title: Scabies: Application of the Novel Identify-Isolate-Inform Tool for Detection and Management

text: Scabies is a highly contagious, globally prevalent, parasitic skin infestation caused by Sarcoptes scabiei var. hominis, also known as the itch mite. There have been outbreaks not only in the developing world, but also in the developed world among refugees and asylum seekers. Once infested with scabies mites, symptomatic patients, as well as asymptomatic carriers, quickly spread the disease through direct skin-to-skin contact. Typically, symptoms of scabies are characterized by an erythematous, papular, pruritic rash associated with burrows. Treatment of scabies involves using topical or systemic scabicides and treating secondary bacterial infections, if present. Given the prevalence and contagiousness of scabies, measures to prevent its spread are essential. Through application of the novel Identify-Isolate-Inform (3I) Tool, emergency medical providers can readily identify risk factors for exposure and important symptoms of the disease, thus limiting its spread through prompt scabicide therapy; isolate the patient until after treatment; and inform local public health authorities and hospital infection prevention, when appropriate. Ultimately, these three actions can aid public health in controlling the transmission of scabies cases, thus ensuring the protection of the general public from this highly contagious skin infestation.


title: Molecular Diagnostic Assays for Infectious Diseases in Cats

text: With the advent of more accessible polymerase chain reaction panels, the use of molecular techniques for the detection of infectious organisms has become more routine in veterinary medicine. The use of molecular diagnostics is best reserved for the detection of organisms that are difficult to detect or identify expediently. In this article, the fundamentals of molecular techniques are reviewed along with an examination of specific feline infectious diseases in which diagnosis via molecular techniques is advantageous.


title: Viral Infections of Rabbits

text: Viral diseases of rabbits have been used historically to study oncogenesis (e.g. rabbit fibroma virus, cottontail rabbit papillomavirus) and biologically to control feral rabbit populations (e.g. myxoma virus). However, clinicians seeing pet rabbits in North America infrequently encounter viral diseases although myxomatosis may be seen occasionally. The situation is different in Europe and Australia, where myxomatosis and rabbit hemorrhagic disease are endemic. Advances in epidemiology and virology have led to detection of other lapine viruses that are now recognized as agents of emerging infectious diseases. Rabbit caliciviruses, related to rabbit hemorrhagic disease, are generally avirulent, but lethal variants are being identified in Europe and North America. Enteric viruses including lapine rotavirus, rabbit enteric coronavirus and rabbit astrovirus are being acknowledged as contributors to the multifactorial enteritis complex of juvenile rabbits. Three avirulent leporid herpesviruses are found in domestic rabbits. A fourth highly pathogenic virus designated leporid herpesvirus 4 has been described in Canada and Alaska. This review considers viruses affecting rabbits by their clinical significance. Viruses of major and minor clinical significance are described, and viruses of laboratory significance are mentioned.


Turning Adversity and Deprivation into Improvements in Medicine – The COVID Opportunity


title: Structures of human antibodies bound to SARS-CoV-2 spike reveal common epitopes and recurrent features of antibodies

text: Summary Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal IgGs and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their focus on RBD epitopes, recognition of alpha- and beta-coronaviruses, and contributions of avidity to increased binding/neutralization of IgGs over Fabs. Using electron microscopy, we examined specificities of polyclonal plasma Fabs, revealing recognition of both S1A and RBD epitopes on SARS-CoV-2 spike. Moreover, a 3.4Å cryo-EM structure of a neutralizing monoclonal Fab-spike complex revealed an epitope that blocks ACE2 receptor binding. Modeling based on these structures suggested different potentials for inter-spike crosslinking by IgGs on viruses and that characterized IgGs would not be affected by identified SARS-CoV-2 spike mutations. Overall, our studies structurally define a recurrent anti-SARS-CoV-2 antibody class derived from VH3-53/VH3-66 and similarity to a SARS-CoV VH3-30 antibody, providing criteria for evaluating vaccine-elicited antibodies.


Tratamiento antimicrobiano frente a la colonización pulmonar por Pseudomonas aeruginosa en el paciente con fibrosis quística


title: Innate immune response in neonate Holstein heifer calves fed fresh or frozen colostrum

text: Abstract The aim of this research was to evaluate the influence of maternal cells from colostrum on the development and function of the innate immune response in Holstein calves. Calves were divided into 2 groups: COL+ (n =10) received fresh colostrum; and COL− (n =10) which received frozen colostrum containing no viable cells. The calves were assessed before colostrum intake (D0), 48h of age (D2), and weekly from D7 up to D28. Blood samples were collected for analysis of the distribution of leukocytes, cellular phenotype and in vitro granulocyte function. COL+ calves tended to have a high number of neutrophils on D7 (p =0.073). COL− calves took up significantly more Escherichia coli (measured as MFI) on D7 (p =0.034). Endogenous production of radicals (as percentage of cells) tended to be higher in COL− calves on D14 (p =0.061). The intensity of endogenous reactive oxygen species (ROS) produced by granulocytes tended to be higher in COL+ calves on D21 (p =0.094). Overall, ROS production (percent of cells, and MFI) induced by Staphylococcus aureus and Escherichia coli were higher in COL+ calves than COL− calves. It was our observation that COL+ calves developed an innate immune response more quickly and efficiently after natural exposure to pathogens after birth. In contrast, COL− calves mounted an innate response more slowly that yielded a persistent inflammatory response after natural exposure to these bacteria agents. This research provides evidence of an advantage to the calf of receiving fresh colostrum on the development and function of the innate immune system.


title: Sustainable vaccine development: a vaccine manufacturer's perspective

text: Vaccination remains the most cost-effective public health intervention after clean water, and the benefits impressively outweigh the costs. The efforts needed to fulfill the steadily growing demands for next-generation and novel vaccines designed for emerging pathogens and new indications are only realizable in a sustainable business model. Vaccine development can be fast-tracked through strengthening international collaborations, and the continuous innovation of technologies to accelerate their design, development, and manufacturing. However, these processes should be supported by a balanced project portfolio, and by managing sustainable vaccine procurement strategies for different types of markets. Collectively this will allow a gradual shift to a more streamlined and profitable vaccine production, which can significantly contribute to the worldwide effort to shape global health.


title: Hsp70 functions as a negative regulator of West Nile virus capsid protein through direct interaction

text: Abstract West Nile virus (WNV) is a member of the Flavivirus family and induces febrile illness, sporadic encephalitis, and paralysis. The capsid (Cp) of WNV is thought to play a role in inducing these symptoms through caspase-3- and caspase-9-dependent apoptosis. Using WNVCp as bait for a yeast two-hybrid assay, we identified that Hsp70 interacted with WNVCp. The interaction between Hsp70 and WNVCp was further substantiated using purified proteins. Deletion analysis of Hsp70 indicated that WNVCp could bind to the substrate binding domain of Hsp70. The presence of WNVCp in the Hsp70-dependent folding system inhibited the refolding of β-galactosidase (β-gal), which showed that WNVCp might function as a negative regulator of Hsp70. Finally, the cytotoxic effect of WNVCp in 293T cells was prevented by ectopic Hsp70, suggesting a negative regulatory role of Hsp70 on WNVCp. Our findings suggest a possible negative regulatory role of Hps70 in the pathway of WNV infection.


title: Trypsin-independent porcine epidemic diarrhea virus US strain with altered virus entry mechanism

text: BACKGROUND: Porcine Epidemic Diarrhea Virus (PEDV) is a coronavirus that infects the intestinal tract and causes diarrhea and vomiting in older pigs or extreme dehydration and death that could reach 100% mortality in neonatal piglets. In the US, the first PEDV outbreaks occurred in 2013 and since then US PEDV strains have quickly spread throughout the US and worldwide, causing significant economic and public health concerns. Currently two conditionally approved vaccines exist in the US, but there is no live attenuated vaccine, which is considered the best option in controlling PEDV by inducing transferrable mucosal immunity to susceptible neonatal piglets. In this study, we passaged an US PEDV isolate under various conditions to generate three strains and characterized their growth and antigenicity in cell culture using various assays including Western blot analysis, serum neutralization assay, sequencing analysis and confocal microscopy. Finally, these strains were evaluated for pathogenicity in nursing piglets (1–4 days old). RESULTS: One of the PEDV strains generated in this study (designated as PEDV 8aa) is able to replicate in cells without any protease and grows to a high titer of >8 log(10) TCID(50)/ml in cell culture. Interestingly, replication of PEDV 8aa was severely reduced by trypsin and this correlated with the inhibition of virus attachment and entry into the cells. In neonatal nursing piglets, PEDV 8aa (passage number 70 or 105) was found to be fully attenuated with limited virus shedding. CONCLUSIONS: These results suggest that applying selective pressure during viral passages can facilitate attainment of viral attenuation and that PEDV 8aa warrants further investigation as an attenuated vaccine.


title: Potential Aggregation-Prone Regions in Complementarity-Determining Regions of Antibodies and Their Contribution Towards Antigen Recognition: A Computational Analysis

text: PURPOSE: To analyze contribution of short aggregation-prone regions (APRs), which may self-associate via cross-β motif and were earlier identified in therapeutic mAbs, towards antigen recognition via structural analyses of antibody-antigen complexes. METHODS: A dataset of 29 publically available high-resolution crystal structures of Fab-antigen complexes was collected. Contribution of APRs towards the surface areas of the Fabs buried by the cognate antigens was computed. Propensities of amino acids to occur in APRs and to be involved in antigen binding were compared. Coincidence between APRs and individual CDR loops was examined. RESULTS: All Fabs in the dataset contain at least one APR in CDR loops and adjacent framework β-strands. The average contribution of APRs towards buried surface area of Fabs is 16.0 ± 10.7%. Aggregation and antigen recognition may be coupled via aromatic residues (Tyr, Trp), which occur with high propensities in both APRs and antigen binding sites. APRs are infrequent in the heavy chain CDR 3 (H3) loops (7%), but are frequent in H2 loops (45%). CONCLUSIONS: Co-incidence of APRs with antigen recognition sites can potentially lead to the loss of function upon aggregation. Rational structure-based design or selection strategies are suggested for biotherapeutics with improved druggability while maintaining potency. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11095-010-0143-5) contains supplementary material, which is available to authorized users.


title: Unique skin manifestations of COVID-19: Is drug eruption specific to COVID-19?

text: • COVID-19 is associated with specific skin manifestations and drug eruption. • This case shows COVID-19–related drug eruption and specific clinical features. • Drug eruption preceding COVID-19 symptoms may facilitate early diagnosis.


Test De Autoevaluación


title: Updates on What ACS Reported: Emerging Evidences of COVID-19 with Nervous System Involvement

text: [Image: see text] With the ongoing pandemic of coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), our knowledge of the pathogenesis of COVID-19 is still in its infancy. Almost every aspect of the pathogen remains largely unknown, ranging from mechanisms involved in infection transmission, interplay with the human immune system, and covert mechanisms of end-organ damage. COVID-19 has manifested itself worldwide with a syndromic appearance that is dominated by respiratory dysregulations. While clinicians are focused on correcting respiratory homeostasis, echoing the original SARS, SARS-CoV-2 is also invading other end-organs, which may not exhibit overt clinical features. Nervous system involvement was not initially considered to play a significant role in patients with COVID-19. However, since this viewpoint was initially published, multiple studies have been released regarding the possible neurovirulence of SARS-CoV-2. In our previous viewpoint, we implored our colleagues to recognize the covert tactics of SARS-CoV-2 and emphasized that symptoms like anosmia, dysgeusia, ataxia, and altered mental status could be early signs of the neurotropic potential of this virus. The past few weeks, after the viewpoint surfaced, it was noticed that it has enabled clinicians and healthcare professionals to compute the neurovirulence associated with SARS-CoV-2 in COVID-19 patients, as evidenced by very recently reported studies.


title: Production of Ebola virus-like particles in Drosophila melanogaster Schneider 2 cells

text: Abstract In this study, we generated recombinant virus-like particles (VLPs) against family Filoviridae, genus Ebolavirus, species Zaire ebolavirus, strain Makona (EBOV) in Drosophila melanogaster Schneider 2 (S2) cells using the EBOV Makona. S2 cells were cotransfected with four viral plasmids encoding EBOV Makona proteins and protein expression was analyzed by immunoblotting. We confirmed that EBOV Makona proteins were successfully expressed in S2 cells. Additionally, we further examined the formation of intracellular and extracellular VLPs by electron microscopy. eVLPs were produced by sucrose gradient ultracentrifugation of S2 cells transfected with EBOV Makona genes, and production of VLPs was confirmed by immunoblot analysis. Collectively, our findings showed that the S2 cell system could be a promising tool for efficient production of eVLPs.


title: Cognitive Processing Therapy for Posttraumatic Stress Disorder via Telehealth: Practical Considerations During the COVID‐19 Pandemic

text: The global outbreak of COVID‐19 has required mental health providers to rapidly rethink and how they provide care. Cognitive processing therapy (CPT) is a trauma‐focused, evidence‐based treatment for posttraumatic stress disorder that is effective when delivered in‐person or via telehealth. Given current limitations on the provision of in‐person mental health treatment during the COVID‐19 pandemic, this article presents guidelines and treatment considerations when implementing CPT via telehealth. Based on lessons learned from prior studies and clinical delivery of CPT via telehealth, recommendations are made with regard to overall strategies for adapting CPT to a telehealth format, including how to conduct routine assessments and ensure treatment fidelity. This article is protected by copyright. All rights reserved


Neglected Tropical Diseases in the Anthropocene: The Cases of Zika, Ebola, and Other Infections


title: Using eHealth to Support COVID-19 Education, Self-Assessment, and Symptom Monitoring in the Netherlands: Observational Study

text: BACKGROUND: The coronavirus disease (COVID-19) situation demands a lot from citizens, health care providers, and governmental institutions. Citizens need to cope with guidelines on social interaction, work, home isolation, and symptom recognition. Additionally, health care providers and policy makers have to cope with unprecedented and unpredictable pressure on the health care system they need to manage. By providing citizens with an app, they always have access to the latest information and can assess their own health. This data could be used to support policy makers and health care providers to get valuable insights in the regional distribution of infection load and health care consumption. OBJECTIVE: The aim of this observational study is to assess people’s use of an app to support them with COVID-19 education, self-assessment, and monitoring of their own health for a 7-day period. In addition, we aim to assess the usability of this data for health care providers and policy makers by applying it to an interactive map and combining it with hospital data. The secondary outcomes of the study were user’s satisfaction with the information provided in the app, perceived usefulness of the app, health care providers they contacted, and the follow-up actions from this contact. METHODS: This observational cohort study was carried out at the nonacademic teaching hospital “Elisabeth Twee Steden” (ETZ) in Tilburg, Netherlands. From April 1, 2020, onwards ETZ offered the COVID-19 education, self-assessment, and symptom tracking diary to their already existing app for patient education and monitoring. RESULTS: Between April 1 and April 20, 2020, a total of 6194 people downloaded the app. The self-assessment functionality was used abundantly to check one’s health status. In total, 5104 people responded to the question about severe symptoms, from which 242 indicated to suffer from severe symptoms. A total of 4929 people responded to the question about mild symptoms, from which 3248 indicated to suffer from these. The data was successfully applied to an interactive map, displaying user demographics and health status. Furthermore, the data was linked to clinical data. App users were satisfied with the information in the app and appreciated the symptom diary functionality. In total, 102 users reached out to a health care provider, leading to 91 contacts. CONCLUSIONS: Our study demonstrated the successful implementation and use of an app with COVID-19 education, self-assessment, and a 7-day symptom diary. Data collected with the app were successfully applied to an interactive map. In addition, we were able to link the data to COVID-19 screening results from the hospital’s microbiology laboratory. This data could be used to support policy makers and health care providers to get valuable insights in the regional distribution of infection load and health care consumption. TRIAL REGISTRATION: Netherlands Trial Register NL8501; https://www.trialregister.nl/trial/8501


title: Factors affecting hospital response in biological disasters: A qualitative study

text: Background: The fatal pandemics of infectious diseases and the possibility of using microorganisms as biological weapons are both rising worldwide. Hospitals are vital organizations in response to biological disasters and have a crucial role in the treatment of patients. Despite the advances in studies about hospital planning and performance during crises, there are no internationally accepted standards for hospital preparedness and disaster response. Thus, this study was designed to explain the effective factors in hospital performance during biological disasters. Methods: Qualitative content analysis with conventional approach was used in the present study. The setting was Ministry of Health and related hospitals, and other relevant ministries responsible at the time of biologic events in Islamic Republic of Iran (IR of Iran) in 2018. Participants were experts, experienced individuals providing service in the field of biological disaster planning and response, policymakers in the Ministry of Health, and other related organizations and authorities responsible for the accreditation of hospitals in IR of Iran. Data were collected using 12 semi-structured interviews in Persian language. Analysis was performed according to Graneheim method. Results: After analyzing 12 interviews, extraction resulted in 76 common codes, 28 subcategories, and 8 categories, which are as follow: detection; treatment and infection control; coordination, Resources; training and exercises; communication and information system; construction; and planning and assessment. Conclusion: Hospital management in outbreaks of infectious diseases (intentional or unintentional) is complex and requires different actions than during natural disasters. In such disasters, readiness to respond and appropriate action is a multifaceted operation. In IR of Iran, there have been few researches in the field of hospital preparation in biologic events, and the possibility of standardized assessment has be reduced due to lack of key skills in confronting biological events. It is hoped that the aggregated factors in the 8 groups of this study can evaluate hospital performance more coherently.


Coronavirus come of age


title: Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion

text: The recent outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 infection in Wuhan, China has posed a serious threat to global public health. To develop specific anti-coronavirus therapeutics and prophylactics, the molecular mechanism that underlies viral infection must first be defined. Therefore, we herein established a SARS-CoV-2 spike (S) protein-mediated cell–cell fusion assay and found that SARS-CoV-2 showed a superior plasma membrane fusion capacity compared to that of SARS-CoV. We solved the X-ray crystal structure of six-helical bundle (6-HB) core of the HR1 and HR2 domains in the SARS-CoV-2 S protein S2 subunit, revealing that several mutated amino acid residues in the HR1 domain may be associated with enhanced interactions with the HR2 domain. We previously developed a pan-coronavirus fusion inhibitor, EK1, which targeted the HR1 domain and could inhibit infection by divergent human coronaviruses tested, including SARS-CoV and MERS-CoV. Here we generated a series of lipopeptides derived from EK1 and found that EK1C4 was the most potent fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and pseudovirus infection with IC50s of 1.3 and 15.8 nM, about 241- and 149-fold more potent than the original EK1 peptide, respectively. EK1C4 was also highly effective against membrane fusion and infection of other human coronavirus pseudoviruses tested, including SARS-CoV and MERS-CoV, as well as SARSr-CoVs, and potently inhibited the replication of 5 live human coronaviruses examined, including SARS-CoV-2. Intranasal application of EK1C4 before or after challenge with HCoV-OC43 protected mice from infection, suggesting that EK1C4 could be used for prevention and treatment of infection by the currently circulating SARS-CoV-2 and other emerging SARSr-CoVs.


title: Coronavirus Disease 2019 in Children: Characteristics, Antimicrobial Treatment, and Outcomes

text: Abstract Background At present, coronavirus disease 2019 (COVID-19) has spread in many countries. We conducted this study to help paediatricians To help pediatricians understand the conditions of COVID-19 in children, we conducted this study. Methods We retrospectively summarized the characteristics, treatment and outcomes of pediatric cases in Wuhan children's hospital which was the only designated hospital for children with COVID-19 in Hubei Province. A Cox proportional hazards regression analysis was used to evaluate factors associated with clinical outcomes. Results As of February 29, 75 children had been discharged, of which only one was has severe pneumonia and one was critical cases. Children younger than 2 years were more susceptible to COVID-19. All patients have received interferon-α nebulization, and eight cases including the severe and critical cases were co-administrated ribavirin. Five patients with mild pneumonia were given arbidol. Twenty-three patients were given traditional Chinese medicine (TCM). The average length of stay (LOS) and the time of SARS-CoV-2 clearance were 10.57 and 6.39 days, respectively. None of the factors was associated with LOS or time of SARS-CoV-2 clearance. Conclusions The severity of COVID-19 in pediatric cases were milder than adults. The efficacy of the antiviral therapy in children with COVID-19 remains to be evaluated.


title: COVID-19 and the re-opening of schools: a policy maker’s dilemma

text: The epidemic of coronavirus disease 2019 (COVID-19) broke out in Wuhan, China, in December 2019 and rapidly spread across the world. In order to counter this epidemic, several countries put in place different restrictive measures, such as the school’s closure and a total lockdown. However, as the knowledge on the disease progresses, clinical evidence showed that children mainly have asymptomatic or mild disease and it has been suggested that they are also less likely to spread the virus. Moreover, the lockdown and the school closure could have negative consequences on children, affecting their social life, their education and their mental health. As many countries have already entered or are planning a phase of gradual lifting of the containment measures of social distancing, it seems plausible that the re-opening of nursery schools and primary schools could be considered a policy to be implemented at an early stage of recovery efforts, putting in place measures to do it safely, such as the maintenance of social distance, the reorganisation of classes into smaller groups, the provision of adequate sanitization of spaces, furniture and toys, the prompt identification of cases in the school environment and their tracing. Therefore, policy makers have the task of balancing pros and cons of the school re-opening strategy, taking into account psychological, educational and social consequences for children and their families. Another issue to be considered is represented by socio-economic disparities and inequalities which could be amplified by school’s closure.


title: Diagnosis and Management of Group A Streptococcal Pharyngitis: A Practice Guideline

text: This is the second in a series of practice guidelines commissioned by the Infectious Diseases Society of America through its Practice Guidelines Committee. The purpose of these guidelines is to provide assistance to clinicians when making decisions on treating the conditions specified in each guideline. The targeted providers are pediatricians, family practitioners, and internists. The targeted patients and setting for the acute pharyngitis guideline are pediatric, adolescent, and adult outpatients with a complaint of sore throat. Funding was provided by the IDSA. Panel members represented experts in adult and pediatric infectious diseases. The guidelines are evidence-based. A standard ranking system was used for the strength of the recommendations and the quality of the evidence cited in the literature reviewed. The document has been subjected to external review by peer reviewers as well as by the Practice Guidelines Committee and was approved by the IDSA Council. An executive summary, algorithms, and tables highlight the major recommendations. Indicators of quality will assist in guideline implementation. The guideline will be listed on the IDSA home page at http://www.idsociety.org.


title: Relationship between Anti-Spike Protein Antibody Titers and SARS-CoV-2 In Vitro Virus Neutralization in Convalescent Plasma

text: Newly emerged pathogens such as SARS-CoV-2 highlight the urgent need for assays that detect levels of neutralizing antibodies that may be protective. We studied the relationship between anti-spike ectodomain (ECD) and anti-receptor binding domain (RBD) IgG titers, and SARS-CoV-2 virus neutralization (VN) titers generated by two different in vitro assays using convalescent plasma samples obtained from 68 COVID-19 patients, including 13 who donated plasma multiple times. Only 23% (16/68) of donors had been hospitalized. We also studied 16 samples from subjects found to have anti-spike protein IgG during surveillance screening of asymptomatic individuals. We report a strong positive correlation between both plasma anti-RBD and anti-ECD IgG titers, and in vitro VN titer. Anti-RBD plasma IgG correlated slightly better than anti-ECD IgG titer with VN titer. The probability of a VN titer ≥160 was 80% or greater with anti-RBD or anti-ECD titers of ≥1:1350. Thirty-seven percent (25/68) of convalescent plasma donors lacked VN titers ≥160, the FDA-recommended level for convalescent plasma used for COVID-19 treatment. Dyspnea, hospitalization, and disease severity were significantly associated with higher VN titer. Frequent donation of convalescent plasma did not significantly decrease either VN or IgG titers. Analysis of 2,814 asymptomatic adults found 27 individuals with anti-RBD or anti-ECD IgG titers of ≥1:1350, and evidence of VN ≥1:160. Taken together, we conclude that anti-RBD or anti-ECD IgG titers can serve as a surrogate for VN titers to identify suitable plasma donors. Plasma anti-RBD or anti-ECD titer of ≥1:1350 may provide critical information about protection against COVID-19 disease.


title: Rice endosperm is cost‐effective for the production of recombinant griffithsin with potent activity against HIV

text: Protein microbicides containing neutralizing antibodies and antiviral lectins may help to reduce the rate of infection with human immunodeficiency virus (HIV) if it is possible to manufacture the components in large quantities at a cost affordable in HIV‐endemic regions such as sub‐Saharan Africa. We expressed the antiviral lectin griffithsin (GRFT), which shows potent neutralizing activity against HIV, in the endosperm of transgenic rice plants (Oryza sativa), to determine whether rice can be used to produce inexpensive GRFT as a microbicide ingredient. The yield of (OS)GRFT in the best‐performing plants was 223 μg/g dry seed weight. We also established a one‐step purification protocol, achieving a recovery of 74% and a purity of 80%, which potentially could be developed into a larger‐scale process to facilitate inexpensive downstream processing. (OS)GRFT bound to HIV glycans with similar efficiency to GRFT produced in Escherichia coli. Whole‐cell assays using purified (OS)GRFT and infectivity assays using crude extracts of transgenic rice endosperm confirmed that both crude and pure (OS)GRFT showed potent activity against HIV and the crude extracts were not toxic towards human cell lines, suggesting they could be administered as a microbicide with only minimal processing. A freedom‐to‐operate analysis confirmed that GRFT produced in rice is suitable for commercial development, and an economic evaluation suggested that 1.8 kg/ha of pure GRFT could be produced from rice seeds. Our data therefore indicate that rice could be developed as an inexpensive production platform for GRFT as a microbicide component.


title: Human virome in nasopharynx and tracheal secretion samples

text: BACKGROUND: In Brazil the implementation of the Sentinel Surveillance System of Influenza began in 2000. Central public health laboratories use reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for diagnosis of respiratory viruses, but this protocol identifies only specific targets, resulted in inconclusive diagnosis for many samples. Thus, high-throughput sequencing (HTS) would be complementary method in the identification of pathogens in inconclusive samples for RT-qPCR or other specific detection protocols. OBJECTIVES: This study aimed to detect unidentified viruses using HTS approach in negative samples of nasopharynx/tracheal secretions by the standard RT-qPCR collected in the Federal District, Brazil. METHODS: Nucleic acids were extracted from samples collected in winter period of 2016 and subjected to HTS. The results were confirmed by the multiplex PR21 RT-qPCR, which identifies 21 respiratory pathogens. FINDINGS: The main viruses identified by HTS were of families Herpesviridae, Coronaviridae, Parvoviridae and Picornaviridae, with the emphasis on rhinoviruses. The presence of respiratory viruses in the samples was confirmed by the PR21 multiplex RT-qPCR. Coronavirus, enterovirus, bocavirus and rhinovirus were found by multiplex RT-qPCR as well as by HTS analyses. MAIN CONCLUSIONS: Wide virus diversity was found by different methodologies and high frequency of rhinovirus occurrence was confirmed in population in winter, showing its relevance for public health.


title: Deduced sequence of the bovine coronavirus spike protein and identification of the internal proteolytic cleavage site

text: Abstract The sequence of the spike (also called peplomer or E2) protein gene of the Mebus strain of bovine coronavirus (BCV) was obtained from cDNA clones of genomic RNA. The gene sequence predicts a 150,825 mol wt apoprotein of 1363 amino acids having an N-terminal hydrophobic signal sequence of 17 amino acids, 19 potential N-linked glycosylation sites, a hydrophobic anchor sequence of approximately 17 amino acids near the C terminus, and a hydrophilic cysteinerich C terminus of 35 amino acids. An internal LysArgArgSerArgArg sequence predicts a protease cleavage site between amino acids 768 and 769 that would separate the S apoprotein into S1 and S2 segments of 85690 and 65153 mol wt, respectively. Amino terminal amino acid sequencing of the virion-derived gp100 spike subunit confirmed the location of the predicted cleavage site, and established that gp120 and gp100 are the glycosylated virion forms of the S1 and S2 subunits, respectively. Sequence comparisons between BCV and the antigenically related mouse hepatitis coronavirus revealed more sequence divergence in the putative knob region of the spike protein (S1) than in the stem region (S2).


title: The role of single N-glycans in proteolytic processing and cell surface transport of the Lassa virus glycoprotein GP-C

text: Lassa virus glycoprotein is synthesised as a precursor (preGP-C) into the lumen of the endoplasmic reticulum. After cotranslational cleavage of the signal peptide, the immature GP-C is posttranslationally processed into the N-terminal subunit GP-1 and the C-terminal subunit GP-2 by the host cell subtilase SKI-1/S1P. The glycoprotein precursor contains eleven potential N-glycosylation sites. In this report, we investigated the effect of each N-glycan on proteolytic cleavage and cell surface transport by disrupting the consensus sequences of eleven potential N-glycan attachment sites individually. Five glycoprotein mutants with disrupted N-glycosylation sites were still proteolytically processed, whereas the remaining N-glycosylation sites are necessary for GP-C cleavage. Despite the lack of proteolytic processing, all cleavage-defective mutants were transported to the cell surface and remained completely endo H-sensitive. The findings indicate that N-glycans are needed for correct conformation of GP-C in order to be cleaved by SKI-1/S1P.


title: Semantic overlay network for large-scale spatial information indexing

text: Abstract The increased demand for online services of spatial information poses new challenges to the combined filed of Computer Science and Geographic Information Science. Amongst others, these include fast indexing of spatial data in distributed networks. In this paper we propose a novel semantic overlay network for large-scale multi-dimensional spatial information indexing, called SON_LSII, which has a hybrid structure integrating a semantic quad-tree and Chord ring. The SON_LSII is a small world overlay network that achieves a very competitive trade-off between indexing efficiency and maintenance overhead. To create SON_LSII, we use an effective semantic clustering strategy that considers two aspects, i.e., the semantic of spatial information that peer holds in overlay network and physical network performances. Based on SON_LSII, a mapping method is used to reduce the multi-dimensional features into a single dimension and an efficient indexing algorithm is presented to support complex range queries of the spatial information with a massive number of concurrent users. The results from extensive experiments demonstrate that SON_LSII is superior to existing overlay networks in various respects, including scalability, maintenance, rate of indexing hits, indexing logical hops, and adaptability. Thus, the proposed SON_LSII can be used for large-scale spatial information indexing.


The search for an HIV vaccine, the journey continues


title: Metformin Inhibits Proliferation of Human Thyroid Cancer TPC-1 Cells by Decreasing LRP2 to Suppress the JNK Pathway

text: OBJECTIVE: To uncover the potential effect of metformin on proliferation and apoptosis of thyroid cancer TPC-1 cell line, and the underlying mechanism. METHODS: Viability, apoptosis and LRP2 level in TPC-1 cells treated with different doses of metformin for different time points were determined. Besides, protein levels of p-JNK1 and c-Jun N-terminal kinases (JNK) in metformin-treated TPC-1 cells were detected by Western blot. Regulatory effects of LRP2 on the JNK pathway and cell viability in metformin-treated TPC-1 cells were assessed. RESULTS: Viability in TPC-1 cells gradually decreased with the treatment of increased doses of metformin either for 24 h or 48 h. The apoptotic rate was concentration-dependently elevated by metformin treatment. Relative levels of LRP2 and p-JNK1 were concentration-dependently downregulated by metformin treatment. In addition, overexpression of LRP2 partially abolished the inhibitory effect of metformin on the viability of TPC-1 cells. CONCLUSION: Metformin treatment suppresses the proliferative ability and induces apoptosis of TPC-1 cells by downregulating LRP2 to block the JNK pathway.


title: The Convoy Model and Later‐Life Family Relationships

text: The convoy model of social relations was developed to provide a heuristic framework for conceptualizing and understanding social relationships. In this Original Voices article, we begin with an overview of the theoretical tenets of the convoy model, including its value in addressing situational and contextual influences, especially variability in family forms and cultural diversity across the life span, but particularly in older adulthood. We also consider the contributions of the convoy model to the field of family gerontology by illustrating concepts, methods, and measures used to test the model, as well as its usefulness and limitations in addressing contemporary issues facing older adults. Finally, we discuss opportunities for innovation and application of the convoy model to the study of later‐life family relationships. In summary, we emphasize the benefits and inclusiveness of the convoy model for guiding current and future research to address challenges facing family gerontology now and in the future.


title: Viral metagenomic analysis of chickens with runting-stunting syndrome in the Republic of Korea

text: BACKGROUND AND AIMS: Runting-stunting syndrome (RSS) in chickens, also known as malabsorption syndrome, which is characterized by mild to severe enteritis and diagnosed through typical histopathologic examination as well as clinical signs, results in considerable economic losses. Despite the many studies carried out over decades to determine the etiologic agents of RSS involved in the disease, several outbreaks remained without the elucidation of, potentially multiple, etiologies involved. METHODS: We performed comparative analysis of viral metagenomes from four chicken flocks affected with RSS using next-generation sequencing. Primers for the detection of chicken enteric viruses were designed from the sequencing data obtained with metagenomics. Multiplex reverse transcription–polymerase chain reaction (PCR) and PCR were performed to detect a variety of etiological agents previously described in natural cases of RSS. RESULTS: The most abundant viral families identified in this study were Astroviridae, Picornaviridae, Parvoviridae, Caliciviridae, Reoviridae and Picobirnaviridae. Chicken astrovirus sequences were present in all four samples, suggesting an association between chicken astrovirus and RSS and chicken astrovirus as a candidate pathogen responsible for RSS. Picobirnavirus and the newly identified chapparvovirus were found in chickens in the Republic of Korea for the first time, and the genetic diversity of enteric viruses and viral communities was showed. CONCLUSIONS: Chicken astrovirus was consistently detected in broilers affected with RSS and the result of this study may contribute to knowledge of enteric diseases and viruses in chickens.


title: Identification of Phytochemicals Targeting c-Met Kinase Domain using Consensus Docking and Molecular Dynamics Simulation Studies

text: c-Met receptor tyrosine kinase is a proto-oncogene whose aberrant activation is attributed to a lower rate of survival in most cancers. Natural product-derived inhibitors known as “fourth generation inhibitors” constitute more than 60% of anticancer drugs. Furthermore, consensus docking approach has recently been introduced to augment docking accuracy and reduce false positives during a virtual screening. In order to obtain novel small-molecule Met inhibitors, consensus docking approach was performed using Autodock Vina and Autodock 4.2 to virtual screen Naturally Occurring Plant-based Anti-cancer Compound–Activity–Target database against active and inactive conformation of c-Met kinase domain structure. Two hit molecules that were in line with drug-likeness criteria, desired docking score, and binding pose were subjected to molecular dynamics simulations to elucidate intermolecular contacts in protein–ligand complexes. Analysis of molecular dynamics simulations and molecular mechanics Poisson–Boltzmann surface area studies showed that ZINC08234189 is a plausible inhibitor for the active state of c-Met, whereas ZINC03871891 may be more effective toward active c-Met kinase domain compared to the inactive form due to higher binding energy. Our analysis showed that both the hit molecules formed hydrogen bonds with key residues of the hinge region (P1158, M1160) in the active form, which is a hallmark of kinase domain inhibitors. Considering the pivotal role of HGF/c-Met signaling in carcinogenesis, our results propose ZINC08234189 and ZINC03871891 as the therapeutic options to surmount Met-dependent cancers.


title: Economic, Mental Health, HIV Prevention and HIV Treatment Impacts of COVID-19 and the COVID-19 Response on a Global Sample of Cisgender Gay Men and Other Men Who Have Sex with Men

text: There is an urgent need to measure the impacts of COVID-19 among gay men and other men who have sex with men (MSM). We conducted a cross-sectional survey with a global sample of gay men and other MSM (n = 2732) from April 16, 2020 to May 4, 2020, through a social networking app. We characterized the economic, mental health, HIV prevention and HIV treatment impacts of COVID-19 and the COVID-19 response, and examined whether sub-groups of our study population are disproportionately impacted by COVID-19. Many gay men and other MSM not only reported economic and mental health consequences, but also interruptions to HIV prevention and testing, and HIV care and treatment services. These consequences were significantly greater among people living with HIV, racial/ethnic minorities, immigrants, sex workers, and socio-economically disadvantaged groups. These findings highlight the urgent need to mitigate the negative impacts of COVID-19 among gay men and other MSM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10461-020-02969-0) contains supplementary material, which is available to authorized users.


Development of a mobile responsive online learning module on Psychosocial and mental health issues related to COVID 19


title: Pre-Treatment with Zirconia Nanoparticles Reduces Inflammation Induced by the Pathogenic H5N1 Influenza Virus

text: BACKGROUND: New approaches are urgently needed to fight influenza viral infection. Previous research has shown that zirconia nanoparticles can be used as anticancer materials, but their antiviral activity has not been reported. Here, we investigated the antiviral effect of zirconia (ZrO(2)) nanoparticles (NPs) against a highly pathogenic avian influenza virus. MATERIALS AND METHODS: In this study, the antiviral effects of ZrO(2) on H5N1 virus were assessed in vivo, and the molecular mechanism responsible for this protection was investigated. RESULTS: Mice treated with 200 nm positively-charged NPs at a dose of 100 mg/kg showed higher survival rates and smaller reductions in weight. 200 nm ZrO(2) activated mature dendritic cells and initially promoted the expression of cytokines associated with the antiviral response and innate immunity. In the lungs of H5N1-infected mice, ZrO(2) treatment led to less pathological lung injury, significant reduction in influenza A virus replication, and overexpression of pro-inflammatory cytokines. CONCLUSION: This antiviral study using zirconia NPs shows protection of mice against highly pathogenic avian influenza virus and suggests strong application potential for this method, introducing a new tool against a wide range of microbial infections.


Glucocorticoids inhibit type I IFN beta signaling and the upregulation of CD73 in human lung


title: Mapping the Scientific Research on Healthcare Workers’ Occupational Health: A Bibliometric and Social Network Analysis

text: In the last few years, the occupational health (OH) of healthcare workers (HCWs) has been shown increasing concern by both health departments and researchers. This study aims to provide academics with quantitative and qualitative analysis of healthcare workers’ occupational health (HCWs+OH) field in a joint way. Based on 402 papers published from 1992 to 2019, we adopted the approaches of bibliometric and social network analysis (SNA) to map and quantify publication years, research area distribution, international collaboration, keyword co-occurrence frequency, hierarchical clustering, highly cited articles and cluster timeline visualization. In view of the results, several hotspot clusters were identified, namely: physical injuries, workplace, mental health; occupational hazards and diseases, infectious factors; community health workers and occupational exposure. As for citations, we employed document co-citation analysis to detect trends and identify seven clusters, namely tuberculosis (TB), strength training, influenza, healthcare worker (HCW), occupational exposure, epidemiology and psychological. With the visualization of cluster timeline, we detected that the earliest research cluster was occupational exposure, then followed by epidemiology and psychological; however, TB, strength training and influenza appeared to gain more attention in recent years. These findings are presumed to offer researchers, public health practitioners a comprehensive understanding of HCWs+OH research.


title: Myxovirus- and coronavirus-induced in vitro stimulation of spontaneous cell-mediated cytotoxicity by porcine blood leukocytes

text: Summary Spontaneous cell-mediated cytotoxicity (SCMC) by porcine blood leukocytes toward human myeloid tumour target cells (K562) was shown by Koren and coworkers in 1978, using a 4-h 51Cr-release assay. In the present paper, SCMC was found to be enhanced following a 24-h incubation of leukocytes with swine influenza virus (SIV) of the H3N2 type, and with the transmissible gastroenteritis virus (TGEV), a porcine coronavirus. In most of our experiments, both SIV and TGEV induced interferon (IFN) production by leukocytes (titres ranging from 30-7,500 units/ml). When porcine leukocytes were incubated with TGEV in the presence of anti-IFN antiserum, no SCMC stimulation occurred, suggesting that the virus-induced SCMC stimulation was mainly due to endogenously produced IFN. On the other hand, when either human αIFN or porcine virus-induced IFN were added to porcine leukocytes, a rapid and marked SCMC increase was observed. Both the SIV-induced SCMC increase and IFN production were suppressed when SIV was UV-inactivated. On the contrary, UV-inactivated TGEV was still able to enhance SCMC and to induce IFN production by porcine leukocytes. On the whole, these results suggest that myxovirus and coronavirus are able to activate porcine leukocyte SCMC via endogenously produced IFN.


title: Disasters can happen to anybody: The case of Korea

text: Abstract In Korea, there is a pervasive feeling of invincibility to the point that people and organizations do not believe that disasters can strike them. This has impact on the level of preparedness for disasters. This study aims to delve into how Korea has to change its governmental policies/practices with some private partners' efforts to mitigate disaster risks. A case study was utilized as the major methodology by comparing exclusive management with inclusive management. These two approaches have been comparatively analyzed via four variables, namely the central government, the local governments, the incident commander, and other stakeholders. The major finding is that Korea's practices and policies have to evolve from the current exclusive management into future-oriented inclusive management. Moreover, the importance of communication, cooperation, collaboration, and multi-discipline coordination is discussed. Additionally, the problem of reductionism and equal participation among all stakeholders, as well as the resistance from vested interests, are recognized and elaborated for Korea and the international community.


title: Study on nucleic acid (CT-DNA and yeast tRNA) binding behaviors and cytotoxic properties of a heterodinuclear Ru(II)–Co(III) polypyridyl complex

text: Abstract A heterodinuclear (Ru(II), Co(III)) metal polypyridyl complex [(phen)2Ru(bpibH2)Co(phen)2]5+ {phen=1,10-phenanthroline, bpibH2 =1,4-bis([1,10]phebanthroline-[5,6-d]imidazol-2-yl)-benzene} has been designed and synthesized. The comparative study on the interactions of the Ru(II)–Co(III) complex with calf thymus DNA (CT-DNA) and yeast tRNA has been investigated by UV–visible spectroscopy, fluorescence spectroscopy, viscosity, as well as equilibrium dialysis and circular dichroism (CD). The antitumor activities of the complex have been evaluated by MTT {3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide} method and Giemsa staining experiment. These results indicate that the structures of nucleic acids have significant effects on the binding behaviors of metal complexes. Furthermore, the complex demonstrates different antitumor activity against selected tumor cell lines in vitro, and can make the cell apoptosis.


title: Ventilator-Associated Pneumonia: The Role of Emerging Diagnostic Technologies

text: Antibiotic resistance has emerged as a key determinant of outcome in patients with serious infections along with the virulence of the underlying pathogen. Within the intensive care unit (ICU) setting, ventilator-associated pneumonia (VAP) is a common nosocomial infection that is frequently caused by multidrug-resistant bacteria. Antimicrobial resistance is a growing challenge in the care of critically ill patients. Escalating rates of antibiotic resistance add substantially to the morbidity, mortality, and cost related to infection in the ICU. Both gram-positive organisms, such as methicillin-resistant Staphylococcus aureus and vancomycin-intermediate S. aureus , and gram-negative bacteria, including Pseudomonas aeruginosa , Acinetobacter species, carbapenem-resistant Enterobacteriaceae , such as the Klebsiella pneumoniae carbapenemase–producing bacteria, and extended spectrum β-lactamase organisms, have contributed to the escalating rates of resistance seen in VAP and other nosocomial infections. The rising rates of antimicrobial resistance have led to the routine empiric administration of broad-spectrum antibiotics even when bacterial infection is not documented. Moreover, there are several new broader-spectrum antibiotics that have recently become available and others scheduled for approval in the near future. The challenge to ICU clinicians is how to most effectively utilize these agents to maximize patient benefits while minimizing further emergence of resistance. Use of rapid diagnostics may hold the key for achieving this important balance. There is an urgent need for integrating the administration of new and existing antibiotics with the emerging rapid diagnostic technologies in a way that is both cost-effective and sustainable for the long run.


title: Intracellular Mono-ADP-Ribosylation in Signaling and Disease

text: A key process in the regulation of protein activities and thus cellular signaling pathways is the modification of proteins by post-translational mechanisms. Knowledge about the enzymes (writers and erasers) that attach and remove post-translational modifications, the targets that are modified and the functional consequences elicited by specific modifications, is crucial for understanding cell biological processes. Moreover detailed knowledge about these mechanisms and pathways helps to elucidate the molecular causes of various diseases and in defining potential targets for therapeutic approaches. Intracellular adenosine diphosphate (ADP)-ribosylation refers to the nicotinamide adenine dinucleotide (NAD(+))-dependent modification of proteins with ADP-ribose and is catalyzed by enzymes of the ARTD (ADP-ribosyltransferase diphtheria toxin like, also known as PARP) family as well as some members of the Sirtuin family. Poly-ADP-ribosylation is relatively well understood with inhibitors being used as anti-cancer agents. However, the majority of ARTD enzymes and the ADP-ribosylating Sirtuins are restricted to catalyzing mono-ADP-ribosylation. Although writers, readers and erasers of intracellular mono-ADP-ribosylation have been identified only recently, it is becoming more and more evident that this reversible post-translational modification is capable of modulating key intracellular processes and signaling pathways. These include signal transduction mechanisms, stress pathways associated with the endoplasmic reticulum and stress granules, and chromatin-associated processes such as transcription and DNA repair. We hypothesize that mono-ADP-ribosylation controls, through these different pathways, the development of cancer and infectious diseases.


title: A mobile loop near the active site acts as a switch between the dual activities of a viral protease/deubiquitinase

text: The positive-strand RNA virus Turnip yellow mosaic virus (TYMV) encodes an ovarian tumor (OTU)-like protease/deubiquitinase (PRO/DUB) protein domain involved both in proteolytic processing of the viral polyprotein through its PRO activity, and in removal of ubiquitin chains from ubiquitylated substrates through its DUB activity. Here, the crystal structures of TYMV PRO/DUB mutants and molecular dynamics simulations reveal that an idiosyncratic mobile loop participates in reversibly constricting its unusual catalytic site by adopting "open", "intermediate" or "closed" conformations. The two cis-prolines of the loop form a rigid flap that in the most closed conformation zips up against the other side of the catalytic cleft. The intermediate and closed conformations also correlate with a reordering of the TYMV PRO/DUB catalytic dyad, that then assumes a classical, yet still unusually mobile, OTU DUB alignment. Further structure-based mutants designed to interfere with the loop's mobility were assessed for enzymatic activity in vitro and in vivo, and were shown to display reduced DUB activity while retaining PRO activity. This indicates that control of the switching between the dual PRO/DUB activities resides prominently within this loop next to the active site. Introduction of mutations into the viral genome revealed that the DUB activity contributes to the extent of viral RNA accumulation both in single cells and in whole plants. In addition, the conformation of the mobile flap was also found to influence symptoms severity in planta. Such mutants now provide powerful tools with which to study the specific roles of reversible ubiquitylation in viral infection.


title: Densification-Induced Structure Changes in Basolite MOFs: Effect on Low-Pressure CH(4) Adsorption

text: Metal-organic frameworks’ (MOFs) adsorption potential is significantly reduced by turning the original powder into pellets or granules, a mandatory step for their use at industrial scale. Pelletization is commonly performed by mechanical compression, which often induces the amorphization or pressure-induced phase transformations. The objective of this work is the rigorous study of the impact of mechanical pressure (55.9, 111.8 and 186.3 MPa) onto three commercial materials (Basolite C300, F300 and A100). Phase transformations were determined by powder X-ray diffraction analysis, whereas morphological changes were followed by nitrogen physisorption. Methane adsorption was studied in an atmospheric fixed bed. Significant crystallinity losses were observed, even at low applied pressures (up to 69.9% for Basolite C300), whereas a structural change occurred to Basolite A100 from orthorhombic to monoclinic phases, with a high cell volume reduction (13.7%). Consequently, adsorption capacities for both methane and nitrogen were largely reduced (up to 53.6% for Basolite C300), being related to morphological changes (surface area losses). Likewise, the high concentration of metallic active centers (Basolite C300), the structural breathing (Basolite A100) and the mesopore-induced formation (Basolite F300) smooth the dramatic loss of capacity of these materials.


EFFECTS OF ISOLATION ON MOOD AND RELATIONSHIPS IN PREGNANT WOMEN DURING THE COVID-19 PANDEMIC


title: COVID-19 pandemic underlines the need to build resilience in commercial restaurants’ food safety

text: In the face of the COVID-19 pandemic, the commercial restaurant sector is struggling to organize itself. Resilience is crucial for a system to be able to respond adequately to events of this magnitude, and is aimed at the recovery and adaptation of the concerned sector in view of the adversities. In the commercial restaurant sector, resilience efforts are primarily intended to protect the health of both those who consume food and those who produce it. Amid the creative initiatives of individuals within their workplaces, restaurants, even unconsciously, seek to build resilience in the pandemic by applying the food safety practices recommended by the sanitary legislation and remaining economically active. Targeting public health preparedness, in this letter, we present an overview of the stages of resilience and their interaction with the COVID-19 pandemic in the context of commercial restaurants.


title: Gene profiling analysis of ALVAC infected human monocyte derived dendritic cells

text: The recombinant canarypox virus ALVAC is being extensively studied as vaccine vector for the development of new vaccine strategies against chronic infectious diseases and cancer. However, the mechanisms by which ALVAC initiates the immune response have not been completely elucidated. In order to determine the type of innate immunity triggered by ALVAC, we characterized the gene expression profile of human monocyte derived dendritic cells (MDDCs) upon ALVAC infection. These cells are permissive to poxvirus infection and play a key role in the initiation of immune responses. The majority of the genes that were up-regulated by ALVAC belong to the type I interferon signaling pathway including IRF7, STAT1, RIG-1, and MDA-5. Genes involved in the NF-κB pathway were not up-regulated. The gene encoding for the chemokine CXCL10, a direct target of the transcription factor IRF3 was among those up-regulated and DC secretion of CXCL10 following exposure to ALVAC was confirmed by ELISA. Many downstream type I interferon activated genes with anti-viral activity (PKR, Mx, ISG15 and OAS among others) were also up-regulated in response to ALVAC. Among these, ISG15 expression in its unconjugated form by Western blot analysis was demonstrated. In view of these results we propose that ALVAC induces type I interferon anti-viral innate immunity via a cytosolic pattern-recognition-receptor (PRR) sensing double-stranded DNA, through activation of IRF3 and IRF7. These findings may aid in the design of more effective ALVAC-vectored vaccines.


title: Post-transplant Viral Respiratory Infections in the Older Patient: Epidemiology, Diagnosis, and Management

text: Organ and stem cell transplantation has been one of the greatest advances in modern medicine, and is the primary treatment modality for many end-stage diseases. As our population ages, so do the transplant recipients, and with that comes many new challenges. Respiratory viruses have been a large contributor to the mortality and morbidity of solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. Respiratory viruses are generally a long-term complication of transplantation and primarily acquired in the community. With the emergence of molecular methods, newer respiratory viruses are being detected. Respiratory viruses appear to cause severe disease in the older transplant population. Influenza vaccine remains the mainstay of prevention in transplant recipients, although immunogenicity of current vaccines is suboptimal. Limited therapies are available for other respiratory viruses. The next decade will likely bring newer antivirals and vaccines to the forefront. Our goal is to provide the most up to date knowledge of respiratory viral infections in our aging transplant population.


title: Relationship between asymptomatic rotavirus infection and jaundice in neonates: a retrospective study

text: BACKGROUND: Rotavirus (RV) infection in neonates can be mild or even asymptomatic. In RV infection, jaundice is often reported, but the relationship between jaundice and RV infection has not been studied. This study aimed to determine the importance of asymptomatic RV screening in neonates with jaundice. METHODS: Neonates from the neonatal intensive care unit (NICU) of Chonbuk National University Hospital, those transferred from local obstetrics and gynecology hospitals and outpatient clinics were selected from 2014 to 2017. The study included only infants aged between 3 and 28 days. Jaundice was defined according to gestational age and birth age, in accordance with the American Academy of Pediatrics guidelines criteria. RV infection was confirmed by a stool test, and RV screening and laboratory tests were performed at admission. RESULTS: Among 596 patients, 166 patients had jaundice. RV infection was observed in 70 (42%) jaundice patients. There were 36 (22%) jaundice patients with asymptomatic RV infection. Patients with onset of jaundice 3–7 days after birth had a high incidence of RV infection. When the RV test was positive, the risk of jaundice was significantly high [odds ratio (OR) 1.89; 95% confidence interval (CI), 1.20–2.98; p = 0.006]. CONCLUSIONS: Infants with the onset of jaundice > 3 days after birth were likely to have RV infection. Therefore, we suggest that screening tests for RV infection be included as part of the evaluation of jaundiced infants presenting to NICU. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12887-018-1352-z) contains supplementary material, which is available to authorized users.


title: The similarity analysis of financial stocks based on information clustering

text: Similarity in time series is an important feature of dynamical systems such as financial systems, with potential use for clustering of series in system. Here, we mainly introduce a novel method: the reconstructed phase space information clustering method to analyze the financial markets. The method is used to examine the similarity of different sequences by calculating the distances between them, which the main difference from previous method is the way to map the original time series to symbolic sequences. Here we make use of the state space reconstruction to construct the symbolic sequences and quantify the similarity of different stock markets and exchange rate markets considering the chaotic behavior between the complex time series. And we compare the results of similarity of artificial and real data using the modified method, information categorization method and system clustering method. We conclude that the reconstructed phase space information clustering method is effective to research the close relationship in time series and for short time series especially. Besides, we report the results of similarity of different exchange rate time series in different periods and find the effect of the exchange rate regime in 2008 on the time series. Also we acquire some characteristics of exchange rate time series in China market, especially for the top four trading partners of China.


title: A new coronavirus-like particle associated with diarrhea in swine

text: Coronavirus-like particles were detected by electron microscopy in the intestinal contents of pigs during a diarrheal outbreak on 4 swine breeding farms. Diarrhea was reproduced in experimental pigs with one of the isolates, designated CV777, which was found to be distinct from the 2 known porcine coronaviruses, transmissible gastroenteritis virus and hemagglutinating encephalomyelitis virus.


title: Two hits to the renin‐angiotensin system may play a key role in severe COVID‐19

text: The spike glycoprotein on the virion surface docking onto the angiotensin‐converting enzyme (ACE) 2 dimer is an essential step in the process of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in human cells—involves downregulation of ACE2 expression with systemic renin‐angiotensin system (RAS) imbalance and promotion of multi‐organ damage. In general, the RAS induces vasoconstriction, hypertension, inflammation, fibrosis, and proliferation via the ACE/Ang II/Ang II type 1 receptor (AT1R) axis and induces the opposite effects via the ACE2/Ang (1‐7)/Mas axis. The RAS may be activated by chronic inflammation in hypertension, diabetes, obesity, and cancer. SARS‐CoV‐2 induces the ACE2 internalization and shedding, leading to the inactivation of the ACE2/Ang (1‐7)/Mas axis. Therefore, we hypothesize that two hits to the RAS drives COVID‐19 progression. In brief, the first hit originates from chronic inflammation activating the ACE/Ang II/AT1R axis, and the second originates from the COVID‐19 infection inactivating the ACE2/Ang (1‐7)/Mas axis. Moreover, the two hits to the RAS may be the primary reason for increased mortality in patients with COVID‐19 who have comorbidities and may serve as a therapeutic target for COVID‐19 treatment.


title: Virological surveillance of influenza and other respiratory viruses during six consecutive seasons from 2006 to 2012 in Catalonia, Spain

text: Abstract Most attention is given to seasonal influenza and respiratory syncytial virus outbreaks, but the cumulative burden caused by other respiratory viruses (RV) is not widely considered. The aim of the present study is to describe the circulation of RV in the general population during six consecutive seasons from 2006 to 2012 in Catalonia, Spain. Cell culture, immunofluorescence and PCR-based assays were used for the RV laboratory-confirmation and influenza subtyping. Phylogenetic and molecular characterizations of viral haemagglutinin, partial neuraminidase and matrix 2 proteins were performed from a representative sampling of influenza viruses. A total of 6315 nasopharyngeal samples were collected, of which 64% were laboratory-confirmed, mainly as influenza A viruses and rhinoviruses. Results show the significant burden of viral aetiological agents in acute respiratory infection, particularly in the youngest cases. The study of influenza strains reveals their continuous evolution through either progressive mutations or by segment reassortments. Moreover, the predominant influenza B lineage was different from that included in the recommended vaccine in half of the studied seasons, supporting the formulation and use of a quadrivalent influenza vaccine. Regarding neuraminidase inhibitors resistance, with the exception of the 2007/08 H275Y seasonal A(H1N1) strains, no other circulating influenza strains carrying known resistance genetic markers were found. Moreover, all circulating A(H1N1)pdm09 and A(H3N2) strains finally became genetically resistant to adamantanes. A wide knowledge of the seasonality patterns of the RV in the general population is well-appreciated, but it is a challenge due to the unpredictable circulation of RV, highlighting the value of local and global RV surveillance.


title: Alveolar lipids in pulmonary disease. A review

text: Lung lipid metabolism participates both in infant and adult pulmonary disease. The lung is composed by multiple cell types with specialized functions and coordinately acting to meet specific physiologic requirements. The alveoli are the niche of the most active lipid metabolic cell in the lung, the type 2 cell (T2C). T2C synthesize surfactant lipids that are an absolute requirement for respiration, including dipalmitoylphosphatidylcholine. After its synthesis and secretion into the alveoli, surfactant is recycled by the T2C or degraded by the alveolar macrophages (AM). Surfactant biosynthesis and recycling is tightly regulated, and dysregulation of this pathway occurs in many pulmonary disease processes. Alveolar lipids can participate in the development of pulmonary disease from their extracellular location in the lumen of the alveoli, and from their intracellular location in T2C or AM. External insults like smoke and pollution can disturb surfactant homeostasis and result in either surfactant insufficiency or accumulation. But disruption of surfactant homeostasis is also observed in many chronic adult diseases, including chronic obstructive pulmonary disease (COPD), and others. Sustained damage to the T2C is one of the postulated causes of idiopathic pulmonary fibrosis (IPF), and surfactant homeostasis is disrupted during fibrotic conditions. Similarly, surfactant homeostasis is impacted during acute respiratory distress syndrome (ARDS) and infections. Bioactive lipids like eicosanoids and sphingolipids also participate in chronic lung disease and in respiratory infections. We review the most recent knowledge on alveolar lipids and their essential metabolic and signaling functions during homeostasis and during some of the most commonly observed pulmonary diseases.


title: Nidovirus papain-like proteases: multifunctional enzymes with protease, deubiquitinating and deISGylating activities

text: Coronaviruses and arteriviruses, members of the order Nidovirales, are positive strand RNA viruses that encode large replicase polyproteins that are processed by viral proteases to generate the nonstructural proteins which mediate viral RNA synthesis. The viral papain-like proteases (PLPs) are critical for processing the amino-terminal end of the replicase and are attractive targets for antiviral therapies. With the analysis of the papain-like protease of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), came the realization of the multifunctional nature of these enzymes. Structural and enzymatic studies revealed that SARS-CoV PLpro can act as both a protease to cleave peptide bonds and also as a deubiquitinating (DUB) enzyme to cleave the isopeptide bonds found in polyubiquitin chains. Furthermore, viral DUBs can also remove the protective effect of conjugated ubiquitin-like molecules such as interferon stimulated gene 15 (ISG15). Extension of these studies to other coronaviruses and arteriviruses led to the realization that viral protease/DUB activity is conserved in many family members. Overexpression studies revealed that viral protease/DUB activity can modulate or block activation of the innate immune response pathway. Importantly, mutations that alter DUB activity but not viral protease activity have been identified and arteriviruses expressing DUB mutants stimulated higher levels of acute inflammatory cytokines after infection. Further understanding of the multifunctional nature of the Nidovirus PLP/DUBs may facilitate vaccine development. Here, we review studies describing the PLPs’ enzymatic activity and their role in virus pathogenesis.


title: Removal of fine and ultrafine particles from indoor air environments by the unipolar ion emission

text: The continuous emission of unipolar ions was evaluated in order to determine its ability to remove fine and ultrafine particles from indoor air environments. The evolution of the indoor aerosol concentration and particle size distribution was measured in real time with the ELPI in a room-size (24.3 m(3)) test chamber where the ion emitter was operating. After the results were compared with the natural decay, the air cleaning factor was determined. The particle aerodynamic size range of ∼0.04–2 μm was targeted because it represents many bioaerosol agents that cause emerging diseases, as well as those that can be used for biological warfare or in the event of bioterrorism. The particle electric charge distribution (also measured in the test chamber with the ELPI) was rapidly affected by the ion emission. It was concluded that the corona discharge ion emitters (either positive or negative), which are capable of creating an ion density of 10(5)–10(6) e(±) cm(−3), can be efficient in controlling fine and ultrafine aerosol pollutants in indoor air environments, such as a typical office or residential room. At a high ion emission rate, the particle mobility becomes sufficient so that the particle migration results in their deposition on the walls and other indoor surfaces. Within the tested ranges of the particle size and ion density, the particles were charged primarily due to the diffusion charging mechanism. The particle removal efficiency was not significantly affected by the particle size, while it increased with increasing ion emission rate and the time of emission. The performance characteristics of three commercially available ionic air purifiers, which produce unipolar ions by corona discharge at relatively high emission rates, were evaluated. A 30-minute operation of the most powerful device among those tested resulted in the removal of about 97% of 0.1 μm particles and about 95% of 1 μm particles from the air in addition to the natural decay effect.


title: Risk for Transportation of 2019 Novel Coronavirus (COVID-19) from Wuhan to Cities in China

text: On January 23, 2020, China quarantined Wuhan to contain an emerging coronavirus (COVID-19). We estimated the probability of transportation of COVID-19 from Wuhan to 369 cities in China before the quarantine. The expected risk is >50% in 130 (95% CI 89–190) cities and >99% in the 4 largest metropolitan areas of China.


title: Segmented Filamentous Bacteria – Metabolism Meets Immunity

text: Segmented filamentous bacteria (SFB) are a group of host-adapted, commensal organisms that attach to the ileal epithelium of vertebrate and invertebrate hosts. A genetic relative of the genus Clostridium, these morphologically unique bacteria display a replication and differentiation lifecycle initiated by epithelial tissue binding and filamentation. SFB intimately bind to the surface of absorptive intestinal epithelium without inducing an inflammatory response. Rather, their presence impacts the generation of innate and differentiation of acquired immunity, which impact the clearance of extracellular bacterial or fungal pathogens in the gastrointestinal and respiratory tracts. SFB have recently garnered attention due to their role in promoting adaptive and innate immunity in mice and rats through the differentiation and maturation of Th17 cells in the intestinal tract and production of immunoglobulin A (IgA). SFB are the first commensal bacteria identified that impact the maturation and development of Th17 cells in mice. Recently, microbiome studies have revealed the presence of Candidatus Arthromitus (occasionally designated as Candidatus Savagella), a proposed candidate species of SFB, in higher proportions in higher-performing flocks as compared to matched lower-performing flocks, suggesting that SFB may serve to establish a healthy gut and protect commercial turkeys from pathogens resulting in morbidity and decreased performance. In this review we seek to describe the life cycle, host specificity, and genetic capabilities of SFB, such as bacterial metabolism, and how these factors influence the host immunity and microbiome. Although the role of SFB to induce antigen-specific Th17 cells in poultry is unknown, they may play an important role in modulating the immune response in the intestinal tract to promote resistance against some infectious diseases and promote food-safety. This review demonstrates the importance of studying and further characterizing commensal, host-specific bacteria in food-producing animals and their importance to animal health.


title: MicroRNAs and human retroviruses

text: MicroRNAs (miRNAs) are small non-coding RNAs that control a multitude of critical processes in mammalian cells. Increasing evidence has emerged that host miRNAs serve in animal cells to restrict viral infections. In turn, many viruses encode RNA silencing suppressors (RSS) which are employed to moderate the potency of the cell’s miRNA selection against viral replication. Some viruses also encode viral miRNAs. In this review, we summarize findings from human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type 1 (HTLV-1) that illustrate examples of host cell miRNAs that target the viruses, of RSS encoded by viruses, and of host cell miRNA profile changes that are seen in infected cells.


title: Contamination by respiratory viruses on outer surface of medical masks used by hospital healthcare workers

text: BACKGROUND: Medical masks are commonly used in health care settings to protect healthcare workers (HCWs) from respiratory and other infections. Airborne respiratory pathogens may settle on the surface of used masks layers, resulting in contamination. The main aim of this study was to study the presence of viruses on the surface of medical masks. METHODS: Two pilot studies in laboratory and clinical settings were carried out to determine the areas of masks likely to contain maximum viral particles. A laboratory study using a mannequin and fluorescent spray showed maximum particles concentrated on upper right, middle and left sections of the medical masks. These findings were confirmed through a small clinical study. The main study was then conducted in high-risk wards of three selected hospitals in Beijing China. Participants (n = 148) were asked to wear medical masks for a shift (6–8 h) or as long as they could tolerate. Used samples of medical masks were tested for presence of respiratory viruses in upper sections of the medical masks, in line with the pilot studies. RESULTS: Overall virus positivity rate was 10.1% (15/148). Commonly isolated viruses from masks samples were adenovirus (n = 7), bocavirus (n = 2), respiratory syncytial virus (n = 2) and influenza virus (n = 2). Virus positivity was significantly higher in masks samples worn for > 6 h (14.1%, 14/99 versus 1.2%, 1/49, OR 7.9, 95% CI 1.01–61.99) and in samples used by participants who examined > 25 patients per day (16.9%, 12/71 versus 3.9%, 3/77, OR 5.02, 95% CI 1.35–18.60). Most of the participants (83.8%, 124/148) reported at least one problem associated with mask use. Commonly reported problems were pressure on face (16.9%, 25/148), breathing difficulty (12.2%, 18/148), discomfort (9.5% 14/148), trouble communicating with the patient (7.4%, 11/148) and headache (6.1%, 9/148). CONCLUSION: Respiratory pathogens on the outer surface of the used medical masks may result in self-contamination. The risk is higher with longer duration of mask use (> 6 h) and with higher rates of clinical contact. Protocols on duration of mask use should specify a maximum time of continuous use, and should consider guidance in high contact settings. Viruses were isolated from the upper sections of around 10% samples, but other sections of masks may also be contaminated. HCWs should be aware of these risks in order to protect themselves and people around them.


title: Quality of life reported by survivors after hospitalization for Middle East respiratory syndrome (MERS)

text: INTRODUCTION: Data are lacking on impact of Middle East Respiratory Syndrome (MERS) on health-related quality of life (HRQoL) among survivors. METHODS: We conducted a cross-sectional survey of MERS survivors who required hospitalization in Saudi Arabia during 2016–2017, approximately 1 year after diagnosis. The Short-Form General Health Survey 36 (SF-36) was administered by telephone interview to assess 8 quality of life domains for MERS survivors and a sample of survivors of severe acute respiratory infection (SARI) without MERS. We compared mean SF-36 scores of MERS and non-MERS SARI survivors using independent t-test, and compared categorical variables using chi-square test. Adjusted analyses were performed using multiple linear regression. RESULTS: Of 355 MERS survivors, 83 were eligible and 78 agreed to participate. MERS survivors were younger than non-MERS SARI survivors (mean ± SD): (44.9 years ±12.9) vs (50.0 years ±13.6), p = 0.031. Intensive care unit (ICU) admissions were similar for MERS and non-MERS SARI survivors (46.2% vs. 57.1%), p = 0.20. After adjusting for potential confounders, there were no significant differences between MERS and non-MERS SARI survivors in physical component or mental component summary scores. MERS ICU survivors scored lower than MERS survivors not admitted to an ICU for physical function (p = 0.05), general health (p = 0.01), vitality (p = 0.03), emotional role (p = 0.03) and physical component summary (p < 0.02). CONCLUSIONS: Functional scores were similar for MERS and non-MERS SARI survivors. However, MERS survivors of critical illness reported lower quality of life than survivors of less severe illness. Efforts are needed to address the long-term medical and psychological needs of MERS survivors.


title: Emerging Infections and Children: Influenza and Acute Necrotizing Encephalopathy

text: Children can play a variety of roles in emerging infectious diseases. They can be victims, as in the vertical transmission of human immunodeficiency virus infection. They can be affected in a minor way compared with adults, as in West Nile virus infection, legionellosis, and coronavirus infection leading to severe acute respiratory syndrome (SARS). Sometimes, however, they play predominant roles—sources for other age groups—as do toddlers in out-of-the-home child care for transmission of penicillinresistant pneumococci and cytomegalovirus to family members. Children have a uniquely central role in transmitting the influenza viruses that cause annual seasonal outbreaks and epidemic disease and could cause global epidemic (or pandemic) disease. Children themselves suffer excessive morbidity and mortality from influenza. Continuous minor changes in virus neuraminidase and haemagglutinin components (antigenic drift) or a major change in either (antigenic shift) render naïve children especially vulnerable. Anticipating that pandemic influenza could occur at any time because of a major change in a human strain of influenza virus or through acquisition of human transmissibility of reassortant avian influenza strain(s) (Nicholson et al., 2003), the international community of healthcare experts are collaborating increasingly, and countries are drafting influenza pandemic preparedness plans. A draft by the U.S. Department of Health and Human Services of “Pandemic Influenza Preparedness and Response Plan” was released for comment in August 2004 (http://www.hhs.gov/nvpo/pandemicplan). All plans highlight the critical importance of international surveillance, openness, and rapid response to investigate and contain emergent avian or human strains.


title: Self‐removing passive drain to facilitate postoperative care via telehealth during the COVID‐19 pandemic

text: BACKGROUND: Telehealth postoperative visits are an attractive strategy to minimize exposure, especially during the SARS‐CoV‐2 (COVID‐19) pandemic. The use of a surgical drain often prevents this minimal‐exposure approach in that patients return to the outpatient clinic for drain removal. METHODS AND RESULTS: Following unilateral neck dissection, the customary closed‐suction drain was replaced with a self‐removing, passive drain dressing to facilitate same‐day discharge and telehealth postoperative follow‐up. The patient removed the dressing and drain at home during a telehealth visit on postoperative day 4 and she healed favorably without any signs of infection or seroma. CONCLUSIONS: When thoughtfully applied in the appropriate clinical context, small practice adaptations like this can facilitate telehealth solutions that diminish unnecessary exposure for patients, their caregivers, and health care staff.


title: Topoisomerase III-ß is required for efficient replication of positive-sense RNA viruses

text: Based on genome-scale loss-of-function screens we discovered that Topoisomerase III-ß (TOP3B), a human topoisomerase that acts on DNA and RNA, is required for yellow fever virus and dengue virus-2 replication. Remarkably, we found that TOP3B is required for efficient replication of all positive-sense-single stranded RNA viruses tested, including SARS-CoV-2. While there are no drugs that specifically inhibit this topoisomerase, we posit that TOP3B is an attractive anti-viral target.


title: Dental autopsy recommendations in SARS-CoV-2 infected cases

text: Abstract Unidentified human remains with unknown medical history can always pose biological hazards to forensic pathologists and odontologists, including hepatitis C, HIV infection, Middle East respiratory syndrome (MERS), hemorrhagic fever viruses such as Ebola, meningitis and now Sars-Cov2. The pandemic of the new coronavirus disease (COVID-19) has reached 185 Countries with an increasing number of deaths. Forensic pathologists and odontologists may find themselves having to perform an identification autopsy to confirmed or suspected Sars-Cov2 positive deaths. By respecting the entire set of universal precautions and recommendations the highlighted risks can be minimized, and best practice in human identification should always be a priority for human rights of the dead. The following article is a summary of the recommendations for conducting dental autopsies and management of suspected COVID-19 cases.


title: Health and Economic Outcomes of Home Maintenance Allergen Immunotherapy in Select Patients with High Health Literacy during the COVID-19 Pandemic: A Cost-Effectiveness Analysis During Exceptional Times

text: Abstract Background Allergen immunotherapy is safe and effective but is typically administered under strict clinic observation to mitigate risk of a systemic reaction to immunotherapy (SRIT). However, in the setting of the global COVID-19 pandemic, alternative care models should be explored. Objective To evaluate the cost-effectiveness of home immunotherapy self-administration (HITSA) in a highly idealized circumstance for provision of maintenance allergen immunotherapy in a shelter-in-place or other scenarios of unforeseen reduction in non-essential medical services. Methods Markov modeling was used to compare in-office clinic allergen immunotherapy in selected patients using cohort analysis and microsimulation from the societal and healthcare perspectives. Results Assuming similar SRIT rates, HITSA was found to be a cost-effective option with an incremental cost-effectiveness ratio (ICER) of $44,554/QALY (quality adjusted life year) when considering both incremental epinephrine autoinjector (EAI) costs and COVID-19 risks. Excluding EAI costs, HISTA dominated other options. However, outside of pandemic considerations, HITSA was not cost effective (ICER $198,877,286) at annual EAI costs above $287. As the incremental HITSA SRIT rate increased above 15%, clinic AIT was the most cost-effective strategy. Excluding both pandemic risks and risk of motor vehicle accident fatality from round-trip clinic transit, clinic AIT dominated other strategies. Clinic AIT was the more cost-effective option at very high fatality relative risk for HITSA or at very low annual risk of contracting COVID-19. Conclusion Under idealized assumptions HITSA can be a safe and cost-effective option during a global pandemic in appropriately selected patients provided home rates of SRIT remain stable.


title: Delayed Newcastle disease virus replication using RNA interference to target the nucleoprotein

text: Abstract Each year millions of chickens die from Newcastle disease virus (NDV) worldwide leading to severe economic and food losses. Current vaccination campaigns have limitations especially in developing countries, due to elevated costs, need of trained personnel for effective vaccine administration, and functional cold chain network to maintain vaccine viability. These problems have led to heightened interest in producing new antiviral strategies, such as RNA interference (RNAi). RNAi methodology is capable of substantially decreasing viral replication at a cellular level, both in vitro and in vivo. In this study, we utilize microRNA (miRNA)-expressing constructs (a type of RNA interference) in an attempt to target and knockdown five NDV structural RNAs for nucleoprotein (NP), phosphoprotein (P), matrix (M), fusion (F), and large (L) protein genes. Immortalized chicken embryo fibroblast cells (DF-1) that transiently expressed miRNA targeting NP mRNA, showed increased resistance to NDV-induced cytopathic effects, as determined by cell count, relative to the same cells expressing miRNA against alternative NDV proteins. Upon infection with NDV, DF-1 cells constitutively expressing the NP miRNA construct had improved cell survival up to 48 h post infection (h.p.i) and decreased viral yield up to 24 h.p.i. These results suggest that overexpression of the NP miRNA in cells and perhaps live animal may provide resistance to NDV.


title: Aspectos y consideraciones generales en la Enfermedad Inflamatoria Intestinal durante la pandemia por COVID-19

text: Resumen Hasta este momento la evidencia disponible sugiere que los pacientes con EII no tienen un mayor riesgo de desarrollar COVID-19. En pacientes con remisión de la EII: los 5-aminosalicilatos (5-ASA) no incrementan el riesgo de infección y se deben continuar sin necesidad de suspenderlos o disminuir la dosis; los fármacos inmunomoduladores como las tiopurinas y metotrexato deben continuarse sin modificar las dosis (a considerar en el paciente con infección por SARS-CoV-2 positiva), y en relación a cualquier tipo de terapia biológica no deberá suspenderse a menos que existan datos de COVID-19. En aquellos pacientes con actividad de la EII: Se deberá optimizar la dosis de 5-ASA en administración oral y/o tópica en caso de recaída de la enfermedad; considerar el uso de budesonida MMX en casos de actividad leve a moderada con el fin de evitar uso de esteroides sistémicos; los esteroides sistémicos deben evitarse en la medida de lo posible ya que dosis mayores de 20 mg al día ejercen efecto inmunosupresor el cual pudiera aumentar la susceptibilidad a cualquier tipo de infección incluyendo COVID-19; evitar el uso combinado de tiopurinas con esteroides y/o agentes anti-TNF ya que puede incrementar el riesgo de infecciones incluyendo el COVID-19 y finalmente el tratamiento biológico con agentes en contra del factor de necrosis tumoral alfa (anti-TNF alfa) o de cualquier otro mecanismo de acción como anti-integrinas o anti-interleucinas deberán de suspenderse en caso de documentarse infección por COVID-19 y podrán reiniciarse en cuanto haya cedido el proceso infeccioso. Abstract So far, available evidence suggests that patients with inflammatory bowel disease (IBD) are not at greater risk for COVID-19 infection. In regard to patients with IBD remission: 5-aminosalycylates (5-ASAs) do not increase the risk for infection and should be continued. There is no need to suspend them or lower the dose. Immunomodulating drugs, such as thiopurines and methotrexate, should be continued, without modifying doses (even in patients with positive SARS-CoV-2 infection). No type of biologic therapy should be suspended, unless patients become infected with COVID-19. Regarding patients with IBD activity: the oral and/or topical 5-ASA dose should be optimized in cases of disease relapse. Budesonide MMX should be considered in cases of mild-to-moderate activity, to avoid systemic steroid use. Systemic steroids should be avoided whenever possible because doses above 20 mg per day have an immunosuppressive effect, which could increase susceptibility to any type of infection, including COVID-19. The combined use of thiopurines with steroids and/or tumor necrosis factor (TNF) monoclonal antibodies should also be avoided because those combinations can increase the risk for infections, including COVID-19. Finally, biologic treatment with anti-TNF-alpha agents or any other mechanism of action, such as anti-integrins or anti-interleukins, should be suspended if patients become infected with COVID-19. The drugs can be restarted once the infectious process is resolved.


title: Biological agent detection technologies

text: The challenge for first responders, physicians in the emergency room, public health personnel, as well as for food manufacturers, distributors and retailers is accurate and reliable identification of pathogenic agents and their corresponding diseases. This is the weakest point in biological agent detection capability today. There is intense research for new molecular detection technologies that could be used for very accurate detection of pathogens that would be a concern to first responders. These include the need for sensors for multiple applications as varied as understanding the ecology of pathogenic micro‐organisms, forensics, environmental sampling for detect‐to‐treat applications, biological sensors for ‘detect to warn’ in infrastructure protection, responses to reports of ‘suspicious powders’, and customs and borders enforcement, to cite a few examples. The benefits of accurate detection include saving millions of dollars annually by reducing disruption of the workforce and the national economy and improving delivery of correct countermeasures to those who are most in need of the information to provide protective and/or response measures.


title: Chapter 16 Combustion, reactive hazard, and bioprocess safety

text: Abstract Is bioprocess dangerous? How to maintain safety? What is reactive hazard? What is biohazard? Chemical or biotransformation means change. Any changes have irreversible consequences. Managing the changes can help us, while changes can also be harmful. The first-line of defense on any potential unwanted transformations is isolation or containment. WHO defines four-risk groups of biosafety levels. There are six key knowledge bases for biosafety. With chemical safety, substance identification is the first step. The global harmonized system (GHS) of classification and labeling is generally agreed by the world bodies. The hazards are divided into three categories—physical, health, and environmental hazards. Chemical reactivity hazard is a situation where an uncontrolled reaction could result directly or indirectly in serious harm to people, property, or equipment. Fire and explosion are common reactivity hazards. To safe guard processes and facility, one needs to first identify the threat, or screening for reactivity hazards. Combustion processes proceed with chain reactions and the reaction is highly exothermic. Combined with the high-activation energy, combustion leads to large-temperature dependence. The overall reaction products can also vary (partial oxidation versus total oxidation). Partial oxidation reactions are important in chemical industry. Pyrolysis and gasification of biomass, for example, are useful technologies in biomass conversion. An explosion is a fast, transient, exothermic reaction. Unintended and accidental explosions can occur due to (1) The accumulation of reactive chemicals (gas, liquid, or solid) in confined space; (2) Leakage of “significant amount” of reactive chemicals (gas, liquid, or solid) to atmosphere or environment; or (3) Reactor runaway. As a bioprocess engineer, you will be responsible for creating safe processes and protecting the lives and health of your colleagues.


title: Comparison of immunofluorescence with monoclonal antibodies and RT-PCR for the detection of human coronaviruses 229E and OC43 in cell culture

text: Abstract Human coronaviruses, with two known serogroups named 229E and OC43, cause up to one third of common colds and may be associated with serious diseases such as nosocomial respiratory infections, enterocolitis, pericarditis and neurological disorders. Reliable methods of detection in clinical samples are needed for a better understanding of their role in pathology. As a first step in the design of such diagnostic procedures, the sensitivities and specificities of two viral diagnostic assays were compared in an experimental cell culture model: an indirect immuno-fluorescence assay using monoclonal antibodies and reverse transcriptase-polymerase chain reaction amplification of viral RNA from infected cells. Immunofluorescence detected human coronaviruses in cells infected at a MOI as low as 10−2 (log TCID50/ml=4.25 for HCV-229E and 2.0 for HCV-OC43; log PFU/ml=4.83 for HCV-229E and 1.84 for HCV-OC43) versus 10−3 (HCV-OC43) or 10−4 (HCV-229E) for reverse transcriptase-polymerase chain reaction amplification (log TCID50/ml=1.75 for HCV-229E and 1.5 for HCV-OC43; log PFU/ml=2.3 for HCV-229E and 1.34 for HCV-OC43). There were no false positive signals with other human respiratory pathogens: influenza virus, respiratory syncytial virus and adenovirus. Moreover, each assay was coronavirus serogroup-specific. These results demonstrate the potential usefulness of immunofluorescence with monoclonal antibodies and reverse transcriptase-polymerase chain reaction RNA amplification for the rapid detection of human coronaviruses in infected cell cultures. Both methods could be applied to clinical specimens for the diagnosis of human infections.