title: Control dynamics of severe acute respiratory syndrome transmission

text: Severe acute respiratory syndrome (SARS) is a serious disease with many puzzling features. We present a simple, dynamic model to assess the epidemic potential of SARS and the effectiveness of control measures. With this model, we analysed the SARS epidemic data in Beijing. The data fitting gives the basic case reproduction number of 2.16 leading to the outbreak, and the variation of the effective reproduction number reflecting the control effect. Noticeably, our study shows that the response time and the strength of control measures have significant effects on the scale of the outbreak and the lasting time of the epidemic.


title: Development of Vaccine Delivery Vehicles Based on Lactic Acid Bacteria

text: Live recombinant bacteria represent attractive antigen delivery systems able to induce both mucosal and systemic immune responses against heterologous antigens. The first live recombinant bacterial vectors developed were derived from attenuated pathogenic microorganisms. In addition to the difficulties often encountered in the construction of stable attenuated mutants of pathogenic organisms, attenuated pathogens may retain a residual virulence level that renders them unsuitable for the vaccination of partially immunocompetent individuals such as infants, the elderly or immunocompromised patients. As an alternative to this strategy, non-pathogenic food-grade lactic acid bacteria (LAB) maybe used as live antigen carriers. This article reviews LAB vaccines constructed using antigens other than tetanus toxin fragment C, against bacterial, viral, and parasitic infective agents, for which protection studies have been performed. The antigens utilized for the development of LAB vaccines are briefly described, along with the efficiency of these systems in protection studies. Moreover, the key factors affecting the performance of these systems are highlighted.


title: Chapter 20 Discovery of Zinc for Human Health and Biomarkers of Zinc Deficiency

text: Abstract Zinc deficiency in humans was recognized for the first time in 1963, and a recommended dietary allowance (RDA) for zinc was established by the US National Academy of Sciences in 1974. The present World Health Organization (WHO) estimate is that nearly 2billion subjects living in the developing world may have zinc deficiency. This is mainly because they subsist on cereal proteins which contain high quantities of organic phosphate compounds, which combine with zinc making it unavailable for absorption. The major adverse clinical effects of zinc deficiency are growth retardation, decreased cell-mediated immunity, impairment of cognitive functions, increased oxidative stress, and upregulation of inflammatory cytokines. Our studies have shown that nearly 30% of healthy, well-to-do elderly subjects living in developed countries may also be zinc deficient due to an increased phytate to zinc molar ratio in their diet. Over 300 enzymes and 2000 transcription factors are now known to require zinc for their functions and stability of their structures, and several studies have now shown that zinc may be a molecular signal for neuronal and immune cells. Fourteen ZIP and 10 ZNT zinc transporters are known to maintain intracellular zinc homeostasis. Therapeutic impacts of zinc on human health are also being investigated. Zinc is being used for the treatment of acute diarrhea in infants and children in developing countries globally, and this has resulted in saving millions of lives. Zinc is now an approved drug for the treatment and maintenance therapy of Wilson's disease, a serious fatal genetic disorder. According to a recent Cochrane Review, zinc is the only treatment which is effective in decreasing the incidence of infections and pain crises in patients with sickle cell disease. Zinc acetate lozenges have been shown to decrease the duration of the common cold by 50%, provided the treatment is started within 24h of the onset of symptoms, the solution chemistry of the zinc preparation is proper, and the zinc dosages are adequate. Age-related macular degeneration (AMD) accounts for a large proportion of legal blindness in elderly subjects throughout the world. The Age-Related Eye Disease Study Group (AREDS) was supported by National Eye Institute. The National Institutes of Health (NIH) has now reported the results of their 10-year zinc supplementation study in patients with AMD. Zinc was effective in decreasing the incidences of blindness and progression of AMD in elderly subjects. Most importantly, zinc-supplemented subjects showed increased longevity and this was due to a decrease in cardiovascular events. No other micronutrient has shown this dramatic effect on decreasing mortality in the elderly. Our placebo-controlled, zinc supplementation trial in the elderly has shown that zinc supplementation decreased the incidence of infections by 66% and improved cell-mediated immunity. Also, we showed that oxidative stress markers and gene expression of inflammatory cytokines were decreased in elderly subjects who received zinc supplementation. These studies suggest that zinc supplementation in the elderly may have a preventive role in atherosclerosis. Plasma zinc is widely used as a biomarker of zinc deficiency in humans. This test is, however, neither specific nor sensitive. Assays of immunological markers such as plasma active thymulin and gene expression of IL-2 in PHA-stimulated lymphocytes are very sensitive and specific for the diagnosis of human zinc deficiency. The assay of zinc in cells such as lymphocytes and granulocytes are better than plasma zinc; however, even these assays are less sensitive than immunological biomarkers.


title: The effect of social distance measures on COVID-19 epidemics in Europe: an interrupted time series analysis

text: Following the introduction of unprecedented “stay-at-home” national policies, the COVID-19 pandemic recently started declining in Europe. Our research aims were to characterize the changepoint in the flow of the COVID-19 epidemic in each European country and to evaluate the association of the level of social distancing with the observed decline in the national epidemics. Interrupted time series analyses were conducted in 28 European countries. Social distance index was calculated based on Google Community Mobility Reports. Changepoints were estimated by threshold regression, national findings were analyzed by Poisson regression, and the effect of social distancing in mixed effects Poisson regression model. Our findings identified the most probable changepoints in 28 European countries. Before changepoint, incidence of new COVID-19 cases grew by 24% per day on average. From the changepoint, this growth rate was reduced to 0.9%, 0.3% increase, and to 0.7% and 1.7% decrease by increasing social distancing quartiles. The beneficial effect of higher social distance quartiles (i.e., turning the increase into decline) was statistically significant for the fourth quartile. Notably, many countries in lower quartiles also achieved a flat epidemic curve. In these countries, other plausible COVID-19 containment measures could contribute to controlling the first wave of the disease. The association of social distance quartiles with viral spread could also be hindered by local bottlenecks in infection control. Our results allow for moderate optimism related to the gradual lifting of social distance measures in the general population, and call for specific attention to the protection of focal micro-societies enriching high-risk elderly subjects, including nursing homes and chronic care facilities.


title: Trends in the chemical and pharmacological research on the tropical trees Calophyllum brasiliense and Calophyllum inophyllum, a global context

text: Tropical trees of Calophyllum genus (Calophyllaceae) have chemical and biological importance as potential source of secondary active metabolites which can lead to the development of new drugs. Research on this species has been rising since 1992 due to the discovering of anti-HIV properties of Calanolide A found in Calophyllum inophyllum leaves. This compound is the most important natural product for potential development of new anti-HIV drugs and phytomedicines. The scientometric analysis (1953–2014) here performed revealed that the most studied species of Calophyllum genus are: C. inophyllum and C. brasiliense, distributed in the Asian, and American continents, respectively. Current research on these species is carried out mainly in India and Brazil, respectively, where these species grow. Research on C. brasiliense is focused mainly on ecological, antiparasitic, cytotoxic properties, and isolation of new compounds. Chemical studies and biodiesel development are the main topics in the case of C. inophyllum. Text mining analysis revealed that coumarins, and xanthones are the main secondary active metabolites responsible for most of the reported pharmacological properties, and are potential compounds for the treatment of leukemia and against intracellular parasites causing American Trypanosomiasis and Leshmaniasis. On the other hand, C. inophyllum represents an important source for the development of 2nd generation biodiesel. Medicinal and industrial applications of these species may impulse sustainable forest plantations. To our knowledge this is the first scientometric and text mining analysis of chemical and biomedical research on Calophyllum genus, C. brasiliense and C. inophyllum.


title: Characteristics of seminal plasma proteins and their correlation with canine semen analysis

text: Abstract The objectives were to separate canine seminal plasma proteins (with SDS-PAGE) and to determine the correlation between specific proteins and semen characteristics. Three ejaculates from 20 mixed-breed dogs, of unknown fertility, were collected by digital manipulation. Ejaculate volume and color, sperm motility, sperm vigor, percentage of morphologically normal spermatozoa, and membrane integrity (hypoosmotic swelling test and fluorescent staining) were assessed. For each dog, seminal plasma was pooled from all three ejaculates and proteins were separated with SDS-PAGE, using polyacrylamide concentrations of 13% and 22% in the separation gels. After staining, gel images were digitized to estimate molecular weights (MW) and integrated optical density (IOD) of each lane and of individual bands. Total seminal plasma protein concentration was 2.19±1.56g/dL (mean±SD; range 1.12–5.19g/dL). A total of 37 protein bands were identified (although no dog had all 37 bands). In the 13% gel, molecular weights ranged from 100.6 to 17.1kDa, with four bands (49.7, 33.2, 26.4, and 19.5kDa) present in samples from all dogs. In the 22% gel, molecular weights ranged from 15.6 to 3.6kDa, with nine bands (15.6, 13.5, 12.7, 11.7, 10.5, 8.7, 7.8, 5.6, and 4.9kDa) present in samples from all dogs. Combined for both gels, the majority of bands (85%) had molecular weights <17kDa, with B20 (15.6kDa) in high concentrations in samples from all dogs. There were positive correlations (P ≤0.01) between two bands, B4 (67kDa) and B5 (58.6kDa), and sperm motility (r =0.66 and r =0.46), sperm vigor (r =0.56 and r =0.66), percentage of morphologically normal spermatozoa (r =0.55 and r =0.59), the hypoosmotic swelling test (r =0.76 and r =0.68), and fluorescent staining (r =0.56 and r =0.59), respectively. In conclusion, 37 proteins were identified in seminal plasma; two were significantly correlated with semen characteristics.


title: Global change of surgical and oncological clinical practice in urology during early COVID-19 pandemic

text: OBJECTIVES: While the coronavirus disease 2019 (COVID-19) pandemic captures healthcare resources worldwide, data on the impact of prioritization strategies in urology during pandemic are absent. We aimed to quantitatively assess the global change in surgical and oncological clinical practice in the early COVID-19 pandemic. METHODS: In this cross-sectional observational study, we designed a 12-item online survey on the global effects of the COVID-19 pandemic on clinical practice in urology. Demographic survey data, change of clinical practice, current performance of procedures, and current commencement of treatment for 5 conditions in medical urological oncology were evaluated. RESULTS: 235 urologists from 44 countries responded. Out of them, 93% indicated a change of clinical practice due to COVID-19. In a 4-tiered surgery down-escalation scheme, 44% reported to make first cancellations, 23% secondary cancellations, 20% last cancellations and 13% emergency cases only. Oncological surgeries had low cancellation rates (%): transurethral resection of bladder tumor (27%), radical cystectomy (21–24%), nephroureterectomy (21%), radical nephrectomy (18%), and radical orchiectomy (8%). (Neo)adjuvant/palliative treatment is currently not started by more than half of the urologists. COVID-19 high-risk-countries had higher total cancellation rates for non-oncological procedures (78% vs. 68%, p = 0.01) and were performing oncological treatment for metastatic diseases at a lower rate (35% vs. 48%, p = 0.02). CONCLUSION: The COVID-19 pandemic has affected clinical practice of 93% of urologists worldwide. The impact of implementing surgical prioritization protocols with moderate cancellation rates for oncological surgeries and delay or reduction in (neo)adjuvant/palliative treatment will have to be evaluated after the pandemic. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00345-020-03333-6) contains supplementary material, which is available to authorized users.


title: Activation of CD8 T Lymphocytes during Viral Infections

text: Abstract CD8 T lymphocytes are a major cell population of the adaptive immune system. A fundamental characteristic of the CD8 T lymphocyte pool is that it is composed of millions of clones; each with a unique T cell receptor capable of recognizing a limited number of peptides displayed at the cell surface bound to the grooves of major histocompatibility complex class I (MHC I) molecules. Naïve CD8 T lymphocytes are normally resting and circulate between the blood and secondary lymphoid organs in search of their cognate peptide–MHC complexes. During viral infections, bone marrow–derived professional antigen-presenting cells (pAPCs) in secondary lymphoid organs display viral peptides on their MHC I molecules. Specific CD8 T lymphocytes that recognize these peptide–MHC adducts become activated (primed), proliferate extensively, and develop into effectors capable of killing infected cells, identified by the presence at their surface of the pertinent viral peptide–MHC complexes. This article describes how the process of priming naïve CD8 T lymphocytes occurs.


title: The War on Severe Acute Respiratory Syndrome: United States Forces Korea’s Campaign Plan

text: A mysterious new respiratory illness known as severe acute respiratory syndrome (SARS) has become the most perplexing infectious disease to emerge in the 21st century. From March to May 2003, it competed daily with the war in Iraq as the most sensational media event of the moment. U.S. personnel serving in the Republic of Korea represented the largest U.S. military population at risk for SARS. With tensions growing between Pyongyang and Washington, the United States/Republic of Korea alliance could not afford to be rendered combat ineffective by SARS. To remain mission ready, the U.S. Forces Korea (USFK) commander declared a “War on SARS” and directed his medical staff to develop a plan to prevent a SARS outbreak among USFK personnel. This article outlines the USFK campaign plan for the SARS epidemic and documents lessons learned for future outbreaks of highly infectious diseases.


title: Theiler’s murine encephalomyelitis virus infection of astrocytes induces the expression of chemokines which attract activated but not resting T lymphocytes

text: In this article, we studied the production of the chemokine CXCL9, also termed Mig (monokine induced by gamma interferon) by cultured SJL/J mouse astrocytes infected with the BeAn strain of Theiler’s murine encephalomyelitis virus (TMEV). This picornavirus induces demyelination in the SJL/J genetically susceptible strain of mice through an immune process mediated by CD4(+) Th1 T cells. Those cells were chemoattracted by chemokines inside the central nervous system (CNS) after blood-brain barrier (BBB) disruption. cRNAs from TMEV- and mock-infected astrocytes cells were hybridized to the Affymetrix murine genome U74v2 DNA microarray. Hybridization data analysis revealed the upregulation of six sequences potentially coding for Mig. We confirmed post infection Mig mRNA increase by quantitative (qPCR) and RT-PCR. The presence of Mig in the supernatants of infected astrocytes was quantified using a specific ELISA. Secreted Mig was biologically active, inducing chemoattraction of mouse activated CD4(+) T lymphocytes. Conversely, attracting activity on CD3(+) resting T cells that can be attributed to chemokines as CXCL12/SDF-1α could not be demonstrated in these supernatants. No overinduction of the gene coding for this chemokine was assessed by DNA hybridization either. Both recombinant IFN-γ and TNF-α inflammatory cytokines were also strong inducers of Mig in SJL/J astrocyte cultures.


title: The influence of collagen film nanostructure on pulmonary stem cells and collagen–stromal cell interactions

text: Abstract We have recently identified a rare subpopulation of lung colony cells with the characteristics of pulmonary stem cells, and discovered that stem cell colonies grew preferentially on type I collagen films in a serum-free medium. In order to further optimize culture conditions and determine stem cell growth in relation to microenvironments (including the stroma, medium and nanostructures of type I collagen films), both primary and pre-sorted stem cells were cultured on the type I collagen films with controllable degree of polymerization and film thickness, as confirmed by an atomic force microscope and surface profiler. We found that in a primary culture, the spreading of stromal cells is greatly restrained and both the size and number of colonies are significantly reduced on highly polymerized collagen films. In contrast, in a pre-sorted stem cell culture without stromal cells, the intrinsic stem cell properties and cell number are independent of the degree of collagen polymerization. Our results indicate that the nanostructures of type I collagen films primarily affect stem colony formation through the collagen–stroma interactions. In those cases, collagen film thickness shows no effect on colony formation.


title: Enhancing the Antiviral Efficacy of RNA-Dependent RNA Polymerase Inhibition by Combination with Modulators of Pyrimidine Metabolism

text: Genome-wide analysis of the mode of action of GSK983, a potent antiviral agent, led to the identification of dihydroorotate dehydrogenase as its target along with the discovery that genetic knockdown of pyrimidine salvage sensitized cells to GSK983. Because GSK983 is an ineffective antiviral in the presence of physiological uridine concentrations, we explored combining GSK983 with pyrimidine salvage inhibitors. We synthesized and evaluated analogs of cyclopentenyl uracil (CPU), an inhibitor of uridine salvage. We found that CPU was converted into its triphosphate in cells. When combined with GSK983, CPU resulted in large drops in cellular UTP and CTP pools. Consequently, CPU-GSK983 suppressed dengue virus replication in the presence of physiological concentrations of uridine. In addition, the CPU-GSK983 combination markedly enhanced the effect of RNA-dependent RNA polymerase (RdRp) inhibition on viral infection. Our findings highlight a new host-targeting strategy for potentiating the antiviral activity of RdRp inhibitors.


title: Viral diseases of fish in Japan

text: Abstract Viruses causing infectious pancreatic necrosis (IPN) and infectious hematopoietic necrosis (IHN) were first isolated in Japan during the 1970s and these two diseases remain among the most serious problems affecting cultured salmonids in Japan. In addition to IHN and IPN, four other viral diseases cause major economic losses among cultured fishes in Japan. These include viral pancreatic hepatic necrosis of yellowtail, rhabdovirus infection of Japanese flounder and black rock fish, Kuchishiro-sho of tiger puffer fish, and epidermal hyperplasia or necrosis of Japanese flounder. Over the years, a number of other viruses have been isolated from, or have been observed by electron microscopy, in moribund fish. Members of 10 of the existing families of animal viruses are represented in this group. Their importance to the aquaculture industry in Japan is reviewed here.


title: A newly established bovine intestinal epithelial cell line is effective for in vitro screening of potential antiviral immunobiotic microorganisms for cattle

text: Abstract We evaluated whether a bovine intestinal epithelial (BIE) cell line could serve as a useful in vitro model system for studying antiviral immune responses in bovine intestinal epithelial cells (IECs) and for the primary screening of immunobiotic microorganisms with antiviral protective capabilities. Immunofluorescent analyses revealed that toll-like receptor 3 (TLR3) was expressed in BIE cells, and the results of real-time quantitative PCR showed that these cells respond to stimulation with poly(I:C) by up-regulating pro-inflammatory cytokines and type I interferons. In addition, we demonstrated that BIE cells are useful for the primary screening of immunobiotic lactic acid bacteria strains which are able to beneficially modulate antiviral immune responses triggered by TLR3 activation in bovine IECs. The characterization of BIE cells performed in the present study represents an important step towards the establishment of a valuable bovine in vitro system that could be used for the development of immunomodulatory feed for bovine hosts.


title: Global shifts in mammalian population trends reveal key predictors of virus spillover risk

text: Emerging infectious diseases in humans are frequently caused by pathogens originating from animal hosts, and zoonotic disease outbreaks present a major challenge to global health. To investigate drivers of virus spillover, we evaluated the number of viruses mammalian species have shared with humans. We discovered that the number of zoonotic viruses detected in mammalian species scales positively with global species abundance, suggesting that virus transmission risk has been highest from animal species that have increased in abundance and even expanded their range by adapting to human-dominated landscapes. Domesticated species, primates and bats were identified as having more zoonotic viruses than other species. Among threatened wildlife species, those with population reductions owing to exploitation and loss of habitat shared more viruses with humans. Exploitation of wildlife through hunting and trade facilitates close contact between wildlife and humans, and our findings provide further evidence that exploitation, as well as anthropogenic activities that have caused losses in wildlife habitat quality, have increased opportunities for animal–human interactions and facilitated zoonotic disease transmission. Our study provides new evidence for assessing spillover risk from mammalian species and highlights convergent processes whereby the causes of wildlife population declines have facilitated the transmission of animal viruses to humans.


title: An efficient lattice Boltzmann model for indoor airflow and particle transport

text: Abstract The three-dimensional multiple-relaxation-time LB (MRT-LB) and Lagrangian particle tracking methods were applied to simulate turbulent airflow and particle dispersion in a ventilated room with a partition. The turbulent airflow was simulated by large eddy simulation (LES) using the MRT-LB method with the Smagorinsky model. This method was verified by comparing it with experimental and other numerical results. Good agreement was observed between airflow simulation and experimental data. It is also demonstrated that the LES carried out by the MRT-LB method can produce airflow results very similar to the RNG LES and provide better prediction than the standard and RNG k–ε models. In order to further improve the efficiency of the MRT-LB method, the multi-block grid refinement (MBGR) technique was used. The accuracy and efficiency of the MBGR and the consistency of physical quantities across the interface were investigated. In simulation of particle dispersion in the model room, particles with diameters of 1 and 10 µm were considered. It is shown that this model can successfully capture dispersion characteristics of particles.


title: Exosome Biogenesis, Regulation, and Function in Viral Infection

text: Exosomes are extracellular vesicles released upon fusion of multivesicular bodies (MVBs) with the cellular plasma membrane. They originate as intraluminal vesicles (ILVs) during the process of MVB formation. Exosomes were shown to contain selectively sorted functional proteins, lipids, and RNAs, mediating cell-to-cell communications and hence playing a role in the physiology of the healthy and diseased organism. Challenges in the field include the identification of mechanisms sustaining packaging of membrane-bound and soluble material to these vesicles and the understanding of the underlying processes directing MVBs for degradation or fusion with the plasma membrane. The investigation into the formation and roles of exosomes in viral infection is in its early years. Although still controversial, exosomes can, in principle, incorporate any functional factor, provided they have an appropriate sorting signal, and thus are prone to viral exploitation. This review initially focuses on the composition and biogenesis of exosomes. It then explores the regulatory mechanisms underlying their biogenesis. Exosomes are part of the endocytic system, which is tightly regulated and able to respond to several stimuli that lead to alterations in the composition of its sub-compartments. We discuss the current knowledge of how these changes affect exosomal release. We then summarize how different viruses exploit specific proteins of endocytic sub-compartments and speculate that it could interfere with exosome function, although no direct link between viral usage of the endocytic system and exosome release has yet been reported. Many recent reports have ascribed functions to exosomes released from cells infected with a variety of animal viruses, including viral spread, host immunity, and manipulation of the microenvironment, which are discussed. Given the ever-growing roles and importance of exosomes in viral infections, understanding what regulates their composition and levels, and defining their functions will ultimately provide additional insights into the virulence and persistence of infections.


title: Parent-collected respiratory specimens—A novel method for respiratory virus and vaccine efficacy research

text: Population-based respiratory research and vaccine efficacy studies have previously required clinic or home visits when a subject had an acute respiratory illness. This method may mean parents are unwilling to enrol their child or report an illness of interest. We conducted a community-based cohort study into respiratory illnesses in 234 pre-school aged children using parent-collected specimens. Between January 2003 and January 2004 there were 563 specimens collected from 730 identified illnesses and these were tested using a panel of respiratory virus polymerase chain reaction (PCR) assays; 409 (73%) were positive for any virus. Specimens were not more likely to be positive when collected by a healthcare worker parent, when they included a throat swab, or when a very good collection technique was reported. A delay from illness onset to specimen collection of up to 5 days did not appear to impact on sensitivity of virus identification, but a delay of six or more days with minor delays in testing saw positivity fall. Combined with daily symptom diary completion and PCR testing, parent-collected specimens are an efficient and acceptable method for the conduct of future vaccine efficacy studies and other community-based respiratory virus research.


title: Generalized lattice graphs for 2D-visualization of biological information

text: Abstract Several graph representations have been introduced for different data in theoretical biology. For instance, complex networks based on Graph theory are used to represent the structure and/or dynamics of different large biological systems such as protein–protein interaction networks. In addition, Randic, Liao, Nandy, Basak, and many others developed some special types of graph-based representations. This special type of graph includes geometrical constrains to node positioning in space and adopts final geometrical shapes that resemble lattice-like patterns. Lattice networks have been used to visually depict DNA and protein sequences but they are very flexible. However, despite the proved efficacy of new lattice-like graph/networks to represent diverse systems, most works focus on only one specific type of biological data. This work proposes a generalized type of lattice and illustrates how to use it in order to represent and compare biological data from different sources. We exemplify the following cases: protein sequence; mass spectra (MS) of protein peptide mass fingerprints (PMF); molecular dynamic trajectory (MDTs) from structural studies; mRNA microarray data; single nucleotide polymorphisms (SNPs); 1D or 2D-Electrophoresis study of protein polymorphisms and protein-research patent and/or copyright information. We used data available from public sources for some examples but for other, we used experimental results reported herein for the first time. This work may break new ground for the application of Graph theory in theoretical biology and other areas of biomedical sciences.


title: COVID-19 pandemic preparedness: A practical guide from clinical pharmacists’ perspective

text: DISCLAIMER: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: To describe our hospital pharmacy department’s preparation for an influx of critically ill patients during the coronavirus disease 2019 (COVID-19) pandemic and offer guidance on clinical pharmacy services preparedness for similar crisis situations. SUMMARY: Personnel within the department of pharmacy at a medical center at the US epicenter of the COVID-19 pandemic proactively prepared a staffing and pharmacotherapeutic action plan in anticipation of an expected surge in admissions of critically ill patients with COVID-19 and expansion of acute care and intensive care unit (ICU) capacity. Guidance documents focusing on supportive care and pharmacotherapeutic treatment options were developed. Repurposing of non–ICU-trained clinical pharmacotherapy specialists to work collaboratively with clinician teams in ICUs was quickly implemented; staff were prepared for these duties through use of shared tools to facilitate education and practice standardization. CONCLUSION: As challenges were encountered at the peak of the pandemic, interdisciplinary collaboration and teamwork was crucial to ensure that all patients were proactively assessed and that their respective pharmacotherapeutic regimens were optimized.


docid: pghkmxds

title: Spatio-temporal spread of infectious pathogens of humans

text: Spatio-temporal aspects in the propagation of infectious pathogens of humans are reviewed. Mathematical modelling of these issues using metapopulation models is presented.


title: Coronavirus impacts on post-pandemic planned travel behaviours

text: • Provides a prompt understanding of a real time pandemic (coronavirus Covid-19); • Analyses the intra-pandemic perception and post-pandemic planned behaviours; • Evaluates planned changes to travel behaviours; • Discusses intra-pandemic effects on perceptions towards tourist destinations.


title: Immunopathology of highly virulent pathogens: insights from Ebola virus

text: Ebola virus is a highly virulent pathogen capable of inducing a frequently lethal hemorrhagic fever syndrome. Accumulating evidence indicates that the virus actively subverts both innate and adaptive immune responses and triggers harmful inflammatory responses as it inflicts direct tissue damage. The host immune system is ultimately overwhelmed by a combination of inflammatory factors and virus-induced cell damage, particularly in the liver and vasculature, often leading to death from septic shock. We summarize the mechanisms of immune dysregulation and virus-mediated cell damage in Ebola virus–infected patients. Future approaches to prevention and treatment of infection will be guided by answers to unresolved questions about interspecies transmission, molecular mechanisms of pathogenesis, and protective adaptive and innate immune responses to Ebola virus.


title: Crisis Standard of Care: Management of Infantile Spasms during COVID‐19

text: The Child Neurology Society collaborated with the Pediatric Epilepsy Research Consortium to issue an online statement April 6, 2020 of immediate recommendations to streamline diagnosis, treatment, and follow up of infantile spasms. The recommendations encourage use of telemedicine, outpatient over inpatient studies, and oral therapies as initial treatment. Each recommendation is earmarked as enduring if intended to outlast the pandemic, and limited if intended only during the duration of the pandemic. This article is protected by copyright. All rights reserved.


docid: yxtkxbag

title: Hydroxychloroquine and the treatment of Sjogren's Syndrome, Chronic Ulcerative Stomatitis, and Oral Lichen Planus in the age of COVID-19

text: The Federal Drug Administration has recently approved the off-label use of Hydroxychloroquine (HCQ) for the treatment of COVID-19 infections. However, a recent study has not only failed to demonstrate HCQ efficacy but has documented an HCQ COVID-19 therapy serious side-effect of QT prolongation and secondary arrhythmia. HCQ has been utilized as an off-label drug and deemed safe and effective for such oral lesions as Sjogren's syndrome (SS), Chronic Ulcerative Stomatitis (CUS), and Oral Lichen Planus (OLP). As HCQ may be appropriately utilized for the off-label treatment of SS, CUS, and OLP, the relevant HCQ safety concerns such as dosage, drug-drug interactions, and QT prolongation and secondary arrhythmia are discussed. Due to the possibility of decreased pharmacy HCQ supplies, replacement drugs with respect to SS, CUS, and OLP patients being successfully treated with HCQ are also discussed.


docid: azkamnpa

title: The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents

text: BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.


title: Porcine Epidemic Diarrhoea Virus in Italy: Disease spread and the role of transportation

text: Porcine Epidemic Diarrhoea Virus (PEDV) causes watery diarrhoea, dehydration, and a high mortality rate among suckling pigs. Recently, PEDV had a large negative economic impact on the swine industries in Asia and North America. In 2014, PEDV re‐emerged in many European countries, but most countries only reported a few sporadic cases. Here, we report the epidemic wave that occurred in Italy from 2015 to 2017. During this time, PEDV was detected by real‐time PCR in 438 farms located mainly in the high‐density pig production area in Northern Italy. Most of the outbreaks were in farrow‐to‐finish, farrow‐to‐wean and finisher farms. Clinical signs were observed mainly in suckling and fattening animals, while mortality rates were higher in piglets, reaching 50%. A sequence analysis showed that a PEDV strain, similar to the OH851 S‐INDEL strain isolated in the USA in January 2014, was responsible for the outbreaks in Italy in 2015 and 2016. However, from January 2017, a recombinant variant strain, containing a portion of the Swine Enteric Coronavirus in the S1 gene, spread and almost completely outcompeted the previous nonrecombinant strain. In total, 14.1% of the environmental swabs collected from trucks at slaughterhouses after animals were unloaded tested positive for PEDV before the trucks were cleaned and disinfected, and 46% remained positive after cleaning and disinfection processes were performed. Moreover, environmental swabs indicated that 17.3% of the empty trucks arriving at the farms to load animals were PEDV‐positive. This study indicates that trucks can have an important role in the spread of PEDV in Italy.


PCR detection and new therapies for COVID-19


title: Altered Gut Microbiota Profiles in Sows and Neonatal Piglets Associated with Porcine Epidemic Diarrhea Virus Infection

text: Porcine epidemic diarrhea virus (PEDV) is a devastating cause of diarrhea in pigs worldwide. Most of studies have focused on molecular and pathogenic characterization of PEDV, whereas there were limited studies in understanding the role of gut microbiota (GM) in viral-associated diarrhea. Here, using the Illumina MiSeq platform, we examined and compared the impact of PEDV infection on the GM of sows and their piglets less than 10 days old. Our results showed that PEDV caused alternations in the structure and abundance of GM from levels of phylum to genus, and even species. For sows, a significant decrease of observed species was found in diarrheal sows than that in healthy sows (p < 0.05). The unweighted and weighted UniFrac distances also revealed considerable segregations of GM structure among healthy, asymptomatic, and diarrheal sows. For piglets, Bacteroidetes, the dominant bacteria in healthy piglets, were replaced by Firmicutes in asymptomatic and diarrheal piglets. The abundances of Fusobacteria and Proteobacteria were also remarkably increased in asymptomatic piglets and diarrheal piglets when compared to those of the healthy piglets. Our findings demonstrated that PEDV infection caused severe perturbations of GM, reduced probiotic bacteria, and enriched pathogenic bacteria.


title: The Membrane Protein of Severe Acute Respiratory Syndrome Coronavirus Functions as a Novel Cytosolic Pathogen-Associated Molecular Pattern To Promote Beta Interferon Induction via a Toll-Like-Receptor-Related TRAF3-Independent Mechanism

text: Most of the intracellular pattern recognition receptors (PRRs) reside in either the endolysosome or the cytoplasm to sense pathogen-derived RNAs, DNAs, or synthetic analogs of double-stranded RNA (dsRNA), such as poly(I:C). However, it remains elusive whether or not a pathogen-derived protein can function as a cytosolic pathogen-associated molecular pattern (PAMP). In this study, we demonstrate that delivering the membrane gene of severe acute respiratory syndrome coronavirus (SARS-CoV) into HEK293T, HEK293ET, and immobilized murine bone marrow-derived macrophage (J2-Mφ) cells significantly upregulates beta interferon (IFN-β) production. Both NF-κB and TBK1-IRF3 signaling cascades are activated by M gene products. M protein rather than M mRNA is responsible for M-mediated IFN-β induction that is preferentially associated with the activation of the Toll-like receptor (TLR) adaptor proteins MyD88, TIRAP, and TICAM2 but not the RIG-I signaling cascade. Blocking the secretion of M protein by brefeldin A (BFA) failed to reverse the M-mediated IFN-β induction. The antagonist of both TLR2 and TLR4 did not impede M-mediated IFN-β induction, indicating that the driving force for the activation of IFN-β production was generated from inside the cells. Inhibition of TRAF3 expression by specific small interfering RNA (siRNA) did not prevent M-mediated IFN-β induction. SARS-CoV pseudovirus could induce IFN-β production in an M rather than M(V68A) dependent manner, since the valine-to-alanine alteration at residue 68 in M protein markedly inhibited IFN-β production. Overall, our study indicates for the first time that a pathogen-derived protein is able to function as a cytosolic PAMP to stimulate type I interferon production by activating a noncanonical TLR signaling cascade in a TRAF3-independent manner.


title: Inactivation of influenza A viruses in the environment and modes of transmission: A critical review

text: Summary Objectives The relative importance of airborne, droplet and contact transmission of influenza A virus and the efficiency of control measures depends among other factors on the inactivation of viruses in different environmental media. Methods We systematically review available information on the environmental inactivation of influenza A viruses and employ information on infectious dose and results from mathematical models to assess transmission modes. Results Daily inactivation rate constants differ by several orders of magnitude: on inanimate surfaces and in aerosols daily inactivation rates are in the order of 1–102, on hands in the order of 103. Influenza virus can survive in aerosols for several hours, on hands for a few minutes. Nasal infectious dose of influenza A is several orders of magnitude larger than airborne infectious dose. Conclusions The airborne route is a potentially important transmission pathway for influenza in indoor environments. The importance of droplet transmission has to be reassessed. Contact transmission can be limited by fast inactivation of influenza virus on hands and is more so than airborne transmission dependent on behavioral parameters. However, the potentially large inocula deposited in the environment through sneezing and the protective effect of nasal mucus on virus survival could make contact transmission a key transmission mode.


title: Different host cell proteases activate the SARS-coronavirus spike-protein for cell–cell and virus–cell fusion

text: Abstract Severe acute respiratory syndrome coronavirus (SARS-CoV) poses a considerable threat to human health. Activation of the viral spike (S)-protein by host cell proteases is essential for viral infectivity. However, the cleavage sites in SARS-S and the protease(s) activating SARS-S are incompletely defined. We found that R667 was dispensable for SARS-S-driven virus–cell fusion and for SARS-S-activation by trypsin and cathepsin L in a virus–virus fusion assay. Mutation T760R, which optimizes the minimal furin consensus motif 758-RXXR-762, and furin overexpression augmented SARS-S activity, but did not result in detectable SARS-S cleavage. Finally, SARS-S-driven cell–cell fusion was independent of cathepsin L, a protease essential for virus–cell fusion. Instead, a so far unknown leupeptin-sensitive host cell protease activated cellular SARS-S for fusion with target cells expressing high levels of ACE2. Thus, different host cell proteases activate SARS-S for virus–cell and cell–cell fusion and SARS-S cleavage at R667 and 758-RXXR-762 can be dispensable for SARS-S activation.


title: Urgent Guidance for Navigating and Circumventing the QTc-Prolonging and Torsadogenic Potential of Possible Pharmacotherapies for Coronavirus Disease 19 (COVID-19)

text: Abstract As the coronavirus disease 19 (COVID-19) global pandemic rages across the globe, the race to prevent and treat this deadly disease has led to the “off-label” repurposing of drugs such as hydroxychloroquine and lopinavir/ritonavir, which has the potential for unwanted QT-interval prolongation and a risk of drug-induced sudden cardiac death. With the possibility that a considerable proportion of the world’s population soon could receive COVID-19 pharmacotherapies with torsadogenic potential for therapy or postexposure prophylaxis, this document serves to help health care professionals mitigate the risk of drug-induced ventricular arrhythmias while minimizing risk of COVID-19 exposure to personnel and conserving the limited supply of personal protective equipment.


title: Ninety-day inhalation study in rats, comparing smoke from cigarettes that heat tobacco with those that burn tobacco

text: Abstract Eight groups of 30 male and 30 female rats were exposed 1 hr per day, 5 days per week for 13 weeks, to smoke from reference (tobacco burned) or test (tobacco only heated) cigarettes, at nicotine concentrations of 5, 15, or 30 μg/liter of air. Similar smoke concentrations of wet total particulate matter and carbon monoxide were produced in each of the test/reference comparisons. There was a pronounced depression of minute ventilation of animals in the reference groups, but not in the test animals. Blood carboxyhemoglobin concentrations were similar in animals exposed to smoke from test and reference cigarettes. Plasma concentrations of nicotine and cotinine in the test groups were higher than in the reference groups. There were no differences between the smoke-exposed groups in terms of body weight or feed consumption. At necropsy, an increase in heart weight was noted in both high exposure groups. There were notable differences in histopathology, with fewer and less-pronounced changes in the test groups than in the reference groups. Many of the histopathological responses induced in the reference groups were absent in the test groups. Overall, the study demonstrated a substantial reduction in the biological activity of smoke from the test cigarette when compared with the reference.


High expression of ACE2 on the keratinocytes reveals skin as a potential target for SARS-CoV-2


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title: SCHIZOPHRENIA AND COVID-19 DELIRIUM.

text: Since its outbreak, coronavirus disease 2019 has been producing atypical manifestations aside from fever, coughing and dysnea. One of the most common is delirium, which, however, is highly overlooked. This has consequences in the treatment of patients and also may lead to underdiagnosing the infection. In this work, we present the case of a man diagnosed with schizophrenia, who had been stable for more than 20 years and that presented with an atypical picture of psychotic and confusional symptoms related to COVID-19 infection.


title: Prevalence and clinical characteristics of human metapneumovirus infections in hospitalized infants in Spain

text: Human metapneumovirus (hMPV), a condition recently described in the Netherlands, causes lower respiratory infections, particularly in young children and among the elderly. The objective of this study was to describe the characteristics of hMPV infections in hospitalized infants <2 years of age and to compare them to those of infections caused by respiratory syncytial virus (RSV). A prospective study was conducted on the clinical characteristics of infants admitted to hospital for respiratory infection through 5 years. Simultaneous detection of influenza A, B, and C viruses, RSV, and adenoviruses was performed in clinical samples by multiple reverse transcription nested‐PCR assay. The presence of hMPV was tested in all samples using two separate RT‐PCR tests. Some respiratory virus was detected in 70.5% of the 1,322 children included in the study. hMPV was found in 101 of the positive nasopharyngeal aspirates (10.8%), and was the most common virus after RSV and rhinovirus. Peak incidence was found in March. Over 80% of children were <12 months. The more common diagnoses were bronchiolitis (49.5%) and recurrent wheezing (45.5%). Fifty‐four percent of cases required oxygen therapy and, one percent, assisted ventilation. Thirty percent were co‐infections, with clinical characteristics indistinguishable from single infections. Seventy‐one hMPV single infections were compared to 88 RSV single infections. hMPV infections were significantly more frequent than RSV in infants older than 6 months (P = 0.04). Recurrent wheezing was diagnosed more frequently in hMPV patients (P = 0.001). All other variables tested were similar, in both groups. hMPV was the third most frequent virus after RSV and rhinovirus in infants <2 years of age, hospitalized for respiratory infection, and was associated with bronchiolitis and recurrent wheezing. hMPV predominantly occurred in spring. Co‐infections were frequent and clinically similar to single infections and RSV infections. Pediatr Pulmonol. © 2006 Wiley‐Liss, Inc.


title: The ventilation of multiple-bed hospital wards in the tropics: A review

text: Abstract Hospital and healthcare facilities have diverse indoor environment due to the different comfort and health needs of its occupants. Currently, most ventilation studies revolve around specialised areas such as operating rooms and isolation rooms. This paper focuses on the ventilation of multiple-bed hospital wards in the tropical climate, taking into account the design, indoor conditions and engineering controls. General ward layouts are described briefly. The required indoor conditions such as temperature, humidity, air movements and indoor air quality in the ward spaces are summarized based on the current guidelines and practices. Also, recent studies and engineering practices in the hospital indoor environment are elaborated. Usage of computational fluid dynamics tools for the ventilation studies is discussed as well. As identified during the review, there is an apparent knowledge gap for ventilation studies in the tropics compared with temperate climates, as fact studies have only been published for hospital wards in countries with a temperate climate. Therefore, it is highlighted that specific tropical studies along with novel engineering controls are required in addressing the ventilation requirements for the tropics.


title: Identification of Candidate COVID-19 Therapeutics using hPSC-derived Lung Organoids

text: The SARS-CoV-2 virus has caused already over 3.5 million COVID-19 cases and 250,000 deaths globally. There is an urgent need to create novel models to study SARS-CoV-2 using human disease-relevant cells to understand key features of virus biology and facilitate drug screening. As primary SARS-CoV-2 infection is respiratory-based, we developed a lung organoid model using human pluripotent stem cells (hPSCs) that could be adapted for drug screens. The lung organoids, particularly aveolar type II cells, express ACE2 and are permissive to SARS-CoV-2 infection. Transcriptomic analysis following SARS-CoV-2 infection revealed a robust induction of chemokines and cytokines with little type I/III interferon signaling, similar to that observed amongst human COVID-19 pulmonary infections. We performed a high throughput screen using hPSC-derived lung organoids and identified FDA-approved drug candidates, including imatinib and mycophenolic acid, as inhibitors of SARS-CoV-2 entry. Pre- or post-treatment with these drugs at physiologically relevant levels decreased SARS-CoV-2 infection of hPSC-derived lung organoids. Together, these data demonstrate that hPSC-derived lung cells infected by SARS-CoV-2 can model human COVID-19 disease and provide a valuable resource to screen for FDA-approved drugs that might be repurposed and should be considered for COVID-19 clinical trials.


docid: itvhobbu

title: Evaluation of an incubation instrument-free reverse transcription recombinase polymerase amplification assay for rapid and point-of-need detection of canine distemper virus

text: Abstract Canine distemper, caused by Canine distemper virus (CDV), is a highly contagious and fatal systemic disease in free-living and captive carnivores worldwide. Accurate, rapid and simple detection of CDV is critical to improve disease management and prevent outbreaks. In this study, a visible and incubation instrument-free reverse-transcription recombinase polymerase amplification assay combined with lateral flow strip (LFS RT-RPA) was developed to detect CDV using primers and lateral flow (LF) probe specific for the nucleocapsid (N) protein gene. The CDV LFS RT-RPA assay was performed in a closed fist using body heat for 15 min, and the products were visible to the naked eyes on the LFS within 5 min. The assay could detect CDV, and there was no cross-reaction with the other viruses tested. Using the in vitro transcribed CDV RNA as template, the analytical sensitivity was 9.4 × 101 copies per reaction, which was the same result as that of a real-time RT-PCR. The assay performance was further evaluated by testing 32 nasal/oropharyngeal swab samples, and CDV RNA positive rate was 62.0% (20/32) by LFS RT-RPA, which was the same result as that of the real-time RT-PCR assay. The performance of the LFS RT-RPA was comparable to real-time RT-PCR, while the LFS RT-RPA assay was much faster and easier to perform. The novel CDV LFS RT-RPA assay provides an attractive and promising tool for rapid and reliable detection of CDV in the underequipped laboratory and point-of-need facility, which is of great significance in CD control in low resource settings.


title: Associations Between Media Exposure and Mental Distress Among U.S. Adults at the Beginning of the COVID-19 Pandemic

text: Introduction Exposure to disaster-related media may be a risk factor for mental distress, but this has not been examined in the context of the coronavirus disease 2019 (COVID-19 pandemic. This study assesses if exposure to social and traditional media during the rise of the COVID-19 pandemic was associated with mental distress among U.S. adults. Methods Data came from the Understanding America Study, a cross-sectional, nationally representative sample of adults who completed surveys online. Participants included 6,329 adults surveyed between March 10 and March 31, 2020. Regression analyses examined associations of: (1) self-reported average time spent on social media in a day (hours) and (2) number of traditional media sources (radio, TV, and newspaper) consulted to learn about COVID-19 with self-reported mental distress (4-item Patient Health Questionnaire). Data were analyzed in April 2020. Results Participants responding at later survey dates reported more time spent on social media (β=0.02, 95% CI=0.01, 0.03), a greater number of traditional media sources consulted to learn about COVID-19 (β=0.01, 95% CI=0.01, 0.02), and greater mental distress (β=0.07, 95% CI=0.04, 0.09). Increased time spent on social media and consulting a greater number of traditional media sources to learn about COVID-19 were independently associated with increased mental distress, even after adjusting for potential confounders (social media: β=0.14, 95% CI=0.05, 0.23; traditional media: β=0.14, 95% CI=0.08, 0.20). Conclusions Exposure to a greater number of traditional media sources and more hours of social media was modestly associated with mental distress during the rise of the COVID-19 pandemic in the U.S.


title: Enhancement of the vaccinia virus/phage T7 RNA polymerase expression system using encephalomyocarditis virus 5'-untranslated region sequences

text: Abstract A recombinant vaccinia virus producing the bacteriophage T7 RNA polymerase was used to express foreign genes in eukaryotic cells. Translation efficiency in this expression system was enhanced significantly by employing the encephalomyocarditis virus (EMCV) 5'-untranslated region (UTR) which confers cap-independent translation by directing internal initiation of translation. The enhancement was accomplished by fusing open reading frames (ORFs) to the N terminus of the EMCV polyprotein coding region, thus utilizing its highly efficient translation initiation site. Expression vectors were constructed to allow cloning in all three reading frames. As reporter genes, we used the lacZ gene and a number of genes encoding coronavirus structural proteins: among others the genes encoding glycoproteins with N-terminal signal sequences. The signal sequences of these glycoproteins are located internally in the primary translation product. We demonstrated that this did not interfere with translocation and glycosylation and yields biologically active proteins. The usefulness of sequences that direct internal initiation was extended by using EMCV UTR s to express two and three ORFs from polycistronic mRNAs.


title: Host-Encoded Reporters for the Detection and Purification of Multiple Enveloped Viruses

text: The identification of host cell factors for virus replication holds great promise for the development of new anti-viral therapies. Recently, high-throughput screening methods have emerged as powerful tools to identify candidate host factors for therapeutic intervention. The development of assay systems suitable for large-scale automated screening is of particular importance for novel viruses with high pathogenic potential for which limited biological information can be developed in a short period of time. This report presents a general enzymatic reporter system for the detection and characterization of multiple enveloped viruses that does not rely on engineering of the virus. Instead, reporter enzymes are incorporated into virus particles by targeting to lipid microdomains in producer cells. The approach allows a variety of human pathogenic enveloped viruses to be detected by sensitive, inexpensive and automatable enzymatic assays. Tagged viruses can be purified quickly and efficiently by a magnetic bead-based capture method. The method allows general detection of enveloped viruses without prior reference to their sequence.


title: Ebola virus outbreak, updates on current therapeutic strategies

text: Filoviruses are enveloped negative‐sense single‐stranded RNA viruses, which include Ebola and Marburg viruses, known to cause hemorrhagic fever in humans with a case fatality of up to 90%. There have been several Ebola virus outbreaks since the first outbreak in the Democratic Republic of Congo in 1976 of which, the recent 2013–2015 epidemic in Guinea, Liberia, and Sierra Leone is the largest in recorded history. Within a few months of the start of the outbreak in December 2013, thousands of infected cases were reported with a significant number of deaths. As of March 2015, according to the Centers for Disease Control and Prevention, there have been nearly 25 000 suspected cases, with 15 000 confirmed by laboratory testing, and over 10 000 deaths. The large number of cases and the high mortality rate, combined with the lack of effective Food and Drug Administration‐approved treatments, necessitate the development of potent and safe therapeutic measures to combat the current and future outbreaks. Since the beginning of the outbreak, there have been considerable efforts to develop and characterize protective measures including vaccines and antiviral small molecules, and some have proven effective in vitro and in animal models. Most recently, a cocktail of monoclonal antibodies has been shown to be highly effective in protecting non‐human primates from Ebola virus infection. In this review, we will discuss what is known about the nature of the virus, phylogenetic classification, genomic organization and replication, disease transmission, and viral entry and highlight the current approaches and efforts, in the development of therapeutics, to control the outbreak. Copyright © 2015 John Wiley & Sons, Ltd.


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title: CASE STUDY: Effects of a blend of prebiotics, probiotics, and hyperimmune dried egg protein on the performance, health, and innate immune responses of Holstein calves

text: ABSTRACT The objectives of this study were to evaluate the effects of supplementing a blend of prebiotics, probiotics, and hyperimmune dried egg protein on the performance, health, and innate immune responses of Holstein calves during the first 21 d of age. Ninety, day-old Holstein bull calves were completely randomized to 1 of 2 treatment groups: prophylactic or control. Prophylactic calves had a proprietary blend of prebiotics, probiotics, and hyperimmune egg protein (Calf-Pro Plus and Calf Life, C and E Agri Products, Baldwin, ND) added directly to the milk replacer at each feeding. Control calves were fed the milk replacer only. Treatment did not influence the performance of Holstein calves. Among calves that voluntarily refused milk replacer, prophylactic calves refused less (P = 0.005) than control calves over the first 4 d of life. Prophylactic treatment reduced the incidence of enteric morbidity (25.0 vs. 51.1% for prophylactic and control calves, respectively; P = 0.011). However, treatment did not influence either total peripheral leukocyte or differential counts. Furthermore, hematocrit and plasma concentrations of haptoglobin, cortisol, glucose, and urea nitrogen were not different between treatments. Last, ex vivo innate immune responses evaluated at 21 d of age were not different between treatments. Calves fed the combination of prebiotics, probiotics, and hyperimmune egg protein rejected less milk replacer during the first 4 d of the experiment and had fewer days with enteric morbidity than did the control calves.


docid: tojgojjf

title: Prior and Novel Coronaviruses, COVID-19, and Human Reproduction: What Is Known?

text: Structured Abstract Objective To summarize current understanding of the effects of novel and prior coronaviruses on human reproduction, specifically male and female gametes, and in pregnancy. Design Review of English publications in PubMed and Embase to April 6, 2020. Methods Manuscripts were screened for reports including coronavirus, reproduction, including pathophysiology and pregnancy. Intervention(s) None. Main Outcome Measure(s) Reproductive outcomes; effects on gametes; pregnancy outcomes; neonatal complications. Results Seventy-nine reports formed the basis of the review. Coronavirus binding to cells involves the S1 domain of the spike protein to receptors present in reproductive tissues, including angiotensin converting enzyme-2 (ACE2), CD26, Ezrin, and cyclophilins. SARS-CoV-1 may cause severe orchitis leading to germ cell destruction in males. Reports indicate decreased sperm concentration and motility for 72-90 days following COVID-19 infection. Gonadotropin-dependent expression of ACE2 was found in human ovaries, but it is unclear whether SARS-CoV-2 adversely affects female gametogenesis. Evidence suggests that COVID-19 infection has a lower maternal case fatality rate than SARS or MERS, but anecdotal reports suggest that infected, asymptomatic women may develop respiratory symptoms postpartum. COVID-19 infections in pregnancy are associated with preterm delivery. Postpartum neonatal transmission from mother to child has been reported. Conclusion COVID-19 infection may adversely affect some pregnant women and their offspring. Additional studies are needed to assess effects of SARS-CoV-2 infection on male and female fertility.


title: Expression, purification and crystallization of the SARS-CoV macro domain

text: Macro domains or X domains are found as modules of multidomain proteins, but can also constitute a protein on their own. Recently, biochemical and structural studies of cellular macro domains have been performed, showing that they are active as ADP-ribose-1′′-phosphatases. Macro domains are also present in a number of positive-stranded RNA viruses, but their precise function in viral replication is still unknown. The major human pathogen severe acute respiratory syndrome coronavirus (SARS-CoV) encodes 16 non-structural proteins (nsps), one of which (nsp3) encompasses a macro domain. The SARS-CoV nsp3 gene region corresponding to amino acids 182–355 has been cloned, expressed in Escherichia coli, purified and crystallized. The crystals belong to space group P2(1), with unit-cell parameters a = 37.5, b = 55.6, c = 108.9 Å, β = 91.4°, and the asymmetric unit contains either two or three molecules. Both native and selenomethionine-labelled crystals diffract to 1.8 Å.


title: Diagnostic Investigation of Emerging Viruses of Companion Animals

text: In this article, the authors are specifically concerned with the timely and accurate detection of emerging diseases of small animals that are viral in origin. Veterinarians are bound to encounter emerging viruses in their practice. The problem is unavoidable, because viruses are highly mutagenic. Even the immune response dictates the nature of virus that evolves in a host. If the clinical signs and diagnostic methods fail to correlate, the veterinarian should work with the diagnostic laboratory to solve the diagnostic puzzle.


Triumphs, trials, and tribulations of the global response to MERS coronavirus


title: Imprint Cytology for Intra-operative Assessment of Surgical Margins for Skeletal Tumours in COVID-19 Pandemic

text: In the current COVID-19 pandemic, tremendous pressure is been exerted on the existing health infrastructure of many developing nations. Limb salvage surgeries in bone and soft tissue sarcomas cannot be delayed beyond a certain time-period and constitute an orthopaedic emergency in certain situations. Evaluation of intra-operative surgical margins forms an important step especially in cases with planned close margins or intercalary resections. Techniques such as imprint cytology can be preferred over frozen sections for evaluation of the surgical margins especially in COVID-19 positive patients. The advantages it offers such as completion of the procedure within the operation room complex, no generation of aerosols, and almost equal sensitivity and specificity when compared with frozen section method do warrant a modification of current surgical practice in the current health crisis especially in resource-constrained nations. Awareness and better communication regarding the same from the pathologist to the surgical team will go a long way in conserving resources and avoid unnecessary exposure to potentially infected aerosols.


title: Childhood cervical lymphadenopathy

text: Abstract Cervical lymphadenopathy is a common problem in children. The condition most commonly represents a transient response to a benign local or generalized infection, but occasionally it might herald the presence of a more serious disorder. Acute bilateral cervical lymphadenopathy usually is caused by a viral upper respiratory tract infection or streptococcal pharyngitis. Acute unilateral cervical lymphadenitis is caused by streptococcal or staphylococcal infection in 40% to 80% of cases. The most common causes of subacute or chronic lymphadenitis are cat scratch disease, mycobacterial infection, and toxoplasmosis. Supraclavicular or posterior cervical lymphadenopathy carries a much higher risk for malignancies than does anterior cervical lymphadenopathy. Generalized lymphadenopathy is often caused by a viral infection, and less frequently by malignancies, collagen vascular diseases, and medications. Laboratory tests are not necessary in the majority of children with cervical lymphadenopathy. Most cases of lymphadenopathy are self-limited and require no treatment. The treatment of acute bacterial cervical lymphadenitis without a known primary source should provide adequate coverage for both Staphylococcus aureus and group A beta hemolytic streptococci.


title: Human Coronavirus NL63 Molecular Epidemiology and Evolutionary Patterns in Rural Coastal Kenya

text: BACKGROUND: Human coronavirus NL63 (HCoV-NL63) is a globally endemic pathogen causing mild and severe respiratory tract infections with reinfections occurring repeatedly throughout a lifetime. METHODS: Nasal samples were collected in coastal Kenya through community-based and hospital-based surveillance. HCoV-NL63 was detected with multiplex real-time reverse transcription PCR, and positive samples were targeted for nucleotide sequencing of the spike (S) protein. Additionally, paired samples from 25 individuals with evidence of repeat HCoV-NL63 infection were selected for whole-genome virus sequencing. RESULTS: HCoV-NL63 was detected in 1.3% (75/5573) of child pneumonia admissions. Two HCoV-NL63 genotypes circulated in Kilifi between 2008 and 2014. Full genome sequences formed a monophyletic clade closely related to contemporary HCoV-NL63 from other global locations. An unexpected pattern of repeat infections was observed with some individuals showing higher viral titers during their second infection. Similar patterns for 2 other endemic coronaviruses, HCoV-229E and HCoV-OC43, were observed. Repeat infections by HCoV-NL63 were not accompanied by detectable genotype switching. CONCLUSIONS: In this coastal Kenya setting, HCoV-NL63 exhibited low prevalence in hospital pediatric pneumonia admissions. Clade persistence with low genetic diversity suggest limited immune selection, and absence of detectable clade switching in reinfections indicates initial exposure was insufficient to elicit a protective immune response.


title: A SARS-CoV-2 infection model in mice demonstrates protection by neutralizing antibodies

text: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic with millions of human infections. One limitation to the evaluation of potential therapies and vaccines to inhibit SARS-CoV-2 infection and ameliorate disease is the lack of susceptible small animals in large numbers. Commercially available laboratory strains of mice are not readily infected by SARS-CoV-2 because of species-specific differences in their angiotensin-converting enzyme 2 (ACE2) receptors. Here, we transduced replication-defective adenoviruses encoding human ACE2 via intranasal administration into BALB/c mice and established receptor expression in lung tissues. hACE2-transduced mice were productively infected with SARS-CoV-2, and this resulted in high viral titers in the lung, lung pathology, and weight loss. Passive transfer of a neutralizing monoclonal antibody reduced viral burden in the lung and mitigated inflammation and weight loss. The development of an accessible mouse model of SARS-CoV-2 infection and pathogenesis will expedite the testing and deployment of therapeutics and vaccines.


title: Radiographic follow‐up of pneumonia in children

text: This study assessed the clinical value of routine follow‐up chest radiographs in hospitalized children with community‐acquired pneumonia. The study population consisted of 196 children hospitalized for community‐acquired pneumonia diagnosed between 1993–1995. Seventeen infective agents (10 viruses and 7 bacteria) were sought. Chest radiographs were taken on admission and 3–7 weeks later. All children were treated with antibiotics. Data on the course of illness over the following 8–10 years were obtained from patient files and questionnaires sent to parents. A potential causative agent was found in 165 (84%) of 196 cases. On follow‐up chest radiographs, residual or new changes were seen in 30% of cases. The residual changes tended to be more common after mixed viral‐bacterial infection (43%) than after sole viral (25%) or sole bacterial (20%) infection. Interstitial infiltrates (66%), atelectasis (46%), and enlarged lymph nodes were the most common sequelae seen on follow‐up. Residual findings on follow‐up radiographs did not affect the treatment of the children. No further chest radiographs were taken. During the 8–10‐year follow‐up of 194 children, no illnesses appeared that were associated with previous pneumonia. Twenty‐six children had a new episode of pneumonia, 7 of them had asthma, and 6 had different underlying illnesses. In conclusion, routine follow‐up chest radiographs are not needed in childhood community‐acquired pneumonia if the child has a clinically uneventful recovery. Pediatr Pulmonol. © 2005 Wiley‐Liss, Inc.


title: Safety of snake antivenom immunoglobulins: Efficacy of viral inactivation in a complete downstream process

text: Viral safety remains a challenge when processing a plasma‐derived product. A variety of pathogens might be present in the starting material, which requires a downstream process capable of broad viral reduction. In this article, we used a wide panel of viruses to assess viral removal/inactivation of our downstream process for Snake Antivenom Immunoglobulin (SAI). First, we screened and excluded equine plasma that cross‐reacted with any model virus, a procedure not published before for antivenoms. In addition, we evaluated for the first time the virucidal capacity of phenol applied to SAI products. Among the steps analyzed in the process, phenol addition was the most effective one, followed by heat, caprylic acid, and pepsin. All viruses were fully inactivated only by phenol treatment; heat, the second most effective step, did not inactivate the rotavirus and the adenovirus used. We therefore present a SAI downstream method that is cost‐effective and eliminates viruses to the extent required by WHO for a safe product. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:972–979, 2013


title: Exploration of the metal coordination region of concanavalin A for its interaction with human norovirus

text: Abstract Rapid methods for the detection and clinical treatment of human norovirus (HuNoV) are needed to control foodborne disease outbreaks, but reliable techniques that are fast and sensitive enough to detect small amounts of HuNoV in food and aquatic environments are not yet available. We explore the interactions between HuNoV and concanavalin A (Con A), which could facilitate the development of a sensitive detection tool for HuNoV. Biophysical studies including hydrogen/deuterium exchange (HDX) mass spectrometry and surface plasmon resonance (SPR) revealed that when the metal coordinated region of Con A, which spans Asp16 to His24, is converted to nine alanine residues (mCon AMCR), the affinity for HuNoV (GII.4) diminishes, demonstrating that this Ca2+ and Mn2+ coordinated region is responsible for the observed virus-protein interaction. The mutated carbohydrate binding region of Con A (mCon ACBR) does not affect binding affinity significantly, indicating that MCR of Con A is a major region of interaction to HuNoV (GII.4). The results further contribute to the development of a HuNoV concentration tool, Con A-immobilized polyacrylate beads (Con A-PAB), for rapid detection of genotypes from genogroups I and II (GI and GII). This method offers many advantages over currently available methods, including a short concentration time. HuNov (GI and GII) can be detected in just 15 min with 90% recovery through Con A-PAB application. In addition, this method can be used over a wide range of pH values (pH 3.0 – 10.0). Overall, this rapid and sensitive detection of HuNoV (GI and GII) will aid in the prevention of virus transmission pathways, and the method developed here may have applicability for other foodborne viral infections.


title: Molecular detection of gastrointestinal viral infections in hospitalized patients

text: Abstract Gastrointestinal viral syndromes are a common cause of morbidity and mortality in humans worldwide. Etiological agents include a large number of viruses encompassing several orders, families, and genera. During the period April 2011 to April 2012, 689 stool samples from as many patients hospitalized at the Fondazione IRCCS Policlinico San Matteo of Pavia exhibiting gastrointestinal syndromes were examined for the presence of rotavirus, norovirus, astrovirus, adenovirus, rhinovirus, enterovirus, parechovirus, bocavirus, coronavirus, sapovirus, cosavirus, and aichi virus using polymerase chain reaction assays. Gastrointestinal viral agents were detected in 246 (36%) patients of the 689 analyzed. Adenovirus and norovirus were the most common viruses in this cohort, while aichi virus was the only gastrointestinal agent not detected. Surprisingly, rhinovirus was one of the most frequently detected viruses. However, a potential association with gastroenteritis remains to be confirmed.


title: Neurological diseases as mortality predictive factors for patients with COVID-19: a retrospective cohort study

text: INTRODUCTION: In the current study, we evaluated factors that increase the coronavirus disease (COVID-19) patient death rate by analyzing the data from two cohort hospitals. In addition, we studied whether underlying neurological diseases are risk factors for death. METHODS: In this retrospective cohort study, we included 103 adult inpatients (aged ≥ 18 years). We evaluated differences in demographic data between surviving and non-surviving COVID-19 patients. RESULTS: In a multivariate logistic analysis, age and the presence of chronic lung disease and Alzheimer’s dementia (AD) were the only significant parameters for predicting COVID-19 non-survival (p < 0.05). However, hypertension, coronary vascular disease, dyslipidemia, chronic kidney disease, diabetes, and history of taking angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors, as well as nonsteroidal anti-inflammatory drugs (NSAIDs), were not significantly associated with the death of COVID-19 patients. The optimal cutoff value obtained from the maximum Youden index was 70 (sensitivity, 80.77%; specificity, 61.04%), and the odds ratio of non-survival increased 1.055 fold for every year of age. CONCLUSIONS: Clinicians should closely monitor and manage the symptoms of COVID-19 patients who are over the age of 70 years or have chronic lung disease or AD.


title: Molecular characterization of noroviruses detected in diarrheic stools of Michigan and Wisconsin dairy calves: circulation of two distinct subgroups

text: Abstract Noroviruses have emerged as the leading worldwide cause of acute non-bacterial gastroenteritis in humans. The presence of noroviruses in diarrheic stool samples from calves on Michigan and Wisconsin dairy farms was investigated by RT-PCR. Norovirus-positive samples were found on all eight farms studied in Michigan and on 2 out of 14 farms in Wisconsin. Phylogenetic analyses of partial polymerase and capsid sequences, derived for a subset of these bovine noroviruses, showed that these strains formed a group which is genetically distinct from the human noroviruses, but more closely related to genogroup I than to genogroup II human noroviruses. Examination of 2 full and 10 additional partial capsid (ORF2) sequences of these bovine strains revealed the presence of two genetic subgroups or clusters of bovine noroviruses circulating on Michigan and Wisconsin farms. One subgroup is “Jena-like”, the other “Newbury agent-2-like”.


title: Excess drug prescriptions during influenza and RSV seasons in the Netherlands: Potential implications for extended influenza vaccination

text: Abstract Influenza and respiratory syncytial virus (RSV) infections are responsible for considerable morbidity, mortality and health-care resource use. For the Netherlands, we estimated age and risk-group specific numbers of antibiotics, otologicals and cardiovascular prescriptions per 10,000 person-years during periods with elevated activity of influenza or RSV, and compared these with peri-season rates. Data were taken from the University of Groningen in-house prescription database (www.iadb.nl) and virological surveillance for the period 1998–2006. During influenza and RSV periods excess antibiotic prescriptions were estimated for all age groups. In the age groups 0–1 and 2–4 years, excess antibiotic prescriptions during periods with elevated RSV activity (65% and 59% of peri-seasonal rates) exceeded the surpluses estimated during the influenza-activity periods (24% and 34% of peri-seasonal rates) while for otologicals excess prescriptions were higher for influenza (22% and 27%) than for RSV (14% and 17%). Among persons of 50 years and older, notably those without medical high-risk conditions, excess prescriptions for cardiovascular medications were estimated during the influenza periods at approximately 10% (this was also already seen in persons aged 45–49). Our results may have implications for influenza vaccination policies. In particular, extension of influenza vaccination to groups of non-elderly adults and young children may lower excess prescriptions during these influenza periods for all three types of drug prescriptions investigated.


title: Discovery of a novel accessory protein NS7a encoded by porcine deltacoronavirus

text: Porcine deltacoronavirus (PDCoV) is an emerging swine enteric coronavirus. Bioinformatics predicts that PDCoV encodes two accessory proteins (NS6 and NS7), the species-specific proteins for coronavirus. In this study, four mAbs against the predicted NS7 were prepared by using the purified recombinant NS7 protein. Indirect immunofluorescence assay demonstrated that all mAbs recognized cells transfected with an NS7 expression construct or infected with PDCoV. Western blot showed that NS7-specific mAbs recognized an additional protein band of about 12 kDa from PDCoV-infected cell lysates but not from cells with the ectopic expression of NS7. Detailed analysis suggested that this additional protein band represented a novel accessory protein, termed NS7a, a 100 amino acid polypeptide identical to the 3′ end of NS7. Moreover, NS7a is encoded by a separate subgenomic mRNA with a non-canonical transcription regulatory sequence. In summary, our results identified a third accessory protein encoded by PDCoV, which will enhance our understanding of PDCoV.


Abstracts und ausgewählte Vorträge der 17. Jahrestagung der Deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI) zusammen mit der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)


title: Strengthening epidemiologic investigation of infectious diseases in Korea: lessons from the Middle East Respiratory Syndrome outbreak

text: The recent outbreak of Middle East Respiratory Syndrome (MERS) coronavirus infection in Korea resulted in large socioeconomic losses. This provoked the Korean government and the general public to recognize the importance of having a well-established system against infectious diseases. Although epidemiologic investigation is one of the most important aspects of prevention, it has been pointed out that much needs to be improved in Korea. We review here the current status of the Korean epidemiologic service and suggest possible supplementation measures. We examine the current national preventive infrastructure, including human resources such as Epidemic Intelligence Service officers, its governmental management, and related policies. In addition, we describe the practical application of these resources to the recent MERS outbreak and the progress in preventive measures. The spread of MERS demonstrated that the general readiness for emerging infectious diseases in Korea is considerably low. We believe that it is essential to increase society’s investment in disease prevention. Fostering public health personnel, legislating management policies, and establishing research centers for emerging infectious diseases are potential solutions. Evaluating international preventive systems, developing cooperative measures, and initiating improvements are necessary. We evaluated the Korean epidemiologic investigation system and the public preventive measures against infectious diseases in light of the recent MERS outbreak. We suggest that governmental authorities in Korea enforce preventive policies, foster the development of highly qualified personnel, and increase investment in the public health domain of infectious disease prevention.


title: CT imaging features of 4121 patients with COVID‐19: A meta‐analysis

text: OBJECTIVE: We systematically reviewed the computed tomography (CT) imaging features of coronavirus disease 2019 (COVID‐19) to provide reference for clinical practice. METHODS: Our article comprehensively searched PubMed, FMRS, EMbase, CNKI, WanFang databases, and VIP databases to collect literatures about the CT imaging features of COVID‐19 from 1 January to 16 March 2020. Three reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies, and then, this meta‐analysis was performed by using Stata12.0 software. RESULTS: A total of 34 retrospective studies involving a total of 4121 patients with COVID‐19 were included. The results of the meta‐analysis showed that most patients presented bilateral lung involvement (73.8%, 95% confidence interval [CI]: 65.9%‐81.1%) or multilobar involvement (67.3%, 95% CI: 54.8%‐78.7%) and just little patients showed normal CT findings (8.4%). We found that the most common changes in lesion density were ground‐glass opacities (68.1%, 95% CI: 56.9%‐78.2%). Other changes in density included air bronchogram sign (44.7%), crazy‐paving pattern (35.6%), and consolidation (32.0%). Patchy (40.3%), spider web sign (39.5%), cord‐like (36.8%), and nodular (20.5%) were common lesion shapes in patients with COVID‐19. Pleural thickening (27.1%) was found in some patients. Lymphadenopathy (5.4%) and pleural effusion (5.3%) were rare. CONCLUSION: The lung lesions of patients with COVID‐19 were mostly bilateral lungs or multilobar involved. The most common chest CT findings were patchy and ground‐glass opacities. Some patients had air bronchogram, spider web sign, and cord‐like. Lymphadenopathy and pleural effusion were rare.


title: Health Care–Acquired Viral Respiratory Diseases

text: Health care–acquired viral respiratory infections are common and cause increased patient morbidity and mortality. Respiratory syncytial virus and influenza virus are frequently transmitted in the hospital setting. Studies report decreased nosocomial transmission when aggressive infection control measures are implemented with more success using a multicomponent approach. Influenza vaccination of health care personnel has been shown to further decrease rates of transmission, thus mandatory vaccination is becoming more common. This article focuses on the epidemiology, transmission, and control of health care–associated respiratory viral infections.


title: Heat shock proteins and superantigenic properties of bacteria from the gastrointestinal tract of patients with Kawasaki disease

text: We previously suggested that gut bacteria may be involved in the onset of Kawasaki disease (KD). In this study, we evaluated the production of heat shock proteins (hsps) and superantigens (sAgs) by microorganisms isolated from the jejunal mucosa of 19 children with KD in the acute phase and from 15 age-matched control children. We identified 13 strains of Gram-negative microbes from patients with KD; these microbes produced large amounts of hsp60 and induced pro-inflammatory cytokine production by peripheral blood mononuclear cells. The Gram-negative microbes also elicited endogenous hsp60 production, leading to the secretion of anti-inflammatory intereukin-10 (IL-10). We also identified 18 strains of Gram-positive cocci that had superantigenic properties and which induced the expansion of Vβ2 T cells in vitro. All bacteria identified in this study were antibiotic resistant. These data suggest that sAg and hsps produced by gut bacteria might be involved in KD.


title: Spatial spread of an epidemic through public transportation systems with a hub

text: Abstract This article investigates an epidemic spreading among several locations through a transportation system, with a hub connecting these locations. Public transportation is not only a bridge through which infections travel from one location to another but also a place where infections occur since individuals are typically in close proximity to each other due to the limited space in these systems. A mathematical model is constructed to study the spread of an infectious disease through such systems. A variant of the next generation method is proposed and used to provide upper and lower bounds of the basic reproduction number for the model. Our investigation indicates that increasing transportation efficiency, and improving sanitation and ventilation of the public transportation system decrease the chance of an outbreak occurring. Moreover, discouraging unnecessary travel during an epidemic also decreases the chance of an outbreak. However, reducing travel by infectives while allowing susceptibles to travel may not be enough to avoid an outbreak.


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title: Is nicotine exposure linked to cardiopulmonary vulnerability to COVID‐19 in the general population?

text: The recent emergence of COVID‐19 has resulted in a worldwide crisis, with large populations locked down and transportation links severed. While approximately 80% of infected individuals have minimal symptoms, around 15–20% need to be hospitalized, greatly stressing global healthcare systems. As of March 10, the death rate appears to be about 3.4%, although this number is highly stratified among different populations. Here, we focus on those individuals who have been exposed to nicotine prior to their exposure to the virus. We predict that these individuals are ‘primed’ to be at higher risk because nicotine can directly impact the putative receptor for the virus (ACE2) and lead to deleterious signaling in lung epithelial cells.


title: Synthetic approaches toward stilbenes and their related structures

text: Compounds belonging to the stilbene family have gained remarkable significance in pharmaceutical as well as material chemistry. The current review covers the various synthetic approaches for the syntheses of stilbene scaffold and related structures over last 30 years. In addition, this review also highlights the role of stilbene intermediates used in the synthesis of important molecules with diverse applications in the field of pharmaceutics and material science.


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title: 2018 international meeting of the Global Virus Network

text: Abstract The Global Virus Network (GVN) was established in 2011 to strengthen research and responses to emerging viral causes of human disease and to prepare against new viral pandemics. There are now 45 GVN Centers of Excellence and 7 Affiliate laboratories in 29 countries. The 10th International GVN meeting was held from November 28–30, 2018 in Veyrier du Lac, France and was co-hosted by the two GVN Centers of Excellence, the Mérieux Foundation and the University of Veterinary Medicine Hannover (TiHo). The theme of this 10th International GVN meeting was “Eradication and control of (re-) emerging viruses”. This report highlights the recent accomplishments of GVN researchers in several important areas of medical virology, including strategies for the eradication of smallpox, measles, polio, SARS and vector-borne or zoonotic infections, emergence and intervention strategies for retroviruses and arboviruses, preparedness for outbreaks of Filo- and other hemophilic viruses, pathogenesis, impact and prevention of respiratory viruses, as well as, viruses affecting the central and peripheral nervous system. Also threats in crisis settings like refugee camps were presented.


In Memoriam: Michael B. Gregg (1930–2008)


title: Nucleocapsid protein of SARS coronavirus tightly binds to human cyclophilin A

text: Abstract Severe acute respiratory syndrome coronavirus (SARS-CoV) is responsible for SARS infection. Nucleocapsid protein (NP) of SARS-CoV (SARS_NP) functions in enveloping the entire genomic RNA and interacts with viron structural proteins, thus playing important roles in the process of virus particle assembly and release. Protein–protein interaction analysis using bioinformatics tools indicated that SARS_NP may bind to human cyclophilin A (hCypA), and surface plasmon resonance (SPR) technology revealed this binding with the equilibrium dissociation constant ranging from 6 to 160nM. The probable binding sites of these two proteins were detected by modeling the three-dimensional structure of the SARS_NP–hCypA complex, from which the important interaction residue pairs between the proteins were deduced. Mutagenesis experiments were carried out for validating the binding model, whose correctness was assessed by the observed effects on the binding affinities between the proteins. The reliability of the binding sites derived by the molecular modeling was confirmed by the fact that the computationally predicted values of the relative free energies of the binding for SARS_NP (or hCypA) mutants to the wild-type hCypA (or SARS_NP) are in good agreement with the data determined by SPR. Such presently observed SARS_NP–hCypA interaction model might provide a new hint for facilitating the understanding of another possible SARS-CoV infection pathway against human cell.


title: A reflection on an adapted approach from face‐to‐face to telephone consultations in our Urology outpatient department during the COVID‐19 pandemic – a pathway for change to future practice?

text: The sudden and unanticipated COVID‐19 viral pandemic of 2020 and its profound impact on the NHS prompted an almost overnight change in the services we are able to offer our patients to fulfil clinical demands. From March 2020 we have changed outpatient appointments from face‐to‐face to telephone led consultations. We have performed an early review of this service to ensure its sustainability during the unknown duration of this current crisis and to establish its potential utility when normal services resume in the future. Our results show a patient satisfaction of 93% with 83% happy to have telephone follow‐up in the future and a clinician satisfaction of 82% in adequacy of the telephone consultation in making a clinical decision. Telephone clinics are a safe and efficient alternative to face‐to‐face outpatient consultations for many patients, particularly non‐complex benign follow‐ups.


title: CORONAVIRUS PROPAGATED FROM PATIENT WITH NON-BACTERIAL GASTROENTERITIS

text: Abstract A fæcal suspension from a patient with gastroenteritis, which contained large numbers of coronavirus particles when examined by electron microscopy, was inoculated into human embryo intestinal-organ cultures and primary human embryo-kidney monolayers. In the organ cultures, the villous epithelium became detached and large numbers of coronavirus particles were seen by electron microscopy both in the medium and in thin sections of the intestinal epithelial cells, where the virus appeared to be multiplying. In organ cultures and in human embryo-kidney cells, intracytoplasmic virus was demonstrated by indirect immunofluorescence with convalescent serum from the patient.


Response to “Novel Middle East respiratory syndrome coronavirus”


title: Pathogen–Host Defense in the Evolution of Depression: Insights into Epidemiology, Genetics, Bioregional Differences and Female Preponderance

text: Significant attention has been paid to the potential adaptive value of depression as it relates to interactions with people in the social world. However, in this review, we outline the rationale of why certain features of depression including its environmental and genetic risk factors, its association with the acute phase response and its age of onset and female preponderance appear to have evolved from human interactions with pathogens in the microbial world. Approaching the relationship between inflammation and depression from this evolutionary perspective yields a number of insights that may reveal important clues regarding the origin and epidemiology of the disorder as well as the persistence of its risk alleles in the modern human genome.


title: COVID-19 pneumonia with hemoptysis: Acute segmental pulmonary emboli associated with novel coronavirus infection

text: Abstract Recent retrospective studies from Wuhan, China suggest Novel Coronavirus Disease 2019 (COVID-19) may be associated with a hypercoagulable state and increased risk for venous thromboembolism. The overlap in the signs and symptoms of COVID-19 associated Acute Respiratory Distress Syndrome (ARDS) and COVID-19 with concurrent pulmonary embolism creates a diagnostic challenge for emergency medicine physicians in patients already at risk for renal impairment. However, identifying features atypical for COVID-19 alone may play a role in the judicious use of Computed Tomography Angiography among these patients. Hemoptysis is seen in roughly 13% of pulmonary embolism cases and infrequently reported among COVID-19 infections. Additionally, the presence of right heart strain on electrocardiography (EKG) is a well described clinical presentations of pulmonary embolism not reported commonly with COVID-19 infections.