title: O(6)-alkylguanine-DNA Alkyltransferases in Microbes Living on the Edge: From Stability to Applicability

text: The genome of living cells is continuously exposed to endogenous and exogenous attacks, and this is particularly amplified at high temperatures. Alkylating agents cause DNA damage, leading to mutations and cell death; for this reason, they also play a central role in chemotherapy treatments. A class of enzymes known as AGTs (alkylguanine-DNA-alkyltransferases) protects the DNA from mutations caused by alkylating agents, in particular in the recognition and repair of alkylated guanines in O(6)-position. The peculiar irreversible self-alkylation reaction of these enzymes triggered numerous studies, especially on the human homologue, in order to identify effective inhibitors in the fight against cancer. In modern biotechnology, engineered variants of AGTs are developed to be used as protein tags for the attachment of chemical ligands. In the last decade, research on AGTs from (hyper)thermophilic sources proved useful as a model system to clarify numerous phenomena, also common for mesophilic enzymes. This review traces recent progress in this class of thermozymes, emphasizing their usefulness in basic research and their consequent advantages for in vivo and in vitro biotechnological applications.


title: Viruses and Bioterrorism ☆

text: Abstract The target for a terrorist attack with a viral agent can range from humans to animals and plants. However, the use of a viral agent may pose a challenge due to problems associated with acquisition, cultivation, and dissemination. Agricultural targets are of concern as they would require relatively little specialized expertise and technology and can have large economic consequences. Viral agents are prone to genetic variation and mutation, and can be manipulated or created in the laboratory. Unlike bacterial diseases, many of which are treatable with antimicrobials, there are fewer medical countermeasures to employ when dealing with viral infections.


title: Integrated wetlands for food production

text: Abstract The widespread use of compound pelleted feeds and chemical fertilizers in modern food production contribute to a vast amount of residual nutrients into the production system and adjacent ecosystem are major factors causing eutrophication. Furthermore, the extensive development and application of chemical compounds (such as chemical pesticides, disinfectants and hormones used in enhancing productivity) in food production process are hazardous to the ecosystems, as well as human health. These unsustainable food production patterns cannot sustain human living in the long run. Wetlands are perceived as self-decontamination ecosystems with high productivities. This review gives an overview about wetlands which are being integrated with food production processes, focusing on aquaculture.


title: A newly discovered human pneumovirus isolated from young children with respiratory tract disease

text: From 28 young children in the Netherlands, we isolated a paramyxovirus that was identified as a tentative new member of the Metapneumovirus genus based on virological data, sequence homology and gene constellation. Previously, avian pneumovirus was the sole member of this recently assigned genus, hence the provisional name for the newly discovered virus: human metapneumovirus. The clinical symptoms of the children from whom the virus was isolated were similar to those caused by human respiratory syncytial virus infection, ranging from upper respiratory tract disease to severe bronchiolitis and pneumonia. Serological studies showed that by the age of five years, virtually all children in the Netherlands have been exposed to human metapneumovirus and that the virus has been circulating in humans for at least 50 years.


title: Acute kidney injury is associated with the mortality of coronavirus disease 2019

text: We read with great interest the recent article "Analysis of 92 deceased patients with COVID-19" by Yang et al. published in the Journal of medical virology. The authors observed that 14 patients suffered renal injury after infection of SARS-CoV-2 in 92 deceased patients with coronavirus disease 2019 (COVID-19), although none of them had chronic renal insufficiency. This article is protected by copyright. All rights reserved.


title: Disease threats to the endangered Iberian lynx (Lynx pardinus)

text: Abstract The Iberian lynx, (Lynx pardinus), is the most endangered felid in the world. To determine whether sympatric carnivores are reservoirs of pathogens posing a disease risk for the lynx, evidence of exposure to 17 viral, bacterial and protozoan agents was investigated in 176 carnivores comprising 26 free-living lynx, 53 domestic cats, 28 dogs, 33 red foxes (Vulpes vulpes), 24 Egyptian mongooses (Herpestes ichneumon), 10 common genets (Genetta genetta) and 2 Eurasian badgers (Meles meles) in the areas inhabited by the last two populations of Iberian lynx, both in Andalusia (South-Western Spain). The results indicated that the lynx had low rates of contact with viral pathogens, with one seropositive finding each for feline leukemia virus, parvovirus and canine adenovirus-1, whereas contact with bacteria and protozoa appeared more frequent. Active infections with parvovirus, Ehrlichia spp., Mycobacterium bovis, Leptospira interrogans and Cytauxzoon spp. were confirmed. In contrast, 53% of the domestic cats were exposed to some infectious agent (prevalence range 4.5–11.4%). Antibodies to canine distemper virus and parvovirus were frequently found in dogs (32% and 42%, respectively) and foxes (30% and 12%). Past or present infections with parvovirus, Ehrlichia spp., Chlamydophila spp., M. bovis, Salmonella enterica, L. interrogans, Toxoplasma gondii, and Neospora caninum were also detected in these and other species surveyed. Questionnaires to owners revealed that 14% of the dogs but none of the cats had been vaccinated, and no cat had been neutered. Based on the apparent absence of acquired immunity of the lynx against infectious agents, the frequent detection of agents among sympatric carnivores, and the reported lack of immunocompetence of the Iberian lynx, a disease outbreak among the local abundant carnivores may pose a serious disease risk for lynx conservation.


title: Easier access to mechanical ventilation worldwide: an urgent need for low income countries, especially in face of the growing COVID-19 crisis

text: Combining easy-to-build noninvasive ventilator and open-source hardware description, may allow for adequate availability of ventilators to patients in low- and middle-income countries. This is urgently needed in the growing COVID-19 epidemic. https://bit.ly/3f8ZkUR


title: Hematologic, hepatic, and renal function changes in hospitalized patients with Middle East respiratory syndrome coronavirus

text: BACKGROUND: There are no longitudinal data on the changes in hematologic, hepatic, and renal function findings in patients with Middle East respiratory syndrome coronavirus (MERS‐CoV) infection. METHODS: This is a retrospective cohort study of 16 MERS‐CoV patients, to describe the hematological, hepatic, and renal findings of patients with MERS‐CoV. RESULTS: During the 21 days of observation, there was no significant change in the hepatic panel or creatinine tests. There was a significant increase in the mean ± SD of the white blood cell count from 8.3 ± 4.6 to 14.53 ± 7 (P value = 0.001) and an increase in mean ± SD of the absolute neutrophil count from 6.33 ± 4.2 to 12 ± 5.5 (P value = 0.015). Leukocytosis was observed in 31% (5/16) of the patients on day 1 and in 80% (4/5) on day 21. Transient leukopenia developed in 6% (1/16) of the patients on day 1 and in 13% (1/8) on day 8. None of the patients had neutropenia. Lymphopenia was a prominent feature with a rate of 44% (7/16) of the patients on day 1 and 60% (3/5) on day 21. Lymphocytosis was not a feature of MERS‐CoV infection. Thrombocytopenia developed in 31% (5/16) of the patients on day 1 and 40% (2/5) on day 21. Thrombocytosis was not a prominent feature and was observed in 6% (1/16) of the patients on day 1 and 17% (1/6) on day 9. CONCLUSIONS: Patients with MERS‐CoV infection showed variable hematologic parameters over time. Lymphocytosis and neutropenia were not features of MERS‐CoV infection.


title: Chapter 2 Virus Replication

text: Abstract The replication processes used by individual viruses is highly variable. However, all viruses must attach to a susceptible host cell, enter the cell, disassemble the virus particle (uncoating), replicate its own genetic material and express the associated proteins, assemble new virus particles, and escape from the infected cell (release). This chapter will outline the general processes involved in each of these steps.


title: Using ICD-10 codes to identify elective epilepsy monitoring unit admissions from administrative billing data: A validation study

text: Video-electroencephalogram (EEG) monitoring in the epilepsy monitoring unit (EMU) is essential for managing epilepsy and seizure mimics. Evaluation of care in the EMU would benefit from a validated code set capable of identifying EMU admissions from administrative databases comprised of large, diverse cohorts. We assessed the ability of code-based queries to parse EMU admissions from administrative billing records in a large academic medical center over a four-year period, 2016–2019. We applied prespecified queries for admissions coded as follows: 1) elective, 2) receiving video-EEG monitoring, and 3) including diagnoses typically required by major US healthcare payers for EMU admission. Sensitivity (Sn), specificity (Sp), and predictive value positive/negative (PVP, PVN) were determined. Two approaches were highly effective. Incorporating epilepsy, seizure, or seizure mimic codes as the admitting diagnosis (assigned at admission; Sn 96.3%, Sp 100.0%, PVP 98.3%, and PVN 100.0%) or the principal diagnosis (assigned after discharge; Sn 94.9%, Sp 100.0%, PVP 98.8%, and PVN 100.0%) identified elective adult EMU admissions with comparable reliability (p = 0.096). The addition of surgical procedure codes further separated EMU admissions for intracranial EEG monitoring. When applied to larger, more comprehensive datasets, these code-based queries should enhance our understanding of EMU utilization and access to care on a scalable basis.


title: Antibody Repertoire of Human Polyclonal Antibodies Against Ebola Virus Glycoprotein Generated After Deoxyribonucleic Acid and Protein Vaccination of Transchromosomal Bovines

text: Several Ebola vaccines and therapeutics are under clinical development. However, limited knowledge exists on the quality of antibody response generated by different Ebola vaccines. In this study, antibody repertoire induced by vaccination of transchromosomal bovine (TcB) with Ebola virus (EBOV) glycoprotein ([GP]; recombinant GP [rGP]) encoded by either deoxyribonucleic acid (DNA) or nanoparticle-based vaccine platform was analyzed using EBOV genome fragment phage display library and surface plasmon resonance (SPR)-based real-time kinetics assay to measure antibody affinity maturation to both native and partially denatured Ebola GP as well as GP containing the receptor binding domain but lacking the mucin-like domain. Immunoglobulin (IgG) obtained from rGP nanoparticle-vaccinated TcB demonstrated ~4-fold higher binding affinity compared with DNA-vaccinated TcB-induced IgG against the native rGP’s. The rGP nanoparticle vaccine generated a more robust and diverse antibody immune response to the native EBOV-GP compared with the DNA vaccine, which may explain the protective efficacy observed for these antibody preparations.


title: Clinical prevention and population health Curriculum framework for health professions

text: Abstract The Clinical Prevention and Population Health Curriculum Framework is the initial product of the Healthy People Curriculum Task Force convened by the Association of Teachers of Preventive Medicine and the Association of Academic Health Centers. The Task Force includes representatives of allopathic and osteopathic medicine, nursing and nurse practitioners, dentistry, pharmacy, and physician assistants. The Task Force aims to accomplish the Healthy People 2010 goal of increasing the prevention content of clinical health professional education. The Curriculum Framework provides a structure for organizing curriculum, monitoring curriculum, and communicating within and among professions. The Framework contains four components: evidence base for practice, clinical preventive services–health promotion, health systems and health policy, and community aspects of practice. The full Framework includes 19 domains. The title “Clinical Prevention and Population Health” has been carefully chosen to include both individual- and population-oriented prevention efforts. It is recommended that all participating clinical health professions use this title when referring to this area of curriculum. The Task Force recommends that each profession systematically determine whether appropriate items in the Curriculum Framework are included in its standardized examinations for licensure and certification and for program accreditation.


title: Population pharmacokinetics and pharmacodynamics of chloroquine in a Plasmodium vivax volunteer infection study

text: Chloroquine has been used for the treatment of malaria for more than 70 years; however, chloroquine pharmacokinetic (PK) and pharmacodynamic (PD) profile in Plasmodium vivax malaria is poorly understood. The objective of this study was to describe the PKPD relationship of chloroquine and its major metabolite, desethylchloroquine, in a P. vivax volunteer infection study. We analyzed data from 24 healthy subjects who were inoculated with blood‐stage P. vivax malaria and administered a standard treatment course of chloroquine. The PK of chloroquine and desethylchloroquine was described by a two‐compartment model with first‐order absorption and elimination. The relationship between plasma and whole blood concentrations of chloroquine and P. vivax parasitemia was characterized by a PKPD delayed response model, where the equilibration half‐lives were 32.7 h (95% CI: 27.4–40.5) for plasma data and 24.1 h (95% CI: 19.0–32.7) for whole blood data. The estimated parasite multiplication rate was 17 folds per 48 hours (95% CI: 14–20) and maximum parasite killing rate by chloroquine was 0.213 h(‐1) (95% CI: 0.196–0.230), translating to a parasite clearance half‐life of 4.5 h (95% CI: 4.1–5.0) and a parasite reduction ratio of 400 every 48 hours (95% CI: 320–500). This is the first study that characterized the PKPD relationship between chloroquine plasma and whole blood concentrations and P. vivax clearance using a semi‐mechanistic population PKPD modelling. This PKPD model can be used to optimize dosing scenarios and to identify optimal dosing regimens for chloroquine where resistance to chloroquine is increasing.


title: Development of Hepatocyte‐like Cell Derived from Human Induced Pluripotent Stem cell as a Host for Clinically Isolated Hepatitis C Virus

text: This unit describes protocols to develop hepatocyte‐like cells (HLCs) starting from mesenchymal stem cells (MSCs) as a natural host for hepatitis C virus (HCV). These include the preparation of MSCs from bone marrow, the reprogramming of MSCs into induced pluripotent stem cells (iPSCs), and the differentiation of iPSCs into HLCs. This unit also incorporates the characterization of the resulting cells at each stage. Another section entails the preparations of HCV. The sources of HCV are either the clinically isolated HCV (HCVser) and the conventional JFH‐1 genotype. The last section is the infection protocol coupled with the measurement of viral titer. © 2017 by John Wiley & Sons, Inc.


title: Mathematical assessment of the impact of non-pharmaceutical interventions on curtailing the 2019 novel Coronavirus

text: A pandemic of a novel Coronavirus emerged in December of 2019 (COVID-19), causing devastating public health impact across the world. In the absence of a safe and effective vaccine or antivirals, strategies for controlling and mitigating the burden of the pandemic are focused on non-pharmaceutical interventions, such as social-distancing, contact-tracing, quarantine, isolation, and the use of face-masks in public. We develop a new mathematical model for assessing the population-level impact of the aforementioned control and mitigation strategies. Rigorous analysis of the model shows that the disease-free equilibrium is locally-asymptotically stable if a certain epidemiological threshold, known as the reproduction number (denoted by [Formula: see text]), is less than unity. Simulations of the model, using data relevant to COVID-19 transmission dynamics in the US state of New York and the entire US, show that the pandemic burden will peak in mid and late April, respectively. The worst-case scenario projections for cumulative mortality (based on the baseline levels of anti-COVID non-pharmaceutical interventions considered in the study) decrease dramatically by 80% and 64%, respectively, if the strict social-distancing measures implemented are maintained until the end of May or June, 2020. The duration and timing of the relaxation or termination of the strict social-distancing measures are crucially-important in determining the future trajectory of the COVID-19 pandemic. This study shows that early termination of the strict social-distancing measures could trigger a devastating second wave with burden similar to those projected before the onset of the strict social-distancing measures were implemented. The use of efficacious face-masks (such as surgical masks, with estimated efficacy [Formula: see text] 70%) in public could lead to the elimination of the pandemic if at least 70% of the residents of New York state use such masks in public consistently (nationwide, a compliance of at least 80% will be required using such masks). The use of low efficacy masks, such as cloth masks (of estimated efficacy less than 30%), could also lead to significant reduction of COVID-19 burden (albeit, they are not able to lead to elimination). Combining low efficacy masks with improved levels of the other anti-COVID-19 intervention strategies can lead to the elimination of the pandemic. This study emphasizes the important role social-distancing plays in curtailing the burden of COVID-19. Increases in the adherence level of social-distancing protocols result in dramatic reduction of the burden of the pandemic, and the timely implementation of social-distancing measures in numerous states of the US may have averted a catastrophic outcome with respect to the burden of COVID-19. Using face-masks in public (including the low efficacy cloth masks) is very useful in minimizing community transmission and burden of COVID-19, provided their coverage level is high. The masks coverage needed to eliminate COVID-19 decreases if the masks-based intervention is combined with the strict social-distancing strategy.


title: Remdesivir for the Treatment of Covid-19 — Preliminary Report

text: BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%). CONCLUSIONS: Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.)


title: Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study

text: BACKGROUND: Over 40 000 patients with COVID-19 have been hospitalised in New York City (NY, USA) as of April 28, 2020. Data on the epidemiology, clinical course, and outcomes of critically ill patients with COVID-19 in this setting are needed. METHODS: This prospective observational cohort study took place at two NewYork-Presbyterian hospitals affiliated with Columbia University Irving Medical Center in northern Manhattan. We prospectively identified adult patients (aged ≥18 years) admitted to both hospitals from March 2 to April 1, 2020, who were diagnosed with laboratory-confirmed COVID-19 and were critically ill with acute hypoxaemic respiratory failure, and collected clinical, biomarker, and treatment data. The primary outcome was the rate of in-hospital death. Secondary outcomes included frequency and duration of invasive mechanical ventilation, frequency of vasopressor use and renal replacement therapy, and time to in-hospital clinical deterioration following admission. The relation between clinical risk factors, biomarkers, and in-hospital mortality was modelled using Cox proportional hazards regression. Follow-up time was right-censored on April 28, 2020 so that each patient had at least 28 days of observation. FINDINGS: Between March 2 and April 1, 2020, 1150 adults were admitted to both hospitals with laboratory-confirmed COVID-19, of which 257 (22%) were critically ill. The median age of patients was 62 years (IQR 51–72), 171 (67%) were men. 212 (82%) patients had at least one chronic illness, the most common of which were hypertension (162 [63%]) and diabetes (92 [36%]). 119 (46%) patients had obesity. As of April 28, 2020, 101 (39%) patients had died and 94 (37%) remained hospitalised. 203 (79%) patients received invasive mechanical ventilation for a median of 18 days (IQR 9–28), 170 (66%) of 257 patients received vasopressors and 79 (31%) received renal replacement therapy. The median time to in-hospital deterioration was 3 days (IQR 1–6). In the multivariable Cox model, older age (adjusted hazard ratio [aHR] 1·31 [1·09–1·57] per 10-year increase), chronic cardiac disease (aHR 1·76 [1·08–2·86]), chronic pulmonary disease (aHR 2·94 [1·48–5·84]), higher concentrations of interleukin-6 (aHR 1·11 [95%CI 1·02–1·20] per decile increase), and higher concentrations of D-dimer (aHR 1·10 [1·01–1·19] per decile increase) were independently associated with in-hospital mortality. INTERPRETATION: Critical illness among patients hospitalised with COVID-19 in New York City is common and associated with a high frequency of invasive mechanical ventilation, extrapulmonary organ dysfunction, and substantial in-hospital mortality. FUNDING: National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, National Institutes of Health, and the Columbia University Irving Institute for Clinical and Translational Research.


title: Group IID, IIE, IIF and III secreted phospholipase A2s

text: Abstract Among the 11 members of the secreted phospholipase A2 (sPLA2) family, group IID, IIE, IIF and III sPLA2s (sPLA2-IID, -IIE, -IIF and -III, respectively) are “new” isoforms in the history of sPLA2 research. Relative to the better characterized sPLA2s (sPLA2-IB, -IIA, -V and -X), the enzymatic properties, distributions, and functions of these “new” sPLA2s have remained obscure until recently. Our current studies using knockout and transgenic mice for a nearly full set of sPLA2s, in combination with comprehensive lipidomics, have revealed unique and distinct roles of these “new” sPLA2s in specific biological events. Thus, sPLA2-IID is involved in immune suppression, sPLA2-IIE in metabolic regulation and hair follicle homeostasis, sPLA2-IIF in epidermal hyperplasia, and sPLA2-III in male reproduction, anaphylaxis, colonic diseases, and possibly atherosclerosis. In this article, we overview current understanding of the properties and functions of these sPLA2s and their underlying lipid pathways in vivo.


title: Viruses in community‐acquired pneumonia in children aged less than 3 years old: High rate of viral coinfection

text: The occurrence of viral coinfections in childhood pneumonia has received little attention, probably because suitable detection methods have been lacking. Between November 2004 and October 2006, the presence of 14 respiratory viruses in children aged less than 3 years old with community‐acquired pneumonia were investigated using molecular or immunochromatographic techniques and/or viral culture. A total of 315 children (338 episodes) were included, and hospitalization was required in 178 episodes. At least one virus was detected in 66.9% of the episodes and simultaneous detection of two or more viruses was frequent (27% of the episodes with viral detection). The most frequently detected virus was respiratory syncytial virus (n = 67: 33 subgroup A, 33 subgroup B, 1 not typed), followed by human bocavirus (n = 48), rhinovirus (n = 46), human metapneumovirus (n = 39: 13 genotype A2, 8 B1, 5 B2, 1 A1, 12 not genotyped) and parainfluenza viruses (n = 38: 1 type 1, 3 type 2, 22 type 3, 11 type 4 and 1 not typed). The 14 viruses investigated were found in viral coinfections, which were more frequent in children aged less than 12 months. Except for adenovirus, the incidence of which was low, the percentage of viral coinfection ranged between 28.2% and 68.8%. Children with viral coinfection more frequently required hospital admission than those with single viral infection. It is concluded that viral coinfections are frequent in children aged less than 3 years old with community‐acquired pneumonia and can be a poor prognostic factor. J. Med. Virol. 80:1843–1849, 2008. © 2008 Wiley‐Liss, Inc.


title: Medically Attended Respiratory Syncytial Virus Infections in Adults Aged ≥50 Years: Clinical Characteristics and Outcomes

text: Background. Few studies have examined respiratory syncytial virus (RSV) infections in adults. We assessed the characteristics and outcomes of RSV relative to other viral infections. Methods. Patients ≥50 years old with acute respiratory illness were recruited for studies of influenza vaccine effectiveness from 2004 through 2010. Nasopharyngeal swabs from enrollees were analyzed for the presence of RSV and other respiratory viruses by multiplex reverse transcription polymerase chain reaction. Clinical data were obtained from interview and medical records. Results. A total of 2225 samples were tested across all seasons. The mean age was 64.2 (SD, 10.7) years; the mean interval from illness onset to sample collection was 4 (SD, 2.2) days. One or more viruses were detected in 1202 (54%) participants. In a multivariable logistic regression model, RSV was associated with ages 65–79 years (vs 50–64 years), symptoms of cough, nasal congestion and wheezing, and longer interval from illness onset to clinical encounter. RSV was not associated with the presence of chronic obstructive pulmonary disease or congestive heart failure in univariate analyses. Hospital admission within 30 days after illness onset was less common among patients with RSV compared to those with influenza (unadjusted odds ratio = 0.54 [95% confidence interval, .29–1.01], P = .06). Conclusions. RSV is a common cause of acute respiratory illness in adults aged ≥50 years; the risk of infection increases with age. Delays in healthcare seeking and reduced risk of hospital admission in patients with RSV suggest a milder course of illness relative to influenza.


title: Tracheobronchial Tumors: Radiologic–Pathologic Correlation of Tumors and Mimics

text: Tracheobronchial masses encompass a broad spectrum of entities, ranging from benign and malignant neoplasms to infectious and inflammatory processes. This article reviews the cross-sectional findings of tracheal tumors and tumor-like entities, correlates imaging findings with histologic pathology, and discusses pearls and pitfalls in accurately diagnosing and classifying tracheal tumors and mimics.


Different epidemiological characteristics of respiratory virus infections in children and adults


title: Knowledge, attitudes and practices of COVID-19 among income-poor households in the Philippines: A cross-sectional study

text: BACKGROUND: The presence of COVID-19 in low- and middle-income countries (LMICs) is raising important concerns about effective pandemic response and preparedness in the context of fragile health systems and the pervasiveness of misinformation. The objective of this study was to gain an understanding of how COVID-19 was perceived by households experiencing extreme poverty in the Philippines. METHODS: This study was conducted in partnership with International Care Ministries (ICM), a Philippine-based non-governmental organization (NGO) that runs a poverty-alleviation program called Transform targeted towards extreme low-income households. We integrated knowledge, attitudes, and practices (KAP) questions into ICM’s cross-sectional program monitoring and evaluation systems from February 20 through March 13, 2020. Frequencies and proportions were calculated to describe the respondents’ responses, and the Kruskal-Wallis test and binomial logistic regression were undertaken to determine the socio-demographic characteristics associated with COVID-19 KAPs. RESULTS: In total, 2224 respondents from 166 communities in rural, urban and coastal settings were surveyed. Although the survey was administered during the earlier stages of the pandemic, 94.0% of respondents had already heard of COVID-19. Traditional media sources such as television (85.5%) and radio (56.1%) were reported as the main sources of information about the virus. Coughing and sneezing were identified as a transmission route by 89.5% of respondents, while indirect hand contact was the least commonly identified transmission route, recognized by 72.6% of respondents. Handwashing was identified by 82.2% of respondents as a preventive measure against the virus, but social distancing and avoiding crowds were only identified by 32.4% and 40.6%, respectively. Handwashing was the most common preventive practice in response to COVID-19, adopted by 89.9% of respondents. A greater number of preventive measures were taken by those with more knowledge of potential transmission routes. CONCLUSIONS: There is a need for targeted health education as a response strategy to COVID-19 in low-income settings, and it is important that strategies are contextually relevant. Understanding KAPs among populations experiencing extreme poverty will be important as tailored guidance for public health response and communication strategies are developed for LMICs.


title: Hydrocortisone therapy in a cat with vasopressor‐refractory septic shock and suspected critical illness‐related corticosteroid insufficiency

text: A 27‐month‐old female cat was presented with septic peritonitis secondary to a ruptured pyometra and subsequent pyothorax. Vasopressor‐refractory septic shock led to a suspicion of critical illness‐related corticosteroid insufficiency, successfully treated with intravenous hydrocortisone. Previous megestrol acetate administration may have played a role in the development of adrenocortical dysfunction.


title: Translating RNA sequencing into clinical diagnostics: opportunities and challenges

text: With the emergence of RNA sequencing (RNA-seq) technologies, RNA-based biomolecules hold expanded promise for their diagnostic, prognostic and therapeutic applicability in various diseases, including cancers and infectious diseases. Detection of gene fusions and differential expression of known disease-causing transcripts by RNA-seq represent some of the most immediate opportunities. However, it is the diversity of RNA species detected through RNA-seq that holds new promise for the multi-faceted clinical applicability of RNA-based measures, including the potential of extracellular RNAs as non-invasive diagnostic indicators of disease. Ongoing efforts towards the establishment of benchmark standards, assay optimization for clinical conditions and demonstration of assay reproducibility are required to expand the clinical utility of RNA-seq. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrg.2016.10) contains supplementary material, which is available to authorized users.


title: Therapien gegen COVID-19 — ein Update: SARS-CoV-2-Pandemie

text: In mehr als 600 Interventionsstudien prüfen Ärzte derzeit Therapien gegen COVID-19. Bislang konnte noch kein Ansatz in kontrollierten Studien überzeugen, für einige Medikamente finden sich aber Hinweise auf einen Nutzen.


In Memoriam: Eugenio Inglese 1945–2020


title: Paraviral eruptions in the era of COVID-19. Do some skin manifestations point to a natural resistance to SARS-CoV-2?

text: Abstract Paraviral eruptions, such as the papular-purpuric gloves and socks syndrome or eruptive pseudoangiomatosis,share the following features that distinguish them from a classic viral eruption: they are highly recognizable; the eruption usually lasts a few weeks; many different viruses and sometimes other agents can trigger them; on microscopic examination, there is no specific cytopathogenic viral effect. SARS-CoV-2 can induce both a classic viral eruption and a paraviral eruption, the meaning of which in terms of pathophysiology and prognosis are very different. Some patients infected with COVID-19 have a papulovesicular eruption involving mainly the trunk. Those patients have active viremia, and some have developed pneumonia and died. Biopsy of the eruption revealed cytopathogenic viral effect, and thus a direct interaction of the virus with the skin; it is, therefore, a classic viral exanthema. Other, mainly young patients, developed chilblains of the fingers and toes 3 or 4weeks after minor signs of COVID-19 or after contact with a diseased person. They did not develop severe COVID-19. Biopsy revealed classic findings of chilblains without cytopathogenic viral effect. Most of those patients did not develop specific antibodies. Those chilblains can be considered as paraviral. Classic viral manifestations are the consequence of a direct interaction of the skin with the virus, while paraviral manifestations result from the activation of the immune system. In the case of paraviral chilblains, I hypothesize that it is the innate immune system that rejects SARS-CoV-2. Chilblains are also observed in rare monogenic disorders called type 1 interferonopathies, where anti-viral innate immunity is abnormally activated. This would explain why these individuals do not develop specific antibodies, because they are probably naturally resistant to SARS-CoV-2 infection via their innate immune system.


title: Changes in air quality related to the control of coronavirus in China: Implications for traffic and industrial emissions

text: Abstract Measures taken to control the disease (Covid-19) caused by the novel coronavirus dramatically reduced the number of vehicles on the road and diminished factory production. For this study, changes in the air quality index (AQI) and the concentrations of six air pollutants (PM2.5, PM10, CO, SO2, NO2, and O3) were evaluated during the Covid-19 control period in northern China. Overall, the air quality improved, most likely due to reduced emissions from the transportation and secondary industrial sectors. Specifically, the transportation sector was linked to the NO2 emission reductions, while lower emissions from secondary industries were the major cause for the reductions of PM2.5 and CO. The reduction in SO2 concentrations was only linked to the industrial sector. However, the reductions in emissions did not fully eliminate air pollution, and O3 actually increased, possibly because lower fine particle loadings led to less scavenging of HO2 and as a result greater O3 production. These results also highlight need to control emissions from the residential sector.


title: Tripeptidyl peptidase II serves as an alternative to impaired proteasome to maintain viral growth in the host cells

text: Abstract The ubiquitin–proteasome system is known to be utilized by coxsackievirus to facilitate its propagation within the host cells. The present study explores the role of tripeptidyl peptidase II (TPPII), a serine peptidase contributing to protein turnover by acting downstream of the proteasome, in regulating coxsackievirus infection. Inhibition of TPPII does not affect virus replication in cells with functional proteasome. However, when the proteasome is impaired, TPPII appears to serve as an alternative to maintain low levels of virus infection. Our results suggest an important function of TPPII in the maintenance of viral growth and may have implications for anti-viral therapy.


title: The mediating role of perceived social support between anxiety symptoms and life satisfaction in pregnant women: a cross-sectional study

text: BACKGROUND: Pregnancy can be stressful for women and families, so the life satisfaction of pregnant women may face significant challenges. This study aimed to identify the relationship among anxiety symptoms, perceived social support and life satisfaction, and to further explore whether perceived social support can play a mediating role. METHODS: This cross-sectional study was conducted from June to September in Shenyang City, China in 2019. 290 effective questionnaires were collected. The Satisfaction with Life Scale (SWLS), the Zung’s Self-Rating Anxiety Scale (SAS), the Multi-Dimensional Scale of Perceived Social Support (MSPSS) as well as demographic variables were included in each questionnaire. Hierarchical multiple regression was conducted to explore the mediating role of perceived social support in the relationship between anxiety symptoms and life satisfaction. Then the mediation model was examined by the PROCESS macro for SPSS. RESULTS: After adjusting control variables, anxiety symptoms were negatively associated with life satisfaction and explained 14.7% of the variance. Higher level of perceived social support was related to higher level of life satisfaction, explaining 21.0% of the variance. Perceived social support partly mediated the relationship between anxiety symptoms and life satisfaction for pregnant women. CONCLUSIONS: Perceived social support played a mediating role between anxiety symptoms and life satisfaction among pregnant women. Strategies and measures to improve perceived social support may be expected to buffer the impact of anxiety symptoms on pregnant women’s life satisfaction.


title: COVID-19 and the case for global development

text: COVID-19 accentuates the case for a global, rather than an international, development paradigm. The novel disease is a prime example of a development challenge for all countries, through the failure of public health as a global public good. The COVID-19 pandemic has highlighted the falsity of any assumption that the global North has all the expertise and solutions to tackle global challenges, and has further highlighted the need for multi-directional learning and transformation in all countries towards a more sustainable and equitable world. We illustrate our argument for a global development paradigm by examining the implications of the COVID-19 pandemic across four themes: global value chains, digitalisation, debt, and climate change. We conclude that development studies must adapt to a very different context from when the field emerged in the mid-20(th) century.


title: Application of next-generation sequencing technologies in virology

text: The progress of science is punctuated by the advent of revolutionary technologies that provide new ways and scales to formulate scientific questions and advance knowledge. Following on from electron microscopy, cell culture and PCR, next-generation sequencing is one of these methodologies that is now changing the way that we understand viruses, particularly in the areas of genome sequencing, evolution, ecology, discovery and transcriptomics. Possibilities for these methodologies are only limited by our scientific imagination and, to some extent, by their cost, which has restricted their use to relatively small numbers of samples. Challenges remain, including the storage and analysis of the large amounts of data generated. As the chemistries employed mature, costs will decrease. In addition, improved methods for analysis will become available, opening yet further applications in virology including routine diagnostic work on individuals, and new understanding of the interaction between viral and host transcriptomes. An exciting era of viral exploration has begun, and will set us new challenges to understand the role of newly discovered viral diversity in both disease and health.


The Millennium Development Goals: a cross-sectoral analysis and principles for goal setting after 2015: Lancet and London International Development Centre Commission


title: Arbidol combined with LPV/r versus LPV/r alone against Corona Virus Disease 2019: A retrospective cohort study

text: Summary Background Corona Virus Disease 2019 (COVID-19) due to the 2019 novel coronavirus (SARS-CoV-2) emerged in Wuhan city and rapidly spread throughout China. We aimed to compare arbidol and lopinavir/ritonavir(LPV/r) treatment for patients with COVID-19 with LPV/r only. Methods In this retrospective cohort study, we included adults (age≥18years) with laboratory-confirmed COVID-19 without Invasive ventilation, diagnosed between Jan 17, 2020, and Feb 13, 2020. Patients, diagnosed after Jan 17, 2020, were given oral arbidol and LPV/r in the combination group and oral LPV/r only in the monotherapy group for 5–21 days. The primary endpoint was a negative conversion rate of coronavirus from the date of COVID-19 diagnosis(day7, day14), and assessed whether the pneumonia was progressing or improving by chest CT (day7). Results We analyzed 16 patients who received oral arbidol and LPV/r in the combination group and 17 who oral LPV/r only in the monotherapy group, and both initiated after diagnosis. Baseline clinical, laboratory, and chest CT characteristics were similar between groups. The SARS-CoV-2 could not be detected for 12(75%) of 16 patients’ nasopharyngeal specimens in the combination group after seven days, compared with 6 (35%) of 17 in the monotherapy group (p < 0·05). After 14 days, 15 (94%) of 16 and 9 (52·9%) of 17, respectively, SARS-CoV-2 could not be detected (p < 0·05). The chest CT scans were improving for 11(69%) of 16 patients in the combination group after seven days, compared with 5(29%) of 17 in the monotherapy group (p < 0·05). Conclusion In patients with COVID-19, the apparent favorable clinical response with arbidol and LPV/r supports further LPV/r only.


title: Heavy metals in submicronic particulate matter (PM(1)) from a Chinese metropolitan city predicted by machine learning models

text: The aim of this study was to establish a method for predicting heavy metal concentrations in PM(1) (aerosol particles with an aerodynamic diameter ≤ 1.0 μm) based on back propagation artificial neural network (BP-ANN) and support vector machine (SVM) methods. The annual average PM(1) concentration was 26.31 μg/m(3) (range: 7.00–73.40 μg/m(3)). The concentrations of most metals were higher in winter and lower in autumn and summer. Mn and Ni had the highest noncarcinogenic risk, and Cr the highest carcinogenic risk. The hazard index was below safe limit, and the integrated carcinogenic risk was less than precautionary value. There were no obvious differences in the simulation performances of BP-ANN and SVM models. However, in both models many elements had better simulation effects when input variables were atmospheric pollutants (SO(2), NO(2), CO, O(3) and PM(2.5)) rather than PM(1) and meteorological factors (temperature, relative humidity, atmospheric pressure and wind speed). Models performed better for Pb, Tl and Zn, as evidenced by training R and test R values consistently >0.85, whereas their performances for Ti and V were relatively poor. Predicted results by the fully trained models showed atmospheric heavy metal pollution was heavier in December and January and lighter in August and July of 2019. For the period covering the COVID-19 outbreak in China, from January to March 2020, most of the predicted element concentrations were lower than in 2018 and 2019, and the concentrations of nearly all metals were lowest during the nationwide implementation of countermeasures taken against the pandemic.


title: Practice considerations for proton beam radiotherapy of uveal melanoma during the COVID-19 pandemic: PTCOG Ocular experience

text: Abstract Uveal melanoma (UM) is a rare but life-threatening cancer of the eye. In light of the COVID-19 pandemic, hospitals and proton eye therapy facilities must analyze several factors to ensure appropriate treatment protocols for patients and provider teams. Practice considerations to limit COVID-19 transmission in the proton ocular treatment setting for UM are necessary. The Particle Therapy Co-Operative Group (PTCOG) is the largest international community of particle/proton therapy providers. Participating experts are/were affiliated with the member institutions of the PTCOG Ocular subcommittee with long-standing high-volume proton ocular programs. The practices reviewed in this document must be taken in conjunction with local hospital procedures, multidisciplinary recommendations, and regional/national guidelines, as each community may have its unique needs, supplies, and protocols. Importantly, as the pandemic evolves, so will the strategies and recommendations. Given the unique circumstances for UM patients, along with indications of potential ophthalmologic transmission as a result of healthcare providers working in close proximity to patients and intrinsic infectious risk from eyelashes, tears and hair, practice strategies may be adapted to reduce the risk of viral transmission. Certainly, providers and health care systems will continue to examine and provide as safe and effective care as possible for patients in the current environment.


title: Sequence-Specific Fidelity Alterations Associated with West Nile Virus Attenuation in Mosquitoes

text: High rates of error-prone replication result in the rapid accumulation of genetic diversity of RNA viruses. Recent studies suggest that mutation rates are selected for optimal viral fitness and that modest variations in replicase fidelity may be associated with viral attenuation. Arthropod-borne viruses (arboviruses) are unique in their requirement for host cycling and may necessitate substantial genetic and phenotypic plasticity. In order to more thoroughly investigate the correlates, mechanisms and consequences of arbovirus fidelity, we selected fidelity variants of West Nile virus (WNV; Flaviviridae, Flavivirus) utilizing selection in the presence of a mutagen. We identified two mutations in the WNV RNA-dependent RNA polymerase associated with increased fidelity, V793I and G806R, and a single mutation in the WNV methyltransferase, T248I, associated with decreased fidelity. Both deep-sequencing and in vitro biochemical assays confirmed strain-specific differences in both fidelity and mutational bias. WNV fidelity variants demonstrated host-specific alterations to replicative fitness in vitro, with modest attenuation in mosquito but not vertebrate cell culture. Experimental infections of colonized and field populations of Cx. quinquefaciatus demonstrated that WNV fidelity alterations are associated with a significantly impaired capacity to establish viable infections in mosquitoes. Taken together, these studies (i) demonstrate the importance of allosteric interactions in regulating mutation rates, (ii) establish that mutational spectra can be both sequence and strain-dependent, and (iii) display the profound phenotypic consequences associated with altered replication complex function of flaviviruses.


title: Coronavirus infection prevention by wearing masks

text: The coronavirus disease 2019 (COVID-19) [2019-nCoV; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] was first detected in Wuhan, China at the end of 2019. In current status, spread of CO-VID-19 in person-to-person could be caused mainly by respiratory droplets, which leads to the spread of the influenza virus in both community and clinicians. Thus, in order to reduce the risk of that, the urgent management strategies against COVID-19 are to block transmission, isolation, protection, and using drug or vaccine updated on an ongoing basis. unfortunately, no drugs or vaccines still has yet been allowed to treat patients with COVID-19, so the rapid detection of effective intercessions against COVID-19 is seemed a major challenge on the all world. Herein, this article attempts summarizing to introduce the characterization of COVID-19, the influence of droplets travel in person-to-person transmission and the effect of wearing masks in the infection prevention of influenza virus, as well as understanding its advantage and role in the coronavirus infection prevention.


title: Comparison and Analysis of Biological Agent Category Lists Based On Biosafety and Biodefense

text: Biological agents pose a serious threat to human health, economic development, social stability and even national security. The classification of biological agents is a basic requirement for both biosafety and biodefense. We compared and analyzed the Biological Agent Laboratory Biosafety Category list and the defining criteria according to the World Health Organization (WHO), the National Institutes of Health (NIH), the European Union (EU) and China. We also compared and analyzed the Biological Agent Biodefense Category list and the defining criteria according to the Centers for Disease Control and Prevention (CDC) of the United States, the EU and Russia. The results show some inconsistencies among or between the two types of category lists and criteria. We suggest that the classification of biological agents based on laboratory biosafety should reduce the number of inconsistencies and contradictions. Developing countries should also produce lists of biological agents to direct their development of biodefense capabilities.To develop a suitable biological agent list should also strengthen international collaboration and cooperation.


title: Nitrogen utilization, preweaning nutrient digestibility, and growth effects of Holstein dairy calves fed 2 amounts of a moderately high protein or conventional milk replacer

text: Abstract Studies have shown that calves fed milk replacers (MR) with crude protein (CP) concentrations greater than 20%, as typically found in conventional MR, have higher dry matter intakes (DMI) and greater average daily gains (ADG) but consume less starter, which can lead to stress during weaning and reduced rumen development. The greater amount of CP being fed to preweaned calves may alter their nitrogen (N) balance, and excess N may be excreted in the urine. The objective of this study was to determine N utilization in preweaned calves fed diets varying in the amount of CP and MR fed. This study used 24 newborn dairy heifer calves blocked by birth and randomly assigned to 1 of 3 treatments: (1) 446g dry matter (DM) of a conventional MR (CON; 20% CP, 20% fat), (2) 669g DM of a moderately high protein MR (moderate; MOD; 26% CP, 18% fat), or (3) 892g DM of a moderately high protein MR (aggressive; AGG; 26% CP, 18% fat). All calves had ad libitum access to starter and water. Both MR and starter were medicated with decoquinate. During weaning (d 43–49), the morning MR feeding ceased. On d 50, all MR feedings ended; however, starter and water intakes were continuously recorded until d 56. At 5wk of age, urine was collected using urinary catheters for 3d and chromium oxide was administered by bolus at 2g/d for 7d to estimate N efficiency. Calves fed MOD and AGG had similar starter intakes, feed efficiencies, and ADG, with the combined treatments having reduced starter intakes (258 vs. 537g/d), greater ADG (674 vs. 422g/d), and improved feed efficiency (0.57 vs. 0.45 gain:feed) compared with CON calves preweaning. However, DMI and water intake were similar across all treatments. Results from the N utilization phase showed that MOD and AGG treatments had similar but lower N efficiency compared with CON calves (45.5 vs. 52.7%). This could be due to MOD- and AGG-fed calves having greater urine volume and thereby, greater combined urine N output compared with CON calves (17.6 vs. 12.1 g/d). In summary, feeding >0.66kg (DM) from a 26% CP MR increased ADG and improved feed efficiency during the preweaning period but reduced starter intake and lowered N efficiency.


title: Unmet needs of symptom management and associated factors among the HIV-positive population in Shanghai, China: A cross-sectional study

text: BACKGROUND: People living with HIV/AIDS (PLWHA) are a vulnerable group who experience multiple physiological and psychological symptoms. A better understanding of unmet symptom management needs will allow researchers to design interventions that are more reflective of deficits in care and more effective at improving patient care. Few studies have focused on unmet needs for symptom management in PLWHA particularly in China. Factors influencing Chinese PLWHA symptom management needs are rarely discussed. AIM: The purpose of this study was to investigate the unmet needs for symptom management of PLWHA and how their symptom burden, HIV perceived stigma, and self-management capacity contributes to HIV-related self-management practices in Shanghai, China. DESIGN: Study participants were recruited from the outpatient and inpatient HIV/AIDS wards in an infectious hospital in Shanghai, China. Self-administered questionnaires were implemented and medical charts were reviewed. RESULTS: A total of 367 participants was recruited from April to September 2017. The results show that 53.1% (195 of 367) of participants presented at least one unmet symptom management need and that symptom burden, as well as perceived stigma, reduced self-management capacity, and no employment significantly affected unmet symptom management needs. CONCLUSION: The findings indicate that there is room for improvement in symptom management for Chinese PLWHA. Culturally appropriate interventions focusing on improving symptom burden, decreasing HIV perceived stigma, and enhancing self-management capacity can enhance symptom management in this population.


title: Structure and Function of Viral Deubiquitinating Enzymes

text: Abstract Post-translational modification of cellular proteins by ubiquitin regulates numerous cellular processes, including innate and adaptive immune responses. Ubiquitin-mediated control over these processes can be reversed by cellular deubiquitinating enzymes (DUBs), which remove ubiquitin from cellular targets and depolymerize polyubiquitin chains. The importance of protein ubiquitination to host immunity has been underscored by the discovery of viruses that encode proteases with deubiquitinating activity, many of which have been demonstrated to actively corrupt cellular ubiquitin-dependent processes to suppress innate antiviral responses and promote viral replication. DUBs have now been identified in diverse viral lineages, and their characterization is providing valuable insights into virus biology and the role of the ubiquitin system in host antiviral mechanisms. Here, we provide an overview of the structural biology of these fascinating viral enzymes and their role innate immune evasion and viral replication.


title: Viral Pathogens Including Human Metapneumovirus Are the Primary Cause of Febrile Respiratory Illness in HIV-Infected Adults Receiving Antiretroviral Therapy

text: To determine the spectrum of pathogens causing acute febrile respiratory illness in human immunodeficiency virus (HIV)-infected adus, we re-analyzed data from a prospective surveillance study involving 50 outpatients (90% of whom received highly active antiretroviral therapy). Nasopharyngeal samples were tested for 23 respiratory viruses by multiplex reverse-transcriptase polymerase chain reaction (PCR) and for atypical bacteria by PCR. Sputum cultures and serological testing were performed. Viruses accounted for 64% of infections. After influenza (22 cases), humanmetapneumovirus infection (6 cases) was most common and was associated with bronchospasm. Bacterial infections occurred in 6 patients (3 of whom had concurrent viral infection). Over 80% of patients received antibiotics. Rapid testing to identify specific viral pathogens could aid in patient management and reduce unnecessary antibiotic exposure.


title: Pandemics, leadership, and social ethics

text: This Viewpoint argues that the absence of worldwide social ethics is at the root of our present social, political, and economic crises. More to the point, the current COVID-19 pandemic is, in part, a consequence of insufficient scientific research, inappropriate education systems, and globally fragile health structures and human services.


title: gH625: A milestone in understanding the many roles of membranotropic peptides

text: Abstract Here, we review the current knowledge about viral derived membranotropic peptides, and we discuss how they may be used for many therapeutic applications. While they have been initially discovered in viral fusion proteins and have been involved in the mechanism of viral entry, it is now clear that their features and their mode of interaction with membrane bilayers can be exploited to design viral inhibitors as well as to favor delivery of cargos across the cell membrane and across the blood–brain barrier. The peptide gH625 has been extensively used for all these purposes and provides a significant contribution to the field. We describe the roles of this sequence in order to close the gap between the many functions that are now emerging for membranotropic peptides.


title: The duty to care in an influenza pandemic: A qualitative study of Canadian public perspectives

text: Abstract Ever since the emergence of SARS, when we were reminded that the nature of health care practitioners' duty to care is greatly contested, it has remained a polarizing issue. Discussions on the nature and limits of health care practitioners' duty to care during disasters and public health emergencies abounds the literature, ripe with arguments seeking to ground its foundations. However, to date there has been little public engagement on this issue. This study involved three Townhall meetings held between February 2008 and May 2010 in three urban settings in Canada in order to probe lay citizens' views about ethical issues related to pandemic influenza, including issues surrounding the duty to care. Participants included Canadian residents aged 18 and over who were fluent in English. Data were collected through day-long facilitated group discussions using case scenarios and focus group guides. Participant's views were organized according to several themes, including the following main themes (and respective sub-themes): 1. Legitimate limits; a) competing obligations; and b) appeal to personal choice; and 2. Legitimate expectations; a) reciprocity; and b) enforcement and planning. Our findings show that participants moved away from categorical notions of the duty to care towards more equivocal and often normative views throughout deliberations. Our analysis contributes a better understanding of the constitutive nature of the duty to care, defined in part by taking account of public views. This broadened understanding can further inform the articulation of acceptable norms of duty to care and policy development efforts. What is more, it illustrates the urgent need for policy-makers and regulators to get clarity on obligations, responsibilities, and accountability in the execution of HCPs' duty to care during times of universal vulnerability.


title: Mixed infections in vitro with different Chlamydiaceae strains and a cell culture adapted porcine epidemic diarrhea virus

text: Abstract Assuming a synergistic or additive effect of Chlamydiaceae in coexistence with other enteropathogenic agents, the viral/bacterial interaction between a cell culture adapted porcine epidemic diarrhea virus (ca-PEDV) and different Chlamydiaceae strains was studied in vitro. Vero cells were dually infected with ca-PEDV and one of the three chlamydial strains Chlamydia trachomatis S45, Chlamydophila abortus S26/3 or Chlamydophila pecorum 1710S. Three experimental protocols were designed varying the inoculation sequence. Cell layers were first inoculated with Chlamydiaceae and 20h later with ca-PEDV in protocol one. In protocol two, both agents were administered concurrently, whereas in protocol three, ca-PEDV was applied 20h in advance of the Chlamydiaceae. Immunofluorescence techniques, immunohistochemical (IH) staining and electron microscopy were subsequently employed to investigate the cell layers. Using indirect immunofluorescence (IF) labeling, all mixed infections revealed dually infected cells, however, only incidentally and in low numbers. Characteristically, ca-PEDV syncytia with one or more chlamydial inclusions were detected but dually infected single cells were absent. Some syncytial cells contained enlarged C. abortus or C. pecorum inclusions with abnormally large developmental forms. In comparison with simultaneously conducted monoinfections, larger chlamydial inclusions were observed in dually infected cell layers. Experiments with C. trachomatis showed significantly increased numbers of chlamydial inclusions in dually infected cell layers compared to monoinfected ones. These findings indicate an influence of ca-PEDV on the chlamydial developmental cycle and in the case of C. trachomatis, a positive effect on chlamydial colonization in mixed infections.


Coronavirus Immunity: From T Cells to B Cells


title: Web GIS in practice III: creating a simple interactive map of England's Strategic Health Authorities using Google Maps API, Google Earth KML, and MSN Virtual Earth Map Control

text: This eye-opener article aims at introducing the health GIS community to the emerging online consumer geoinformatics services from Google and Microsoft (MSN), and their potential utility in creating custom online interactive health maps. Using the programmable interfaces provided by Google and MSN, we created three interactive demonstrator maps of England's Strategic Health Authorities. These can be browsed online at – Google Maps API (Application Programming Interface) version, – Google Earth KML (Keyhole Markup Language) version, and – MSN Virtual Earth Map Control version. Google and MSN's worldwide distribution of "free" geospatial tools, imagery, and maps is to be commended as a significant step towards the ultimate "wikification" of maps and GIS. A discussion is provided of these emerging online mapping trends, their expected future implications and development directions, and associated individual privacy, national security and copyrights issues. Although ESRI have announced their planned response to Google (and MSN), it remains to be seen how their envisaged plans will materialize and compare to the offerings from Google and MSN, and also how Google and MSN mapping tools will further evolve in the near future.


title: Eukaryotic expression: developments for structural proteomics

text: The production of sufficient quantities of protein is an essential prelude to a structure determination, but for many viral and human proteins this cannot be achieved using prokaryotic expression systems. Groups in the Structural Proteomics In Europe (SPINE) consortium have developed and implemented high‐throughput (HTP) methodologies for cloning, expression screening and protein production in eukaryotic systems. Studies focused on three systems: yeast (Pichia pastoris and Saccharomyces cerevisiae), baculovirus‐infected insect cells and transient expression in mammalian cells. Suitable vectors for HTP cloning are described and results from their use in expression screening and protein‐production pipelines are reported. Strategies for co‐expression, selenomethionine labelling (in all three eukaryotic systems) and control of glycosylation (for secreted proteins in mammalian cells) are assessed.


title: Protective and Therapeutic Effects of Licorice in Rats With Acute Tubular Necrosis

text: Objectives Various protective and therapeutic effects such as antioxidant, anti-inflammatory, anticancer, antihistaminic, and antibacterial effects have been depicted for licorice. However, its biological effects in the kidney are still not clear. Therefore, we aimed to investigate the efficiency of licorice in rats with gentamicin (GM)-induced acute tubular necrosis. Design and Methods Rats were randomized into the control group (only saline for 12 days), licorice group (licorice for 12 days), GM group (GM for 12 days), GM + licorice group, and licorice-treated GM group (licorice for 12 days after taking GM for 12 days). Blood urea, creatinine, and uric acid levels were measured and histopathological analyses of the kidneys were performed. The oxidative side of oxidant-antioxidant balance was evaluated by detecting lipid peroxidation (LPO) and total peroxide levels, and antioxidative side was determined by measuring total antioxidant capacity (TAC) and reduced glutathione (GSH) levels in plasma and kidney tissues. Results The oxidant-antioxidant balance seemed to be shifted to the oxidative side in the GM group when compared with the control and GM + licorice groups. In GM group, biochemical profiles showed a remarkable increase in blood uric acid, urea, and creatinine levels, and depletion of renal tissue and plasma TAC and GSH levels. In addition, histopathologic studies revealed severe acute tubular necrosis, congestion, and hyaline casts, verifying GM-induced nephrotoxicity. Licorice was effective in reduction of blood urea, creatinine, and uric acid levels, and also effective in decreasing the tubular necrosis score. Licorice treatment also significantly reduced LPO and total peroxide levels, and increased TAC and GSH levels in both renal tissue and blood. Moreover, these changes in rats subjected to the combined therapy (GM + licorice) were significantly less than those of GM group. Conclusions Licorice ameliorates GM-induced nephrotoxicity and oxidative damage by scavenging oxygen free radicals, decreasing LPO, and improving antioxidant defense.


title: Diagnosis of canine coronavirus infection using nested-PCR

text: Abstract The results of polymerase chain reaction (PCR) and nested polymerase chain reaction (n-PCR) assays for the diagnosis of canine coronavirus (CCV) infection, and the comparison with other diagnostic techniques, such as electron microscopy (EM) and virus isolation using A-72 cell line are reported. The study was carried out on 71 faecal samples of pups with enteritis. Of 71 samples examined 14 were positive in PCR, whereas 30 samples resulted positive in the n-PCR assay. CCV was detected by EM examination in only four out of 45 samples, and by virus isolation in three out of 30 samples n-PCR positive.


title: Lipid metabolites as potential diagnostic and prognostic biomarkers for acute community acquired pneumonia

text: Abstract Early diagnosis of acute community-acquired pneumonia (CAP) is important in patient triage and treatment decisions. To identify biomarkers that distinguish patients with CAP from non-CAP controls, we conducted an untargeted global metabolome analysis for plasma samples from 142 patients with CAP (CAP cases) and 97 without CAP (non-CAP controls). Thirteen lipid metabolites could discriminate between CAP cases and non-CAP controls with area-under-the-receiver-operating-characteristic curve of >0.8 (P ≤ 10−9). The levels of glycosphingolipids, sphingomyelins, lysophosphatidylcholines and L-palmitoylcarnitine were higher, while the levels of lysophosphatidylethanolamines were lower in the CAP cases than those in non-CAP controls. All 13 metabolites could distinguish CAP cases from the non-infection, extrapulmonary infection and non-CAP respiratory tract infection subgroups. The levels of trihexosylceramide (d18:1/16:0) were higher, while the levels of lysophosphatidylethanolamines were lower, in the fatal than those of non-fatal CAP cases. Our findings suggest that lipid metabolites are potential diagnostic and prognostic biomarkers for CAP.


title: Particulate matter (PM(10)) enhances RNA virus infection through modulation of innate immune responses()

text: Sensing of pathogens by specialized receptors is the hallmark of the innate immunity. Innate immune response also mounts a defense response against various allergens and pollutants including particulate matter present in the atmosphere. Air pollution has been included as the top threat to global health declared by WHO which aims to cover more than three billion people against health emergencies from 2019 to 2023. Particulate matter (PM), one of the major components of air pollution, is a significant risk factor for many human diseases and its adverse effects include morbidity and premature deaths throughout the world. Several clinical and epidemiological studies have identified a key link between the PM existence and the prevalence of respiratory and inflammatory disorders. However, the underlying molecular mechanism is not well understood. Here, we investigated the influence of air pollutant, PM(10) (particles with aerodynamic diameter less than 10 μm) during RNA virus infections using highly pathogenic avian influenza (HPAI) – H5N1 virus. We thus characterized the transcriptomic profile of lung epithelial cell line, A549 treated with PM(10) prior to H5N1infection, which is known to cause severe lung damage and respiratory disease. We found that PM(10) enhances vulnerability (by cellular damage) and regulates virus infectivity to enhance overall pathogenic burden in the lung cells. Additionally, the transcriptomic profile highlights the connection of host factors related to various metabolic pathways and immune responses which were dysregulated during virus infection. Collectively, our findings suggest a strong link between the prevalence of respiratory illness and its association with the air quality.


title: Retrospective serosurveillance of bovine norovirus (GIII.2) and nebovirus in cattle from selected feedlots and a veal calf farm in 1999 to 2001 in the United States

text: There is a dearth of information on the seroprevalence of bovine norovirus (BoNoV) and nebovirus in cattle of the US. In this retrospective study, serum IgG antibodies to two bovine enteric caliciviruses, GIII.2 BoNoV (Bo/CV186-OH/00/US) and genetically and antigenically distinct nebovirus (Bo/NB/80/US), were evaluated in feedlot and veal calves from different regions of the US during 1999-2001. Three groups of 6- to 7-month-old feedlot calves from New Mexico (NM) (n=103), Arkansas (AR) (n=100) and Ohio (OH) (n=140) and a group of 7- to 10-day-old Ohio veal calves (n=47) were studied. Serum samples were collected pre-arrival or at arrival to the farms for the NM, AR and OH calves and 35 days after arrival for all groups for monitoring seroconversion rates during the period. Virus-like particles of Bo/CV186-OH/00/US and Bo/NB/80/US were expressed using the baculovirus expression system and were used in ELISA to measure antibodies. A high seroprevalence of 94-100 % and 78-100 % was observed for antibodies to GIII.2 BoNoV and nebovirus, respectively, in the feedlot calves tested. In the Ohio veal farm, an antibody seroprevalence of 94-100 % and 40-66 % was found for GIII.2 BoNoV and nebovirus, respectively. Increased seropositive rates of 38-85 % for GIII.2 BoNoV and 26-83 % for nebovirus were observed at 35 days after arrival and commingling on farms for all groups. Infection of calves with either GIII.2 BoNoV or nebovirus, or both viruses, appeared to be common in the regions studied in the US during 1999-2001. These two viruses likely remain endemic because no commercial vaccines are available.


title: Chapter 13 Biology and Diseases of Cats

text: Domestic cats (Felis cattus) comprise a small (2%) percentage of the non-rodent animals used in biomedical research. In 2011, 21,700 cats of a total 1,134,693 non-rodent animals were used in research (APHIS, 2011). According to the National Research Council Committee on Scientific and Humane Issues in the Use of Random Source Dogs and Cats in Research (National Research Council, 2009), peak use of cats occurred in 1974. Since that time, the number of cats used in research has fallen by 71%, with more than 98% of those cats being purpose bred for research. Cats are a U.S. Department of Agriculture (USDA) covered species with special housing requirements defined in the Animal Welfare Act and the Guide for the Care and Use of Laboratory Animals (NRC, 2011). At the request of congress, a committee of experts formed by the National Research Council examined the use of random source dogs and cats and concluded that obtaining dogs and cats from Class B dealers is not necessary for NIH funded research (National Research Council, 2009). While the number of cats used in biomedical research has declined, cats continue to contribute uniquely to biomedical science and are valuable research model for several disciplines, including aspects of neurology involved in locomotion and spinal trauma, retrovirus and zoonotic disease research, and for developing therapeutic strategies for inherited diseases.


title: MISMIS – A comprehensive decision support system for stock market investment

text: Abstract Nowadays, stock market is becoming a popular investment platform for both institutional and individual investors. The current financial information systems serve to provide latest information. However, they lack sophisticated analytical tools. This paper proposes a new architecture for financial information systems. The developed prototype is entitled as the Multi-level and Interactive Stock Market Investment System (MISMIS). It is specially designed for investors to build their financial models to forecast stock price and index. The performance of the financial models can be evaluated on a virtual trading platform. There are other features in MISMIS that are tailor-made to handle financial data; these include synchronized time frame, time series prediction techniques, preprocessing and transformation functions, multi-level modeling and interactive user interface. To illustrate the capability of MISMIS, we have evaluated strategies of trading the future options of Hang Seng Index (HSI). We find that historical HSI, Dow Jones Index, property price index, retailing sales figure, prime lending rate, and consumer price index in Hong Kong are essential factors affecting the performance of the trading of HSI’s future option. Also there are some feedbacks from the in-depth interviews of six financial consultant upon how they perceived the prototype MISMIS.


title: The case for a 3rd generation supraglottic airway device facilitating direct vision placement

text: Although 1st and 2nd generation supraglottic airway devices (SADs) have many desirable features, they are nevertheless inserted in a similar ‘blind’ way as their 1st generation predecessors. Clinicians mostly still rely entirely on subjective indirect assessments to estimate correct placement which supposedly ensures a tight seal. Malpositioning and potential airway compromise occurs in more than half of placements. Vision-guided insertion can improve placement. In this article we propose the development of a 3rd generation supraglottic airway device, equipped with cameras and fiberoptic illumination, to visualise insertion of the device, enable immediate manoeuvres to optimise SAD position, verify whether correct 1st and 2nd seals are achieved and check whether size selected is appropriate. We do not provide technical details of such a ‘3rd generation’ device, but rather present a theoretical analysis of its desirable properties, which are essential to overcome the remaining limitations of current 1st and 2nd generation devices. We also recommend that this further milestone improvement, i.e. ability to place the SAD accurately under direct vision, be eligible for the moniker ‘3rd generation’. Blind insertion of SADs should become the exception and we anticipate, as in other domains such as central venous cannulation and nerve block insertions, vision-guided placement becoming the gold standard.


title: Avian Group D Rotaviruses: Structure, Epidemiology, Diagnosis, and Perspectives on Future Research Challenges

text: In 1981, a new virus (virus 132) was described for the first time with morphological and biochemical similarities to rotaviruses (RVs), but without antigenic similarity to any of the previously known rotavirus groups. Subsequently, it was re-designated as D/132, and formed a new serogroup among rotaviruses, the group D rotavirus (RVD). Since their identification, RVs are the leading cause of enteritis and diarrhea in humans and various animal species, and are also associated with abridged growth, particularly in avian species. Recently, RVD has been suggested to play a role in the pathogenesis of runting and stunting syndrome (RSS), alongside other viruses such as reovirus, astrovirus, coronavirus, and others, all of which cause colossal economic losses to the poultry industry. RVD has been reported from several countries worldwide, and to date, only one complete genome sequence for RVD is available. Neither an immunodiagnostic nor a vaccine is available for the detection and prevention of RVD infection. Despite our growing understanding about this particular group, questions remain regarding its exact prevalence and pathogenecity, and the disease-associated annual losses for the poultry industry. Here, we describe the current knowledge about the identification, epidemiology, diagnosis, and prevention of RVD in poultry.


title: Chapter 20 Autoimmunity in visual loss

text: Abstract There are a number of autoimmune disorders which can affect visual function. There are a very large number of mechanisms in the visual pathway which could potentially be the targets of autoimmune attack. In practice it is the retina and the anterior visual pathway (optic nerve and chiasm) that are recognised as being affected in autoimmune disorders. Multiple Sclerosis is one of the commonest causes of visual loss in young adults because of the frequency of attacks of optic neuritis in that condition, however the basis of the inflammation in Multiple Sclerosis and the confirmation of autoimmunity is lacking. The immune process is known to be highly unusual in that it is not systemic and confined to the CNS compartment. Previously an enigmatic partner to Multiple Sclerosis, Neuromyelitis Optica is now established to be autoimmune and two antibodies – to Aquaporin4 and to Myelin Oligodendrocyte Glycoprotein – have been implicated in the pathogenesis. The term Chronic Relapsing Inflammatory Optic Neuropathy is applied to those cases of optic neuritis which require long term immunosuppression and hence are presumed to be autoimmune but where no autoimmune pathogenesis has been confirmed. Optic neuritis occurring post-infection and post vaccination and conditions such as Systemic Lupus Erythematosus and various vasculitides may cause direct autoimmune attack to visual structures or indirect damage through occlusive vasculopathy. Chronic granulomatous disorders such as Sarcoidosis affect vision commonly by a variety of mechanisms, whether and how these are placed in the autoimmune panoply is unknown. As far as the retina is concerned Cancer Associated Retinopathy and Melanoma Associated Retinopathy are well characterised clinically but a candidate autoantibody (recoverin) is only described in the former disorder. Other, usually monophasic, focal retinal inflammatory disorders (Idiopathic Big Blind Spot Syndrome, Acute Zonal Occult Outer Retinopathy and Acute Macular Neuroretinitis) are of obscure pathogenesis but an autoimmune disorder of the post-infectious type is plausible. Visual loss in autoimmunity is an expanding field: the most significant advances in research have resulted from taking a well characterised phenotype and making educated guesses at the possible molecular targets of autoimmune attack.


title: Rapid detection of equine coronavirus by reverse transcription loop-mediated isothermal amplification

text: Abstract A reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for the rapid detection of equine coronavirus (ECoV). This assay was conducted at 60°C for 40min. Specificity of the RT-LAMP assay was confirmed using several equine intestinal and respiratory pathogens in addition to ECoV. The novel assay failed to cross-react with the other pathogens tested, suggesting it is highly specific for ECoV. Using artificially synthesized ECoV RNA, the 50% detection limit of the RT-LAMP assay was 101.8 copies/reaction. This is a 50-fold greater sensitivity than conventional reverse transcription polymerase chain reaction (RT-PCR) assays, but a 4-fold lower sensitivity than quantitative RT-PCR (qRT-PCR) assays. Eighty-two fecal samples collected during ECoV outbreaks were analyzed. ECoV was detected in 59 samples using the RT-LAMP assay, and in 30 and 65 samples using RT-PCR or qRT-PCR assays, respectively. Although the RT-LAMP assay is less sensitive than qRT-PCR techniques, it can be performed without the need for expensive equipment. Thus, the RT-LAMP assay might be suitable for large-scale surveillance and diagnosis of ECoV infection in laboratories with limited resources.


Early Reflection on the Global Impact of COVID19, and Implications for Physiotherapy


title: Chapter 8 Tannins: Major Sources, Properties and Applications

text: Publisher Summary This chapter provides a brief historical introduction and the distinction between hydrolysable and condensed tannins, a description of their chemistry and a short historical review on their use in leather tanning, the more recent developments in tannins for adhesives with and without the use of any aldehyde-yielding compounds, even without the use of any hardeners. Examples of the use of tannins for other industrial, nonleather, applications are reported. In particular, this chapter focuses briefly on their new intended use in the medical and pharmaceutical fields. New data on their antiviral effectiveness against a great number of different viruses compared to their higher, lower, or absent cytotoxicity are also presented.


title: Middle East respiratory syndrome (MERS): A new zoonotic viral pneumonia

text: Coronaviruses have traditionally been associated with mild upper respiratory tract infections throughout the world. In the fall of 2002, a new coronavirus emerged in in Asia causing severe viral pneumonia, i.e., severe acute respiratory syndrome (SARS). Nearly a decade following the SARS epidemic, a new coronavirus causing severe viral pneumonia has emerged, i.e., middle east respiratory syndrome (MERS). Since the initial case of MERS-CoV occurred in June of 2012 in Saudi Arabia there have been 688 confirmed cases and 282 deaths in 20 countries. Although both SARS and MERS are caused by coronaviruses, SARS was characterized by efficient human transmission and relatively low mortality rate. In contrast, MERS is relatively inefficiently transmitted to humans but has a high mortality rate. Given the potential overlap in presentation and manifestation, it is important to understand the clinical and epidemiologic differences between MERS, SARS and influenza.


title: Recommendations for head and neck surgical procedures during the COVID-19 pandemic

text: The coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread exponentially worldwide. In Brazil, the number of infected people diagnosed has been increasing and, as in other countries, it has been associated with a high risk of contamination in healthcare teams. For healthcare professionals, the full use of personal protective equipment (PPE) is mandatory, such as wearing surgical or filtering facepiece class 2 (FFP2) masks, waterproof aprons, gloves, and goggles, in addition to training in care processes. A reduction in the number of face-to-face visits and non-essential elective procedures is also recommended. However, surgery should not be postponed in the case of the most essential elective indications (mostly associated with head and neck cancers). As malignant tumors of the head and neck are clinically time sensitive, neither consultations for these tumors nor their treatment should be postponed. Postponing surgical treatment can result in a change in the disease stage and alter an individual's chance of survival. In this situation, planning of all treatments must begin with the request for, in addition to routine examinations, a nasal swab polymerase chain reaction for SARS-CoV-2 and chest computed tomography. Only if the results of these tests are positive or if fever or other symptoms suggestive of COVID-19 are present should the surgical procedure be postponed until the patient completely recovers. This is mandatory not only because of the risk of contamination of the surgical team but also because of the increased risk of postoperative complications and high risk of death. During this pandemic, the most effective safety measures are social distancing for the general public and the adequate availability and use of PPE in the healthcare field. The treatment of other chronic diseases, such as cancer, should be continued, as the damming of cases of these diseases will have a deleterious effect on the public healthcare system.


title: Pneumococcal colonisation is an asymptomatic event in healthy adults using an experimental human colonisation model

text: INTRODUCTION: Pneumococcal colonisation is regarded as a pre-requisite for developing pneumococcal disease. In children previous studies have reported pneumococcal colonisation to be a symptomatic event and described a relationship between symptom severity/frequency and colonisation density. The evidence for this in adults is lacking in the literature. This study uses the experimental human pneumococcal challenge (EHPC) model to explore whether pneumococcal colonisation is a symptomatic event in healthy adults. METHODS: Healthy participants aged 18–50 were recruited and inoculated intra-nasally with either Streptococcus pneumoniae (serotypes 6B, 23F) or saline as a control. Respiratory viral swabs were obtained prior to inoculation. Nasal and non-nasal symptoms were then assessed using a modified Likert score between 1 (no symptoms) to 7 (cannot function). The rate of symptoms reported between the two groups was compared and a correlation analysis performed. RESULTS: Data from 54 participants were analysed. 46 were inoculated with S. pneumoniae (29 with serotype 6B, 17 with serotype 23F) and 8 received saline (control). In total, 14 became experimentally colonised (30.4%), all of which were inoculated with serotype 6B. There was no statistically significant difference in nasal (p = 0.45) or non-nasal symptoms (p = 0.28) between the inoculation group and the control group. In those who were colonised there was no direct correlation between colonisation density and symptom severity. In the 22% (12/52) who were co-colonised, with pneumococcus and respiratory viruses, there was no statistical difference in either nasal or non-nasal symptoms (virus positive p = 0.74 and virus negative p = 1.0). CONCLUSION: Pneumococcal colonisation using the EHPC model is asymptomatic in healthy adults, regardless of pneumococcal density or viral co-colonisation.


title: Coronaviruses and their therapy

text: Abstract Coronaviruses may cause respiratory, enteric and central nervous system diseases in many species, including humans. Until recently, the relatively low burden of disease in humans caused by few of these viruses hampered development of coronavirus specific therapeutics. However, the emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) has prompted the discovery of such drugs. Subsequent studies in animal models demonstrated the efficacy of SARS-CoV specific monoclonal antibodies, pegylated-interferon-α and siRNAs against SARS-CoV. Furthermore, several antivirals shown to be effective against other viruses were tested in vitro. Because of availability and shown efficacy, the use of interferons may be considered should SARS-CoV or a related coronavirus (re)-emerge. The more recent design of wide-spectrum inhibitors targeting the coronavirus main proteases may lead to the discovery of new antivirals against multiple coronavirus induced diseases.


title: Immunoinformatics: Current trends and future directions

text: Immunoinformatics has recently emerged as a critical field for accelerating immunology research. Although still an evolving process, computational models now play instrumental roles, not only in directing the selection of key experiments, but also in the formulation of new testable hypotheses through detailed analysis of complex immunologic data that could not be achieved using traditional approaches alone. Immunomics, which combines traditional immunology with computer science, mathematics, chemistry, biochemistry, genomics and proteomics for the large-scale analysis of immune system function, offers new opportunities for future bench-to-bedside research. In this article, we review the latest trends and future directions of the field.


title: On integration and adaptation in complex service systems

text: The services sector employs a large and growing proportion of workers in the industrialized nations, and it is increasingly dependent on information and communication technologies. While the interdependences, similarities and complementarities of manufacturing and services are significant, there are considerable differences between goods and services, including the shift in focus from mass production to mass customization (whereby a service is produced and delivered in response to a customer’s stated or imputed needs). In general, services can be considered to be knowledge-intensive agents or components which work together as providers and consumers to create or co-produce value. Like manufacturing systems, an efficient service system must be an integrated system of systems, leading to greater connectivity and interdependence. Integration must occur over the physical, temporal, organizational and functional dimensions, and must include methods concerned with the component, the management, and the system. Moreover, an effective service system must also be an adaptable system, leading to greater value and responsiveness. Adaptation must occur over the dimensions of monitoring, feedback, cybernetics and learning, and must include methods concerned with space, time, and system. In sum, service systems are indeed complex, especially due to the uncertainties associated with the human-centered aspects of such systems. Moreover, the system complexities can only be dealt with methods that enhance system integration and adaptation. The paper concludes with several insights, including a plea to shift the current misplaced focus on developing a science or discipline for services to further developing a systems engineering approach to services, an approach based on the integration and adaptation of a host of sciences or disciplines (e.g., physics, mathematics, statistics, psychology, sociology, etc.). In fact, what is required is a services-related transdisciplinary - beyond a single disciplinary - ontology or taxonomy as a basis for disciplinary integration and adaptation.


title: A simple procedure for the analysis of the structural proteins of influenza and parainfluenza viruses involving adsorption to erythrocytes

text: Abstract A simple procedure for the analysis of the structural proteins of influenza and parainfluenza viruses utilizing adsorption to erythrocytes is described. The method involves virus growth in the presence of [35S]methionine, adsorption of clarified culture medium with a 0.5% suspension of either guinea-pig or chicken erythrocytes and analysis of the virus-erythrocyte aggregates by sodium dodecyl sulphate-polya-crylamide gel electrophoresis (SDS-PAGE). All of the structural proteins can be detected using this procedure, and the protein profiles of virus-adsorbed erythrocyte complexes compare extremely well with those of sucrose density gradient purified virus preparations.


title: Immunogenicity of Different Forms of Middle East Respiratory Syndrome S Glycoprotein

text: The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 during the first Middle East respiratory syndrome (MERS) outbreaks. MERS-CoV causes an acute lower-respiratory infection in humans, with a fatality rate of ~35.5%. Currently, there are no registered vaccines or means of therapeutic protection against MERS in the world. The MERS-CoV S glycoprotein plays the most important role in the viral life cycle (virus internalization). The S protein is an immunodominant antigen and the main target for neutralizing antibodies. In the present study, the immunogenicities of five different forms of the MERS-CoV S glycoprotein were compared: the full-length S glycoprotein, the full-length S glycoprotein with the transmembrane domain of the G glycoprotein of VSV (S-G), the receptor-binding domain (RBD) of the S glycoprotein, the membrane-fused RBD (the RBD fused with the transmembrane domain of the VSV G glycoprotein (RBD-G)), and the RBD fused with Fc of human IgG1 (RBD-Fc). Recombinant vectors based on human adenoviruses type 5 (rAd5) were used as delivery vehicles. Vaccination with all of the developed rAd5 vectors elicited a balanced Th1/Th2 response in mice. The most robust humoral immune response was induced after the animal had been vaccinated with the membrane-fused RBD (rAd5-RBD-G). Only immunization with membrane forms of the glycoprotein (rAd5-S, rAd5-S-G, and rAd5-RBD-G) elicited neutralizing antibodies among all vaccinated animals. The most significant cellular immune response was induced after vaccination of the animals with the full-length S (rAd5-S). These investigations suggest that the full-length S and the membrane form of the RBD (RBD-G) are the most promising vaccine candidates among all the studied forms of S glycoprotein.


Pseudoparticle Neutralization Assay for Detecting Ebola- Neutralizing Antibodies in Biosafety Level 2 Settings


title: Canine Reproductive, Respiratory, and Ocular Diseases due to Canine Herpesvirus

text: This review documents how clinical inquiry expands as our knowledge base about canine herpesvirus (CHV) increases. We must understand the various forms of CHV infection that may occur in the dog population. This has prompted the veterinary community to develop more sensitive diagnostic assays. CHV is more common than we considered a decade ago. Up to 70% of some high-risk dog populations have been infected with and are latent carriers of CHV. Recognition of the various forms of CHV-induced disease, availability of diagnostic assays with increased sensitivity, and the formation of reliable biosecurity measures will allow for better control steps.


Diagnosing COVID-19-associated pulmonary aspergillosis


title: Development and validation a nomogram for predicting the risk of severe COVID-19: A multi-center study in Sichuan, China

text: BACKGROUND: Since December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan and spread across the globe. The objective of this study is to build and validate a practical nomogram for estimating the risk of severe COVID-19. METHODS: A cohort of 366 patients with laboratory-confirmed COVID-19 was used to develop a prediction model using data collected from 47 locations in Sichuan province from January 2020 to February 2020. The primary outcome was the development of severe COVID-19 during hospitalization. The least absolute shrinkage and selection operator (LASSO) regression model was used to reduce data size and select relevant features. Multivariable logistic regression analysis was applied to build a prediction model incorporating the selected features. The performance of the nomogram regarding the C-index, calibration, discrimination, and clinical usefulness was assessed. Internal validation was assessed by bootstrapping. RESULTS: The median age of the cohort was 43 years. Severe patients were older than mild patients by a median of 6 years. Fever, cough, and dyspnea were more common in severe patients. The individualized prediction nomogram included seven predictors: body temperature at admission, cough, dyspnea, hypertension, cardiovascular disease, chronic liver disease, and chronic kidney disease. The model had good discrimination with an area under the curve of 0.862, C-index of 0.863 (95% confidence interval, 0.801–0.925), and good calibration. A high C-index value of 0.839 was reached in the interval validation. Decision curve analysis showed that the prediction nomogram was clinically useful. CONCLUSION: We established an early warning model incorporating clinical characteristics that could be quickly obtained on admission. This model can be used to help predict severe COVID-19 and identify patients at risk of developing severe disease.