title: Re-imagining the future of diagnosis of Neglected Tropical Diseases

text: Neglected Tropical Diseases (NTDs) affect an estimated 1 billion people in 149 countries. The World Health Organization (WHO) prioritised 17 NTDs for control and elimination by 2020 and defined a Road Map to help countries reach these goals. Improved diagnostics for NTDs are essential for guiding treatment strategies at different thresholds of control, interruption of transmission, elimination and post-elimination surveillance. While substantial progress has been made in the last decade with chemotherapy, the same cannot be said of diagnostics, largely due to the perceived lack of a commercially viable market for NTD diagnostics. New sample in-answer out nucleic acid amplification technologies that can be performed at the point-of-care offer improved performance over current technologies and the potential to test for multiple pathogens using a single specimen. Finding commonalities for different NTDs in terms of geographic overlap, sentinel populations and treatment strategy will allow NTD programs to leverage these innovations to build cost-effective multiplex surveillance platforms. Connectivity solutions linking data from diagnostic laboratories and POC test readers/devices provide opportunities for automated surveillance systems to make health systems more efficient, improving patient outcomes and assessing impact of interventions in real time. New models of public–private product development partnerships are critical in leveraging diagnostic innovation in other priority area for better diagnosis, control and elimination of NTDs.


A SARS-CoV–Specific Protein Enhances Virulence of an Attenuated Strain of Mouse Hepatitis Virus


title: PSYCOVID-19, dispositif de soutien psychologique dans les champs de la santé mentale, du somatique et du médico-social

text: Résumé Au mois de décembre 2019, l’Organisation Mondiale de la Santé (OMS) recense les premiers cas d’une maladie infectieuse apparue en Chine en novembre de la même année. Générée par le nouveau coronavirus SARS-CoV2, elle est nommée COVID-19 pour COronaVirus Infectious Disease 2019. Rapidement, la diffusion de cette maladie inconnue a un retentissement planétaire : la contagiosité du virus est extrêmement importante et les suites sont potentiellement mortelles. En France, la population réagit initialement avec incrédulité, jusqu’à ce que la maladie atteigne l’Europe et que les premiers cas apparaissent sur le territoire français fin janvier 2020. Quelques semaines plus tard, le 16 mars 2020, le Président Macron déclare le pays « en guerre » contre le Covid-19. Le lendemain, la population est placée en confinement. L’activité du pays est à l’arrêt. Les écoles, les entreprises, les commerces, sont fermés. Les Français sont sidérés. Ils doivent soudainement affronter la peur : celle qu’eux ou leurs proches puissent tomber malades, celle de l’enfermement et de la restriction de libertés, celle de la précarité économique. Et surtout celle de l’inconnu. Afin de prévenir les conséquences désastreuses du séisme, des cellules d’écoute et de soutien psychologiques sont créées dans l’urgence, à l’échelon national. Elles sont destinées à soutenir le corps soignant, les malades et plus largement la population générale. Celle dédiée au département de la Gironde s’organise en quelques heures, sur le week-end du 21 mars 2020. La plateforme d’écoute COVIDPSY33 est ainsi mise en place à Bordeaux, par le Centre Hospitalier Charles Perrens, avec le soutien de l’Agence Régionale de Santé Nouvelle-Aquitaine (ARS). La cellule PSYCOVID-19 est créée de manière concomitante. Cette cellule de soutien d’aval travaille en collaboration avec la plateforme COVIDPSY33 et propose une aide psychologique à la population générale et aux soignants du secteur Bordeaux Rive Droite, Bordeaux Gare, Rives de Garonne, Rives d’Arcins et Sud Gironde. Elle couvre ainsi un territoire équivalent à environ la moitié du plus vaste département de France métropolitaine, la Gironde. Dans cet entretien, Samantha Al Joboory et Florence Monello, psychiatre et psychologue coordinatrices de PSYCOD-19, présentent ce dispositif de soutien psychologique. Abstract In December 2019 the World Health Organization (WHO) recorded the first cases of an infectious disease that appeared in China in November of the same year. Generated by the new coronavirus SARS-CoV2, it is quickly named COVID-19 for COronaVirus Infectious Disease 2019. The spread of this unknown disease will soon have worldwide consequences: the contagiousness of the virus is extremely high and potentially lethal. In France, the population initially reacted with disbelief until the disease reached Europe and the first cases appeared on French territory, at the end of January. A few weeks later, on 16 March 2020, President Macron declared the country "at war" against COVID-19. The next day the population was placed in lockdown. At the present time, the country's activity is at a standstill. Schools, businesses and shops are closed. The French citizens are astounded. They suddenly have to face fear: fear of falling ill or that a close relative may fall ill, fear of being locked up and experiencing restrictions of liberties, fear of economic precariousness. And, above all, fear of uncertainty. In order to prevent the mental consequences of this crisis, psychological support units have been created with urgency at national scale. These units are intended to support the healthcare professionals as well as the patients and more broadly, the general population.The unit responsible for the department of Gironde has been set up quickly, over the weekend of March 21, 2020. The COVIDPSY33 listening unit has thus been created in Bordeaux by the Charles Perrens Hospital with support from the AgenceRégionale de Santé Nouvelle-Aquitaine (ARS). Simultaneously, the PSYCOVID-19 unit was created. This additional unit works in collaboration with the COVIDPSY33 platform and offers psychological assistance to the general population and caregivers in the sectors of Bordeaux Rive Droite, Bordeaux Gare, Rives de Garonne, Rives d’Arcins and Sud Gironde. It thus covers an area equivalent to approximately half of Gironde, the largest department in metropolitan France. In the present interview, Samantha Al Joboory and Florence Monello, psychiatrist and psychologist coordinating PSYCOD-19, present this psychological support unit.


title: Topical rh‐aFGF: An effective therapeutic agent for facemask wearing‐induced pressure sores

text: Protecting healthcare workers is crucial during coronavirus disease 2019 (COVID‐19) pandemic and facemask wearing is considered an effective measure to prevent severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. However, long‐time use of a facemask can cause pressure sores on the ears and nose bridge and increase the risk of infection. The topical recombinant human acidic fibroblast growth factor (rh‐aFGF) was used to cure pressure sores for healthcare workers at Zhongfaxincheng campus of Tongji Hospital. The results from a small sample size survey conducted in Zhongfaxincheng campuses of Tongji Hospital showed that treatment with topical rh‐aFGF could significantly inhibit the progression of pressure sores and accelerate the wound healing with no apparent ill‐effects. Therefore, we propose that topical rh‐aFGF is an effective therapeutic agent for facemask wearing‐induced pressure sores and worth of popularizing and applying. This article is protected by copyright. All rights reserved.


title: Immune regulation and cytotoxic T cell activation of IL-10 agonists – Preclinical and clinical experience

text: Abstract The expansion and activation of tumor antigen reactive CD8+ T cells are primary goals of immunotherapies for cancer. IL-10 is an anti-inflammatory cytokine with an essential role in the development and proliferation of regulatory T cells, restricting myeloid and chronic inflammatory T cell responses. However, IL-10 is also essential for the expansion of antigen activated, tumor specific CD8+ T cells, leading to spontaneous tumor development in IL-10 deficient patients and mice. IL-10 induces IFNγ and cytotoxic mediators in antigen activated T cells. In clinical trials, monotherapy with recombinant, pegylated IL-10 (Pegilodecakin) induced objective responses in cancer patients. Patients receiving pegilodecakin had a systemic increase of IFNγ and granzymes, proliferation and expansion of immune checkpoint positive CD8+ T cells. Combination of pegilodecakin with anti-PD-1 appeared to improve on the efficacy of the single agents.


title: COVID-19 Silver Linings

text: A heightened state of alert due to the COVID-19 outbreak was declared by the Singapore Ministry of Health on February 7th, 2020. Within the hospital, team reorganizations, workflow revisions and physical segregation caused anxiety among healthcare workers (HCWs). Fear of the unknown, emotional and physical fatigue started to take their toll on HCWs. We share our learning journey over the first 8 weeks of COVID-19: the importance of acknowledging fears and questions, and transforming them to collective knowledge; the role of empathic, hands-on leadership which brings camaraderie and calms scepticism; the importance of validating efforts and acknowledging hardship; and most importantly, the security that comes from camaraderie, breaking down hierarchical barriers and motivating each other to keep on going.


title: Digital microbiology

text: BACKGROUND: Digitalisation and artificial intelligence have an important impact on the way microbiology laboratories will work in the near future. Opportunities and challenges lay ahead to digitalise the microbiological workflows. Making an efficient use of big data, machine learning, and artificial intelligence in clinical microbiology requires a profound understanding of data handling aspects. OBJECTIVE: This review article summarizes the most important concepts of digital microbiology. The article provides microbiologists, clinicians and data scientists a viewpoint and practical examples along the diagnostic process. SOURCES: We used peer-reviewed literature identified by a Pubmed search for digitalisation, machine learning, artificial intelligence and microbiology. CONTENT: We describe the opportunities and challenges of digitalisation in microbiological diagnostic process with various examples. We also provide in this context key aspects of data structure and interoperability, as well as legal aspects. Finally, we outline the way for applications in a modern microbiology laboratory. IMPLICATIONS: We predict that digitalization and the usage of machine learning will have a profound impact on the daily routine of the laboratory staff. Along the analytical process, the most important steps should be identified, where digital technologies can be applied and provide a benefit. The education of all staff involved should be adapted to prepare for the advances in digital microbiology.


title: Return to Normalcy? Principles on Resuming Surgical Services in the COVID-19 Era

text: The rapidly changing health care climate related to coronavirus disease 2019 (COVID-19) has resulted in numerous changes to health care systems and in practices that protect both the public and the workers who serve in hospitals around the country. As a result, these past few months have seen a drastic reduction in outpatient visits and surgical volumes. With phased reopening and appropriate guidance, health care systems are attempting to return to normal. Our institution has had the unique opportunity to already return operations back to full capacity. The experiences and lessons learned are described, and we provide guiding principles to allow for a safe and effective return to patient care.


The year of the nurses and the midwife: Nursing professionalism shining in the frontline of anti-epidemic and to be strengthened in the future


title: TaqMan real time RT-PCR assays for detecting ferret innate and adaptive immune responses

text: Abstract The ferret is an excellent model for many human infectious diseases including influenza, SARS-CoV, henipavirus and pneumococcal infections. The ferret is also used to study cystic fibrosis and various cancers, as well as reproductive biology and physiology. However, the range of reagents available to measure the ferret immune response is very limited. To address this deficiency, high-throughput real time RT-PCR TaqMan assays were developed to measure the expression of fifteen immune mediators associated with the innate and adaptive immune responses (IFNα, IFNβ, IFNγ, IL1α, IL1β, IL2, IL4, IL6, IL8, IL10, IL12p40, IL17, Granzyme A, MCP1, TNFα), as well as four endogenous housekeeping genes (ATF4, HPRT, GAPDH, L32). These assays have been optimized to maximize reaction efficiency, reduce the amount of sample required (down to 1ng RNA per real time RT-PCR reaction) and to select the most appropriate housekeeping genes. Using these assays, the expression of each of the tested genes could be detected in ferret lymph node cells stimulated with mitogens or infected with influenza virus in vitro. These new tools will allow a more comprehensive analysis of the ferret immune responses following infection or in other disease states.


title: Crystallization and preliminary crystallographic analysis of the heptad‐repeat complex of SARS coronavirus spike protein

text: The aetiological agent of an emergent outbreak of atypical pneumonia, severe acute respiratory syndrome (SARS), is a positive‐stranded RNA virus (SARS‐CoV) belonging to the Coronaviridae family with a genome that differs substantially from those of other known coronaviruses. Highly conserved heptad‐repeat (HR1 and HR2) regions in class I viral fusion proteins, including spike protein from SARS coronavirus, interact with each other to form a six‐helix bundle, which is called a fusion core. The crystal structure of the fusion core is expected to greatly facilitate drug design. Crystals of the fusion core of SARS‐CoV spike protein have been grown at 291 K using PEG 4000 as precipitant. The diffraction pattern of the crystal extends to 2.8 Å resolution at 100 K in‐house. The crystals have unit‐cell parameters a = 121.2, b = 66.3, c = 70.0 Å, α = γ = 90, β = 107.4° and belong to space group C2. Assuming the presence of six molecules per asymmetric unit, the solvent content is estimated to be about 28%.


title: Psychopharmacology of COVID-19

text: BACKGROUND: With the rapid, global spread of SARS-CoV-2, hospitals have become inundated with patients suffering from COVID-19. Consultation-liaison psychiatrists are actively involved in managing these patients and should familiarize themselves with how the virus and its proposed treatments can affect psychotropic management. The only FDA approved drug to treat COVID-19 is remdesivir, and other off-label medications used include chloroquine and hydroxychloroquine, tocilizumab, lopinavir/ritonavir, favipiravir, convalescent plasma therapy, azithromycin, vitamin C, corticosteroids, interferon and colchicine. PURPOSE: To provide an overview of the major safety considerations relevant to clinicians who prescribe psychotropics to patients with COVID-19, both related to the illness and its proposed treatments. METHODS: In this targeted review we performed structured literature searches in PubMed to identify articles describing the impacts of COVID-19 on different organ systems, the neuropsychiatric adverse effects of treatments, and any potential drug interactions with psychotropics. The articles most relevant to this manuscript were included. RESULTS: COVID-19 impacts multiple organ systems, including gastrointestinal, renal, cardiovascular, pulmonary, immunological, and hematological systems. This may lead to pharmacokinetic changes that impact psychotropic medications and increase sensitivity to psychotropic-related adverse effects. Additionally, several proposed treatments for COVID-19 have neuropsychiatric effects and potential interactions with commonly used psychotropics. CONCLUSION: Clinicians should be aware of the need to adjust existing psychotropics or avoid using certain medications in some COVID-19 patients. They should also be familiar with neuropsychiatric effects of medications being used to treat this disease. Further research is needed to identify strategies to manage psychiatric issues in this population.


title: Preprints in medical research: Progress and principles

text: In this month’s editorial, the PLOS Medicine Editors discuss the role of preprints in human health research and propose a 3-part framework for ensuring benefit.


title: Comparing Human Metapneumovirus and Respiratory Syncytial Virus: Viral Co-Detections, Genotypes and Risk Factors for Severe Disease

text: BACKGROUND: It is unclarified as to whether viral co-detection and human metapneumovirus (HMPV) genotypes relate to clinical manifestations in children with HMPV and lower respiratory tract infection (LRTI), and if the clinical course and risk factors for severe LRTI differ between HMPV and respiratory syncytial virus (RSV). METHODS: We prospectively enrolled hospitalized children aged <16 years with LRTI from 2006 to 2015. Children were clinically examined, and nasopharyngeal aspirates were analyzed using semi-quantitative, real-time polymerase chain reaction tests for HMPV, RSV and 17 other pathogens. HMPV-positive samples were genotyped. RESULTS: A total of 171 children had HMPV infection. HMPV-infected children with single virus (n = 106) and co-detections (n = 65) had similar clinical manifestations. No clinical differences were found between HMPV genotypes A (n = 67) and B (n = 80). The HMPV-infected children were older (median 17.2 months) than RSV-infected children (median 7.3 months, n = 859). Among single virus-infected children, no differences in age-adjusted LRTI diagnoses were found between HMPV and RSV. Age was an important factor for disease severity among single virus-infected children, where children <6 months old with HMPV had a milder disease than those with RSV, while in children 12–23 months old, the pattern was the opposite. In multivariable logistic regression analysis for each virus type, age ≥12 months (HMPV), and age <6 months (RSV), prematurity, ≥1 chronic disease and high viral loads of RSV, but not high HMPV viral loads, were risk factors for severe disease. CONCLUSIONS: Among hospitalized children with LRTI, HMPV manifests independently of viral co-detections and HMPV genotypes. Disease severity in HMPV- and RSV-infected children varies in relation to age. A history of prematurity and chronic disease increases the risk of severe LRTI among HMPV- and RSV-infected children.


title: Comparative sequence analysis of a polymorphic region of the spike glycoprotein S1 subunit of enteric bovine coronavirus isolates

text: Complementary oligonucleotide primers which flank a 1146-nucleotide gene fragment (S1B: nt 1185 to 2333) encompassing a polymorphic region (nt 1368 to 1776) of the S1 subunit of bovine coronavirus spike glycoprotein were used for enzymatic amplification by PCR. We chose four clinical isolates, recovered from cases of epidemic diarrhea in neonatal calves in Québec dairy herds between 1987–1990, to specifically amplify and analyze their sequences in the selected genomic area. Nucleotide sequence analysis of the four clinical isolates indicated that their S1B gene fragments were highly conserved. We also compared the S1B gene sequences of the Québec BCV isolates to the published corresponding sequences from BCV-L9 [37], BCV-MEB [1], and BCV-F15 [3] reference strains. A high degree of similarity was demonstrated for all viruses, no deletions or insertions were observed, and the only variations that were identified consisted of nucleotide substitutions. The differing nucleotides and amino acids (aa) were not distributed randomly over the entire sequence but rather were clustered in the polymorphic region. Of these, four sporadic aa changes were located in antigenic domain II (aa residues 517 to 720) of S1. This correlates with varied antigenicity observed among the BCV Québec isolates when reacting with MAbs directed against the S glycoprotein of the Mebus strain. The other mutations seem to be fixed in all Québec isolates.


title: Identification of potential binders of the main protease 3CL(pro) of the COVID-19 via structure-based ligand design and molecular modeling

text: We have applied a computational strategy, using a combination of virtual screening, docking and molecular dynamics techniques, aimed at identifying possible lead compounds for the non-covalent inhibition of the main protease 3CL(pro) of the SARS-CoV2 Coronavirus. Based on the X-ray structure (PDB code: 6LU7), ligands were generated using a multimodal structure-based design and then docked to the monomer in the active state. Docking calculations show that ligand-binding is strikingly similar in SARS-CoV and SARS-CoV2 main proteases. The most potent docked ligands are found to share a common binding pattern with aromatic moieties connected by rotatable bonds in a pseudo-linear arrangement.


title: Frequency of lupus anticoagulant in Covid‐19 patients

text: We have recently published in the Journal of Thrombosis and Haemostasis the presence of lupus anticoagulant (LAC) at high frequency in Covid‐19 patients (Harzallah et al.(1)). Bowles et al.(2) and Helms et al.(3) have confirmed these results in new publications. Tang(4) has reported discordant data. He has found that very few tested covid‐19 patients had positive LAC in a small series (n=12). Bowles et al. have found that LAC were positive in 91% of patients (n=34) with high activated partial thromboplastin time (aPTT).


title: Merkel cell polyomavirus DNA in immunocompetent and immunocompromised patients with respiratory disease

text: Merkel cell polyomavirus (MCPyV) was identified originally in association with a rare but aggressive skin cancer, Merkel cell carcinoma. The virus has since been found in the respiratory tract of some patients with respiratory disease. However, the role of MCPyV in the causation of respiratory disease has not been established. To determine the prevalence of MCPyV in 305 respiratory samples from immunocompetent and immunocompromised patients and evaluate their contribution to respiratory diseases, specimens were screened for MCPyV using single, multiplex, or real‐time PCR; co‐infection with other viruses was examined. Of the 305 samples tested, 10 (3.27%) were positive for MCPyV. The virus was found in two groups of patients: in 6 (2%) nasopharyngeal aspirate samples from children aged 26 days to 7 months who were immunocompetent; and in 4 (1.3%) of nasopharyngeal aspirate samples taken from patients aged 41 to 69 years who were severely immunosuppressed from leukemia or transplant therapy. Both groups had upper or lower respiratory tract infection. Co‐infections with other viruses were found in 30% of the MCPyV positive samples. The data present a pattern of infection similar to that seen with the polyomaviruses JC and BK in which the virus is acquired during childhood, probably by the respiratory route. The viruses then establish latency and become reactivated in the event of immunosuppression. J. Med. Virol. 83:2220–2224, 2011. © 2011 Wiley Periodicals, Inc.


title: When could human challenge trials be deployed to combat emerging infectious diseases? Lessons from the case of a Zika virus human challenge trial

text: Human challenge trials (HCTs) deliberately infect participants in order to test vaccines and treatments in a controlled setting, rather than enrolling individuals with natural exposure to a disease. HCTs are therefore potentially powerful tools to prepare for future outbreaks of emerging infectious diseases. Yet when an infectious disease is emerging, there is often substantial risk and uncertainty about its complications, and few available interventions, making an HCT ethically complex. In light of the need to consider ethical issues proactively as a part of epidemic preparedness, we use the case of a Zika virus HCT to explore whether and when HCTs might be ethically justified to combat emerging infectious diseases. We conclude that emerging infectious diseases could be appropriate candidates for HCTs and we identify relevant considerations and provide a case example to illustrate when they might be ethically acceptable.


title: Lithium chloride inhibits early stages of foot‐and‐mouth disease virus (FMDV) replication in vitro

text: Foot‐and‐mouth disease virus (FMDV) causes an economically important and highly contagious disease of cloven‐hoofed animals such as cattle, swine, and sheep. FMD vaccine is the traditional way to protect against the disease, which can greatly reduce its occurrence. However, the use of FMD vaccines to protect early infection is limited. Therefore, the alternative strategy of applying antiviral agents is required to control the spread of FMDV in outbreak situations. As previously reported, LiCl has obviously inhibition effects on a variety of viruses such as transmissible gastroenteritis virus (TGEV), infectious bronchitis coronavirus (IBV), and pseudorabies herpesvirus and EV‐A71 virus. In this study, our findings were the first to demonstrate that LiCl inhibition of the FMDV replication. In this study, BHK‐21 cell was dose‐dependent with LiCl at various stages of FMDV. Virus titration assay was calculated by the 50% tissue culture infected dose (TCID(50)) with the Reed and Muench method. The cytotoxicity assay of LiCl was performed by the CCK8 kit. The expression level of viral mRNA was measured by RT‐qPCR. The results revealed LiCl can inhibit FMDV replication, but it cannot affect FMDV attachment stage and entry stage in the course of FMDV life cycle. Further studies confirmed that the LiCl affect the replication stage of FMDV, especially the early stages of FMDV replication. So LiCl has potential as an effective anti‐FMDV drug. Therefore, LiCl may be an effective drug for the control of FMDV. Based on that, the mechanism of the antiviral effect of LiCl on FMDV infection is need to in‐depth research in vivo.


AHPBA Webinar about Covid-19: Lessons Learned Responding to a Pandemic


title: Current Resources for Evidence-Based Practice, May 2020

text: Abstract An extensive review of new resources to support the provision of evidence-based care for women and infants. The current column includes a discussion of a new National Academy of Medicine report on planned place of birth and implications during the SARS-CoV-2 pandemic and commentaries on reviews focused on anorectal sexually transmitted infections and feeding methods following cleft lip repair in infants.


title: Efficacy and Safety of Bortezomib in Multiple Myeloma Patients with Hepatitis B: A Multicenter Retrospective Study

text: BACKGROUND: The efficacy and safety evidence of bortezomib in multiple myeloma (MM) patients with hepatitis B is vacant. This study aimed to investigate the efficacy and safety of bortezomib in MM patients with hepatitis B in China. METHODS: From 2006 to 2011, 739 newly diagnosed MM patients were screened for serum hepatitis B virus (HBV) biomarkers. HBV-infected patients were followed for HBV reactivation by monitoring of serum alanine transaminase (ALT) and HBV DNA load. The pattern of HBV reactivation in relation to bortezomib was evaluated. Seven hundred thirty-nine MM patients were included in this study. RESULTS: The prevalence of MM patients infected with HBV was 3.4% (n = 25), of which 17 cases were treated with bortezomib. Bortezomib had no significant influence on liver function (ALT before and after treatment: 36.69 ± 8.90 U/L vs. 11.31 ± 2.74 U/L, P = 0.19) and HBV DNA of MM patients with HBV (detectable HBV DNA percentage: 5.9% vs. 11.8%, P = 0.12). CONCLUSIONS: Bortezomib can be used safely and effectively in MM patients with hepatitis B. HBV prophylaxis and surveillance are recommended during the MM treatment.


title: plethy: management of whole body plethysmography data in R

text: BACKGROUND: Characterization of respiratory phenotypes can enhance complex trait and genomic studies involving allergic/autoimmune and infectious diseases. Many aspects of respiration can be measured using devices known as plethysmographs that can measure thoracic movement. One such approach (the Buxco platform) performs unrestrained whole body plethysmography on mice which infers thoracic movements from pressure differences from the act of inhalation and exhalation. While proprietary software is available to perform basic statistical analysis as part of machine’s bundled software, it is desirable to be able to incorporate these analyses into high-throughput pipelines and integrate them with other data types, as well as leverage the wealth of analytic and visualization approaches provided by the R statistical computing environment. RESULTS: This manuscript describes the plethy package which is an R/Bioconductor framework for pre-processing and analysis of plethysmography data with emphasis on larger scale longitudinal experiments. The plethy package was designed to facilitate quality control and exploratory data analysis. We provide a demonstration of the features of plethy using a dataset assessing the respiratory effects over time of SARS and Influenza infection in mice. CONCLUSION: The plethy package provides functionality for users to import, perform quality assessment and exploratory data analysis in a manner that allows interoperability with existing modelling tools. Our package is implemented in R and is freely available as part of the Bioconductor project http://www.bioconductor.org/packages/release/bioc/html/plethy.html. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-015-0547-7) contains supplementary material, which is available to authorized users.


title: Type 1 diabetes and technology at time of COVID ‐19. A case report

text: Intermittent acute illness contribute to blood glucose dysregulation in Patients with Type 1 diabetes mellitus (T1DM): systemic inflammation, insulin resistance, unpredictable eating, fever, nausea, vomiting, among other factors lead to blood glucose instability with a significant risk of hypoglycemia and represent a difficult challenge for Patients (1). Hyperglycemia (with or without diabetes) is a double edge sword : is depend on the acute illness and by itself negatively contribute to a more severe prognosis.


title: Applications of selective neutrality tests to molecular ecology

text: This paper reviews how statistical tests of neutrality have been used to address questions in molecular ecology are reviewed. The work consists of four major parts: a brief review of the current status of the neutral theory; a review of several particularly interesting examples of how statistical tests of neutrality have led to insight into ecological problems; a brief discussion of the pitfalls of assuming a strictly neutral model if it is false; and a discussion of some of the opportunities and problems that molecular ecologists face when using neutrality tests to study natural selection.


title: QSAR Studies on Andrographolide Derivatives as α-Glucosidase Inhibitors

text: Andrographolide derivatives were shown to inhibit α-glucosidase. To investigate the relationship between activities and structures of andrographolide derivatives, a training set was chosen from 25 andrographolide derivatives by the principal component analysis (PCA) method, and a quantitative structure-activity relationship (QSAR) was established by 2D and 3D QSAR methods. The cross-validation r(2) (0.731) and standard error (0.225) illustrated that the 2D-QSAR model was able to identify the important molecular fragments and the cross-validation r(2) (0.794) and standard error (0.127) demonstrated that the 3D-QSAR model was capable of exploring the spatial distribution of important fragments. The obtained results suggested that proposed combination of 2D and 3D QSAR models could be useful in predicting the α-glucosidase inhibiting activity of andrographolide derivatives.


title: Understanding community perceptions, social norms and current practice related to respiratory infection in Bangladesh during 2009: a qualitative formative study

text: BACKGROUND: Respiratory infections are the leading cause of childhood deaths in Bangladesh. Promoting respiratory hygiene may reduce infection transmission. This formative research explored community perceptions about respiratory infections. METHODS: We conducted 34 in-depth interviews and 16 focus group discussions with community members and school children to explore respiratory hygiene related perceptions, practices, and social norms in an urban and a rural setting. We conducted unstructured observations on respiratory hygiene practices in public markets. RESULTS: Informants were not familiar with the term "respiratory infection"; most named diseases that had no relation to respiratory dysfunction. Informants reported that their community identified a number of 'good behaviors' related to respiratory hygiene, but they also noted, and we observed, that very few people practiced these. All informants cited hot/cold weather changes or using cold water as causes for catching cold. They associated transmission of respiratory infections with close contact with a sick person's breath, cough droplets, or spit; sharing a sick person's utensils and food. Informants suggested that avoiding such contact was the most effective method to prevent respiratory infection. Although informants perceived that handwashing after coughing or sneezing might prevent illness, they felt this was not typically feasible or practical. CONCLUSION: Community perceptions of respiratory infections include both concerns with imbalances between hot and cold, and with person-to-person transmission. Many people were aware of measures that could prevent respiratory infection, but did not practice them. Interventions that leverage community understanding of person-to-person transmission and that encourage the practice of their identified 'good behaviors' related to respiratory hygiene may reduce respiratory disease transmission.


title: The Baltic Sea Virome: Diversity and Transcriptional Activity of DNA and RNA Viruses

text: Metagenomic and metatranscriptomic data were generated from size-fractionated samples from 11 sites within the Baltic Sea and adjacent marine waters of Kattegat and freshwater Lake Torneträsk in order to investigate the diversity, distribution, and transcriptional activity of virioplankton. Such a transect, spanning a salinity gradient from freshwater to the open sea, facilitated a broad genome-enabled investigation of natural as well as impacted aspects of Baltic Sea viral communities. Taxonomic signatures representative of phages within the widely distributed order Caudovirales were identified with enrichments in lesser-known families such as Podoviridae and Siphoviridae. The distribution of phage reported to infect diverse and ubiquitous heterotrophic bacteria (SAR11 clades) and cyanobacteria (Synechococcus sp.) displayed population-level shifts in diversity. Samples from higher-salinity conditions (>14 practical salinity units [PSU]) had increased abundances of viruses for picoeukaryotes, i.e., Ostreococcus. These data, combined with host diversity estimates, suggest viral modulation of diversity on the whole-community scale, as well as in specific prokaryotic and eukaryotic lineages. RNA libraries revealed single-stranded DNA (ssDNA) and RNA viral populations throughout the Baltic Sea, with ssDNA phage highly represented in Lake Torneträsk. Further, our data suggest relatively high transcriptional activity of fish viruses within diverse families known to have broad host ranges, such as Nodoviridae (RNA), Iridoviridae (DNA), and predicted zoonotic viruses that can cause ecological and economic damage as well as impact human health. IMPORTANCE Inferred virus-host relationships, community structures of ubiquitous ecologically relevant groups, and identification of transcriptionally active populations have been achieved with our Baltic Sea study. Further, these data, highlighting the transcriptional activity of viruses, represent one of the more powerful uses of omics concerning ecosystem health. The use of omics-related data to assess ecosystem health holds great promise for rapid and relatively inexpensive determination of perturbations and risk, explicitly with regard to viral assemblages, as no single marker gene is suitable for widespread taxonomic coverage.


title: Zinc Sulfate in Narrow Range as an In Vitro Anti-HSV-1 Assay

text: This report explains the employing of a combination test of traditional cell culture with a quantitative real-time PCR for assessment of the antiviral effect of zinc sulfate (ZnSO(4)) on herpes simplex virus (HSV)-infected Vero cells. Our evidence showed that the treatment with 0.3 mM ZnSO(4) strongly inhibited the replication of virus progeny (MOI 0.001) at least 68-fold less. On the other hand, the IC50 demonstrated that the highest activity of ZnSO(4) was at the 0.23 mM concentration.


title: A rigorous approach to facilitate and guarantee the correctness of the genetic testing management in human genome information systems

text: BACKGROUND: Recent medical and biological technology advances have stimulated the development of new testing systems that have been providing huge, varied amounts of molecular and clinical data. Growing data volumes pose significant challenges for information processing systems in research centers. Additionally, the routines of genomics laboratory are typically characterized by high parallelism in testing and constant procedure changes. RESULTS: This paper describes a formal approach to address this challenge through the implementation of a genetic testing management system applied to human genome laboratory. We introduced the Human Genome Research Center Information System (CEGH) in Brazil, a system that is able to support constant changes in human genome testing and can provide patients updated results based on the most recent and validated genetic knowledge. Our approach uses a common repository for process planning to ensure reusability, specification, instantiation, monitoring, and execution of processes, which are defined using a relational database and rigorous control flow specifications based on process algebra (ACP). The main difference between our approach and related works is that we were able to join two important aspects: 1) process scalability achieved through relational database implementation, and 2) correctness of processes using process algebra. Furthermore, the software allows end users to define genetic testing without requiring any knowledge about business process notation or process algebra. CONCLUSIONS: This paper presents the CEGH information system that is a Laboratory Information Management System (LIMS) based on a formal framework to support genetic testing management for Mendelian disorder studies. We have proved the feasibility and showed usability benefits of a rigorous approach that is able to specify, validate, and perform genetic testing using easy end user interfaces.


title: Identification of diverse viruses in upper respiratory samples in dromedary camels from United Arab Emirates

text: Camels are known carriers for many viral pathogens, including Middle East respiratory syndrome coronavirus (MERS-CoV). It is likely that there are additional, as yet unidentified viruses in camels with the potential to cause disease in humans. In this study, we performed metagenomic sequencing analysis on nasopharyngeal swab samples from 108 MERS-CoV-positive dromedary camels from a live animal market in Abu Dhabi, United Arab Emirates. We obtained a total of 846.72 million high-quality reads from these nasopharyngeal swab samples, of which 2.88 million (0.34%) were related to viral sequences while 512.63 million (60.5%) and 50.87 million (6%) matched bacterial and eukaryotic sequences, respectively. Among the viral reads, sequences related to mammalian viruses from 13 genera in 10 viral families were identified, including Coronaviridae, Nairoviridae, Paramyxoviridae, Parvoviridae, Polyomaviridae, Papillomaviridae, Astroviridae, Picornaviridae, Poxviridae, and Genomoviridae. Some viral sequences belong to known camel or human viruses and others are from potentially novel camel viruses with only limited sequence similarity to virus sequences in GenBank. A total of five potentially novel virus species or strains were identified. Co-infection of at least two recently identified camel coronaviruses was detected in 92.6% of the camels in the study. This study provides a comprehensive survey of viruses in the virome of upper respiratory samples in camels that have extensive contact with the human population.


title: Unusual histiocytic disease in a Somali cat

text: An 8-year-old Somali cat presented with a 9-month history of inappetence, vomiting and weight loss. The disease progressed to involve neurological signs associated with a mass lesion at the level of the first lumbar vertebra. Histopathology identified the condition as malignant histiocytosis affecting the lungs, stomach, mesenteric lymph nodes, liver, spleen, brain and spinal cord. However, the presentation of this case differs from previously reported cases of malignant histiocytosis, and may therefore represent a variant form of histiocytic disease.


title: Lack of group X secreted phospholipase A2 increases survival following pandemic H1N1 influenza infection

text: Abstract The role of Group X secreted phospholipase A2 (GX-sPLA2) during influenza infection has not been previously investigated. We examined the role of GX-sPLA2 during H1N1 pandemic influenza infection in a GX-sPLA2 gene targeted mouse (GX−/−) model and found that survival after infection was significantly greater in GX−/− mice than in GX+/+ mice. Downstream products of GX-sPLA2 activity, PGD2, PGE2, LTB4, cysteinyl leukotrienes and Lipoxin A4 were significantly lower in GX−/− mice BAL fluid. Lung microarray analysis identified an earlier and more robust induction of T and B cell associated genes in GX−/− mice. Based on the central role of sPLA2 enzymes as key initiators of inflammatory processes, we propose that activation of GX-sPLA2 during H1N1pdm infection is an early step of pulmonary inflammation and its inhibition increases adaptive immunity and improves survival. Our findings suggest that GX-sPLA2 may be a potential therapeutic target during influenza.


title: Mild SARS-COV-2 infections in children might be based on evolutionary biology and linked with host reactive oxidative stress (ROS) and antioxidant capabilities

text: Summary Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection leads to significant morbidity and mortality in elderly. Children typically have mild illness with rare mortalities. Age and comorbid medical conditions are the most important determinant of the infection outcome. Currently there is no clear explanation for difference in disease severity and outcome in different age groups. Based on evolutionary biology and translational research this review suggests that high antioxidant capacity of children leading to a balanced redox state is the key factor for mild SARS-COV-2 infections in this age group. On the other hand, elderly with low antioxidant capacity and ACE2 expression is prone to severe infections by redox sensitive immune modulation.


title: Global Preparedness Against COVID-19: We Must Leverage the Power of Digital Health

text: The coronavirus disease (COVID-19) pandemic has revealed many areas of public health preparedness that are lacking, especially in lower- and middle-income countries. Digital interventions provide many opportunities for strengthening health systems and could be vital resources in the current public health emergency. We provide several use cases for infection control, home-based diagnosis and screening, empowerment through information, public health surveillance and epidemiology, and leveraging crowd-sourced data. A thoughtful, concerted effort—leveraging existing experience and robust enterprise-grade technologies—can have a substantive impact on the immediate and distal consequences of COVID-19.


title: Why do I need it? I am not at risk! Public perceptions towards the pandemic (H1N1) 2009 vaccine

text: BACKGROUND: On the 30th September 2009, the pandemic (H1N1) 2009 influenza vaccine was made available to adults and children aged 10 years and over, in Australia. Acceptance of a novel vaccine is influenced by perceptions of risk including risk of infection, risk of death or severe illness and risk of serious vaccine side-effects. We surveyed a sample of residents from Sydney, Australia to ascertain their risk perception, attitudes towards the pandemic and willingness to accept the pandemic (H1N1) 2009 influenza vaccine. METHODS: We sampled residents using a cross-sectional intercept design during the WHO Phase 6. Members of the public were approached in shopping and pedestrian malls to undertake the survey during September and October 2009. The survey measured perceived risk, seriousness of disease, recent behavioural changes, likely acceptance of the pandemic (H1N1) 2009 vaccine and issues relating to uptake and perceived safety. RESULTS: Of the 627 respondents, the majority felt that they had a "very low to low" (332/627, 52.9%) risk of acquiring H1N1. 24.5% (154/627) of respondents believed that the disease would "very seriously or extremely" affect their health. Nearly half (305/627, 48.6%) reported that in response to the "swine flu" outbreak they had undertaken one or more of the investigated behavioural changes. Overall, the self-reported likelihood of accepting vaccination against novel H1N1 was 54.7% (343/627). CONCLUSIONS: While, most participants did not believe they were at high risk of acquiring pandemic H1N1 2009, over half of the sample indicated that they would accept the vaccine. Participants who were vaccinated against the seasonal influenza were more likely to receive the H1N1 vaccine. Concerns about safety, the possibility of side effects and the vaccine development process need to be addressed.


Submissions and publications in Corona times


title: Might renin–angiotensin system blockers play a role in the COVID-19 pandemic?

text: Since December 2019, a new coronavirus, named SARS-CoV-2, has spread globally, affecting >200 000 people worldwide with the so-called COVID-19 disease. The scientific community is actively and constantly working to identify the mechanisms involved in the diffusion of this virus and the pathogenesis of the infection, with its most frequent and severe complication, namely interstitial pneumonia. To date, SARS-CoV-2 is known to enter the host cells via the angiotensin-converting enzyme 2 protein. For this reason, the hypothesis that drugs capable of increasing the expression of this protein may have a role in the spread of the virus and in the symptomatology of affected patients has taken hold. The purpose of this Editorial is to briefly show the evidence currently available in this regard and to provide ideas for future research.


title: Metagenomic Sequencing Detects Respiratory Pathogens in Hematopoietic Cellular Transplant Patients

text: Current microbiologic diagnostics often fail to identify the etiology of lower respiratory tract infections (LRTI) in hematopoietic cellular transplant recipients (HCT), which precludes the implementation of targeted therapies. To address the need for improved LRTI diagnostics, we evaluated the utility of metagenomic next generation sequencing (mNGS) of bronchoalveolar lavage (BAL) to detect microbial pathogens in HCT patients with acute respiratory illnesses. We enrolled 22 post-HCT adults ages 19-69 years with acute respiratory illnesses who underwent BAL at the University of Michigan between January 2012 and May 2013. mNGS was performed on BAL fluid to detect microbes and simultaneously assess the host transcriptional response. Results were compared against conventional microbiologic assays. mNGS demonstrated 100% sensitivity for detecting respiratory microbes (human metapneumovirus, respiratory syncytial virus, Stenotrophomonas maltophilia, human herpesvirus 6 and cytomegalovirus) when compared to standard testing. Previously unrecognized LRTI pathogens were identified in six patients for whom standard testing was negative (human coronavirus 229E, human rhinovirus A, Corynebacterium propinquum and Streptococcus mitis); findings were confirmed by independent PCR and 16S rRNA sequencing. Relative to patients without infection, patients with infection had increased expression of immunity related genes (p=0.022) and significantly lower diversity of their respiratory microbiome (p=0.017). Compared to conventional diagnostics, mNGS enhanced detection of pathogens in BAL fluid from HCT patients. Furthermore, our results suggest that combining unbiased microbial pathogen detection with assessment of host gene biomarkers of immune response may hold promise for enhancing the diagnosis of post-HCT respiratory infections.


title: Patterns of Metastasis in Merkel Cell Carcinoma

text: BACKGROUND: Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine malignancy with a propensity for regional and distant spread. Because of the relative infrequency of this disease, the patterns of metastasis in MCC are understudied. METHODS: Patients with American Joint Committee on Cancer (8th edition) stage I–IV MCC treated at our institution were identified (1/1/2008–2/28/2018). The first site of metastasis was classified as regional [regional lymph node (LN) basin, in-transit] or distant. Distant metastasis-free (DMFS) and MCC-specific (MSS) survival were estimated. RESULTS: Of 133 patients, 64 (48%) had stage I, 13 (10%) stage II, 48 (36%) stage III, and 8 (6%) stage IV disease at presentation. The median follow-up time in patients who remained alive was 36 (interquartile range 20–66) months. Regional or distant metastases developed in 78 (59%) patients. The first site was regional in 87%, including 73% with isolated LN involvement, and distant in 13%. Thirty-seven (28%) patients eventually developed distant disease, which most commonly involved the abdominal viscera (51%) and distant LNs (46%) first. The lung (0%) and brain (3%) were rarely the first distant sites. Stage III MCC at presentation was significantly associated with worse DMFS (hazard ratio 4.87, P = 0.001) and stage IV disease with worse MSS (hazard ratio 6.30, P = 0.002). CONCLUSIONS: Regional LN metastasis is the most common first metastatic event in MCC, confirming the importance of nodal evaluation. Distant disease spread appears to have a predilection for certain sites. Understanding these patterns could help to guide surveillance strategies.


title: Amino acid changes in the spike protein of feline coronavirus correlate with systemic spread of virus from the intestine and not with feline infectious peritonitis

text: Recent evidence suggests that a mutation in the spike protein gene of feline coronavirus (FCoV), which results in an amino acid change from methionine to leucine at position 1058, may be associated with feline infectious peritonitis (FIP). Tissue and faecal samples collected post mortem from cats diagnosed with or without FIP were subjected to RNA extraction and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) to detect FCoV RNA. In cats with FIP, 95% of tissue, and 81% of faecal samples were PCR-positive, as opposed to 22% of tissue, and 60% of faecal samples in cats without FIP. Relative FCoV copy numbers were significantly higher in the cats with FIP, both in tissues (P < 0.001) and faeces (P = 0.02). PCR-positive samples underwent pyrosequencing encompassing position 1058 of the FCoV spike protein. This identified a methionine codon at position 1058, consistent with the shedding of an enteric form of FCoV, in 77% of the faecal samples from cats with FIP, and in 100% of the samples from cats without FIP. In contrast, 91% of the tissue samples from cats with FIP and 89% from cats without FIP had a leucine codon at position 1058, consistent with a systemic form of FCoV. These results suggest that the methionine to leucine substitution at position 1058 in the FCoV spike protein is indicative of systemic spread of FCoV from the intestine, rather than a virus with the potential to cause FIP.


‘One Health’ for the people of Hong Kong and the world


title: Herbal management of hepatocellular carcinoma through cutting the pathways of the common risk factors

text: Abstract Hepatocellular carcinoma (HCC) is considered the most frequent tumor that associated with high mortality rate. Several risk factors contribute to the pathogenesis of HCC, such as chronic persistent infection with hepatitis C virus or hepatitis B virus, chronic untreated inflammation of liver with different etiology, oxidative stress and fatty liver disease. Several treatment protocols are used in the treatment of HCC but they also associated with diverse side effects. Many natural products are helpful in the co-treatment and prevention of HCC. Several mechanisms are involved in the action of these herbal products and their bioactive compounds in the prevention and co-treatment of HCC. They can inhibit the liver cancer development and progression in several ways as protecting against liver carcinogens, enhancing effects of chemotherapeutic drugs, inhibiting tumor cell growth and metastasis, and suppression of oxidative stress and chronic inflammation. In this review, we will discuss the utility of diverse natural products in the prevention and co-treatment of HCC, through its capturing of the common risk factors known to lead to HCC and shed the light on their possible mechanisms of action. Our theory assumes that shutting down the risk factor to cancer development pathways is a critical strategy in cancer prevention and management. We recommend the use of these plants side by side to recent chemical medications and after stopping these chemicals, as a maintenance therapy to avoid HCC progression and decrease its global incidence.


title: DNA-AuNP networks on cell membranes as a protective barrier to inhibit viral attachment, entry and budding

text: Abstract Viral infections have caused numerous diseases and deaths worldwide. Due to the emergence of new viruses and frequent virus variation, conventional antiviral strategies that directly target viral or cellular proteins are limited because of the specificity, drug resistance and rapid clearance from the human body. Therefore, developing safe and potent antiviral agents with activity against viral infection at multiple points in the viral life cycle remains a major challenge. In this report, we propose a new modality to inhibit viral infection by fabricating DNA conjugated gold nanoparticle (DNA-AuNP) networks on cell membranes as a protective barrier. The DNA-AuNPs networks were found, via a plaque formation assay and viral titers, to have potent antiviral ability and protect host cells from human respiratory syncytial virus (RSV). Confocal immunofluorescence image analysis showed 80 ± 3.8% of viral attachment, 91.1 ± 0.9% of viral entry and 87.9 ± 2.8% of viral budding were inhibited by the DNA-AuNP networks, which were further confirmed by real-time fluorescence imaging of the RSV infection process. The antiviral activity of the networks may be attributed to steric effects, the disruption of membrane glycoproteins and limited fusion of cell membrane bilayers, all of which play important roles in viral infection. Therefore, our results suggest that the DNA-AuNP networks have not only prophylactic effects to inhibit virus attachment and entry, but also therapeutic effects to inhibit viral budding and cell-to-cell spread. More importantly, this proof-of-principle study provides a pathway for the development of a universal, broad-spectrum antiviral therapy.


title: Forecasting tourist arrivals by using the adaptive network-based fuzzy inference system

text: Abstract Since accurate forecasting of tourist arrivals is very important for planning for potential tourism demand and improving the tourism infrastructure, various tourist arrivals forecasting methods have been developed. The purpose of this study is to apply the adaptive network-based fuzzy inference system (ANFIS) model to forecast the tourist arrivals to Taiwan and demonstrate the forecasting performance of this model. Based on the mean absolute percentage errors and statistical results, we can see that the ANFIS model has better forecasting performance than the fuzzy time series model, grey forecasting model and Markov residual modified model. Thus, the ANFIS model is a promising alternative for forecasting the tourist arrivals. We also use the ANFIS model to forecast the monthly tourist arrivals to Taiwan from Japan, Hong Kong and Macao, and the United States.


title: Evaluation of safety, humoral immune response and faecal shedding in horses inoculated with a modified‐live bovine coronavirus vaccination

text: Equine coronavirus (ECoV) is considered an emerging enteric virus with reported morbidity rates ranging from 10 to 83% and fatality rates ranging from 7 to 27% in adult horses; a vaccine for ECoV is currently not available. This study investigated the safety, humoral response and viral shedding in horses inoculated with a commercially available modified‐live bovine coronavirus (BCoV) vaccine. Twelve healthy adult horses were vaccinated twice, 3 weeks apart, either orally, intranasally or intrarectally. Two healthy unvaccinated horses served as sentinel controls. Following each vaccine administration, horses were monitored daily for physical abnormalities whilst the onset and duration of BCoV shedding was determined by quantitative PCR (qPCR) in nasal secretions and faeces. Whole blood was collected every 3 weeks to determine BCoV‐specific antibody response. With the exception of transient and self‐limiting changes in faecal character observed in seven vaccinated and one control horse, no additional abnormal clinical findings were found in the study horses. Following the first and second vaccine administration, two and one horse, respectively, tested qPCR‐positive for BCoV in nasal secretions 1‐day post intranasal vaccination. No vaccinated horses tested qPCR‐positive for BCoV in faeces following each vaccine administration. One of the two horses that shed BCoV seroconverted to BCoV after the first vaccine administration and an additional two vaccinated horses (oral and intrarectal) seroconverted to BCoV after the second vaccine administration. In conclusion, the results show that the modified‐live BCoV is safe to administer to horses via various routes, causes minimal virus shedding and results in detectable antibodies to BCoV in 27% of the vaccinates.


title: Evaluation of variation in D-dimer levels among COVID-19 and bacterial pneumonia: a retrospective analysis

text: In the recent outbreak of novel coronavirus infection worldwide, the risk of thrombosis and bleeding should be concerned. We aimed to observe the dynamic changes of D-dimer levels during disease progression to evaluate their value for thrombosis. In this study, we report the clinical and laboratory results of 57 patients with confirmed COVID-19 pneumonia and 46 patients with confirmed community-acquired bacterial pneumonia (CAP). And their concentrations of D-dimer, infection-related biomarkers, and conventional coagulation were retrospectively analyzed. The Padua prediction score is used to identify patients at high risk for venous thromboembolism (VTE). The results found that, on admission, both in COVID-19 patients and CAP patients, D-dimer levels were significantly increased, and compared with CAP patients, D-dimer levels were higher in COVID-19 patients (P < 0.05). Besides, we found that in COVID-19 patients, D-dimer were related with markers of inflammation, especially with hsCRP (R = 0.426, P < 0.05). However, there was low correlation between VTE score and D-dimer levels (Spearman’s R = 0.264, P > 0.05) weakened the role of D-dimer in the prediction of thrombosis. After treatments, D-dimer levels decreased which was synchronous with hsCRP levels in patients with good clinical prognosis, but there were still some patients with anomalous increasing D-dimer levels after therapy. In conclusion, elevated baseline D-dimer levels are associated with inflammation but not with VTE score in COVID-19 patients, suggesting that it is unreasonable to judge whether anticoagulation is needed only according to D-dimer levels. However, the abnormal changes of D-dimer and inflammatory factors suggest that anticoagulant therapy might be needed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11239-020-02171-y) contains supplementary material, which is available to authorized users.


title: Elucidating the Role of Host Long Non-Coding RNA during Viral Infection: Challenges and Paths Forward

text: Research over the past decade has clearly shown that long non-coding RNAs (lncRNAs) are functional. Many lncRNAs can be related to immunity and the host response to viral infection, but their specific functions remain largely elusive. The vast majority of lncRNAs are annotated with extremely limited knowledge and tend to be expressed at low levels, making ad hoc experimentation difficult. Changes to lncRNA expression during infection can be systematically profiled using deep sequencing; however, this often produces an intractable number of candidate lncRNAs, leaving no clear path forward. For these reasons, it is especially important to prioritize lncRNAs into high-confidence “hits” by utilizing multiple methodologies. Large scale perturbation studies may be used to screen lncRNAs involved in phenotypes of interest, such as resistance to viral infection. Single cell transcriptome sequencing quantifies cell-type specific lncRNAs that are less abundant in a mixture. When coupled with iterative experimental validations, new computational strategies for efficiently integrating orthogonal high-throughput data will likely be the driver for elucidating the functional role of lncRNAs during viral infection. This review highlights new high-throughput technologies and discusses the potential for integrative computational analysis to streamline the identification of infection-related lncRNAs and unveil novel targets for antiviral therapeutics.


title: Maternal T-cell engraftment impedes with diagnosis of a SCID-ADA patient

text: Abstract We describe the case of a child affected by severe combined immunodeficiency (SCID) with adenosine deaminase (ADA) deficiency showing a maternal T-cell engraftment, a finding that has never been reported before. The presence of engrafted maternal T cells was misleading. Although ADA enzymatic levels were suggestive of ADA-SCID, the child did not present the classical signs of ADA deficiency; therefore, the initial diagnosis was of a conventional SCID. However, ADA toxic metabolites and molecular characterization confirmed this diagnosis. Polyethylene glycol-modified bovine (PEG) ADA therapy progressively decreased the number of maternal engrafted T cells. The child was grafted with full bone marrow from a matched unrelated donor, after a reduced conditioning regimen, and the result was the complete immunological reconstitution.


title: Plasmacytoid dendritic cells: development, regulation and function

text: Plasmacytoid dendritic cells (pDCs) are a unique sentinel cell type that can detect pathogen-derived nucleic acids and respond with rapid and massive production of type I interferon. This review summarizes our current understanding of pDC biology, including transcriptional regulation, heterogeneity, role in antiviral immune responses, and involvement in immune pathology, particularly in autoimmune diseases, immunodeficiency and cancer. We also highlight the remaining gaps in our knowledge and important questions for the field, such as the molecular basis of unique interferon-producing capacity of pDCs. A better understanding of cell type-specific positive and negative control of pDC function should pave the way for translational applications focused on this immune cell type.


title: What Should I Do?

text: The aim of the study was to examine the conflicting duties of a practicing surgeon who is at high risk for morbidity and mortality from Covid-19 infection. Should he opt out of the care of these patients or does his duty to care override other considerations? Older adults and those with serious medical conditions are at much greater risk for severe disease and death from Covid-19 infection. As a practicing frontline surgeon in a high risk group, the hospital offered the author, and other health care providers at high risk, the option to opt out of the care Covid-19 suspected or infected patients before an anticipated surge. What should the surgeon and other health care providers do? This is a question many are asking and having to answer. In this article, the author describes how difficult the situation of having any choice at all was and then how difficult it was to arrive at a decision. The duty to care and its limits, as well as obligations to society, family, co-workers, and to self, are examined. The author considers how he and others can contribute in other ways to patients and providers. The author arrives at a morally permissible and a rational decision to opt out. Health care workers at high risk can contribute in other ways to patients and providers. It still may not feel right.


Management of patients with Hidradenitis Suppurativa during the COVID‐19 pandemic


title: Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430

text: Filoviruses are emerging pathogens and causative agents of viral haemorrhagic fever. Case fatality rates of filovirus disease outbreaks are among the highest reported for any human pathogen, exceeding 90% (ref. 1). Licensed therapeutic or vaccine products are not available to treat filovirus diseases. Candidate therapeutics previously shown to be efficacious in non-human primate disease models are based on virus-specific designs and have limited broad-spectrum antiviral potential. Here we show that BCX4430, a novel synthetic adenosine analogue, inhibits infection of distinct filoviruses in human cells. Biochemical, reporter-based and primer-extension assays indicate that BCX4430 inhibits viral RNA polymerase function, acting as a non-obligate RNA chain terminator. Post-exposure intramuscular administration of BCX4430 protects against Ebola virus and Marburg virus disease in rodent models. Most importantly, BCX4430 completely protects cynomolgus macaques from Marburg virus infection when administered as late as 48 hours after infection. In addition, BCX4430 exhibits broad-spectrum antiviral activity against numerous viruses, including bunyaviruses, arenaviruses, paramyxoviruses, coronaviruses and flaviviruses. This is the first report, to our knowledge, of non-human primate protection from filovirus disease by a synthetic drug-like small molecule. We provide additional pharmacological characterizations supporting the potential development of BCX4430 as a countermeasure against human filovirus diseases and other viral diseases representing major public health threats. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature13027) contains supplementary material, which is available to authorized users.


title: Origin and evolution of pathogenic coronaviruses

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are two highly transmissible and pathogenic viruses that emerged in humans at the beginning of the 21st century. Both viruses likely originated in bats, and genetically diverse coronaviruses that are related to SARS-CoV and MERS-CoV were discovered in bats worldwide. In this Review, we summarize the current knowledge on the origin and evolution of these two pathogenic coronaviruses and discuss their receptor usage; we also highlight the diversity and potential of spillover of bat-borne coronaviruses, as evidenced by the recent spillover of swine acute diarrhoea syndrome coronavirus (SADS-CoV) to pigs.


title: Practical considerations for measuring the effective reproductive number, R(t)

text: Estimation of the effective reproductive number, R(t), is important for detecting changes in disease transmission over time. During the COVID-19 pandemic, policymakers and public health officials are using R(t) to assess the effectiveness of interventions and to inform policy. However, estimation of R(t) from available data presents several challenges, with critical implications for the interpretation of the course of the pandemic. The purpose of this document is to summarize these challenges, illustrate them with examples from synthetic data, and, where possible, make methodological recommendations. For near real-time estimation of R(t), we recommend the approach of Cori et al. (2013), which uses data from before time t and empirical estimates of the distribution of time between infections. Methods that require data from after time t, such as Wallinga and Teunis (2004), are conceptually and methodologically less suited for near real-time estimation, but may be appropriate for some retrospective analyses. We advise against using methods derived from Bettencourt and Ribeiro (2008), as the resulting R(t) estimates may be biased if the underlying structural assumptions are not met. A challenge common to all approaches is reconstruction of the time series of new infections from observations occurring long after the moment of transmission. Naive approaches for dealing with observation delays, such as subtracting delays sampled from a distribution, can introduce bias. We provide suggestions for how to mitigate this and other technical challenges and highlight open problems in R(t) estimation.


title: Use of Throat Swab or Saliva Specimens for Detection of Respiratory Viruses in Children

text: Background. Nasopharyngeal (NP) specimens are commonly used for the detection of respiratory viruses, but throat and saliva specimens are easier to obtain. The objective of this study was to compare the viral yield of direct fluorescent antigen detection of NP specimens and nucleic acid amplification tests (NAT) of direct fluorescent antigen-negative NP specimens with the viral yield of NAT of throat swab and saliva specimens. Methods. NP, throat swab, and saliva specimens were obtained from children and adolescents aged ⩽17 years. Direct fluorescent antigen testing of the NP specimen for respiratory syncytial virus, influenza A and B viruses, and parainfluenza virus was performed. If no virus was detected, NAT was performed for these 4 viruses, adenovirus, and human metapneumovirus. If a virus was detected by either method, NAT for the same virus was performed for the corresponding throat swab and saliva specimens. Results. A virus was detected in 105 of the 137 NP specimens. The same virus was detectable by NAT in 87 (83%) of 105 throat swab specimens and 77 (74%) of 104 saliva specimens. The likelihood of viral detection among throat swab and saliva swab specimens was higher when the NP specimen tested positive by direct fluorescent antigen testing, compared with NAT alone, and when the specimens were obtained within 3 days after symptom onset, compared with later in the illness. Conclusions. Throat swab and saliva specimens are inferior to NP specimens for the detection of respiratory viruses but might be acceptable for screening in a setting where it is impractical to obtain an NP specimen.


title: The role of tacit knowledge in communication and decision-making during emerging public health incidents

text: Strong communication systems for knowledge exchange are required to prevent, respond to and mitigate the effects of emerging public health incidents (EPHIs). The objective of this paper is to examine how “tacit knowledge” – implicit knowledge used to guide everyday practice – is employed in professional relationships and communication processes between public health and acute care settings. A qualitative study design was used to explore the experiences of key informants from public health and acute care settings in Ontario, Canada, to examine how specific dimensions of tacit knowledge are employed in communications about EPHIs. Twenty-six in-depth interviews were conducted from 2014 to 2015. The results describe the way in which participants employ discretion and knowledge of local context, and rely on relationships built on trust and credibility, to facilitate decision-making and communication during EPHIs. Given the uncertainty characterizing most EPHIs, communicators rely a great deal on their informal knowledge and networks which allow them to remain flexible and respond quickly to changing situations. The results reveal that communication about public health guidance during emergencies is a complex and active process that draws from past experiences of the individuals involved, and is shaped by the requirements of local circumstances. The broader implications of these findings for building resilient and responsive health systems are considered. In particular, for rethinking the authority of standardized forms of evidence in public health decision-making, and the importance of knowledge which is grounded in the uniqueness of specific local contexts.


title: Influenza pandemics: past, present and future challenges

text: Influenza epidemics occur regularly and prediction of their conversion to pandemics and their impact is difficult. Coordination of efforts on a global scale to control or reduce the impact is fraught with potential for under and overreaction. In light of the 1956 pandemic and more recently the SARS and H1N1 pandemics, the public health community took steps toward strengthening global surveillance and a coordinated response in keeping with the continuing memory of the tragedy seen in 1918. The scientific, professional, and technical resources of the 21(st) century are now advanced far beyond those then available. The H1N1 pandemic which commenced in 2009 progressed differently than predicted; its course was difficult to predict with any degree of certainty. Public responses to national immunization programs against the H1N1 virus have been weak. International movement of diseases can lead to creation of new endemic areas and continuous spread such as that which happened with West Nile Fever and Chikungunya. The lessons learned and the public and political responses to each actual or threatened pandemic will serve public health well in dealing with future challenges.


title: Urgent need of a management plan for survivors of COVID-19

text: Acute exacerbations of COPD (AECOPD) or “COPD crises” [1], are crucial events in the natural course of COPD. Although they can occur at any severity stage, their impact increases as patients develop more severe airflow limitation.


title: Challenges in mucosal vaccination of cattle

text: Abstract Recognition of the mucosal portal of entry for many infectious diseases and of the relevance of mucosal immune response to protection has encouraged the development of vaccines administered by mucosal routes, principally oral and intranasal, for stimulation of intestinal and nasopharyngeal lymphoid tissues respectively. The oral route is problematic in cattle and other ruminants where antigen degradation in the rumen is likely, prior to transit to the intestine. On the other hand, rumination can be exploited for exposure of nasopharyngeal tissues during cudding if vaccine antigen is expressed by a fibrous feed like alfalfa. An increase in anti-leukotoxin (Lkt) IgA was demonstrated in nasal secretions of calves following feeding of alfalfa expressing a truncated Lkt50 from Mannheimia haemolytica, and there is evidence suggesting that such vaccination may protect against experimentally induced pneumonia. Intranasal vaccination is an alternative approach for use in pre-ruminating calves. Intranasal administration of ISCOMs carrying soluble antigens of M. haemolytica, including native Lkt, induced Lkt specific IgA in nasal secretions after vaccination at 4 and 6 weeks of age. Subcutaneous (s.c.) administration of the same vaccine induced Lkt specific IgG in both serum and nasal secretions, whereas s.c. administration of a commercial M. haemolytica vaccine did not. Regardless of the vaccination strategy employed it is difficult to assess the immunogenicity of mucosally administered vaccines because production of secreted antibodies tends to be transient, and they do not persist on the mucosal surface in the absence of ongoing antigenic stimulation. An additional challenge is demonstration of vaccine efficacy in response to experimental infection. Protection of the mucosally vaccinated animal will most probably result from recall response, which may not amplify sufficiently to counter the effects of experimental pulmonary delivery of a large bolus of virulent bacteria, even though the response would suffice over the more prolonged and gradual infection that occurs in natural induction of pneumonia.


title: Erosive polyarthritis associated with Mycoplasma gateae in a cat

text: Erosive polyarthritis was diagnosed in an 11-month-old neutered male Egyptian Mau-cross cat with concurrent glucocorticoid-responsive dermatitis. Clinical signs, synovial fluid analysis, serological tests and radiographic appearance could not differentiate between immune-mediated and infective arthritis. Mycoplasma gateae was isolated by strictly anaerobic culture of the synovial fluid. Treatment with Enrofloxacin led to a rapid improvement of the cat's condition. Two months later the cat was euthanased because of severe glomerulonephritis and direct Coombs' test positive anaemia, possibly caused by mycoplasma infection. M gateae could not be isolated at post-mortem examination.


title: Acute phase protein changes in calves during an outbreak of respiratory disease caused by bovine respiratory syncytial virus

text: Abstract Bovine acute phase proteins (APPs), lipopolysaccharide binding protein (LBP), serum amyloid A (SAA), haptoglobin (Hp) and alpha1-acid glycoprotein (AGP) were evaluated as inflammatory markers during an outbreak of bovine respiratory disease (BRD) caused by bovine respiratory syncytial virus (BRSV). Calves (n =10) presented mild to moderate signs of respiratory disease. Secondary bacterial infections, Pasteurella multocida and Mycoplasma dispar as major species, were detected in tracheobronchial lavage samples. Concentrations of SAA and LBP increased at week 1 had the highest values at week 3 and decreased at week 4 of outbreak. Some calves had high Hp concentrations at week 3, but AGP concentrations did not rise during respiratory disease. Higher SAA, LBP and Hp concentrations at a later stage of BRD (week 3) were associated with the low BRSV-specific IgG1 production, suggesting that these calves had enhanced inflammatory response to the secondary bacterial infection. In conclusion, APPs (especially SAA and LBP) are sensitive markers of respiratory infection, and they may be useful to explore host response to the respiratory infections in clinical research.


title: Infectious diseases in children and adolescents in the Republic of Korea; Past & recent status

text: Compared to the past decades, in recent decades, environmental and hygienic conditions in the Republic of Korea have improved along with socioeconomic developments, and the incidence of most infectious diseases, especially vaccine-preventable diseases, has greatly decreased due to active immunization with the developed level of health care. However, the incidence of some diseases has been increasing, and new diseases have been emerging. To cope with such changes actively, the government put the "Law for Control and Prevention of Infectious Diseases" into effect; this law was entirely revised on December 30, 2010. In this report, I review the past and recent status of infectious diseases in the Republic of Korea, following the introduction of this law, on the basis of data in the "National Notifiable Disease Surveillance System", which had been accumulated between the years 1960 and 2010.


title: Trajectories for Post-traumatic Stress Disorder Symptoms Among Local Disaster Recovery Workers Following the Great East Japan Earthquake: Group-based Trajectory Modeling

text: BACKGROUND: As many local municipality and medical workers were involved in disaster recovery duties following the Great East Japan Earthquake (GEJE) on March 11, 2011, the aim of this work was to elucidate the distinct trajectories for post-traumatic stress disorder (PTSD) symptoms and associated factors among these personnel. They confronted a diverse range of stressors both as survivors and as relief workers; however, little is known about their longitudinal PTSD symptoms. METHODS: The participants were 745 local municipality and hospital medical workers [average age: 43.6 ± 9.5 years, range: 20 – 66 years; 306 (59%) women] involved in disaster recovery duties following the GEJE. PTSD symptoms were measured using the Japanese version of the PTSD Checklist Specific Version (PCL-S) at four time points: 14, 30, 43, and 54 months after the GEJE. Using group-based trajectory modeling, distinct trajectories were elucidated. RESULTS: We identified five distinct PTSD symptoms profiles: resistance (n = 467, 62.7%), subsyndromal (n = 181, 24.3%), recovery (n = 47, 6.3%), fluctuating (n = 26, 3.5%), and chronic (n = 24, 3.2%). The trajectories differed according to the post-disaster working conditions and personal disaster experiences. LIMITATIONS: Potential selection bias resulting from the limited number of participants who completed all waves. The survey was conducted in one region of the disaster area. CONCLUSIONS: The majority of participants remained stable, with a relatively small group classified as chronic and fluctuating. Our results highlight the importance of improved working conditions and sustained monitoring of workers responding to natural disasters.


title: The role of visceral adiposity in the severity of COVID-19: highlights from a unicenter cross-sectional pilot study in Germany

text: BACKGROUND AND AIMS. Overall obesity has recently been established as an independent risk factor for critical illness in patients with coronavirus disease 2019 (COVID-19). The role of fat distribution and especially that of visceral fat, which is often associated with metabolic syndrome, remains unclear. Therefore, this study aims at investigating the association between fat distribution and COVID-19 severity. METHODS: Thirty patients with COVID-19 and a mean age of 65.6 ± 13.1 years from a level-one medical center in Berlin, Germany, were included in the present cross-sectional analysis. COVID-19 was confirmed by polymerase chain reaction (PCR) from nasal and throat swabs. A severe clinical course of COVID-19 was defined by hospitalization in the intensive care unit (ICU) and/or invasive mechanical ventilation. Fat was measured at the level of the first lumbar vertebra on routinely acquired low-dose chest computed tomography (CT). RESULTS: An increase in visceral fat area (VFA) by ten square centimeters was associated with a 1.37-fold higher likelihood of ICU treatment and a 1.32-fold higher likelihood of mechanical ventilation (adjusted for age and sex). For upper abdominal circumference, each additional centimeter of circumference was associated with a 1.13-fold higher likelihood of ICU treatment and a 1.25-fold higher likelihood of mechanical ventilation. CONCLUSIONS: Our proof-of-concept study suggests that visceral adipose tissue and upper abdominal circumference specifically increase the likelihood of COVID-19 severity. CT-based quantification of visceral adipose tissue and upper abdominal circumference in routine chest CTs may therefore be a simple tool for risk assessment in COVID-19 patients.


Cholecystectomy during the COVID-19 pandemic: current evidence and an understanding of the ‘new’ critical view of safety: Correspondence


title: COVID-19: Initial experience of an international group of hand surgeons

text: Abstract The emergence of the COVID-19 pandemic has severely affected medical treatment protocols throughout the world. While the pandemic does not affect hand surgeons at first glance, they have a role to play. The purpose of this study was to describe the different measures that have been put in place in response to the COVID-19 pandemic by hand surgeons throughout the world. The survey comprised 47 surgeons working in 34 countries who responded to an online questionnaire. We found that the protocols varied in terms of visitors, health professionals in the operating room, patient waiting areas, wards and emergency rooms. Based on these preliminary findings, an international consensus on hand surgery practices for the current viral pandemic, and future ones, needs to be built rapidly.


title: 2-Cys peroxiredoxin function in intracellular signal transduction: therapeutic implications

text: H2O2 is a reactive oxygen species that has drawn much interest because of its role as a second messenger in receptor-mediated signaling. Mammalian 2-Cys peroxiredoxins have been shown to eliminate efficiently the H2O2 generated in response to receptor stimulation. 2-Cys peroxiredoxins are members of a novel peroxidase family that catalyze the H2O2 reduction reaction in the presence of thioredoxin, thioredoxin reductase and NADPH. Several lines of evidence suggest that 2-Cys peroxiredoxins have dual roles as regulators of the H2O2 signal and as defenders of oxidative stress. In particular, 2-Cys peroxiredoxin appears to provide selective, specific and localized control of receptor-mediated signal transduction. Thus, the therapeutic potential of 2-Cys peroxiredoxins is clear for diseases, such as cancer and cardiovascular diseases, that involve reactive oxygen species.


title: Risk factors for detection failures of chest radiography in diagnosing pneumonia

text: BACKGROUND: Little is known about clinical factors associated with undetectable pneumonic shadows on chest radiographs (CRs) for diagnosing pneumonia in the primary care setting. METHODS: A retrospective assessment of CRs was conducted to compare chest computed tomography (CT) images of patients admitted to Kesennuma City Motoyoshi Municipal Hospital who were diagnosed with pneumonia from April 2014 to June 2016. RESULTS: Eighty‐three patients were included, and their average age was 83.8 years. Sixty‐eight patients (81.9%) were officially certified as requiring long‐term care or support. Twenty‐nine of the 83 patients (34.9%) had either negative or normal findings on CRs, and positive findings consistent with pneumonia on CT. There were no significant differences in gender, age, cardiothoracic ratio on CR, or severity between the CR‐negative and CR‐positive groups. The proportion of negative CRs was significantly higher in patients with certified care level 5 under the long‐term care system in Japan and tube feeding. CONCLUSION: The failure rate of CRs for detecting pneumonic shadows was significantly higher in patients with certified care level 5 and tube feeding.


Un Servicio de Neurología de un hospital terciario en la pandemia COVID-19


title: Awareness regarding COVID-19 and problems being faced by young adults with type 1 diabetes mellitus amid nationwide lockdown in India: A qualitative interview study

text: AIMS: To assess the awareness about COVID-19 and the problems being faced by young adults with T1DM amid nationwide lockdown in India. METHODS: A cross-sectional telephone-based qualitative interview study was conducted in young adults (aged 18–30 years) with T1DM amid lockdown. Following verbal consent, participants were asked 8 open-ended questions, 5 on awareness about COVID-19 and 3 catering to problems being faced concerning diet, physical activity and treatment amid lockdown. On average, 3 interviews were conducted per day with each lasting for 15−20 min. Interviews were recorded, transcribed and analyzed by qualitative content analysis. RESULTS: Thirty-two participants were interviewed; after exclusion of two poorly recorded interviews, 30 were finally analyzed. Mean age of participants was 22.4 ± 4.0 years (M:F = 8:7). Only 30%, 40% and 53% of participants were aware of modes of transmission (respiratory droplets and fomites), cardinal symptoms (fever, cough and breathing difficulty) and means of prevention (staying indoors, social distancing and regular hand washing), respectively. Majority of participants were unaware of additional risks associated with COVID-19 in diabetes mellitus. Most participants could continue with their routine diet and prescribed treatment regime, however, 90% reported a reduction in physical activity and 72% experienced worsening of glycemic control amid lockdown. CONCLUSIONS: Young adults with T1DM lack adequate awareness about COVID-19. Increasing awareness and imparting diabetes self-management education via digital/print media is needed.


Advancing global health and strengthening the HIV response in the era of the Sustainable Development Goals: the International AIDS Society—Lancet Commission


title: Practice of habitual and volitional health behaviors to prevent severe acute respiratory syndrome among Chinese adolescents in Hong Kong

text: Abstract Purpose To explore factors relating to the practice of habitual and volitional health behaviors against the severe acute respiratory syndrome (SARS) among Chinese adolescents in Hong Kong. Methods A community telephone survey was conducted with 230 Chinese adolescents. Random-digit dialing of the local residential telephone directory was used to select respondents, who were asked to provide information on their practice of SARS preventive health behaviors and associated factors as specified by the Health Belief Model. These factors included perceived threat of SARS, perceived benefits and barriers in practicing SARS preventive health behaviors, cues to action, knowledge of SARS, and self-efficacy. Hierarchical regression analyses were conducted to determine salient correlates of habitual and volitional health behaviors against SARS. Results About 54.8% of respondents reported practicing all three recommended habitual health behaviors. Another 47.8% indicated consistent practice of volitional health behavior of facemask-wearing to prevent SARS. Results of hierarchical regression analyses showed that habitual health behaviors against SARS were related to perceived health threat and environmental cues. For facemask-wearing, salient correlates were environmental cues, rates of SARS habitual health behaviors, younger age, and perceived health threat. Conclusions The Health Belief Model is useful in understanding Chinese adolescents’ practice of health behaviors, especially volitional health behaviors.


title: Computational analysis of SARS-CoV-2/COVID-19 surveillance by wastewater-based epidemiology locally and globally: Feasibility, economy, opportunities and challenges

text: Abstract With the economic and practical limits of medical screening for SARS-CoV-2/COVID-19 coming sharply into focus worldwide, scientists are turning now to wastewater-based epidemiology (WBE) as a potential tool for assessing and managing the pandemic. We employed computational analysis and modeling to examine the feasibility, economy, opportunities and challenges of enumerating active coronavirus infections locally and globally using WBE. Depending on local conditions, detection in community wastewater of one symptomatic/asymptomatic infected case per 100 to 2,000,000 non-infected people is theoretically feasible, with some practical successes now being reported from around the world. Computer simulations for past, present and emerging epidemic hotspots (e.g., Wuhan, Milan, Madrid, New York City, Teheran, Seattle, Detroit and New Orleans) identified temperature, average in-sewer travel time and per-capita water use as key variables. WBE surveillance of populations is shown to be orders of magnitude cheaper and faster than clinical screening, yet cannot fully replace it. Cost savings worldwide for one-time national surveillance campaigns are estimated to be in the million to billion US dollar range (US$), depending on a nation's population size and number of testing rounds conducted. For resource poor regions and nations, WBE may represent the only viable means of effective surveillance. Important limitations of WBE rest with its inability to identify individuals and to pinpoint their specific locations. Not compensating for temperature effects renders WBE data vulnerable to severe under-/over-estimation of infected cases. Effective surveillance may be envisioned as a two-step process in which WBE serves to identify and enumerate infected cases, where after clinical testing then serves to identify infected individuals in WBE-revealed hotspots. Data provided here demonstrate this approach to save money, be broadly applicable worldwide, and potentially aid in precision management of the pandemic, thereby helping to accelerate the global economic recovery that billions of people rely upon for their livelihoods.


title: Prevalence of Bartonella henselae antibodies in serum of cats with and without clinical signs of central nervous system disease

text: Bartonella henselae is occasionally associated with neurological dysfunction in people and some experimentally infected cats. The purpose of this study was to determine whether B henselae seroprevalence or titer magnitude varies among cats with neurological disease, cats with non-neurological diseases, and healthy cats while controlling for age and flea exposure. There was no difference in B henselae seroprevalence rates between cats with seizures and cats with other neurological diseases. Cats with non-neurological disease and healthy cats were more likely than cats with neurological disease to be seropositive. While the median B henselae antibody titer was greater in cats with seizures than in cats with other neurological disease, the median B henselae antibody titer was also greater in healthy cats than cats with seizures. The results suggest that titer magnitude cannot be used alone to document clinical disease associated with B henselae infection and that presence of B henselae antibodies in serum of cats with neurological disease does not prove the clinical signs are related to B henselae.


title: cis acting RNA sequences control the gag-pol translation readthrough in murine leukemia virus

text: Abstract The pol gene of the Moloney murine leukemia virus (M-MuLV) is expressed as a Gag-Pol fusion protein through an in-frame suppression of the UAG termination codon located between the two genes. The role of nucleotide context in suppression was investigated, in a rabbit reticulocyte lysate translation system, using site-directed mutagenesis. The results indicate that the translational readthrough is mediated by at least 50 bases long RNA sequence located 3′ to the gag UAG termination codon. Within this sequence a short purine-rich sequence adjacent to the amber codon, highly conserved among different retroviruses, appears essential for M-MuLV suppression. Two alternative putative stem and loop like RNA structures can be drawn at the gag-pol junction, one abutting the gag UAG codon, and the second downstream to it. None of these structures appears to be important to the suppression process.


title: Preparation and Evaluation of Poly-Butylcyanoacrylate Nanoparticles for Oral Delivery of Thymopentin

text: Abstract Thymopentin (Tp5) was loaded in poly-butylcyanoacrylate (PBCA) nanoparticles (NP) in order to enhance the oral bioavailability of Tp5. PBCA-Tp5-NP was prepared by nanoprecipitation methods. Dialyzing membrane method was employed to examine the in vitro release of PBCA-Tp5-NP in PBS, and Tp5 samples in the release medium were detected by HPLC. The cell proliferation test (3H-thymidine) was conducted to verify the PBCA-Tp5-NP bioactivity in vitro. The pharmacodynamical studies were performed on preimmunoinhibited rats and in flow cytometer. The size and the entrapment efficiency of PBCA-Tp5-NP were 178±39 nm and 92.21±1.08%, respectively. In vitro release data show that less than 60% Tp5 was released from lyophilized PBCA-Tp5-NP while 80% Tp5 was released from the colloidal PBCA-Tp5-NPs in 48 h. The proliferation test showed that PBCA-Tp5-NP had the similar effect as Tp5. The in vivo data showed that oral PBCA-Tp5-NPs had similar function as what intravenous Tp5 did. The oral bioavailability of Tp5 could be enhanced by PBCA nanoparticles. PBCA-Tp5-NP had the property of sustained-release and the efficacy of Tp5 was not changed after formulation.


Notes from the Field: E-cigarette, or Vaping, Product Use–Associated Lung Injury Cases During the COVID-19 Response — California, 2020


title: Crystal Structure of Human Enterovirus 71 3C Protease

text: Abstract Human enterovirus 71 (EV71) is the major pathogen that causes hand, foot and mouth disease that particularly affects young children. Growing hand, foot and mouth disease outbreaks were observed worldwide in recent years and caused devastating losses both economically and politically. However, vaccines or effective drugs are unavailable to date. The genome of EV71 consists of a positive sense, single-stranded RNA of ∼7400 bp, encoding a large precursor polyprotein that requires proteolytic processing to generate mature viral proteins. The proteolytic processing mainly depends on EV71 3C protease (3Cpro) that possesses both proteolysis and RNA binding activities, which enable the protease to perform multiple tasks in viral replication and pathogen–host interactions. The central roles played by EV71 3Cpro make it an appealing target for antiviral drug development. We determined the first crystal structure of EV71 3Cpro and analyzed its enzymatic activity. The crystal structure shows that EV71 3Cpro has a typical chymotrypsin-like fold that is common in picornaviral 3Cpro. Strikingly, we found an important surface loop, also denoted as β-ribbon, which adopts a novel open conformation in EV71 3Cpro. We identified two important residues located at the base of the β-ribbon, Gly123 and His133, which form hinges that govern the intrinsic flexibility of the ribbon. Structure-guided mutagenesis studies revealed that the hinge residues are important to EV71 3Cpro proteolytic activities. In summary, our work provides the first structural insight into EV71 3Cpro, including a mobile β-ribbon, which is relevant to the proteolytic mechanism. Our data also provides a framework for structure-guided inhibitor design against EV71 3Cpro.