title: Optimizing the refolding conditions of self-assembling polypeptide nanoparticles that serve as repetitive antigen display systems

text: Abstract Nanoparticles show great promise as potent vaccine candidates since they are readily taken up by the antigen presenting cells of the immune system. The particle size and the density of the B cell epitopes on the surface of the particles greatly influences the strength of the humoral immune response. We have developed a novel type of nanoparticle composed of peptide building blocks (Raman et al., 2006) and have used such particles to design vaccines against malaria and SARS (Kaba et al., 2009; Pimentel et al., 2009). Here we investigate the biophysical properties and the refolding conditions of a prototype of these self-assembling polypeptide nanoparticles (SAPNs). SAPNs are formed from a peptide containing a pentameric and a trimeric coiled-coil domain. At near physiological conditions the peptide self-assembles into about 27nm, roughly spherical SAPNs. The average size of the SAPNs increases with the salt concentration. The optimal pH for their formation is between 7.5 and 8.5, while aggregation occurs at lower and higher values. A glycerol concentration of about 5% v/v is required for the formation of SAPNs with regular spherical shapes. These studies will help to optimize the immunological properties of SAPNs.


title: Application of CRISPR/Cas9 to human-induced pluripotent stem cells: from gene editing to drug discovery

text: Human-induced pluripotent stem cells (hiPSCs) and CRISPR/Cas9 gene editing system represent two instruments of basic and translational research, which both allow to acquire deep insight about the molecular bases of many diseases but also to develop pharmacological research. This review is focused to draw up the latest technique of gene editing applied on hiPSCs, exploiting some of the genetic manipulation directed to the discovery of innovative therapeutic strategies. There are many expediencies provided by the use of hiPSCs, which can represent a disease model clinically relevant and predictive, with a great potential if associated to CRISPR/Cas9 technology, a gene editing tool powered by ease and precision never seen before. Here, we describe the possible applications of CRISPR/Cas9 to hiPSCs: from drug development to drug screening and from gene therapy to the induction of the immunological response to specific virus infection, such as HIV and SARS-Cov-2.


Infectio: contribución al conocimiento de las enfermedades infecciosas en Colombia


title: Isoxazolidine Conjugates of N3-Substituted 6-Bromoquinazolinones—Synthesis, Anti-Varizella-Zoster Virus, and Anti-Cytomegalovirus Activity

text: 1,3-Dipolar cycloaddition of N-methyl C-(diethoxyphosphoryl) nitrone to N3-substituted 6-bromo-2-vinyl-3H-quinazolin-4-ones gave (3-diethoxyphosphoryl) isoxazolidines substituted at C5 with quinazolinones modified at N3. All isoxazolidine cycloadducts were screened for antiviral activity against a broad spectrum of DNA and RNA viruses. Several isoxazolidines inhibited the replication of both thymidine kinase wild-type and deficient (TK(+) and TK(−)) varicella-zoster virus strains at EC(50) in the 5.4–13.6 μΜ range, as well as human cytomegalovirus (EC(50) = 8.9–12.5 μΜ). Isoxazolidines trans-11b, trans-11c, trans-11e, trans-11f/cis-11f, trans-11g, trans-11h, and trans-11i/cis-11i exhibited moderate cytostatic activity towards the human lymphocyte cell line CEM (IC(50) = 9.6–17 μM).


title: Development of chemical inhibitors of the SARS coronavirus: Viral helicase as a potential target

text: Abstract Severe acute respiratory syndrome (SARS) was the first pandemic in the 21st century to claim more than 700 lives worldwide. However, effective anti-SARS vaccines or medications are currently unavailable despite being desperately needed to adequately prepare for a possible SARS outbreak. SARS is caused by a novel coronavirus, and one of its components, a viral helicase, is emerging as a promising target for the development of chemical SARS inhibitors. In the following review, we describe the characterization, family classification, and kinetic movement mechanisms of the SARS coronavirus (SCV) helicase—nsP13. We also discuss the recent progress in the identification of novel chemical inhibitors of nsP13 in the context of our recent discovery of the strong inhibition of the SARS helicase by natural flavonoids, myricetin and scutellarein. These compounds will serve as important resources for the future development of anti-SARS medications.


title: Teicoplanin: an alternative drug for the treatment of coronavirus COVID-19?

text: In December 2019, a new coronavirus, named SARS-CoV-2, has emerged from China causing pneumonia outbreaks first in the Wuhan region and have now spread worldwide because of its probable high transmission efficiency. Due to the lack of efficient and specific treatments and the need to contain the epidemic, drug repurposing appears to be the best tool to find therapeutic solution. Chloroquine, remdesivir, lopinavir, ribavirin or ritonavir have shown efficacy to inhibit coronavirus in vitro. Teicoplanin, an antibiotic used to treat staphylococci infection, previously showed efficacy to inhibit the first stage of MERS-coronarivus viral cycle in human cells. This activity is conserved on the SARS-Cov-2, thus placing teicoplanin as a potential treatment for patients with this virus.


COVID-19: What is next for nursing in public health emergency?


title: SCHOOL of nature: ligand-independent immunomodulatory peptides

text: Groundbreaking studies in protein biophysics have identified the mechanisms of transmembrane signaling at the level of druggable protein–protein interactions (PPIs). This resulted in the development of the signaling chain homooligomerization (SCHOOL) strategy to modulate cell responses using receptor-specific peptides. Inspired by nature, these short peptides use ligand-independent mechanisms of receptor inhibition and demonstrate potent efficacy in vitro and in vivo. The SCHOOL strategy is especially important when receptor ligands are unknown. An example is the triggering receptor expressed on myeloid cells-1 (TREM-1) receptor, an emerging therapeutic target involved in the pathogenesis of most inflammatory diseases. Here, I discuss advances in the field with a focus on TREM-1 inhibitory SCHOOL peptides that offer new hope for a ‘magic bullet’ cure for cancer, arthritis, sepsis, retinopathy, and other medical challenges.


title: The need to manage the risk of thromboembolism in COVID-19 patients

text: COVID-19 first presented in Wuhan, Hubei Province, China, in December 2019. Thought to be of zoonotic origin, it has been named SARS-CoV-2 (COVID-19) and has spread rapidly. As of April 20(th), 2020, there have been more than 2.4 million cases recorded worldwide. The inflammatory process, cytokine storm, and lung injury that are associated with COVID-19 can put patients at an increased risk of thrombosis. It is uncertain what the total incidences of thrombotic events in COVID-19 patients is currently at. Those with more severe disease and with other risk factors, including increasing age, male sex, obesity, cancer, comorbidities, and intensive care unit admission, are at higher risk of these events. However, there is little international guidance on managing these risks in COVID-19 patients. In this paper, we explore the current evidence and theories surrounding thrombosis in these unique patients and reflect on experience from our center.


title: The clinical value of two combination regimens in the Management of Patients Suffering from Covid-19 pneumonia: a single centered, retrospective, observational study

text: BACKGROUND: There is no identified pharmacological therapy for COVID-19 patients, where potential therapeutic strategies are underway to determine effective therapy under such unprecedented pandemic. Therefore, combination therapies may have the potential of alleviating the patient’s outcome. This study aimed at comparing the efficacy of two different combination regimens in improving outcomes of patients infected by novel coronavirus (COVID-19). METHODS: This is a single centered, retrospective, observational study of 60 laboratory-confirmed COVID-19 positive inpatients (≥18 years old) at two wards of the Baqiyatallah Hospital, Tehran, Iran. Patient’s data including clinical and laboratory parameters were recorded. According to the drug regimen, the patients were divided into two groups; group I who received regimen I consisting azithromycin, prednisolone, naproxen, and lopinavir/ritonavir and group II who received regimen II including meropenem, levofloxacin, vancomycin, hydroxychloroquine, and oseltamivir. RESULTS: The oxygen saturation (SpO2) and temperature were positively changed in patients receiving regimen I compared to regimen II (P = 0.013 and P = 0.012, respectively). The serum level of C-reactive protein (CRP) changed positively in group I (P < 0.001). Although there was a significant difference in platelets between both groups (75.44 vs 51.62, P < 0.001), their change did not clinically differ between two groups. The findings indicated a significant difference of the average length of stay in hospitals (ALOS) between two groups, where the patients under regimen I showed a shorter ALOS (6.97 vs 9.93, P = 0.001). CONCLUSION: This study revealed the beneficial effect of the short-term use of low-dose prednisolone in combination with azithromycin, naproxen and lopinavir/ritonavir (regimen I), in decreasing ALOS compared to regimen II. Since there is still lack of evidence for safety of this regimen, further investigation in our ongoing follow-up to deal with COVID-19 pneumonia is underway. [Figure: see text]


title: Chapter 1 Fundamentals of Viruses and Their Proteases

text: Abstract Viruses are major pathogenic agents that can cause a variety of diseases, such as AIDS, hepatitis, respiratory diseases, and many more, in humans, plants, and animals. The most prominent of them have been adenoviruses, alphaviruses, flaviviruses, hepatitis C virus, herpesviruses, human immunodeficiency virus of type 1, and picornaviruses. This chapter presents an introductory remark on such viruses, mechanisms of their invasion, and diseases related to them. The inhibition of these viruses is of great concern to human beings. Each of these viruses encodes one or more proteases that play crucial roles in their replication, and thus they are important targets for the design and development of potent antiviral agents. The chapter, therefore, also introduces the readers to such proteases and their structures and functions. This chapter is thus a prelude to the remaining chapters in the book, which present in detail about the different viruses and their proteases.


title: Cholesterol-25-hydroxylase Is a Chicken ISG That Restricts ALV-J Infection by Producing 25-hydroxycholesterol

text: The avian leukosis virus subgroup J (ALV-J) belongs to the chicken retrovirus that causes enormous economic losses in the poultry industry. Interferon-stimulated genes (ISGs) are critical for controlling virus infections. Here, we identified 897 type I ISGs induced by interferon-α (IFN-α) in chicken peripheral blood mononuclear cell (PBMC) by RNA-Seq. In addition, we further identified 152 potential anti-ALV-J chicken type I ISGs. Among these potential anti-ALV-J ISGs, chicken cholesterol 25-hydroxylase (chCH25H) was selected for further antiviral mechanism studies in chicken embryo fibroblast cell lines (DF1). The gene chCH25H is located on chromosome 6 and clustered in a distinct group with mammals CH25H in the phylogenetic tree. The core promoter region of chCH25H was located within −75/−1 sequence. We found that chCH25H was induced by chicken IFN-α and ALV-J in DF1 cells. The overexpression of chCH25H significantly inhibited ALV-J replication in DF1 cells at 48 h post infection (hpi). In addition, ALV-J replication was significantly enhanced in the chCH25H- knockout DF1 cells. Furthermore, we demonstrated that chCH25H restricted ALV-J infection through the production of 25-hydroxycholesterol (25HC), rather than type I and II interferon. Our results identified 152 potential anti-ALV-J chicken type I ISGs and revealed that 25HC, the product of chCH25H, could be used as a natural antiviral agent to control ALV-J infection.


How Many Lives Will Delay of Colon Cancer Surgery Cost During the COVID-19 Pandemic? An Analysis Based on the U.S. National Cancer Database


title: How can airborne transmission of COVID-19 indoors be minimised?

text: Abstract During the rapid rise in COVID-19 illnesses and deaths globally, and notwithstanding recommended precautions, questions are voiced about routes of transmission for this pandemic disease. Inhaling small airborne droplets is probable as a third route of infection, in addition to more widely recognized transmission via larger respiratory droplets and direct contact with infected people or contaminated surfaces. While uncertainties remain regarding the relative contributions of the different transmission pathways, we argue that existing evidence is sufficiently strong to warrant engineering controls targeting airborne transmission as part of an overall strategy to limit infection risk indoors. Appropriate building engineering controls include sufficient and effective ventilation, possibly enhanced by particle filtration and air disinfection, avoiding air recirculation and avoiding overcrowding. Often, such measures can be easily implemented and without much cost, but if only they are recognised as significant in contributing to infection control goals. We believe that the use of engineering controls in public buildings, including hospitals, shops, offices, schools, kindergartens, libraries, restaurants, cruise ships, elevators, conference rooms or public transport, in parallel with effective application of other controls (including isolation and quarantine, social distancing and hand hygiene), would be an additional important measure globally to reduce the likelihood of transmission and thereby protect healthcare workers, patients and the general public.


title: Extended use of face masks during the COVID-19 pandemic - Thermal conditioning and spray-on surface disinfection

text: The current COVID-19 pandemic has resulted in globally constrained supplies for face masks and personal protective equipment (PPE). Production capacity is limited in many countries and the future course of the pandemic will likely continue with shortages for high quality masks and PPE in the foreseeable future. Hence, expectations are that mask reuse, extended wear and similar approaches will enhance the availability of personal protective measures. Repeated thermal disinfection could be an important option and likely easier implemented in some situations, at least on the small scale, than UV illumination, irradiation or hydrogen peroxide vapor exposure. An overview on thermal responses and ongoing filtration performance of multiple face mask types is provided. Most masks have adequate material properties to survive a few cycles (i.e. 30 min disinfection steps) of thermal exposure in the 75 °C regime. Some are more easily affected, as seen by the fusing of plastic liner or warping, given that preferred conditioning temperatures are near the softening point for some of the plastics and fibers used in these masks. Hence adequate temperature control is equally important. As guidance, disinfectants sprayed via dilute solutions maintain a surface presence over extended time at 25 and 37 °C. Some spray-on alcohol-based solutions containing disinfectants were gently applied to the top surface of masks. Neither moderate thermal aging (less than 24 h at 80 and 95 °C) nor gentle application of surface disinfectant sprays resulted in measurable loss of mask filter performance. Subject to bio-medical concurrence (additional checks for virus kill efficiency) and the use of low risk non-toxic disinfectants, such strategies, either individually or combined, by offering additional anti-viral properties or short term refreshing, may complement reuse options of professional masks or the now ubiquitous custom-made face masks with their often unknown filtration effectiveness.


title: Roles of the hemagglutinin of influenza A virus in viral entry and development of antiviral therapeutics and vaccines

text: Seasonal influenza epidemics and influenza pandemics caused by influenza A virus (IAV) has resulted in millions of deaths in the world. The development of anti-IAV vaccines and therapeutics is urgently needed for prevention and treatment of IAV infection and for controlling future influenza pandemics. Hemagglutinin (HA) of IAV plays a critical role in viral binding, fusion and entry, and contains the major neutralizing epitopes. Therefore, HA is an attractive target for developing anti-IAV drugs and vaccines. Here we have reviewed the recent progress in study of conformational changes of HA during viral fusion process and development of HA-based antiviral therapeutics and vaccines.


title: Relationship between microbiology of throat swab and clinical course among primary care patients with acute cough: a prospective cohort study

text: BACKGROUND: Acute lower respiratory tract infections (ALRTIs) account for most antibiotics prescribed in primary care despite lack of efficacy, partly due to clinician uncertainty about aetiology and patient concerns about illness course. Nucleic acid amplification tests could assist antibiotic targeting. METHODS: In this prospective cohort study, 645 patients presenting to primary care with acute cough and suspected ALRTI, provided throat swabs at baseline. These were tested for respiratory pathogens by real-time polymerase chain reaction and classified as having a respiratory virus, bacteria, both or neither. Three hundred fifty-four participants scored the symptoms severity daily for 1 week in a diary (0 = absent to 4 = severe problem). RESULTS: Organisms were identified in 346/645 (53.6%) participants. There were differences in the prevalence of seven symptoms between the organism groups at baseline. Those with a virus alone, and those with both virus and bacteria, had higher average severity scores of all symptoms combined during the week of follow-up than those in whom no organisms were detected [adjusted mean differences 0.204 (95% confidence interval 0.010 to 0.398) and 0.348 (0.098 to 0.598), respectively]. There were no differences in the duration of symptoms rated as moderate or severe between organism groups. CONCLUSIONS: Differences in presenting symptoms and symptoms severity can be identified between patients with viruses and bacteria identified on throat swabs. The magnitude of these differences is unlikely to influence management. Most patients had mild symptoms at 7 days regardless of aetiology, which could inform patients about likely symptom duration.


title: Genetic diversity in the yellow head nidovirus complex

text: Abstract Penaeus monodon shrimp collected from across the Indo-Pacific region during 1997–2004 were screened for the presence of yellow head-related viruses. Phylogenetic analyses of amplified ORF1b gene segments identified at least six distinct genetic lineages (genotypes). Genotype 1 (YHV) was detected only in shrimp with yellow head disease. Genotype 2 (GAV) was detected in diseased shrimp with the less severe condition described as mid-crop mortality syndrome and in healthy shrimp from Australia, Thailand and Vietnam. Other genotypes occurred commonly in healthy shrimp. Sequence comparisons of structural protein genes (ORF2 and ORF3), intergenic regions (IGRs) and the long 3′-UTR supported the delineation of genotypes and identified both conserved and variant structural features. In putative transcription regulating sequences (TRSs) encompassing the sub-genomic mRNA 5′-termini, a core motif (5′-GUCAAUUACAAC-3′) is absolutely conserved. A small (83 nt) open reading frame (ORF4) in the 3′-UTR of GAV is variously truncated in all other genotypes and a TRS-like element preceding ORF4 is invariably corrupted by a A > G/U substitution in the central core motif (5′-UU(G/U)CAAC-3′). The data support previous evidence that ORF4 is a non-functional gene under construction or deconstruction. The 3′-UTRs also contain predicted 3′-terminal hairpin-loop structures that are preserved in all genotypes by compensatory nucleotide substitutions, suggesting a role in polymerase recognition for minus-strand RNA synthesis.


title: Optimizing the Management of the Main Acute Infections in Pediatric ORL: Tonsillitis, Sinusitis, Otitis media

text: Summary Sinusitis, acute otitis media and tonsillitis are very frequent in children. Most of these infections are caused by viruses, but are generally treated with antibiotics. Inappropriate use of antibiotics favors the selection, growth and spread of resistant bacteria; these bacteria colonize the airways and affect the entire community. With the emergence of antibiotic-resistant bacteria, respiratory infections have become more difficult to treat. Effective strategies are needed to restrict the use of antibiotics without harming children that truly need these drugs. Aim to present a critical analysis of the results of randomized and controlled studies on clinical and laboratory criteria used in diagnosing and treating tonsillitis, sinusitis and otitis. Methods a review of randomized and controlled studies about these conditions published in MEDLINE and SCIELO from 2000 to 2006. Conclusions Given that most of these infections progress favorably without antibiotics, the use of these drugs should be avoided unless the child belongs to a high risk group for complications, or symptoms persist or worsen with despite symptomatic treatment. Physicians and laypersons should have better knowledge about the natural evolution of acute respiratory infections.


title: Epidemiological and Clinical Characteristics of 6635 COVID-19 Patients: a Pooled Analysis

text: An unidentified pneumonia outbreak was first observed in Wuhan, the capital of Hubei Province, China, in December 2019. WHO officially named the disease, Coronavirus Disease 2019 (COVID-19), and declared it as pandemic on Mar 11, 2020. Globally, there are more than 3 million confirmed cases with nearly 200,000 deaths. Hence, we aimed to perform a systematic review and pooled analysis of the current published literature on COVID-19 to provide an insight on the epidemiological and clinical characteristics of COVID-19 patients. A systematic search of published peer-reviewed articles that reported cases with demographical and clinical features of real-time reverse transcriptase polymerase chain reaction (rRT-PCR)–confirmed SARS-CoV-2 infection using MOOSE guidelines was conducted from December 1, 2019, to April 27, 2020, and 50 eligible articles were included for the final analysis. Review articles, opinion articles, and letters not presenting original data as well as studies with incomplete information were excluded. We included a total of 6635 patients from 50 articles, with 54.5 % being male. The predominant symptoms were fever (80.3%), cough (64.2%), and fatigue/myalgia (36.5%) and other symptoms including dyspnea, chest pain, and sore throat. We also found patients with GI symptoms like diarrhea (9.2%) and nausea/vomiting (5.2%). Comorbidities were found in 3,435 (51.7%) patients with the most common being hypertension (22.67%) followed by diabetes mellitus (12.78%). COVID-19 pandemic is not only leading a huge burden on health care facilities but significant disruption in the world society. Patients with coexisting comorbidities are at higher risk and need more utilization of health care resources. As this virus is spreading globally, all countries have to join hands and prepare at all levels of human resources, infrastructure, and facilities to combat the COVID-19 disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s42399-020-00393-y) contains supplementary material, which is available to authorized users.


title: Predictive molecular pathology in the time of COVID-19

text: AIMS: In the time of COVID-19, predictive molecular pathology laboratories must still timely select oncological patients for targeted treatments. However, the need to respect social distancing measures may delay results generated by laboratory-developed tests based on sequential steps a long hands-on time. Laboratory workflows should now be simplified. METHODS: The organisation of the University of Naples Federico II predictive pathology laboratory was assessed before (March–April 2019) and during (March–April 2020) the Italian lockdown. RESULTS: The number of patients undergoing single or multiple biomarker testing was similar in 2019 (n=43) and in 2020 (n=45). Considering adequate samples for molecular testing, before the outbreak, next-generation sequencing was mostly used (35/42, 83.3%). Testing six genes had a reagent cost of €98/patient. Conversely, in 2020, almost all cases (38/41, 92.7%) were analysed by automated testing. This latter had for any single assay/gene a significant reagent cost (€95–€136) and a faster mean turnaround time (5.3 vs 7.9 working days). CONCLUSION: In the times of coronavirus, laboratory fully automated platforms simplify predictive molecular testing. Laboratory staff may be more safely and cost-effectively managed.


title: Chronic Cough Related to Acute Viral Bronchiolitis in Children CHEST Expert Panel Report

text: Background Acute bronchiolitis is common in young children, and some children develop chronic cough after their bronchiolitis. We thus undertook systematic reviews based on key questions (KQs) using the PICO (Population, Intervention, Comparison, Outcome) format. The KQs were: Among children with chronic cough (> 4 weeks) after acute viral bronchiolitis, how effective are the following interventions in improving the resolution of cough?: (1) Antibiotics. If so what type and for how long? (2) Asthma medications (inhaled steroids, beta2 agonist, montelukast); and (3) Inhaled osmotic agents like hypertonic saline? Methods We used the CHEST expert cough panel’s protocol and the American College of Chest Physicians (CHEST) methodological guidelines and GRADE framework. Data from the systematic reviews in conjunction with patients’ values and preferences and the clinical context were used to form these suggestions. Delphi methodology was used to obtain consensus. Results Several studies and systematic reviews on the efficacy of the three types of interventions listed in the introduction were found but no data were relevant to our KQs. Thus, no recommendations on using the interventions above could be formulated. Conclusions The panel made several consensus-based suggestions and identified directions for future studies to advance the field of managing chronic cough post-acute bronchiolitis in children.


title: No novel coronaviruses identified in a large collection of human nasopharyngeal specimens using family-wide CODEHOP-based primers

text: Novel viruses might be responsible for numerous disease cases with unknown etiology. In this study, we screened 1800 nasopharyngeal samples from adult outpatients with respiratory disease symptoms and healthy individuals. We employed a reverse transcription (RT)-PCR assay and CODEHOP-based primers (CT12-mCODEHOP) previously developed to recognize known and unknown corona- and toroviruses. The CT12-mCODEHOP assay detected 42.0 % (29/69) of samples positive for human coronaviruses (HCoV), including HCoV-229 (1/16), HCoV-NL63 (9/17), and HCoV-OC43 (19/36), and additionally HCoV-HKU1 (3), which was not targeted by the diagnostic real-time PCR assays. No other coronaviruses were identified in the analyzed samples.


IS HUMAN RIGHTS PREPARED? RISK, RIGHTS AND PUBLIC HEALTH EMERGENCIES


title: First isolation of West Nile virus from a dromedary camel

text: Although antibodies against West Nile virus (WNV) have been detected in the sera of dromedaries in the Middle East, North Africa and Spain, no WNV has been isolated or amplified from dromedary or Bactrian camels. In this study, WNV was isolated from Vero cells inoculated with both nasal swab and pooled trachea/lung samples from a dromedary calf in Dubai. Complete-genome sequencing and phylogenetic analysis using the near-whole-genome polyprotein revealed that the virus belonged to lineage 1a. There was no clustering of the present WNV with other WNVs isolated in other parts of the Middle East. Within lineage 1a, the dromedary WNV occupied a unique position, although it was most closely related to other WNVs of cluster 2. Comparative analysis revealed that the putative E protein encoded by the genome possessed the original WNV E protein glycosylation motif NYS at E154–156, which contained the N-linked glycosylation site at N-154 associated with increased WNV pathogenicity and neuroinvasiveness. In the putative NS1 protein, the A70S substitution observed in other cluster 2 WNVs and P250, which has been implicated in neuroinvasiveness, were present. In addition, the foo motif in the putative NS2A protein, which has been implicated in neuroinvasiveness, was detected. Notably, the amino-acid residues at 14 positions in the present dromedary WNV genome differed from those in most of the closely related WNV strains in cluster 2 of lineage 1a, with the majority of these differences observed in the putative E and NS5 proteins. The present study is the first to demonstrate the isolation of WNV from dromedaries. This finding expands the possible reservoirs of WNV and sources of WNV infection.


title: Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study

text: Abstract Spinal muscular atrophy (SMA) is a neurodegenerative disease associated with severe muscle atrophy and weakness in the limbs and trunk. We report interim efficacy and safety outcomes as of March 29, 2019 in 25 children with genetically diagnosed SMA who first received nusinersen in infancy while presymptomatic in the ongoing Phase 2, multisite, open-label, single-arm NURTURE trial. Fifteen children have two SMN2 copies and 10 have three SMN2 copies. At last visit, children were median (range) 34.8 [25.7–45.4] months of age and past the expected age of symptom onset for SMA Types I or II; all were alive and none required tracheostomy or permanent ventilation. Four (16%) participants with two SMN2 copies utilized respiratory support for ≥6 h/day for ≥7 consecutive days that was initiated during acute, reversible illnesses. All 25 participants achieved the ability to sit without support, 23/25 (92%) achieved walking with assistance, and 22/25 (88%) achieved walking independently. Eight infants had adverse events considered possibly related to nusinersen by the study investigators. These results, representing a median 2.9 years of follow up, emphasize the importance of proactive treatment with nusinersen immediately after establishing the genetic diagnosis of SMA in presymptomatic infants and emerging newborn screening efforts.


title: Vaporized Hydrogen Peroxide Decontamination of N95 Respirators in a Dedicated Animal Research Facility for Reuse During a Novel Coronavirus Pandemic

text: INTRODUCTION: During the COVID-19 pandemic, health care systems and safety providers have faced an unprecedented challenge of limited access to personal protective equipment (PPE) to conduct patient and public care. In federal emergencies, reuse of PPE after disinfection can occur by processes, like vaporized hydrogen peroxide (VHP), recommended by the Centers for Disease and Control and Prevention. We identified a vacant animal holding facility at our institution to repurpose into a regional VHP decontamination center. METHODS: The facility is a multiroom, 20 000 ft(2) building with control of HVAC to adjust to VHP conditional requirements. H(2)O(2) was delivered to rooms using robotic HaloFoggers, dispersing H(2)O(2) vapor and increasingly concentrated microdroplets as a fog for a timed period based on cubic footage of rooms. RESULTS: Fogging cycles eliminated 6-log Geobacillus stearothermophilus up to 7 days postcycle. Functional efficacy of treated N95s was confirmed by fit tests of institutional personnel. Signage, process flow mapping, and training materials facilitated ease of workflow and adherence to safety expectations within the building. DISCUSSION AND CONCLUSION: Our study determined that a variety of N95 respirator types and sizes were able to be cleared of potential bacterial and viral agents using VHP in a controlled fog/dwell/exhaust cycle. This repurposed animal facility has the capacity to decontaminate up to 6700 respirators daily, which will address the predicted surge of COVID-19 cases in the state, and ultimately allow each respirator to be reused multiple times. There is no other public site in the region with our capacity to offset the continued supply chain issues for PPE needs.


title: Identification of aberrantly expressed of serum microRNAs in patients with hormone-induced non-traumatic osteonecrosis of the femoral head

text: Abstract Objective The non-translation RNA-microRNA (miRNA) has been demonstrated to correlate to various disease occurrence in body. Serum miRNA was gradually considered as molecular markers for disease diagnosis. This study was designed to analyze differential serum miRNAs level in hormone-induced non-traumatic osteonecrosis of the femoral head (hormone-NOFH) patients. Methods We selected 30 patients with hormone-NOFH as case group, and 30 healthy volunteers were recruited as control group. miRCURYTM LNA miRNA chip and quantitative RT-PCR were used to examine differential miRNAs expression. Correlation assay was performed between miRNAs and NOFH trait. Results We found that 9 miRNAs were upregulated while 3 miRNAs were downregulated in hormone-TOFH patient serum by result of miRNA chip. QRT-PCR assay revealed that the level of miR-423-5p was significantly increased and miR-10a-5p was significantly decreased. Using Spearman correlation analysis, we observed that miR-423-5p serum level is positive association to FHC levels whereas miR-10a-5p has no association with FHC levels. Furthermore, miR-423-5p is negatively correlated to its downstream molecule-adiponectin. Conclusion We report a miRNA profile of hormone-NOFH and provide a new perspective to understand this intricate disease. This novel information suggests the potential roles of miR-423-5p in the diagnosis, prognosis biomarkers, or therapy targets of hormone-NOFH.


title: Canine Hepacivirus NS3 Serine Protease Can Cleave the Human Adaptor Proteins MAVS and TRIF

text: Canine hepacivirus (CHV) was recently identified in domestic dogs and horses. The finding that CHV is genetically the virus most closely related to hepatitis C virus (HCV) has raised the question of whether HCV might have evolved as the result of close contact between dogs and/or horses and humans. The aim of this study was to investigate whether the NS3/4A serine protease of CHV specifically cleaves human mitochondrial antiviral signaling protein (MAVS) and Toll-IL-1 receptor domain-containing adaptor inducing interferon-beta (TRIF). The proteolytic activity of CHV NS3/4A was evaluated using a bacteriophage lambda genetic screen. Human MAVS- and TRIF-specific cleavage sites were engineered into the lambda cI repressor. Upon infection of Escherichia coli cells coexpressing these repressors and a CHV NS3/4A construct, lambda phage replicated up to 2000-fold more efficiently than in cells expressing a CHV protease variant carrying the inactivating substitution S139A. Comparable results were obtained when several HCV NS3/4A constructs of genotype 1b were assayed. This indicates that CHV can disrupt the human innate antiviral defense signaling pathway and suggests a possible evolutionary relationship between CHV and HCV.


title: Prevalence and risk factors of chlamydia infection in Hong Kong: A population-based geospatial household survey and testing

text: BACKGROUND: Chlamydia causes infertility and increases risk of HIV infection, and population-based studies provide essential information for effective infection control and prevention. This study examined Chlamydia trachomatis prevalence and risk factors among a representative sample of 18-49-year-old residents in Hong Kong. METHODS: Census boundary map of 412 constituency areas was used as primary sampling units to construct the sampling frame and, residential buildings and units were randomly selected using geospatial modelling. A questionnaire on sexual practice and health was conducted, and polymerase chain reaction was used to test the urine for genital chlamydial infection. Invitation letters were sent to the selected households and a team of interviewers were sent to recruit one subject per household. Prevalence data was weighted according to the 2011 census and risk factors identified through logistic regression. RESULTS: Among 881 participants (response rate of 24.5%), the overall Chlamydia trachomatis prevalence was low at 1.4% (95%CI 0.8–2.5%) but sexually active young (18–26 years) women had relatively high prevalence (5.8%, 95%CI 1.7–18.2%) in Hong Kong. A unique U-shape disease burden was observed with peaks in younger and older (40–49 years) women. Amongst the sexually active women, the risk factors of Chlamydia trachomatis infection were: younger age (aOR = 25.4, 95% CI 2.81–230); living alone (aOR = 8.99, 95% CI 1.46–55.40); and, among all the sexually active participants, males (including the male partners of the female participants) who had travelled out of Hong Kong in the previous 12 months had higher risks of infection (aOR = 5.35; 95% CI 1.25–22.8). A core-peripheral geographical distribution of Chlamydia trachomatis prevalence was also observed. CONCLUSION: Young and older sexually active women in Hong Kong have high prevalence of chlamydia. Routine screening for sexually active women and young men should be considered. Further research on testing feasibility and linkage-to-care are urgently needed to control the infection.


title: Effect of Crop Volume on Contraction Rate in Adult House Fly

text: The functional aspects of the adult house fly crop have not been studied even though various human and domestic animal pathogens have been discovered within the crop lumen. The average volume consumed (midgut and crop) by flies starved for 24 h was 3.88 μl by feeding both sexes on a sucrose phosphate glutamate buffer. In addition, various volumes of a solution (0.125 M sucrose plus Amaranth dye) were fed to 3-d-old adult female house flies to quantify the crop contraction rate as affected by crop volume. As crop volume increased, the contraction rate increased until it reached a peak at 2 μl, after which it declined. It is hypothesized that the high contraction rate of the crop, which in house fly is almost twice the rate of three other fly species, is one of the factors that makes house fly an excellent vector. The mechanism for such a high contraction rate needs to be investigated.


title: Isolation and sequence analysis of canine respiratory coronavirus

text: Abstract Canine respiratory coronavirus (CRCoV) has frequently been detected in respiratory samples from dogs by RT-PCR. In this report the first successful isolation of CRCoV from a dog with respiratory disease is described. The isolate CRCoV-4182 was cultured in HRT-18 cells but failed to replicate in a number of other cell lines. The nucleotide sequence of the 3′-terminal portion of the CRCoV genome was determined including all open reading frames from the NS2 gene to the N gene. Comparison with other coronavirus sequences showed a high similarity to bovine coronavirus (BCoV). The region between the spike and the E gene was found to be the most variable and was used for phylogenetic analysis of several CRCoV strains. CRCoV-4182 showed a mutation within the non-structural protein region downstream of the S gene leading to the translation of an 8.8kDa putative protein comprising a fusion of the equivalent of the BCoV 4.9kDa protein to a truncated version of the BCoV 4.8kDa protein. The culture of CRCoV will enable analysis of the expression and function of this and other CRCoV proteins as well as allowing the study of the role of CRCoV in the aetiology of canine infectious respiratory disease.


Are patients with multiple sclerosis (MS) at higher risk of COVID-19 infection?


Artists explore new ways of knowing in a time of information overload.


title: An Analysis on the Detection of Biological Contaminants Aboard Aircraft

text: The spread of infectious disease via commercial airliner travel is a significant and realistic threat. To shed some light on the feasibility of detecting airborne pathogens, a sensor integration study has been conducted and computational investigations of contaminant transport in an aircraft cabin have been performed. Our study took into consideration sensor sensitivity as well as the time-to-answer, size, weight and the power of best available commercial off-the-shelf (COTS) devices. We conducted computational fluid dynamics simulations to investigate three types of scenarios: (1) nominal breathing (up to 20 breaths per minute) and coughing (20 times per hour); (2) nominal breathing and sneezing (4 times per hour); and (3) nominal breathing only. Each scenario was implemented with one or seven infectious passengers expelling air and sneezes or coughs at the stated frequencies. Scenario 2 was implemented with two additional cases in which one infectious passenger expelled 20 and 50 sneezes per hour, respectively. All computations were based on 90 minutes of sampling using specifications from a COTS aerosol collector and biosensor. Only biosensors that could provide an answer in under 20 minutes without any manual preparation steps were included. The principal finding was that the steady-state bacteria concentrations in aircraft would be high enough to be detected in the case where seven infectious passengers are exhaling under scenarios 1 and 2 and where one infectious passenger is actively exhaling in scenario 2. Breathing alone failed to generate sufficient bacterial particles for detection, and none of the scenarios generated sufficient viral particles for detection to be feasible. These results suggest that more sensitive sensors than the COTS devices currently available and/or sampling of individual passengers would be needed for the detection of bacteria and viruses in aircraft.


title: Emerging pathogens and their implications for the blood supply and transfusion transmitted infections

text: The threat of infection by conventional transfusion‐transmitted agents has been essentially eliminated from the blood supply in developed countries, thus focusing attention on the potential risk from emerging infections. Over recent years, actions have been taken to manage a number of such risks to blood safety. These illustrate the inherent variability of the agents concerned and of the measures needed to define and control the risk.


title: Ear nose throat-related symptoms with a focus on loss of smell and/or taste in COVID-19 patients

text: PURPOSE: To determine the frequency and severity of general and ear nose throat (ENT)- related symptoms, especially smell and/or loss of sense of taste (STL) in COVID-19 disease, as well as to investigate the recovery process of STL. MATERIALS AND METHODS: Patients with a positive COVID-19 diagnosis were given a questionnaire consisting of general questions (age, sex, date of symptoms, smoking history, concomitant diseases), questions about the most obvious symptom at presentation (one option only), the severity and frequency of symptoms (general and ENT), and STL (recovery time and degree of recovery). RESULTS: The study population consisted of 172 patients, 18–65 years old (mean age, 37.8 ± 12.5 years; 51.2% female; 76.2% nonsmokers). Cough (n = 30, 17.4%) and loss of sense of smell (n = 18, 10.4%) were the most obvious general and ENT symptoms, respectively. Eighty-eight patients (51.2%) reported loss of sense of smell, and 81 patients (47.1%) reported loss of sense of taste. The mean recovery times for loss of sense of smell and loss of sense of taste were 8.02 ± 6.41 and 8.20 ± 7.07 days, respectively. The loss of sense of smell and loss of sense of taste were the unique symptoms in four (4.54%) and one (1.23%) patients, respectively. CONCLUSION: STL is a common symptom in COVID-19 and may be the first and/or only symptom of this disease. In patients presenting with STL complaints, surveillance for possible COVID-19 disease and screening tests will facilitate the struggle against the disease.


title: Lifestyle at Time of COVID-19: How Could Quarantine Affect Cardiovascular Risk

text: COVID-19 is causing a global pandemic with a high number of deaths and infected people. To contain the diffusion of COVID-19 virus, governments have enforced restrictions on outdoor activities or even collective quarantine on the population. Quarantine carries some long-term effects on cardiovascular disease, mainly related to unhealthy lifestyle and anxiety.


title: Ventilation and laboratory confirmed acute respiratory infection (ARI) rates in college residence halls in College Park, Maryland

text: Abstract Strategies to protect building occupants from the risk of acute respiratory infection (ARI) need to consider ventilation for its ability to dilute and remove indoor bioaerosols. Prior studies have described an association of increased self-reported colds and influenza-like symptoms with low ventilation but have not combined rigorous characterization of ventilation with assessment of laboratory confirmed infections. We report a study designed to fill this gap. We followed laboratory confirmed ARI rates and measured CO2 concentrations for four months during the winter-spring of 2018 in two campus residence halls: (1) a high ventilation building (HVB) with a dedicated outdoor air system that supplies 100% of outside air to each dormitory room, and (2) a low ventilation building (LVB) that relies on infiltration as ventilation. We enrolled 11 volunteers for a total of 522 person-days in the HVB and 109 volunteers for 6069 person-days in the LVB, and tested upper-respiratory swabs from symptomatic cases and their close contacts for the presence of 44 pathogens using a molecular assay. We observed one ARI case in the HVB (0.70/person-year) and 47 in the LVB (2.83/person-year). Simultaneously, 154 CO2 sensors distributed primarily in the dormitory rooms collected 668,390 useful data points from over 1 million recorded data points. Average and standard deviation of CO2 concentrations were 1230 ppm and 408 ppm in the HVB, and 1492 ppm and 837 ppm in the LVB, respectively. Importantly, this study developed and calibrated multi-zone models for the HVB with 229 zones and 983 airflow paths, and for the LVB with 529 zones and 1836 airflow paths by using a subset of CO2 data for model calibration. The models were used to calculate ventilation rates in the two buildings and potential for viral aerosol migration between rooms in the LVB. With doors and windows closed, the average ventilation rate was 12 L/s in the HVB dormitory rooms and 4 L/s in the LVB dormitory rooms. As a result, residents had on average 6.6 L/(s person) of outside air in the HVB and 2.3 L/(s person) in the LVB. LVB rooms located at the leeward side of the building had smaller average ventilation rates, as well as a somewhat higher ARI incidence rate and average CO2 concentrations when compared to those values in the rooms located at the windward side of the building. Average ventilation rates in twenty LVB dormitory rooms increased from 2.3 L/s to 7.5 L/s by opening windows, 3.6 L/s by opening doors, and 8.8 L/s by opening both windows and doors. Therefore, opening both windows and doors in the LVB dormitory rooms can increase ventilation rates to the levels comparable to those in the HVB. But it can also have a negative effect on thermal comfort due to low outdoor temperatures. Simulation results identified an aerobiologic pathway from a room occupied by an index case of influenza A to a room occupied by a possible secondary case.


title: Investigation of the role of major respiratory viruses in the aetiology of nasal polyps using polymerase chain reaction technique

text: OBJECTIVE: We aimed to identify the role of major respiratory viruses in the aetiology of human nasal polyps using polymerase chain reaction technique. METHODS: Thirty patients with nasal polyps and a group of 20 healthy patients (control group) were included in this study. Mucosa was obtained from the polyps of patients with nasal polyposis and from the middle turbinate of the control group patients by means of biopsy. The samples were stored at −80 °C until molecular analysis by polymerase chain reaction was carried out. RESULTS: In the control group, the human coronavirus and human rhinovirus were diagnosed in one of the patients and the human respiratory syncytial virus in another. In the group with nasal polyposis, the influenza B virus was identified in one of the patients and the human coronavirus in another. CONCLUSION: The results did not demonstrate a statistically significant relationship between nasal polyposis and respiratory viruses.


title: Basic aspects of immunomodulation through active immunization

text: Abstract This paper reviews how immunomodulation through active vaccination has evolved in the past 25 years. Although initially it progressed isolated from the main stream of immunological research and vaccine development, lately it merged with this main stream and is taking full advantage of the newest developments in vaccinology. The first immunomodulation vaccine is already on the market, while various others are close to it. Not in the least because one of the major stumbling blocks of immunomodulation through active vaccination, the inherent low immunogenicity of ‘self’ antigens, has in a number of other cases been solved. Most progress has been made in veterinary applications and has helped to formulate practical rules, necessary to break immunotolerance. It is not unlikely that these rules will be used to design better immunomodulation vaccines to be used in humans; notably to control fertility or combat tumours.


title: Role of Antimicrobial Agents in the Management of Exacerbations of COPD

text: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a common occurrence and characterize the natural history of the disease. Over the past decade, new knowledge has substantially enhanced our understanding of the pathogenesis, outcome and natural history of AECOPD. The exacerbations not only greatly reduce the quality of life of these patients, but also result in hospitalization, respiratory failure, and death. The exacerbations are the major cost drivers in consumption of healthcare resources by COPD patients. Although bacterial infections are the most common etiologic agents, the role of viruses in COPD exacerbations is being increasingly recognized. The efficacy of antimicrobial therapy in acute exacerbations has established a causative role for bacterial infections. Recent molecular typing of sputum isolates further supports the role of bacteria in AECOPD. Isolation of a new strain of Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae was associated with a considerable risk of an exacerbation. Lower airway bacterial colonization in stable patients with COPD instigates airway inflammation, which leads to a protracted self-perpetuating vicious circle of progressive lung damage and disease progression. A significant proportion of patients treated for COPD exacerbation demonstrate incomplete recovery, and frequent exacerbations contribute to decline in lung function. The predictors of poor outcome include advanced age, significant impairment of lung function, poor performance status, comorbid conditions and history of previous frequent exacerbations requiring antibacterials or systemic corticosteroids. These high-risk patients, who are likely to harbor organisms resistant to commonly used antimicrobials, should be identified and treated with antimicrobials with a low potential for failure. An aggressive management approach in complicated exacerbations may reduce costs by reducing healthcare utilization and hospitalization.


title: Cell Culture and Electron Microscopy for Identifying Viruses in Diseases of Unknown Cause

text: During outbreaks of infectious diseases or in cases of severely ill patients, it is imperative to identify the causative agent. This report describes several events in which virus isolation and identification by electron microscopy were critical to initial recognition of the etiologic agent, which was further analyzed by additional laboratory diagnostic assays. Examples include severe acute respiratory syndrome coronavirus, and Nipah, lymphocytic choriomeningitis, West Nile, Cache Valley, and Heartland viruses. These cases illustrate the importance of the techniques of cell culture and electron microscopy in pathogen identification and recognition of emerging diseases.


title: The importance of the Social License to Operate at the investment and operations stage of coal mining projects: Application using a Decision Support System

text: The Social License to Operate (SLO) and the Value Chain business model are basic elements that need to be considered both at the planning and operation stages of mining operations and in particular in coal mining projects. If a coal mining enterprise loses its SLO, it may face risks in operations, which may lead to value chain risks. One of the causes of enterprise failure as related to coal mining operations is the inability to reliably assess/manage risk holistically and the inability to understand that lack of SLO is a critical risk. Although financial risks are typically assessed for mining projects, lack of SLO risk should also be taken into account starting as early as the bankable feasibility study. Furthermore, as it is difficult to establish a proactive decision-making policy for SLO risk in coal mining operations, the Operational Risk Management (ORM) methodology is probably a good tool to apply towards that goal. For this reason, a Mining Operational Risk Management Model (MORMM) was developed to incorporate risk probabilities and risk severities evaluated by experts. The final risk assessment is coded using Risk Assessment Codes (RACs). A hypothetical scenario was developed utilizing the MORMM model in order to illustrate how risks can be managed during the SLO granting process. This scenario describes a hypothetical coal mining project evaluated by virtual risk evaluators under specific hazard categories. Risk evaluation involves the assessment of risk probability and risk severity. Through this scenario this paper presents ways: (i) to establish a baseline ORM process that will be applicable to any coal mining operation environment, and (ii) to provide a theoretical example to demonstrate how the method can be applied to coal mining operations. The resulting RACs can provide critical information to decision makers regarding the rejection, acceptance or re-engineering of the mining business plan.


title: Couchsurfing involvement in non-profit peer-to-peer accommodations and its impact on destination image, familiarity, and behavioral intentions

text: Abstract Accommodation is a fundamental part of tourism, and it plays an important role in the tourist experience. The emerging economy and especially the peer-to-peer accommodations (P2P) have shaken up the conventional accommodations sector. While most P2P accommodation studies have focused on the monetary platform, which includes Airbnb, there is little knowledge about the linkages of involvement and behavioral intentions on the non-profit accommodation users. This empirical study applied a multiple-methods approach to investigate the positive impacts of involvement on couchsurfing, such as P2P accommodations on the destination image, familiarity, and the behavioral intentions. The data was collected from 609 travelers who have used couchsurfing while traveling to Turkey from 2016 to 2017. The results revealed that involvement in couchsurfing improved the destination image, familiarity, the E-WoM, and the revisit intention of couchsurfers. This study also discusses the practical implications.


Cancer treatment during COVID-19 pandemic: do not postpone but decide wisely


title: Transmissible Gastroenteritis Virus Infection Enhances SGLT1 and GLUT2 Expression to Increase Glucose Uptake

text: Transmissible gastroenteritis virus (TGEV) is a coronavirus that causes villus atrophy, followed by crypt hyperplasia, reduces the activities of intestinal digestive enzymes, and disrupts the absorption of intestinal nutrients. In vivo, TGEV primarily targets and infects intestinal epithelial cells, which play an important role in glucose absorption via the apical and basolateral transporters Na(+)-dependent glucose transporter 1 (SGLT1) and facilitative glucose transporter 2 (GLUT2), respectively. In this study, we therefore sought to evaluate the effects of TGEV infection on glucose uptake and SGLT1 and GLUT2 expression. Our data demonstrate that infection with TGEV resulted in increased glucose uptake and augmented expression of EGFR, SGLT1 and GLUT2. Moreover, inhibition studies showed that EGFR modulated glucose uptake in control and TGEV infected cells. Finally, high glucose absorption was subsequently found to promote TGEV replication.


Febrile Hypotensive Reactions Following ABVD Chemotherapy in Patients With EBV-associated Classical Hodgkin Lymphoma


title: A health-based assessment of particulate air pollution in urban areas of Beijing in 2000–2004

text: Abstract Particulate air pollution is a serious problem in Beijing. The annual concentration of particulate matter with aerodynamic diameter less than 10 μm (PM10), ranging from 141 to 166 μg m−3 in 2000–2004, could be very harmful to human health. In this paper, we presented the mortality and morbidity effects of PM10 pollution based on statistical data and the epidemiological exposure–response function. The economic costs to health during the 5 years were estimated to lie between US$1670 and $3655 million annually, accounting for about 6.55% of Beijing's gross domestic product each year. The total costs were apportioned into two parts caused by: the local emissions and long-range transported pollution. The contribution from local emissions dominated the total costs, accounting on average for 3.60% of GDP. However, the contributions from transported pollution cannot be neglected, and the relative percentage to the total costs from the other regions could account for about 45%. An energy policy and effective measures should be proposed to reduce particulate matter, especially PM2.5 pollution in Beijing to protect public health. The Beijing government also needs to cooperate with the other local governments to reduce high background level of particulate air pollution.


title: Chapter 5 Size-exclusion chromatography

text: Publisher Summary Size-exclusion chromatography (SEC), also called “gel-permeation chromatography,” “molecular-sieve chromatography,” or “gel filtration,” separates molecules according to their sizes. Smaller molecules are retarded on a column, whereas larger ones are eluted more rapidly. As the retention time can be directly correlated with the sizes of molecules, this method is particularly useful for the determination of molecular weight. SEC is generally applicable to the separation of molecules in the range of 0.5–1000 kDa, but larger proteins or other giant molecules can also be separated. SEC can also physically separate folded macromolecules from the unfolded ones, particularly in the case of slow equilibria. The major applications of SEC include the determination of molecular weight and molecular-weight distribution of natural and synthetic polymers. Separation strongly depends on many factors such as column packing, column dimensions, flow rate, sample volume, and mobile-phase composition. Capillary SEC provides a separation strategy for microscale purification. Capillary SEC columns are best suited for direct coupling to electrospray ionization–mass spectrometry (ESI–MS) because they have comparable flow rates that can be delivered to the ESI source without splitting.


title: Impact of rhinoviruses on pediatric community-acquired pneumonia

text: This study of 592 children seen in our Emergency Department with radiographically confirmed community-acquired pneumonia (CAP) was designed to evaluate the role of rhinoviruses (RVs) in the disease. The respiratory secretions of each child were assayed using RVP Fast in order to detect 17 respiratory viruses, and the RV-positive samples were characterised by means of real-time polymerase chain reaction and sequencing. RVs were identified in 172 cases (29.0%): 48/132 children aged <1 year (36.3%), 80/293 aged 1–3 years (27.3%), and 44/167 aged ≥4 years (26.3%). Sequencing demonstrated that 82 RVs (49.1%) were group A, 17 (10.1%) group B, and 52 (31.1%) group C; 21 (12.2%) were untyped. RVs were found as single agents in 99 cases, and together with two or more other viruses in 73 (40.7%). There were only marginal differences between the different RV groups and between single RV infection and RV co-infections. RV CAP is frequent not only in younger but also in older children, and RV-A is the most common strain associated with it. The clinical relevance of RV CAP seems to be mild to moderate without any major differences between the A and B strains and the recently identified RV C.


title: Parasite and viral species richness of Southeast Asian bats: Fragmentation of area distribution matters

text: Interest in bat-borne diseases and parasites has grown in the past decade over concerns for human health. However, the drivers of parasite diversity among bat host species are understudied as are the links between parasite richness and emerging risks. Thus, we aimed at exploring factors that explain macro and microparasite species richness in bats from Southeast Asia, a hotspot of emerging infectious diseases. First, we identified bat species that need increased sampling effort for pathogen discovery. Our approach highlights pathogen investigation disparities among species within the same genus, such as Rhinolophus and Pteropus. Secondly, comparative analysis using independent contrasts method allowed the identification of likely factors explaining parasite and viral diversity of bats. Our results showed a key role of bat distribution shape, an index of the fragmentation of bat distribution, on parasite diversity, linked to a decrease for both viral and endoparasite species richness. We discuss how our study may contribute to a better understanding of the link between parasite species richness and emergence.


title: Emerging regulation and functions of autophagy

text: Autophagy maintains cell, tissue and organism homeostasis through degradation. Complex post-translational modulation of the Atg (autophagy-related) proteins adds additional entry points for crosstalk with other cellular processes and helps define cell-type-specific regulations of autophagy. Beyond the simplistic view of a process exclusively dedicated to the turnover of cellular components, recent data have uncovered unexpected functions for autophagy and the autophagy-related genes, such as regulation of metabolism, membrane transport and modulation of host defenses — indicating the novel frontiers lying ahead.


title: Temporäre Hyposmie bei COVID-19-Patienten

text: BACKGROUND: This is a report on the high incidence of olfactory dysfunction in COVID-19 patients in the first cohort of COVID-19 patients in Germany (Webasto cluster). METHODS: Loss of sense of smell and/or taste was reported by 26 of 63 COVID-19 patients (41%), whereas only 31% of the patients experiencing hyposmia had simultaneous symptoms of rhinitis. Smell tests were performed in 14 of these patients and taste tests in 10. The measurements were conducted in a patient care setting in an early COVID-19 cohort. RESULTS: An olfactory disorder was present in 10/14 patients, before as well as after nasal decongestion. In 2 of these patients, hyposmia was the leading or only symptom of SARS-CoV‑2 infection. All tested patients reported recovery of smell and/or taste within 8 to 23 days. CONCLUSION: The data imply that a) COVID-19 can lead to hyposmia in a relevant number of patients, the incidence was approximately 30% in this cohort; b) in most cases, the olfactory disturbance was not associated with nasal obstruction, thus indicating a possible neurogenic origin; and c) the olfactory disorder largely resolved within 1–3 weeks after the onset of COVID-19 symptoms. There were no indications of an increased incidence of dysgeusia. These early data may help in the interpretation of COVID-19-associated hyposmia as well as in the counseling of patients, given the temporary nature of hyposmia observed in this study. Furthermore, according to the current experience, hyposmia without rhinitic obstruction can be the leading or even the only symptom of a SARS-CoV‑2 infection.


title: The interplay between virus infection and the cellular RNA interference machinery

text: RNA interference (RNAi) plays a pivotal role in the regulation of gene expression to control cell development and differentiation. In plants, insects and nematodes RNAi also functions as an innate defence response against viruses. Similarly, there is accumulating evidence that RNAi functions as an antiviral defence mechanism in mammalian cells. Viruses have evolved highly sophisticated mechanisms for interacting with the host cell machinery, and recent evidence indicates that this also involves RNAi pathways. The cellular RNAi machinery can inhibit virus replication, but viruses may also exploit the RNAi machinery for their own replication. In addition, viruses can encode proteins or RNA molecules that suppress existing RNAi pathways or trigger the silencing of specific host genes. Besides the natural interplay between RNAi and viruses, induced RNAi provides an attractive therapy approach for the fight against human pathogenic viruses. Here, we summarize the latest news on virus–RNAi interactions and RNAi based antiviral therapy.


title: Antitumor activity and biochemical effects of topsentin

text: Abstract Topsentin, a bis(indolyl)imidazole marine natural product, inhibited the proliferation of cultured human and murine tumor cells at micromolar concentrations (ic50 values ranged from 4 to 40 μM) and was active against in vivo P388 leukemia (% T C = 137, 150 mg/kg , QD1-5) and B16 melanoma (% T C = 144, 37.5 mg/kg , QD1-9) tumors. Effects of 30 μM topsentin (1-hr exposures) on incorporation of radiolabeled precursors by P388 cells indicated inhibition of DNA synthesis (91%) and to a lesser extent RNA synthesis (57%), whereas synthesis of protein was unaffected (0%). Fluorescence spectral changes and competitive binding experiments with ethidium bromide indicated that topsentin interacted with DNA. No evidence for intercalation was observed in DNA unwinding studies, but competitive binding experiments with Hoechst 33342 and CC-1065 indicated that topsentin bound to DNA in the minor groove.


title: Asymptomatic MERS-CoV Infection in Humans Possibly Linked to Infected Dromedaries Imported from Oman to United Arab Emirates, May 2015

text: In May 2015 in United Arab Emirates, asymptomatic Middle East respiratory syndrome coronavirus infection was identified through active case finding in 2 men with exposure to infected dromedaries. Epidemiologic and virologic findings suggested zoonotic transmission. Genetic sequences for viruses from the men and camels were similar to those for viruses recently detected in other countries.


title: 4.25 Mitigation and Adaptation Strategies to Reduce Climate Vulnerabilities and Maintain Ecosystem Services

text: Abstract Increasing temperatures and altered precipitation regimes associated with human-caused changes in the earth s climate are having substantial impacts on ecological systems and human well-being. Maintaining functioning ecosystems, the provision of ecosystem services, and healthy human populations into the future will require integrating adaptation and mitigation strategies. Adaptation strategies are actions that help human and natural systems accommodate changes. Mitigation strategies are actions that reduce anthropogenic influences on climate. Here, we provide an overview of what will likely be some of the most effective and most important mitigation and adaptation strategies for addressing climate change. In addition to describing the ways in which these strategies can address impacts to natural and human systems, we discuss the social considerations that we believe must be incorporated into the development and application of mitigation or adaptation strategies to address political situations, cultural differences, and economic limitations.


title: Hospital-based influenza morbidity and mortality surveillance system for influenza-like illnesses: a comparison with national influenza surveillance systems

text: The Hospital-based Influenza Morbidity and Mortality (HIMM) surveillance system is an emergency room (ER)-based influenza surveillance system in Korea that was established in 2011. The system was established under the assumption that integrated clinical and virologic surveillance could be performed rapidly and easily at seven tertiary hospitals' ER. Here, we assessed the correlation between data generated from the HIMM surveillance system and the Korean national influenza surveillance systems during the 2011–2012 influenza season using cross-correlation analysis and found strong correlations. Rapid antigen-test-based HIMM surveillance would predict the start of influenza epidemic earlier than pre-existing influenza-like-illness-based surveillance.


title: The utility of delta neutrophil index in differentiation of pulmonary tuberculosis from community acquired pneumonia

text: No data exist on the usefulness of the delta neutrophil index (DNI) to discriminate pulmonary tuberculosis (PTB) from community-acquired pneumonia (CAP). We performed a retrospective cohort study involving patients with PTB (n = 62) and CAP (n = 215), and compared their initial DNI levels. The median DNI values were 0% (interquartile ranges [IQR] 0–0.2%) and 1.6% (IQR 0.7–2.9%) in PTB and CAP, respectively, which was significantly lower in PTB patients (P < 0.001). Sixty-nine percent of patients with PTB had DNI value of 0%; however, only 15% of patients with CAP had 0% DNI. The discriminatory power of the DNI for diagnosing PTB was high with 89% sensitivity and 67% specificity at a DNI cut-off ≤ 1.0% (area under the curve, 0.852). The diagnostic sensitivity and negative predictive value (NPV) for PTB were 89% (55/62) and 95% (145/152) at the DNI cut-off ≤ 1.0%, respectively, and in multivariate analyses after adjusting for other factors (smoking, no fever, upper lobe involvement), DNI ≤ 1.0% remained significant (odds ratio, 15.265; P < 0.001). We demonstrated that the DNI was lower in PTB compared with CAP, and an initially elevated DNI (>1.0%) may be useful to rule out the possibility of PTB due to its high NPV.


title: Diagnostics as the first line of defense in global health security

text: The creation of the Global Health Security Agenda is a key step in the goal of combatting outbreaks in an increasingly interconnected world. It is too bad that the initiative is so woefully underfunded.


title: Developing vaccines to counter bioterrorist threats

text: Large and innovative research programs are underway to define the immune parameters for vaccines against a wide array of pathogens considered to represent a potential bioterrorist threat. However, the development and utilization of such vaccines presents a number of predicaments that have not previously been addressed by the field of vaccinology.


title: Proteomic Profiling of Purified Rabies Virus Particles

text: While host proteins incorporated into virions during viral budding from infected cell are known to play essential roles in multiple process of the life cycle of progeny virus, these characteristics have been largely neglected in studies on rabies virus (RABV). Here, we purified the RABV virions with good purity and integrity, and analyzed their proteome by nano LC–MS/MS, followed by the confirmation with immunoblot and immuno-electronic microscopy. In addition to the 5 viral proteins, 49 cellular proteins were reproducibly identified to be incorporated into matured RABV virions. Function annotation suggested that 24 of them were likely involved in virus replication. Furthermore, cryo-EM was employed to observe the purified RABV virions, generating high-resolution pictures of the bullet-shaped virion structure of RABV. This study has provided new insights into the host proteins composition in RABV virion and shed the light for further investigation on molecular mechanisms of RABV infection, as well as the discovery of new anti-RABV therapeutics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-019-00157-6) contains supplementary material, which is available to authorized users.


title: Illicit Wildlife Trade, Wet Markets, and COVID‐19: Preventing Future Pandemics

text: Although the exact origin of SARS‐CoV‐2, the etiologic agent of COVID‐19, is currently unknown, there is substantial evidence to suggest the source of transmission of the virus occurred within the Wuhan wet market. In these markets, bats and wild animals are frequently sold and stored in close contact. During several of the world's past pandemics, bats were essential to the spread of zoonotic diseases from bat to another animal or to humans directly. Live animal markets create the perfect conditions for novel viruses such as COVID‐19 to emerge. This paper suggests that to prevent future pandemics, the sale of exotic animals be banned at wet markets. It also advocates for the integration of the analysis of illicit trade with the study of zoonotic disease transmission and pandemics.


title: Suspicious minds: cinematic depiction of distrust during epidemic disease outbreaks

text: One key factor that appears to be crucial in the rejection of quarantines, isolation and other social controls during epidemic outbreaks is trust—or rather distrust. Much like news reporting and social media, popular culture such as fictional novels, television shows and films can influence people’s trust, especially given that the information provided about an epidemic disease is sometimes seen as grounded in ‘scientific fact’ by societies. As well as providing information on the ‘correct science’ behind disease transmission, spread and illness in films and literature, popular culture can also inform societies about how to feel and how to react during epidemics—that is to say create some expectations about the kinds of societal responses that could potentially occur. In this article we closely analyse three films that centre around epidemic diseases—Contagion (Steven Soderbergh, 2011), Blindness (Fernando Meirelles, 2008) and The Painted Veil (John Curran, 2006)—in order to highlight three categories of distrust that have recently been identified and conceptualised in broader discussions regarding trust and health: institutional, social and interpersonal. These films raise two key issues about trust and social responses during epidemics. First, while certain aspects of trust are badly diminished during epidemic disease outbreaks, epidemics can also interact with pre-existing structural inequalities within society—based on race, gender or wealth—to create mixed outcomes of discord, prejudice and fear that coexist with new forms of cohesion. Second, the breakdown in trust seen at certain levels during epidemics, such as at the institutional level between communities and authorities or elites, might be mediated or negotiated, perhaps even compensated for, by heightened solidity of trust at the social level, within or between communities.


title: Unconventional RNA‐binding proteins step into the virus–host battlefront

text: The crucial participation of cellular RNA‐binding proteins (RBPs) in virtually all steps of virus infection has been known for decades. However, most of the studies characterizing this phenomenon have focused on well‐established RBPs harboring classical RNA‐binding domains (RBDs). Recent proteome‐wide approaches have greatly expanded the census of RBPs, discovering hundreds of proteins that interact with RNA through unconventional RBDs. These domains include protein–protein interaction platforms, enzymatic cores, and intrinsically disordered regions. Here, we compared the experimentally determined census of RBPs to gene ontology terms and literature, finding that 472 proteins have previous links with viruses. We discuss what these proteins are and what their roles in infection might be. We also review some of the pioneering examples of unorthodox RBPs whose RNA‐binding activity has been shown to be critical for virus infection. Finally, we highlight the potential of these proteins for host‐based therapies against viruses. RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications. RNA in Disease and Development > RNA in Disease. RNA Interactions with Proteins and Other Molecules > RNA–Protein Complexes.


title: Guidance on Diagnosis, Prevention and Treatment of Thromboembolic Complications in COVID-19: a position paper of the Brazilian Society of Thrombosis and Hemostasis and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy

text: Abstract Hemostatic abnormalities and thrombotic risk associated with coronavirus disease 2019 (COVID-19) are among the most discussed topics in the management of this disease. The aim of this position paper is to provide the opinion of Brazilian experts on the thromboprophylaxis and management of thrombotic events in patients with suspected COVID-19, in the sphere of healthcare in Brazil. To do so, the Brazilian Society of Thrombosis and Hemostasis (BSTH) and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) have constituted a panel of experts to carefully review and discuss the available evidence about this topic. The data discussed in this document was reviewed by May 9, 2020. Recommendations and suggestions reflect the opinion of the panel and should be reviewed periodically as new evidence emerges.


title: Development of an enhanced Acute Care Surgery service in response to the COVID-19 global pandemic: Assessment of clinical patient outcomes and staff psychological well-being

text: Background: As the COVID-19 pandemic sweeps across the world, healthcare departments must adapt to meet the challenges of service provision and staff/patient protection. Unlike elective surgery, ACS workloads cannot be artificially reduced providing a unique challenge for administrators to balance healthcare resources between the COVID-19 surge and regular patient admissions. Methods: An enhanced ACS (eACS) model of care is described with the aim of limiting COVID-19 healthcare worker and patient cross-infection as well as providing 24/7 management of emergency general surgical (GS) and trauma patients. The eACS service comprised 5 independent teams covering a rolling 1:5 24-hr call. Attempts to completely separate eACS teams and patients from the elective side were made. The service was compared to the existing ACS service in terms of clinical and efficiency outcomes. Finally, a survey of staff attitudes towards these changes, concerns regarding COVID-19 and psychological well-being was assessed. Results: There were no staff/patient COVID-19 cross-infections. Compared to the ACS service, eACS patients had reduced overall length of stay (2-days), time spent in the Emergency Room (46 minutes) and time from surgery to discharge (2.4-hours). The eACS model of care saved financial resources and bed-days for the organisation. The changes were well received by team-members who also felt that their safety was prioritised. Conclusion: In healthcare systems not overwhelmed by COVID-19, an eACS model may assist in preserving psychological well-being for healthcare staff whilst providing 24/7 care for emergency GS and trauma patients.


Smell and taste disorders: warning signs for SARS-CoV-2 infection()


title: Antibody response to infectious diseases and other factors accurately predict COVID-19 infection and severity risk 10–14 years later: a retrospective UK Biobank cohort study

text: BACKGROUND: Several risk factors have emerged for novel 2019 coronavirus disease (COVID-19) infection and severity. Yet, it is unknown to what degree these risk factors alone or in combination can accurately predict who is most at risk. It is also worthwhile to consider serological antibody titers to non COVID-19 infectious diseases, which may influence host immunity to COVID-19. METHODS: In this retrospective study of multicenter UK Biobank participants, as of May 26(th) 2020, all COVID-19 testing data was collected by Public Health England for older adult in- and out-patients (69.6 ± 8.8 years). We used linear discriminant analysis with cross-validation and bootstrapping to determine the accuracy, specificity, and sensitivity of baseline data from 2006–2010 to predict COVID-19 infection and presumptive severity (i.e., testing at hospital). Receiver operating characteristic (ROC) curves were used to derive the area under the curve (AUC). FINDINGS: This retrospective study included 4,510 unique participants and 7,539 testing instances (i.e., test cases). Testing resulted in 5,329 negative cases and 2,210 positive cases, split into 996 mild and 1,214 severe disease outcomes. Baseline data including demographics, bioimpedance-derived body composition, vitals, serum biochemistry, self-reported illness/disability, and complete blood count. A randomized subset of 80 participants with 124 test cases also had antibody titers for 20 common to rare infectious diseases. Among all test cases, accuracy was modest for final diagnostic models of COVID-19 infection (70.2%; AUC=0.570, CI=0.556–0.584) and severity (58.3%; AUC=0.592, CI=0.568–0.615). In the serology sub-group, by contrast, final models predicted infection and severity with an accuracy of 93.5% (AUC=0.969, CI=0.934–1.000) and 74.4% (AUC=0.803, CI=0.663–0.943) respectively. Models included titers to common pathogens (e.g., human cytomegalovirus), age, blood cell counts, lipids, and other biochemical markers. INTERPRETATION: Risk profiles including serological titers and other risk factors could help policy makers and clinicians better identify who may get COVID-19 and require hospitalization.


title: Adenoviruses as vaccine vectors

text: Adenoviruses have transitioned from tools for gene replacement therapy to bona fide vaccine delivery vehicles. They are attractive vaccine vectors as they induce both innate and adaptive immune responses in mammalian hosts. Currently, adenovirus vectors are being tested as subunit vaccine systems for numerous infectious agents ranging from malaria to HIV-1. Additionally, they are being explored as vaccines against a multitude of tumor-associated antigens. In this review we describe the molecular biology of adenoviruses as well as ways the adenovirus vectors can be manipulated to enhance their efficacy as vaccine carriers. We describe methods of evaluating immune responses to transgene products expressed by adenoviral vectors and discuss data on adenoviral vaccines to a selected number of pathogens. Last, we comment on the limitations of using human adenoviral vectors and provide alternatives to circumvent these problems. This field is growing at an exciting and rapid pace, thus we have limited our scope to the use of adenoviral vectors as vaccines against viral pathogens.


title: Multi-host pathogens and carnivore management in southern Africa

text: Abstract A retrospective serosurvey of multi-host feline and canine viruses among carnivore species in southern Africa (n =1018) identified widespread pathogen exposure even in remote protected areas. In contrast to mortality experienced in East African predators, canine distemper virus (CDV) infection among African wild dogs (Lycaon pictus) in Botswana was not associated with identifiable change in pup survivorship or disease related mortality of adults. A disease outbreak of unknown aetiology occurred in the same population over 4 weeks in 1996. Outbreak boundaries coincided with ecotones, not the spatial distribution of contiguous packs, highlighting the potential importance of landscape heterogeneities in these processes. Direct management of pathogens in domestic animal reservoirs is complicated by the apparent complexity of pathogen maintenance and transmission in these large systems. Conservation effort should be focused at securing large metapopulations able to compensate for expected episodic generalist pathogen invasion and attention directed to addressing underlying causes of population depression such as habitat loss and wildlife conflict.


title: Flattening the curve in oncologic surgery: Impact of Covid‐19 on surgery at tertiary care cancer center

text: INTRODUCTION: Covid‐19 has ushered in drastic changes to the healthcare system in order to “flatten the curve”; in particular, surgical operations that can consume vital, limited resources, not to mention the risk to staff, anesthesiologists, and surgeons. However, under unique circumstances with diligent preparation, vital oncologic operations can be performed safely. METHODS: Prospective comparison of surgical cases during the pandemic from December 2019 to May 2020 to the correlating time frame from December 2018 to May 2019. RESULTS: A significant decline in case volume was not appreciated until the United States declared a national state of emergency, allowing patients with cancer to continue to undergo curative tumor resection until then (428.3 ± 51.5 vs 166.6 ± 59.8 cases/week; P < .001). The decrease was consistent with the mean case volume during the holidays (213.8 ± 76.8 vs 166.6 ± 59.8 case/week; P = .648). Evaluation of surgical subspecialties demonstrated a significant decrease for all subspecialties with the greatest decline in sarcoma (P = .002) and endocrine (P = .001) surgeries, while vascular (P = .004) and thoracic (P = .011) surgeries had the least. CONCLUSIONS: The novel coronavirus has drastically reduced oncologic operations, but with proper evaluation of patients and allocation of resources, surgery can be performed safely without compromising the aim to flatten the curve and control the coronavirus pandemic.


title: Legal aspects of public health: How law frames communicable disease control in Greece

text: We reviewed Greek law (legislation, historic Royal Decrees, and modern Presidential ones, 1833–2010) pertinent to control of communicable diseases and compared this body of Greek law with the revised International Health Regulations. Greece authorizes and regulates communicable disease control commensurate with public health risks, and integrates the principles of equality, objectivity, and respect for human rights. Despite strength at the level of principles, Greek law lacks coherence, clarity, and systematization. An inadequate body of regulations means legislation falls short of adequate implementing authority and guidelines; public health authorities often cannot find or understand the laws, nor are they certain about allocation of jurisdictional authority. We identified areas for improvement.


title: Production of Defective Interfering Particles of Influenza A Virus in Parallel Continuous Cultures at Two Residence Times—Insights From qPCR Measurements and Viral Dynamics Modeling

text: Defective interfering particles (DIPs) are a natural byproduct of influenza A virus (IAV) replication. DIPs interfere with the propagation and spread of infectious standard virus (STV), reduce virus yields by competing for viral and cellular resources, and induce antiviral responses. These properties open exciting possibilities for the development of DIP-based antivirals. Exploring options for cell culture-based DIP production, we have established a fully continuous cultivation process, where one bioreactor is used to grow cells that are fed to two bioreactors operated in parallel for virus production. This system allows head-to-head comparisons of STV and DIP replication dynamics over extended time periods. Cultivations were performed at two residence times (RT, 22 and 36 h) using MDCK suspension cells grown in a fully defined medium. For infection, we used a virus seed generated by reverse genetics containing STVs and a known DIP carrying a deletion in segment 1 (delS1(1)). Four days post infection, DIPs achieved maximum concentrations of 7.0·10(9) virions/mL and 8.4·10(9) virions/mL for RTs of 22 and 36 h, respectively. Furthermore, oscillations in virus titers with two to three maxima were found for DIP accumulation at 36 and 22 h RT, respectively. To complement the study, a basic mathematical model using simple kinetics and a reasonable number of parameters to describe DIP-propagation in continuous cultures was established. Upon fitting the model individually to each of the two data sets, oscillations in the viral dynamics and the cell population dynamics were described well. Modeling suggests that both STV inactivation and virus degradation have to be taken into account to achieve good agreement of simulations and experimental data for longer RTs. Together, the high DIP titers obtained, and the successful simulation of the experimental data showed that the combination of continuous bioreactors and mathematical models can enable studies regarding DIP dynamics over extended time periods and allow large scale manufacturing of DIP-based antivirals.


title: Hydrogen peroxide and viral infections: a literature review with research hypothesis definition in relation to the current covid-19 pandemic

text: We reviewed the literature concerning the innate response from nasal and oral epithelial cells and their reaction to hydrogen peroxide (H(2)O(2)). Hydrogen peroxide is produced physiologically by oral bacteria and plays a significant role in the balance of oral microecology since it is an important antimicrobial agent. In the epithelial cells, the enzyme superoxide dismutase catalyzes a reaction leading from hydrogen peroxide to the ion superoxide. The induced oxidative stress stimulates a local innate response via activation of the toll-like receptors and the NF-κB. Those kinds of reactions are also activated by viral infections. Virus-induced oxidative stress plays an important role in the regulation of the host immune system and the specific oxidant-sensitive pathway is one of the effective strategies against viral infections. Therefore, nose/mouth/throat washing with hydrogen peroxide may enhance those local innate responses to viral infections and help protect against the current coronavirus pandemic. We strongly encourage the rapid development of randomized controlled trials in both SARS-CoV-2 positive and negative subjects to test the preliminary findings from the in-vitro and in-vivo observational studies that we identified.


title: Diagnostic accuracy of an automated chemiluminescent immunoassay for anti‐SARS‐CoV‐2 IgM and IgG antibodies: an Italian experience

text: A pandemic of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been spreading throughout the world. Though molecular diagnostic tests are the gold standard for COVID‐19, serological testing is emerging as a potential surveillance tool, in addition to its complementary role in COVID‐19 diagnostics. Indubitably quantitative serological testing provides greater advantages than qualitative tests but today there is still little known about serological diagnostics and what the most appropriate role quantitative tests might play. Sixty‐one COVID‐19 patients and 64 patients from a control group were tested by iFlash1800 CLIA analyzer for anti‐SARS CoV‐2 antibodies IgM and IgG. All COVID‐19 patients were hospitalized in San Giovanni di Dio Hospital (Florence, Italy) and had a positive oro/nasopharyngeal swab reverse‐transcription polymerase chain reaction result. The highest sensitivity with a very good specificity performance was reached at a cutoff value of 10.0 AU/mL for IgM and of 7.1 for IgG antibodies, hence near to the manufacturer's cutoff values of 10 AU/mL for both isotypes. The receiver operating characteristic curves showed area under the curve values of 0.918 and 0.980 for anti‐SARS CoV‐2 antibodies IgM and IgG, respectively. iFlash1800 CLIA analyzer has shown highly accurate results for the anti‐SARS‐CoV‐2 antibodies profile and can be considered an excellent tool for COVID‐19 diagnostics.


title: Detection and characterization of three zoonotic viruses in wild rodents and shrews from Shenzhen city, China

text: Diverse species of rodents and shrews, which are abundant worldwide, harbor a variety of viruses; some of these are closely related to human viruses and possess zoonotic potential. Previously studies have demonstrated that the mammarenavirus and hantavirus carried by rodents or shrews could cause diseases in human population. To determine the distribution of zoonotic viruses in Shenzhen city, the major city in southern China with a high population density, we analyzed 225 rodents (Rattus norvegicus and Rattus flavipectus) and 196 shrews (Suncus murinus) from urban and rural districts for the presence of mammarenavirus, hantavirus, and hepatitis E virus (HEV) by RT-PCR targeting the conserved regions. The infection rates for mammarenavirus, hantaviruses, and HEV in rodents and shrews were 3.56%, 6.89%, and 1.66%, respectively. Partial genome fragment analysis indicated that mammarenavirus and hantavirus strains had more than 90% and 99% nucleic acid identity with Cardamones virus and Seoul virus, respectively, which cause diseases in humans. Although the present HEV strains identified are typically found worldwide, phylogenetic analysis demonstrated a divergence of 16%. To our knowledge, the present work is the first report of the prevalence of mammarenavirus, hantaviruses, and rat HEV strains in rodents and shrews from Shenzhen city, China. Our findings highlight the zoonotic potential of rodent- and shrew-borne mammarenavirus and hantavirus, and the biodiversity of rat HEV isolates in Shenzhen city. The present work suggests that utilization of good hygiene habits is important to minimize the risk of zoonosis.


title: Autographa californica Multiple Nucleopolyhedrovirus Ac34 Protein Retains Cellular Actin-Related Protein 2/3 Complex in the Nucleus by Subversion of CRM1-Dependent Nuclear Export

text: Actin, nucleation-promoting factors (NPFs), and the actin-related protein 2/3 complex (Arp2/3) are key elements of the cellular actin polymerization machinery. With nuclear actin polymerization implicated in ever-expanding biological processes and the discovery of the nuclear import mechanisms of actin and NPFs, determining Arp2/3 nucleo-cytoplasmic shuttling mechanism is important for understanding the function of nuclear actin. A unique feature of alphabaculovirus infection of insect cells is the robust nuclear accumulation of Arp2/3, which induces actin polymerization in the nucleus to assist in virus replication. We found that Ac34, a viral late gene product encoded by the alphabaculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV), is involved in Arp2/3 nuclear accumulation during virus infection. Further assays revealed that the subcellular distribution of Arp2/3 under steady-state conditions is controlled by chromosomal maintenance 1 (CRM1)-dependent nuclear export. Upon AcMNPV infection, Ac34 inhibits CRM1 pathway and leads to Arp2/3 retention in the nucleus.


title: Common variations in TERT-CLPTM1L locus are reproducibly associated with the risk of nasopharyngeal carcinoma in Chinese populations

text: Associations between single nucleotide polymorphisms (SNPs) at 5p15 (TERT-CLPTM1L) and multiple cancer types have been reported. We examined whether polymorphisms in the TERT-CLPTM1L locus were related to the risk of developing nasopharyngeal carcinoma (NPC) among Chinese populations. In the first stage, 26 tag SNPs were genotyped in a Guangxi population (855 patients and 1036 controls). In the second stage, the SNPs, which showed significant association, were further genotyped in a Guangdong population (997 patients and 972 controls). Functional analyses were conducted to verify the biological relevance of the associated polymorphism. In the 1st stage, four SNPs (rs2736098, rs2735845, rs402710, and rs401681) were significantly associated with the risk of developing NPC. After the 2nd stage validation, rs2735845 and rs401681 were independently associated with the risk of developing NPC in the additive model (rs2735845, OR = 1.19, 95% CI = 1.04–1.37, P = 0.011; rs401681, OR = 0.85, 95% CI = 0.74–0.99, P = 0.034). Furthermore, we observed higher CLPTM1L messenger RNA levels in fetal mesenchymal stem cells from the rs2735845 G allele carriers compared with that from non-carriers. In addition, using an immunohistochemistry assay, we observed higher TERT and CLPTM1L levels in NPC tissues compared with that in non-cancerous nasopharyngeal tissues. Our findings suggest that polymorphisms in the TERT-CLPTM1L locus may play a role in mediating the susceptibility to NPC in Chinese populations.


title: Recent advances in one-stage conversion of lipid-based biomass-derived oils into fuel components – aromatics and isomerized alkanes

text: Nowadays, production of biofuels is a rather hot topic due to depleting of conventional fossil fuel feedstocks and a number of other factors. Plant lipid-based feedstocks are very important for production of diesel-, kerosene-, and gasoline-like hydrocarbons. Usually, (hydro)deoxygenation processes are aimed at obtaining of linear hydrocarbons known to have poor fuel characteristics compared to the branched ones. Thus, further hydroisomerization is required to improve their properties as motor fuel components. This review article is focused on conversion of lipid-based feedstocks and model compounds into high-quality fuel components for a single step – direct cracking into aromatics and merged hydrodeoxygenation-hydroisomerization to obtain isoparaffins. The second process is quite novel and a number of the research articles presented in the literature is relatively low. As auxiliary subsections, hydroisomerization of straight hydrocarbons and techno-economic analysis of renewable diesel-like fuel production are briefly reviewed as well.