title: Urban inequalities in the 21st century economy

text: Abstract In the last decade or so, inequality studies have assumed renewed prominence across the social sciences. In this introduction to a special issue of Applied Geography, we set out to articulate the importance of urban spatial context in broader present-day inequality debates. We argue that the information-based economy is emphatically urban-based and that it has forged new spatial inequalities in and between cities and among urban populations. Income gaps have widened, inter-city disparities have grown, suburbs have been re-sorted into a wide array on the basis of class and race or ethnicity, and many central cities have assumed a renewed importance within metropolitan areas. We argue that attention to urban spatial dimensions at various scales is critical to understanding current inequality trends, from intra-urban to regional and global scales. Contributions to this special issue from North America, Europe, South America, and China suggest that deepening urban inequalities are pervasive across the globe.


title: Chapter 23 Infectious Diseases

text: This chapter reviews the naturally occurring viral, bacterial, fungal, protozoal, and parasitic diseases of guinea pigs (Cavia porcellus) with an emphasis on those diseases found in captive guinea pigs. For each organism, etiology, epizootiology, pathogenesis, clinical manifestations, pathology, diagnosis, prevention, and therapy are discussed. Major viruses include adenoviruses, herpesviruses, lymphocytic choriomeningitis virus, paramyxoviruses (including Sendai virus), and cavian leukemia virus. Common bacterial organisms are Clostridia sp., Corynebacterium, Staphylococcus, Streptococcus, Bordetella, Chlamydia, Klebsiella, Lawsonia intercellularis, Leptospira, Pasteurella multocida, Salmonella, Streptobacillus moniliformis, and Yersinia pseudotuberculosis. Common fungal organisms include Trichophyton mentagrophytes, Microsporum canis, Microsporum gypseum, and Encephalitozoon cuniculi. Major protozoal diseases are Amoebiasis, Balantidiasis, Cryptosporidiosis, Eimeria, Giardiasis, Klossiella cobayae, Leishmaniasis, Toxoplasmosis, and Tritrichomonas caviae. Common external parasites include lice (Gyropus ovalis, Gliricola porcelli and Trimenopon hispidum) and mites (Chirodiscoides caviae and Trixacarus caviae). Internal parasites are cestodes, Pelodera strongyloides, Baylisascaris, Paraspidodera uncinata, Trichinella, and Fasciola spp.


title: Systems analysis of West Nile virus infection

text: Emerging and re-emerging mosquito-borne viruses continue to pose a significant threat to human health throughout the world. Over the past decade, West Nile virus (WNV), Dengue virus (DENV), and Chikungunya virus (CHIKV), have caused annual epidemics of virus-induced encephalitis, hemorrhagic fever\shock syndromes, and arthritis, respectively. Currently, no specific antiviral therapies or vaccines exist for use in humans to combat or prevent these viral infections. Thus, there is a pressing need to define the virus-host interactions that govern immunity and infection outcome. Recent technological breakthroughs in ‘omics’ resources and high-throughput based assays are beginning to accelerate antiviral drug discovery and improve on current strategies for vaccine design. In this review, we highlight studies with WNV and discuss how traditional and systems based approaches are being used to rapidly identify novel host targets for therapeutic intervention and develop a deeper conceptual understanding of the host response to virus infection.


title: Rational Design of Peptide Vaccines Against Multiple Types of Human Papillomavirus

text: Human papillomavirus (HPV) occurs in many types, some of which cause cervical, genital, and other cancers. While vaccination is available against the major cancer-causing HPV types, many others are not covered by these preventive measures. Herein, we present a bioinformatics study for the designing of multivalent peptide vaccines against multiple HPV types as an alternative strategy to the virus-like particle vaccines being used now. Our technique of rational design of peptide vaccines is expected to ensure stability of the vaccine against many cycles of mutational changes, elicit immune response, and negate autoimmune possibilities. Using the L1 capsid protein sequences, we identified several peptides for potential vaccine design for HPV 16, 18, 33, 35, 45, and 11 types. Although there are concerns about the epitope-binding affinities for the peptides identified in this process, the technique indicates possibilities of multivalent, adjuvanted, peptide vaccines against a wider range of HPV types, and tailor-made different combinations of the peptides to address frequency variations of types over different population groups as required for prophylaxis and at lower cost than are in use at the present time.


title: Viral infections in patients with an acute exacerbation of idiopathic interstitial pneumonia

text: Abstract Background Patients with slowly progressive idiopathic interstitial pneumonia, including idiopathic pulmonary fibrosis, often deteriorate, thus suggesting that the clinical course may be unpredictable. Such episodes are termed acute exacerbation of idiopathic interstitial pneumonia. The etiology of an acute exacerbation of idiopathic interstitial pneumonia is unknown. In this study, we tested the hypothesis that an acute exacerbation of idiopathic interstitial pneumonia is induced by respiratory viral infections. Methods Bronchoalveolar lavage fluid obtained from patients with an acute exacerbation of idiopathic interstitial pneumonia was tested for viral nucleic acid using polymerase chain reaction. Results Only 1 of the 14 patients with an acute exacerbation of idiopathic interstitial pneumonia exhibited evidence of respiratory syncytial virus B, and 2 patients exhibited evidence of cytomegalovirus. Seven patients fulfilled the diagnostic criteria of idiopathic pulmonary fibrosis. Conclusions Most cases with an acute exacerbation of idiopathic interstitial pneumonia are not caused by a viral infection.


title: Diagnostic Considerations in Acute Disseminated Encephalomyelitis and the Interface with MOG Antibody

text: Acute disseminated encephalomyelitis (ADEM) is a common yet clinically heterogenous syndrome characterized by encephalopathy, focal neurologic findings, and abnormal neuroimaging. Differentiating ADEM from other demyelinating disorders of childhood can be difficult and appropriate interpretation of the historical, clinical, and neurodiagnostic components of a patient's presentation is critical. Myelin oligodendrocyte glycoprotein (MOG) antibody-associated diseases are a recently recognized set of disorders, which include ADEM presentations, among other phenotypes. This review article discusses the clinical diagnosis, differential diagnosis, interpretation of data, and treatment/prognosis of this unique syndrome with distinctive review of the spectrum of MOG antibodies.


title: Doomsday preppers and the architecture of dread

text: Abstract Prepping is a practice of anticipating and adaptating to impending conditions of calamity, ranging from low-level crises to extinction-level events. The 2020 COVID-19 pandemic, which preppers consider a 'mid-level' event, and which many of them were well-prepared for, makes clear that scholarly attention to prepper's motivations and methods is both timely and valuable. Drawing from a three-year ethnographic research project with preppers, this paper traces the activity of a single bunker builder who has constructed a technically sophisticated private underground community. Supplemented by additional fieldwork, the paper argues that the boltholes preppers are building in closed communities built to survive the collapse of society, order, and even the environment itself, refract the seemingly irresolvable problems we are failing to address as a species. In the prepper ideology, faith in adaptation has supplanted hope of mitigation, making contemporary bunkers more speculative than reactionary and more temporal than spatial. The bunkers preppers build are an ark to cross through a likely (but often unspecified) catastrophe; they are a chrysalis from which to be reborn - potentially even into an improved milieu.


title: An evaluation of the inhibitory effects against rotavirus infection of edible plant extracts

text: BACKGROUND: Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The developments of specific, potent and accessible antiviral treatments that restrain rotavirus infection remain important to control rotavirus disease. METHODS: 150 plant extracts with nutritional applications were screened in vitro on MA-104 cells for their antiviral activity against rhesus rotavirus (RRV). One extract (Aspalathus linearis (Burm.f.) R.Dahlgren) was also tested for its effect on the loss of transepithelial resistance (TER) of Caco-2 cells caused by simian rotavirus (SA-11) infection. RESULTS: Aqueous extracts of Nelumbo nucifera Gaertn. fruit, Urtica dioica L. root, Aspalathus linearis (Burm.f.) R.Dahlgren leaves, Glycyrrhiza glabra L. root and Olea europaea L. leaves were found to have strong significant antiviral activity with a 50% inhibitory concentration (IC50) < 300 μg/ml. The pure compound 18ß-glycyrrhetinic acid from Glycyrrhiza glabra was found to have the strongest antiviral activity (IC50 46 μM), followed by luteolin and vitexin from Aspalathus linearis (IC50 respectively 116 μM and 129 μM) and apigenin-7-O-glucoside from Melissa officinalis (IC50 150 μM). A combination of Glycyrrhiza glabra L. + Nelumbo nucifera Gaertn. and Urtica dioica L. + Nelumbo nucifera Gaertn. showed synergy in their anti-viral activities. Aspalathus linearis (Burm.f.) R.Dahlgren showed no positive effect on the maintenance of the TER. CONCLUSIONS: These results indicate that nutritional intervention with extracts of Nelumbo nucifera Gaertn., Aspalathus linearis (Burm.f.) R.Dahlgren, Urtica dioica L., Glycyrrhiza glabra L. and Olea europaea L. might be useful in the treatment of diarrhea caused by rotavirus infection.


title: The challenges of treating tracheobronchitis in a laryngectomee due to nontypeable Haemophilus influenzae: a case report

text: BACKGROUND: Laryngectomees run the risk of developing severe respiratory tract infections especially during the winter and when they do not wear a stoma cover. A case of severe tracheobronchitis in a laryngectomee is presented that illustrates the risks and difficulties encountered in managing this infection in a neck breather. CASE PRESENTATION: A 76-year-old Caucasian man, a laryngectomee, presented with bacterial tracheobronchitis and conjunctivitis due to beta-lactamase-producing nontypeable Haemophilus influenzae. He was febrile (38.9 °C; 102.0 F), and had repeated episodes of hypertension. He was treated with levofloxacin 500 mg/day, ciprofloxacin eye drops, acetaminophen, and guaifenesin. Humidification of his trachea and the airway was sustained by insertions of saline into the stoma as well as breathing humidified air. The main challenge was to maintain the patency of his airway as the mucus was very dry and viscous and tended to stick to the walls of his trachea and the stoma. His condition improved within 7 days and he had a complete recovery. CONCLUSIONS: Maintaining the patency of the airway in laryngectomees who suffer from lower respiratory tract infection is of utmost importance as the mucus can be very dry and viscous and can stick to the walls of the trachea and the stoma.


title: Dynamically-Driven Inactivation of the Catalytic Machinery of the SARS 3C-Like Protease by the N214A Mutation on the Extra Domain

text: Despite utilizing the same chymotrypsin fold to host the catalytic machinery, coronavirus 3C-like proteases (3CLpro) noticeably differ from picornavirus 3C proteases in acquiring an extra helical domain in evolution. Previously, the extra domain was demonstrated to regulate the catalysis of the SARS-CoV 3CLpro by controlling its dimerization. Here, we studied N214A, another mutant with only a doubled dissociation constant but significantly abolished activity. Unexpectedly, N214A still adopts the dimeric structure almost identical to that of the wild-type (WT) enzyme. Thus, we conducted 30-ns molecular dynamics (MD) simulations for N214A, WT, and R298A which we previously characterized to be a monomer with the collapsed catalytic machinery. Remarkably, three proteases display distinctive dynamical behaviors. While in WT, the catalytic machinery stably retains in the activated state; in R298A it remains largely collapsed in the inactivated state, thus implying that two states are not only structurally very distinguishable but also dynamically well separated. Surprisingly, in N214A the catalytic dyad becomes dynamically unstable and many residues constituting the catalytic machinery jump to sample the conformations highly resembling those of R298A. Therefore, the N214A mutation appears to trigger the dramatic change of the enzyme dynamics in the context of the dimeric form which ultimately inactivates the catalytic machinery. The present MD simulations represent the longest reported so far for the SARS-CoV 3CLpro, unveiling that its catalysis is critically dependent on the dynamics, which can be amazingly modulated by the extra domain. Consequently, mediating the dynamics may offer a potential avenue to inhibit the SARS-CoV 3CLpro.


2019-nCoV-SARS-CoV-2 (COVID-19) infection: Crucıalıty of Furın and relevance wıth cancer


title: Chilblain‐like lesions during COVID‐19 pandemic: a serological study on a case series

text: The outbreak of chilblain‐like lesions (CLL) coincidentally to the COVID‐19 pandemic is a topic of great concern. SARS‐CoV‐2 has been hypothesized as the etiologic agent of CLL, on the basis of the temporal correlation between the “burst” of skin manifestations and the viral pandemic. However, the relationship between CLL and COVID‐19 remains unclear, since authors failed to confirm the SARS‐CoV‐2 infection in these patients using a real‐time reverse transcription polymerase chain reaction (rt‐PCR) test from nasopharyngeal swabs, which seldom resulted positive. Indeed, the most recent articles on the prevalence of the SARS‐CoV‐2 infection in CLL reported a positive swab test in only about a fifth of these patients.


title: Preparation and biological properties of 2-thio-containing pyrimidines and their condensed analogs

text: [Image: see text] The known methods for synthesis of thioxopyrimidines and their condensed analogs with exocyclic sulfur atom are summarized and discussed. The most popular approaches are based on [3+3], [4+2], [5+1] cyclization processes or domino reactions. The literature data analysis shows that the title compounds possess diverse biological activities, such as antioxidant, radioprotective, analgesic, antiinflammatory, antihypertensive, anxiolytic, anamnestic, anticonvulsant, antimicrobial, fungicidal, herbicidal, antiviral, and anticancer.


title: Chapter 18 Acute Disseminated Encephalomyelitis

text: Abstract Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating syndrome with encephalopathy. ADEM typically affects young children, is often postinfectious, and is typically monophasic. MRI neuroimaging, which shows new lesions with poorly demarcated borders, but not old and established lesions, is essential to diagnosis. Autoantibodies against myelin oligodendrocyte glycoprotein (MOG) are found in ∼40% of ADEM patients, and these patients have different clinical and neuroimaging features to seronegative patients. Treatment in the acute phase is typically with high-dose corticosteroids and intravenous immunoglobulin or plasma exchange for refractory patients. Outcome is usually good, but residual cognitive, inattentive, and executive issues are likely underestimated. In patients who have a relapse, biomarkers and imaging should help differentiate multiphasic ADEM, neuromyelitis optica spectrum disorder, anti-MOG antibody–associated relapsing demyelination, and multiple sclerosis.


title: A Bivalent Human Adenovirus Type 5 Vaccine Expressing the Rabies Virus Glycoprotein and Canine Distemper Virus Hemagglutinin Protein Confers Protective Immunity in Mice and Foxes

text: The development of a safe and efficient multivalent vaccine has great prospects for application. Both rabies virus (RABV) and canine distemper virus (CDV) are highly infectious antigens, causing lethal diseases in domestic dogs and other carnivores worldwide. In this study, a replication-deficient human adenovirus 5 (Ad5)-vectored vaccine, rAd5-G-H, expressing RABV glycoprotein (G) and CDV hemagglutinin (H) protein was constructed. The RABV G and CDV H protein of rAd5-G-H were expressed and confirmed in infected HEK-293 cells by indirect immunofluorescence assay. The rAd5-G-H retained a homogeneous icosahedral morphology similar to rAd5-GFP under an electron microscope. A single dose of 10(8) GFU of rAd5-G-H administered to mice by intramuscular injection elicited rapid and robust neutralizing antibodies against RABV and CDV. Flow cytometry assays indicated that the dendritic cells and B cells in inguinal lymph nodes were significantly recruited in rAd5-G-H-immunized mice in comparison with the mock and rAd5-GFP groups. rAd5-G-H also activated the Th1- and Th2-mediated cell immune responses against RABV and CDV in mice, which contributed to 100% survival of a lethal-dose RABV challenge without any clinical signs. In foxes, a single dose of 10(9) GFU of rAd5-G-H could elicit high levels of neutralizing antibodies against both RABV and CDV in comparison with the mock and rAd5-GFP groups. All foxes in the rAd5-GFP and mock groups died, while the foxes inoculated with rAd5-G-H all survived and showed no clinical signs of disease after being challenged with a lethal wild-type CDV strain. These results suggested that rAd5-G-H has great potential as a bivalent vaccine against rabies and canine distemper in highly susceptible dogs and wildlife animals.


title: An Overview of Signal Processing Techniques for Remote Health Monitoring Using Impulse Radio UWB Transceiver

text: Non-invasive remote health monitoring plays a vital role in epidemiological situations such as SARS outbreak (2003), MERS (2015) and the recently ongoing outbreak of COVID-19 because it is extremely risky to get close to the patient due to the spread of contagious infections. Non-invasive monitoring is also extremely necessary in situations where it is difficult to use complicated wired connections, such as ECG monitoring for infants, burn victims or during rescue missions when people are buried during building collapses/earthquakes. Due to the unique characteristics such as higher penetration capabilities, extremely precise ranging, low power requirement, low cost, simple hardware and robustness to multipath interferences, Impulse Radio Ultra Wideband (IR-UWB) technology is appropriate for non-invasive medical applications. IR-UWB sensors detect the macro as well as micro movement inside the human body due to its fine range resolution. The two vital signs, i.e., respiration rate and heart rate, can be measured by IR-UWB radar by measuring the change in the magnitude of signal due to displacement caused by human lungs, heart during respiration and heart beating. This paper reviews recent advances in IR- UWB radar sensor design for healthcare, such as vital signs measurements of a stationary human, vitals of a non-stationary human, vital signs of people in a vehicle, through the wall vitals measurement, neonate’s health monitoring, fall detection, sleep monitoring and medical imaging. Although we have covered many topics related to health monitoring using IR-UWB, this paper is mainly focused on signal processing techniques for measurement of vital signs, i.e., respiration and heart rate monitoring.


title: Three new coumarins from Saposhnikovia divaricata and their porcine epidemic diarrhea virus (PEDV) inhibitory activity

text: Swine based agro-industries throughout the world are in big threat of new PEDV infection due to lack of efficient prophylactic defenses as well as dependable curing agents. Bioactivity-guided fractionation of a methanol soluble extract from radix of Saposhnikovia divaricata led to the isolation of three new (1–3) together with 10 known coumarins (4–13). The structures of new isolates (1–3) were established by extensive spectroscopic analysis and their absolute configurations were assigned based on ECD spectra calculation and analysis. Among all isolates, compound 5 revealed strongest inhibitory effect on PEDV replication. Quantitative real-time PCR data showed inhibitory effect of 5 on genes responsible for synthesis of PEDV vital structural proteins (GP6 nucleocapsid, GP2 spike, and GP5 membrane) in a dose-dependent manner. Also, compound 5 demonstrated the inhibitory effect on PEDV GP6 nucleocapsid and GP2 spike protein synthesis as analyzed by western blotting. This study represents a new class of chemical entities for developing anti-PEDV agents.


title: The Psychological and Mental Impact of Coronavirus Disease 2019 (COVID-19) on Medical Staff and General Public – A Systematic Review and Meta-analysis

text: The coronavirus disease 2019 (COVID-19) pandemic has caused enormous psychological impact worldwide. We conducted a systematic review and meta-analysis on the psychological and mental impact of COVID-19 among healthcare workers, the general population, and patients with higher COVID-19 risk published between 1 Nov 2019 to 25 May 2020. We conducted literature researching used Embase, PubMed, Google scholar and WHO COVID-19 databases. Among the initial search of 9207 studies, 62 studies with 162,639 participants from 17 countries were included in the review. The pooled prevalence of anxiety and depression was 33% (95% confidence interval: 28%-38%) and 28% (23%-32%), respectively. The prevalence of anxiety and depression was the highest among patients with pre-existing conditions and COVID-19 infection (56% [39%-73%] and 55% [48%-62%]), and it was similar between healthcare workers and the general public. Studies from China, Italy, Turkey, Spain and Iran reported higher-than-pooled prevalence among healthcare workers and the general public. Common risk factors included being women, being nurses, having lower socioeconomic status, having high risks of contracting COVID-19, and social isolation. Protective factors included having sufficient medical resources, up-to-date and accurate information, and taking precautionary measures. In conclusion, psychological interventions targeting high-risk populations with heavy psychological distress are in urgent need.


title: Awareness and compliance of dental students and interns toward infection control at Riyadh Elm University

text: Aim: Dental students have increasing patient contact during their education and clinical years, putting them at high risk of cross-infection; therefore, the purpose of this study was to determine the level of infection control practices among dental students and interns at Riyadh Elm University, Riyadh, Saudi Arabia. Methods: Total of 400 questionnaires were distributed among interns and clinical students at Riyadh Elm University. The questionnaire comprised 32 items assessing infection control practices, and the data were tabulated and analyzed by SPSS to produce descriptive statistics. Results: Three hundred nine questionnaires were answered (response rate 77%).The implementation of different infection control measures was good to excellent, except for hepatitis B vaccination and wearing eye protection: only 76% of males and 83% of females were vaccinated against HBV, and only 30% of males and 26% of females always wore protective glasses. Conclusion: Compared to previous studies, an increased awareness regarding infection control practices among dental students and interns was noticeable. However, greater emphasis on the importance of infection control, especially compliance with HBV vaccination and wearing protective eyewear, is necessary.


Maps, masks and media – Traveller and practitioner resources for 2019 novel coronavirus (2019-nCoV) acute respiratory virus


title: Migraine Care in the Era of COVID‐19: Clinical Pearls and Plea to Insurers

text: OBJECTIVE: To outline strategies for the treatment of migraine which do not require in‐person visits to clinic or the emergency department, and to describe ways that health insurance companies can remove barriers to quality care for migraine. BACKGROUND: COVID‐19 is a global pandemic causing widespread infections and death. To control the spread of infection we are called to observe “social distancing” and we have been asked to postpone any procedures which are not essential. Since procedural therapies are a mainstay of headache care, the inability to do procedures could negatively affect our patients with migraine. In this manuscript we review alternative therapies, with particular attention to those which may be contra‐indicated in the setting of COVID‐19 infection. DESIGN/RESULTS: The manuscript reviews the use of telemedicine visits and acute, bridge, and preventive therapies for migraine. We focus on evidence‐based treatment where possible, but also describe “real world” strategies which may be tried. In each section we call out areas where changes to rules from commercial health insurance companies would facilitate better migraine care. CONCLUSIONS: Our common goal as health care providers is to maximize the health and safety of our patients. Successful management of migraine with avoidance of in‐person clinic and emergency department visits further benefits the current urgent societal goal of maintaining social distance to contain the COVID‐19 pandemic.


title: A primer on proning in the emergency department

text: Historically, the prone position was used almost exclusively in the ICU for patients suffering from refractory hypoxemia due to acute respiratory distress syndrome (ARDS). Amidst the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic, however, this technique has been increasingly utilized in settings outside of the ICU, particularly in the emergency department. With emerging evidence that patients diagnosed with COVID‐19 who are not intubated and mechanically ventilated may benefit from the prone position, this strategy should not be isolated to only those with critical illness. This is a review of the pertinent physiology and evidence supporting prone positioning along with a step‐by‐step guide meant to familiarize those who are not already comfortable with the maneuver. Placing a patient in the prone position helps to improve ventilation‐perfusion matching, dorsal lung recruitment, and ultimately gas exchange. Evidence also suggests there is improved oxygenation in both mechanically ventilated patients and those who are awake and spontaneously breathing, further reinforcing the utility of the prone position in non‐ICU settings. Given present concerns about resource limitations because of the pandemic, prone positioning has especially demonstrable value as a technique to delay or even prevent intubation. Patients who are able to self‐prone should be directed into the ''swimmer's position'' and then placed in reverse Trendelenburg position if further oxygenation is needed. If a mechanically ventilated patient is to be placed in the prone position, specific precautions should be taken to ensure the patient's safety and to prevent any unwanted sequelae of prone positioning.


title: Teaching the Basics: Core Competencies in Global Health

text: Compelling moral, ethical, professional, pedagogical, and economic imperatives support the integration of global health topics within medical school curriculum. Although the process of integrating global health into medical education is well underway at some medical schools, there remain substantial challenges to initiating global health training in others. As global health is a new field, faculties and schools may benefit from resources and guidance to develop global health modules and teaching materials. This article describes the Core Competencies project undertaken by the Global Health Education Consortium and the Association of Faculties of Medicine of Canada’s Global Health Resource Group.


title: Identification of Cystoisospora ohioensis in a Diarrheal Dog in Korea

text: A 3-month-old female Maltese puppy was hospitalized with persistent diarrhea in a local veterinary clinic. Blood chemistry and hematology profile were analyzed and fecal smear was examined. Diarrheal stools were examined in a diagnostic laboratory, using multiplex real-time polymerase chain reaction (PCR) against 23 diarrheal pathogens. Sequence analysis was performed using nested PCR amplicon of 18S ribosomal RNA. Coccidian oocysts were identified in the fecal smear. Although multiplex real-time PCR was positive for Cyclospora cayetanensis, the final diagnosis was Cystoisospora ohioensis infection, confirmed by phylogenetic analysis of 18S rRNA. To our knowledge, this the first case report of C. ohioensis in Korea, using microscopic examination and phylogenetic analysis.


title: The transcriptomic response to viral infection of two strains of shrimp (Litopenaeus vannamei)()

text: The extent to which data-intensive studies of the transcriptome can provide insight into biological responses is not well defined, especially in the case of species (such as shrimp) where much physiological and biochemical knowledge is missing. In this study we took a transcriptomic approach to gain insight into the response to viral infection of two strains of the Pacific whiteleg shrimp (Litopenaeus vannamei) that differ in their resistance to Taura Syndrome Virus (TSV). Changes in gene expression in the hepatopancreas following infection with TSV and Yellow Head Virus (YHV) were assessed using a cDNA microarray containing 2469 putative unigenes. The null hypothesis tested was that significant differences between the transcriptomic responses to viral infection of resistant and sensitive strains would not be detected. This hypothesis was broadly rejected, with the most surprising observation being that the baseline (control, unchallenged) sensitive and resistant strains expressed distinguishable transcriptomic signatures. The resistant line was pre-disposed to lower expression of genes encoding viral (and host) proteins. Many of the genes differentiating resistant and sensitive lines are involved in protein metabolism, cellular trafficking, immune defense and stress response, although it was not possible to clearly identify candidate genes responsible for TSV resistance. In contrast to TSV challenge, YSV either failed to perturb the host transcriptome or created a “confused” response that was difficult to interpret.


A virtual oral cancer clinical competency examination administered during the COVID‐19 pandemic


In Memoriam: Physicians Who Have Died of COVID-19 in the United States()


title: The primary structure and expression of the second open reading frame of the polymerase gene of the coronavirus MHV-A59; a highly conserved polymerase is expressed by an efficient ribosomal frameshifting mechanism.

text: Sequence analysis of a substantial part of the polymerase gene of the murine coronavirus MHV-A59 revealed the 3' end of an open reading frame (ORF1a) overlapping with a large ORF (ORF1b; 2733 amino acids) which covers the 3' half of the polymerase gene. The expression of ORF1b occurs by a ribosomal frameshifting mechanism since the ORF1a/ORF1b overlapping nucleotide sequence is capable of inducing ribosomal frameshifting in vitro as well as in vivo. A stem-loop structure and a pseudoknot are predicted in the nucleotide sequence involved in ribosomal frameshifting. Comparison of the predicted amino acid sequence of MHV ORF1b with the amino acid sequence deduced from the corresponding gene of the avian coronavirus IBV demonstrated that in contrast to the other viral genes this ORF is extremely conserved. Detailed analysis of the predicted amino acid sequence revealed sequence elements which are conserved in many DNA and RNA polymerases.


title: The Wisconsin Upper Respiratory Symptom Survey is responsive, reliable, and valid

text: Abstract Objective To assess reliability, responsiveness, importance to patients, and convergent validity for the Wisconsin Upper Respiratory Symptom Survey (WURSS-44) and to develop a short-form WURSS. Study Design and Setting Community-based recruitment of participants with colds. Prospective monitoring from within 48 hours of first symptom until 2 days after end of cold. The WURSS-44 includes 1 global illness severity item, 32 symptom-based items, 10 functional quality-of-life items, and 1 item assessing global change. The SF-36, SF-8, and the Jackson cold scale were used as external comparators. Results Participants included 104 women and 45 men, aged 18 to 80 years, self-reporting on 1,681 person-days of illness. Factor analysis suggested 10 dimensions, with reliability coefficients from 0.62 to 0.93. Comparing daily WURSS-44 to Jackson and SF-8 yielded Pearson correlation coefficients from 0.73 to 0.93, and from −0.60 to −0.84, respectively. Importance to patients and responsiveness assessment yielded a short version, the WURSS-21. Guyatt's responsiveness index was 0.54 for the SF-8, 0.61 for the Jackson, 0.71 for the WURSS-44, and 0.80 for the WURSS-21, suggesting that a two-armed trial would require 74 participants for the WURSS-21, 92 for the WURSS-44, 124 for the Jackson scale, and 156 for the SF-8. Conclusions The construct validity of WURSS-44 is supported by measures of reliability, responsiveness, importance to patients, and convergence. A shorter version, the WURSS-21, may be even more responsive.


title: Anti‐hepatitis C virus compounds obtained from Glycyrrhiza uralensis and other Glycyrrhiza species

text: Development of complementary and/or alternative drugs for treatment of hepatitis C virus (HCV) infection is still much needed from clinical and economic points of view. Antiviral substances obtained from medicinal plants are potentially good targets to study. Glycyrrhiza uralensis and G. glabra have been commonly used in both traditional and modern medicine. In this study, extracts of G. uralensis roots and their components were examined for anti‐HCV activity using an HCV cell culture system. It was found that a methanol extract of G. uralensis roots and its chloroform fraction possess anti‐HCV activity with 50%‐inhibitory concentrations (IC(50)) of 20.0 and 8.0 μg/mL, respectively. Through bioactivity‐guided purification and structural analysis, glycycoumarin, glycyrin, glycyrol and liquiritigenin were isolated and identified as anti‐HCV compounds, their IC(50) being 8.8, 7.2, 4.6 and 16.4 μg/mL, respectively. However, glycyrrhizin, the major constituent of G. uralensis, and its monoammonium salt, showed only marginal anti‐HCV activity. It was also found that licochalcone A and glabridin, known to be exclusive constituents of G. inflata and G. glabra, respectively, did have anti‐HCV activity, their IC(50) being 2.5 and 6.2 μg/mL, respectively. Another chalcone, isoliquiritigenin, also showed anti‐HCV activity, with an IC(50) of 3.7 μg/mL. Time‐of‐addition analysis revealed that all Glycyrrhiza‐derived anti‐HCV compounds tested in this study act at the post‐entry step. In conclusion, the present results suggest that glycycoumarin, glycyrin, glycyrol and liquiritigenin isolated from G. uralensis, as well as isoliquiritigenin, licochalcone A and glabridin, would be good candidates for seed compounds to develop antivirals against HCV.


title: The Ocular Surface and the Coronavirus Disease 2019: Does a Dual ‘Ocular Route’ Exist?

text: Coronavirus disease 2019 (COVID-19) is an important health problem that was defined as a pandemic by the World Health Organization on 11 March 2020. Although great concern has been expressed about COVID-19 infection acquired through ocular transmission, its underlying mechanism has not currently been clarified. In the current work, we analyzed and elucidated the two main elements that should be taken into account to understand the “ocular route”, both from a clinical and molecular point of view. They are represented by the dynamism of the ocular surface system (e.g., the tear film turnover) and the distribution of ACE2 receptors and TMPRSS2 protein. Although it seems, at the moment, that there is a low risk of coronavirus spreading through tears, it may survive for a long time or replicate in the conjunctiva, even in absence of conjunctivitis signs, indicating that eye protection (e.g., protective goggles alone or in association with face shield) is advisable to prevent contamination from external droplets and aerosol.


title: Immunoglobulin E response during viral infections

text: Abstract One hundred and three patients (90 nonatopics and 13 atopics) with respiratory infections to various viral agents were studied retrospectively with respect to IgE immunoglobulin levels during acute (1 to 7 days) and convalescent (8 to 30 days) phases of infection. It was found that 59% of patients had a decrease of 20% or more in IgE level, 27% remained the same, and only 14% showed a rise of 20% or more from the acute to the convalescent phases of infection. IgE levels decreased up to 3 to 4 wk after symptoms and the degree of decrease was more apparent for the nonatopics who had higher IgE levels in their acute phase of infection. Less dramatic decrease in IgE was observed for the 13 atopics studied. The changes in IgE levels during the viral infectious period are discussed in terms of possible cellular mechanisms that may control IgE immunoglobulin.


title: Changes in emergency service access after spread of COVID19 across Italy

text: The Italian National Health System is currently living through some catastrophic days, owing to the rapid spread of COVID‐19 across the country. At the time of writing, our Government has passed emergency laws (March 11, 2020), with a view to preventing widespread viral infection among the population, which may well lead to an increase in the number of people requiring intensive care unit (ICU) hospital treatment. Currently, most of the northern Italian regions are close to saturation point in terms of the number of available ICU inpatient beds.


title: Immune derangement occurs in patients with H7N9 avian influenza

text: INTRODUCTION: Currently, little is known about the immunological characteristics of patients with avian influenza A (H7N9) virus infection. METHODS: The numbers and percentages of peripheral blood immune cells were measured in 27 patients with laboratory-confirmed H7N9 virus infection and 30 healthy controls (HCs). The functional phenotypes of T cells and monocytes, as well as serum cytokine levels, were analyzed by flow cytometry. RESULTS: There were 19 patients (70.4%) with acute respiratory distress syndrome, 13 (48.1%) with secondary respiratory infection, 20 (74%) with systemic inflammatory response syndrome (SIRS; defined as having at least two concurrent SIRS components), 18 (66.7%) with lymphocytopenia and 11 (40.7%) with reduced numbers of monocytes. In comparison with levels in the HCs, the levels of serum interleukin 6 (IL-6), IL-8 and IL-10 and the percentages of CD38+ or Tim-3+ T cells were significantly increased. However, the percentages of human leukocyte antigen-DR + and Tim-3+ monocytes were significantly decreased in patients compared with HCs. CONCLUSIONS: Patients with avian H7N9 virus infection display profound SIRS concomitantly with an anti-inflammatory response, which may be associated with the rapid progression of and high mortality associated with this novel viral disease.


docid: qaurriwg

title: Budding Yeast SKP1 Encodes an Evolutionarily Conserved Kinetochore Protein Required for Cell Cycle Progression

text: Abstract The budding yeast SKP1gene, identified as a dosage suppressor of a known kinetochore protein mutant, encodes an intrinsic 22.3 kDa subunit of CBF3, a multiprotein complex that binds centromere DNA in vitro. Temperature-sensitive mutations in SKP1 define two distinct phenotypic classes. skp1-4 mutants arrest predominantly as large budded cells with a G2 DNA content and short mitotic spindle, consistent with a role in kinetochore function. skp1-3 mutants, however, arrest predominantly as multiply budded cells with a G1 DNA content, suggesting an additional role during the G1/S phase. Identification of Skp1p homologs from C. elegans, A. thaliana, and H. sapiens indicates that SKP1 is evolutionarily highly conserved. Skp1p therefore represents an intrinsic kinetochore protein conserved throughout eukaryotic evolution and may be directly involved in linking kinetochore function with the cell cycle-regulatory machinery.


title: A SIMPLE MODEL EXPLAINS THE DYNAMICS OF PREFERENTIAL HOST SWITCHING AMONG MAMMAL RNA VIRUSES

text: A growing number of studies support a tendency toward preferential host switching, by parasites and pathogens, over relatively short phylogenetic distances. This suggests that a host switch is more probable if a potential host is closely related to the original host than if it is a more distant relative. However, despite its importance for the health of humans, livestock, and wildlife, the detailed dynamics of preferential host switching have, so far, been little studied. We present an empirical test of two theoretical models of preferential host switching, using observed phylogenetic distributions of host species for RNA viruses of three mammal orders (primates, carnivores, and ungulates). The analysis focuses on multihost RNA virus species, because their presence on multiple hosts and their estimated ages of origin indicate recent host switching. Approximate Bayesian computation was used to compare observed phylogenetic distances between hosts with those simulated under the theoretical models. The results support a decreasing sigmoidal model of preferential host switching, with a strong effect from increasing phylogenetic distance, on all three studied host phylogenies. This suggests that the dynamics of host switching are fundamentally similar for RNA viruses of different mammal orders and, potentially, a wider range of coevolutionary systems.


title: Rapid detection of porcine circovirus type 2 by loop-mediated isothermal amplification

text: Abstract A method of loop-mediated isothermal amplification (LAMP) was employed to develop a rapid and simple detection system for porcine circovirus type 2 (PCV2). The amplification could be finished in 60min under isothermal condition at 64°C by employing a set of four primers targeting the cap gene of PCV2. The LAMP assay showed higher sensitivity than the conventional PCR, with a detection limit of five copies per tube of purified PCV2 genomic DNA. No cross-reactivity was observed from the samples of other related viruses including porcine circovirus type 1 (PCV1), porcine parvovirus (PPV), porcine pseudorabies virus (PRV) and porcine reproductive and respiratory syndrome virus (PRRSV). The detection rate of PCV2 LAMP for 86 clinical samples was 96.5% and appeared greater than that of the PCR method. The LAMP assay reported can provide a rapid yet simple test of PCV2 suitable for laboratory diagnosis and pen-side detection due to ease of operation and the requirement of only a regular water bath or heat block for the reaction.


title: Dendritic cells: Immunological sentinels with a central role in health and disease

text: Immunological effector cells must be sensitive to the antigens or environmental signals that indicate that a pathogen is present. To this end, a group of cells known as the professional antigen‐presenting cells have the ability to educate T, B and NK cells as to the fingerprints of specific infections. The most adept of these cells are a closely related family termed dendritic cells (DC). A subset of these act as peripheral sentinels, specializing in the uptake, processing and presentation of antigenic material combined with an ability to detect a wide variety of ‘danger’ signals. These ‘danger’ or activation signals induce profound changes in dendritic cell physiology, facilitating the efficient stimulation of both adaptive and innate immunity. In the present review, a number of recent advances in the understanding of DC biology are discussed. These advances offer insights into the pathogenesis of a wide variety of diseases and point towards future strategies for immunotherapy.


title: Molecular characterization of a unique variant of avian infectious bronchitis virus in Tunisia

text: ABSTRACT Avian infectious bronchitis virus (IBV) is responsible of significant economic losses for poultry industry around the world, through evolution of its pathogenicity, inadequacy of vaccines, and virus evasion. Such evasion is related to the unstable nature of its RNA, in particular the S glycoprotein encoding gene, which raises great challenges with regard to the control of the disease, along with the lack of proof reading mechanisms of the RNA polymerase. The emergence of new variants might be a reason for the endemic outbreaks that are being reported in Tunisia, in addition to poor vaccination techniques and ineffective prophylactic programs. In the present study, partial nucleotide sequences of the S1 glycoprotein gene and the 3′-untranslated region (UTR) of 2 Tunisian isolates, TN1011/16 and TN1012/16, identified in 2016, were determined. Specific mutations were found in S1 gene as well as in 3′UTR region. Phylogenetic analysis of the S1 nucleotide sequences showed that both isolates are closely related to the Algerian strains, and formed a common cluster within the genotype I. In addition, these isolates were non-recombinant ones, confirming that they are unique variants. Based on their S1 gene sequences, TN1011/16 and TN1012/16 strains were distant from the H120 vaccine strain, commercially used in Tunisia along with the variant vaccine 793B type (4/91). A comparison between nucleotide sequences of their 3′UTR region and S1 gene showed a difference in IBV classification. The obtained results have confirmed that the IBVsequence continues to drift and brings valuable information in relation with its evolution, vaccine development and better control of the disease.


title: Identifying Research Trends and Gaps in the Context of COVID-19

text: The COVID-19 pandemic has affected the world in different ways. Not only are people’s lives and livelihoods affected, but the virus has also affected people’s lifestyles. In the research sector, there have been significant changes, and new research is coming very strongly in the related fields of virology and epidemiology. Similar trends were observed after the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) episodes of 2003 and 2012, respectively. Analyzing 20 years of published scientific papers, this article points out the highlights of coronavirus-related research. Significant progress is observed in the past research related to virology, epidemiology, infectious diseases among others. However, in research linked to public health, its governance, technology, and risk communication there seem to be gap areas. Although the World Health Organization (WHO) global research road map has identified social science-related research as a priority area, more focus needs to be given in the upcoming days for multi, cross and trans-disciplinary research related to public health and disaster risk reduction.


title: Ayudas desde la red para el control de la epidemia

text: Resumen Multitud de portales informáticos aparecen día a día, sobresaturando de información a la comunidad médica y no médica, y que no siempre es confiable y puede encubrir motivos comerciales y propaganda diseminada sin control alguno. Este maremágnum informático en épocas de pandemia puede ser muy peligroso, al llevar a las personas sin formación adecuada conceptos que, al ser mal interpretados o mal difundidos, pueden acabar en ansiedad y confusión. Afortunadamente, de este caos informático surgen aspectos positivos, como es el hecho de aprovechar las indagaciones que sobre síntomas o enfermedades –específicamente, influenza A (H1N1)– realiza la población, en los principales motores de búsqueda de internet (Google o Yahoo), para detectar tempranamente la emergencia de una epidemia local o global. Este método de localización de brotes parece ser de tanta utilidad que, incluso, ha dado origen a una nueva rama del conocimiento: la “infodemiología” que, a través de la “infovigilancia”, vigila los eventos en el instante mismo en que van ocurriendo, o incluso antes, mediante el análisis continuo y estructurado de la información disponible en internet. Otro aspecto por resaltar es la calidad y prontitud en la información dispuesta en las páginas web de las instituciones encargadas del control de infecciones en el mundo (Organización Mundial de la Salud) y en varios países de América, lo cual ha permitido seguir la emergencia de la pandemia y actuar para controlarla. Abstract A huge number of web sites appear every day, overcrowding the existing body of medical and non-medical information in the net; Sources are not always reliable and usually covers commercial and propaganda purposes. This may arise an special concern regarding the dissemination of mislead concepts and practices on the response to pandemic Flu. But not everything is negative on this specific matter. An example of this is the possibility of early detection of new cases of Flu, due to the easy access to information regarding clinical symptoms that search engines like Google or Yahoo, provide to the general population. A new online-based method of outbreak surveillance, appear to be a useful tool, an it’ been denominated “infodemiology”. This method allows a real-time monitoring of cases and predicts the expansion of the disease, through continuous and structured analysis of information available on the internet. Another aspect to remark is the quality and promptness of information available on the web, provided by the institutions responsible for controlling infections in the world (e.g World Health Organization), improving the response to a pandemic threat.


title: Safety and tolerability of a novel, polyclonal human anti-MERS coronavirus antibody produced from transchromosomic cattle: a phase 1 randomised, double-blind, single-dose-escalation study

text: Summary Background Middle East respiratory syndrome (MERS) is a severe respiratory illness with an overall mortality of 35%. There is no licensed or proven treatment. Passive immunotherapy approaches are being developed to prevent and treat several human medical conditions where alternative therapeutic options are absent. We report the safety of a fully human polyclonal IgG antibody (SAB-301) produced from the hyperimmune plasma of transchromosomic cattle immunised with a MERS coronavirus vaccine. Methods We did a phase 1 double-blind, placebo-controlled, single-dose escalation trial at the National Institutes of Health Clinical Center. We recruited healthy participants aged 18–60 years who had normal laboratory parameters at enrolment, a body-mass index of 19–32 kg/m2, and a creatinine clearance of 70 mL/min or more, and who did not have any chronic medical problems that required daily oral medications, a positive rheumatoid factor (≥15 IU/mL), IgA deficiency (<7 mg/dL), or history of allergy to intravenous immunoglobulin or human blood products. Participants were randomly assigned by a computer-generated table, made by a masked pharmacist, to one of six cohorts (containing between three and ten participants each). Cohorts 1 and 2 had three participants, randomly assigned 2:1 to receive active drug SAB-301 versus normal saline placebo; cohorts 3 and 4 had six participants randomised 2:1; and cohorts 5 and 6 had ten participants, randomised 4:1. Participants received 1 mg/kg, 2·5 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg, or 50 mg/kg of SAB-301, or equivalent volume placebo (saline control), on day 0, and were followed up by clinical, laboratory, and pharmacokinetic assessments on days 1, 3, 7, 21, 42, and 90. The primary outcome was safety, and immunogenicity was a secondary outcome. We analysed the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02788188. Findings Between June 2, 2016, and Jan 4, 2017, we screened 43 participants, of whom 38 were eligible and randomly assigned to receive SAB-301 (n=28) or placebo (n=10). 97 adverse events were reported: 64 adverse events occurred in 23 (82%) of 28 participants receiving SAB-301 (mean 2·3 adverse events per participant). 33 adverse events occurred in all ten participants receiving placebo (mean 3·3 adverse events per participant). The most common adverse events were headache (n=6 [21%] in participants who received SAB-301 and n=2 [20%] in those receiving placebo), albuminuria (n=5 [18%] vs n=2 [20%]), myalgia (n=3 [11%] vs n=1 [10%]), increased creatine kinase (n=3 [11%] vs 1 [10%]), and common cold (n=3 [11%] vs n=2 [20%]). There was one serious adverse event (hospital admission for suicide attempt) in one participant who received 50 mg/kg of SAB-301. The area under the concentration–time curve (AUC) in the 50 mg/kg dose (27 498 μg × days per mL) is comparable to the AUC that was associated with efficacy in a preclinical model. Interpretation Single infusions of SAB-301 up to 50 mg/kg appear to be safe and well tolerated in healthy participants. Human immunoglobulin derived from transchromosomic cattle could offer a new platform technology to produce fully human polyclonal IgG antibodies for other medical conditions. Funding National Institute of Allergy and Infectious Diseases, National Institutes of Health, and Biomedical Advanced Research and Development Authority.


title: An easy operating pathogen microarray (EOPM) platform for rapid screening of vertebrate pathogens

text: BACKGROUND: Infectious diseases emerge frequently in China, partly because of its large and highly mobile population. Therefore, a rapid and cost-effective pathogen screening method with broad coverage is required for prevention and control of infectious diseases. The availability of a large number of microbial genome sequences generated by conventional Sanger sequencing and next generation sequencing has enabled the development of a high-throughput high-density microarray platform for rapid large-scale screening of vertebrate pathogens. METHODS: An easy operating pathogen microarray (EOPM) was designed to detect almost all known pathogens and related species based on their genomic sequences. For effective identification of pathogens from EOPM data, a statistical enrichment algorithm has been proposed, and further implemented in a user-friendly web-based interface. RESULTS: Using multiple probes designed to specifically detect a microbial genus or species, EOPM can correctly identify known pathogens at the species or genus level in blinded testing. Despite a lower sensitivity than PCR, EOPM is sufficiently sensitive to detect the predominant pathogens causing clinical symptoms. During application in two recent clinical infectious disease outbreaks in China, EOPM successfully identified the responsible pathogens. CONCLUSIONS: EOPM is an effective surveillance platform for infectious diseases, and can play an important role in infectious disease control.


title: Recreational ‘mud fever’: Leptospira interrogans induced diffuse alveolar hemorrhage and severe acute respiratory distress syndrome in a U.S. Navy seaman following ‘mud-run’ in Hawaii

text: A 23-year-old man with a viral-like prodrome developed sudden severe dyspnea and was found to have renal failure, anemia, shock, and diffuse alveolar hemorrhage with acute respiratory distress syndrome, requiring emergent endotracheal intubation and extracorporeal membrane oxygenation (ECMO). Travel and exposure history from peripheral sources revealed that the patient had participated in a ‘mud-run’ in Hawaii two weeks prior to symptom onset. The patient was subsequently diagnosed with leptospirosis and treated with ceftriaxone and doxycycline. He was discharged on hospital day 13 with full recovery. Leptospirosis is associated with exposure to water, soil, or other matter contaminated with urine of carrier animals. It has been associated with a multitude of activities over time; most recently recreational water-based activities including ‘mud-runs’ in endemic areas have been added to the list of routes of exposure. This case underscores the importance of obtaining a thorough epidemiological exposure and travel history and being aware of areas of endemicity for life-threatening infections. Additionally, to our knowledge this is the second case of a patient in the United States treated with ECMO for leptospirosis induced pulmonary hemorrhage.


title: Cis-acting Regulatory Elements in the Potato Virus X 3′ Non-translated Region Differentially Affect Minus-strand and Plus-strand RNA Accumulation

text: Abstract The 72nt 3′ non-translated region (NTR) of potato virus X (PVX) RNA is identical in all sequenced PVX strains and contains sequences that are conserved among all potexviruses. Computer folding of the 3′ NTR sequence predicted three stem-loop structures (SL1, SL2, and SL3 in the 3′ to 5′ direction), which generally were supported by solution structure analyses. The importance of these sequence and/or structural elements to PVX RNA accumulation was further analyzed by inoculation of Nicotiana tabacum (NT-1) protoplasts with PVX transcripts containing mutations in the 3′ NTR. Analyses of RNA accumulation by S1 nuclease protection indicated that multiple sequence elements throughout the 3′ NTR were important for minus-strand RNA accumulation. Formation of SL3 was required for accumulation of minus-strand RNA, whereas SL1 and SL2 formation were less important. However, sequences within all of these predicted structures were required for minus-strand RNA accumulation, including a conserved hexanucleotide sequence element in the loop of SL3, and the CU nucleotide in a U-rich sequence within SL2. In contrast, 13 nucleotides that were predicted to reside in SL1 could be deleted without any significant reduction in minus or plus-strand RNA levels. Potential polyadenylation signals (near upstream elements; NUEs) in the 3′ NTR of PVX RNA were more important for plus-strand RNA accumulation than for minus-strand RNA accumulation. In addition, one of these NUEs overlapped with other sequence required for optimal minus-strand RNA levels. These data indicate that the PVX 3′ NTR contains multiple, overlapping elements that influence accumulation of both minus and plus-strand RNA.


Immunosuppressive treatment for systemic sclerosis – therapeutic challenges during the COVID‐19 pandemic.


Corona conspiracies: a call for urgent anthropological attention


Blood system changes since recognition of transfusion‐associated AIDS


title: Analysis of cell fusion induced by bovine coronavirus infection

text: Polykaryon formation in bovine fetal spleen (BFS) cells infected with bovine coronavirus L9 occurred only in media supplemented with trypsin. A single 1 to 2 h trypsin treatment 10 h and later after infection induced formation of polykaryons. Trypsin treatment at pH 7.5 and 8.0 induced polykaryons while treatments at lower or higher pH levels did not. Cell fusion activity was partially suppressed by the presence of antibody.


Actualización de las recomendaciones ALAT sobre la neumonía adquirida en la comunidad


title: Certain heptapeptide and large sequences representing an entire helix, strand or coil conformation in proteins are associated as chameleon sequences

text: Helices, strands and coils in proteins of known three-dimensional structure, corresponding to heptapeptide and large sequences (‘probe’ peptides), were scanned against peptide sequences of variable length, comprising seven or more residues that correspond to a different conformation (‘target’ peptides) in protein crystal structures available from the Protein Data Bank (PDB). Where the ‘probe’ and ‘target’ peptide sequences exactly match, they correspond to ‘chameleon’ sequences in protein structures. We observed ∼548 heptapeptide and large chameleon sequences that included peptides in the coil conformation from 53,794 PDB files that were analyzed. However, after excluding several chameleon peptides based on the quality of protein structure data, redundancy and peptides associated with cloning artifacts, such as, histidine-tags, we observed only ten chameleon peptides in structurally different proteins and the maximum length comprised seven amino acid residues. Our analysis suggests that the quality of protein structure data is important for identifying possibly, the ‘true chameleons’ in PDB. Majority of the chameleon sequences correspond to an entire strand in one protein that is observed as part of helix sequence in another protein. The heptapeptide chameleons are characterized with a high propensity of alanine, leucine and valine amino acid residues. The total hydropathy values range between −11.2 and 22.9, the difference in solvent accessibility between 2.0 Å(2) and 373 Å(2) units and the difference in total number of residue neighbor contacts between 0 and 7 residues. Our work identifies for the first time heptapeptide and large sequences that correspond to a single complete helix, strand or coil, which adopt entirely different secondary structures in another protein.


title: Elastic Theory of Defects in Toroidal Crystals

text: We report a comprehensive analysis of the ground state properties of axisymmetric toroidal crystals based on the elastic theory of defects on curved substrates. The ground state is analyzed as a function of the aspect ratio of the torus, which provides a non-local measure of the underlying Gaussian curvature, and the ratio of the defect core-energy to the Young modulus. Several structural features are discussed,including a spectacular example of curvature-driven amorphization in the limit of the aspect ratio approaching one. The outcome of the elastic theory is then compared with the results of a numerical study of a system of point-like particles constrained on the surface of a torus and interacting via a short range potential.


Might the many positive COVID19 subjects in Italy have been caused by resident bat‐derived zoonotic β‐coronaviruses instead of the Wuhan (China) outbreak?


title: Clinical Implications of SARS-Cov2 Interaction with Renin Angiotensin System

text: Abstract SARS-CoV2 host cell infection is mediated by the binding to angiotensin-converting enzyme 2 (ACE2). Systemic dysregulation observed in SARS-CoV was previously postulated to be due to ACE2/Ang1-7/Mas axis downregulation, increased ACE2 activity was shown to mediate disease protection. Since angiotensin II receptor blockers (ARBs), ACE inhibitors, and mineralocorticoid receptor antagonists (MRAs) increase ACE2 receptor expression, it has been tacitly believed that the use of these agents may facilitate viral disease, thus they should not be used in high-risk patients with cardiovascular disease. Based on the anti-inflammatory benefits of the upregulation of the ACE2/Ang1-7/Mas axis and previously demonstrated benefits of lung function improvement in SARS-CoV infections, we hypothesize that the benefits of treatment with renin-angiotensin system inhibitors in SARS-COV2 may outweigh the risks and at the very least should not be withheld.


title: Public Health Threat of New, Reemerging, and Neglected Zoonoses in the Industrialized World

text: Microbiologic infections acquired from animals, known as zoonoses, pose a risk to public health. An estimated 60% of emerging human pathogens are zoonotic. Of these pathogens, >71% have wildlife origins. These pathogens can switch hosts by acquiring new genetic combinations that have altered pathogenic potential or by changes in behavior or socioeconomic, environmental, or ecologic characteristics of the hosts. We discuss causal factors that influence the dynamics associated with emergence or reemergence of zoonoses, particularly in the industrialized world, and highlight selected examples to provide a comprehensive view of their range and diversity.


title: Understanding variation in covid-19 reported deaths with a novel Shewhart chart application

text: OBJECTIVE: Motivated by the covid-19 pandemic, we developed a novel Shewhart chart to visualize and learn from variation in reported deaths in an epidemic. CONTEXT: Without a method to understand if day-to-day variation in outcomes may be attributed to meaningful signals of change—rather than variability we would expect—care providers, improvement leaders, policy-makers, and the public will struggle to recognize if epidemic conditions are improving. METHODS: We developed a novel hybrid C-Chart and I-Chart to detect within a geographic area the start and end of exponential growth in reported deaths. Reported deaths were the unit of analysis owing to erratic reporting of cases from variability in local testing strategies. We used simulation and case studies to assess chart performance and define technical parameters. This approach also applies to other critical measures related to a pandemic when high-quality data are available. CONCLUSIONS: The hybrid chart detected the start of exponential growth and identified early signals that the growth phase was ending. During a pandemic, timely reliable signals that an epidemic is waxing or waning may have mortal implications. This novel chart offers a practical tool, accessible to system leaders and front-line teams, to visualize and learn from daily reported deaths during an epidemic. Without Shewhart charts and, more broadly, a theory of variation in our epidemiological arsenal, we lack a scientific method for real-time assessment of local conditions. Shewhart charts should become a standard method for learning from data in the context of a pandemic or epidemic.


title: Selective Naked-Eye Detection of SARS-CoV-2 Mediated by N Gene Targeted Antisense Oligonucleotide Capped Plasmonic Nanoparticles

text: [Image: see text] The current outbreak of the pandemic coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) demands its rapid, convenient, and large-scale diagnosis to downregulate its spread within as well as across the communities. But the reliability, reproducibility, and selectivity of majority of such diagnostic tests fail when they are tested either to a viral load at its early representation or to a viral gene mutated during its current spread. In this regard, a selective “naked-eye” detection of SARS-CoV-2 is highly desirable, which can be tested without accessing any advanced instrumental techniques. We herein report the development of a colorimetric assay based on gold nanoparticles (AuNPs), when capped with suitably designed thiol-modified antisense oligonucleotides (ASOs) specific for N-gene (nucleocapsid phosphoprotein) of SARS-CoV-2, could be used for diagnosing positive COVID-19 cases within 10 min from the isolated RNA samples. The thiol-modified ASO-capped AuNPs agglomerate selectively in the presence of its target RNA sequence of SARS-CoV-2 and demonstrate a change in its surface plasmon resonance. Further, the addition of RNaseH cleaves the RNA strand from the RNA–DNA hybrid leading to a visually detectable precipitate from the solution mediated by the additional agglomeration among the AuNPs. The selectivity of the assay has been monitored in the presence of MERS-CoV viral RNA with a limit of detection of 0.18 ng/μL of RNA having SARS-CoV-2 viral load. Thus, the current study reports a selective and visual “naked-eye” detection of COVID-19 causative virus, SARS-CoV-2, without the requirement of any sophisticated instrumental techniques.


title: Beyond Thrombosis The Versatile Platelet in Critical Illness

text: Sepsis, acute lung injury, and ARDS contribute substantially to the expanding burden of critical illness within our ICUs. Each of these processes is characterized by a myriad of injurious events, including apoptosis, microvascular dysfunction, abnormal coagulation, and dysregulated host immunity. Only recently have platelets—long considered merely effectors of thrombosis—been implicated in inflammatory conditions and the pathobiology of these disease processes. A growing body of evidence suggests a prominent role for maladaptive platelet activation and aggregation during sepsis and ARDS and has begun to underscore the pluripotential influence of platelets on outcomes in critical illness. Not only do platelets enhance vascular injury through thrombotic mechanisms but also appear to help orchestrate pathologic immune responses and are pivotal players in facilitating leukocyte recruitment to vulnerable tissue. These events contribute to the organ damage and poor patient outcomes that still plague the care of these high-risk individuals. An understanding of the role of platelets in critical illness also highlights the potential for both the development of risk stratification schema and the use of novel, targeted therapies that might alter the natural history of sepsis, acute lung injury, and ARDS. Future studies of adenosine, platelet polyphosphates, and the platelet transcriptome/proteome also should add considerably to our ability to unravel the mysteries of the versatile platelet.


title: Alu RNA regulates the cellular pool of active ribosomes by targeted delivery of SRP9/14 to 40S subunits

text: The human genome contains about 1.5 million Alu elements, which are transcribed into Alu RNAs by RNA polymerase III. Their expression is upregulated following stress and viral infection, and they associate with the SRP9/14 protein dimer in the cytoplasm forming Alu RNPs. Using cell-free translation, we have previously shown that Alu RNPs inhibit polysome formation. Here, we describe the mechanism of Alu RNP-mediated inhibition of translation initiation and demonstrate its effect on translation of cellular and viral RNAs. Both cap-dependent and IRES-mediated initiation is inhibited. Inhibition involves direct binding of SRP9/14 to 40S ribosomal subunits and requires Alu RNA as an assembly factor but its continuous association with 40S subunits is not required for inhibition. Binding of SRP9/14 to 40S prevents 48S complex formation by interfering with the recruitment of mRNA to 40S subunits. In cells, overexpression of Alu RNA decreases translation of reporter mRNAs and this effect is alleviated with a mutation that reduces its affinity for SRP9/14. Alu RNPs also inhibit the translation of cellular mRNAs resuming translation after stress and of viral mRNAs suggesting a role of Alu RNPs in adapting the translational output in response to stress and viral infection.


title: Detection of severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein in human serum using a localized surface plasmon coupled fluorescence fiber-optic biosensor

text: In order to enhance the sensitivity of conventional immunoassay technology for the detection of SARS coronavirus (SARS-CoV) nucleocapsid protein (N protein), we developed a localized surface plasmon coupled fluorescence (LSPCF) fiber-optic biosensor that combines sandwich immunoassay with the LSP technique. Experimentally, a linear relationship between the fluorescence signal and the concentration of recombinant SARS-CoV N (GST-N) protein in buffer solution could be observed from 0.1 pg/mL to 1 ng/mL. In addition, the concentration of GST-N protein in diluted serum across a similar range could also be measured. The correlation coefficients (linear scale) for these two measurements were 0.9469 and 0.9624, respectively. In comparison with conventional enzyme linked immunosorbent assay (ELISA), the detection limit of the LSPCF fiber-optic biosensor for the GST-N protein was improved at least 10(4)-fold using the same monoclonal antibodies. Therefore, the LSPCF fiber-optic biosensor shows an ability to detect very low concentration (∼1 pg/mL) of SARS-CoV N protein in serum. The biosensor should help with the early diagnosis of SARS infection.


title: The COVID‐19 Pandemic: Anticipating its Effects on Canada's Agricultural Trade

text: With the deep recession now forecast for the world economy, trade can be expected to fall even more steeply. Agricultural trade will be less significantly affected, being insulated by its relatively low income elasticities of demand. However, a drop in the range of 12 to 20 percent in real trade value should be expected. Canada can be expected to share in this, but, within agricultural exports, cereals will be least affected. This minimal expected impact to cereals stems from the risk of wheat export bans by Russia and Kazakhstan, due to the resulting increase in wheat prices. Livestock, pulses, and horticulture can be expected to face a larger decline in trade prospects and revenues. An equally large threat to falling incomes in our trade partners is their policy responses, particularly the potential increase in import restrictions. These may take the form of more costly inspections, tightened SPS and food safety regulations, and protectionist measures from competing domestic producers. This article is protected by copyright. All rights reserved


title: Graphical presentation of diagnostic information

text: BACKGROUND: Graphical displays of results allow researchers to summarise and communicate the key findings of their study. Diagnostic information should be presented in an easily interpretable way, which conveys both test characteristics (diagnostic accuracy) and the potential for use in clinical practice (predictive value). METHODS: We discuss the types of graphical display commonly encountered in primary diagnostic accuracy studies and systematic reviews of such studies, and systematically review the use of graphical displays in recent diagnostic primary studies and systematic reviews. RESULTS: We identified 57 primary studies and 49 systematic reviews. Fifty-six percent of primary studies and 53% of systematic reviews used graphical displays to present results. Dot-plot or box-and- whisker plots were the most commonly used graph in primary studies and were included in 22 (39%) studies. ROC plots were the most common type of plot included in systematic reviews and were included in 22 (45%) reviews. One primary study and five systematic reviews included a probability-modifying plot. CONCLUSION: Graphical displays are currently underused in primary diagnostic accuracy studies and systematic reviews of such studies. Diagnostic accuracy studies need to include multiple types of graphic in order to provide both a detailed overview of the results (diagnostic accuracy) and to communicate information that can be used to inform clinical practice (predictive value). Work is required to improve graphical displays, to better communicate the utility of a test in clinical practice and the implications of test results for individual patients.


title: The relationship between porcine circovirus 2 antigen score and antibody titre and histology of lymph nodes in 375 euthanased sick and healthy pigs from 113 British pig farms with and without postweaning multisystemic wasting syndrome

text: Abstract Data from a cross-sectional study of 113 British pig herds carried out in 2004 were used to investigate the associations between postweaning multisystemic wasting (PMWS) in pigs and herds and porcine circovirus 2 (PCV2) antigen score and antibody titre, and associated histological signs in lymph nodes. The sensitivity and specificity of published herd definitions for PMWS were tested on the study farms to consider the role of PCV2 in PMWS. Herds were defined as PMWS-affected, -unaffected or -recovered based on current and past postweaning mortality (PWM), grower pigs with clinical signs of rapid wasting, hairiness and pallor and no other known cause of death on the farm. PCV2 antigen and antibody were not used in the definition of PMWS. In each PMWS-affected herd, up to three sick pigs with the clinical signs above and one healthy pig of a similar age were taken for postmortem examination (PME). In all other herds at least one healthy pig was taken for PME. Lymph nodes were analysed for PCV2 antigen and histological changes, and serum samples were analysed for PCV2 antibody. PCV2 antibody was present in all the herds sampled. There was a non-linear association between PCV2 antigen and antibody. There was no association between the presence of high scores of PCV2 antigen in pigs and the presence of high PWM in herds. PCV2 antigen score was significantly higher in sick than healthy pigs within farms, and high PCV2 score was associated with giant cells, coalescence and absence of germinal centres in lymph nodes. These results did not vary by PMWS-affected, -unaffected or -recovered farms. PCV2 antigen was present at high scores in approximately 10% of healthy pigs on all farms. All three herd definitions of PMWS were highly sensitive, defining PMWS-affected herds as affected, but had a specificity ranging from 23% to 43%. We conclude that the current diagnostic tests for PCV2 indicated higher scores of virus in sick pigs but were not useful to define pigs or herds with PMWS. The ubiquity of PCV2 and the lack of specificity of the PCV2 tests indicate that PCV2 may be a necessary but not sufficient cause of PMWS disease. Linking this with the knowledge that the herd breakdowns occurred in a space time epidemic indicates that another infectious co-factor may be necessary for disease to occur.


title: Effects of indoor environmental parameters related to building heating, ventilation, and air conditioning systems on patients' medical outcomes: A review of scientific research on hospital buildings

text: The indoor environment of a mechanically ventilated hospital building controls infection rates as well as influences patients’ healing processes and overall medical outcomes. This review covers the scientific research that has assessed patients’ medical outcomes concerning at least one indoor environmental parameter related to building heating, ventilation, and air conditioning (HVAC) systems, such as indoor air temperature, relative humidity, and indoor air ventilation parameters. Research related to the naturally ventilated hospital buildings was outside the scope of this review article. After 1998, a total of 899 papers were identified that fit the inclusion criteria of this study. Of these, 176 papers have been included in this review to understand the relationship between the health outcomes of a patient and the indoor environment of a mechanically ventilated hospital building. The purpose of this literature review was to summarize how indoor environmental parameters related to mechanical ventilation systems of a hospital building are impacting patients. This review suggests that there is a need for future interdisciplinary collaborative research to quantify the optimum range for HVAC parameters considering airborne exposures and patients’ positive medical outcomes.


Drought, fire, flood and COVID – complex systems and disruption


title: Mendelian resistance to human norovirus infections

text: Abstract Noroviruses have emerged as a major cause of acute gastroenteritis in humans of all ages. Despite high infectivity of the virus and lack of long-term immunity, volunteer and authentic studies has suggested the existence of inherited protective factors. Recent studies have shown that histo-blood group antigens (HBGAs) and in particular secretor status controlled by the α1,2fucosyltransferase FUT2 gene determine susceptibility to norovirus infections, with nonsecretors (FUT2−/−), representing 20% of Europeans, being highly resistant to symptomatic infections with major strains of norovirus. Moreover, the capsid protein from distinct strains shows different HBGA specificities, suggesting a host–pathogen co-evolution driven by carbohydrate–protein interactions.


title: B95: A new respirator for health care personnel

text: BACKGROUND: Respiratory protection relies heavily on user compliance to be effective, but compliance among health care personnel is less than ideal. METHODS: In 2008, the Department of Veterans Affairs formed the Project Better Respiratory Equipment using Advanced Technologies for Healthcare Employees (BREATHE) Working Group, composed of a variety of federal stakeholders, to discuss strategies for improving respirator compliance, including the need for more comfortable respirators. RESULTS: The Working Group developed 28 desirable performance characteristics that can be grouped into 4 key themes: (1) respirators should perform their intended function safely and effectively; (2) respirators should support, not interfere, with occupational activities; (3) respirators should be comfortable and tolerable for the duration of wear; and (4) respiratory protective programs should comply with federal/state standards and guidelines and local policies. As a necessary next step, the Working Group identified the need for a new class of respirators, to be called “B95,” which would better address the unique needs of health care personnel. CONCLUSION: This article summarizes the outputs of the Project BREATHE Working Group and provides a national strategy to develop clinically validated respirator test methods, to promulgate B95 respirator standards, and to invent novel design features, which together will lead to commercialized B95 respirators.


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title: Tegumentary leishmaniasis mimicking visceralization in a cirrhotic patient: atypical cutaneous lesions and local immunological features

text: Tegumentary leishmaniasis (TL) diagnosis is challenging due to the lack of a gold standard diagnostic tool. The diagnosis is significantly harder in regions where visceral leishmaniasis (VL) is also prevalent since immunological tests may present cross-reactivity. A cirrhotic patient from an endemic Brazilian region for TL and VL presented with atypical cutaneous lesions, a usual clinico-laboratory feature of VL (including a positive rk39 test result), but he was diagnosed with TL histopathologically; VL was ruled out by necropsy. Physicians working in co-prevalent areas should be aware of atypical features, unusual clinical course, and unexpected laboratory findings of leishmaniasis.


Pathogen dissemination in health care facilities: what to do when traditional assumptions fail


title: Structural and functional conservation of cis-acting RNA elements in coronavirus 5'-terminal genome regions

text: Abstract Structure predictions suggest a partial conservation of RNA structure elements in coronavirus terminal genome regions. Here, we determined the structures of stem-loops (SL) 1 and 2 of two alphacoronaviruses, human coronavirus (HCoV) 229E and NL63, by RNA structure probing and studied the functional relevance of these putative cis-acting elements. HCoV-229E SL1 and SL2 mutants generated by reverse genetics were used to study the effects on viral replication of single-nucleotide substitutions predicted to destabilize the SL1 and SL2 structures. The data provide conclusive evidence for the critical role of SL1 and SL2 in HCoV-229E replication and, in some cases, revealed parallels with previously characterized betacoronavirus SL1 and SL2 elements. Also, we were able to rescue viable HCoV-229E mutants carrying replacements of SL2 with equivalent betacoronavirus structural elements. The data obtained in this study reveal a remarkable degree of structural and functional conservation of 5′-terminal RNA structural elements across coronavirus genus boundaries.


title: Genetic diversity of avian infectious bronchitis coronavirus strains isolated in China between 1995 and 2004

text: Twenty-six avian infectious bronchitis (IB) viruses (IBV) were isolated from outbreaks in chickens in China between 1995 and 2004. They were characterized by comparison with twenty-six Chinese reference strains and five other IBV strains. Chinese IBVs, which were mainly nephropathogenic, were placed into seven genotypes. Fourteen Chinese IBV isolates were placed in genotype I, having small evolutionary distances from each other. Genotype II included 6 strains that were isolated in the 1990s in China. Genotype III consisted of eight Chinese isolates that showed close relationship with Korean IBV isolates. Another eight IBV isolates clustered in genotype IV and showed larger evolutionary distances. The Massachusetts serotype was present in China in 1990s and was in a separate genotype. Two isolates, HN99 and CK/CH/LHN/00I, which might be a reisolation of vaccine strains, clustered into genotype VI. Four Chinese IBV isolates formed another genotype and showed larger evolutionary distances from other Chinese IBV genotypes (genotype VII). IBVs in same genotypes showed more than 90% amino acid sequence similarities, whereas most of the viruses in different genotypes showed less than 90%. The results showed that IBVs in China came from genetic changes both in IBV populations that existed before the advent of vaccination and in the viruses that were introduced through live vaccines. IBVs showing various genetic differences are cocirculating in China.


title: Synthesis of fluorinated acyclic nucleoside phosphonates with 5-azacytosine base moiety

text: Abstract With respect to the strong antiviral activity of (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine various types of its side chain fluorinated analogues were prepared. The title compound, (S)-1-[3-fluoro-2-(phosphonomethoxy)propyl]-5-azacytosine (FPMP-5-azaC) was synthesised by the condensation reaction of (S)-2-[(diisopropoxyphosphoryl)methoxy)-3-fluoropropyl p-toluenesulfonate with a sodium salt of 5-azacytosine followed by separation of appropriate N 1 and O 2 regioisomers and ester hydrolysis. Transformations of FPMP-5-azaC to its 5,6-dihydro-5-azacytosine counterpart, amino acid phosphoramidate prodrugs and systems with an annelated five-membered imidazole ring, i.e. imidazo [1,2-a][1,3,5]triazine derivatives were also carried out. 1-(2-Phosphonomethoxy-3,3,3-trifluoropropyl)-5-azacytosine was prepared from 5-azacytosine and trifluoromethyloxirane to form 1-(3,3,3-trifluoro-2-hydroxypropyl)-5-azacytosine which was treated with diisopropyl bromomethanephosphonate followed by deprotection of esters. Antiviral activity of all newly prepared compounds was studied. FPMP-5-azaC diisopropyl ester inhibited the replication of herpes viruses with EC50 values that were about three times higher than that of the reference anti-HCMV drug ganciclovir without displaying cytotoxicity.


title: Histophilus somni causes extracellular trap formation by bovine neutrophils and macrophages

text: Abstract Histophilus somni (formerly Haemophilus somnus) is a Gram-negative pleomorphic coccobacillus that causes respiratory, reproductive, cardiac and neuronal diseases in cattle. H. somni is a member of the bovine respiratory disease complex that causes severe bronchopneumonia in cattle. Previously, it has been reported that bovine neutrophils and macrophages have limited ability to phagocytose and kill H. somni. Recently, it was discovered that bovine neutrophils and macrophages produce extracellular traps in response to Mannheimia haemolytica, another member of the bovine respiratory disease complex. In this study, we demonstrate that H. somni also causes extracellular trap production by bovine neutrophils in a dose- and time-dependent manner, which did not coincide with the release of lactate dehydrogenase, a marker for necrosis. Neutrophil extracellular traps were produced in response to outer membrane vesicles, but not lipooligosacchride alone. Using scanning electron microscopy and confocal microscopy, we observed H. somni cells trapped within a web-like structure. Further analyses demonstrated that bovine neutrophils trapped and killed H. somni in a DNA-dependent manner. Treatment of DNA extracellular traps with DNase I freed H. somni cells and diminished bacterial death. Treatment of bovine monocyte-derived macrophages with H. somni cells also caused macrophage extracellular trap formation. These findings suggest that extracellular traps may play a role in the host response to H. somni infection in cattle.


title: Ozone efficacy for the control of airborne viruses: Bacteriophage and norovirus models

text: This study was designed to test the efficacy of an air treatment using ozone and relative humidity (RH) for the inactivation of airborne viruses. Four phages (φX174, PR772, MS2 and φ6) and one eukaryotic virus (murine norovirus MNV-1) were exposed to low ozone concentrations (1.23 ppm for phages and 0.23 ppm for MNV-1) and various levels of RH for 10 to 70 minutes. The inactivation of these viruses was then assessed to determine which of the tested conditions provided the greatest reduction in virus infectivity. An inactivation of at least two orders of magnitude for φX174, MS2 and MNV-1 was achieved with an ozone exposure of 40 minutes at 85% RH. For PR772 and φ6, exposure to the reference condition at 20% RH for 10 minutes yielded the same results. These findings suggest that ozone used at a low concentration is a powerful disinfectant for airborne viruses when combined with a high RH. Air treatment could therefore be implemented inside hospital rooms ventilated naturally.


title: Neutrophil Dysfunction in the Airways of Children with Acute Respiratory Failure Due to Lower Respiratory Tract Viral and Bacterial Coinfections

text: Neutrophils are recruited to the airways of patients with acute respiratory distress syndrome (ARDS) where they acquire an activated pro-survival phenotype with an enhanced respiratory burst thought to contribute to ARDS pathophysiology. Our in vitro model enables blood neutrophil transepithelial migration into cell-free tracheal aspirate fluid from patients to recapitulate the primary airway neutrophil phenotype observed in vivo. Neutrophils transmigrated through our model toward airway fluid from children with lower respiratory viral infections coinfected with bacteria had elevated levels of neutrophil activation markers but paradoxically exhibited an inability to kill bacteria and a defective respiratory burst compared with children without bacterial coinfection. The airway fluid from children with bacterial coinfections had higher levels of neutrophil elastase activity, as well as myeloperoxidase levels compared to children without bacterial coinfection. Neutrophils transmigrated into the aspirate fluid from children with bacterial coinfection showed decreased respiratory burst and killing activity against H. influenzae and S. aureus compared to those transmigrated into the aspirate fluid from children without bacterial coinfection. Use of a novel transmigration model recapitulates this pathological phenotype in vitro that would otherwise be impossible in a patient, opening avenues for future mechanistic and therapeutic research.


title: Evaluation of a Carbapenem-Saving Strategy Using Empirical Combination Regimen of Piperacillin-Tazobactam and Amikacin in Hemato-Oncology Patients

text: We implemented a carbapenem-saving strategy in hemato-oncology patients from 2013, using an empirical combination of piperacillin-tazobactam and amikacin for high-risk hemato-oncology patients with febrile neutropenia, who remain hemodynamically unstable > 72 hours despite initial cefepime treatment. All-cause mortality was not different between the two periods (6.54 and 6.57 deaths per 1,000 person-day, P = 0.926). Group 2 carbapenem use significantly decreased after strategy implementation (78.43 vs. 67.43 monthly days of therapy, P = 0.018), while carbapenem-resistant gram-negative bacilli did not show meaningful changes during the study period. Our carbapenem-saving strategy could effectively suppress carbapenem use without an increase of overall mortality.


title: Fluid Therapy for Pediatric Patients

text: Young puppies and kittens have unique physiologic needs in regards to fluid therapy, which must address hydration, vascular fluid volume, electrolyte disturbances, or hypoglycemia. Pediatric patients have a higher fluid requirement compared with adults and can rapidly progress from mild dehydration to hypovolemia. Simultaneously, their small size makes overhydration a real possibility. Patient size complicates fluid administration because catheters used in larger pets may be difficult to place. Routes of fluid administration used in the neonate or pediatric patient include oral, subcutaneous, intraperitoneal, intraosseous, and intravenous. Clinicians should be aware of the pros and cons of each route.


title: Health care workers indicate ill preparedness for Ebola Virus Disease outbreak in Ashanti Region of Ghana

text: BACKGROUND: The recent Ebola Virus Disease (EVD) epidemic that hit some countries in West Africa underscores the need to train front line high-risk health workers on disease prevention skills. Although Ghana did not record (and is yet to) any case, and several health workers have received numerous training schemes, there is no record of any study that assessed preparedness of healthcare workers (HCWS) regarding EVD and any emergency prone disease in Ghana. We therefore conducted a hospital based cross sectional study involving 101 HCWs from two facilities in Kumasi, Ghana to assess the level of preparedness of HCWs to respond to any possible EVD. METHODS: We administered a face-to-face questionnaire using an adapted WHO (2015) and CDC (2014) Checklist for Ebola Preparedness and assessed overall knowledge gaps, and preparedness of the Ghanaian HCWs in selected health facilities of the Ashanti Region of Ghana from October to December 2015. RESULTS: A total 92 (91.09%) HCWs indicated they were not adequately trained to handle an EVD suspected case. Only 25.74% (n = 26) considered their facilities sufficiently equipped to handle and manage EVD patients. When asked which disinfectant to use after attending to and caring for a suspected patient with EVD, only 8.91% (n = 9) could correctly identify the right disinfectant (χ(2) = 28.52, p = 0.001). CONCLUSION: Our study demonstrates poor knowledge and ill preparedness and unwillingness of many HCWs to attend to EVD. Beyond knowledge acquisition, there is the need for more training from time to time to fully prepare HCWs to handle any possible EVD case.


title: Cost Benefit Analysis of Limited Reopening Relative to a Herd Immunity Strategy or Shelter in Place for SARS-CoV-2 in the United States

text: BACKGROUND: Fierce debate about the health and financial tradeoffs presented by different COVID-19 pandemic mitigation strategies highlights the need for rigorous quantitative evaluation of policy options. OBJECTIVE: To quantify the economic value of the costs and benefits of a policy of continued limited reopening with social distancing relative to alternative COVID-19 response strategies in the United States. DESIGN: We estimate the number and value of quality-adjusted life-years (QALY) gained from mortality averted, with a value of $125,000 per QALY, and compare these benefits to the associated costs in terms of plausible effects on US GDP under a policy of continued limited reopening with social distancing relative to a policy of full reopening toward herd immunity. Using the same QALY value assumptions, we further evaluate cost-effectiveness of a return to Shelter-in-Place relative to a policy of limited reopening. SETTING: United States MEASUREMENTS: QALY and cost as percent of GDP of limited reopening with continued social distancing relative to a strategy of full reopening aimed at achieving herd immunity; a limited reopening “budget” measured in the number of months before this strategy fails to demonstrate cost-effectiveness relative to a full reopening; a shelter-in-place “threshold” measured in the number of lives saved at which a month of sheltering in place demonstrates cost effectiveness relative to the limited reopening strategy. RESULTS: QALY benefits from mortality averted by continued social distancing and limited reopening relative to a policy of full reopening exceed projected GDP costs if an effective vaccine or therapeutic can be developed within 11.1 months from late May 2020. White House vaccine projections fall within this date, supporting a partial reopening strategy. One month of shelter-in-place restrictions provides QALY benefits from averted mortality that exceed the associated GDP costs relative to limited reopening if the restrictions prevent at least 154,586 additional COVID-19 deaths over the course of the pandemic. Current models of disease progression suggest that limited reopening will not cause this many additional deaths, again supporting a limited reopening strategy. LIMITATION: Limited horizon of COVID-19 mortality projections; infection fatality ratio stable across strategies, ignoring both the potential for ICU overload to increase mortality and the deployment of partially effective therapeutics to decrease mortality; effect on GDP modeled as constant within a given phase of the pandemic; accounts for age and sex distribution of QALYs, but not effect of comorbidities; only considers impact from QALY lost due to mortality and from changes in GDP, excluding numerous other considerations, such as non-fatal COVID-19 morbidity, reduced quality of life caused by prolonged social distancing, or educational regression associated with prolonged school closures and restrictions. CONCLUSIONS: A limited reopening to achieve partial mitigation of COVID-19 is cost effective relative to a full reopening if an effective therapeutic or vaccine can be deployed within 11.1 months of late May 2020. One additional month of shelter-in-place restrictions should only be imposed if it saves at least 154,586 lives per month before the development of an effective therapeutic or vaccine relative to limited reopening.


Emerging infectious agents and the nation’s blood supply: responding to potential threats in the 21st century


title: Identification of Viral Peptide Fragments for Vaccine Development

text: We report a simple method for identifying foldable viral surface protein fragments in a random but systematic manner. The method involves digestion and reassembly of a target gene to generate a pool of smaller DNA fragments with random ends but controllable lengths, followed by screening for foldable fragments using green fluorescent protein (GFP) as a folding reporter. The surface glycoproteins of SARS-CoV and HIV-1 were used as model proteins. Two foldable fragments for SARS-CoV spike protein were identified, which coincide with various anti-SARS-CoV peptides. A similar treatment of the HIV-1 gp120 yielded a number of fragments that are associated with the critical CD4 binding site, or the partially buried CCR5 binding site of the protein. The random dissection approach described here should be applicable to other viral proteins for isolating soluble viral surface protein fragments, and may provide alternatives to the full-length proteins (subunits) or linear short peptides in search for antigen or vaccine candidates.