title: Labor and delivery guidance for COVID-19

text: This document addresses the current coronavirus disease 2019 (COVID-19) pandemic for providers and patients in labor and delivery (L&D). The goals are to provide guidance regarding methods to appropriately screen and test pregnant patients for COVID-19 prior to, and at admission to L&D reduce risk of maternal and neonatal COVID-19 disease through minimizing hospital contact and appropriate isolation; and provide specific guidance for management of L&D of the COVID-19–positive woman, as well as the critically ill COVID-19–positive woman. The first 5 sections deal with L&D issues in general, for all women, during the COVID-19 pandemic. These include Section 1: Appropriate screening, testing, and preparation of pregnant women for COVID-19 before visit and/or admission to L&D Section 2: Screening of patients coming to L&D triage; Section 3: General changes to routine L&D work flow; Section 4: Intrapartum care; Section 5: Postpartum care; Section 6 deals with special care for the COVID-19–positive or suspected pregnant woman in L&D and Section 7 deals with the COVID-19–positive/suspected woman who is critically ill. These are suggestions, which can be adapted to local needs and capabilities.


title: Identifying and hurdling obstacles to translational research

text: Although there is overwhelming pressure from funding agencies and the general public for scientists to bridge basic and translational studies, the fact remains that there are significant hurdles to overcome in order to achieve this goal. The purpose of this Opinion article is to examine the nature of these hurdles and to provide food for thought on the main obstacles that impede this process.


title: COVID-19 challenges to Pakistan: Is GIS analysis useful to draw solutions?

text: Abstract The outbreak of novel coronavirus (COVID-19) is a public health emergency that had caused disastrous results in more than 100 countries. The ability to detect disease outbreaks in the early stages is a key component of efficient disease control and prevention. With the increased availability of electronic health-care data and spatial analysis techniques, there is great potential to develop algorithms to enable more effective disease surveillance. The research focuses to develop a transparent user-friendly method to simulate the outbreak data. The paper describes the GIS tools to identify and define the field of investigation which requires consideration of the strengths and limitations of data collection instruments, facility of locational data collection, accuracy of locational data, and pertinent attributes for understanding disease risk. Using such information, it is quite easy for authorities to locate the highly effected area and take appropriate actions in that particular areas. However, GIS techniques, resources, and methods can be used in Pakistan for more effective investigation of vulnerable geographical locations.


title: Molecular characterization of a new PToV strain. Evolutionary implications

text: Abstract Toroviruses are emergent viruses, belonging to the Nidovirales order, that remain mostly ignored, despite they are able to infect different species of domestic animals and humans, causing enteric diseases and diarrhea. Thus far, only five variants of porcine torovirus (PToV) have been identified. In this report we describe the identification and partial characterization of a new strain of porcine torovirus (PToV-BRES) that was detected by RT-PCR in a swine faecal specimen from a farm in Brescia (Italy). The complete genes coding for the nucleocapsid (N), hemagglutinin-esterase (HE) and membrane (M) proteins were amplified, and sequence analysis showed that PToV-BRES is a new PToV strain that, based on the HE gene sequence, is phylogenetically related to P4 strain, that was up to now the only member of a distinct PToV lineage. The nucleocapsid protein from PToV-BRES was expressed in insect cells as a his-tagged protein, purified by affinity chromatography and used to develop an ELISA method to detect antibodies against PToV. This assay was evaluated using a serum collection including 45 samples from three commercial farms from Spain. High antibody prevalence against PToV was observed in the three farms, both in adult animals and in piglets, which could suggest that PToV might be endemic in Spanish porcine population. The ELISA method developed in this work could be useful in future epidemiological surveys about toroviruses.


title: Improving VOCs control strategies based on source characteristics and chemical reactivity in a typical coastal city of South China through measurement and emission inventory

text: Abstract In China, the corresponding control directives for volatile organic compounds (VOCs) have been based on primary emissions, rarely considering reactive speciation. To seek more effective VOCs control strategies, we investigated 107 VOC species in a typical coastal city (Beihai) of South China, from August to November 2018. Meanwhile, a high-resolution anthropogenic VOCs monthly emission inventory (EI) was established for 2018. For source apportionments (SAs) reliability, comparisons of source structures derived from positive matrix factorization (PMF) and EI were made mainly in terms of reaction losses, uncertainties and specific ratios. Finally, for the source–end control, a comprehensive reactivity control index (RCI) was established by combing SAs with reactive speciation profiles. Ambient measurements showed that the average concentration of VOCs was 26.38 ppbv, dominated by alkanes (36.7%) and oxygenated volatile organic compounds (OVOCs) (29.4%). VOC reactivity was estimated using ozone formation potential (52.35 ppbv) and propylene-equivalent concentration (4.22 ppbv). EI results displayed that the entire VOC, OFP, and propylene-equivalent emissions were 40.98 Gg, 67.98 Gg, and 105.93 Gg, respectively. Comparisons of source structures indicated that VOC SAs agreed within ±100% between two perspectives. Both PMF and EI results showed that petrochemical industry (24.0% and 33.0%), food processing and associated combustion (19.1% and 29.2%) were the significant contributors of anthropogenic VOCs, followed by other industrial processes (22.2% and 13.3%), transportation (18.9% and 12.0%), and solvent utilization (9.1% and10.5%). Aimed at VOCs abatement according to RCI: for terminal control, fifteen ambient highly reactive species (predominantly alkenes and alkanes) were targeted; for source control, the predominant anthropogenic sources (food industry, solvent usage, petrochemical industry and transportation) and their emitted highly reactive species were determined. Particularly, with low levels of ambient VOC and primary emissions, in this VOC and NOx double-controlled regime, crude disorganized emission from food industry contributed a high RCI.


title: Detection of SARS-CoV-2-specific humoral and cellular immunity in COVID-19 convalescent individuals

text: Summary The World Health Organization has declared SARS-CoV-2 virus outbreak a world-wide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free and therefore were discharged, and detected SARS-CoV-2-specific humoral and cellular immunity in 8 newly discharged patients. Follow-up analysis on another cohort of 6 patients 2 weeks post discharge also revealed high titers of IgG antibodies. In all 14 patients tested, 13 displayed serum neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. Our work provides a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It has also implications in developing an effective vaccine to SARS-CoV-2 infection.


title: COVID-19 Outpatient Screening: a Prediction Score for Adverse Events

text: BACKGROUND. We sought to develop an automatable score to predict hospitalization, critical illness, or death in patients at risk for COVID-19 presenting for urgent care during the Massachusetts outbreak. METHODS. Single-center study of adult outpatients seen in respiratory illness clinics (RICs) or the emergency department (ED), including development (n = 9381, March 7-May 2) and prospective (n = 2205, May 3–14) cohorts. Data was queried from Partners Enterprise Data Warehouse. Outcomes were hospitalization, critical illness or death within 7 days. We developed the COVID-19 Acuity Score (CoVA) using automatically extracted data from the electronic medical record and learning-to-rank ordinal logistic regression modeling. Calibration was assessed using predicted-to-observed ratio (E/O). Discrimination was assessed by C-statistics (AUC). RESULTS. In the development cohort, 27.3%, 7.2%, and 1.1% of patients experienced hospitalization, critical illness, or death, respectively; and in the prospective cohort, 26.1%, 6.3%, and 0.5%. CoVA showed excellent performance in the development cohort (concurrent validation) for hospitalization (E/O: 1.00, AUC: 0.80); for critical illness (E/O: 1.00, AUC: 0.82); and for death (E/O: 1.00, AUC: 0.87). Performance in the prospective cohort (prospective validation) was similar for hospitalization (E/O: 1.01, AUC: 0.76); for critical illness (E/O 1.03, AUC: 0.79); and for death (E/O: 1.63, AUC=0.93). Among 30 predictors, the top five were age, diastolic blood pressure, blood oxygen saturation, COVID-19 testing status, and respiratory rate. CONCLUSIONS. CoVA is a prospectively validated automatable score to assessing risk for adverse outcomes related to COVID-19 infection in the outpatient setting.


title: The epidemiologic and clinical features of suspected and confirmed cases of imported 2019 novel coronavirus pneumonia in north Shanghai, China.

text: Background A recent cluster of pneumonia cases in Wuhan (China) is known to be caused by a novel beta-coronavirus named the corona virus disease 2019 (COVID-19) and can be spread through human-to-human transmission. Methods Data of 21 patients with laboratory-confirmed COVID-19 and 84 patients with suspected COVID-19 were analyzed by RT-PCR. The epidemiologic and clinical features as well as clinical outcomes were compared between the confirmed and suspected cases. Results Altogether 105 patients had been enrolled in this study by February 15, 2020 in north Shanghai, including 21 confirmed cases and 84 suspected cases of COVID-19. The incubation period of these confirmed patients with imported COVID-19 was 17.6 days (IQR 5-34 days) and the median time from symptom onset to diagnosis was 145.64 h (IQR 21-441 h). More than 50% of the confirmed patients were older than 51 (range, 51-60) years. Fifty (59.5%) of the 84 probably patients were younger than 40 years, including 27 (32%) patients younger than 30 years. Most confirmed patients were men (61.9%, 13/21), and less than 50% of them had underlying diseases, including diabetes (9.5%, 2/21), hypertension (19%, 4/21), COPD (23.8%, 5/21), and CD (23.8%, 5/21). In addition, 10 (47.6%) of the 21 confirmed patients were ordinary employees, and 12 (57.2%) of them had recently been to Wuhan or had close contacts with people from Wuhan. Of the 84 suspected patients, 28 (33.3%) were retired employees; 69 (82.1%) had recently been to supermarkets and groceries or had a history of traveling abroad or to other cities of China. The common onset symptoms of the patients in both groups were fever and cough. The symptom of Sputum production was more pronounced in probably patients (40.5%, 34/84) than that in confirmed patients (9.5%, 2/21). More than 50% imported patients (53.3%, 56/105) had one and two affected lobes. Twenty-nine (27.6%) of the 105 imported patients had been discharged, no patient had died, and all the other patients are still in hospital. Conclusions The overall incubation period in this cohort of imported confirmed COVID-19 patients was longer than that in Wuhan, mostly infecting older men. The disease onset of imported COVID-19 infection was occult, and the clinical symptoms were usually mild, mostly presenting as low fever, fatigue, light cough, and mild dyspnea.


title: Ligation-mediated amplification for effective rapid determination of viral RNA sequences (RDV)

text: Abstract Background Emerging infectious diseases pose a significant risk to public health. Methods for rapid detection of pathogens are needed to effectively treat these diseases. Recently, we developed new methods for the rapid determination of viral RNA sequences, RDV ver1.0 and ver2.0. We demonstrated that these methods were able to simultaneously detect cDNA fragments of many different viruses without using sequence specific primers. However, some species of viruses, including the Yokose virus (YOKV), a flavivirus, could not be detected using the conventional procedures. Objective The RDV method was further modified to reduce the candidate PCR primer sets. Study design Primer sets were reduced to 256 sets in the improved RDV ver3.0, and theoretically, all viral cDNA fragments ligated by two kinds of adaptors after digestion by two restriction enzymes could be amplified in the PCR step for direct sequencing. Results We succeeded in obtaining 118 YOKV cDNA fragments of the 141 sequence fragments. The cDNA fragments covered diverse range of viral genome. Conclusion We were able to reduce the combinations of PCR primer sets used in the RDV method. This RDV method ver3.0 has a potential to detect viral cDNA fragments of both known and unknown RNA viruses rapidly and conveniently.


title: Dipeptidyl peptidase 4 inhibitors and their potential immune modulatory functions

text: Abstract Dipeptidyl peptidase 4 (DPP4) inhibitors (DPP4is) are oral anti-diabetic drugs (OADs) for the treatment of type 2 diabetes mellitus (T2DM) through inhibiting the degradation of incretin peptides. Numerous investigations have been focused on the effects of DPP4is on glucose homeostasis. However, there are limited evidences demonstrating their Potential modulatory functions in the immune system. DPP4, originally known as the lymphocyte cell surface protein CD26, is widely expressed in many types of immune cells including CD4(+) and CD8(+) T cells, B cells, NK cells, dendritic cells, and macrophages; and regulate the functions of these cells. In addition, DPP4 is capable of modulating plenty of cytokines, chemokines and peptide hormones. Accordingly, DPP4/CD26 is speculated to be involved in various immune/inflammatory diseases and DPP4is may become a new drug class applied in these diseases. This review focuses on the regulatory effects of DPP4is on immune functions and their possible underlying mechanisms. Further clinical studies will be necessitated to fully evaluate the administration of DPP4is in diabetic patients with or without immune diseases.


title: Pleiotropic roles of the ubiquitin-proteasome system during viral propagation

text: Abstract Protein ubiquitination is a highly conserved post-translational modification affecting various biological processes including viral propagation. Ubiquitination has multiple effects on viral propagation, including viral genome uncoating, viral replication, and immune evasion. Ubiquitination of viral proteins is triggered by the ubiquitin-proteasome system (UPS). This involves the covalent attachment of the highly conserved 76 amino acid residue ubiquitin protein to target proteins by the consecutive actions of E1, E2 and E3 enzymes, and the 26S proteasome that together form a multiprotein complex that degrades target proteins. The UPS is the primary cytosolic proteolytic machinery for the selective degradation of various forms of proteins including viral proteins, thereby limiting viral growth in host cells. To combat this host anti-viral machinery, viruses have evolved the ability to employ or subvert the UPS to inactivate or degrade cellular proteins to favour viral propagation. This review highlights our current knowledge on the different roles of the UPS during viral propagation.


docid: qblrokpg

title: The Emerging Roles of Viroporins in ER Stress Response and Autophagy Induction during Virus Infection

text: Viroporins are small hydrophobic viral proteins that oligomerize to form aqueous pores on cellular membranes. Studies in recent years have demonstrated that viroporins serve important functions during virus replication and contribute to viral pathogenicity. A number of viroporins have also been shown to localize to the endoplasmic reticulum (ER) and/or its associated membranous organelles. In fact, replication of most RNA viruses is closely linked to the ER, and has been found to cause ER stress in the infected cells. On the other hand, autophagy is an evolutionarily conserved “self-eating” mechanism that is also observed in cells infected with RNA viruses. Both ER stress and autophagy are also known to modulate a wide variety of signaling pathways including pro-inflammatory and innate immune response, thereby constituting a major aspect of host-virus interactions. In this review, the potential involvement of viroporins in virus-induced ER stress and autophagy will be discussed.


title: MT-PCR panel detection of canine parvovirus (CPV-2): Vaccine and wild-type CPV-2 can be difficult to differentiate in canine diagnostic fecal samples

text: Abstract Canine parvovirus (CPV-2) remains an important cause of devastating enteritis in young dogs. It can be successfully prevented with live attenuated CPV-2 vaccines when given at the appropriate age and in the absence of maternal antibody interference. Rapid diagnosis of parvoviral enteritis in young dogs is essential to ensuring suitable barrier nursing protocols within veterinary hospitals. The current diagnostic trend is to use multiplexed PCR panels to detect an array of pathogens commonly responsible for diarrhea in dogs. The multiplexed PCR assays do not distinguish wild from vaccine CPV-2. They are highly sensitive and detect even a low level of virus shedding, such as those caused by the CPV-2 vaccine. The aim of this study was to identify the CPV-2 subtypes detected in diagnostic specimens and rule out occult shedding of CPV-2 vaccine strains. For a total of 21 samples that tested positive for CPV-2 in a small animal fecal pathogens diagnostic multiplexed tandem PCR (MT-PCR) panel during 2014–2016 we partially characterized the VP2 gene of CPV-2. Vaccine CPV-2 strain, wild type CPV-2a subtypes and vaccine-like CPV-2b subtypes were detected. High copy number was indicative of wild-type CPV-2a presence, but presence of vaccine-like CPV-2b had a variable copy number in fecal samples. A yardstick approach to a copy number or Ct-value to discriminate vaccine strain from a wild type virus of CPV-2 can be, in some cases, potentially misleading. Therefore, discriminating vaccine strain from a wild type subtype of CPV-2 remains ambitious.


title: Encoded metal nanoparticle-based molecular beacons for multiplexed detection of DNA

text: In this paper we describe a molecular beacon format assay in which encoded nanowire particles are used to achieve multiplexing. We demonstrate this principle with the detection of five viral pathogens; Hepatitis A virus, Hepatitis C virus, West Nile Virus, Human Immune Deficiency virus and Severe Acute Respiratory Syndrome virus. Oligonucleotides are designed complementary to a target sequence of interest containing a 3′ universal fluorescence dye. A 5′ thiol causes the oligonucleotides to self-assemble onto the metal nanowire. The single-stranded oligonucleotide contains a self-complementary hairpin stem sequence of 10 bases that forces the 3′ fluorophore to come into contact with the metallic nanowire surface, thereby quenching the fluorescence. Upon addition of target DNA, there is hybridization with the complementary oligonucleotides. The resulting DNA hybrid is rigid, unfolds the hairpin structure, and causes the fluorophore to be moved away from the surface such that it is no longer quenched. By using differently encoded nanowires, each conjugated with a different oligonucleotide sequence, multiplexed DNA assays are possible using a single fluorophore, from a multiplexed RT-PCR reaction.


title: The Main Biological Hazards in Animal Biosafety Level 2 Facilities and Strategies for Control

text: Concern about the biological hazards involved in microbiological research, especially research involving laboratory animals, has increased in recent years. Working in an animal biosafety level 2 facility (ABSL-2), commonly used for research on infectious diseases, poses various biological hazards. Here, the regulations and standards related to laboratory biosafety in China are introduced, the potential biological hazards present in ABSL-2 facilities are analyzed, and a series of strategies to control the hazards are presented.


Cruise Ships, Nursing Homes and Prisons as COVID-19 Epicenters: A ‘Wicked Problem” with Breakthrough Solutions?


title: HIV infection and antiretroviral therapy lead to unfolded protein response activation

text: BACKGROUND: The unfolded protein response (UPR) is one of the pathways triggered to ensure quality control of the proteins assembled in the endoplasmic reticulum (ER) when cell homeostasis is compromised. This mechanism is primarily composed of three transmembrane proteins serving as stress sensors: PKR-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1 (IRE1). These three proteins’ synergic action elicits translation and transcriptional downstream pathways, leading to less protein production and activating genes that encode important proteins in folding processes, including chaperones. Previous reports showed that viruses have evolved mechanisms to curtail or customize this UPR signaling for their own benefit. However, HIV infection’s effect on the UPR has scarcely been investigated. METHODS: This work investigated UPR modulation by HIV infection by assessing UPR-related protein expression under in vitro and in vivo conditions via Western blotting. Antiretroviral (ARV) drugs’ influence on this stress response was also considered. RESULTS: In in vitro and in vivo analyses, our results confirm that HIV infection activates stress-response components and that ARV therapy contributes to changes in the UPR’s activation profile. CONCLUSIONS: This is the first report showing UPR-related protein expression in HIV target cells derived directly from HIV-infected patients receiving different ARV therapies. Thus, two mechanisms may occur simultaneously: interference by HIV itself and the ARV drugs’ pharmacological effects as UPR activators. New evidence of how HIV modulates the UPR to enhance its own replication and secure infection success is also presented. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0298-0) contains supplementary material, which is available to authorized users.


Surge capacity and updated admission criteria: response of the NHS-commissioned national respiratory ECMO network to the COVID-19 pandemic


title: A rapid, inexpensive yeast-based dual-fluorescence assay of programmed—1 ribosomal frameshifting for high-throughput screening

text: Programmed −1 ribosomal frameshifting (−1 PRF) is a mechanism that directs elongating ribosomes to shift-reading frame by 1 base in the 5′ direction that is utilized by many RNA viruses. Importantly, rates of −1 PRF are fine-tuned by viruses, including Retroviruses, Coronaviruses, Flavivriuses and in two endogenous viruses of the yeast Saccharomyces cerevisiae, to deliver the correct ratios of different viral proteins for efficient replication. Thus, −1 PRF presents a novel target for antiviral therapeutics. The underlying molecular mechanism of −1 PRF is conserved from yeast to mammals, enabling yeast to be used as a logical platform for high-throughput screens. Our understanding of the strengths and pitfalls of assays to monitor −1 PRF have evolved since the initial discovery of −1 PRF. These include controlling for the effects of drugs on protein expression and mRNA stability, as well as minimizing costs and the requirement for multiple processing steps. Here we describe the development of an automated yeast-based dual fluorescence assay of −1 PRF that provides a rapid, inexpensive automated pipeline to screen for compounds that alter rates of −1 PRF which will help to pave the way toward the discovery and development of novel antiviral therapeutics.


docid: eaatmzwg

title: Smilax guianensis Vitman extract prevents LPS-induced inflammation by inhibiting the NF-κB pathway in RAW 264.7 cells

text: Nutraceutical treatments can reduce inflammation and prevent the development of inflammatory diseases In this study, the anti-inflammatory effects of Smilax guianensis Vitman extract (SGE) were examined SGE suppressed lipopolysaccharide (LPS)-mediated nitrite production in RAW 264 7 cells SGE also prevented the LPS-induced expression of inducible nitric oxide synthase (iNOS) but not cyclooxygenase (COX)-2 Western blot analysis showed that SGE attenuated LPS-induced phosphorylation of IκB kinase, inhibitor of kappa B (IκB), and p65 Additionally, SGE inhibited LPS-induced IκB degradation in RAW 264 7 cells Western blot analysis of the cytosolic and nuclear fractions, as well as immunofluorescence assay results, revealed that SGE suppressed LPS-induced p65 nuclear translocation in RAW 264 7 cells Moreover, SGE reduced LPS-induced interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) mRNA expression and IL-1β and IL-6 protein expression in RAW 264 7 cells Collectively, these results indicate that SGE suppresses the NF-κB signaling pathway and thereby inhibits the production of NO, IL-1β, and IL-6


title: Hospital management of adults with severe acute respiratory syndrome (SARS) if SARS re-emerges—updated 10 February 2004

text: Abstract Severe Acute Respiratory Syndrome (SARS) is a potentially severe and highly infectious disease to which healthcare workers involved in the management of cases are particularly vulnerable. These guidelines briefly summarise optimal and safe practice for clinicians involved in the emergency care of patients with probable or confirmed SARS.


docid: hxhmplkn

title: Identification of a Bacillus thuringiensis Cry11Ba toxin-binding aminopeptidase from the mosquito, Anopheles quadrimaculatus

text: BACKGROUND: Aminopeptidase N (APN) type proteins isolated from several species of lepidopteran insects have been implicated as Bacillus thuringiensis (Bt) toxin-binding proteins (receptors) for Cry toxins. We examined brush border membrane vesicle (BBMV) proteins from the mosquito Anopheles quadrimaculatus to determine if APNs from this organism would bind mosquitocidal Cry toxins that are active to it. RESULTS: A 100-kDa protein with APN activity (APN(Anq )100) was isolated from the brush border membrane of Anopheles quadrimaculatus. Native state binding analysis by surface plasmon resonance shows that APN(Anq )100 forms tight binding to a mosquitocidal Bt toxin, Cry11Ba, but not to Cry2Aa, Cry4Ba or Cry11Aa. CONCLUSION: An aminopeptidase from Anopheles quadrimaculatus mosquitoes is a specific binding protein for Bacillus thuringiensis Cry11Ba.


title: Antiproliferative cyclodepsipeptides from the marine actinomycete Streptomyces sp. P11-23B downregulating the tumor metabolic enzymes of glycolysis, glutaminolysis, and lipogenesis

text: Abstract Two cyclodepsipeptides and a known cyclodepsipeptide valinomycin were isolated from a culture of the marine actinomycete Streptomyces sp. P11-23B. Their structures were established based on NMR, HRESIMS, and MS-MS spectroscopic interpretation as well as by chemical degradation. Both streptodepsipeptides P11A and P11B inhibited proliferation of different glioma cell lines, with IC50 values ranging from 0.1 μM to 1.4 μM. Streptodepsipeptide P11A was found to block the cell cycle at the G0/G1 phase and induce apoptosis in glioma cells. Further investigation demonstrated that streptodepsipeptide P11A downregulated expression of HK2, PFKFB3, PKM2, GLS, and FASN, important tumor metabolic enzymes. Data from this study suggested that targeting multiple tumor metabolic regulators might be one anti-glioma mechanism of streptodepsipeptide P11A. A possible mechanism for this class of streptodepsipeptides is reported herein.


title: Burden of influenza infection in hospitalised children below 6 months of age and above in Hong Kong from 2005 to 2011()

text: The World Health Organization recommends vaccination of pregnant women for seasonal influenza that can also protect infants aged below 6 months. We estimated incidence and disease burden of influenza in hospitalised children below and above 6 months of age in Hong Kong during a 6 year period. Discharge diagnoses for all admissions to public Hong Kong Hospital Authority hospitals, recorded in a central computerised database (Clinical Management System, CMS), were analysed for the period April 2005 to March 2011. Incidence estimates of influenza disease by age group were derived from CMS ICD codes 487–487.99. Laboratory-confirmed influenza infections from a single surveillance hospital were then linked to the CMS entries to assess possible over- and under-diagnosis of influenza based on CMS codes alone. Influenza was recorded as any primary or any secondary diagnosis in 1.3% (1158/86,582) of infants aged above 6 days to below 6 months and 4.3% (20,230/471,482) of children above 6 days to below 18 years. The unadjusted incidence rates per 100,000 person-years based on any CMS diagnosis of influenza in all admission to Hong Kong public hospitals were 627 in the below 2 months of age group and 1762 in the 2 month to below 6 month group. Incidence of hospitalisation for influenza in children was highest from 2 months to below 6 months. In the absence of vaccines for children below 6 months of age, effective vaccination of pregnant women may have a significant impact on reducing influenza hospitalisations in this age group.


title: Viral survival

text: How long do viruses like cold, flu and coronavirus survive outside the body? What factors affect this? Douglas Fairchild, Two Harbors, Minnesota, US


title: Implicaciones de la pandemia por COVID-19 para el paciente con insuficiencia cardiaca, trasplante cardiaco y asistencia ventricular. Recomendaciones de la Asociación de Insuficiencia Cardiaca de la Sociedad Española de Cardiología

text: Resumen La irrupción de la pandemia por COVID-19 está suponiendo un verdadero reto social y sanitario. Su rápida expansión hace que sean muchos los pacientes afectos que desarrollan clínica asociada, incluyendo síntomas cardiológicos. Los pacientes con afectación cardiaca son un grupo especialmente vulnerable, por su mayor riesgo de contagio y gravedad de la enfermedad. La insuficiencia cardiaca, incluyendo al trasplante cardiaco y las asistencias ventriculares, supone un grupo relevante dentro de los pacientes cardiológicos. Por ello, la Asociación de Insuficiencia Cardiaca de la Sociedad Española de Cardiología ha elaborado una serie de recomendaciones para el abordaje de estos pacientes, en los diferentes escenarios en los que se pueden encontrar: ambulatorio y hospitalizado, con y sin COVID-19. Abstract The outbreak of the COVID-19 pandemic is a real social and healthcare system challenge. Its rapid expansion implies that many affected patients develop associated symptoms, including cardiological symptoms. Patients with cardiological diseases are at increased risk of being infected and the severity of the disease. Heart failure, including heart transplantation and ventricular assist devices, is a relevant group within the cardiological patients. For this reason, the following text has been intended to give a series of recommendations for the management of these patients, in the different scenarios in which they can be found: outpatient and hospitalized, with and without COVID-19.


title: Gastrointestinal Diseases of Rabbits

text: Gastrointestinal stasis syndrome is a very common presentation of an ill rabbit to the veterinarian. The causes involved in this syndrome are often multifactorial, and an inappropriate diet puts the rabbit at a greater risk of developing this syndrome. Complications of this disorder can lead to gastrointestinal obstruction, a life-threatening condition that necessitates aggressive medical and in some case surgical therapy. Rabbits may also be presented with signs of diarrhea. However, abnormal cecotrophs must be differentiated from true intestinal diarrhea. The common causes, diagnosis and management of diarrhea including dysbiosis and enteritis are discussed. Other important causes of gastrointestinal disease are infectious disease and liver lobe torsion. Rabbit hemorrhagic disease virus has a new variant that has been identified in mainland Europe, the United Kingdom, and Australia. Subclinical infection of intestinal coccidiosis is a common cause of weight loss in adult rabbits. Liver lobe torsion is a challenging condition to diagnose in rabbits; this chapter discusses the presenting signs, diagnostic techniques, and therapeutic options.


title: The effect of grafted methoxypoly(ethylene glycol) chain length on the inhibition of respiratory syncytial virus (RSV) infection and proliferation

text: Abstract Respiratory syncytial virus (RSV) is a significant cause of morbidity in humans. To date, no effective treatments exist and current prophylactic therapy access is limited and is only ∼50% effective. To attenuate the risk of RSV infection, we hypothesized that bioengineering of either the virus particle or host cell via the covalent grafting of methoxypoly(ethylene glycol) [mPEG] would prevent infection. To this end, the anti-viral effects of grafting concentration, linker chemistry and polymer length on RSV infection was assessed. For viral modification, short chain polymers (2kDa) were significantly more effective than long chain (20kDa) polymers. In contrast, modification of host cells with small polymers provided no (∼0%) protection while long chain polymers effectively prevented infection. For example, at 48hours post-infection at a multiplicity of infection of 0.5 and grafting concentrations of 5, 7.5, and 15mm, 20kDa mPEG decreased infection by 45, 83, and 91%, respectively. Importantly, both viral and host cell PEGylation strategies were able to provide near complete protection against RSV infection of both non-polarized and polarized cells. In conclusion, mPEG-modification of either RSV or the host cell is a highly effective prophylactic strategy for preventing viral infection.


title: Host gene expression profiles in ferrets infected with genetically distinct henipavirus strains

text: Henipavirus infection causes severe respiratory and neurological disease in humans that can be fatal. To characterize the pathogenic mechanisms of henipavirus infection in vivo, we performed experimental infections in ferrets followed by genome-wide gene expression analysis of lung and brain tissues. The Hendra, Nipah-Bangladesh, and Nipah-Malaysia strains caused severe respiratory and neurological disease with animals succumbing around 7 days post infection. Despite the presence of abundant viral shedding, animal-to-animal transmission did not occur. The host gene expression profiles of the lung tissue showed early activation of interferon responses and subsequent expression of inflammation-related genes that coincided with the clinical deterioration. Additionally, the lung tissue showed unchanged levels of lymphocyte markers and progressive downregulation of cell cycle genes and extracellular matrix components. Infection in the brain resulted in a limited breadth of the host responses, which is in accordance with the immunoprivileged status of this organ. Finally, we propose a model of the pathogenic mechanisms of henipavirus infection that integrates multiple components of the host responses.


title: EMS in Taiwan: Past, present, and future

text: Abstract Taiwan is a small island country located in East Asia. From around 1995 modern concepts of the EMS were imported and supported by legislation. Considerable progress has since been made towards the construction of an effective pre-hospital care system. This article introduces the current status of the EMS in Taiwan, including the systems, response configurations, funding, personnel, medical directorship, and outcome research. The features and problems of in-hospital emergency care are also discussed. Key areas for further development in the country vary depending on regional differences in available resource and population density. An analysis of the strength, weakness, opportunity, and threats of the evolving EMS in Taiwan could be an example for other countries where the EMS is undergoing a similar process of development and optimisation.


COVID-19: immense necessity and challenges in meeting the needs of minorities, especially asylum seekers and undocumented migrants


Magdeleine of Martinique


title: A Recombinant Avian Infectious Bronchitis Virus Expressing a Heterologous Spike Gene Belonging to the 4/91 Serotype

text: We have shown previously that replacement of the spike (S) gene of the apathogenic IBV strain Beau-R with that from the pathogenic strain of the same serotype, M41, resulted in an apathogenic virus, BeauR-M41(S), that conferred protection against challenge with M41 [1]. We have constructed a recombinant IBV, BeauR-4/91(S), with the genetic backbone of Beau-R but expressing the spike protein of the pathogenic IBV strain 4/91(UK), which belongs to a different serogroup as Beaudette or M41. Similar to our previous findings with BeauR-M41(S), clinical signs observations showed that the S gene of the pathogenic 4/91 virus did not confer pathogenicity to the rIBV BeauR-4/91(S). Furthermore, protection studies showed there was homologous protection; BeauR-4/91(S) conferred protection against challenge with wild type 4/91 virus as shown by the absence of clinical signs, IBV RNA assessed by qRT-PCR and the fact that no virus was isolated from tracheas removed from birds primarily infected with BeauR-4/91(S) and challenged with IBV 4/91(UK). A degree of heterologous protection against M41 challenge was observed, albeit at a lower level. Our results confirm and extend our previous findings and conclusions that swapping of the ectodomain of the S protein is a precise and effective way of generating genetically defined candidate IBV vaccines.


title: A three-dimensional A549 cell culture model to study respiratory syncytial virus infections

text: Abstract Background Respiratory syncytial virus (RSV) is a primary cause of morbidity and mortality worldwide, affecting infants, young children, and immune-compromised patients; however, currently no vaccine is available for prevention of RSV infections. The overwhelming majority of our knowledge of how RSV causes infection is based upon studies that have been carried out using traditional 2D methods, with cells cultured on flat plastic dishes. Although these simplified culture systems are essential to gain an insight into the fundamentals of host-pathogen interactions, cells in 2D are not exposed to the same conditions as cells in 3D tissues in the body and are therefore a poor representation of thein vivo microenvironment. In this study, we aim to develop the first 3D culture model for RSV infection using A549 cells to test its utility for RSV pathogenesis. Methods To generate spheroids, A549 cells were cultured using ultra-low attachment plates to generate 25 × 103 cell spheroids. The viability of the spheroids was assessed by trypan blue exclusion assay and flow cytometry showing prominent live cells throughout the spheroids confirming high viability over seven days of incubation. Results Immunostaining of A549 spheroids inoculated with RSV, showed time-dependent dissemination of the viral antigen RSV-F within the spheroid, resulting in syncytia formation and a 3-fold increase in mucin secretion compared to the uninfected cells. Additionally, RSV successfully replicated in the spheroids producing infectious virus as early as day one post-inoculation and was sustained for up to 7 days post-inoculation. Conclusions Results show that A549 spheroids are susceptible and permissive for RSV since they exhibit the characteristics of RSV infection including syncytia formation and mucin overexpression, suggesting that A549 spheroids can be used a promising model for studying RSV in vitro.


title: SARS outbreaks in Ontario, Hong Kong and Singapore: the role of diagnosis and isolation as a control mechanism

text: Abstract In this article we use global and regional data from the SARS epidemic in conjunction with a model of susceptible, exposed, infective, diagnosed, and recovered classes of people (“SEIJR”) to extract average properties and rate constants for those populations. The model is fitted to data from the Ontario (Toronto) in Canada, Hong Kong in China and Singapore outbreaks and predictions are made based on various assumptions and observations, including the current effect of isolating individuals diagnosed with SARS. The epidemic dynamics for Hong Kong and Singapore appear to be different from the dynamics in Toronto, Ontario. Toronto shows a very rapid increase in the number of cases between March 31st and April 6th, followed by a significant slowing in the number of new cases. We explain this as the result of an increase in the diagnostic rate and in the effectiveness of patient isolation after March 26th. Our best estimates are consistent with SARS eventually being contained in Toronto, although the time of containment is sensitive to the parameters in our model. It is shown that despite the empirically modeled heterogeneity in transmission, SARS’ average reproductive number is 1.2, a value quite similar to that computed for some strains of influenza (J. Math. Biol. 27 (1989) 233). Although it would not be surprising to see levels of SARS infection higher than 10% in some regions of the world (if unchecked), lack of data and the observed heterogeneity and sensitivity of parameters prevent us from predicting the long-term impact of SARS. The possibility that 10 or more percent of the world population at risk could eventually be infected with the virus in conjunction with a mortality rate of 3–7% or more, and indications of significant improvement in Toronto support the stringent measures that have been taken to isolate diagnosed cases.


Organisations for patients with cancer feel the brunt of COVID-19 pandemic


title: Modeling and forecasting the COVID-19 pandemic in India

text: In India, 1,00,340 confirmed cases and 3,155 confirmed deaths due to COVID-19 were reported as of May 18, 2020. Due to absence of specific vaccine or therapy, non-pharmacological interventions including social distancing, contact tracing are essential to end the worldwide COVID-19. We propose a mathematical model that predicts the dynamics of COVID-19 in 17 provinces of India and the overall India. A complete scenario is given to demonstrate the estimated pandemic life cycle along with the real data or history to date, which in turn divulges the predicted inflection point and ending phase of SARS-CoV-2. The proposed model monitors the dynamics of six compartments, namely susceptible (S), asymptomatic (A), recovered (R), infected (I), isolated infected (I(q)) and quarantined susceptible (S(q)), collectively expressed SARII(q)S(q). A sensitivity analysis is conducted to determine the robustness of model predictions to parameter values and the sensitive parameters are estimated from the real data on the COVID-19 pandemic in India. Our results reveal that achieving a reduction in the contact rate between uninfected and infected individuals by quarantined the susceptible individuals, can effectively reduce the basic reproduction number. Our model simulations demonstrate that the elimination of ongoing SARS-CoV-2 pandemic is possible by combining the restrictive social distancing and contact tracing. Our predictions are based on real data with reasonable assumptions, whereas the accurate course of epidemic heavily depends on how and when quarantine, isolation and precautionary measures are enforced.


SARS‐CoV2 as a potential trigger of neurodegenerative diseases


title: Challenges posed by new and re-emerging infectious diseases in livestock production, wildlife and humans

text: Abstract In today's world, emerging and re-emerging diseases have a significant impact on global economies and public health, and with bioterrorism a constant threat this has become a very topical subject in recent years. Bernard Vallat, director general of the OIE, made the statement, “As a result of globalisation and climate change we are currently facing an unprecedented worldwide impact of emerging and re-emerging animal diseases and zoonoses”. He is not alone in this thinking, but are we facing an unprecedented impact of diseases and are globalisation and climate change the main driving forces? This paper examines some historical disease outbreaks and the factors that played a role in their emergence and compares these with recent emerging diseases. In doing so it highlights certain challenges that face livestock producers and decision makers today as they grapple with emerging diseases. One of the driving forces for the emergence of diseases is translocation of people and their livestock and this has often been coupled with invading armies or peoples, political unrest and a concurrent environment of socio-economic upheaval. Contact between wild animals, domestic animals and people is another driving force involving the interaction between naïve population groups that induces the emergence of new diseases. Pandemics are not new to human society and nor are many of the driving forces that caused them to occur in the past; what has changed is our increased knowledge and awareness of disease dynamics, allowing identification of challenges for the future and ways of addressing these. Modern farming practices often serve to amplify emerging infectious diseases and modern trade and transport mechanisms and routes have served to sometimes accelerate the spread of disease. How can we reduce the risks and should we only be worried about emerging infectious diseases or are emerging non-communicable diseases just as important in our modern society? This paper serves to explain some of the reasons for the emergence of diseases and to try and answer some of the pressing questions that confront livestock producers today.


docid: uyqqalyv

title: An enzyme-linked immunosorbent assay using canine coronavirus-infected CRFK cells as antigen for detection of anti-coronavirus antibody in cat

text: Abstract From the reasons that canine coronavirus (CCV) grows more efficiently than feline coronavirus in a cell culture and they are mutually related in their antigenicities, an enzyme-linked immunosorbent assay (ELISA) using CCV-infected feline kidney (CRFK) cells as substrate antigens was developed for detection of anti-coronavirus antibodies in cats. It was indispensable for generating coronavirus-specific ELISA antibody activities that the sample was applied to the mock-infected, normal CRFK cells in parallel with the CCV-infected cells and then the optical density values given by the mock-infected cell antigen were subtracted from those given by the virus-infected cell antigen. On the basis of ELISA antibody titers obtained in sera from the cats experimentally infected with CCV and from the spontaneous feline infectious peritonitis (FIP) cases, the ELISA described in the present study was found to be applicable as a simple and easy serologic test which was able to detect anti-coronavirus antibodies as efficiently as the indirect immunofluorescence assay with homologous FIP virus.


title: Effects of Methylprednisolone Pulse Therapy on Refractory Mycoplasma pneumoniae Pneumonia in Children

text: PURPOSE: Mycoplasma pneumoniae (M. pneumoniae) is one of the most common causes of community-acquired pneumonia in children. The clinical course is typically self-limited and benign; however, rare cases of severe pneumonia can develop despite appropriate antibiotic therapy. We studied the effects of methylprednisolone pulse therapy on severe refractory M. pneumoniae pneumonia in children. METHODS: The clinical effects of methylprednisolone therapy were evaluated retrospectively in 12 children with severe refractory M. pneumoniae pneumonia, which was diagnosed serologically. All patients developed respiratory distress, high fever, and initial lobar pneumonic consolidation based on radiological findings. All clinical symptoms deteriorated despite appropriate antibiotic therapy. Thus, children were treated with intravenous methylprednisolone pulse therapy in addition to antibiotics. RESULTS: The average febrile period before admission was 4.9±1.7 days, and fever persisted in all children until steroid administration. Methylprednisolone pulse therapy (30 mg/kg) was given 5.4±2.5 days after admission. After methylprednisolone pulse therapy, clinical symptoms improved in all patients without adverse events. The fever subsided 0-2 h after initiation of corticosteroid therapy. The abnormal radiological findings resolved within 2.6±1.3 days, and the high C-reactive protein levels (6.7±5.9 mg/dL) on admission decreased to 1.3±1.7 mg/dL within 3.0±1.1 days after starting corticosteroid therapy. CONCLUSIONS: Three-day methylprednisolone pulse therapy could be applied to treatment of refractory M. pneumoniae pneumonia despite appropriate antibiotic therapy and appeared to be efficacious and well-tolerated.


title: Associations between Single Nucleotide Polymorphisms in Cellular Viral Receptors and Attachment Factor-Related Genes and Humoral Immunity to Rubella Vaccination

text: BACKGROUND: Viral attachment and cell entry host factors are important for viral replication, pathogenesis, and the generation and sustenance of immune responses after infection and/or vaccination, and are plausible genetic regulators of vaccine-induced immunity. METHODS: Using a tag-SNP approach in candidate gene study, we assessed the role of selected cell surface receptor genes, attachment factor-related genes, along with other immune genes in the genetic control of immune response variations after live rubella vaccination in two independent study cohorts. RESULTS: Our analysis revealed evidence for multiple associations between genetic variants in the PVR, PVRL2, CD209/DC-SIGN, RARB, MOG, IL6 and other immune function-related genes and rubella-specific neutralizing antibodies after vaccination (meta p-value <0.05). CONCLUSION: Our results indicate that multiple SNPs from genes involved in cell adhesion, viral attachment, and viral entry, as well as others in genes involved in signaling and/or immune response regulation, play a role in modulating humoral immune responses following live rubella vaccination.


title: Innovative “Bring-Service-Near-Your-Home” Operations under Corona-Virus (COVID-19/SARS-CoV-2) Outbreak: Can Logistics Become the Messiah?

text: Abstract The corona virus (COVID-19/SARS-CoV-2) outbreak has created serious disruptions to many business operations. Among them, many service operations, which require customers to travel and visit a place indoor, become almost infeasible to run in a crowded city like Hong Kong. Motivated by a recent reported real case on an innovative service operation in Hong Kong, we build analytical models to explore how logistics and technologies together can transform the “static service operations” to become the “bring-service-near-your-home” mobile service operations. We also highlight how the government may provide the subsidy to support the above mentioned mobile service operation (MSO) to make it financially viable. We specifically show that the government may adopt the fixed-cost-subsidy (FCS) scheme, operations-cost-subsidy (OCS) scheme or safety-technology-support (STS) scheme to help. We further uncover that the OCS scheme would bring a larger consumer surplus than the FCS scheme and is hence more preferable. In the extended models, we first study the case when service fee cannot be changed because of corona virus outbreak (CVO). We then explore the feasibility of adopting MSO in the long run as a financially self-sustainable service operation and derive the analytical conditions under which MSO is a win-win business model for both the service provider and consumers. Finally, we study the optimal safety technology investment problem.


title: Characterization of anti-porcine epidemic diarrhea virus neutralizing activity in mammary secretions

text: Abstract Porcine epidemic diarrhea virus (PEDV) causes a severe clinical enteric disease in suckling neonates with up to 100% mortality, resulting in devastating economic losses to the pork industry in recent years. Maternal immunity via colostrum and milk is a vital source to neonates of passive protection against diarrhea, dehydration and death caused by PEDV. Comprehensive information on neutralizing activity (NA) against PEDV in mammary secretions is critically important for assessing the protective capacity of sows. Therefore, the objectives of this study were to characterize anti-PEDV neutralizing activity in mammary secretions. Anti-PEDV NA was present in colostrum, milk and serum from PEDV-infected sows as determined both by immunofluorescence and ELISA-based neutralizing assays, with neutralization levels higher in colostrum and milk than in serum. The highest NA was observed in colostrum on day 1, and decreased rapidly in milk at day 3, then gradually declined from day 3 to day 19 post-farrowing. Notably, the NA in mammary secretions showed various patterns of decline over time of lactation that may contribute to variation in sow protective capacities. The kinetics of NA decline were associated with total IgA and IgG antibody levels. Neutralizing activity significantly correlated with specific IgA primarily to spike domain 1 (S1) and domain 2 (S2) proteins of PEDV rather than to specific IgG in colostrum. Subsequently, the NA in milk was mainly related to specific IgA to S1 and S2 during lactation.


title: The first confirmed case of COVID-19 in Tanzania: recommendations based on lesson learned from China

text: As the coronavirus disease (COVID-19) takes its course outside China, the number of imported cases to other countries is on the rise. Currently, Tanzania has received the first imported case on 16 March 2020. This letter serves to describe this specific event and put forth a number of recommendations including establishing more testing points, discouraging all forms of public and religious gatherings, and tailoring a unique model for lockdown and social distancing to prevent further spread of the disease. The letter has also suggested ways to further improve the efforts already in place so as to strengthen the prevention and control system.


title: COVID-19: A Revelation – A reply to Ian Mitroff

text: Abstract This is a rejoinder of Dr. Ian Mitroff's perspective titled "Corona Virus: A Prime Example of A Wicked Mess". While I agree with Dr. Mitroff on the complexity of the COVID-19 outbreak and the urgency to address it, I disagree with him on points related to the role of wet market in this specific outbreak and whether China had acknowledged the existence of the outbreak. I also consider key highlights of the outbreak are the importance of collaboration across national and state borders and a balance between privacy and public health under such situations.


title: Conduction abnormalities in hydroxychloroquine add on therapy to lopinavir/ritonavir in COVID‐19

text: COVID-19 is a contagious disease caused by Severe Adult Respiratory Syndrome Corona Virus-2 (SARS-CoV-2). Currently the role of HCQ in COVID-19 remains controversial but HCQ continued to be used in the absence of any effective therapy. We showed that cardiac conduction abnormalities were common in patients with HCQ added on to lopinavir/ritonavir. After starting HCQ, there were 5 (45.5%) new events of which four (36.3%) were attributed to HCQ: QTc prolongations in 3 patients with additional development of conduction blocks (fascicular block and right bundle brunch block in one patient respectively) and one patient with bradycardia. All conduction abnormalities settled after discontinuation of HCQ. Therefore monitoring is recommended when considering HCQ in treating patients with COVID-19. This article is protected by copyright. All rights reserved.


title: The influence of stabilizers and rates of freezing on preserving of structurally different animal viruses during lyophilization and subsequent storage

text: AIMS: To make a comparative evaluation of the effects of different stabilizers and freezing rates on structurally different viruses during lyophilization and storage. METHODS AND RESULTS: Two virus strains from each of six animal virus families, including both enveloped and nonenveloped viruses, were lyophilized in (i) culture medium, (ii) with the addition of gelatine–sucrose and (iii) skim milk–sodium glutamate. All the virus suspensions were frozen (i) at −80°C or (ii) in liquid nitrogen before lyophilization. Virus titre assay after lyophilization and after 8 months storage at 4°C revealed that the efficacy of stabilizers depended on virus structure. Generally, the best protective quality for enveloped viruses was achieved with gelatine–sucrose, which best maintained their infectivity and envelope morphology. Even additive‐free culture medium proved adequate for nonenveloped viruses. Differences in stabilizer efficacy were also found between virus families and were expressed immediately after lyophilization; the activity of stabilizers in the course of storage was very similar. Freezing in liquid nitrogen proved beneficial for picornaviruses. CONCLUSIONS: The choice of an appropriate stabilizer with respect to virus type is crucial for effective lyophilization. SIGNIFICANCE AND IMPACT OF THE STUDY: This study contributes to the establishment of general guidelines for animal virus lyophilization, with particular respect to differences in virus structure.


title: Identification of Oxidative Stress and Toll-like Receptor 4 Signaling as a Key Pathway of Acute Lung Injury

text: Multiple lung pathogens such as chemical agents, H5N1 avian flu, or SARS cause high lethality due to acute respiratory distress syndrome. Here we report that Toll-like receptor 4 (TLR4) mutant mice display natural resistance to acid-induced acute lung injury (ALI). We show that TLR4-TRIF-TRAF6 signaling is a key disease pathway that controls the severity of ALI. The oxidized phospholipid (OxPL) OxPAPC was identified to induce lung injury and cytokine production by lung macrophages via TLR4-TRIF. We observed OxPL production in the lungs of humans and animals infected with SARS, Anthrax, or H5N1. Pulmonary challenge with an inactivated H5N1 avian influenza virus rapidly induces ALI and OxPL formation in mice. Loss of TLR4 or TRIF expression protects mice from H5N1-induced ALI. Moreover, deletion of ncf1, which controls ROS production, improves the severity of H5N1-mediated ALI. Our data identify oxidative stress and innate immunity as key lung injury pathways that control the severity of ALI.


title: The Socio-economic and Psychosocial Impact of Covid-19 Pandemic on Urban Refugees in Uganda

text: Abstract Considering the COVID-19 global public health crisis, this paper examines the socio-cultural, economic and psychosocial impact of the pandemic on urban refugees in Uganda. We analyse the living conditions of urban refugees that make it problematic for them to adhere to public health measures. Since COVID-19 is perceived as “imported”, refugees are assumed as its potential transmitters, consequently experiencing heightened stigma and isolation. Lack of culturally and linguistically accessible information and services excludes them from on-going efforts to prevent the pandemic. The lockdown has affected refugee livelihoods and increased income insecurity, sexual and gender-based violence and anxiety. Given the paucity of Government-led services to contain the epidemic, we argue that contingency planning must involve refugees and their communities to access accurate and relevant information in appropriate languages. It is also important to build the capacity of frontline workers to understand the specific needs of refugees to deliver appropriate protection in the context of the pandemic.


title: QT prolongation, torsades de pointes and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: a systematic review

text: Chloroquine and hydroxychloroquine are now being widely used as treatments for COVID-19. Both medications prolong the QT interval and accordingly may put patients at increased risk of torsades de pointes and sudden death. Published guidance documents vary in their recommendations for monitoring and managing these potential adverse effects. Accordingly, we set out to conduct a systematic review of the arrhythmogenic effect of short courses of chloroquine or hydroxychloroquine. We searched in MEDLINE and Embase, as well as grey literature up to April 17, 2020, on the risk of QT prolongation, torsades, ventricular arrhythmia, and sudden death with short-term chloroquine and hydroxychloroquine usage. This resulted in 390 unique records, of which fourteen were ultimately selected for qualitative synthesis and which included data on 1515 COVID-19 patients. Approximately 10% of COVID-19 patients treated with these drugs developed QT prolongation. We found evidence of ventricular arrhythmia in two COVID-19 patients out of a group of 28 treated with high-dose chloroquine. A limitation of these results is unclear follow-up and possible publication/reporting bias, but there is compelling evidence that chloroquine and hydroxychloroquine induce significant QT interval prolongation and potentially increase the risk of arrhythmia. Daily ECG monitoring and other risk mitigation strategies should be considered in order to prevent possible harms from what is currently an unproven therapy.


title: Outbreak of febrile illness caused by coxsackievirus A4 in a nursery school in Beijing, China

text: BACKGROUND: Coxsackievirus A4 (CV-A4) is classified as human enterovirus A according to its serotype. CV-A4, an etiological agent of hand, foot, and mouth disease, affects children worldwide and can circulate in closed environments such as schools and hospitals for long periods. FINDINGS: An outbreak of febrile illness at a nursery school in Beijing, China, was confirmed to be caused by CV-A4. Phylogenetic analysis of the complete genome of the isolated strain showed that the virus belongs to the same cluster as the predominant CV-A4 strain in China. This outbreak was controlled by effective measures. CONCLUSIONS: The early identification of the pathogen and timely intervention may be the most critical factors in controlling an outbreak caused by CV-A4 in a preschool.


title: Clinical evaluation of commercial nucleic acid amplification tests in patients with suspected sepsis

text: BACKGROUND: Sepsis is a serious medical condition requiring timely administered, appropriate antibiotic therapy. Blood culture is regarded as the gold standard for aetiological diagnosis of sepsis, but it suffers from low sensitivity and long turnaround time. Thus, nucleic acid amplification tests (NAATs) have emerged to shorten the time to identification of causative microbes. The aim of the present study was to evaluate the clinical utility in everyday practice in the emergency department of two commercial NAATs in patients suspected with sepsis. METHODS: During a six-week period, blood samples were collected consecutively from all adult patients admitted to the general emergency department for suspicion of a community-onset sepsis and treated with intravenous antibiotics. Along with conventional blood cultures, multiplex PCR (Magicplex™) was performed on whole blood specimens whereas portions from blood culture bottles were used for analysis by microarray-based assay (Prove-it™). The aetiological significance of identified organisms was determined by two infectious disease physicians based on clinical presentation and expected pathogenicity. RESULTS: Among 382 episodes of suspected sepsis, clinically relevant microbes were detected by blood culture in 42 episodes (11%), by multiplex PCR in 37 episodes (9.7%), and by microarray in 32 episodes (8.4%). Although moderate agreement with blood culture (kappa 0.50), the multiplex PCR added diagnostic value by timely detection of 15 clinically relevant findings in blood culture-negative specimens. Results of the microarray corresponded very well to those of blood culture (kappa 0.90), but were available just marginally prior to blood culture results. CONCLUSIONS: The use of NAATs on whole blood specimens in adjunct to current culture-based methods provides a clinical add-on value by allowing for detection of organisms missed by blood culture. However, the aetiological significance of findings detected by NAATs should be interpreted with caution as the high analytical sensitivity may add findings that do not necessarily corroborate with the clinical diagnosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-0938-4) contains supplementary material, which is available to authorized users.


Is there a Link between endocrine disruptors and COVID-19 severe pneumonia?


docid: jdjoxkwg

title: Acute phase protein response to viral infection and vaccination

text: Abstract Organisms respond in multiple ways to microbial infections. Pathogen invasion tipically triggers an inflammatory response where acute phase proteins (APP) have a key role. Pentraxins (PTX) are a family of highly conserved APP that play a part in the host defense against infection. The larger proteins of the family are simply named pentraxins, while c-reactive proteins (CRP) and serum amyloid proteins (SAA, SAP) are known as short pentraxins. Although high APP levels have been broadly associated with bacterial infections, there is a growing body of evidence revealing increased PTX, CRP and SAP expression upon viral infection. Furthermore, CRP, PTX and SAP have shown their potential as diagnostic markers and predictors of disease outcome. Likewise, the measurement of APP levels can be valuable to determine the efficacy of antiviral therapies and vaccines. From the practical point of view, the ability of APP to reduce viral infectivity has been observed in several virus-host models. This has prompted investigation efforts to assess the role of acute phase response proteins as immunoregulatory molecules and their potential as therapeutic reagents. This work aims to present an overview of the APP response to viral infections reviewing the current knowledge in the field.


title: Oral Mutian®X stopped faecal feline coronavirus shedding by naturally infected cats

text: Abstract Feline coronavirus (FCoV) is common among cats living indoors in groups. In about 10% of infected cats, a potentially lethal disease, feline infectious peritonitis (FIP) occurs. Virus transmission is faecal-oral. Mutian® Xraphconn (Mutian X) is a product marketed to treat cats with FIP but is also being used to stop virus shedding, although no clear guidelines exist for its use for this purpose. The aim of this study was to establish the minimum dose and treatment duration required to ensure viral clearance from the faeces of asymptomatic virus-shedding cats. In five multicat households, 29 cats naturally infected with FCoV and actively shedding virus in the faeces were given Mutian X pills. Virus shedding was monitored using reverse-transcription quantitative polymerase chain reaction (RT-qPCR) controlled for faecal inhibitors to ensure sensitivity. Mutian X given orally cleared the virus in 29 cats; although four cats required a repeated course to finally stop virus shedding. A dose of 4 mg/kg q24 h for four days was found to be the optimal treatment protocol: 2 mg/kg cleared only 80% of cats. Post-treatment using a sensitive RT-qPCR test was essential to ensure that virus clearance had been achieved, since failure to clear even one cat can result in re-infection of the others. Records of virus shedding by cats before treatment provided a retrospective control: significantly more cats stopped shedding virus after Mutian X than recovered from infection during the control period (p < .00001). This is the first report of the successful elimination of faecal FCoV shedding in chronically infected cats.


title: Characterization of novel monoclonal antibodies against MERS-coronavirus spike protein

text: Abstract Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes severe pulmonary infection, with ∼35 % mortality. Spike glycoprotein (S) of MERS-CoV is a key target for vaccines and therapeutics because S mediates viral entry and membrane-fusion to host cells. Here, four different S subunit proteins, receptor-binding domain (RBD; 358–606 aa), S1 (1–751 aa), S2 (752–1296 aa), and SΔTM (1–1296 aa), were generated using the baculoviral system and immunized in mice to develop neutralizing antibodies. We developed 77 hybridomas and selected five neutralizing mAbs by immunization with SΔTM against MERS-CoV EMC/2012 strain S-pseudotyped lentivirus. However, all five monoclonal antibodies (mAb) did not neutralize the pseudotyped V534A mutation. Additionally, one mAb RBD-14F8 did not show neutralizing activity against pseudoviruses with amino acid substitution of L506 F or D509 G (England1 strain, EMC/2012 L506 F, and EMC/2012 D509 G), and RBD-43E4 mAb could not neutralize the pseudotyped I529 T mutation, while three other neutralizing mAbs showed broad neutralizing activity. This implies that the mutation in residue 506–509, 529, and 534 of S is critical to generate neutralization escape variants of MERS-CoV. Interestingly, all five neutralizing mAbs have binding affinity to RBD, although most mAbs generated by RBD did not have neutralizing activity. Additionally, chimeric antibodies of RBD-14F8 and RBD-43E4 with human Fc and light chain showed neutralizing effect against wild type MERS-CoV KOR/KNIH/002, similar to the original mouse mAbs. Thus, our mAbs can be utilized for the identification of specific mutations of MERS-CoV.


title: Coronavirus 3CL(pro )proteinase cleavage sites: Possible relevance to SARS virus pathology

text: BACKGROUND: Despite the passing of more than a year since the first outbreak of Severe Acute Respiratory Syndrome (SARS), efficient counter-measures are still few and many believe that reappearance of SARS, or a similar disease caused by a coronavirus, is not unlikely. For other virus families like the picornaviruses it is known that pathology is related to proteolytic cleavage of host proteins by viral proteinases. Furthermore, several studies indicate that virus proliferation can be arrested using specific proteinase inhibitors supporting the belief that proteinases are indeed important during infection. Prompted by this, we set out to analyse and predict cleavage by the coronavirus main proteinase using computational methods. RESULTS: We retrieved sequence data on seven fully sequenced coronaviruses and identified the main 3CL proteinase cleavage sites in polyproteins using alignments. A neural network was trained to recognise the cleavage sites in the genomes obtaining a sensitivity of 87.0% and a specificity of 99.0%. Several proteins known to be cleaved by other viruses were submitted to prediction as well as proteins suspected relevant in coronavirus pathology. Cleavage sites were predicted in proteins such as the cystic fibrosis transmembrane conductance regulator (CFTR), transcription factors CREB-RP and OCT-1, and components of the ubiquitin pathway. CONCLUSIONS: Our prediction method NetCorona predicts coronavirus cleavage sites with high specificity and several potential cleavage candidates were identified which might be important to elucidate coronavirus pathology. Furthermore, the method might assist in design of proteinase inhibitors for treatment of SARS and possible future diseases caused by coronaviruses. It is made available for public use at our website: .


title: Ribavirin and interferon-β synergistically inhibit SARS-associated coronavirus replication in animal and human cell lines

text: Abstract Initial in vitro investigations demonstrated type I interferons (IFNs: IFN-α, IFN-β) to inhibit replication of SARS coronavirus (SARS-CoV), but found the nucleoside analogue ribavirin ineffective in Vero cells. In this report, ribavirin was shown to inhibit SARS-CoV replication in five different cell types of animal or human origin at therapeutically achievable concentrations. Since clinical anti-SARS-CoV activity of type I interferons or ribavirin is limited, we investigated the combination of IFN-β and ribavirin. Determination of the virus yield indicated highly synergistic anti-SARS-CoV action of the combination suggesting the consideration of ribavirin plus IFN-β for the treatment of SARS.


title: Massive peptide sharing between viral and human proteomes

text: Thirty viral proteomes were examined for amino acid sequence similarity to the human proteome, and, in parallel, a control of 30 sets of human proteins was analyzed for internal human overlapping. We find that all of the analyzed 30 viral proteomes, independently of their structural or pathogenic characteristics, present a high number of pentapeptide overlaps to the human proteome. Among the examined viruses, human T-lymphotropic virus 1, Rubella virus, and hepatitis C virus present the highest number of viral overlaps to the human proteome. The widespread and ample distribution of viral amino acid sequences through the human proteome indicates that viral and human proteins are formed of common peptide backbone units and suggests a fluid compositional chimerism in phylogenetic entities canonically classified distantly as viruses and Homo sapiens. Importantly, the massive viral to human peptide overlapping calls into question the possibility of a direct causal association between virus–host sharing of amino acid sequences and incitement to autoimmune reactions through molecular recognition of common motifs.


title: Reply to: Neurological, Cognitive and Behavioral Disorders During COVID‐19: The Nitric Oxide Track

text: This letter comments on the letter by Cedric Annweiler


title: Phage display in the study of infectious diseases

text: Microbial infections are dependent on the panoply of interactions between pathogen and host and identifying the molecular basis of such interactions is necessary to understand and control infection. Phage display is a simple functional genomic methodology for screening and identifying protein–ligand interactions and is widely used in epitope mapping, antibody engineering and screening for receptor agonists or antagonists. Phage display is also used widely in various forms, including the use of fragment libraries of whole microbial genomes, to identify peptide–ligand and protein–ligand interactions that are of importance in infection. In particular, this technique has proved successful in identifying microbial adhesins that are vital for colonization.


title: Plagues in the ICU: A Brief History of Community-Acquired Epidemic and Endemic Transmissible Infections Leading to Intensive Care Admission

text: The ability to diagnose and treat infectious diseases and handle infectious disease outbreaks continues to improve. For the most part, the major plagues of antiquity remain historical footnotes, yet, despite many advances, there is clear evidence that major pandemic illness is always just one outbreak away. In addition to the HIV pandemic, the smaller epidemic outbreaks of Legionnaire's disease, hantavirus pulmonary syndrome, and severe acute respiratory syndrome, among many others, points out the potential risk associated with a lack of preplanning and preparedness. Although pandemic influenza is at the top of the list when discussing possible future major infectious disease outbreaks, the truth is that the identity of the next major pandemic pathogen cannot be predicted with any accuracy. We can only hope that general preparedness and the lessons learned from previous outbreaks suffice.


title: Traditional Chinese Medicine: an effective treatment for 2019 novel coronavirus pneumonia (NCP)

text: ABSTRACT The novel coronavirus pneumonia broke out in 2019 and spread rapidly. In 30 different countries, there are over seventy thousand patients have been diagnosed in total. Therefore, it is urgent to develop the effective program to prevent and treat for the novel coronavirus pneumonia. In view of Traditional Chinese Medicine has accumulated a solid theoretical foundation of plague in ancient and recent decades. Meanwhile, Traditional Chinese Medicine can provide the more effective and personalized treatment via adjusting the specific medicine for each patient based on the different syndromes. In addition, TCM often has different effect on the distinct stages of diseases, contributing to the prevention, treatment and rehabilitation. Nowadays, TCM has exhibited decent effect in the in the fight against NCP. Therefore, it is convinced that Traditional Chinese Medicine is an effective treatment for 2019 novel coronavirus pneumonia.


title: Current knowledge of COVID-19 and infection prevention and control strategies in healthcare settings: A global analysis

text: OBJECTIVE: In the current absence of a vaccine for COVID-19, public health responses aim to break the chain of infection by focusing on the mode of transmission. We reviewed the current evidence on the transmission dynamics and on pathogenic and clinical features of COVID-19 to critically identify any gaps in the current infection prevention and control (IPC) guidelines. METHODS: In this study, we reviewed global COVID-19 IPC guidelines by organizations such as the World Health Organization (WHO), the US Centers for Disease Control and Prevention (CDC), and the European Centre for Disease Prevention and Control (ECDC). Guidelines from 2 high-income countries (Australia and United Kingdom) and from 1 middle-income country (China) were also reviewed. We searched publications in English on ‘PubMed’ and Google Scholar. We extracted information related to COVID-19 transmission dynamics, clinical presentations, and exposures that may facilitate transmission. We then compared these findings with the recommended IPC measures. RESULTS: Nosocomial transmission of SARS-CoV-2 in healthcare settings occurs through droplets, aerosols, and the oral–fecal or fecal–droplet route. However, the IPC guidelines fail to cover all transmission modes, and the recommendations also conflict with each other. Most guidelines recommend surgical masks for healthcare providers during routine care and N95 respirators for aerosol-generating procedures. However, recommendations regarding the type of face mask varied, and the CDC recommends cloth masks when surgical masks are unavailable. CONCLUSION: IPC strategies should consider all the possible routes of transmission and should target all patient care activities involving risk of person-to-person transmission. This review may assist international health agencies in updating their guidelines.


title: Valosin-containing protein (VCP/p97) plays a role in the replication of West Nile virus

text: Abstract Valosin-containing protein (VCP) is classified as a member of the type II AAA+ ATPase protein family. VCP functions in several cellular processes, including protein degradation, membrane fusion, vesicular trafficking and disassembly of stress granules. Moreover, VCP is considered to play a role in the replication of several viruses, albeit through different mechanisms. In the present study, we have investigated the role of VCP in West Nile virus (WNV) infection. Endogenous VCP expression was inhibited using either VCP inhibitors or by siRNA knockdown. It could be shown that the inhibition of endogenous VCP expression significantly inhibited WNV infection. The entry assay revealed that silencing of endogenous VCP caused a significant reduction in the expression levels of WNV-RNA compared to control siRNA-treated cells. This indicates that VCP may play a role in early steps either the binding or entry steps of the WNV life cycle. Using WNV virus like particles and WNV-DNA-based replicon, it could be demonstrated that perturbation of VCP expression decreased levels of newly synthesized WNV genomic RNA. These findings suggest that VCP is involved in early steps and during genome replication of the WNV life cycle.


title: Identification of two antiviral inhibitors targeting 3C-like serine/3C-like protease of porcine reproductive and respiratory syndrome virus and porcine epidemic diarrhea virus

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine epidemic diarrhea virus (PEDV) are highly virulent and contagious porcine pathogens that cause tremendous economic losses to the swine industry worldwide. Currently, there is no effective treatment for PRRSV and PEDV, and commercial vaccines do not induce sterilizing immunity. In this study, we screened a library of 1000 compounds and identified two specific inhibitors, designated compounds 2 and 3, which target the PRRSV 3C-like serine protease (3CLSP). First, we evaluated the inhibitory effects of compounds 2 and 3 on PRRSV 3CLSP activity. Next, we determined the anti-PRRSV capacity of compounds 2 and 3 in MARC-145 cells and obtained EC50 and CC50 values of 57μM (CC50 =479.9μM) and 56.8μM (CC50 =482.8μM), respectively. Importantly, compounds 2 and 3 also targeted the PEDV 3C-like protease (3CL protease) and inhibited PEDV replication, showing EC50 and CC50 values of 100μM (CC50 =533.8μM) and 57.9μM (CC50 =522.3μM), respectively. Finally, our results indicated that the active sites (His39 in 3CLSP and His41 in 3CL protease) were conservative, and contacted compounds 2 and 3 via hydrogen bonds and hydrophobic forces in the putative substrate-binding models. In summary, compounds 2 and 3 exhibit broad-spectrum antiviral activity and may facilitate the development of antiviral drugs against PRRSV and PEDV.


title: Treatment-Refractory Headache in the Setting of COVID-19 Pneumonia: Migraine or Meningoencephalitis? Case Report

text: The coronavirus responsible for the COVID-19 pandemic, SARS-2-CoV, most commonly involves the respiratory tract; however, more severe cases have been found to have multi-organ involvement, including the central nervous system. Headache has been documented as a presenting symptom of COVID-19, which may prompt neurology consultation. To date, few cases of COVID-19 meningitis have been confirmed, but it must remain in the differential diagnosis for patients with headache and fever. A 58-year-old female with multiple sclerosis on fingolimod, chronic migraine well-controlled on fremanezumab, and cerebrovascular disease presented with fevers and respiratory symptoms, as well as acute treatment-refractory headache with associated neck stiffness and transient behavioral abnormalities. Although not confirmed with cerebrospinal fluid testing, we suspect this patient had COVID-19 meningoencephalitis, highlighting the need to consider secondary headaches in patients with coronavirus infection, even in the setting of chronic migraine. We offer anecdotal treatment recommendations for acutely refractory secondary headache and guidance for the consulting neurologist during the COVID-19 pandemic.


title: Extensive coronavirus-induced membrane rearrangements are not a determinant of pathogenicity

text: Positive-strand RNA (+RNA) viruses rearrange cellular membranes during replication, possibly in order to concentrate and arrange viral replication machinery for efficient viral RNA synthesis. Our previous work showed that in addition to the conserved coronavirus double membrane vesicles (DMVs), Beau-R, an apathogenic strain of avian Gammacoronavirus infectious bronchitis virus (IBV), induces regions of ER that are zippered together and tethered open-necked double membrane spherules that resemble replication organelles induced by other +RNA viruses. Here we compared structures induced by Beau-R with the pathogenic lab strain M41 to determine whether membrane rearrangements are strain dependent. Interestingly, M41 was found to have a low spherule phenotype. We then compared a panel of pathogenic, mild and attenuated IBV strains in ex vivo tracheal organ culture (TOC). Although the low spherule phenotype of M41 was conserved in TOCs, each of the other tested IBV strains produced DMVs, zippered ER and spherules. Furthermore, there was a significant correlation for the presence of DMVs with spherules, suggesting that these structures are spatially and temporally linked. Our data indicate that virus induced membrane rearrangements are fundamentally linked to the viral replicative machinery. However, coronavirus replicative apparatus clearly has the plasticity to function in different structural contexts.


Test ARN para SARS-CoV-2 positivos recurrentes en pacientes recuperados y dados de alta hospitalaria


docid: fcgcittn

title: SAA is a biomarker to distinguish the severity and prognosis of Coronavirus Disease 2019 (COVID-19)

text: Abstract Background To explore the significance of SAA in evaluating the severity and prognosis of COVID-19. Methods A total of 132 patients with confirmed COVID-19 who were admitted to a designated COVID-19 hospital in Wuhan, China from January 18, 2020 to February 26, 2020 were collected. The dynamic changes of blood SAA, CRP, PCT, WBC, Lymphocyte (L), PLT, CT imaging, and disease progression were studied. All patients completed at least twice laboratory data collection and clinical condition assessment at three time points indicated for this study; The length of hospital stay was longer than 14 days prior to February 26, 2020. Results COVID-19 patients had significantly increased SAA and CRP levels, while L count decreased, and PCT, WBC, and PLT were in the normal range. As disease progressed from mild to critically severe, SAA and CRP gradually increased, while L decreased, and PLT, WBC, and PCT had no significant changes; ROC curve analysis suggests that SAA/L, CRP, SAA, and L count are valuable in evaluating the severity of COVID-19 and distinguishing critically ill patients from mild ones; Patients with SAA consistently trending down during the course of disease have better prognosis, compared with the patients with SAA continuously rising; The initial SAA level is positively correlated with the dynamic changes of the serial CT scans. Patient with higher initial SAA level are more likely to have poor CT imaging. Conclusions SAA and L are sensitive indicators in evaluating the severity and prognosis of COVID-19. Monitoring dynamic changes of SAA, combined with CT imaging could be valuable in diagnosis and treatment of COVID-19.


title: Epidemic spreading in metapopulation networks with heterogeneous infection rates

text: Abstract In this paper, we study epidemic spreading in metapopulation networks wherein each node represents a subpopulation symbolizing a city or an urban area and links connecting nodes correspond to the human traveling routes among cities. Differently from previous studies, we introduce a heterogeneous infection rate to characterize the effect of nodes’ local properties, such as population density, individual health habits, and social conditions, on epidemic infectivity. By means of a mean-field approach and Monte Carlo simulations, we explore how the heterogeneity of the infection rate affects the epidemic dynamics, and find that large fluctuations of the infection rate have a profound impact on the epidemic threshold as well as the temporal behavior of the prevalence above the epidemic threshold. This work can refine our understanding of epidemic spreading in metapopulation networks with the effect of nodes’ local properties.


Risk-stratifying COVID-19 Patients the Right Way


title: Strategy of using personal protective equipment during aerosol generating medical procedures with COVID-19

text: • Compared the effectiveness and cost-effectiveness between masks and respirators for the COVID-19 transmission; • Discussed the strategy to avoid severe nosocomial infection through aerosol-generating medical procedures; • Suggestions for healthcare workers to choose proper personal protective equipment.


title: Using predicted imports of 2019-nCoV cases to determine locations that may not be identifying all imported cases

text: Cases from the ongoing outbreak of atypical pneumonia caused by the 2019 novel coronavirus (2019-nCoV) exported from mainland China can lead to self-sustained outbreaks in other populations. Internationally imported cases are currently being reported in several different locations. Early detection of imported cases is critical for containment of the virus. Based on air travel volume estimates from Wuhan to international destinations and using a generalized linear regression model we identify locations which may potentially have undetected internationally imported cases.


COVID-19 - Where have all the STEMIs gone?


title: Respiratory viral infection in exacerbations of COPD

text: Summary Background Patients with COPD have frequent exacerbations. The role of respiratory viral infection is just emerging. We wished to determine prospectively the incidence of viral infection in exacerbated and stable COPD patients as well as smokers who do not have airways obstruction. Methods Stable and exacerbated COPD patients were recruited along with a group of patients who had smoked but who did not have any airways obstruction. Spirometry was performed and sputum specimens were tested for a range of 12 different respiratory viruses using PCR. Results One hundred and thirty-six patients with exacerbations of COPD, 68 stable COPD patients and 16 non-obstructed smokers were recruited. A respiratory virus was detected in 37% of exacerbations, 12% of stable COPD patients and 12% of non-obstructed smokers, p <0.0005. Rhinovirus was most frequently detected. The symptom of fever was associated with virus detection, p <0.05. Infection with more than one virus was only found in the exacerbated COPD patients. Conclusion Respiratory viral infection is associated with exacerbations of COPD. Rhinovirus was the most common infecting agent identified and in two cases human metapneumovirus was also detected. Dual infections were only seen amongst those patients admitted to hospital with acute exacerbations of COPD. Viruses were more commonly detected in those with more severe airways disease.


docid: wwalsxzi

title: Avian infectious bronchitis and deep pectoral myopathy—A case control study

text: Abstract Infectious bronchitis is caused by a coronavirus, infectious bronchitis virus (IBV). Infectious bronchitis is an acute and highly contagious disease of economic importance due to the reduction in weight gain observed with infected broilers and the drop in egg quality and production associated with infected laying hens. The presence of deep pectoral myopathy has been associated with IBV variants. This lesion is detected at slaughterhouses and is characterized by paleness and atrophy of the deep pectoral muscle, including necrosis of the region, leading to condemnations of the breast muscle, a valuable meat cut in the market. This work aimed to study the relationship between deep pectoral myopathy and IBV by describing tracheal and muscle lesions and comparing the frequency of IBV detection via reverse-transcription (RT) PCR in muscle, tracheal, and cecal tonsil samples from broilers with and without myopathy. A case-control study was conducted in 40 broiler flocks vaccinated with the Massachusetts strain. The case group consisted of 23 flocks that presented myopathic lesions under sanitary inspection and a control group of 17 flocks without myopathic lesions. The tracheal, cecal tonsil, and supracoracoid muscle (with and without lesions) samples from the 40 broiler flocks were screened by RT-PCR to detect IBV. Histopathology of muscle and tracheal tissue was carried out. Upon microscopic examination, the muscle samples from the case group presented extensive necrosis, intense mononuclear inflammatory infiltration, muscle fiber fragmentation, and fibrotic tissue, confirming myopathy, whereas muscles from the control group showed no alterations. The tracheal samples presented a large number of infiltrated mononuclear inflammatory cells that in some areas formed submucosal nodules. A total of 25 flocks tested IBV positive by RT-PCR: 14 from the case group and 11 from the control group. The IBV was detected by RT-PCR directly in muscle samples. Despite that, the relationship between deep pectoral myopathy and IBV was not established. The higher positive IBV RT-PCR percentage noted in the cecal tonsil samples demonstrates how important the choice of organs is for diagnostic purposes.


title: ACE2 Expression is Increased in the Lungs of Patients with Comorbidities Associated with Severe COVID-19

text: The pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in several thousand deaths worldwide in just a few months. Patients who died from Coronavirus disease 2019 (COVID-19) often had comorbidities, such as hypertension, diabetes, and chronic obstructive lung disease. The angiotensin-converting enzyme 2 (ACE2) was identified as a crucial factor that facilitates SARS-CoV2 to bind and enter host cells. To date, no study has assessed the ACE2 expression in the lungs of patients with these diseases. Here, we analyzed over 700 lung transcriptome samples of patients with comorbidities associated with severe COVID-19 and found that ACE2 was highly expressed in these patients, compared to control individuals. This finding suggests that patients with such comorbidities may have higher chances of developing severe COVID-19. We also found other genes, such as RAB1A, that can be important for SARS-CoV-2 infection in the lung. Correlation and network analyses revealed many potential regulators of ACE2 in the human lung, including genes related to histone modifications, such as HAT1, HDAC2, and KDM5B. In fact, epigenetic marks found in ACE2 locus were compatible to with those promoted by KDM5B. Our systems biology approach offers a possible explanation for increase of COVID-19 severity in patients with certain comorbidities.


title: Plant lectins are potent inhibitors of coronaviruses by interfering with two targets in the viral replication cycle

text: Abstract We describe the antiviral activity of plant lectins with specificity for different glycan structures against the severe acute respiratory syndrome coronavirus (SARS-CoV) and the feline infectious peritonitis virus (FIPV) in vitro. The SARS-CoV emerged in 2002 as an important cause of severe lower respiratory tract infection in humans, and FIPV infection causes a chronic and often fatal peritonitis in cats. A unique collection of 33 plant lectins with different specificities were evaluated. The plant lectins possessed marked antiviral properties against both coronaviruses with EC50 values in the lower microgram/ml range (middle nanomolar range), being non-toxic (CC50) at 50–100μg/ml. The strongest anti-coronavirus activity was found predominantly among the mannose-binding lectins. In addition, a number of galactose-, N-acetylgalactosamine-, glucose-, and N-acetylglucosamine-specific plant agglutinines exhibited anti-coronaviral activity. A significant correlation (with an r-value of 0.70) between the EC50 values of the 10 mannose-specific plant lectins effective against the two coronaviruses was found. In contrast, little correlation was seen between the activity of other types of lectins. Two targets of possible antiviral intervention were identified in the replication cycle of SARS-CoV. The first target is located early in the replication cycle, most probably viral attachment, and the second target is located at the end of the infectious virus cycle.


title: Clinical characteristics and cytokine profiles of children with acute lower respiratory tract infections caused by human rhinovirus

text: The clinical profile of human rhinovirus (HRV) with regard to lower respiratory infections remains unclear. We analyzed the clinical features and cytokine responses of HRV isolates in children with respiratory infections. Quantitative analysis and genotyping of the HRV-positive samples from 601 nasopharyngeal aspirates (NPAs) were performed using VP4/VP2 sequencing. To compare T-helper1 (Th1) type (IFN-γ, TNF-α) and Th2 type (IL-4, IL-10) cytokine responses between HRV-A, B and C, the levels of the four cytokines were measured. The HRV-positive children had shorter fever duration (P = 0.018), and higher frequencies of chest retraction (P = 0.002) and wheezing (P = 0.022) than did the HRV-negative group. HRV-A was identified in 55 cases (58.5%), HRV-B in 8 (8.5%), and HRV-C in 31 (33.0%). There were no significant differences in the clinical data or NPA cytokines levels between patients with HRV-A and HRV-C infections. HRV is an important pathogen of the lower respiratory tract in young children. HRV-A and HRV-C are the dominant species that cause respiratory difficulty in young children.


title: Commonly circulating human coronaviruses do not have a significant role in the etiology of gastrointestinal infections in hospitalized children

text: Abstract Background Human coronaviruses (HCoVs) OC43, 229E, NL63 and HKU1 are common causes of respiratory infections. Over the years, it has been proposed that HCoVs play a possible role in gastrointestinal infections. Objectives To assess the role of HCoVs in acute gastroenteritis (AGE) in children. Study design Study was conducted at Tampere University Hospital over 2 years. Both stool and nasal swab samples were collected from 172 children with AGE, 545 with acute respiratory tract infection (ARTI) and 238 with symptoms of both. The samples were tested for HCoVs by RT-PCR. Results HCoVs were detected in 52 (5.4%) children: in 6.4% of those with AGE, 4.4% with ARTI and 7.1% with symptoms of both. HCoVs OC43, HKU1, 229E and NL63 were encountered in 13, 11, 13 and 15 cases, respectively. HCoVs were detected simultaneously in stool and nasal swab samples in 17 children, in nasal swabs alone in 33 children, and in the stools alone in two children. HCoVs were present in the stools of eight (4.7%) of the 172 children with AGE; in six of these cases, the nasal swab sample was also positive for the respective HCoV. Additionally, in six of the eight cases, the stool sample contained either rotavirus or calicivirus. Conclusions HCoVs can be detected in the stools of children with AGE, but usually together with well-known gastroenteritis viruses, and concomitantly in the respiratory tract. It appears that commonly circulating HCoVs do not have a significant role in the AGE of children admitted to hospital.