title: Th17 serum cytokines in relation to laboratory‐confirmed respiratory viral infection: A pilot study

text: BACKGROUND: Th17 cytokines are associated with modulation of inflammation and may be beneficial in clearing influenza infection in experimental models. The Th17 cytokine profile was evaluated in a pilot study of respiratory virus infections. METHODS: Consecutive patients with symptoms of respiratory tract infection visiting the emergency department of a tertiary care hospital during the winter influenza season of 2014 to 2015 were evaluated. CLART PneumoVir kit, (GENOMICA, Madrid, Spain) was used for viral detection of all known respiratory viruses. Th17 cytokine profile was evaluated with the MILLIPLEX MAP Human TH17 Magnetic Bead Panel (Millipore Corp., Billerica, MA). Correlation of the TH17 profile with viral detection was performed with univariate and multivariate analysis. RESULTS: Seventy‐six patients were evaluated (median age 56 years, 51.3% female); a respiratory virus was identified in 60 (78.9%) patients; 45% had confirmed influenza. Influenza A (H3N2) correlated with higher levels of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), interleukin 1β (IL‐1β), IL‐17A, IL‐17E, IL‐17F, IL‐21, IL‐22, and IL‐23 (P < 0.05 by analysis of variance [ANOVA]) compared with respiratory syncytial virus (RSV). Parainfluenza virus (PIV) similarly had higher levels of GM‐CSF, IL‐1b, IL‐17A, IL‐22 compared with those detected in RSV, influenza B and any other virus infection ( P < 0.05; ANOVA). Increasing age (β‐coefficient = 1.11, 95% CI, 1.04‐1.2, P < 0.01) as well as IL‐17A levels (β‐coefficient = 1.03, 95% CI, 1.001‐1.05, P = 0.04) predicted hospital admission. CONCLUSION: Main Th17 cell effector cytokines were upregulated in laboratory‐confirmed A(H3N2) influenza and PIV. Excessive amounts of Th17 cytokines may be implicated in the pathogenesis and immune control of acute influenza and PIV infection in humans and may predict the severity of disease.


title: Cryptogenic organizing pneumonia

text: Cryptogenic organizing pneumonia is a rare, distinct disorder that is sufficiently different from the other diseases in the group of idiopathic interstitial pneumonias to be designated as a separate entity. In its most typical presentation, it is characterized by dyspnea and cough, with multiple patchy alveolar opacities on pulmonary imaging. Definite diagnosis is obtained by the finding of buds of granulation tissue in the distal airspaces at lung biopsy. No cause (as infection, drug reaction, or associated disease as connective tissue disease) is found. Corticosteroid treatment is rapidly effective, but relapses are common on reducing or stopping treatment.


COVID19 - moving forward


title: Non‐parametric estimation of the case fatality ratio with competing risks data: an application to Severe Acute Respiratory Syndrome (SARS)

text: For diseases with some level of associated mortality, the case fatality ratio measures the proportion of diseased individuals who die from the disease. In principle, it is straightforward to estimate this quantity from individual follow‐up data that provides times from onset to death or recovery. In particular, in a competing risks context, the case fatality ratio is defined by the limiting value of the sub‐distribution function, F (1)(t) = Pr(T ⩽t and J = 1), associated with death, as t → ∞, where T denotes the time from onset to death (J = 1) or recovery (J = 2). When censoring is present, however, estimation of F (1)(∞) is complicated by the possibility of little information regarding the right tail of F (1), requiring use of estimators of F (1)(t(*)) or F (1)(t (*))/(F (1)(t (*))+F (2)(t (*))) where t (*) is large, with F (2)(t) = Pr(T ⩽t and J = 2) being the analogous sub‐distribution function associated with recovery. With right censored data, the variability of such estimators increases as t (*) increases, suggesting the possibility of using estimators at lower values of t (*) where bias may be increased but overall mean squared error be smaller. These issues are investigated here for non‐parametric estimators of F (1) and F (2). The ideas are illustrated on case fatality data for individuals infected with Severe Acute Respiratory Syndrome (SARS) in Hong Kong in 2003. Copyright © 2006 John Wiley & Sons, Ltd.


title: Short-term PsychoEducation for Carers To Reduce Over Medication of people with intellectual disabilities (SPECTROM): study protocol

text: INTRODUCTION: Psychotropic medications that are primarily licenced for the treatment of psychiatric disorders are used widely (32%–85%) among people with intellectual disabilities (ID) often for the management of problem (challenging) behaviour in the absence of a psychiatric disorder. Care staff play a pivotal role in the prescribing process. Currently, no staff training programme exists to address the issue of overprescribing of psychotropic medication in people with ID, thus highlighting an urgent need for developing a psychoeducational programme (PEP) specifically designed to address this issue. We propose to develop a PEP for care staff using the methodology described in the UK Medical Research Council guide for complex interventions. METHODS AND ANALYSIS: The development of the PEP will involve (1) gathering information on available relevant training programmes, (2) running four focus groups with care staff and other professionals to establish the content and format of the PEP, and (3) organising a co-design event involving all relevant stakeholders to discuss the format of the PEP. A core project team will develop the PEP under guidance from the PEP Development Group which will consist of 10–12 relevant stakeholder representatives. Feedback from selected stakeholders on a draft PEP will allow us to refine the PEP before implementation. The PEP will have web-based modules supplemented by face to face training sessions. When the final draft is ready, we will field test the PEP on six to eight care staff from community care homes for people with ID. After completing the field test, we will run a focus group involving participants in the PEP to get feedback on the PEP. ETHICS AND DISSEMINATION: Ethics approval for this study was waived by the UK Health Regulatory Authority as the study does not collect any patient related information and only include care staff outside the UK NHS. This will be the first ever such universally freely available PEP supported by training manual and slides.


title: Competitive Pricing of Substitute Products under Supply Disruption

text: There has been an increased interest in optimizing pricing and sourcing decisions under supplier competition with supply disruptions. In this paper, we conduct an analytical game-theoretical study to examine the effects of supply capacity disruption timing on pricing decisions for substitute products in a two-supplier one-retailer supply chain setting. We investigate whether the timing of disruption may significantly impact the optimal pricing strategy of the retailer. We derive the optimal pricing strategy and ordering levels with both disruption timing and product substitution. By exploring both the Nash and Stackelberg games, we find that the order quantity with the disrupted supplier depends on price leadership and it tends to increase when the non-disrupted supplier is the leader. Moreover, the equilibrium market retail prices are higher under higher levels of disruption for the Nash game, compared to the Stackelberg game. We also uncover that the non-disruptive supplier can always charge the highest wholesale price if the disruption occurs before orders are received. This highlights the critical role of order timing. The insights can help operations managers to proper design risk mitigation ordering strategies and re-design the supply contracts in the presence of product substitution under supply disruptions.


title: G-quadruplex-interacting compounds alter latent DNA replication and episomal persistence of KSHV

text: Kaposi's sarcoma associated herpesvirus (KSHV) establishes life-long latent infection by persisting as an extra-chromosomal episome in the infected cells and by maintaining its genome in dividing cells. KSHV achieves this by tethering its epigenome to the host chromosome by latency associated nuclear antigen (LANA), which binds in the terminal repeat (TR) region of the viral genome. Sequence analysis of the TR, a GC-rich DNA element, identified several potential Quadruplex G-Rich Sequences (QGRS). Since quadruplexes have the tendency to obstruct DNA replication, we used G-quadruplex stabilizing compounds to examine their effect on latent DNA replication and the persistence of viral episomes. Our results showed that these G-quadruplex stabilizing compounds led to the activation of dormant origins of DNA replication, with preferential bi-directional pausing of replications forks moving out of the TR region, implicating the role of the G-rich TR in the perturbation of episomal DNA replication. Over time, treatment with PhenDC3 showed a loss of viral episomes in the infected cells. Overall, these data show that G-quadruplex stabilizing compounds retard the progression of replication forks leading to a reduction in DNA replication and episomal maintenance. These results suggest a potential role for G-quadruplex stabilizers in the treatment of KSHV-associated diseases.


I08 Development of transfusion medicine in Europe A challenge for physicians, scientists and politicians


title: Sequential biogenesis of host cell membrane rearrangements induced by hepatitis C virus infection

text: Like most positive-strand RNA viruses, hepatitis C virus (HCV) forms a membrane-associated replication complex consisting of replicating RNA, viral and host proteins anchored to altered cell membranes. We used a combination of qualitative and quantitative electron microscopy (EM), immuno-EM, and the 3D reconstruction of serial EM sections to analyze the host cell membrane alterations induced by HCV. Three different types of membrane alteration were observed: vesicles in clusters (ViCs), contiguous vesicles (CVs), and double-membrane vesicles (DMVs). The main ultrastructural change observed early in infection was the formation of a network of CVs surrounding the lipid droplets. Later stages in the infectious cycle were characterized by a large increase in the number of DMVs, which may be derived from the CVs. These DMVs are thought to constitute the membranous structures harboring the viral replication complexes in which viral replication is firmly and permanently established and to protect the virus against double-stranded RNA-triggered host antiviral responses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00018-012-1213-0) contains supplementary material, which is available to authorized users.


title: Introduction of Asian canine parvovirus in Europe through dog importation

text: Canine parvovirus (CPV) is an important infectious agent of domestic and wild carnivores, responsible for severe and often fatal haemorrhagic gastroenteritis and leukopenia. This paper reports the genomic characterization of a CPV strain collected from a dog recently imported to Italy from Thailand. The virus was detected in all tissue samples collected. The whole genome encompassing the two open reading frames encoding for non‐structural (NS1/NS2) and structural (VP1/VP2) proteins was amplified and sequenced. On the basis of genetic analysis of the VP2 gene, the isolate was characterized as CPV‐2c, but it presented genetic signatures typical of Asian strains. Sequence analysis revealed the presence of amino acid changes never observed in European CPV‐2c strains (NS1: Ile60Val, Tyr544Phe, Glu545Val, Leu630Pro; VP2: Ala5Gly, Phe267Tyr, Tyr324Ile, Gln370Arg). By phylogenetic analysis of full‐length VP2 gene, the analysed strain clustered together with Asian viruses. Therefore, a possible introduction of the virus from Asia through the imported dog was suggested, thus confirming the important role of movement of dogs in the global spread of viruses. In addition, full‐length genome analysis could help better trace the spread of canine viruses through different continents.


title: Stay Strong: Aboriginal leaders deliver COVID‐19 health messages

text: COVID-19 caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) has constituted a pandemic unparalleled in modern history. The spread, case numbers, and socioeconomic consequences have resulted in pandemic control measures attempting to "flatten the curve". Australia recorded its first case of COVID-19 on the 25th of January 2020. The federal government responded to the virus spread by escalating human movement controls: during February any person arriving from countries with high rates of infection were expected to quarantine for 14 days in a third country before entering Australia.


title: Intravenous infusion of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells as a potential treatment for patients with COVID-19 pneumonia

text: The novel coronavirus disease 2019 (COVID-19) has grown to be a global public health emergency since patients were first detected in Wuhan, China. Thus far, no specific drugs or vaccines are available to cure the patients with COVID-19 infection. The immune system and inflammation are proposed to play a central role in COVID-19 pathogenesis. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. Intravenous infusion of MSCs has shown promising results in COVID-19 treatment. Here, we report a case of a severe COVID-19 patient treated with human umbilical cord Wharton’s jelly-derived MSCs (hWJCs) from a healthy donor in Liaocheng People’s Hospital, China, from February 24, 2020. The pulmonary function and symptoms of the patient with COVID-19 pneumonia was significantly improved in 2 days after hWJC transplantation, and recovered and discharged in 7 days after treatment. After treatment, the percentage and counts of lymphocyte subsets (CD3(+), CD4(+), and CD8(+) T cell) were increased, and the level of IL-6, TNF-α, and C-reactive protein is significantly decreased after hWJC treatment. Thus, the intravenous transplantation of hWJCs was safe and effective for the treatment of patients with COVID-19 pneumonia, especially for the patients in a critically severe condition. This report highlights the potential of hWJC infusions as an effective treatment for COVID-19 pneumonia.


Interpretation of the 7th edition of the “diagnosis and treatment guidelines of coronavirus disease 2019 in China”: Progress and challenges


title: Feature Selection Methods for Identifying Genetic Determinants of Host Species in RNA Viruses

text: Despite environmental, social and ecological dependencies, emergence of zoonotic viruses in human populations is clearly also affected by genetic factors which determine cross-species transmission potential. RNA viruses pose an interesting case study given their mutation rates are orders of magnitude higher than any other pathogen – as reflected by the recent emergence of SARS and Influenza for example. Here, we show how feature selection techniques can be used to reliably classify viral sequences by host species, and to identify the crucial minority of host-specific sites in pathogen genomic data. The variability in alleles at those sites can be translated into prediction probabilities that a particular pathogen isolate is adapted to a given host. We illustrate the power of these methods by: 1) identifying the sites explaining SARS coronavirus differences between human, bat and palm civet samples; 2) showing how cross species jumps of rabies virus among bat populations can be readily identified; and 3) de novo identification of likely functional influenza host discriminant markers.


title: Twelve Essentials of Science-based Policy

text: This article presents a systematic framework of 12 essentials, or basic elements, of science-based policy. The 12 essentials are grouped into three categories, or areas, as follows: 1) knowledge generation, which includes credible design, accurate data, sound analysis, and comprehensive synthesis; 2) knowledge exchange, which includes relevant content, appropriate translation, timely dissemination, and modulated release; and 3) knowledge uptake, which includes accessible information, readable message, motivated user, and rewarding outcome.


title: Molecular detection of human rhinoviruses in respiratory samples: a comparison of Taqman probe-, SYBR green I- and BOXTO-based real-time PCR assays

text: BACKGROUND: Human Rhinoviruses (HRV) are major causative agents of acute respiratory tract infections in all age group and important contributing factors of childhood morbidity and mortality. Clinical presentation is poorly specific and the great antigenic and genetic variability of HRVs renders the biological diagnosis complex. Here, we have evaluated several molecular diagnostic protocols, including Taqman probe-based and intercalating agent-based RT-PCR assays. METHODS: 5,627 respiratory samples sent to the laboratory of Virology of the University Hospitals of Marseille, France, from March 2011 to February 2012, were tested using a real-time RT-PCR assay in the 5’NCR of the rhinoviral genome that associated a Taqman probe and the detection of DNA-BOXTO-dye complexes. A sample of 500 BOXTO-positive samples were further tested using the same probe assay (without BOXTO), and a SYBR Green assay (using the same amplification primers). The specific amplification of HRV sequences was assessed by NGS amplicon sequencing. RESULTS: The Taqman probe RT-PCR assay identified 696/5,627 samples (12,4%) as HRV-positive. BOXTO-positive samples included all probe-positive samples and 1,913 additional samples, of which only 24.3% were confirmed by sequencing. The SYBR Green assay was more specific (16/550 samples were probe-negative/SYBR Green-positive, all confirmed by 5′NCR sequencing), but 3/500 samples were probe-positive/SYBR Green-negative. CONCLUSIONS: Our results highlight the difficulty in detecting HRVs in clinical samples using a single molecular detection system. Amongst the 3 systems tested, the best compromise was obtained with the SYBR Green assay, which, by comparison with our probe-based assay provided an improved sensitivity without altering the detection specificity. Interestingly, a majority of probe-negative/BOXTO- or SYBR Green-positive samples were not associated with mutations in the sequence targeted by the probe. Sequence-based modifications of the secondary structure of the HRV 5′NCR may be associated with a limited access to the probe hybridisation region. Further investigations may identify a test combining a probe based- and an intercalating agent-based detection, which will significantly improve the diagnosis of HRV infections.


title: Intersecting U.S. Epidemics: COVID-19 and Lack of Health Insurance

text: The COVID-19 pandemic has led to an unprecedented surge in unemployment in the United States. For many, job loss carries the added sting of losing health insurance. The authors discuss the problem of lack of health insurance during a time of risk for severe illness and offer potential solutions that policymakers should consider to mitigate harm.


title: The psychological impact of COVID-19 on the mental health in the general population

text: As a result of the emergence of coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Chinese city of Wuhan, a situation of socio-economic crisis and profound psychological distress rapidly occurred worldwide. Various psychological problems and important consequences in terms of mental health including stress, anxiety, depression, frustration, uncertainty during COVID-19 outbreak emerged progressively. This work aimed to comprehensively review the current literature about the impact of COVID-19 infection on the mental health in the general population. The psychological impact of quarantine related to COVID-19 infection has been additionally documented together with the most relevant psychological reactions in the general population related to COVID-19 outbreak. The role of risk and protective factors against the potential to develop psychiatric disorders in vulnerable individuals has been addressed as well. The main implications of the present findings have been discussed.


COVID‐19: Emerging compassion, courage and resilience in the face of misinformation and adversity


title: The Impact of COVID-19 Partial Lockdown on Primary Pollutant Concentrations in the Atmosphere of Rio de Janeiro and São Paulo Megacities (Brazil)

text: As COVID-19 spread all over the world, most of the countries adopted some kind of restrictions to avoid the collapse of health systems. In Brazil, São Paulo and Rio the Janeiro, the two most populated cities in the country, were the first to determine social distancing. In this study, the impact of the social distancing measures on the concentrations of the three main primary air pollutants (PM(10), NO(2) and CO) was analyzed. CO levels showed the most significant reductions (up to 100%) since it is related to light-duty vehicular emissions. NO(2) also showed reductions (9.1%–41.8%) while PM(10) levels were only reduced in the 1st lockdown week. The decrease of pollutants was not directly proportional to the vehicular flux reduction, because it depends on other factors such as the transport of air masses from industrial and rural areas. The differences observed can be explained considering the fleet characteristics in the two cities and the response of the population to the social distancing recommendations.


title: Uso de ribavirina en virus distintos de la hepatitis C. Una revisión de la evidencia

text: Ribavirin is a molecule with antiviral activity against different viruses. In clinical practice, it has made its niche almost exclusively for the treatment of the hepatitis C virus. However, there are other diseases in which it could be of benefit and it has the advantage of being suitable for oral, intravenous and inhaled administration. We conducted a review of the indications of the main drug agencies (Spanish, European and American) and other possible indications, mainly haemorrhagic fevers and coronavirus.


title: Virus detection and identification using random multiplex (RT)-PCR with 3'-locked random primers

text: BACKGROUND: PCR-based detection and identification of viruses assumes a known, relatively stable genome. Unfortunately, high mutation rates may lead to extensive changes in viral nucleic acid sequences making dedicated PCR primer use problematic. Furthermore, in bioterrorism, viral consensus sequences can be genetically modified as a countermeasure to RT-PCR and DNA chip detection. Accordingly, there is a great need for the development of rapid and universal virus detection and identification technologies. RESULTS: We report herein that viral genomic DNA or RNA can be separated from host nucleic acids in plasma by filtration and nuclease digestion, and randomly amplified in a single PCR using a mixture of primers designed to be resistant to primer-dimer amplification (5'-VVVVVVVVAA-3', V = A, G or C; 3(8 )or 6561 primers). We have termed this novel PCR method Random Multiplex (RT)-PCR since hundreds of overlapping PCR amplifications occur simultaneously. Using this method, we have successfullydetected and partially sequenced 3 separate viruses in human plasma without using virus-specific reagents (i.e., Adenovirus Type 17, Coxsackievirus A7, and Respiratory Syncytial Virus B). The method is sensitive to ~1000 genome equivalents/ml and may represent the fastest means of detection of unknown viruses. CONCLUSION: These studies suggest that the further development of random multiplex (RT)-PCR may lead to a diagnostic assay that can universally detect viruses in donated blood products as well as in patients suffering with idiopathic disease states of possible viral etiology.


title: Warned, but Not Well Armed: Preventing Viral Upper Respiratory Infections in Households

text: ABSTRACT The purpose of this state‐of‐the‐science review was to identify strategies and household‐level interventions for public health nurses to help prevent the acquisition and spread of viral upper respiratory infections (URI) in the community. Even though viral URI are a major global economic and social problem, surprisingly little research has been conducted to attempt to prevent them or reduce their transmission, probably because URI (with the exception of epidemic influenza) are generally considered to be mild and self‐limited. Based on the research to date, public health nurses can use several promising strategies for prevention: (a) provide more tailored educational messages regarding preventive strategies such as vaccination, hand hygiene, spatial separation of infected household members, avoidance of antibiotics to treat viral URI, and environmental cleaning (e.g., for toys or other shared items), which are delivered personally rather than passively (e.g., pamphlets placed in a waiting room); (b) use each patient encounter in any setting to encourage influenza vaccination for relevant risk groups; (c) encourage use of alcohol hand sanitizers by household members during the cold and flu season; and (d) provide opportunities for skill development for adult and child household members (e.g., cover your cough, when to seek care or an antibiotic).


title: Elevated thrombopoietin and platelet indices confirm active thrombopoiesis but fail to predict clinical severity of puumala hantavirus infection

text: We evaluated the mechanisms of thrombocytopenia and procoagulant changes in relation with clinical variables in a cohort of patients with acute hantavirus disease. Blood samples of 33 prospectively recruited, consecutive, hospitalized patients with acute Puumala virus–induced hemorrhagic fever with renal syndrome (HFRS) were collected acutely and at the recovery visit (control). Serum thrombopoietin (TPO) and activity of plasma microparticles (MPs) from various cell sources were measured with enzyme-linked immunosorbent assay-based methods. The results were related to data on platelet indices and functions, coagulation variables, and clinical disease. Serum TPO was nearly 4-fold higher acutely compared with the control (median 207 pg/mL, range 56–1258 pg/mL vs. median 58 pg/mL, range 11–241 pg/mL, P < 0.001) and coincided with high mean platelet volume (MPV) and immature platelet fraction (IPF%). Prothrombin fragments and D-dimer were high acutely compared with the control (F1 + 2 median 704 pmol/L, range 284–1875 pmol/L vs. median 249 pmol/L, range 118–556 pmol/L, P < 0.001; d-dimer median 2.8 mg/L, range 0.6–34.0 mg/L vs. median 0.4 mg/L, range 0.2–1.1 mg/L, P < 0.001), and associated with low platelet count and severe acute kidney injury (AKI). MPs’ procoagulant activity was high acutely only among patients with mild AKI (plasma creatinine below the median at the time of the measurement). Upregulated TPO together with high MPV and IPF% confirm active thrombopoiesis, but do not predict severity of HFRS. Simultaneously, elevated prothrombin fragments and d-dimer suggest increased consumption of platelets in patients with severe AKI. Activity of platelet-derived MPs in HFRS should be studied with flow cytometry in a larger cohort of patients.


title: Hemorrhagic encephalopathy associated with COVID-19

text: The mechanisms for neurological complications of COVID-19, the disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are not yet well understood. We present a critically ill man with a COVID-19-associated hemorrhagic encephalopathy. SARS-CoV-2 RNA was not detected in cerebrospinal fluid (CSF) or blood. CSF analyses suggested dysregulation of pro-inflammatory cytokine pathways, particularly tumor necrosis factor-α and interleukin-6, consistent with a cytokine release syndrome. The patient gradually recovered with supportive care and neurological rehabilitation. Awareness of this clinical entity may facilitate the identification of patients with a potentially remediable cause of encephalopathy in COVID-19.


Socioeconomical Transformation and Mental Health Impact by the COVID-19's ultimate VUCA Era: Toward the New Normal, the New Japan, and the New World


title: Mutant p53 as an Antigen in Cancer Immunotherapy

text: The p53 tumor suppressor plays a pivotal role in cancer and infectious disease. Many oncology treatments are now calling on immunotherapy approaches, and scores of studies have investigated the role of p53 antibodies in cancer diagnosis and therapy. This review summarizes the current knowledge from the preliminary evidence that suggests a potential role of p53 as an antigen in the adaptive immune response and as a key monitor of the innate immune system, thereby speculating on the idea that mutant p53 antigens serve as a druggable targets in immunotherapy. Except in a few cases, the vast majority of published work on p53 antibodies in cancer patients use wild-type p53 as the antigen to detect these antibodies and it is unclear whether they can recognize p53 mutants carried by cancer patients at all. We envision that an antibody targeting a specific mutant p53 will be effective therapeutically against a cancer carrying the exact same mutant p53. To corroborate such a possibility, a recent study showed that a T cell receptor-like (TCLR) antibody, initially made for a wild-type antigen, was capable of discriminating between mutant p53 and wild-type p53, specifically killing more cancer cells expressing mutant p53 than wild-type p53 in vitro and inhibiting the tumour growth of mice injected with mutant p53 cancer cells than mice with wild-type p53 cancer cells. Thus, novel antibodies targeting mutant p53, but not the wild-type isoform, should be pursued in preclinical and clinical studies.


title: Repurposing approved drugs as inhibitors of SARS-CoV-2 S-protein from molecular modeling and virtual screening

text: Herein, molecular modeling techniques were used with the main goal to obtain candidates from a drug database as potential targets to be used against SARS-CoV-2. This novel coronavirus, responsible by the COVID-19 outbreak since the end of 2019, became a challenge since there is not vaccine for this disease. The first step in this investigation was to solvate the isolated S-protein in water for molecular dynamics (MD) simulation, being observed a transition from “up” to “down” conformation of receptor-binding domain (RBD) of the S-protein with angle of 54.3 and 43.0 degrees, respectively. The RBD region was more exposed to the solvent and to the possible drugs due to its enhanced surface area. From the equilibrated MD structure, virtual screening by docking calculations were performed using a library contained 9091 FDA approved drugs. Among them, 24 best-scored ligands (14 traditional herbal isolate and 10 approved drugs) with the binding energy below –8.1 kcal/mol were selected as potential candidates to inhibit the SARS-CoV-2 S-protein, preventing the human cell infection and their replication. For instance, the ivermectin drug (present in our list of promise candidates) was recently used successful to control viral replication in vitro. MD simulations were performed for the three best ligands@S-protein complexes and the binding energies were calculated using the MM/PBSA approach. Overall, it is highlighted an important strategy, some key residues, and chemical groups which may be considered on clinical trials for COVID-19 outbreak.


title: Impact of air pollution on educational attainment for respiratory health treated students: A cross sectional data linkage study

text: INTRODUCTION: There is some evidence that exam results are worse when students are acutely exposed to air pollution. Studies investigating the association between air pollution and academic attainment have been constrained by small sample sizes. METHODS: Cross sectional educational attainment data (2009–2015) from students aged 15–16 years in Cardiff, Wales were linked to primary health care data, modelled air pollution and measured pollen data, and analysed using multilevel linear regression models. Annual cohort, school and individual level confounders were adjusted for in single and multi-pollutant/pollen models. We stratified by treatment of asthma and/or Seasonal Allergic Rhinitis (SAR). RESULTS: A unit (10μg/m3) increase of short-term exposure to NO(2) was associated with 0.044 (95% CI: −0.079, −0.008) reduction of standardised Capped Point Score (CPS) after adjusting for individual and household risk factors for 18,241 students. This association remained statistically significant after controlling for other pollutants and pollen. There was no association of PM(2.5), O(3), or Pollen with standardised CPS remaining after adjustment. We found no evidence that treatment for asthma or SAR modified the observed NO(2) effect on educational attainment. CONCLUSION: Our study showed that short-term exposure to traffic-related air pollution, specifically NO(2,) was associated with detrimental educational attainment for students aged 15–16. Longitudinal investigations in different settings are required to confirm this possible impact and further work may uncover the long-term economic implications, and degree to which impacts are cumulative and permanent.


title: Enterovirus 71 Induces Mitochondrial Reactive Oxygen Species Generation That is Required for Efficient Replication

text: Redox homeostasis is an important host factor determining the outcome of infectious disease. Enterovirus 71 (EV71) infection has become an important endemic disease in Southeast Asia and China. We have previously shown that oxidative stress promotes viral replication, and progeny virus induces oxidative stress in host cells. The detailed mechanism for reactive oxygen species (ROS) generation in infected cells remains elusive. In the current study, we demonstrate that mitochondria were a major ROS source in EV71-infected cells. Mitochondria in productively infected cells underwent morphologic changes and exhibited functional anomalies, such as a decrease in mitochondrial electrochemical potential ΔΨ(m) and an increase in oligomycin-insensitive oxygen consumption. Respiratory control ratio of mitochondria from infected cells was significantly lower than that of normal cells. The total adenine nucleotide pool and ATP content of EV71-infected cells significantly diminished. However, there appeared to be a compensatory increase in mitochondrial mass. Treatment with mito-TEMPO reduced eIF2α phosphorylation and viral replication, suggesting that mitochondrial ROS act to promote viral replication. It is plausible that EV71 infection induces mitochondrial ROS generation, which is essential to viral replication, at the sacrifice of efficient energy production, and that infected cells up-regulate biogenesis of mitochondria to compensate for their functional defect.


title: SARS: responding to an unknown virus

text: The severe acute respiratory syndrome (SARS) is an emerging infection caused by a novel coronavirus which first appeared in southern China at the end of 2002. In early 2003, through a single incident, it spread to Hong Kong, Singapore, Canada and Vietnam. For busy clinicians in large public hospitals, the response to the virus was initially based on ensuring a high level of protection for staff. However, as the epidemic progressed and more information became available about the virus, procedures were rationalized and the virus is currently under control worldwide. There are, however, numerous unanswered questions concerning super-spreading events, the modes of transmission of the virus and, perhaps most importantly, the rapid detection of the virus early in the course of disease. These issues need to be addressed in case the virus becomes more widespread in the near future.


title: Experience of Using Simulation Technology and Analytics During the Ebola Crisis to Empower Frontline Health Workers and Improve the Integrity of Public Health Systems

text: Abstract The Ebola outbreak highlighted the challenge of health security and particularly of how best to give frontline workers the knowledge, confidence and competence to respond effectively. The goal was to develop a tool to improve infection prevention and control through local capacity building within the context of an emergency response. The research showed that digital technology could be a powerful ‘force multiplier’ allowing much greater access to high fidelity training during an outbreak and keeping it current as protocols evolved or new safety critical steps were identified. Tailoring training to the local context was crucial to its relevance and accessibility. This initiative used a novel approach to the development of the training tool – ebuddi. It used agile development to co-create the tool with active participation of local communities. A further pilot showed how it could be extended to meet the longer term needs of triage training and ensure better quality assurance. In the longer term it may have the potential to improve compliance with International Health Regulations, be adapted for future emergencies, and contribute to global health security.


Is the European Union going to help us overcome the COVID-19 crisis?


The long journey inside immigration detention centres in the USA


title: Genetic characterization of the first chiropteran papillomavirus, isolated from a basosquamous carcinoma in an Egyptian fruit bat: The Rousettus aegyptiacus papillomavirus type 1

text: Abstract The complete genomic DNA of a novel papillomavirus (PV) was isolated from a basosquamous carcinoma on the wing of an Egyptian fruit bat (Rousettus aegyptiacus). Initial short sequences of the E1 and L1 genes of this virus were retrieved by PCR with degenerate papillomavirus-specific primers, and the entire R. aegyptiacus papillomavirus type 1 (RaPV-1) DNA was then amplified by long template PCR, cloned and sequenced with a transposon insertion method. The RaPV-1 genome counts 7970 basepairs and contains the typical papillomavirus open reading frames (ORF) (E1, E2, E4, E6, E7, L1 and L2). Based on a concatenated alignment of the E1, E2, L1 and L2 open reading frames of RaPV-1 and 46 other human and animal papillomavirus type species, a neighbor-joining phylogenetic tree was constructed. This phylogenetic analysis shows that RaPV-1 has a close-to-root position in the papillomavirus evolutionary tree. Since RaPV-1 is only distantly related to other papillomaviruses (with maximally 50% nucleotide sequence identity across the L1 open reading frame), it cannot be assigned to one of the existing papillomavirus genera and therefore represents the first member of a novel, as yet unnamed, close-to-root papillomavirus genus. This is the first time a papillomavirus has been isolated and characterized from a member of the Chiroptera order.


Case report: caring for suspected severe acute respiratory syndrome (SARS) patients


COVID-19 pandemic and mental health: Surgeons role in re-engaging patients


title: Role of corticosteroid in the management of COVID-19: A systemic review and a Clinician’s perspective

text: BACKGROUND AND AIMS: Interest in corticosteroid therapy in COVID-19 has been rekindled after the results from Randomized Evaluation of COVid-19 thERapY (RECOVERY) Trial. However, the World health Organization has not recommended corticosteroid in the treatment of COVID-19. We sought to conduct a systematic review on the role of corticosteroid in the management of patients of COVID-19. METHODS: A systematic electronic search of PubMed, Cochrane and MedRxiv database using specific keywords was made up till June 17, 2020. Full text of all the original articles with supplementary appendix that fulfilled the inclusion criteria were retrieved and a detailed analysis of results were represented. RESULTS: Of the 5 studies (4 retrospective studies and 1 quasi-prospective study) conducted for evaluating the role of corticosteroids, 3 studies have shown benefit, while 2 studies shown no benefit and there was a suggestion of significant harm in critical cases in one sub-study. RECOVERY trial is the only randomized controlled trial that has shown a significant reduction of death by 35% in ventilated patients and by 20% amongst patients on supplemental oxygen therapy with the dexamethasone, although no benefit was observed in mild cases. CONCLUSIONS: While the results from retrospective studies are heterogenous and difficult to infer of a definitive protective benefit with corticosteroids, RECOVERY trial found a significantly better outcome with dexamethasone, mostly in severe cases. Nonetheless, more studies are needed to replicate the outcome shown in RECOVERY trial for a substantial conclusion.


Delivering pediatric oncology services during a COVID‐19 pandemic in India


title: Intra-host Ebola viral adaption during human infection

text: The onsite next generation sequencing (NGS) of Ebola virus (EBOV) genomes during the 2013–2016 Ebola epidemic in Western Africa provides an opportunity to trace the origin, transmission, and evolution of this virus. Herein, we have diagnosed a cohort of EBOV patients in Sierra Leone in 2015, during the late phase of the outbreak. The surviving EBOV patients had a recovery process characterized by decreasing viremia, fever, and biochemical parameters. EBOV genomes sequenced through the longitudinal blood samples of these patients showed dynamic intra-host substitutions of the virus during acute infection, including the previously described short stretches of 13 serial T>C mutations. Remarkably, within individual patients, samples collected during the early phase of infection possessed Ts at these nucleotide sites, whereas they were replaced by Cs in samples collected in the later phase, suggesting that these short stretches of T>C mutations could emerge independently. In addition, up to a total of 35 nucleotide sites spanning the EBOV genome were mutated coincidently. Our study showed the dynamic intra-host adaptation of EBOV during patient recovery and gave more insight into the complex EBOV-host interactions.


title: Designing a novel mRNA vaccine against SARS-CoV-2: An immunoinformatics approach

text: SARS-CoV-2 is the deadly virus behind COVID-19, the disease that went on to ravage the world and caused the biggest pandemic 21st century has witnessed so far. On the face of ongoing death and destruction, the urgent need for the discovery of a vaccine against the virus is paramount. This study resorted to the emerging discipline of immunoinformatics in order to design a multi-epitope mRNA vaccine against the spike glycoprotein of SARS-CoV-2. Various immunoinformatics tools were utilized to predict T and B lymphocyte epitopes. The epitopes were channeled through a filtering pipeline comprised of antigenicity, toxicity, allergenicity, and cytokine inducibility evaluation with the goal of selecting epitopes capable of generating both T and B cell-mediated immune responses. Molecular docking simulation between the epitopes and their corresponding MHC molecules was carried out. 13 epitopes, a highly immunogenic adjuvant, elements for proper sub-cellular trafficking, a secretion booster, and appropriate linkers were combined for constructing the vaccine. The vaccine was found to be antigenic, almost neutral at physiological pH, non-toxic, non-allergenic, capable of generating a robust immune response and had a decent worldwide population coverage. Based on these parameters, this design can be considered a promising choice for a vaccine against SARS-CoV-2.


title: Efficacy of prednisolone in children hospitalized for recurrent wheezing

text: Data on the efficacy of corticosteroids on respiratory picornavirus‐induced wheezing are limited. To determine whether prednisolone is effective in rhinovirus‐ or enterovirus‐induced recurrent wheezing, we conducted a controlled trial comparing oral prednisolone (2 mg/kg/day in three divided doses for 3 days) with placebo in hospitalized wheezing children and studied post hoc virus‐specific efficacy in early wheezing (<3 episodes, reported elsewhere) and in recurrent wheezing (≥3 episodes). Virus‐negative children where excluded. Our primary endpoint was the time until children were ready for discharge. Secondary endpoints included oxygen saturation and exhaled nitric oxide during hospitalization, duration of symptoms, blood eosinophil count, and impulse oscillometry 2 wk after discharge, and occurrence of relapses during the following 2 months. Virus‐specific effects were analyzed with interaction analysis in a multivariate regression model. During the study period, 661 patients were hospitalized, 293 randomized, and 59 were accepted in this analysis (mean age 2.6 yr, s.d. 1.3). Prednisolone did not significantly decrease the time until ready for discharge in all patients (prednisolone vs. placebo, medians, 18 vs. 24 h, p = 0.11). However, prednisolone decreased the time until ready for discharge in children with picornavirus infection (respectively, 12 vs. 24 h, p = 0.0022) and more specifically, in children with enterovirus infection (6 vs. 35 h, p = 0.0007). In the secondary endpoints, prednisolone decreased the duration of cough and dyspnea in rhinovirus‐affected children (p = 0.033 for both). Prospectively designed clinical trial is needed to test the hypothesis that prednisolone reduces symptoms in picornavirus‐affected wheezing children.


title: Characterization of Human Metapneumoviruses Isolated from Patients in North America

text: Human metapneumovirus (HMPV) was recently identified in The Netherlands and was linked to acute respiratory tract illness. In this study, 11 isolates from 10 patients with respiratory disease from Quebec, Canada, were tested by a reverse-transcriptase polymerase chain reaction based on the fusion protein gene. Identified sequences were consistent with HMPV. The patients were 2 months to 87 years of age (median age, 58 years) and presented with acute respiratory tract illness during the winter season. Sequence studies of the nucleocapsid, fusion, and polymerase genes identified 2 main lineages of HMPV and cocirculation of both lineages during the same year. These findings support a previous finding that HMPV is a human respiratory pathogen that merits further study.


title: Study on the interaction mechanism between DNA and the main active components in Scutellaria baicalensis Georgi

text: Abstract Binding of baicalein, wogonin and baicalin to fish sperm DNA was studied by using ethidium bromide dye as a fluorescence probe. To study the binding mechanism, the absorption, fluorescence, melting temperature and viscosity measurement were carried out. The experimental results indicated that the planar of flavonoids intercalated to the DNA helix. When bound to DNA, flavonoids showed hyperchromic and blue shift in the absorption spectra and fluorescence quenching (>50%) in the fluorescence spectra. Furthermore, the intercalative binding was consistent with the red shift in the position of λ max in the fluorescence spectra. It was also found that ionic strength had little or no effect on the binding of flavonoids and DNA. Stern–Volmer plots at 25 and 37°C showed that the quenching of fluorescence by flavonoids was a combined quenching process. The binding site number n, apparent binding constant K A at 25 and 37°C, and the corresponding thermodynamic parameters ΔG, ΔH, ΔS at 25°C were obtained. The interaction of flavonoid–metal complexes with DNA was also studied by spectral methods, and the results suggested that the complexes intercalated into DNA.


title: Mycobacterium tuberculosis pili (MTP), a putative biomarker for a tuberculosis diagnostic test

text: Summary Novel biomarkers are urgently needed for point of care TB diagnostics. In this study, we investigated the potential of the pilin subunit protein encoded by the mtp gene as a diagnostic biomarker. BLAST analysis of the mtp gene on published genome databases, and amplicon sequencing were performed in Mycobacterium tuberculosis Complex (MTBC) strains and other organisms. The protein secondary structure of the amino acid sequences of non-tuberculous Mycobacteria that partially aligned with the mtp sequence was analysed with PredictProtein software. The mtp gene and corresponding amino acid sequence of MTBC were 100% homologous with H37Rv, in contrast to the partial alignment of the non-tuberculous Mycobacteria. The mtp gene was present in all 91 clinical isolates of MTBC. Except for 2 strains with point mutations, the sequence was 100% conserved among the clinical strains. The mtp gene could not be amplified in all non-tuberculous Mycobacteria and respiratory organisms. The predicted MTP protein structure of Mycobacterium avium, Mycobacterium ulcerans and Mycobacterium abscessus differed significantly from that of the M. tuberculosis, which was similar to Mycobacterium marinum. The absence of the mtp gene in non-tuberculous Mycobacteria and other respiratory bacteria suggests that its encoded product, the pilin subunit protein of M. tuberculosis may be a suitable marker for a point of care TB test.


Letter to the editor. Concerning the Article Entitled ‘‘Guillain Barre syndrome associated with COVID-19 infection: A case report”


title: Diagnostic considerations for COVID-19 in recipients of allogeneic hematopoietic cell transplantation

text: SARS-CoV-2 in hematopoietic cell transplant (HCT) recipients is associated with severe coronavirus disease-2019 (COVID-19) and higher mortality. SARS-CoV-2 infection is definitively diagnosed by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) typically using nasopharyngeal (NP) swabs, and less commonly, samples from the lower respiratory tract, including bronchoalveolar lavage (BAL). In highly prevalent regions, stepwise evaluation, and management, as in the pre-COVID era, risks false-negatives and delay in therapy for COVID-19.


title: Spread, Circulation, and Evolution of the Middle East Respiratory Syndrome Coronavirus

text: The Middle East respiratory syndrome coronavirus (MERS-CoV) was first documented in the Kingdom of Saudi Arabia (KSA) in 2012 and, to date, has been identified in 180 cases with 43% mortality. In this study, we have determined the MERS-CoV evolutionary rate, documented genetic variants of the virus and their distribution throughout the Arabian peninsula, and identified the genome positions under positive selection, important features for monitoring adaptation of MERS-CoV to human transmission and for identifying the source of infections. Respiratory samples from confirmed KSA MERS cases from May to September 2013 were subjected to whole-genome deep sequencing, and 32 complete or partial sequences (20 were ≥99% complete, 7 were 50 to 94% complete, and 5 were 27 to 50% complete) were obtained, bringing the total available MERS-CoV genomic sequences to 65. An evolutionary rate of 1.12 × 10(−3) substitutions per site per year (95% credible interval [95% CI], 8.76 × 10(−4); 1.37 × 10(−3)) was estimated, bringing the time to most recent common ancestor to March 2012 (95% CI, December 2011; June 2012). Only one MERS-CoV codon, spike 1020, located in a domain required for cell entry, is under strong positive selection. Four KSA MERS-CoV phylogenetic clades were found, with 3 clades apparently no longer contributing to current cases. The size of the population infected with MERS-CoV showed a gradual increase to June 2013, followed by a decline, possibly due to increased surveillance and infection control measures combined with a basic reproduction number (R(0)) for the virus that is less than 1.


title: Hypothesis for potential pathogenesis of SARS-CoV-2 infection–a review of immune changes in patients with viral pneumonia

text: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with droplets and contact as the main means of transmission. Since the first case appeared in Wuhan, China, in December 2019, the outbreak has gradually spread nationwide. Up to now, according to official data released by the Chinese health commission, the number of newly diagnosed patients has been declining, and the epidemic is gradually being controlled. Although most patients have mild symptoms and good prognosis after infection, some patients developed severe and die from multiple organ complications. The pathogenesis of SARS-CoV-2 infection in humans remains unclear. Immune function is a strong defense against invasive pathogens and there is currently no specific antiviral drug against the virus. This article reviews the immunological changes of coronaviruses like SARS, MERS and other viral pneumonia similar to SARS-CoV-2. Combined with the published literature, the potential pathogenesis of COVID-19 is inferred, and the treatment recommendations for giving high-doses intravenous immunoglobulin and low-molecular-weight heparin anticoagulant therapy to severe type patients are proposed.


title: Rapid generation of neutralizing antibody responses in COVID-19 patients

text: SARS-CoV-2 is currently causing a devastating pandemic and there is a pressing need to understand the dynamics, specificity, and neutralizing potency of the humoral immune response during acute infection. Herein, we report the dynamics of antibody responses to the receptor-binding domain (RBD) of the spike protein and virus neutralization activity in 44 COVID-19 patients. RBD-specific IgG responses were detectable in all patients 6 days after PCR confirmation. Using a clinical isolate of SARS-CoV-2, neutralizing antibody titers were also detectable in all patients 6 days after PCR confirmation. The magnitude of RBD-specific IgG binding titers correlated strongly with viral neutralization. In a clinical setting, the initial analysis of the dynamics of RBD-specific IgG titers was corroborated in a larger cohort of PCR-confirmed patients (n=231). These findings have important implications for our understanding of protective immunity against SARS-CoV-2, the use of immune plasma as a therapy, and the development of much-needed vaccines.


title: Virus demyelination

text: A number of viruses can initiate central nervous system (CNS) diseases that include demyelination as a major feature of neuropathology. In humans, the most prominent demyelinating diseases are progressive multifocal leukoencephalopathy, caused by JC papovirus destruction of oligodendrocytes, and subacute sclerosing panencephalitis, an invariably fatal childhood disease caused by persistent measles virus. The most common neurological disease of young adults in the developed world, multiple sclerosis, is also characterized by lesions of inflammatory demyelination; however, the etiology of this disease remains an enigma. A viral etiology is possible, because most demyelinating diseases of known etiology in both man and animals are viral. Understanding of the pathogenesis of virus-induced demyelination derives for the most part from the study of animal models. Studies with neurotropic strains of mouse hepatitis virus, Theiler’s virus, and Semliki Forest virus have been at the forefront of this research. These models demonstrate how viruses enter the brain, spread, persist, and interact with immune responses. Common features are an ability to infect and persist in glial cells, generation of predominantly CD8(+) responses, which control and clear the early phase of virus replication but which fail to eradicate the infection, and lesions of inflammatory demyelination. In most cases demyelination is to a limited extent the result of direct virus destruction of oligodendrocytes, but for the most part is the consequence of immune and inflammatory responses. These models illustrate the roles of age and genetic susceptibility and establish the concept that persistent CNS infection can lead to the generation of CNS autoimmune responses.


title: Child pneumonia – focus on the Western Pacific Region

text: Summary Worldwide, pneumonia is the leading cause of death in infants and young children (aged <5 years). We provide an overview of the global pneumonia disease burden, as well as the aetiology and management practices in different parts of the world, with a specific focus on the WHO Western Pacific Region. In 2011, the Western Pacific region had an estimated 0.11 pneumonia episodes per child-year with 61,900 pneumonia-related deaths in children less than 5 years of age. The majority (>75%) of pneumonia deaths occurred in six countries; Cambodia, China, Laos, Papua New Guinea, the Philippines and Viet Nam. Historically Streptococcus pneumoniae and Haemophilus influenzae were the commonest causes of severe pneumonia and pneumonia-related deaths in young children, but this is changing with the introduction of highly effective conjugate vaccines and socio-economic development. The relative contribution of viruses and atypical bacteria appear to be increasing and traditional case management approaches may require revision to accommodate increased uptake of conjugated vaccines in the Western Pacific region. Careful consideration should be given to risk reduction strategies, enhanced vaccination coverage, improved management of hypoxaemia and antibiotic stewardship.


Thromboelastometry and D-dimer elevation in COVID-19


title: Regional health governance: A suggested agenda for Southern African health diplomacy

text: Regional organisations can effectively promote regional health diplomacy and governance through engagement with regional social policy. Regional bodies make decisions about health challenges in the region, for example, the Union of South American Nations (UNASUR) and the World Health Organisation South East Asia Regional Office (WHO-SEARO). The Southern African Development Community (SADC) has a limited health presence as a regional organisation and diplomatic partner in health governance. This article identifies how SADC facilitates and coordinates health policy, arguing that SADC has the potential to promote regional health diplomacy and governance through engagement with regional social policy. The article identifies the role of global health diplomacy and niche diplomacy in health governance. The role of SADC as a regional organisation and the way it functions is then explained, focusing on how SADC engages with health issues in the region. Recommendations are made as to how SADC can play a more decisive role as a regional organisation to implement South–South management of the regional social policy, health governance and health diplomacy agenda.


title: Protecting dental manpower from COVID‐19 infection

text: World Health Organization declared on 11 March, COVID 19 as a pandemic infection that has spread rapidly across the globe. Covid-19 currently has no known treatment or a vaccine. Oral health professionals are at risk of developing COVID 19 infection as they come into close contact with patients and accompanying relatives who may be carrying the virus. Since January 2020, and by the end of April this year, more than 150 medical doctors in Italy and over 100 National Health Service workers in the UK have died in the COVID-19 crisis. While the transmission of COVID 19 via human ex-haled droplets and direct contact is clear, the potential for aerosol transmission is a significant risk particularly for dental practices. The objective of this brief review is to highlight ways how dental manpower could protect from the spread of disease.


title: Bats as ‘special’ reservoirs for emerging zoonotic pathogens

text: The ongoing West African Ebola epidemic highlights a recurring trend in the zoonotic emergence of virulent pathogens likely to come from bat reservoirs that has caused epidemiologists to ask ‘Are bats special reservoirs for emerging zoonotic pathogens?’ We collate evidence from the past decade to delineate mitochondrial mechanisms of bat physiology that have evolved to mitigate oxidative stress incurred during metabolically costly activities such as flight. We further describe how such mechanisms might have generated pleiotropic effects responsible for tumor mitigation and pathogen control in bat hosts. These synergisms may enable ‘special’ tolerance of intracellular pathogens in bat hosts; paradoxically, this may leave them more susceptible to immunopathological morbidity when attempting to clear extracellular infections such as ‘white-nose syndrome’ (WNS).


title: Tackling COVID‐19 infection through complement‐targeted immunotherapy

text: The complement system is an ancient part of innate immunity sensing highly pathogenic coronaviruses by mannan‐binding lectin (MBL) resulting in lectin pathway activation and subsequent generation of the anaphylatoxins (AT) C3a and C5a as important effector molecules. Complement deposition on endothelial cells and high blood C5a serum levels have been reported in COVID‐19 patients with severe illness, suggesting vigorous complement activation leading to systemic thrombotic microangiopathy (TMA). Complement regulator gene variants prevalent in African Americans have been associated with a higher risk for severe TMA and multi‐organ injury. Strikingly, SARS‐CoV‐2‐infected African Americans suffer from high mortality. These findings allow us to apply our knowledge from other complement‐mediated diseases to COVID‐19 infection to better understand severe disease pathogenesis. Here we will discuss the multiple aspects of complement activation, regulation, crosstalk with other parts of the immune system and the options to target complement in COVID‐19 patients to halt disease progression and death.


title: Current status of potential therapeutic candidates for the COVID-19 crisis

text: Abstract As of April 15, 2020, the ongoing coronavirus disease 2019 (COVID-2019) pandemic has swept through 213 countries and infected more than 1,870,000 individuals, posing an unprecedented threat to international health and the economy. There is currently no specific treatment available for patients with COVID-19 infection. The lessons learned from past management of respiratory viral infections have provided insights into treating COVID-19. Numerous potential therapies, including supportive intervention, immunomodulatory agents, antiviral therapy, and convalescent plasma transfusion, have been tentatively applied in clinical settings. A number of these therapies have provided substantially curative benefits in treating patients with COVID-19 infection. Furthermore, intensive research and clinical trials are underway to assess the efficacy of existing drugs and identify potential therapeutic targets to develop new drugs for treating COVID-19. Herein, we summarize the current potential therapeutic approaches for diseases related to COVID-19 infection and introduce their mechanisms of action, safety, and effectiveness.


title: Emergency reconstruction of large general hospital under the perspective of new COVID-19 prevention and control

text: OBJECTIVE: To summarize the successful experience of timely crisis management, correct measures, and successful display of the hospital image in the First Affiliated Hospital of Zhejiang University (FAHZU), to improve the ability of emergency response. METHODS: The FAHZU, as the earliest designated hospital, accomplished the transformation from general hospital to infectious disease hospital under the guiding ideology of centralized patients, centralized experts, centralized resources, and centralized treatment with measures to transfer the Zhijiang campus hospitalized patients quickly, complete the space layout, create diagnosis and treatment space, streamline logistics, and transform logistics facilities within 48 h. As of 5 March, the hospital had admitted 104 patients. RESULTS: Of the severe cases in Zhejiang province 95% underwent centralized treatment with the goal of zero deaths for severely ill patients, zero misdiagnoses for infected patients, and zero infections for medical staff, and this served as a reference for large medical institutions regarding how to manage such a public health emergency. CONCLUSION: The successful cases of FAHZU provided a valuable experience for large medical institutions on how to address public health emergencies and how to carry out diagnosis and treatment and streamline the layout and related facilities in emergency reconstruction.


title: Telemedicine and Smart Working: Recommendations of the European Association of Urology

text: CONTEXT: Telemedicine provides remote clinical support using technological tools. It may facilitate health care delivery while reducing unnecessary visits to the clinic. The coronavirus disease 2019 (COVID-19) outbreak has caused an abrupt change in our daily urological practice, converting many of us to be reliant on telehealth. OBJECTIVE: To provide practical recommendations for effective use of technological tools in telemedicine. EVIDENCE ACQUISITION: A Medline-based and gray literature search was conducted through April 2020. We selected the most relevant articles related to “telemedicine” and “smart working” that could provide important information. EVIDENCE SYNTHESIS: Telemedicine refers to the use of electronic information and telecommunications tools to provide remote clinical health care support. Smart working is a model of work that uses new or existing technologies to improve performance. Telemedicine is becoming a useful invaluable tool during and even beyond the COVID-19 pandemic. It is time for us to formalize the place of telemedicine in routine urological practice, and it is our responsibility to adapt and learn about all the tools and possible strategies for their optimal implementation during the pandemic to ensure that the quality of care received by patients and the outcomes of patients and their families are of the highest standard. CONCLUSIONS: Telemedicine facilitates specialized urological clinical support at a distance, solves problems of limitations in mobility, reduces unnecessary visits to clinics, and is useful for reducing the risk of viral transmission in the current COVID-19 outbreak. Furthermore, both personal and societal considerations may favor continued use of telemedicine, even beyond the COVID-19 pandemic. PATIENT SUMMARY: Telemedicine in urology offers specialized remote clinical support to patients, similar to face-to-face visits. It is very useful for reducing unnecessary visits to the clinic, as well as reducing the risk of contagion in the current coronavirus disease 2019 (COVID-19) pandemic.


title: Pharmacological Approach to Smoking Cessation: An Updated Review for Daily Clinical Practice

text: Tobacco use is one of the major public health concerns and it is the most preventable cause of morbidity and mortality worldwide. Smoking cessation reduces subsequent cardiovascular events and mortality. Smoking is a real chronic disorder characterized by the development of an addiction status mainly due to nicotine. This condition makes the smokers generally unable to quit smoking without help. Different strategies are available to treat smoking dependence that include both non-pharmacological (behavioral counselling) and pharmacological therapies. Currently, it is well accepted that smoking cessation drugs are effective and safe in real-world settings. Nicotine replacement therapy (NRT), varenicline, bupropion and cytisine are the main pharmacological strategies available for smoking cessation. Their efficacy and safety have been proved even in patients with chronic cardiovascular disease. Each of these drugs has peculiar characteristics and the clinician should customize the smoking cessation strategy based on currently available scientific evidence and patient's preference, paying particular attention to those patients having specific cardiovascular and psychiatric comorbidities. The present document aims to summarize the current viable pharmacological strategies for smoking cessation, also discussing the controversial issue regarding the use of alternative tobacco products, in order to provide useful practical indications to all physicians, mainly to those involved in cardiovascular prevention.


title: The geographic concentrations of air traffic and economic development: A spatiotemporal analysis of their association and decoupling in Brazil

text: This paper examines the evolution of the geographic concentration of the Brazilian air transport network with a focus on its determinants and possible detachments from the spatial patterns of socioeconomic activity. We develop an econometric framework employing and contrasting the results of Gini, Herfindahl-Hirschman and Theil indexes, with and without normalisation to account for economic and demographic spatial dynamics. Our results suggest that the spatial dynamics of the air network and that of the country's economy and population are strongly tied for the majority of the considered determinants. However, we find suggestive evidence that the time trend after deregulation has produced some asymmetries in the evolution of these dimensions. As such, our analysis presents some implications for airline network planning and regulators, as it offers additional information to be considered for the understanding of extra-economic and extra-demographic impacts which may be inducive of significant changes in air transport markets.


COVID-19: Evidence of the Eye


title: What do surgeons need to know about the digestive disorders and paraclinical abnormalities induced by COVID-19?

text: Abstract The symptoms associated with COVID-19 are mainly characterized by a triad composed of fever, dry cough and dyspnea. However, digestive symptoms have also been reported; at first considered as infrequent, they in fact seem to affect (to some extent) more than half of patients. The symptoms are mainly manifested by anorexia, diarrhea, nausea and/or vomiting and abdominal pain. Even though prognosis is associated with lung injury, digestive symptoms seem significantly more frequent in patients presenting with severe COVID-19 infection. Digestive forms, which may be isolated or which can precede pulmonary symptoms, have indeed been reported, with diarrhea as a leading clinical sign. The main biological abnormalities that can suggest COVID-19 infection at an early stage are lymphopenia, elevated CRP and heightened ASAT transaminases. Thoraco-abdominal scan seems useful as a means of on the one hand ruling out digestive pathology not connected with coronavirus and on the other hand searching for pulmonary images compatible with COVID-19 infection. No data exist on the interest of digestive endoscopy in cases of persistent digestive symptoms. Moreover, the endoscopic surgeons may themselves be at significant risk of contamination. Fecal-oral transmission of the infection is possible, especially insofar as viral shedding in stools seems frequent and of longer duration than at the ENT level, including in patients with negative throat swab and without digestive symptoms. In some doubtful cases, virologic assessment of stool samples can yield definitive diagnosis. In the event of prolonged viral shedding in stools, a patient’s persistent contagiousness is conceivable but not conclusively established. Upcoming serology should enable identification of the patients having been infected by the COVID-19 epidemic, particularly among previously undetected pauci-symptomatic members of a health care staff. Resumption of medico-surgical activity should be the object of a dedicated strategy preceding deconfinement.


title: Comparative proteome analysis of tracheal tissues in response to infectious bronchitis coronavirus, Newcastle disease virus, and avian influenza virus H9 subtype virus infection

text: Infectious bronchitis coronavirus (IBV), Newcastle disease virus (NDV), and avian influenza virus (AIV) H9 subtype are major pathogens of chickens causing serious respiratory tract disease and heavy economic losses. To better understand the replication features of these viruses in their target organs and molecular pathogenesis of these different viruses, comparative proteomic analysis was performed to investigate the proteome changes of primary target organ during IBV, NDV, and AIV H9 infections, using 2D‐DIGE followed MALDI‐TOF/TOF‐MS. In total, 44, 39, 41, 48, and 38 proteins were identified in the tracheal tissues of the chickens inoculated with IBV (ck/CH/LDL/97I, H120), NDV (La Sota), and AIV H9, and between ck/CH/LDL/97I and H120, respectively. Bioinformatics analysis showed that IBV, NDV, and AIV H9 induced similar core host responses involved in biosynthetic, catabolic, metabolic, signal transduction, transport, cytoskeleton organization, macromolecular complex assembly, cell death, response to stress, and immune system process. Comparative analysis of host response induced by different viruses indicated differences in protein expression changes induced by IBV, NDV, and AIV H9 may be responsible for the specific pathogenesis of these different viruses. Our result reveals specific host response to IBV, NDV, and AIVH9 infections and provides insights into the distinct pathogenic mechanisms of these avian respiratory viruses.


title: What Synthesis Methodology Should I Use? A Review and Analysis of Approaches to Research Synthesis

text: BACKGROUND: When we began this process, we were doctoral students and a faculty member in a research methods course. As students, we were facing a review of the literature for our dissertations. We encountered several different ways of conducting a review but were unable to locate any resources that synthesized all of the various synthesis methodologies. Our purpose is to present a comprehensive overview and assessment of the main approaches to research synthesis. We use ‘research synthesis’ as a broad overarching term to describe various approaches to combining, integrating, and synthesizing research findings. METHODS: We conducted an integrative review of the literature to explore the historical, contextual, and evolving nature of research synthesis. We searched five databases, reviewed websites of key organizations, hand-searched several journals, and examined relevant texts from the reference lists of the documents we had already obtained. RESULTS: We identified four broad categories of research synthesis methodology including conventional, quantitative, qualitative, and emerging syntheses. Each of the broad categories was compared to the others on the following: key characteristics, purpose, method, product, context, underlying assumptions, unit of analysis, strengths and limitations, and when to use each approach. CONCLUSIONS: The current state of research synthesis reflects significant advancements in emerging synthesis studies that integrate diverse data types and sources. New approaches to research synthesis provide a much broader range of review alternatives available to health and social science students and researchers.


title: Atmospheric dispersion modelling of bioaerosols that are pathogenic to humans and livestock – A review to inform risk assessment studies

text: Abstract In this review we discuss studies that applied atmospheric dispersion models (ADM) to bioaerosols that are pathogenic to humans and livestock in the context of risk assessment studies. Traditionally, ADMs have been developed to describe the atmospheric transport of chemical pollutants, radioactive matter, dust, and particulate matter. However, they have also enabled researchers to simulate bioaerosol dispersion. To inform risk assessment, the aims of this review were fourfold, namely (1) to describe the most important physical processes related to ADMs and pathogen transport, (2) to discuss studies that focused on the application of ADMs to pathogenic bioaerosols, (3) to discuss emission and inactivation rate parameterisations, and (4) to discuss methods for conversion of concentrations to infection probabilities (concerning quantitative microbial risk assessment). The studies included human, livestock, and industrial sources. Important factors for dispersion included wind speed, atmospheric stability, topographic effects, and deposition. Inactivation was mainly governed by humidity, temperature, and ultraviolet radiation. A majority of the reviewed studies, however, lacked quantitative analyses and application of full quantitative microbial risk assessments (QMRA). Qualitative conclusions based on geographical dispersion maps and threshold doses were encountered frequently. Thus, to improve risk assessment for future outbreaks and releases, we recommended determining well-quantified emission and inactivation rates and applying dosimetry and dose–response models to estimate infection probabilities in the population at risk.


title: Is it super-spreading?

text: If the covid-19 virus is transmitted largely by superspreaders, it might not go pandemic, reports Debora MacKenzie


title: Secondary Syphilis in Cali, Colombia: New Concepts in Disease Pathogenesis

text: Venereal syphilis is a multi-stage, sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum (Tp). Herein we describe a cohort of 57 patients (age 18–68 years) with secondary syphilis (SS) identified through a network of public sector primary health care providers in Cali, Colombia. To be eligible for participation, study subjects were required to have cutaneous lesions consistent with SS, a reactive Rapid Plasma Reagin test (RPR-titer ≥1∶4), and a confirmatory treponemal test (Fluorescent Treponemal Antibody Absorption test- FTA-ABS). Most subjects enrolled were women (64.9%), predominantly Afro-Colombian (38.6%) or mestizo (56.1%), and all were of low socio-economic status. Three (5.3%) subjects were newly diagnosed with HIV infection at study entry. The duration of signs and symptoms in most patients (53.6%) was less than 30 days; however, some patients reported being symptomatic for several months (range 5–240 days). The typical palmar and plantar exanthem of SS was the most common dermal manifestation (63%), followed by diffuse hypo- or hyperpigmented macules and papules on the trunk, abdomen and extremities. Three patients had patchy alopecia. Whole blood (WB) samples and punch biopsy material from a subset of SS patients were assayed for the presence of Tp DNA polymerase I gene (polA) target by real-time qualitative and quantitative PCR methods. Twelve (46%) of the 26 WB samples studied had quantifiable Tp DNA (ranging between 194.9 and 1954.2 Tp polA copies/ml blood) and seven (64%) were positive when WB DNA was extracted within 24 hours of collection. Tp DNA was also present in 8/12 (66%) skin biopsies available for testing. Strain typing analysis was attempted in all skin and WB samples with detectable Tp DNA. Using arp repeat size analysis and tpr RFLP patterns four different strain types were identified (14d, 16d, 13d and 22a). None of the WB samples had sufficient DNA for typing. The clinical and microbiologic observations presented herein, together with recent Cali syphilis seroprevalence data, provide additional evidence that venereal syphilis is highly endemic in this region of Colombia, thus underscoring the need for health care providers in the region to be acutely aware of the clinical manifestations of SS. This study also provides, for the first time, quantitative evidence that a significant proportion of untreated SS patients have substantial numbers of circulating spirochetes. How Tp is able to persist in the blood and skin of SS patients, despite the known presence of circulating treponemal opsonizing antibodies and the robust pro-inflammatory cellular immune responses characteristic of this stage of the disease, is not fully understood and requires further study.


title: Clinical and Transmission Characteristics of Covid-19 — A Retrospective Study of 25 Cases from a Single Thoracic Surgery Department

text: The outbreak of corona virus disease 2019 (Covid-19) imposes a major challenge in managing patients undergoing surgical operation. In this study, we analyzed clinical and transmission features of 25 cases of Covid-19 from a single thoracic department, including 13 patients and 12 health care staff. There were 13 males and 12 females. The median age of the patients was 61 (range: 51 to 69) years. The median age of the health care staff was 35 (range: 22 to 51) years. By the end of follow-up date (Mar. 3, 2020), there were 16 non-severe cases (64%) and 9 severe cases (36%), 5 cases were dead (20%). Nineteen (76%) of the infected cases were confirmed by SARS-CoV-2 nucleic acid test, the rest were clinically diagnosed as suspected Covid-19 cases, and 19 (76%) of the infected cases had positive exposure history. We found that COPD was significantly associated with severity and death (P=0.040, and P=0.038, respectively), and chest operation was significantly associated with death for Covid-19 patients (P=0.039). A potential “super spreader” may be the source of the transmission before the implementation of quarantine and comprehensive protection. It was concluded that Covid-19 is associated with poor prognosis for patients undergoing thoracic operation, especially for those with COPD. Implementation of comprehensive protective measures is important to control nosocomial infection.


Utilization and Appropriateness of Transthoracic Echocardiography In Response to the COVID-19 Pandemic


title: Caution in the management of SARS‐CoV‐2 infection in males

text: The coronavirus 2 (SARS‐CoV‐2) pandemic carries clinical, economic and social burdens that are currently being disclosed. The key steps of virus life cycle have been recently clarified, highlighting the role of host type 2 angiotensin converting enzyme (ACE2) and TMPRSS2 serine protease in virus‐cell binding and entry, respectively. Importantly, major concerns derive from the androgen‐dependent tissue‐expression of both TMPRSS2 and ACE2, suggesting a differential clinical course of the infection between genders. In agreement with this model, available epidemiological data show that the disease in males has an higher risk to display an heavier pattern and associates with both an increased access to critical care unit and higher mortality rate. In this opinion article, available evidence linking the androgen activity with the gender differences observed in SARS‐CoV‐2 infection are discussed, hypothesizing possible therapeutic approaches in male based on the disruption of androgen signaling. On these bases, gender‐specific recommendations for the management of male patients affected by SARS‐CoV‐2 infection are warmly suggested, in order to improve the clinical course of the disease.


title: Remdesivir potently inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 as the causative agent of the novel pandemic viral disease COVID-19. With no approved therapies, this pandemic illustrates the urgent need for safe, broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV), a monophosphoramidate prodrug of an adenosine analog, potently inhibits SARS-CoV-2 replication in human lung cells and primary human airway epithelial cultures (EC50 = 0.01 μM). Weaker activity was observed in Vero E6 cells (EC50 = 1.65 μM) due to their low capacity to metabolize RDV. To rapidly evaluate in vivo efficacy, we engineered a chimeric SARS-CoV encoding the viral target of RDV, the RNA-dependent RNA polymerase, of SARS-CoV-2. In mice infected with chimeric virus, therapeutic RDV administration diminished lung viral load and improved pulmonary function as compared to vehicle treated animals. These data provide evidence that RDV is potently active against SARS-CoV-2 in vitro and in vivo, supporting its further clinical testing for treatment of COVID-19.


title: Regulatory, Legal, and Ethical Considerations of Telemedicine

text: Sleep telemedicine practitioners must ensure their practice complies with all applicable institutional, state, and federal regulations. Providers must be licensed in any state in which they provide care, have undergone credentialing and privileging procedures at outside facilities, and avoid real or perceived conflicts of interest while providing that care. Internet-based prescribing remains limited to certain circumstances. Whether or not a malpractice insurance policy covers telemedicine depends on the insurer, especially if interstate care is provided. All telemedicine programs must protect patient health information. Similarly, bioethical principles of autonomy, beneficence, nonmaleficence, and justice apply to both in-person and telemedicine-based care.


Virus con denominación de origen en español: el virus del Nilo Occidental


title: The COVID-19 infection: lessons from the Italian experience

text: The first case of the new coronavirus, COVID-19, was reported in China on 17 November 2019. By the end of March 2020, the rapid global spread of infection affected over 1 million people. Italy is one of the countries most impacted, with over 100,000 positive cases identified. The first detected cases were reported on 21 February 2020 in two Italian towns: Vo’ Euganeo in the Province of Padua, Veneto region, and Codogno, in the Province of Lodi, Lombardy. In the next weeks the epidemic spread quickly across the country but mainly in the north of Italy. The two regions: Veneto and Lombardy, implemented different strategies to control the viral spread. In Veneto, health personnel tested both symptomatic and asymptomatic subjects, while in Lombardy only symptomatic cases were investigated. We analyzed the evolution of the epidemic in these regions and showed that testing both symptomatic and asymptomatic cases is a more effective strategy to mitigate the epidemic impact. We strongly recommend that decision-makers: ensure early isolation of symptomatic patients and rapid identification of their contacts; maximize testing rapidly, especially among people with multiple daily contacts with infected populations, high exposure to the public in essential services; rapidly increase diagnostic capacity by mobilizing trained personnel capable of performing rRT-PCR on respiratory samples; equip the population with protective masks.


Assembling the Transmembrane Domain of Vpu from HIV-1


title: Selective Preference of Parallel DNA Triplexes Is Due to the Disruption of Hoogsteen Hydrogen Bonds Caused by the Severe Nonisostericity between the G*GC and T*AT Triplets

text: Implications of DNA, RNA and RNA.DNA hybrid triplexes in diverse biological functions, diseases and therapeutic applications call for a thorough understanding of their structure-function relationships. Despite exhaustive studies mechanistic rationale for the discriminatory preference of parallel DNA triplexes with G(*)GC & T(*)AT triplets still remains elusive. Here, we show that the highest nonisostericity between the G(*)GC & T(*)AT triplets imposes extensive stereochemical rearrangements contributing to context dependent triplex destabilisation through selective disruption of Hoogsteen scheme of hydrogen bonds. MD simulations of nineteen DNA triplexes with an assortment of sequence milieu reveal for the first time fresh insights into the nature and extent of destabilization from a single (non-overlapping), double (overlapping) and multiple pairs of nonisosteric base triplets (NIBTs). It is found that a solitary pair of NIBTs, feasible either at a G(*)GC/T(*)AT or T(*)AT/G(*)GC triplex junction, does not impinge significantly on triplex stability. But two overlapping pairs of NIBTs resulting from either a T(*)AT or a G(*)GC interruption disrupt Hoogsteen pair to a noncanonical mismatch destabilizing the triplex by ~10 to 14 kcal/mol, implying that their frequent incidence in multiples, especially, in short sequences could even hinder triplex formation. The results provide (i) an unambiguous and generalised mechanistic rationale for the discriminatory trait of parallel triplexes, including those studied experimentally (ii) clarity for the prevalence of antiparallel triplexes and (iii) comprehensive perspectives on the sequence dependent influence of nonisosteric base triplets useful in the rational design of TFO’s against potential triplex target sites.


title: Isolation and characterization of a variant porcine epidemic diarrhea virus in China

text: An outbreak of diarrhea in pigs started in Guangdong, South China in January 2011. Cases were characterized by watery diarrhea, dehydration and vomiting, with 80–100% morbidity and 50–90% mortality in suckling piglets. The causative agent of the diarrhea was ultimately identified as porcine epidemic diarrhea virus (PEDV). In this study, we isolated a PEDV strain designated CHGD-01 from piglet intestines using Vero cell cultures, and its specific cytopathic effects were confirmed in susceptible cells by direct immunofluorescence testing and electron microscopy. The complete genome of CHGD-01 was shown to be 28,035 nucleotides in length, with a similar structure to that of PEDV reference strains. Phylogenetic analyses based on the whole genome revealed that CHGD-01 shared nucleotide sequence identities of 98.2–98.4% with two other Chinese isolates reported in the same year, thus constituting a new cluster. Amino acid sequence analysis based on individual virus genes indicated a close relationship between the spike protein gene of CHGD-01 and the field strain KNU0802 in Korea. Its ORF3 and nucleoprotein genes, however, were divergent from all other sequenced PEDV isolate clusters and therefore formed a new group, suggesting a new variant PEDV isolate in China. Further studies will be required to determine the immunogenicity and pathogenicity of this new variant.


title: MRPrimerV: a database of PCR primers for RNA virus detection

text: Many infectious diseases are caused by viral infections, and in particular by RNA viruses such as MERS, Ebola and Zika. To understand viral disease, detection and identification of these viruses are essential. Although PCR is widely used for rapid virus identification due to its low cost and high sensitivity and specificity, very few online database resources have compiled PCR primers for RNA viruses. To effectively detect viruses, the MRPrimerV database (http://MRPrimerV.com) contains 152 380 247 PCR primer pairs for detection of 1818 viruses, covering 7144 coding sequences (CDSs), representing 100% of the RNA viruses in the most up-to-date NCBI RefSeq database. Due to rigorous similarity testing against all human and viral sequences, every primer in MRPrimerV is highly target-specific. Because MRPrimerV ranks CDSs by the penalty scores of their best primer, users need only use the first primer pair for a single-phase PCR or the first two primer pairs for two-phase PCR. Moreover, MRPrimerV provides the list of genome neighbors that can be detected using each primer pair, covering 22 192 variants of 532 RefSeq RNA viruses. We believe that the public availability of MRPrimerV will facilitate viral metagenomics studies aimed at evaluating the variability of viruses, as well as other scientific tasks.


Reply to: ‘Interaction between RAAS inhibitors and ACE2 in the context of COVID-19’


title: Potential Pathogens Reported in Species of the Family Viverridae and Their Implications for Human and Animal Health

text: The Viverridae is a family of nocturnal carnivores including civets, genets and African linsangs. While a list of known organisms isolated from a species is an essential tool for population management, this review represents the first attempt to collate published reports of organisms isolated from viverrids. A wide range of organisms, including 11 viruses, eight bacterial species, one internal arthropod species, representatives from eight genera of protozoan, 21 genera of nematode, seven genera of cestode, eight genera of trematode and six genera of external arthropod (mites, ticks and louse), have been reported in literature spanning over a century of research. Many of these are capable of infecting multiple hosts, including humans. This is of concern given the anthropogenic factors that bring humans and domestic species into close contact with viverrids, facilitating transmission and spillover of organisms between groups. These factors include trade in viverrids for human consumption, captive management in zoos, rescue centres or on commercial breeding farms, and the increasing overlap of free‐ranging viverrid distribution and human settlement.


title: Counselling and psychotherapy post‐COVID‐19

text: We consider how the prolonged, complex and uncertain aftermath of the COVID‐19 crisis will present challenges and opportunities for counselling and psychotherapy. Increased mental strain on populations, individuals and professionals is likely to be compounded by further constraints in therapeutic resources. Nevertheless, emerging needs and priorities will offer ground for systems thinking in linking the application of a range of therapeutic frameworks, theories to address global challenges, integration of counselling and psychotherapy into new sectors, service models for the most vulnerable, use of digital approaches, support mechanisms for professionals and interdisciplinary research.


title: Lower Respiratory Infections Among Hospitalized Children in New Caledonia: A Pilot Study for the Pneumonia Etiology Research for Child Health Project

text: We conducted a prospective pilot study over a 1-year period in New Caledonia in preparation for the Pneumonia Research for Child Health (PERCH) project. The pathogens associated with hospitalized lower respiratory infections in children were identified through the use of culture of induced sputum and blood, urinary antigen detection, polymerase chain reaction (PCR) on respiratory specimens, and serology on paired sera. Respiratory viruses were detected on respiratory specimens by immunofluorescence and PCR, and by serology on paired sera. Pathogens were detected in 87.9% of the 108 hospitalized cases. Viruses represented 81.6% of the 152 pathogens detected. Respiratory syncytial virus and rhinovirus were the most frequent, accounting for 32.2% and 24.3% of the pathogens identified, respectively. Only 26.3% of 99 induced sputum specimens collected were determined to be of good quality, which may be a consequence of the collection method used.


title: Direct Diagnostic Tests for Lyme Disease

text: Borrelia burgdorferi was discovered to be the cause of Lyme disease in 1983, leading to seroassays. The 1994 serodiagnostic testing guidelines predated a full understanding of key B. burgdorferi antigens and have a number of shortcomings. These serologic tests cannot distinguish active infection, past infection, or reinfection. Reliable direct-detection methods for active B. burgdorferi infection have been lacking in the past but are needed and appear achievable. New approaches have effectively been applied to other emerging infections and show promise in direct detection of B. burgdorferi infections.


title: Numeracy, adult education, and vulnerable adults: a critical view of a neglected field

text: This survey paper examines selected issues related to the intersection of three broad scholarly areas: numeracy, adult education, and vulnerability. Numeracy encompasses the ways in which people cope with the mathematical, quantitative, and statistical demands of adult life, and is viewed as an important outcome of schooling and as a foundational skill for all adults. The focus on vulnerability stems from the realization that concerns of policy makers and educators alike often center on populations seen as vulnerable. The paper is organized in five sections. After a brief introduction, Section 2 examines adult numeracy, focusing on five numeracy domains (health, financial, digital, civic, and workplace numeracy), literacy–numeracy linkages, functional and critical aspects of numeracy, and the centrality of numeracy practices, and notes sources of vulnerability for each of these. Section 3 sketches formal, non-formal and informal contexts in which adults learn or develop their numeracy, and examines factors that may be potential sources of vulnerability, including systemic factors and dispositional and affect factors. Section 4 reflects more broadly on the concept of vulnerability, introduces selected aspects of the papers published in this issue of ZDM Mathematics Education, and points to findings regarding adult learners who may be deemed vulnerable. The closing section summarizes conclusions and research directions regarding the intersection of the three core domains. Overall, the paper points to emerging research needs and educational challenges that are relevant to scholars, practitioners, and policy makers interested in developing the numeracy of adults as well as in the mathematics education of younger learners.


title: Intranasal fluticasone propionate does not prevent acute otitis media during viral upper respiratory infection in children()()

text: Background: Acute otitis media (AOM) is the most common complication of a viral upper respiratory infection (URI) in children. The virus-induced host inflammatory response in the nasopharynx plays a key role in the pathogenesis of AOM. Suppression of this inflammatory process might prevent the development of AOM as a complication. Objective: We sought to assess the effect of intranasally administered fluticasone propionate on prevention of AOM during a viral respiratory infection. Methods: A total of 210 children (mean age, 2.1 years; range, 0.7-3.9 years) with normal middle ear status and URI of 48 hours’ duration or less were randomly allocated to receive either fluticasone (100 μg twice daily) or placebo for 7 days. The specific viral cause of the infection was determined from nasopharyngeal aspirates obtained at the first visit. The children were re-examined at the end of the 7-day medication period. Results: In the fluticasone group AOM developed in 40 (38.1%) of 105 children compared with 29 (28.2%) of 103 children receiving placebo (P = .13). The viral cause of the respiratory infection was determined in 167 (86.1%) of 194 children from whom a nasopharyngeal aspirate was obtained. In children with rhinovirus infection, AOM developed significantly more often in the fluticasone group (45.7%) than in the placebo group (14.7%, P = .005). Conclusion: Intranasally administered fluticasone does not prevent the development of AOM during URI but may increase the incidence of AOM during rhinovirus infection. (J Allergy Clin Immunol 2000;106:467-71.)