title: Removal of bioaerosols by the combination of a photocatalytic filter and negative air ions

text: Abstract This study focused on the investigation of the effectiveness of negative air ionization (NAI), photocatalytic oxidation (PCO), and the combination of NAI and PCO on the removal of aerosolized Escherichia coli, Candida famata, and λ vir phage under different relative humidity. The experiments were conducted with a stainless steel reactor equipped with a negative air ion generator, a photocatalytic filter, and two ultraviolet lamps with 365nm wavelength. The removal efficiency ( η ) , defined as one minus the ratio of the outlet concentration to the inlet concentration of the appropriate bioaerosol, was used to evaluate the effectiveness of the removal methods. The combination of NAI and PCO was the most efficient removal method for aerosolized E. coli ( η = 0.304 ± 0.06 – 0.364 ± 0.008 ) , C. famata ( η = 0.433 ± 0.08 – 0.598 ± 0.047 ) , and λ vir phage ( η = 0.689 ± 0.02 – 0.903 ± 0.06 ) . In this removal method, the contributions of NAI were higher than those of PCO for the removal of E. coli and C. famata; for the removal of λ virus phage the contributions of NAI and PCO were comparable NAI was the least efficient removal method for bioaerosols, and the removal efficiencies are: η = 0.175 ± 0.04 – 0.245 ± 0.03 for E. coli; η = 0.216 ± 0.007 – 0.297 ± 0.044 for C. famata; and η = 0.299 ± 0.12 – 0.384 ± 0.02 for λ vir phage.


title: Global health risks and cosmopolitisation: from emergence to interference

text: According to Beck’s ‘World at Risk’ theory, global risks push nations towards a cosmopolitisation of their health policy and open opportunities for a democratic turn. This article provides an empirical analysis of Beck’s theory, based on the experience of Vietnamese authorities from 2003 to 2007 in managing the emerging avian flu virus. It shows how Vietnam’s framing of avian flu has shifted, under the pressure from international organisations and the US administration, from an epizootic and zoonotic risk (or a classic risk) to a pandemic threat (or a late modern risk). Vietnam’s response was part of its overall strategy to join the World Trade Organization and it was limited by Vietnam’s defence of its sovereignty. This strategy has been successful for Vietnam but has limited the possibility of cosmopolitan and democratic transformations. The case study highlights the constructed dimension of risks of late modernity and their possible instrumentalisation: it minimises the role of a community of fear relative to a community of trade.


title: Guide for Nuclear Medicine Applications During the COVID-19 Outbreak

text: A viral pneumonia rapidly spread from Wuhan, China to all countries in late 2019. In February 2020, WHO named as Coronavirus Disease 2019 (COVID-19) and declared the pandemic on March 11, 2020. To prevent the spread of COVID-19, Ministry of Health of Republic of Turkey and international institutions have published documents defining hygiene rules. After the lung computerized tomography (CT) findings which are important in the diagnosis of COVID-19 are described, protection measures against infection were defined in radiology departments. There is no publication involving protection measures for diagnostic and therapeutic procedures in nuclear medicine (NM) (appointment, patient acceptance, imaging and treatment procedures, disinfection etc). There are two reports on CT findings suggesting COVID-19 in (18)F--fluorodeoxyglucose positron emission tomography/CT scan. These lung findings detected in hybrid images will be helpful in the early diagnosis of pulmonary involvement. Infected cases may be asymptomatic and can unintentionally disseminate the virus to surrounding people. This advisory guide has been prepared to avoid infection risk in NM clinics. During the COVID-19 outbreak, staff must use proper personal protective equipment and patients should be evaluated as the elective case according to clinical status. A questionnaire should be made for COVID-19. In cancer cases requiring urgent treatment, radionuclide treatment (RNT) should be planned according to the COVID-19 test result. If the result is negative, RNT can be applied; but if not or if the symptoms are present, RNT must be postponed. Following imaging procedures, scanners and room surfaces should be cleaned by personnel with proper disinfection training.


title: Emerging and re-emerging viruses in Malaysia, 1997–2007

text: Summary Over the past decade, a number of unique zoonotic and non-zoonotic viruses have emerged in Malaysia. Several of these viruses have resulted in significant morbidity and mortality to those affected and they have imposed a tremendous public health and economic burden on the state. Amongst the most devastating was the outbreak of Nipah virus encephalitis in 1998, which resulted in 109 deaths. The culling of more than a million pigs, identified as the amplifying host, ultimately brought the outbreak under control. A year prior to this, and subsequently again in 2000 and 2003, large outbreaks of hand-foot-and-mouth disease due to enterovirus 71, with rare cases of fatal neurological complications, were reported in young children. Three other new viruses – Tioman virus (1999), Pulau virus (1999), and Melaka virus (2006) – whose origins have all been linked to bats, have been added to the growing list of novel viruses being discovered in Malaysia. The highly pathogenic H5N1 avian influenza has also been detected in Malaysia with outbreaks in poultry in 2004, 2006, and 2007. Fortunately, no human infections were reported. Finally, the HIV/AIDS epidemic has seen the emergence of an HIV-1 recombinant form (CRF33_01B) in HIV-infected individuals from various risk groups, with evidence of ongoing and rapid expansion.


Acute respiratory tract infections in elderly patients increase systemic levels of hemostatic proteins


title: Bactericidal and Virucidal Activity of Povidone-Iodine and Chlorhexidine Gluconate Cleansers in an In Vivo Hand Hygiene Clinical Simulation Study

text: INTRODUCTION: Standard in vitro and in vivo tests help demonstrate efficacy of hand hygiene products; however, there is no standard in vivo test method for viruses. We investigated the bactericidal and virucidal efficacy of povidone-iodine (PVP-I) 7.5% scalp and skin cleanser, chlorhexidine gluconate (CHG) 4% hand cleanser and the reference hand wash (soft soap) in 15 healthy volunteers following European Standard EN1499 (hygienic hand wash test method for bacteria), which was adapted for virucidal testing. METHODS: Separate test series were performed for bactericidal (Escherichia coli) and virucidal [murine norovirus (MNV)] testing. After pre-washing and artificial contamination of hands with test organisms, volunteers underwent testing with 3 and 5 mL of each product for contact times of 15, 30 and 60 s according to a Latin-square randomization. The number of test organisms released from fingertips into sampling fluids was assessed before and after hand washing and mean log(10) reduction factor (RF) was calculated. RFs (test-reference) were compared using a Wilcoxon–Wilcox multiple comparisons test per EN1499; efficacy was concluded if p ≤ 0.01. RESULTS: PVP-I 7.5% and CHG 4% cleansers both passed EN1499 requirements against E. coli, with statistically significantly greater (p ≤ 0.01) mean log(10) RFs compared with reference soft soap across all tests (PVP-I: 4.09–5.27; CHG: 4.12–5.22; soap: 2.75–3.11). The experimental design using EN1499 was applicable to testing with MNV as discriminatory and reproducible results were generated. Mean log(10) RFs of MNV were statistically significantly greater for PVP-I (1.57–2.57) compared with soft soap (1.24–1.62), while mean log(10) RFs with CHG (0.90–1.34) were lower than for soft soap across all tests. CONCLUSION: PVP-I 7.5% cleanser showed superior efficacy against MNV compared to soft soap and CHG 4% cleanser, while both PVP-I and CHG were superior to soft soap against E. coli. The experimental set-up may be applicable to future testing for antiviral hand washes. FUNDING: Mundipharma Manufacturing Pte Ltd. PLAIN LANGUAGE SUMMARY: Plain language summary available for this article.


“Social Distancing” Amid a Crisis in Social Isolation and Loneliness


title: A high-throughput neutralizing antibody assay for COVID-19 diagnosis and vaccine evaluation

text: Virus neutralization remains the gold standard for determining antibody efficacy. Therefore, a high-throughput assay to measure SARS-CoV-2 neutralizing antibodies is urgently needed for COVID-19 serodiagnosis, convalescent plasma therapy, and vaccine development. Here we report on a fluorescence-based SARS-CoV-2 neutralization assay that detects SARS-CoV-2 neutralizing antibodies in COVID-19 patient specimens and yields comparable results to plaque reduction neutralizing assay, the gold standard of serological testing. Our approach offers a rapid platform that can be scaled to screen people for antibody protection from COVID-19, a key parameter necessary to safely reopen local communities.


Resurrection of an “Extinct” SARS-CoV Isolate GD03 from LATE 2003


title: Variable responses of formyl peptide receptor haplotypes toward bacterial peptides

text: The chemoattractant neutrophil formyl peptide receptor (FPR) binds bacterial and mitochondrial N-formylated peptides, which allows the neutrophils to find the bacterial source and/or site of tissue damage. Certain inflammatory disorders may be due in part to an impaired innate immune system that does not respond to acute bacterial damage in a timely fashion. Because the human FPR is encoded by a large number of different haplotypes arising from ten single-nucleotide polymorphisms, we examined the possibility that some of these haplotypes are functionally distinct. We analyzed the response of three common FPR haplotypes to peptides from Escherichia coli, Mycobacterium avium ssp. paratuberculosis, and human mitochondria. All three haplotypes responded similarly to the E. coli and mitochondrial peptides, whereas one required a higher concentration of the M. avium peptide fMFEDAVAWF for receptor downregulation, receptor signaling, and chemotaxis. This raises the possibility of additional bacterial species differences in functional responses among FPR variants and establishes a precedent with potentially important implications for our innate immune response against bacterial infections. We also investigated whether certain FPR haplotypes are associated with rheumatoid arthritis (RA) by sequencing FPR1 from 148 Caucasian individuals. The results suggested that FPR haplotypes do not significantly contribute toward RA.


In Regard to "Radiation for Glioblastoma in the Era of COVID-19: Patient Selection and Hypofractionation to Maximize Benefit and Minimize Risk"


title: Single-Round Infectious Particle Antiviral Screening Assays for the Japanese Encephalitis Virus

text: Japanese Encephalitis virus (JEV) is a mosquito-borne flavivirus with a positive-sense single-stranded RNA genome that contains a big open reading frame (ORF) flanked by 5′- and 3′- untranslated regions (UTRs). Nearly 30,000 JE cases with 10,000 deaths are still annually reported in East Asia. Although the JEV genotype III vaccine has been licensed, it elicits a lower protection against other genotypes. Moreover, no effective treatment for a JE case is developed. This study constructed a pBR322-based and cytomegaloviruses (CMV) promoter-driven JEV replicon for the production of JEV single-round infectious particles (SRIPs) in a packaging cell line expressing viral structural proteins. Genetic instability of JEV genome cDNA in the pBR322 plasmid was associated with the prokaryotic promoter at 5′ end of the JEV genome that triggers the expression of the structural proteins in E. coli. JEV structural proteins were toxic E. coli, thus the encoding region for structural proteins was replaced by a reporter gene (enhanced green fluorescent protein, EGFP) that was in-frame fused with the first eight amino acids of the C protein at N-terminus and the foot-and-mouth disease virus (FMDV) 2A peptide at C-terminus in a pBR322-based JEV-EGFP replicon. JEV-EGFP SRIPs generated from JEV-EGFP replicon-transfected packaging cells displayed the infectivity with cytopathic effect induction, self-replication of viral genomes, and the expression of EGFP and viral proteins. Moreover, the combination of JEV-EGFP SRIP plus flow cytometry was used to determine the half maximal inhibitory concentration (IC50) values of antiviral agents according to fluorescent intensity and positivity of SRIP-infected packaging cells post treatment. MJ-47, a quinazolinone derivative, significantly inhibited JEV-induced cytopathic effect, reducing the replication and expression of JEV-EGFP replicon in vitro. The IC50 value of 6.28 µM for MJ-47 against JEV was determined by the assay of JEV-EGFP SRIP infection in packaging cells plus flow cytometry that was more sensitive, effective, and efficient compared to the traditional plaque assay. Therefore, the system of JEV-EGFP SRIPs plus flow cytometry was a rapid and reliable platform for screening antiviral agents and evaluating antiviral potency.


title: Hepatitis C Virus NS2 Protein Suppresses RNA Interference in Cells

text: RNAi interference (RNAi) is an evolutionarily conserved post-transcriptional gene silencing mechanism and has been well recognized as an important antiviral immunity in eukaryotes. Numerous viruses have been shown to encode viral suppressors of RNAi (VSRs) to antagonize antiviral RNAi. Hepatitis C virus (HCV) is a medically important human pathogen that causes acute and chronic hepatitis. In this study, we screened all the nonstructural proteins of HCV and found that HCV NS2 could suppress RNAi induced either by small hairpin RNAs (shRNAs) or small interfering RNAs (siRNAs) in mammalian cells. Moreover, we demonstrated that NS2 could suppress RNAi via its direct interaction with double-stranded RNAs (dsRNAs) and siRNAs, and further identified that the cysteine 184 of NS2 is required for the RNAi suppression activity through a serial of point mutation analyses. Together, our findings uncovered that HCV NS2 can act as a VSR in vitro, thereby providing novel insights into the life cycle and virus-host interactions of HCV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-019-00182-5) contains supplementary material, which is available to authorized users.


title: Drug repurposing against SARS-CoV-2 using E-pharmacophore based virtual screening, molecular docking and molecular dynamics with main protease as the target

text: Since its first report in December 2019 from China, the COVID-19 pandemic caused by the beta-coronavirus SARS-CoV-2 has spread at an alarming pace infecting about 5.59 million, and claiming the lives of more than 0.35 million individuals across the globe. The lack of a clinically approved vaccine or drug remains the biggest bottleneck in combating the pandemic. Drug repurposing can expedite the process of drug development by identifying known drugs which are effective against SARS-CoV-2. The SARS-CoV-2 main protease is a promising drug target due to its indispensable role in viral multiplication inside the host. In the present study an E-pharmacophore hypothesis was generated using a crystal structure of the viral protease in complex with an imidazole carbaximide inhibitor. Drugs available in the superDRUG2 database were used to identify candidate drugs for repurposing. The hits obtained from the pharmacophore based screening were further screened using a structure based approach involving molecular docking at different precisions. The binding energies of the most promising compounds were estimated using MM-GBSA. The stability of the interactions between the selected drugs and the target were further explored using molecular dynamics simulation at 100 ns. The results showed that the drugs Binifibrate and Bamifylline bind strongly to the enzyme active site and hence they can be repurposed against SARS-CoV-2. However, U.S Food and Drug Administration have withdrawn Binifibrate from the market as it was having some adverse health effects on patients. Communicated by Ramaswamy H. Sarma


title: Cultivation and partial characterization of bovine astrovirus

text: Abstract Bovine astrovirus serotype 2 (US2) was adapted to primary neonatal kidney cell (NBK) cultures by the addition of 50 μg ml−1 of trypsin in the medium. Infectious virus was released from the cells within 7 days post-infection in early passages and within 3 days in later passages. In the absence of trypsin, neither passage infected cells nor release of infectious virus occurred. The virus was shown to be similar to the fecal astrovirus by a neutralization test and by ultrastructural studies of infected cells. Primary embryo bovine kidney (EBK) and NBK cell cultures supported infection with both fecal and tissue culture adapted (TCA) astrovirus. The time-related development of infection, as studied by immunofluorescence, was similar for both fecal and TCA astrovirus and for both cell culture types. The first indication of viral infection and expression of viral antigens occurred at 7 h post-infection and was characterized by the appearance of a diffuse faint immunofluorescence (IF) of the cytoplasm. Soon after, two or three brilliant IF granules were observed in the nucleus, which appeared to involve the nucleoli. Subsequently, dense granular IF was seen in the perinuclear region of the cytoplasm, which later extended to involve all the cytoplasmic area. In both EBK and NBK cultures infected with either fecal or tissue culture adapted astrovirus, only a minority of cells became infected, even when the multiplicity of infections exceeded one. Occasionally 10–20% of cells were infected, but in most cultures the proportion did not exceed 2% and in NBK cultures, from 3 9 calves, no infected cells were observed. The virus did not infect bovine cell lines. Infectivity of the virus was not removed by treatment with chloroform, and iododeoxyuridine and actinomycin D when added to the medium, did not block replication. Masses of virions were observed by electron microscopy in discrete areas in the cytoplasm, with similar distributions as the viral antigen foci as seen by IF. The mean diameter of the virions was 34 nm. In conclusion, bovine astrovirus lacks both essential lipids and an envelope, probably has an RNA genome, may have a nuclear phase of replication involving the nucleoli which is not blocked by DNA inhibitors, and has a selective cell tropism.


title: Structures and diseases

text: Structural biology is making significant contributions toward an understanding of molecular constituents and mechanisms underlying human diseases at an atomic resolution, as discussed at the international Murnau Conference on Structural Biology of Disease Mechanisms held in September 2007 in Murnau, Germany.


title: Pocket-sized epidemiology Ibrahim Abubakar Helen R Stagg

text: Unknown


title: How Much Support Is There for the Recommendations Made to the General Population during Confinement? A Study during the First Three Days of the COVID–19 Quarantine in Spain

text: Background: Recommendations on lifestyles during quarantine have been proposed by researchers and institutions since the COVID–19 crisis emerged. However, most of these have never been tested under real quarantine situations or derive from older investigations conducted mostly in China and Canada in the face of infections other than COVID–19. The present study aimed at exploring the relationship between a comprehensive set of recommended lifestyles, socio–demographic, and personality variables and mood during the first stages of quarantine. Methods: A virtual snow–ball recollection technique was used to disseminate the survey across the general population in Spain starting the first day of mandatory quarantine (15 March 2020) until three days later (17 March). In total, 2683 Spanish adults (mean age = 34.86 years, SD = 13.74 years; 77.7% women) from the general population completed measures on socio–demographic, COVID–related, behavioral, personality/cognitive, and mood characteristics. Results: In the present study, depression and anger were higher than levels reported in a previous investigation before the COVID–19 crisis, while vigor, friendliness, and fatigue were lower. Anxiety levels were comparable. The expected direction of associations was confirmed for the majority of predictors. However, effect sizes were generally small and only a subset of them correlated to most outcomes. Intolerance of unpleasant emotions, neuroticism, and, to a lesser extent, agreeableness, sleep quality, young age, and time spent Internet surfing were the most robust and strongest correlates of mood states. Conclusions: Some recommended lifestyles (i.e., maintaining good quality of sleep and reducing Internet surfing) might be more important than others during the first days of quarantine. Promoting tolerance to unpleasant emotions (e.g., through online, self–managed programs) might also be of upmost importance. So far, recommendations have been made in general, but certain subgroups (e.g., certain personality profiles and young adults) might be especially vulnerable and should receive more attention.


title: Early estimates of the indirect effects of the COVID-19 pandemic on maternal and child mortality in low-income and middle-income countries: a modelling study

text: BACKGROUND: While the COVID-19 pandemic will increase mortality due to the virus, it is also likely to increase mortality indirectly. In this study, we estimate the additional maternal and under-5 child deaths resulting from the potential disruption of health systems and decreased access to food. METHODS: We modelled three scenarios in which the coverage of essential maternal and child health interventions is reduced by 9·8–51·9% and the prevalence of wasting is increased by 10–50%. Although our scenarios are hypothetical, we sought to reflect real-world possibilities, given emerging reports of the supply-side and demand-side effects of the pandemic. We used the Lives Saved Tool to estimate the additional maternal and under-5 child deaths under each scenario, in 118 low-income and middle-income countries. We estimated additional deaths for a single month and extrapolated for 3 months, 6 months, and 12 months. FINDINGS: Our least severe scenario (coverage reductions of 9·8–18·5% and wasting increase of 10%) over 6 months would result in 253 500 additional child deaths and 12 200 additional maternal deaths. Our most severe scenario (coverage reductions of 39·3–51·9% and wasting increase of 50%) over 6 months would result in 1 157 000 additional child deaths and 56 700 additional maternal deaths. These additional deaths would represent an increase of 9·8–44·7% in under-5 child deaths per month, and an 8·3–38·6% increase in maternal deaths per month, across the 118 countries. Across our three scenarios, the reduced coverage of four childbirth interventions (parenteral administration of uterotonics, antibiotics, and anticonvulsants, and clean birth environments) would account for approximately 60% of additional maternal deaths. The increase in wasting prevalence would account for 18–23% of additional child deaths and reduced coverage of antibiotics for pneumonia and neonatal sepsis and of oral rehydration solution for diarrhoea would together account for around 41% of additional child deaths. INTERPRETATION: Our estimates are based on tentative assumptions and represent a wide range of outcomes. Nonetheless, they show that, if routine health care is disrupted and access to food is decreased (as a result of unavoidable shocks, health system collapse, or intentional choices made in responding to the pandemic), the increase in child and maternal deaths will be devastating. We hope these numbers add context as policy makers establish guidelines and allocate resources in the days and months to come. FUNDING: Bill & Melinda Gates Foundation, Global Affairs Canada.


title: Mapping Potential Amplification and Transmission Hotspots for MERS-CoV, Kenya

text: Dromedary camels have been implicated consistently as the source of Middle East respiratory syndrome coronavirus (MERS-CoV) human infections and attention to prevent and control it has focused on camels. To understanding the epidemiological role of camels in the transmission of MERS-CoV, we utilized an iterative empirical process in Geographic Information System (GIS) to identify and qualify potential hotspots for maintenance and circulation of MERS-CoV, and produced risk-based surveillance sites in Kenya. Data on camel population and distribution were used to develop camel density map, while camel farming system was defined using multi-factorial criteria including the agro-ecological zones (AEZs), production and marketing practices. Primary and secondary MERS-CoV seroprevalence data from specific sites were analyzed, and location-based prevalence matching with camel densities was conducted. High-risk convergence points (migration zones, trade routes, camel markets, slaughter slabs) were profiled and frequent cross-border camel movement mapped. Results showed that high camel-dense areas and interaction (markets and migration zones) were potential hotspot for transmission and spread. Cross-border contacts occurred with in-migrated herds at hotspot locations. AEZ differential did not influence risk distribution and plausible risk factors for spatial MERS-CoV hotspots were camel densities, previous cases of MERS-CoV, high seroprevalence and points of camel convergences. Although Kenyan camels are predisposed to MERS-CoV, no shedding is documented to date. These potential hotspots, determined using anthropogenic, system and trade characterizations should guide selection of sampling/surveillance sites, high-risk locations, critical areas for interventions and policy development in Kenya, as well as instigate further virological examination of camels. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10393-018-1317-6) contains supplementary material, which is available to authorized users.


title: Chapter 4 Molecular Modeling of Major Structural Protein Genes of Avian Coronavirus: Infectious Bronchitis Virus Mass H120 and Italy02 Strains

text: Abstract In Morocco, the epidemiological situation of infectious bronchitis virus (IBV) is very complex, because of the antigenic diversity associated with the emergence of new serotypes/genotypes and variants. The IBV strains circulating in poultry farms are serotypes/genotypes Italy02 and Massachusetts (Mass) identified during 2010–14. The appearance of these variants hinders the prophylactic strategy carried out by the breeders of the Moroccan poultry farm. To solve this problem, we have opted for the rational design of candidate vaccines in order to study the structure of the three-dimensional (3D) S1 spicule protein of serotype Italy02 and Mass H120, through molecular modeling, using the I-TASSER server, then the COACH, and another Meta server to determine and predict the common immunogenic active sites between these two IBV strains circulating in Morocco. The obtained results showed that the two strains studied had identical spatial conformation of the S1 protein structure with a similarity percentage of 81% and an average stability of the modeled sequences. Thus both serotypes share active antigenic sites common in the hypervariable region, located at residues 229, 230, 232, 233, and 235, with a magnesium molecule association around the Alanine 280 region responsible for stimulating immunogenicity. The quality of the 3D conformation, the stability, and the percentage make it possible to have accessibility to the common predicted neutralizing epitopes. Based on these data, we can conclude that it is highly probable that the H120 vaccine strain confers cross-protection against a challenge with new strains Italy02 circulating in Morocco.


title: 10 “C” in COVID19

text: World war “C”(1) has set in against an invisible virus. The routes of transmission include *Contact of contaminated objects,*Circulating droplets in the air called aerosols disseminated through *Cough, sneeze, ocular secretions(2) from an infected individual.


title: SARS-CoV-2 and SARS-CoV Spike-RBD Structure and Receptor Binding Comparison and Potential Implications on Neutralizing Antibody and Vaccine Development

text: SARS-CoV-2 and SARS-CoV share a common human receptor ACE2. Protein-protein interaction structure modeling indicates that spike-RBD of the two viruses also has similar overall binding conformation and binding free energy to ACE2. In vitro assays using recombinant ACE2 proteins and ACE2 expressing cells confirmed the two coronaviruses’ similar binding affinities to ACE2. The above studies provide experimental supporting evidences and possible explanation for the high transmissibility observed in the SARS-CoV-2 outbreak. Potent ACE2-blocking SARS-CoV neutralizing antibodies showed limited cross-binding and neutralizing activities to SARS-CoV-2. ACE2-non-blocking SARS-CoV RBD antibodies, though with weaker neutralizing activities against SARS-CoV, showed positive cross-neutralizing activities to SARS-CoV-2 with an unknown mechanism. These findings suggest a trade-off between the efficacy and spectrum for therapeutic antibodies to different coronaviruses, and hence highlight the possibilities and challenges in developing broadly protecting antibodies and vaccines against SARS-CoV-2 and its future mutants.


title: Reshaping ophthalmology training after COVID-19 pandemic

text: BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on practical activities and didactic teaching of residents and fellows. This survey aimed to propose long-term changes for ophthalmology training based on the changes experienced by trainees and their perception of new training opportunities. METHODS: An online survey was distributed to ophthalmology trainees in multiple countries. Descriptive statistics were used to analyse the data. RESULTS: A total of 504 analyzable responses were collected from 32 different countries. The current impact of COVID-19 pandemic was described as “severe” by most trainees (55.2%); however, the future perspective was more optimistic as demonstrated by the greater number of responses reporting a presumed “moderate” (37.3%), “mild” (14.1%) or “slight” (4.2%) long-term impact. The vast majority of trainees reported a decrease ≥50% of clinical activity (76.4%) and >75% of surgical activity (74.6%). Although an initial gap in didactic teaching has been experienced by many (55.4%), regular web-based teaching was reportedly attended by 67.7% of the respondents. A strong agreement was found regarding the worthwhile role of web-based case-presentations in clinical training (91.7%), web-based discussion of edited surgical videos (85.7%) and simulation-based practice (86.9%) in surgical training. CONCLUSIONS: This survey, focusing on trainees’ perspective, strongly reinforces the need to promptly include new technology-based training tools, such as web-based teaching, virtual surgical simulators, and telementoring, in long-term reorganisation of ophthalmology training to ensure its continuity and effectiveness, which would remain available even in the face of another unpredictable crisis within the health system.


title: Differential proteomic analysis of virus-enriched fractions obtained from plasma pools of patients with dengue fever or severe dengue

text: BACKGROUND: Dengue is the most widespread mosquito-borne viral disease of public health concern. In some patients, endothelial cell and platelet dysfunction lead to life-threatening hemorrhagic dengue fever or dengue shock syndrome. Prognostication of disease severity is urgently required to improve patient management. The pathogenesis of severe dengue has not been fully elucidated, and the role of host proteins associated with viral particles has received little exploration. METHODS: The proteomes of virion-enriched fractions purified from plasma pools of patients with dengue fever or severe dengue were compared. Virions were purified by ultracentrifugation combined with a water-insoluble polyelectrolyte-based technique. Following in-gel hydrolysis, peptides were analyzed by nano-liquid chromatography coupled to ion trap mass spectrometry and identified using data libraries. RESULTS: Both dengue fever and severe dengue viral-enriched fractions contained identifiable viral envelope proteins and host cellular proteins. Canonical pathway analysis revealed the identified host proteins are mainly involved in the coagulation cascade, complement pathway or acute phase response signaling pathway. Some host proteins were over- or under-represented in plasma from patients with severe dengue compared to patients with dengue fever. ELISAs were used to validate differential expression of a selection of identified host proteins in individual plasma samples of patients with dengue fever compared to patients with severe dengue. Among 22 host proteins tested, two could differentiate between dengue fever and severe dengue in two independent cohorts (olfactomedin-4: area under the curve (AUC), 0.958; and platelet factor-4: AUC, 0.836). CONCLUSION: A novel technique of virion-enrichment from plasma has allowed to identify two host proteins that have prognostic value for classifying patients with acute dengue who are more likely to develop a severe dengue. The impact of these host proteins on pathogenicity and disease outcome are discussed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-1271-7) contains supplementary material, which is available to authorized users.


Un éditorial dans la crise


B lines in COVID‐19: “Unspecificity” is not “meaningless”


title: More Than Just a Barrier: The Immune Functions of the Airway Epithelium in Asthma Pathogenesis

text: Allergic bronchial asthma is a chronic disease of the airways that is characterized by symptoms like respiratory distress, chest tightness, wheezing, productive cough, and acute episodes of broncho-obstruction. This symptom-complex arises on the basis of chronic allergic inflammation of the airway wall. Consequently, the airway epithelium is central to the pathogenesis of this disease, because its multiple abilities directly have an impact on the inflammatory response and thus the formation of the disease. In turn, its structure and functions are markedly impaired by the inflammation. Hence, the airway epithelium represents a sealed, self-cleaning barrier, that prohibits penetration of inhaled allergens, pathogens, and other noxious agents into the body. This barrier is covered with mucus that further contains antimicrobial peptides and antibodies that are either produced or specifically transported by the airway epithelium in order to trap these particles and to remove them from the body by a process called mucociliary clearance. Once this first line of defense of the lung is overcome, airway epithelial cells are the first cells to get in contact with pathogens, to be damaged or infected. Therefore, these cells release a plethora of chemokines and cytokines that not only induce an acute inflammatory reaction but also have an impact on the alignment of the following immune reaction. In case of asthma, all these functions are impaired by the already existing allergic immune response that per se weakens the barrier integrity and self-cleaning abilities of the airway epithelium making it more vulnerable to penetration of allergens as well as of infection by bacteria and viruses. Recent studies indicate that the history of allergy- and pathogen-derived insults can leave some kind of memory in these cells that can be described as imprinting or trained immunity. Thus, the airway epithelium is in the center of processes that lead to formation, progression and acute exacerbation of asthma.


title: Epidemiology of Viral Infections and Evaluation of the Potential Benefit of OM-85 BV on the Virologie Status of Children Attending Day-Care Centers

text: Viral investigations were performed during 4 winter seasons (88/89, 89/90, 92/93, 93/94) in children attending day-care centers (DCCs) in the Rhone Département in eastern France. Over the total observation period of 4 winter seasons, 780 children were screened with a nasal swab for the presence of viruses. Of those, 230 (29.5%) had a positive viral culture. The viruses identified were respiratory syncytial virus (RSV), influenza A and B virus, parain-fluenza virus, coronavirus, rhinovirus, adenovirus and enterovirus. During that time, 83 epidemic events in 47 DCC were recorded. A particular virus was judged to be causally related to an epidemic if the identical virus was isolated in ≥ 3 children during the same outbreak of respiratory diseases. Thus, in 51 cases (61.4%) of all epidemics, the following viruses were responsible for an epidemic: RSV (n = 23), coronavirus (n = 10) (only during the season of 1993-1994), influenza A virus (n = 6), rhinovirus (n = 4), enterovirus (n = 4), adenovirus (n = 3) and parainfluenza virus (n = 1). Except for the somewhat surprising accumulation of coronavirus epidemics during the winter of 1993-1994, there were only minor seasonal variations from one year to another. As expected, RSV accounted for about one third of all respiratory tract infections in children attending DCCs and was therefore the most important single causative agent. These results are compared with data from children who did not attend a DCC and were cared for in a private practice. During the winter of 1989-1990, the viral epidemiological survey was performed at the same time and in parallel to a double-blind, placebo-controlled clinical study investigating the efficacy of OM-85 BV, an immunoactive bacterial extract. This study, enrolling 423 children attending DCCs demonstrated a protective effect of OM-85 BV in significantly reducing the risk of recurrent infections of the upper respiratory tract during the treatment period with the compound. 34% of all participating children (75 in the verum group, 70 in the placebo group) were enrolled in an additional virological study. In these patients, RSV was isolated 10 times in the placebo group, but only 5 times in the treated group (p < 0.05) and influenza A virus was present in 4 children in the placebo group, but only in 1 infant in the verum group giving a total of 14 positive virologie results in the placebo group versus 6 in the verum group (p < 0.05). Despite the small numbers of children investigated for their virologie status during respiratory infectious outbreaks, there was a statistically significant difference in the prevalence of virus carriers in favor of the children treated with OM-85 BV. These results corroborate the clinical findings.


title: The role of phospholipase C signaling in bovine herpesvirus 1 infection

text: Bovine herpesvirus 1 (BoHV-1) infection enhanced the generation of inflammatory mediator reactive oxidative species (ROS) and stimulated MAPK signaling that are highly possibly related to virus induced inflammation. In this study, for the first time we show that BoHV-1 infection manipulated phospholipase C (PLC) signaling, as demonstrated by the activation of PLCγ-1 at both early stages [at 0.5 h post-infection (hpi)] and late stages (4–12 hpi) during the virus infection of MDBK cells. Viral entry, and de novo protein expression and/or DNA replication were potentially responsible for the activation of PLCγ-1 signaling. PLC signaling inhibitors of both U73122 and edelfosine significantly inhibited BoHV-1 replication in both bovine kidney cells (MDBK) and rabbit skin cells (RS-1) in a dose-dependent manner by affecting the virus entry stage(s). In addition, the activation of Erk1/2 and p38MAPK signaling, and the enhanced generation of ROS by BoHV-1 infection were obviously ameliorated by chemical inhibition of PLC signaling, implying the requirement of PLC signaling in ROS production and these MAPK pathway activation. These results suggest that the activation of PLC signaling is a potential pathogenic mechanism for BoHV-1 infection.


title: Antiviral Agents in Development for Zika Virus Infections

text: In 1947, Zika virus (ZIKV), a mosquito-borne flavivirus was identified in Uganda and subsequently spread to Asia and the Pacific regions. In 2015, it was introduced in Brazil causing an important social and sanitary alarm due to its increased virulence and rapid dissemination. Importantly, ZIKV infections have been associated with severe neurological complications such as Guillain–Barré syndrome and microcephaly in fetuses and newborns. Although enormous efforts were made by investigators in the development of effective countermeasures against ZIKV, there is still no approved specific antiviral drug for the treatment of ZIKV infections. Herein, we review several anti ZIKV candidates including drugs targeting both the virus (structural proteins and enzymes) and cellular elements.


title: The impact of COVID‐19 in the diagnosis and treatment of obsessive‐compulsive disorder

text: Obsessive‐compulsive disorder (OCD) is characterized by unwanted and distressing thoughts, images or urges (obsessions) and repetitive behaviors or mental acts that aim to decrease the resulting distress or according to rigid rules (compulsions) (APA, 2013). Different studies suggest OCD to affect up to 3.1 % of the general population and to be associated with substantial disability and decreased quality of life (Fontenelle, Mendlowicz, & Versiani, 2006; Ruscio, Stein, Chiu, & Kessler, 2010). This article is protected by copyright. All rights reserved.


title: Bioactive properties of Sambucus nigra L. as a functional ingredient for food and pharmaceutical industry

text: Abstract European black elderberry naturally occurs in most of Europe and has been introduced into various parts of the world for fruit and flower production. Elderberry is rich in nutrients, such as carbohydrates, proteins, fats, fatty acids, organic acids, minerals, vitamins and essential oils. Elderberry also contains cyanogenic glycosides which are potentially toxic. Polyphenols, known for their free radical scavenging (antioxidant) activity, are the most important group of bioactive compounds present in elderberry in relatively high concentration. The high antioxidant activity of elderberry fruit and flowers is associated with their therapeutic properties. Elderberry has for a long time been used in folk medicine as a diaphoretic, antipyretic and diuretic agent. In recent years it was also found to have antibacterial, antiviral antidepressant and antitumour and hypoglycemic properties, and to reduce body fat and lipid concentration. Due to its health-promoting and sensory properties, elderberry is used primarily in food and pharmaceutical industry.


title: COVID‐19 outbreak represents a new way of mental health service delivery

text: Increased mental health disorders, prolonged isolation, hospital bed adequacy, lost revenue and staff safety are among the myriad of concerns the field is dealing with in the wake of the COVID‐19 epidemic. And for some staff, protective gear is in order.


Statement on the prevention and treatment of COVID‐19 in patients with pediatric cancer in Japan


title: In vitro translation of a subgenomic mRNA from purified virions of the Spanish field isolate AST/89 of Rabbit Hemorrhagic Disease Virus (RHDV)

text: Abstract Purified preparations of the Spanish field isolate of rabbit hemorrhagic disease virus AST/89 were found to contain the plus-stranded genomic RNA of more than 7.4 kilobases (kb) and large amounts of a subgenomic mRNA of 2.4 kb. The smaller RNA was translated in vitro and shown to code for a 60 kDa protein which was immunoprecipitated using anti-RHDV as well as anti-VP60 sera.


title: What the stock market tells us about the post-COVID-19 world

text: The stock market provides a view of what investors expect for the future. It is precisely in complex situations such as the COVID-19 outbreak that the prescience of the market is particularly valuable, argues Alexander F. Wagner.


title: Molecular Diagnosis of Diarrhea: Current Status and Future Potential

text: Determining the microbiologic etiology of enteric infection remains an elusive goal. Conventional approaches, including culture, microscopy, and antigen-based tests have significant limitations such as limit of detection and the need for multiple procedures. Molecular diagnostics, especially PCR based tests, are rapidly changing research and practice in infectious diseases. Diarrheal disease, with its broad range of potential infectious etiologies, is well suited for multiplex molecular testing. This review highlights examples of currently employed molecular tests, as well as ways in which these tests can be applied in the future. The absence of a gold standard for the microbiologic cause of diarrhea means that the clinical significance of detected organisms may not always be clear. Conventional wisdom is that there should be one main pathogen causing diarrhea, however our thinking is challenged by increased detection of mixed infections. Thus, the successful incorporation of molecular diagnostics for diarrheal disease into practice will require both a careful understanding of the technical aspects and research to define their clinical utility.


title: Changes in Cytokine Levels and NK Cell Activation Associated with Influenza

text: Several studies have highlighted the important role played by murine natural killer (NK) cells in the control of influenza infection. However, human NK cell responses in acute influenza infection, including infection with the 2009 pandemic H1N1 influenza virus, are poorly documented. Here, we examined changes in NK cell phenotype and function and plasma cytokine levels associated with influenza infection and vaccination. We show that absolute numbers of peripheral blood NK cells, and particularly those of CD56(bright) NK cells, decreased upon acute influenza infection while this NK cell subset expanded following intramuscular influenza vaccination. NK cells exposed to influenza antigens were activated, with higher proportions of NK cells expressing CD69 in study subjects infected with seasonal influenza strains. Vaccination led to increased levels of CD25+ NK cells, and notably CD56(bright) CD25+ NK cells, whereas decreased amounts of this subset were present in the peripheral blood of influenza infected individuals, and predominantly in study subjects infected with the 2009 pandemic H1N1 influenza virus. Finally, acute influenza infection was associated with low plasma concentrations of inflammatory cytokines, including IFN-γ, MIP-1β, IL-2 and IL-15, and high levels of the anti-inflammatory cytokines IL-10 and IL-1ra. Altogether, these data suggest a role for the CD56(bright) NK cell subset in the response to influenza, potentially involving their recruitment to infected tissues and a local production and/or uptake of inflammatory cytokines.


A hard little lesson: Squeezed nanospheres grow superstrong


title: Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication

text: Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I). This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU) activity is key to prevent early induction of double-stranded RNA (dsRNA) host cell responses. Replication of EndoU-deficient coronaviruses is greatly attenuated in vivo and severely restricted in primary cells even during the early phase of the infection. In macrophages we found immediate induction of IFN-I expression and RNase L-mediated breakdown of ribosomal RNA. Accordingly, EndoU-deficient viruses can retain replication only in cells that are deficient in IFN-I expression or sensing, and in cells lacking both RNase L and PKR. Collectively our results demonstrate that the coronavirus EndoU efficiently prevents simultaneous activation of host cell dsRNA sensors, such as Mda5, OAS and PKR. The localization of the EndoU activity at the site of viral RNA synthesis–within the replicase complex—suggests that coronaviruses have evolved a viral RNA decay pathway to evade early innate and intrinsic antiviral host cell responses.


title: MERS-CoV NSP16 necessary for IFN resistance and viral pathogenesis

text: Coronaviruses encode a mix of highly conserved and novel genes as well as genetic elements necessary for infection and pathogenesis, raising the possibility for common targets for attenuation and therapeutic design. In this study, we focus on the highly conserved nonstructural protein (NSP) 16, a viral 2’O methyl-transferase (MTase) that encodes critical functions in immune modulation and infection. Using reverse genetics, we disrupted a key motif in the conserved KDKE motif of MERS NSP16 (D130A) and evaluated the effect on viral infection and pathogenesis. While the absence of 2’O MTase activity had only marginal impact on propagation and replication in Vero cells, the MERS dNSP16 mutant demonstrated significant attenuation relative to control both in primary human airway cultures and in vivo. Further examination indicated the MERS dNSP16 mutant had a type I IFN based attenuation and was partially restored in the absence of IFIT molecules. Importantly, the robust attenuation permitted use of MERS dNSP16 as a live attenuated vaccine platform protecting from challenge with a mouse adapted MERS-CoV strain. These studies demonstrate the importance of the conserved 2’O MTase activity for CoV pathogenesis and highlight NSP16 as a conserved universal target for rapid live attenuated vaccine design in an expanding CoV outbreak setting. Significance Coronavirus emergence in both human and livestock represents a significant threat to global public health, as evidenced by the sudden emergence of SARS-CoV, MERS-CoV, PEDV and swine delta coronavirus in the 21st century. These studies describe an approach that effectively targets the highly conserved 2’O methyl-transferase activity of coronaviruses for attenuation. With clear understanding of the IFN/IFIT based mechanism, NSP16 mutants provide a suitable target for a live attenuated vaccine platform as well as therapeutic development for both current and future emergent CoV strains. Importantly, other approaches targeting other conserved pan-coronavirus functions have not yet proven effective against MERS-CoV, illustrating the broad applicability of targeting viral 2’O MTase function across coronaviruses.


title: Fogarty International Center collaborative networks in infectious disease modeling: Lessons learnt in research and capacity building

text: Abstract Due to a combination of ecological, political, and demographic factors, the emergence of novel pathogens has been increasingly observed in animals and humans in recent decades. Enhancing global capacity to study and interpret infectious disease surveillance data, and to develop data-driven computational models to guide policy, represents one of the most cost-effective, and yet overlooked, ways to prepare for the next pandemic. Epidemiological and behavioral data from recent pandemics and historic scourges have provided rich opportunities for validation of computational models, while new sequencing technologies and the ‘big data’ revolution present new tools for studying the epidemiology of outbreaks in real time. For the past two decades, the Division of International Epidemiology and Population Studies (DIEPS) of the NIH Fogarty International Center has spearheaded two synergistic programs to better understand and devise control strategies for global infectious disease threats. The Multinational Influenza Seasonal Mortality Study (MISMS) has strengthened global capacity to study the epidemiology and evolutionary dynamics of influenza viruses in 80 countries by organizing international research activities and training workshops. The Research and Policy in Infectious Disease Dynamics (RAPIDD) program and its precursor activities has established a network of global experts in infectious disease modeling operating at the research-policy interface, with collaborators in 78 countries. These activities have provided evidence-based recommendations for disease control, including during large-scale outbreaks of pandemic influenza, Ebola and Zika virus. Together, these programs have coordinated international collaborative networks to advance the study of emerging disease threats and the field of computational epidemic modeling. A global community of researchers and policy-makers have used the tools and trainings developed by these programs to interpret infectious disease patterns in their countries, understand modeling concepts, and inform control policies. Here we reflect on the scientific achievements and lessons learnt from these programs (h-index = 106 for RAPIDD and 79 for MISMS), including the identification of outstanding researchers and fellows; funding flexibility for timely research workshops and working groups (particularly relative to more traditional investigator-based grant programs); emphasis on group activities such as large-scale modeling reviews, model comparisons, forecasting challenges and special journal issues; strong quality control with a light touch on outputs; and prominence of training, data-sharing, and joint publications.


title: News and Perspectives Is There an Association Between Oral Health and Severity of COVID-19 Complications?

text: Most patients with severe complications from COVID-19 have underlying conditions such as obesity, diabetes, and hypertension. In parallel, there is growing evidence for a link between periodontitis and non-oral systemic diseases. The oral cavity is also a reservoir for respiratory pathogens, and patients with periodontal disease are more likely to develop hospital-acquired pneumonia than healthy individuals. We therefore hypothesize that improving oral health could decrease the severity of COVID-19 symptoms and reduce the associated morbidity.


title: Estimating the distance to an epidemic threshold

text: The epidemic threshold of the susceptible–infected–recovered model is a boundary separating parameters that permit epidemics from those that do not. This threshold corresponds to parameters where the system's equilibrium becomes unstable. Consequently, we use the average rate at which deviations from the equilibrium shrink to define a distance to this threshold. However, the vital dynamics of the host population may occur slowly even when transmission is far from threshold levels. Here, we show analytically how such slow dynamics can prevent estimation of the distance to the threshold from fluctuations in the susceptible population. Although these results are exact only in the limit of long-term observation of a large system, simulations show that they still provide useful insight into systems with a range of population sizes, environmental noise and observation schemes. Having established some guidelines about when estimates are accurate, we then illustrate how multiple distance estimates can be used to estimate the rate of approach to the threshold. The estimation approach is general and may be applicable to zoonotic pathogens such as Middle East respiratory syndrome-related coronavirus (MERS-CoV) as well as vaccine-preventable diseases like measles.


title: Incidence of respiratory viruses among travelers with a febrile syndrome returning from tropical and subtropical areas

text: Fifty million people are estimated to travel from industrial countries to the tropics annually. In spite of exhaustive studies and widely different diagnosis among returned patients, some cases of febrile illnesses remain without an etiological diagnosis, suggesting that these cases could be due to viral respiratory tract infections. From August 2005 to October 2006, 118 febrile patients without a specific diagnosis in their first visit at the Center for International Health of the Hospital Clínic of Barcelona were included. In all of them, in order to study respiratory viruses, a nasopharyngeal swab was collected. Clinical and radiological features and epidemiological data, as well as other samples for microbiologic studies, were also collected during consultation. Based on the physician's judgment at the time of consultation, patients were classified into four groups: respiratory symptoms (62%), febrile syndrome with nonspecific symptoms (24%), digestive symptoms (10%), and patients presenting both respiratory and digestive symptoms (4%). A pathogen microorganism was detected in 61 patients (52%). Respiratory viruses were detected in 44 out of 118 (37%) travelers included in the study, representing 56% of the patients with respiratory symptoms. The most frequently viruses detected were influenza virus (38%), rhinovirus (23%), adenovirus (9%), and respiratory syncytial virus (9%). Respiratory viruses have been shown to play an important role in imported fever. In light of the fact that international tourism is an increasing phenomenon, new strategies to prevent the spread of respiratory viruses should be considered, specially for influenza when a vaccine is available. J. Med. Virol. 80:711–715, 2008. © 2008 Wiley‐Liss, Inc.


title: A step by step guide for conducting a systematic review and meta-analysis with simulation data

text: BACKGROUND: The massive abundance of studies relating to tropical medicine and health has increased strikingly over the last few decades. In the field of tropical medicine and health, a well-conducted systematic review and meta-analysis (SR/MA) is considered a feasible solution for keeping clinicians abreast of current evidence-based medicine. Understanding of SR/MA steps is of paramount importance for its conduction. It is not easy to be done as there are obstacles that could face the researcher. To solve those hindrances, this methodology study aimed to provide a step-by-step approach mainly for beginners and junior researchers, in the field of tropical medicine and other health care fields, on how to properly conduct a SR/MA, in which all the steps here depicts our experience and expertise combined with the already well-known and accepted international guidance. We suggest that all steps of SR/MA should be done independently by 2–3 reviewers’ discussion, to ensure data quality and accuracy. CONCLUSION: SR/MA steps include the development of research question, forming criteria, search strategy, searching databases, protocol registration, title, abstract, full-text screening, manual searching, extracting data, quality assessment, data checking, statistical analysis, double data checking, and manuscript writing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s41182-019-0165-6) contains supplementary material, which is available to authorized users.


title: Developing a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model in a Viral Membrane

text: [Image: see text] This technical study describes all-atom modeling and simulation of a fully glycosylated full-length SARS-CoV-2 spike (S) protein in a viral membrane. First, starting from PDB: 6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite. Then, using the recently determined most occupied glycoforms, 22 N-glycans and 1 O-glycan of each monomer were modeled using Glycan Reader & Modeler in CHARMM-GUI. These fully glycosylated full-length S protein model structures were assessed and further refined against the low-resolution data in their respective experimental maps using ISOLDE. We then used CHARMM-GUI Membrane Builder to place the S proteins in a viral membrane and performed all-atom molecular dynamics simulations. All structures are available in CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19) so that researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.


title: Evolution of Biochip Technology: A Review from Lab-on-a-Chip to Organ-on-a-Chip

text: Following the advancements in microfluidics and lab-on-a-chip (LOC) technologies, a novel biomedical application for microfluidic based devices has emerged in recent years and microengineered cell culture platforms have been created. These micro-devices, known as organ-on-a-chip (OOC) platforms mimic the in vivo like microenvironment of living organs and offer more physiologically relevant in vitro models of human organs. Consequently, the concept of OOC has gained great attention from researchers in the field worldwide to offer powerful tools for biomedical researches including disease modeling, drug development, etc. This review highlights the background of biochip development. Herein, we focus on applications of LOC devices as a versatile tool for POC applications. We also review current progress in OOC platforms towards body-on-a-chip, and we provide concluding remarks and future perspectives for OOC platforms for POC applications.


title: Influenza virus and cell signaling pathways

text: Influenza viruses comprise a major class of human respiratory pathogens, responsible for causing morbidity and mortality worldwide. Influenza A virus, due to its segmented RNA genome, is highly subject to mutation, resulting in rapid formation of variants. During influenza infection, viral proteins interact with host proteins and exploit a variety of cellular pathways for their own benefit. Influenza virus inhibits the synthesis of these cellular proteins and facilitates expression of its own proteins for viral transcription and replication. Infected cell pathways are hijacked by an array of intracellular signaling cascades such as NF-κB signaling, PI3K/Akt pathway, MAPK pathway, PKC/PKR signaling and TLR/RIG-I signaling cascades. This review presents a research update on the subject and discusses the impact of influenza viral infection on these cell signaling pathways.


A Local Response to COVID-19 for Advanced Liver Disease: Current Model of Care, Challenges and Opportunities


title: Viral networks and detection of potential zoonotic viruses in bats and rodents: A worldwide analysis

text: Bats and rodents are recognized to host a great diversity of viruses and several important viral zoonoses, but how this viral diversity is structured and how viruses are connected, shared and distributed among host networks is not well understood. To address this gap in knowledge, we compared the associative capacity of the host–virus networks in rodents and bats with the identification of those viruses with zoonotic potential. A virus database, detected by molecular methods, was constructed in the two taxonomic groups. We compiled 5,484 records: 825 in rodents and 4,659 in bats. We identified a total of 173 and 166 viruses, of which 53 and 40 are zoonotic viruses, in rodents and bats, respectively. Based on a network theory, a non‐directed bipartite host–virus network was built for each group. Subsequently, the networks were collapsed to represent the connections among hosts and viruses. We identified both discrete and connected communities. We observed a greater degree of connectivity in bat viruses and more discrete communities in rodents. The Coronaviridae recorded in bats have the highest values of degree, betweenness and closeness centralities. In rodents, higher degree positions were distributed homogeneously between viruses and hosts. At least in our database, a higher proportion of rodent viruses were zoonotic. Rodents should thus not be underestimated as important reservoirs of zoonotic disease. We found that viruses were more frequently shared among bats than in rodents. Network theory can reveal some macroecological patterns and identify risks that were previously unrecognized. For example, we found that parvovirus in megabats and Gbagroube virus in rodents may represent a zoonotic risk due to the proximity to humans and other zoonotic viruses. We propose that epidemiological surveillance programmes should consider the connectivity of network actors as a measure of the risks of dispersion and transmission.


title: β-Glucan extracts from the same edible shiitake mushroom Lentinus edodes produce differential in-vitro immunomodulatory and pulmonary cytoprotective effects — Implications for coronavirus disease (COVID-19) immunotherapies

text: Abstract Coronavirus pneumonia is accompanied by rapid virus replication, where a large number of inflammatory cell infiltration and cytokine storm may lead to acute lung injury, acute respiratory distress syndrome (ARDS) and death. The uncontrolled release of pro-inflammatory cytokines, including interleukin (IL)-1β and IL-6, is associated with ARDS. This constituted the first study to report on the variability in physicochemical properties of β-glucans extracts from the same edible mushroom Lentinus edodes on reduction of these pro-inflammatory cytokines and oxidative stress. Specifically, the impact on the immunomodulatory and cytoprotective properties of our novel ‘in house’ (IH-Lentinan, IHL) and a commercial (Carbosynth-Lentinan, CL) Lentinan extract were investigated using in vitro models of lung injury and macrophage phagocytosis. CL comprised higher amounts of α-glucans and correspondingly less β-glucans. The two lentinan extracts demonstrated varying immunomodulatory activities. Both Lentinan extracts reduced cytokine induced NF-κB activation in human alveolar epithelial A549 cells, with the IHL extract proving more effective at lower doses. In contract, in activated THP-1 derived macrophages, the CL extract more effectively attenuated pro-inflammatory cytokine production (TNF-α, IL-8, IL-2, IL-6, IL-22) as well as TGF-β and IL-10. The CL extract attenuated oxidative stress induced early apoptosis, while the IHL extract attenuated late apoptosis. Our findings demonstrate significant physicochemical differences between Lentinan extracts, which produce differential in vitro immunomodulatory and pulmonary cytoprotective effects that may also have positive relevance to candidate COVID-19 therapeutics targeting cytokine storm.


title: CKD of Unknown Origin in Central America: The Case for a Mesoamerican Nephropathy

text: An epidemic of chronic kidney disease of unknown origin has emerged in the last decade in Central America and has been named Mesoamerican nephropathy. This form of chronic kidney disease is present primarily in young male agricultural workers from communities along the Pacific coast, especially workers in the sugarcane fields. In general, these men have a history of manual labor under very hot conditions in agricultural fields. Clinically, they usually present with normal or mildly elevated systemic blood pressure, asymptomatic yet progressive reduction in estimated glomerular filtration rate, low-grade non-nephrotic proteinuria, and often hyperuricemia and or hypokalemia. Diabetes is absent in this population. Kidney biopsies that have been performed show a chronic tubulointerstitial disease with associated secondary glomerulosclerosis and some signs of glomerular ischemia. The cause of the disease is unknown; this article discusses and analyzes some of the etiologic possibilities currently under consideration. It is relevant to highlight that recurrent dehydration is suggested in multiple studies, a condition that possibly could be exacerbated in some cases by other conditions, including the use of nonsteroidal anti-inflammatory agents. At present, Mesoamerican nephropathy is a medical enigma yet to be solved.


title: Membrane Potential Depolarization as a Triggering Mechanism for Vpu-Mediated HIV-1 Release

text: Vpu, a component unique to HIV-1, greatly enhances the efficiency of viral particle release by unclear mechanisms. This Vpu function is intrinsically linked to its channel-like structure, which enables it to interfere with homologous transmembrane structures in infected cells. Because Vpu interacts destructively with host background K(+) channels that set the cell resting potential, we hypothesized that Vpu might trigger viral release by destabilizing the electric field across a budding membrane. Here, we found that the efficiency of Vpu-mediated viral release is inversely correlated with membrane potential polarization. By inhibiting the background K(+) currents, Vpu dissipates the voltage constraint on viral particle discharge. As a proof of concept, we show that HIV-1 release can be accelerated by externally imposed depolarization alone. Our findings identify the trigger of Vpu-mediated release as a manifestation of the general principle of depolarization-stimulated exocytosis.


title: The effect of collaboration and IT competency on reverse logistics competency - Evidence from Brazilian supply chain executives

text: Business models have being designed, worldwide, to create sustainability competencies and in particular to incorporate reverse logistics, but Brazilian executives have not yet fully adhered to Law 12,305 on solid waste and reverse logistics. What would be the Brazilian executives' perception about reverse logistics competency and the support provided by a collaborative and IT competency? The objective of the paper is to investigate the effects of collaboration and IT competency in developing reverse logistics competency, as a strategy, and its consequences in economic and environmental performance. A survey was performed with 320 Brazilian supply chain executives and analyzed using Structural Equation Modeling. The models demonstrated that collaboration has a direct positive influence on the development of reverse logistics competency, by executives' point of view. The moderation effect between collaboration and IT competency for reverse logistics was not confirmed, since it was adopted a strategic view of reverse logistics. Therefore, despite there was not a moderation effect, IT presented a lower direct effect on reverse logistics competency. Results reinforce that organizations that develop reverse logistics competency tend to improve their economic and environmental performances.


title: Differential premature termination of transcription as a proposed mechanism for the regulation of coronavirus gene expression.

text: We propose that the different subgenomic mRNA levels of coronaviruses are controlled through differential premature termination of transcription, and are modulated by the relative strength of transcriptional initiation/blockage events. We present the complete set of sequences covering the leader encoding and intergenic regions of the MHV-A59 strain. A computer-assisted analysis of the two now complete sets of these sequences of strain IBV-M42 and MHV-A59 shows that, in contrast to the previous theory, differences amongst stabilities of intermolecular base-pairings between the leader and the intergenic regions are not sufficient to determine the mRNA gradients in both MHV and IBV infected cells. Neither can the accessibility of the interacting regions on the leader and the negative stranded genome, as revealed by secondary structure analysis, explain the mRNA levels. The nested gene organisation itself, on the other hand, could be responsible for observed mRNA levels gradually increasing with gene order. Relatively slow new initiation events at intergenic regions are proposed to block elongation of passing transcripts which, via temporary pausing, can cause premature termination of transcription. This effects longer transcripts more than shorter ones.


title: Zoonotic origin and transmission of Middle East respiratory syndrome coronavirus in the UAE

text: Since the emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, there have been a number of clusters of human-to-human transmission. These cases of human-to-human transmission involve close contact and have occurred primarily in healthcare settings, and they are suspected to result from repeated zoonotic introductions. In this study, we sequenced whole MERS-CoV genomes directly from respiratory samples collected from 23 confirmed MERS cases in the United Arab Emirates (UAE). These samples included cases from three nosocomial and three household clusters. The sequences were analysed for changes and relatedness with regard to the collected epidemiological data and other available MERS-CoV genomic data. Sequence analysis supports the epidemiological data within the clusters, and further, suggests that these clusters emerged independently. To understand how and when these clusters emerged, respiratory samples were taken from dromedary camels, a known host of MERS-CoV, in the same geographic regions as the human clusters. Middle East respiratory syndrome coronavirus genomes from six virus-positive animals were sequenced, and these genomes were nearly identical to those found in human patients from corresponding regions. These data demonstrate a genetic link for each of these clusters to a camel and support the hypothesis that human MERS-CoV diversity results from multiple zoonotic introductions.


title: SARS Molecular Detection External Quality Assurance

text: Inactivated severe acute respiratory syndrome–associated coronavirus samples were used for an external quality assurance study within the World Health Organization SARS Reference and Verification Network and other reference institutions. Of 58 participants, 51 correctly detected virus in all samples >9,400 RNA copies per milliliter and none in negative samples. Commercial test kits significantly improved the outcome.


title: Analysis of synonymous codon usage in Hepatitis A virus

text: BACKGROUND: Hepatitis A virus is the causative agent of type A viral hepatitis, which causes occasional acute hepatitis. Nevertheless, little information about synonymous codon usage pattern of HAV genome in the process of its evolution is available. In this study, the key genetic determinants of codon usage in HAV were examined. RESULTS: The overall extent of codon usage bias in HAV is high in Picornaviridae. And the patterns of synonymous codon usage are quite different in HAV genomes from different location. The base composition is closely correlated with codon usage bias. Furthermore, the most important determinant that results in such a high codon bias in HAV is mutation pressure rather than natural selection. CONCLUSIONS: HAV presents a higher codon usage bias than other members of Picornaviridae. Compositional constraint is a significant element that influences the variation of synonymous codon usage in HAV genome. Besides, mutation pressure is supposed to be the major factor shaping the hyperendemic codon usage pattern of HAV.


title: Diagnosis and Monitoring of Hepatic Injury. II. Recommendations for Use of Laboratory Tests in Screening, Diagnosis, and Monitoring

text: Purpose: To review information on the use of laboratory tests in screening, diagnosis, and monitoring of acute and chronic hepatic injury. Data Sources and Study Selection: A MEDLINE search was performed for key words related to hepatic diseases, including acute hepatitis, chronic hepatitis, alcoholic hepatitis, cirrhosis, hepatocellular carcinoma, and etiologic causes. Abstracts were reviewed, and articles discussing use of laboratory tests selected for review. Additional articles were selected from the references. Guideline Preparation and Review: Drafts of the guidelines were posted on the Internet, presented at the AACC Annual Meeting in 1999, and reviewed by experts. Areas requiring further amplification or literature review were identified for further analysis. Specific recommendations were made based on analysis of published data and evaluated for strength of evidence and clinical impact. Recommendations: Although many specific recommendations are made in the guidelines, only some summary recommendations are listed here. In acute hepatic injury, prothrombin time and, to a lesser extent, total bilirubin are the best indicators of severity of disease. Although ALT is useful for detecting acute and chronic hepatic injury, it is not related to severity of acute hepatic injury and only weakly related to severity of chronic hepatic injury. Specific tests of viral markers should be the initial differential tests in both acute and chronic hepatic injury; when positive, they are also useful for monitoring recovery from hepatitis B and C.


title: Effectively Communicating the Uncertainties Surrounding Ebola Virus Transmission

text: The current Ebola virus outbreak has highlighted the uncertainties surrounding many aspects of Ebola virus virology, including routes of transmission. The scientific community played a leading role during the outbreak—potentially, the largest of its kind—as many of the questions surrounding ebolaviruses have only been interrogated in the laboratory. Scientists provided an invaluable resource for clinicians, public health officials, policy makers, and the lay public in understanding the progress of Ebola virus disease and the continuing outbreak. Not all of the scientific communication, however, was accurate or effective. There were multiple instances of published articles during the height of the outbreak containing potentially misleading scientific language that spurred media overreaction and potentially jeopardized preparedness and policy decisions at critical points. Here, we use articles declaring the potential for airborne transmission of Ebola virus as a case study in the inaccurate reporting of basic science, and we provide recommendations for improving the communication about unknown aspects of disease during public health crises.


title: Development and evaluation of multiplex real-time RT-PCR assays for seasonal, pandemic A/H1pdm09 and avian A/H5 influenza viruses detection

text: Since the pandemic influenza A (H1N1) 2009 ((H1N1)pdm09) virus spread all over the world, the (H1N1)pdm09 virus has been circulating with seasonal influenza viruses. We developed rapid and sensitive one-step multiplex real-time RT-PCR assays (rRT-PCR) for simultaneous detection of influenza viruses currently circulating in humans, and the avian A/H5 virus. The detection limit of each assay was 4.8 to 1 copies per reaction and no cross-reactivity with other major respiratory pathogens was found. Analytical positive predictive value (PPV), negative predictive value (NPV) sensitivity and specificity were 100%, 94.1%, 93.7% and 100%, respectively. Clinical evaluation revealed that 1,976 (16.5%) of 11,963 throat swabs from patients with respiratory symptoms were confirmed as 1,651 (83.6%) A/H1pdm09, 308 (15.6%) A/H3 and 17 (0.8%) B virus during the 2010–2011 influenza season. Collectively, the multiplex rRT-PCR assays described here provide a practical tool for reliable implementation of influenza surveillance and diagnosis.


title: Serological and molecular rapid diagnostic tests for Toxoplasma infection in humans and animals

text: Infection by Toxoplasma gondii is prevalent worldwide. The parasite can infect a broad spectrum of vertebrate hosts, but infection of fetuses and immunocompromised patients is of particular concern. Easy-to-perform, robust, and highly sensitive and specific methods to detect Toxoplasma infection are important for the treatment and management of patients. Rapid diagnostic methods that do not sacrifice the accuracy of the assay and give reproducible results in a short time are highly desirable. In this context, rapid diagnostic tests (RDTs), especially with point-of-care (POC) features, are promising diagnostic methods in clinical microbiology laboratories, especially in areas with minimal laboratory facilities. More advanced methods using microfluidics and sensor technology will be the future trend. In this review, we discuss serological and molecular-based rapid diagnostic tests for detecting Toxoplasma infection in humans as well as animals.


title: Funding gap for locust crisis

text: East Africa is experiencing the worst desert locust outbreak in decades. Climate events have facilitated breeding of the swarming pest across the region, and with a surge in the locust population expected in coming weeks urgent action is needed to avert a humanitarian crisis.


title: Manifestations cutanées de la panleucopénie féline chez un chat

text: Résumé Un chat adulte exprimant une forme nerveuse et entéritique de la panleucopénie féline développe des lésions cutanées purpuriques. L’analyse histopathologique de biopsies cutanées met en évidence des lésions de vascularite non leucocytoclasique à prédominance mononucléée. Les vascularites sont particulièrement rares chez le chat et souvent idiopathiques. La démarche diagnostique comprend l’éviction de plusieurs hypothèses, médicamenteuses ou virales (virus d’immunodéficience féline [FIV], virus leucémogène félin [FeLV], péritonite infectieuse féline [PIF]). Ce cas rappelle le purpura Henoch-Schönlein, cause la plus fréquente de vascularite chez les enfants, qui serait associé à diverses causes dont une infection par le parvovirus B19. Summary Purpuric cutaneous lesions occurred on an adult neutered cat diagnosed with a nervous and enteritic form of panleukopenia. Histopathology of cutaneous samples revealed predominant mononuclear non-leukocytoclasic vasculitis. Feline vasculitis has rarely been reported and etiological agents are difficult to identify. Differential diagnosis ruled out cutaneous drug reaction and several viral hypotheses such as FIV, FeLV and FIP. This case is similar to the children's most frequently vasculitis: the Henoch-Schönlein purpura, which is probably caused by the parvovirus B19.


title: Emerging priorities for microbial metagenome research

text: Overwhelming anthropogenic activities lead to deterioration of natural resources and the environment. The microorganisms are considered desirable, due to their suitability for easy genetic manipulation and handling. With the aid of modern biotechnological techniques, the culturable microorganisms have been widely exploited for the benefit of mankind. Metagenomics, a powerful tool to access the abundant biodiversity of the environmental samples including the unculturable microbes, to determine microbial diversity and population structure, their ecological roles and expose novel genes of interest. This review focuses on the microbial adaptations to the adverse environmental conditions, metagenomic techniques employed towards microbial biotechnology. Metagenomic approach helps to understand microbial ecology and to identify useful microbial derivatives like antibiotics, toxins, and enzymes with diverse and enhanced function. It also summarizes the application of metagenomics in clinical diagnosis, improving microbial ecology, therapeutics, xenobiotic degradation and impact on agricultural crops.


title: Chapter Sixteen Toward Mucosal DNA Delivery: Structural Modularity in Vaccine Platform Design

text: Abstract Hepatitis E virus is a small, nonenveloped RNA virus that is feco-orally transmitted and causes viral hepatitis in humans. A virus-like particle (VLP) expressed and purified from insect cells shares several properties with the virion but can be manipulated quite extensively through genetic engineering or chemical modification. This has exciting implications for exploiting the VLP as a nanocarrier for foreign epitopes or encapsulated deliverables. By exhaustively studying the structure of the virus, we have been successful in designing and synthesizing chimerized VLPs that either carry foreign epitopes, are capable of encapsulating foreign DNA, or both. Preliminary studies show that these particles provide specific and strong immune responses in mice when orally delivered. To appreciate the full potential of HEV VLPs, we have highlighted various properties of the virus with a strong focus on the VLP structure and the key features that make it suitable for oral delivery.


title: The establishment of reference sequence for SARS‐CoV‐2 and variation analysis

text: Starting around December 2019, an epidemic of pneumonia, which was named COVID‐19 by the World Health Organization, broke out in Wuhan, China, and is spreading throughout the world. A new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses was soon found to be the cause. At present, the sensitivity of clinical nucleic acid detection is limited, and it is still unclear whether it is related to genetic variation. In this study, we retrieved 95 full‐length genomic sequences of SARAS‐CoV‐2 strains from the National Center for Biotechnology Information and GISAID databases, established the reference sequence by conducting multiple sequence alignment and phylogenetic analyses, and analyzed sequence variations along the SARS‐CoV‐2 genome. The homology among all viral strains was generally high, among them, 99.99% (99.91%‐100%) at the nucleotide level and 99.99% (99.79%‐100%) at the amino acid level. Although overall variation in open‐reading frame (ORF) regions is low, 13 variation sites in 1a, 1b, S, 3a, M, 8, and N regions were identified, among which positions nt28144 in ORF 8 and nt8782 in ORF 1a showed mutation rate of 30.53% (29/95) and 29.47% (28/95), respectively. These findings suggested that there may be selective mutations in SARS‐COV‐2, and it is necessary to avoid certain regions when designing primers and probes. Establishment of the reference sequence for SARS‐CoV‐2 could benefit not only biological study of this virus but also diagnosis, clinical monitoring and intervention of SARS‐CoV‐2 infection in the future.


title: Significant Changes of Peripheral T Lymphocyte Subsets in Patients with Severe Acute Respiratory Syndrome

text: This report demonstrates that a rapid decrease of peripheral T cell subsets is a unique characteristic in patients with SARS during acute infection, although total white blood cell counts, red blood cell counts, and platelet counts remain relatively normal. In recovering patients, a rapid and dramatic restoration of peripheral T cell subsets was seen in the periphery. Although the underlying mechanism of the acute decrease of peripheral T cell subsets observed in patients with SARS during the acute stage remains unknown, this clinical characteristic can facilitate an earlier and more accurate diagnosis of SARS.


title: Emodin is a novel alkaline nuclease inhibitor that suppresses herpes simplex virus type 1 yields in cell cultures

text: BACKGROUND AND PURPOSE: Most antiviral therapies directed against herpes simplex virus (HSV) infections are limited to a small group of nucleoside analogues that target the viral polymerase. Extensive clinical use of these drugs has led to the emergence of resistant viral strains, mainly in immunocompromised patients. This highlights the need for the development of new anti-herpesviral drugs with novel targets. Herein the effects of a plant anthraquinone, emodin, on the HSV-1 alkaline nuclease activity and virus yields were investigated. EXPERIMENTAL APPROACH: HSV-1 alkaline nuclease activity was examined by nuclease activity assay. Inhibition of virus yields was measured by plaque reduction assay and immunohistochemical staining. Interaction between emodin and alkaline nuclease was analysed by docking technology. KEY RESULTS: Emodin specifically inhibited the nuclease activity of HSV-1 UL12 alkaline nuclease in a biochemical assay. Plaque reduction assay revealed that emodin reduced the plaque formation with an EC(50) of 21.5±4.4 μM. Immunohistochemical staining using the anti-nucleocapsid protein antibody demonstrated that emodin induced the accumulation of viral nucleocapsids in the nucleus in a dose-dependent manner. Docking analysis further suggested that the inhibitory effect of emodin on the UL12 activity may result from the interaction between emodin and critical catalytic amino acid residues of UL12. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that emodin is a potent anti-HSV agent that inhibits the yields of HSV-1 via the suppression of a novel target, UL12.


title: Global biosecurity in a complex, dynamic world

text: Biosecurity is emerging as a major global health priority for which innovative and unprecedented solutions are needed. Biosecurity is a challenging biocomplexity problem involving multifaceted processes such as interactions between humans and nonhuman biota, anthropogenic environmental and ecological factors, and socioeconomic and political pressures. Key to an effective biosecurity strategy will be fundamental understanding of evolutionary, anthropogenic and environmental driving forces at play in transmission and perpetuation of infectious diseases. Biosecurity solutions will depend on increased support of basic biomedical research and public education, enhanced healthcare preparedness, alternative strategies for ensuringsafety, and improved interagency cooperation regarding global health policy. © 2008 Wiley Periodicals, Inc. Complexity, 2008.


Unexpected high mortality in COVID-19 and diabetic ketoacidosis()()


title: Outbreaks of Middle East Respiratory Syndrome in Two Hospitals Initiated by a Single Patient in Daejeon, South Korea

text: BACKGROUND: A Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak in South Korea in 2015 started by a single imported case and was amplified by intra- and inter-hospital transmission. We describe two hospital outbreaks of MERS-CoV infection in Daejeon caused by a single patient who was infected by the first Korean case of MERS. MATERIALS AND METHODS: Demographic and clinical information involving MERS cases in the Daejeon cluster were retrospectively collected and potential contacts and exposures were assessed. The incubation periods and serial intervals were estimated. Viral RNAs were extracted from respiratory tract samples obtained from the index case, four secondary cases and one tertiary case from each hospital. The partial S2 domain of the MERS-CoV spike was sequenced. RESULTS: In Daejeon, a MERS patient (the index case) was hospitalized at Hospital A in the first week of illness and was transferred to Hospital B because of pneumonia progression in the second week of illness, where he received a bronchoscopic examination and nebulizer therapy. A total of 23 secondary cases (10 in Hospital A and 13 in Hospital B) were detected among patients and caregivers who stayed on the same ward with the index case. There were no secondary cases among healthcare workers. Among close hospital contacts, the secondary attack rate was 15.8% (12/76) in Hospital A and 14.3% (10/70) in Hospital B. However, considering the exposure duration, the incidence rate was higher in Hospital B (7.7/100 exposure-days) than Hospital A (3.4/100 exposure-days). In Hospital B, the median incubation period was shorter (4.6 days vs. 10.8 days), the median time to pneumonia development was faster (3 days vs. 6 days) and mortality was higher (70% vs. 30.8%) than in Hospital A. MERS-CoV isolates from 11 cases formed a single monophyletic clade, with the closest similarity to strains from Riyadh. CONCLUSION: Exposure to the MERS case in the late stage (2nd week) of diseases appeared to increase the risk of transmission and was associated with shorter incubation periods and rapid disease progression among those infected. Early detection and isolation of cases is critical in preventing the spread of MERS in the hospital and decreasing the disease severity among those infected.


title: COVID-19 preparedness: Clinical pharmacy services remote staffing in a quaternary, level I trauma and comprehensive stroke center

text: DISCLAIMER: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: The rapid spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has strained the resources of healthcare systems around the world. In accordance with recommendations from the World Health Organization, Centers for Disease Control and Prevention, and US Department of Defense, Intermountain Medical Center (IMED) in Murray, UT, has developed a plan to provide remote clinical pharmacy services to protect the health of pharmacy caregivers while maintaining appropriate clinical pharmacy coverage to optimally care for patients. SUMMARY: The utilization of telemedicine technology permits clinical pharmacists to readily communicate with nurses, physicians, other caregivers, and patients. We have identified strategies to allow clinical pharmacists to continue to participate in daily rounds, provide consultations under collaborative practice agreements, verify medication orders, collect medication histories, provide antimicrobial stewardship, and deliver medication education to patients from off-site locations. The pharmacy department at IMED proactively tested telemedicine technologies, defined the roles of clinical pharmacists, and identified communication strategies prior to a rapid rise of COVID-19 in the state of Utah. CONCLUSION: The proactive measures described can help ensure that pharmacy caregivers have appropriate remote access and are capable of confidently using the resources. These steps allow for optimal care of hospitalized patients and promote social distancing, which may have the added benefit of decreasing the spread of SARS-CoV-2 among patients and caregivers.


title: Response to SARS-CoV-2 Pandemic in a Non-COVID-19 Designated Latin-American Neurosurgery Department

text: BACKGROUND Mexico declared the first case of novel coronavirus disease (COVID-19) in February 2020. At the time we write this article, our country is facing a community spread phase, expecting a rapid increase in the number of cases and fatalities. The Fray Antonio Alcalde Civil Hospital of Guadalajara has been declared a non-COVID-19 hospital with the mission of providing care to patients already registered and also those transferred from neurosurgical departments of neighboring centers, which have been converted into COVID-19 only hospitals. METHODS An organized response regarding personnel, surgical case selection, operating room behavior, and facility reorganization were designed to prevent an internal coronavirus outbreak in the neurosurgery department at the Fray Antonio Alcalde Civil Hospital of Guadalajara. RESULTS Distancing actions by the staff and residents, including ward case discussions, neurosurgery rounds, and classes, will be carried out virtually. We classified neurosurgical patients into 4 groups depending on whether their condition demands care in 0-6 hours, 6-48 hours, 48 hours to 14 days, and >14 days. Subsequently, a questionnaire with epidemiologic, radiologic, clinical, and serologic criteria will be applied to determine the risk of COVID-19 infection to define to which area they are going to be transferred according to the different risk zones in our facility. CONCLUSIONS Despite not being a COVID-19 center, we consider all patients at the neurosurgical ward and staff members as asymptomatic carriers or infected in the preclinical period. Specific measures must be taken to ensure the safety and care of neurosurgical patients and medical staff during the community spread phase.


title: Swine enteric colibacillosis: diagnosis, therapy and antimicrobial resistance

text: Intestinal infection with enterotoxigenic Escherichia coli (ETEC) is an important disease in swine resulting in significant economic losses. Knowledge about the epidemiology, the diagnostic approach and methods of control are of fundamental importance to tackle the disease. The ETEC causing neonatal colibacillosis mostly carry the fimbriae F4 (k88), F5 (k99), F6 (987P) or F41, while the ETEC of post-weaning diarrhoea carry the fimbriae F4 (k88) and F18. These fimbriae adhere to specific receptors on porcine intestinal brush border epithelial cells (enterocytes), starting the process of enteric infection. After this colonization, the bacteria produce one or more enterotoxins inducing diarrhoea, such as the heat stable toxin a (STa), the heat stable toxin b (STb), and the heat labile toxin (LT). A role in the pathogenesis of the disease was demonstrated for these toxins. The diagnosis of enteric colibacillosis is based on the isolation and quantification of the pathogenic E.coli coupled with the demonstration by PCR of the genes encoding for virulence factors (fimbriae and toxins). The diagnostic approach to enteric colibacillosis must consider the differential diagnosis and the potential different causes that can be involved in the outbreak. Among the different methods of control of colibacillosis, the use of antimicrobials is widely practiced and antibiotics are used in two main ways: as prophylactic or metaphylactic treatment to prevent disease and for therapeutic purposes to treat diseased pigs. An accurate diagnosis of enteric colibacillosis needs an appropriate sampling for the isolation and quantification of the ETEC responsible for the outbreak by using semi-quantitative bacteriology. Definitive diagnosis is based on the presence of characteristic lesions and results of bacteriology along with confirmation of appropriate virulence factors to identify the isolated E.coli. It is important to confirm the diagnosis and to perform antimicrobial sensitivity tests because antimicrobial sensitivity varies greatly among E. coli isolates. Growing concern on the increase of antimicrobial resistance force a more rational use of antibiotics and this can be achieved through a correct understanding of the issues related to antibiotic therapy and to the use of antibiotics by both practitioners and farmers.