. Within the study period, 54,078 patients visited our ED. Of 5,628 febrile adults, 214 (3.8%) had elevated CRP level and normal WBC count. The major cause of febrility was infection (82.24%). Most of these patients were admitted (92.99%). There were 32 patients with malignant neoplasm, nine with liver cirrhosis, 66 with diabetes mellitus and 11 with uremia. There were no significant differences in age and gender between patients with and those without neoplasm. However, a higher inhospital mortality rate and other causes of febrility were noted in patients with neoplasm. It was not rare in febrile patients who visited the ED to have a high CRP level but normal WBC count. These patients did not necessarily have an underlying malignant neoplasm or hematologic illness. Factors other than malignant neoplasm or hematologic illness may be associated with the WBC response, and CRP may be a better indicator of infection under such conditions.


title: Genosensor on gold films with enzymatic electrochemical detection of a SARS virus sequence

text: Abstract A hybridisation-based genosensor was designed on a 100nm sputtered gold film. This material worked as an immobilisation and transduction surface. A 30-mer sequence that encodes a short lysine-rich region, unique to SARS (severe acute respiratory syndrome) virus, was chosen as target. A complementary strand (probe), labelled with a thiol group at the 3′-end, was immobilised on the film. After blocking the surface, hybridisation with the biotin-conjugated SARS strand (at the 3′-end) took place. Interaction with alkaline phosphatase-labelled streptavidin permits amplified indirect electrochemical detection. The analytical signal is constituted by an electrochemical process of indigo carmine, the soluble product of the enzymatic hydrolysis of 3-indoxyl phosphate. The use of a sensitive electrochemical technique such as square wave voltammetry allowed a detection limit of 6pM to be obtained for this DNA sequence, lower than any other found in the bibliography. The parameters affecting the methodology were studied, with special attention being placed on selectivity. Specificity was clearly enhanced when interaction time and stringency (in the form of formamide percentage) were increased. With 1h of strand interaction and employing 50% of formamide in the hybridisation buffer, a 3-base mismatch strand was perfectly distinguished from the complementary.


title: Neuronal Survival Strategies in the Face of RNA Viral Infection

text: Neurons of the mammalian central nervous system (CNS) are an essential and largely nonrenewable cell population. Thus, viral infections that result in neuronal depletion, either by viral lysis or by induction of the cytolytic immune response, would likely lead to profound neurologic impairment. However, many viral infections that result in tissue destruction elsewhere in the host produce few overt symptoms in the CNS, despite readily detectable virus expression. This observation has lead to the speculation that neurons possess strategies to limit the replication and spread of otherwise cytopathic viruses. These strategies either favor the clearance of virus in the absence of appreciable neuronal loss or promote the establishment of noncytolytic persistent infections. This review discusses some of these strategies, with an emphasis on how such survival techniques lessen the potential for CNS neuropathology


title: Collateral Damage: Medical Care Avoidance Behavior Among Patients With Myocardial Infarction During the COVID-19 Pandemic

text: The coronavirus disease-2019 (COVID-19) pandemic has caused an enormous strain on healthcare systems and society on a global scale. We report a new phenomenon of medical care avoidance among patients with acute coronary syndrome, which is due to concerns about contracting severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection during hospital stay, ultimately leading to dire clinical outcomes. (Level of Difficulty: Beginner.)


title: Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines

text: Viral subunit vaccines often contain immunodominant non-neutralizing epitopes that divert host immune responses. These epitopes should be eliminated in vaccine design, but there is no reliable method for evaluating an epitope's capacity to elicit neutralizing immune responses. Here we introduce a new concept ‘neutralizing immunogenicity index' (NII) to evaluate an epitope's neutralizing immunogenicity. To determine the NII, we mask the epitope with a glycan probe and then assess the epitope's contribution to the vaccine's overall neutralizing immunogenicity. As proof-of-concept, we measure the NII for different epitopes on an immunogen comprised of the receptor-binding domain from MERS coronavirus (MERS-CoV). Further, we design a variant form of this vaccine by masking an epitope that has a negative NII score. This engineered vaccine demonstrates significantly enhanced efficacy in protecting transgenic mice from lethal MERS-CoV challenge. Our study may guide the rational design of highly effective subunit vaccines to combat MERS-CoV and other life-threatening viruses.


We Got This and We Don't: Pediatricians Going to Battle for the “Big Children” of COVID-19


title: Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People's Republic of China, in February, 2003

text: Summary Background An epidemic of severe acute respiratory syndrome (SARS) has been associated with an outbreak of atypical pneumonia originating in Guangdong Province, People's Republic of China. We aimed to identify the causative agent in the Guangdong outbreak and describe the emergence and spread of the disease within the province. Methods We analysed epidemiological information and collected serum and nasopharyngeal aspirates from patients with SARS in Guangdong in mid-February, 2003. We did virus isolation, serological tests, and molecular assays to identify the causative agent. Findings SARS had been circulating in other cities of Guangdong Province for about 2 months before causing a major outbreak in Guangzhou, the province's capital. A novel coronavirus, SARS coronavirus (CoV), was isolated from specimens from three patients with SARS. Viral antigens were also directly detected in nasopharyngeal aspirates from these patients. 48 of 55 (87%) patients had antibodies to SARS CoV in their convalescent sera. Genetic analysis showed that the SARS CoV isolates from Guangzhou shared the same origin with those in other countries, and had a phylogenetic pathway that matched the spread of SARS to the other parts of the world. Interpretation SARS CoV is the infectious agent responsible for the epidemic outbreak of SARS in Guangdong. The virus isolated from patients in Guangdong is the prototype of the SARS CoV in other regions and countries.


docid: duzvoaqr

title: Detection of canine astrovirus in dogs with diarrhea in Japan

text: Canine astrovirus (CAstV) is the causative agent of gastroenteritis in dogs. We collected rectal swabs from dogs with or without diarrhea symptoms in Japan and examined the feces for the presence of CAstV by RT-PCR with primers based on a conserved region of the ORF1b gene. The ORF1b gene of CAstV was not detected in the 42 dogs without clinical illness but was present in three pups out of the 31 dogs with diarrhea symptoms. Based on the full-length capsid protein, the CAstV KU-D4-12 strain that we detected in this study shared high homology with the novel virulent CAstV VM-2011 strain.


title: T cell epitope: Friend or Foe? Immunogenicity of biologics in context

text: Abstract Like vaccines, biologic proteins can be very immunogenic for reasons including route of administration, dose frequency and the underlying antigenicity of the therapeutic protein. Because the impact of immunogenicity can be quite severe, regulatory agencies are developing risk-based guidelines for immunogenicity screening. T cell epitopes are at the root of the immunogenicity issue. Through their presentation to T cells, they activate the process of anti-drug antibody development. Preclinical screening for T cell epitopes can be performed in silico, followed by in vitro and in vivo validation. Importantly, screening for immunogenicity is complicated by the discovery of regulatory T cell epitopes, which suggests that immunogenicity testing must now take regulatory T cells into consideration. In this review, we address the application of computational tools for preclinical immunogenicity assessment, the implication of the discovery of regulatory T cell epitopes, and experimental validation of those assessments.


title: Recombinant Newcastle disease virus (NDV) expressing Duck Tembusu virus (DTMUV) pre-membrane and envelope proteins protects ducks against DTMUV and NDV challenge

text: Abstract The newly emerged Duck Tembusu virus (DTMUV) is responsible for considerable economic loss in waterfowl-raising areas in China since 2010. Meanwhile, the virulent Newcastle disease virus (NDV) has also caused sporadic outbreaks in waterfowl. The individual vaccines against both diseases are available, however, there is no bivalent or combined vaccine for either disease. Here, we constructed a recombinant NDV-vectored vaccine candidate that expresses the pre-membrane (prM) and envelope (E) genes from DTMUV, designated as aGM/prM + E. The foreign prM and E proteins were stably expressed in aGM/prM + E and exhibited similar pathogenicity but higher growth kinetics than those of the parental virus. The aGM/prM + E carries a fusion cleavage site in accordance with avirulent viruses that have been frequently isolated from waterfowl, and induced remarkably (p < 0.001) higher NDV-specific hemagglutination inhibition (HI) titers than commercially available live NDV vaccines (LaSota strain). The aGM/prM + E also elicited significantly higher (p < 0.05) virus neutralization (VN) titers than commercially available DTMUV inactivated vaccines (HB strain). The aGM/prM + E not only provided complete protection against NDV challenge but also reduced the gross lesions on ovarian folliculi and provided 80% protection against DTMUV in ducks. We note that the aGM/prM + E vaccine can prevent challenged ducks from shedding of NDV and DTMUV. Our results suggest that the candidate vaccine aGM/prM + E would help decrease NDV and DTMUV transmissions in waterfowl raising areas in China.


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docid: lmuvzmdd

title: Serum biomarkers of oxidative stress in cats with feline infectious peritonitis

text: Abstract The purpose of this study was to elucidate the possible presence of oxidative stress in cats naturally affected by feline infectious peritonitis (FIP) by investigating two antioxidant biomarkers in serum: paraoxonase-1 (PON1) and total antioxidant capacity (TAC). PON1 was measured by spectrophotometric assays using three different substrates: p-nitrophenyl acetate (pNA), phenyl acetate (PA) and 5-thiobutil butyrolactone (TBBL), in order to evaluate possible differences between them. The PA and TBBL assays for PON1 and the assay for TAC were validated, providing acceptable precision and linearity although PA and TAC assays showed limit of detection higher than the values found in some cats with FIP. Cats with FIP and other inflammatory conditions showed lower PON1 values compared with a group of healthy cats with the three assays used, and cats with FIP showed significant decreased TAC concentrations. This study demonstrated the existence of oxidative stress in cats with FIP.