niryuu/sni-each-converted huggingface dataset:
Kenneth L. Meyer is a Foreign Service Officer with the U.S. Department of State, currently assigned to the Tri-Mission in Rome, Italy. During his 17-plus years with State, he has served in Asia, Europe, the Middle East, and the United States. The opinions expressed in this article are his alone and do not necessarily reflect those of the U.S. government. Abstract: One of the most devastating shocks to global security imaginable is a pandemic. As history helps to demonstrate, this catastrophe and its reverberations could in today's world create a scene not unlike that depicted in the Book of Revelation, when the pale horse and its rider Death sow destruction "with sword and with famine and with pestilence." To protect our own interests and security, it is imperative that the United States take preventive actions against a potential pandemic. This article argues that one important area for mitigation is climate change interacting with the growing urbanization of the world's population. These two factors combined promise massive shocks to global security, and because of the destructive potential, it is critical that U.S. national-security professionals consider this worst-case future when developing policies and strategies. If a large-scale pandemic does occur, as many scientists believe possible, are we prepared to handle it? Have we taken the actions necessary to mitigate the worst-case outcome? This article also argues that a lead actor in prevention efforts should be the U.S. military, which has the reach and resources that others do not. Biological threats-whether naturally occurring, accidental, or deliberate in origin-are among the most serious threats facing the United States and the international community. -The United States National Biodefense Strategy 1 The bane of stable international systems is their near total inability to envision mortal challenge. -Henry Kissinger 2
Output: Confronting the Pandemic Superthreat of Climate Change and Urbanization
Background In December 2019, novel coronavirus (SARS-CoV-2) infected pneumonia occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of SARS-CoV-2 pneumonia without comorbidities compared to normal controls in Chinese Han population is limited. Our objective is to describe the epidemiological and clinical characteristics of SARS-CoV-2 pneumonia without comorbidities compared to normal controls in the Chinese Han population. Methods Retrospective, multi-center case series of the 69 consecutive hospitalized patients with confirmed SARS-CoV-2 pneumonia, The study population included 69 hospitalized patients with confirmed SARS-CoV-2 pneumonia without comorbidities and 14,117 normal controls. 50.7% patients were male and 49.3% were female; 1.5% patients were asymptomatic cases, 63.8% patients were mild cases, and 36.2% patients were severe or critical cases. Compared with mild patients (n=44), severe or critical patients (n=25) were significantly older (median age, 67 years [IQR, vs. 49 years [IQR, 36-60]; p<0.01). Fever was present in 98.6% of the patients. The second most common symptom was cough (62.3%), fatigue (58.0%), sputum (39.1%), and headache (33.3%). The median incubation period was 4 days (IQR, 2 to 7). Leukocyte count was 74.1% of normal controls and lymphocyte count was 45.9% of normal controls. The phenomenon of lymphocyte depletion (PLD) observed in severe or critical cases in 100%. Levels of lactate dehydrogenase, D-dimer, procalcitonin, and interleukin-6 were showed significant differences between mild and severe or critical cases. Chest computed tomographic scans showed bilateral patchy patterns (49.3%), local patchy shadowing (29.0%), and ground glass opacity (21.7%). 7.3% patients were diagnosed ARDS, 7.3% patients were diagnosed acute cardiac injury (troponin I >28 pg/mL) and 4.4% patients were diagnosed fungal infections or shock. 4.3% patients have been discharged; 1.5% patient had died; 1.5% patient had recovery. Conclusions In this multicenter case series of 69 patients without comorbidities, the full All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. : medRxiv preprint 3 spectrum of asymptomatic, mild, severe, and critical cases is described. 50.7% patients were male and 49.3% were female; 1.5% patients were asymptomatic cases, 63.8% patients were mild cases, and 36.2% patients were severe or critical cases. 4.3% patients have been discharged; 1.5% patient had died; 1.5% patient had recovery. Among the 25 patients with severe or critical disease, 12.0% patients were underwent non-invasive mechanical ventilation, 8.0% patients underwent invasive mechanical ventilation, and 4.0% patients died. All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
Output: Clinical Characteristics of SARS-CoV-2 Pneumonia Compared to Controls in Chinese Han Population
Viral infections affect three to five million patients annually. While commonly used antivirals often show limited efficacy and serious adverse effects, herbal extracts have been in use for medicinal purposes since ancient times and are known for their antiviral properties and more tolerable side effects. Thus, naturally based pharmacotherapy may be a proper alternative for treating viral diseases. With that in mind, various pharmaceutical formulations and delivery systems including micelles, nanoparticles, nanosuspensions, solid dispersions, microspheres and crystals, self-nanoemulsifying and self-microemulsifying drug delivery systems (SNEDDS and SMEDDS) have been developed and used for antiviral delivery of natural products. These diverse technologies offer effective and reliable delivery of medicinal phytochemicals. Given the challenges and possibilities of antiviral treatment, this review provides the verified data on the medicinal plants and related herbal substances with antiviral activity, as well as applied strategies for the delivery of these plant extracts and biologically active phytochemicals.
Output: Antiviral effect of phytochemicals from medicinal plants: Applications and drug delivery strategies
The replication of numerous pathogenic viruses depends on host proteases, which therefore emerged as potential antiviral drug targets. In some cases, e.g., for influenza viruses, their function during the viral propagation cycle is relatively well understood, where they cleave and activate viral surface glycoproteins. For other viruses, e.g., Ebola virus, the function of host proteases during replication is still not clear. Host proteases may also contribute to the pathogenicity of virus infection by activating proinflammatory cytokines. For some coronaviruses, human proteases can also serve in a nonproteolytical fashion simply as receptors for virus entry. However, blocking of such protein-protein contacts is challenging, because receptor surfaces are often flat and difficult to address with small molecules. In contrast, many proteases possess well-defined binding pockets. Therefore, they can be considered as well-druggable targets, especially, if they are extracellularly active. The number of their experimental crystal structures is steadily increasing, which is an important prerequisite for a rational structure-based inhibitor design using computational chemistry tools in combination with classical medicinal chemistry approaches. Moreover, host proteases can be considered as stable targets, and their inhibition should prevent rapid resistance developments, which is often observed when addressing viral proteins. Otherwise, the inhibition of host proteases can also affect normal physiological processes leading to a higher probability of side effects and a narrow therapeutic window. Therefore, they should be preferably used in combination therapies with additional antiviral drugs. This strategy should provide a stronger antiviral efficacy, allow to use lower drug doses, and minimize side effects. Despite numerous experimental findings on their antiviral activity, no small-molecule inhibitors of host proteases have been approved for the treatment of virus infections, so far. Protease Inhibitors
Output: The Antiviral Potential of Host Protease Inhibitors
Reporter genes inserted into viral genomes enable the easy and rapid quantification of virus replication, which is instrumental to efficient in vitro screening of antiviral compounds or in vivo analysis of viral spread and pathogenesis. Based on a published design, we have generated several replication competent influenza A viruses carrying either fluorescent proteins or Gaussia luciferase. Reporter activity could be readily quantified in infected cultures, but the virus encoding Gaussia luciferase was more stable than viruses bearing fluorescent proteins and was therefore analyzed in detail. Quantification of Gaussia luciferase activity in the supernatants of infected culture allowed the convenient and highly sensitive detection of viral spread, and enzymatic activity correlated with the number of infectious particles released from infected cells. Furthermore, the Gaussia luciferase encoding virus allowed the sensitive quantification of the antiviral activity of the neuraminidase inhibitor (NAI) zanamivir and the host cell interferon-inducible transmembrane (IFITM) proteins 1-3, which are known to inhibit influenza virus entry. Finally, the virus was used to demonstrate that influenza A virus infection is sensitive to a modulator of endosomal cholesterol, in keeping with the concept that IFITMs inhibit viral entry by altering cholesterol levels in the endosomal membrane. In sum, we report the characterization of a novel influenza A reporter virus, which allows fast and sensitive detection of viral spread and its inhibition, and we show that influenza A virus entry is sensitive to alterations of endosomal cholesterol levels.
Output: Influenza A Virus Encoding Secreted Gaussia Luciferase as Useful Tool to Analyze Viral Replication and Its Inhibition by Antiviral Compounds and Cellular Proteins
Cellular C-type lectins have been reported to facilitate filovirus infection by binding to glycans on filovirus glycoprotein (GP). However, it is not clearly known whether interaction between C-type lectins and GP mediates all the steps of virus entry (i.e., attachment, internalization, and membrane fusion). In this study, we generated vesicular stomatitis viruses pseudotyped with mutant GPs that have impaired structures of the putative receptor binding regions and thus reduced ability to infect the monkey kidney cells that are routinely used for virus propagation. We found that infectivities of viruses with the mutant GPs dropped in C-type lectin-expressing cells, parallel with those in the monkey kidney cells, whereas binding activities of these GPs to the Ctype lectins were not correlated with the reduced infectivities. These results suggest that C-type lectin-mediated entry of filoviruses requires other cellular molecule(s) that may be involved in virion internalization or membrane fusion.
Output: C-type lectins do not act as functional receptors for filovirus entry into cells
The outbreaks of Middle East respiratory syndrome (MERS) previously in Middle East and recently in South Korea have raised serious concerns world-wide, reinforcing the importance of developing effective and safe vaccines against MERS-coronavirus (MERS-CoV). A number of vaccine candidates have been developed on the basis of viral vectors, recombinant proteins, DNAs, nanoparticles, and recombinant MERS-CoV, and some of them have shown efficacy in laboratory animals. However, the paucity of financial support has made it difficult to transfer effective candidates from the preclinical stage to clinical trials. Here, we summarize currently available MERS vaccine candidates and illustrate strategies for future development, with the aim of provoking government agencies and Big Pharma to invest more funds for developing efficacious and safe MERS vaccines.
Output: Middle East respiratory syndrome: current status and future prospects for vaccine development
The + 1 frameshift mutation, M5631, which is located in the gene (oxil) for cytochrome c oxidase II (COXII) of the yeast mitochondrial genome, is suppressed spontaneously to a remarkably high extent (20%-30%). The full-length wild-type COXII produced as a result of suppression allows the mutant strain to grow with a "leaky" phenotype on non-fermentable medium. In order to elucidate the factors and interactions involved in this translational suppression, the strain with the frameshift mutation was mutated by MnC12 treatment and a large number of mutants showing restriction of the suppression were isolated. Of 20 mutants exhibiting a strong, restricted, respiration-deficient (RD) phenotype, 6 were identified as having mutations in the mitochondrial genome. Furthermore, genetic analyses mapped one mutation to the vicinity of the gene for tRNA pr° and two others to a region of the tRNA cluster where two-thirds of all mitochondrial tRNA genes are encoded. The degree of restriction of the spontaneous frameshift suppression was characterized at the translational level by in vivo 3SS-labeling of the mitochondrial translational products and immunoblotting. These results showed that in some of these mutant strains the frameshift suppression product is synthesized to the same extent as in the leaky parent strain. It is suggested that more than one ÷ 1 frame-shifted product is made as a result of suppression in these strains : one is as functional as the wild-type COXII, the other(s) is (are) nonfunctional and prevent leaky growth on non-fermentable medium. A possible mechanism for this heterogenous frameshift suppression is discussed.
Output: Mitochondrial mutations restricting spontaneous translational frameshift suppression in the yeast Saccharomyces cerevisiae
We have studied the oligomerization of the membrane glycoproteins of Punta Toro virus (PTV), a member of the Phlebovirus genus of the family Bunyaviridae, and the effect of glycosylation on protein stability and transport. By using sucrose gradient centrifugation, the Gl and G2 glycoproteins in PTV-infected or recombinant-transfected cells were found to sediment as dimers after DSP cross-linking, suggesting that the G 1 and G2 proteins are associated as dimers by non-covalent interactions. Pulse-chase and two-dimensional gel analysis indicate that dimerization occurs between newly synthesized Gl and G2 proteins, and that a small fraction of the G2 proteins is assembled into G2 homodimers. The amounts of Gl and G2 proteins were substantially decreased, while the amounts of nucleocapsid protein remained nearly unchanged, when PTV-infected cells were treated with the glycosylation inhibitor tunicamycin, indicating that the Gl and G2 proteins are unstable if glycosylation is prevented.
Output: Assembly of Gl and G2 glycoprotein oligomers in Punta Toro virus-infected cells *
Introduction: The aim of the study was to demonstrate interleukin-18 (IL-18) expression in keratinocytes from psoriatic lesions in comparison to keratinocytes from uninvolved skin and to study the change of expression after therapeutic interventions. Material and methods: This study included 16 patients of different clinical subtypes of psoriasis. Interleukin-18 gene expression analysis was performed using real time quantitative PCR. Three biopsies were obtained from each patient. Two were taken from the lesional psoriatic skin and from uninvolved skin before starting treatment. A third lesional skin biopsy was taken at the end of 2 months of treatment. The treatment was in the form of topical steroids or oral systemic methotrexate. Results: Of all 16 studied patients, significantly increased IL-18 expression was noted in keratinocytes from psoriatic lesions before and after treatment when compared to keratinocytes from uninvolved skin (p = 0.001 and p = 0.002 respectively). The IL-18 expression in the skin lesions after treatment was significantly lower than lesional skin before treatment (p = 0.023). In psoriatic skin lesions of all studied patients IL-18 expression was significantly correlated with disease duration (r = 0.40 and p = 0.01) and clinical severity of psoriasis (r = 0.72 and p = 0.001). Conclusions: Increased IL-18 expression in keratinocytes from psoriatic lesions of our patients and its correlation with disease duration and severity supported the concept of psoriasis as a T cell mediated autoimmune disease. This could establish therapeutic and preventive approaches for psoriasis that ultimately lead to improved outcomes for patients.
Output: Interleukin-18 expression and the response to treatment in patients with psoriasis
The purpose of this subacute 22-day study was to evaluate methods for canine circulating immunoglobulins (IgM, IgG, and IgE) and select B-and T-lymphocyte populations (CD4-helpers, CD8-suppressors, pan-T and pan-B) for immunotoxicity testing using an organ system (concordance) approach. The challenge substance for immunoglobulin testing was repeated immunization with six-way distemper vaccination (DHLAPP), while the challenge substance for leukocyte subpopulations was treatment with cyclophosphamide. Immunoglobulin measurements were made by capture enzyme-linked immunosorbent assay (ELISA), and leukocyte immunophenotyping by fluorescein isothiocyanate/phycoerythrin conjugation (flow cytometry). A battery of parameters that would be used in a typical regulatory study were taken to aid interpretation of the data generated by these methods. Body weights, food consumption, clinical observations, complete clinical chemistry and urinalysis measurements were taken. Gross pathology and micropathology of sternal bone marrow, spleen, mesenteric and retropharyngeal lymph nodes, thymus, liver and kidney were completed. The ELISA method demonstrated acceptable intra-assay reproducibility for IgM, IgG and IgE, with values in good agreement as reported for radial immunodiffusion. The immunologic challenge demonstrated a biological trend of an increase in IgM that preceded an increase in IgG with no discernible trend in IgE response, and no abnormalities in lymphocyte subpopulations. Principle flow cytometry findings related to cyclophosphamide were that the relative percent of B cells decreased dramatically and progressively after compound administration; being statistically decreased in males on day 22 compared with day − 5. The relative percent CD4 and CD8 contribution increased, but the CD4/CD8 ratio remained relatively unchanged as total white blood cells decreased progressively. The increase in relative percent CD4 (males only) was statistically significant according to a two-sample t-test on days 17, 20 and 22 when compared with the pre-treatment day − 5. There was a relative percent increase in CD5-panT, but absolute numbers were dramatically decreased. We conclude that an organ system approach to assessment of the immune system which incorporates humoral antibody, enumeration of lymphocyte populations and pathologic evaluation of the lymphoreticular organs assists in the interpretation of an adverse toxicological response. The ELISA method for measurement of Igs detected the expected levels of IgG, IgM and IgE due to repeated vaccinations and to cyclophosphamide treatment. The flow cytometry method was acceptable for www.elsevier.com/locate/toxlet : S 0 3 7 8 -4 2 7 4 ( 0 0 ) 0 0 1 7 3 -9 R.D. Jones et al. / Toxicology Letters 115 (2000) 33-44 34 measuring select canine lymphocyte populations and detecting the expected decrease in B cells due to cyclophosphamide treatment. Both methods may be added to a testing battery for assessing immunotoxicity in canine regulatory studies.
Output: Capture ELISA and flow cytometry methods for toxicologic assessment following immunization and cyclophosphamide challenges in beagles
To develop effective mucosal vaccine formulation against porcine epidemic diarrhea virus (PEDV) infection, the DNA fragments encoding spike protein immunodominant region S1 and nucleocapsid N of PEDV were inserted into pPG1 (surface-displayed) or pPG2 (secretory) plasmids followed by electrotransformation into Lactobacillus casei (Lc) to yield four recombinant strains: PG1-S1, PG2-S1, PG1-N, and PG2-N. After intragastric administration, it was observed that live Lc-expressing S1 protein combined with Lc-expressing N protein could elicit much more potent mucosal and systemic immune responses than the former alone (P<0.001), however slightly inferior to the latter alone (P>0.05). Furthermore, the surface-displayed mixture (PG1-S1+ PG1-N) revealed stronger immunogenicity than the secretory mixture (PG2-S1+ PG2-N) as well as PEDV-neutralizing potency in vitro (P<0.001). On 49th day after the last immunization, splenocytes were prepared from mice immunized with surface-displayed mixture, secretory mixture and negative control to be stimulated by purified N and S protein, respectively. The results of ELISA analysis showed that N protein was capable of inducing a higher level of IL-4 (P<0.001) and IFN-γ (P<0.001) than S1 protein in the immunized mice. Taken together, Lc-expressed N protein as molecular adjuvant or immunoenhancer was able to effectively facilitate the induction of mucosal and systemic immune responses by Lc-expressing S1 region.
Output: High-level mucosal and systemic immune responses induced by oral administration with Lactobacillus-expressed porcine epidemic diarrhea virus (PEDV) S1 region combined with Lactobacillus-expressed N protein
Diversity and plasticity are two hallmarks of macrophages. M1 macrophages (classically activated macrophages) are pro-inflammatory and have a central role in host defense against infection, while M2 macrophages (alternatively activated macrophages) are associated with responses to anti-inflammatory reactions and tissue remodeling, and they represent two terminals of the full spectrum of macrophage activation. Transformation of different phenotypes of macrophages regulates the initiation, development, and cessation of inflammatory diseases. Here we reviewed the characters and functions of macrophage polarization in infection, atherosclerosis, obesity, tumor, asthma, and sepsis, and proposed that targeting macrophage polarization and skewing their phenotype to adapt to the microenvironment might hold great promise for the treatment of inflammatory diseases.
Output: Macrophage Polarization in Inflammatory Diseases
This article reports on the design, implementation and evaluation of a module in the MEd (Business) in the Faculty of Education at the University of Hong Kong in which an explicit problem-based learning (PBL) approach was used to investigate the challenges associated with the adoption and use of information and communication technologies (ICT) in Hong Kong secondary school classrooms. PBL influenced both the way the curriculum was developed and the process by which students (n = 18) investigated topics related to the integration of ICT in business studies classrooms. The evaluation was based on five evaluative questions dealing with the implementation of PBL, the extent to which PBL facilitated academic discourse, the extent of ÔnewÕ knowledge about ICT that had been created, the role of the tutor, and the online learning environment provided. The evaluation revealed that PBL provided a practical approach to investigating ICT in both face-to-face and online learning environments, leading to ÔnewÕ knowledge about challenges associated with the adoption and use of new technologies in various educational settings.
Output: Investigating ICT using problem-based learning in face-to-face and online learning environments
Vaccine design efforts against the human immunodeficiency virus (HIV) have been greatly stimulated by the observation that many infected patients eventually develop highly potent, broadly neutralizing antibodies (bnAbs). Importantly, these bnAbs have evolved to recognize not only the two protein components of the viral envelope protein (Env), but also the numerous glycans that form a protective barrier on the Env protein. Because Env is vastly overglycosylated compared to host glycoproteins, the glycans have become targets for the antibody response. Therefore, considerable efforts have been made in developing and validating biophysical methods to elucidate the complex structure of the Env spike glycoprotein with its combination of glycan and protein epitopes. We illustrate here how the application of robust biophysical methods have transformed our understanding of the structure and function of the HIV Env spike and stimulated innovation in vaccine design strategies that takes into account the essential glycan components.
Output: Structure and Immune Recognition of the HIV Glycan Shield
This review reports the research progress in the abatement of major pollutants in air and water by environmental catalysis. For air pollution control, the selective catalytic reduction of NO x (SCR) by ammonia and hydrocarbons on metal oxide and zeolite catalysts are reviewed and discussed, as is the removal of Hg from flue gas by catalysis. The oxidation of Volatile organic compounds (VOCs) by photo-and thermal-catalysis for indoor air quality improvement is reviewed. For wastewater treatment, the catalytic elimination of inorganic and organic pollutants in wastewater is presented. In addition, the mechanism for the procedure of abatement of air and water pollutants by catalysis is discussed in this review. Finally, a research orientation on environment catalysis for the treatment of air pollutants and wastewater is proposed. Keywords air pollution control, wastewater treatment, DeNO x , selective catalytic reduction (SCR), Volatile organic compounds (VOCs), environmental catalysis 2.1 The development of NH 3 -SCR catalysts 2.1.1 Chemical reaction and mechanism of NH 3 -SCR at high temperature The commercial catalysts for stationary sources, such as power plants and industrial boilers, are based on a hightemperature SCR (HT-SCR) catalyst, V 2 O 5 -WO 3 (or MoO 3 )/TiO 2 , that operates in the high-temperature range of 350°C-430°C [1]. V 2 O 5 is the main active component for the catalytic reduction of NO x , whereas WO 3 is used as an additive to increase the catalytic activity and the thermal
Output: The abatement of major pollutants in air and water by environmental catalysis
Receptors for the Fc portion of immunoglobulins (FcRs) account for most cell-mediated biological activities of antibodies. The majority of FcRs are encoded by a set of genes, clustered in the fcr locus, on chromosome 1 in humans and on chromosome 1 and 3 in mice. Eight (in humans) and six (in mice) new genes were found, intermixed with FcR genes in corresponding fcr loci, which encode FcR-like molecules (FcRLs). FcRs and FcRLs are genetically, phylogenetically, structurally, and functionally related. FcRs and FcRLs, however, markedly differ by their ligands, their tissue distribution, and, therefore, by the biological functions they control. A systematic comparison of their biological properties leads to the conclusion that FcRLs are not like FcRs. They altogether form a single family within the immunoreceptor family, whose members fulfill distinct but complementary roles in immunity by differentially controlling innate and adaptive responses.
Output: Fc Receptors and Fc Receptor-Like Molecules within the Immunoreceptor Family
Total petroleum hydrocarbons (TPH) and polycyclic aromatic hydrocarbons (PAHs) are important pollutants that affect public health in urban areas, especially in developing and oil-rich countries such as Iran. This assesses the relationship between TPH and PAHs in street dust and suspended dust, and investigates toxicity level in the urban environment of the most important petrochemical center in Iran. For this purpose, 21 and 48 street dust samples were collected for TPH analysis and PAH analysis, respectively, in Asaluyeh County. Moreover, seven air dust samples were taken for PAH analysis. TPH concentrations ranged between 240 and 4400 mg kg −1 , with a mean of 1371.43 mg kg −1 . The maximum ∑PAH concentration (6016.3 mg kg −1 ) was detected in a petrochemical complex while the minimum ∑PAHs content (16.93 mg kg −1 ) was measured in an urban area. The mean concentrations of total PAHs in street dust particles were 491.35 mg kg −1 in summer and 304.04 mg kg −1 in winter. The results indicated that PAH concentration in summer was higher. PAH sources were identified using both PAHs ratios and robust statistical methods such as Generalized Estimating Equations (GEE), backward GEE, logistic regression, principal components analysis (PCA) in conjunction with multiple linear regression (MLR) and positive matrix factorization (PMF). The results showed that PAH species generally originate from pyrogenic sources and about 0.08% of TPH was typically PAHs. However, petrogenic sources of PAHs in the industrial areas were 11.2 times more abundant than in urban areas. Also, backward GEE model demonstrated that TPH is more influenced by HMW PAHs, particularly indene. Estimated incremental lifetime cancer risk (ILCR) was higher than 10 -4 , showing that Asaluyeh inhabitants (especially children and indoor workers) are probably exposed to cancer risk, particularly through dermal contact and dust ingestion.
Output: Source identification of total petroleum hydrocarbons and polycyclic aromatic hydrocarbons in PM 10 and street dust of a hot spot for petrochemical production: Asaluyeh County, Iran
Double-stranded RNA-dependent protein kinase (PKR) regulates antiviral activity, immune responses, apoptosis and neurotoxicity. Gliatropic coronavirus infection induced PKR activation in infected as well uninfected cells within the central nervous system (CNS). However, PKR deficiency only modestly increased viral replication and did not affect IFN-α/β or IL-1β expression. Despite reduced Il-6, Ccl5, and Cxcl10 mRNA, protein levels remained unaltered. Furthermore, PKR deficiency selectively reduced IL-10 production in CD4, but not CD8 T cells, without affecting CNS pathology. The results demonstrate the ability of PKR to balance neuroinflammation by selectively modulating key cytokines and chemokines in CNS resident and CD4 T cells.
Output: PKR mediated regulation of inflammation and IL-10 during viral encephalomyelitis
Objective To determine the frequency rate of C. pneumoniae, rhinovirus, respiratory syncytial virus (RSV), influenza virus, metapneumovirus, adenovirus', parainfluenza virus and coronavirus in acute respiratory tract infections in children. Methods One hundred nine pediatric patients having respiratory tract infections were included in this study. Real time PCR, DFA and cell culture method were used for detection of C. pneumoniae, RSV antigen and influenza virus respectively. Multiplex PCR was used for detection of other viruses. Results No C. pneumoniae DNA was detected in the samples. Virus was detected in 43 cases from larynx swabs (43/ 109, 39.4 %). The frequency order of the viral agents detected were as follows; rhinoviruses 14.7 %, RSV B 7.3 %, influenza A 6.4 %, metapneumovirus 3.6 %, adenovirus 3.6 %, coronavirus 0.9 %, parainfluenzavirus type 3, 0.9 %, parainfluenzavirus type 4, 0.9 % and RSV A 0.9 %. Sensitivity of the PCR and DFA methods for the diagnosis of RSV infections were detected as 100 % and 100 %, respectively. Specificity of the PCR and DFA methods for RSV infections were detected as 97 % and 100 % respectively. Sensitivity of the PCR and cell culture methods for influenzavirus infections were detected as 100 % and 100 %, respectively. Specificity of the PCR and DFA methods for RSV infections were detected as 96 % and 100 % respectively. Conclusions Prevalence of viral agents was detected as 39.4 %. Influenza viruses and RSV were common. Metapneumovirus was also frequent (3.6 %). C. pneumoniae was not found to be a common agent for acute respiratory disease in children.
Output: Frequency of Common Viruses in Etiology of Acute Respiratory Tract Infections
► This birth cohort study has documented the influence of ARI on infant's pulmonary function test indices as indicated by significantly lower infant pulmonary function test (IPFT) indices for forced expiratory volume and flow rate, and higher indices reflecting airway resistance. ► Apart from respiratory syncytial virus and rhinovirus, human coronavirus, and human metapneumovirus infections were also significantly associated with impairment of IPFT indices. ► This is one of the first prospective birth cohort studies from Asia which has demonstrated objectively the association between ARI in infancy, irrespective of their aetiology, and impaired IPFT indices reflecting flow limitation and increased resistance at 3 years of age. Introduction Acute respiratory infections (ARIs) in infancy may have a long-term impact on the developing respiratory system. We planned a prospective cohort study to determine the impact of ARI during infancy on the pulmonary function test indices at 3 years of age. Methods A cohort of normal, full-term newborns were followed up 6 monthly and during ARI episodes. Infant pulmonary function tests (IPFTs) were performed at baseline and each follow-up visit using tidal breathing flow-volume loop, rapid thoracoabdominal compression (RTC) and raised volume RTC manoeuvres. During each ARI episode, nasopharyngeal aspirates were tested for respiratory pathogens by real-time PCR. Results We screened 3421 neonates; 310 were enrolled; IPFT was performed in 225 (boys: 125 (55.6%)) at 3 years. During infancy, 470 ARI episodes were documented in 173 infants. At 3 years, children with history of any ARI episode during infancy had lower forced expiratory volume in 1 s (FEV 1.0 ), forced expiratory volume in 0.75 s (FEV 0.75 ), forced expiratory volume in 0.5 s (FEV 0.5 ), forced expiratory flow between 25% and 75% of FVC (FEF 25-75 ), and maximal expiratory flow at 25% of FVC (MEF 25 ) as compared with those without any ARI episode during infancy. The ratio of tidal expiratory flow (TEF) at 25% or 50% of tidal expiratory volume to peak TEF (TEF 50 or TEF 25 /peak TEF) at 3 years was significantly increased in children who had ARI in infancy. Conclusions ARI during infancy is associated with impaired pulmonary function indices such as increased resistance and decreased forced expiratory flow and volume at 3 years of age.
Output: Effect of acute respiratory infections in infancy on pulmonary function test at 3 years of age: a prospective birth cohort study Paediatric lung disease
Background: Human adenovirus type 55 is a re-emerging human respiratory pathogen that is associated with several respiratory infections outbreaks in military and school populations. In this study, we describe the first HAdV55-associated hospital outbreak documented in Guangdong, China. Active surveillance was conducted in the involved neurosurgical inpatient department. All staff and patients in the involved neurosurgical department were surveyed for any symptoms of fever (≥38°C) and enlarged tonsils during the outbreak period. Throat swabs and demographic information were collected for all cases. For each specimen, assays for common respiratory viruses were performed using one-step reverse transcription-polymerase chain reaction. HAdV-positive samples were inoculated onto Hep-2 cells for isolation. Hexon genes, fiber genes, penton genes, and whole genomes were sequenced. A phylogenetic tree was constructed. Forty-three cases, including 24 laboratory-confirmed cases and 19 possible cases, were identified. Nurses had the highest attack rate of infection, with a rate of 36.4%. The attack rate for doctors and inpatients was 20.0% and 16.7%, respectively. HAdV55 was the sole pathogen identified during this outbreak. The hexon, fiber, and penton genes from seven isolated HAdV55 stains were sequenced. All these genes showed 100% homology and fell into the HAdV55 [P14H11F14] cluster, indicating that HAdV55 was the single viral strain for the outbreak. While not conclusive, the epidemic investigation revealed that the outbreak was introduced by nurses from sources outside the hospital. It was likely that a transmission from staff to inpatients had occurred. hospital infection, human adenovirus type 55, respiratory disease | 329 YI et al.
Output: A cluster of adenovirus type B55 infection in a neurosurgical inpatient department of a general hospital in Guangdong, China Background: Human adenovirus type 55 is a re-emerging human respiratory pathogen
COVID-19 has spread from China to the rest of the world in a span of just over three months, escalating into a pandemic that poses several humanitarian as well as scientific challenges. We here investigated the geographical expansion of the infection and correlate it with the annual indexes of air quality observed from the Sentinel-5 satellite orbiting around China, Italy and the U.S.A. Controlling for population size, we find more viral infections in those areas afflicted by Carbon Monoxide (CO) and Nitrogen Dioxide (NO2). Higher mortality was also correlated with poor air quality, namely with high PM2.5, CO and NO2 values. In Italy, the correspondence between poor air quality and SARS-CoV-2 appearance and induced mortality was the starkest. Similar to smoking, people living in polluted areas are more vulnerable to SARS-CoV-2 infections and induced mortality. This further suggests the detrimental impact of climate change on the prevention of epidemics.
Output: Initial evidence of higher morbidity and mortality due to SARS-CoV-2 in regions with lower air quality
Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PdCV) cause indistinguishable clinical signs and pathological changes in swine. Here we investigated the antigenic relationship between PEDV and PdCV. We provide the first evidence that conserved epitope(s) on the respective viral nucleocapsid proteins cross-react with each other although virus neutralization cross-reactivity was not observed. As a practical matter, prevention of these two very similar diseases of swine will require the development of separate virus-specific vaccine products.
Output: Two-way antigenic cross-reactivity between porcine epidemic diarrhea virus and porcine deltacoronavirus
Coronaviruses have large positive-strand RNA genomes that are 5′ capped and 3′ polyadenylated. The 5′-terminal two-thirds of the genome contain two open reading frames (ORFs), 1a and 1b, that together make up the viral replicase gene and encode two large polyproteins that are processed by viral proteases into 15-16 nonstructural proteins, most of them being involved in viral RNA synthesis. ORFs located in the 3′-terminal one-third of the genome encode structural and accessory proteins and are expressed from a set of 5′ leader-containing subgenomic mRNAs that are synthesized by a process called discontinuous transcription. Coronavirus protein synthesis not only involves cap-dependent translation mechanisms but also employs regulatory mechanisms, such as ribosomal frameshifting. Coronavirus replication is known to affect cellular translation, involving activation of stress-induced signaling pathways, and employing viral proteins that affect cellular mRNA translation and RNA stability. This chapter describes our current understanding of the mechanisms involved in coronavirus mRNA translation and changes in host mRNA translation observed in coronavirus-infected cells.
Output: Viral and Cellular mRNA Translation in Coronavirus-Infected Cells
Flaviviruses bud into the endoplasmic reticulum and are transported through the secretory pathway, where the mildly acidic environment triggers particle rearrangement and allows furin processing of the prM protein to pr and M. The peripheral pr peptide remains bound to virus at low pH and inhibits virus-membrane interaction. Upon exocytosis, the release of pr at neutral pH completes virus maturation to an infectious particle. Together this evidence suggests that pr may shield the flavivirus fusion protein E from the low pH environment of the exocytic pathway. Here we developed an in vitro system to reconstitute the interaction of dengue virus (DENV) pr with soluble truncated E proteins. At low pH recombinant pr bound to both monomeric and dimeric forms of E and blocked their membrane insertion. Exogenous pr interacted with mature infectious DENV and specifically inhibited virus fusion and infection. Alanine substitution of E H244, a highly conserved histidine residue in the pr-E interface, blocked pr-E interaction and reduced release of DENV virus-like particles. Folding, membrane insertion and trimerization of the H244A mutant E protein were preserved, and particle release could be partially rescued by neutralization of the low pH of the secretory pathway. Thus, pr acts to silence flavivirus fusion activity during virus secretion, and this function can be separated from the chaperone activity of prM. The sequence conservation of key residues involved in the flavivirus pr-E interaction suggests that this protein-protein interface may be a useful target for broad-spectrum inhibitors.
Output: In Vitro and In Vivo Studies Identify Important Features of Dengue Virus pr-E Protein Interactions
Background: In the lung, melanoma is mostly arranged as patterns of multiple nodules, solitary nodules, or miliary invasions. Very rarely, it also displays a "crazy paving" pattern (also described as a "paving stone," "flagstone," or "slabstone" pattern), which is rarer still in discrete bilateral nodules. This pattern is considered to be caused by pulmonary alveolar proteinosis, but its association with various diseases is unclear. Case presentation: A 60-year-old man was diagnosed with pulmonary melanoma. Computed tomography revealed discrete bilateral nodules surrounded by a "paving" pattern. A literature review found more than 40 types of diseases that have presented with "paving" patterns in the lung-predominantly pulmonary alveolar proteinosis, viral pneumonia, exogenous lipoid pneumonia, bacterial pneumonia, pulmonary alveolar microlithiasis, interstitial pneumonia, ARDS, squalene aspiration pneumonia, radiation pneumonitis, drug-induced pneumonitis, pulmonary leptospirosis, pulmonary hemorrhage, and pulmonary nocardiosis. Conclusions: We describe the first case of pulmonary melanoma in the form of discrete bilateral nodules accompanied with a computed tomography paving pattern. Although pulmonary paving patterns are rare, more than 40 diseases reportedly display them; clinicians should consider melanoma of the lung in differential diagnoses for patients who show such a pattern.
Output: Pulmonary melanoma and "crazy paving" patterns in chest images: a case report and literature review
Background: Acute respiratory infections (ARI) are a leading cause of morbidity and mortality globally, and are often linked to seasonal and/or meteorological conditions. Globally, Indigenous peoples may experience a different burden of ARI compared to non-Indigenous peoples. This protocol outlines our process for conducting a systematic review to investigate whether associations between ARI and seasonal or meteorological parameters differ between Indigenous and non-Indigenous groups residing in the same geographical region. Methodology: A search string will be used to search PubMed ® , CAB Abstracts/CAB Direct © , and Science Citation Index ® aggregator databases. Articles will be screened using inclusion/exclusion criteria applied first at the title and abstract level, and then at the full article level by two independent reviewers. Articles maintained after full article screening will undergo risk of bias assessment and data will be extracted. Heterogeneity tests, meta-analysis, and forest and funnel plots will be used to synthesize the results of eligible studies. Discussion and registration: This protocol paper describes our systematic review methods to identify and analyze relevant ARI, season, and meteorological literature with robust reporting. The results are intended to improve our understanding of potential associations between seasonal and meteorological parameters and ARI and, if identified, whether this association varies by place, population, or other characteristics. The protocol is registered in the PROSPERO database (#38051).
Output: A protocol for a systematic literature review: comparing the impact of seasonal and meteorological parameters on acute respiratory infections in Indigenous and non-Indigenous peoples
Miller virulent strain of transmissible gastroenteritis virus (TGEV) were generated and characterized. In a cell culture immunofluorescence (CCIF) assay, three MAbs directed against peplomer protein (E 2) had perinuclear fluorescence and four unclassified MAbs showed cell membrane fluorescence. Six of these seven MAbs neutralized both attenuated and virulent TGEV, and the seventh (an unclassified MAb) neutralized only the latter virus. Two MAbs able to bind the cell membrane of infected cells had low neutralizing antibody titers (8 to 72) but were able to distinguish between virulent and attenuated TGEV (9-to 72-fold differences in neutralizing titers). Two E 2-specific MAbs had higher neutralizing antibody titers (782 to 34,117) and showed 4-to 13-fold differences in titers against the attenuated and virulent TGEV strains. Five MAbs which were specific for nucleocapsid (N) protein had cytoplasmic, particulate fluorescence in CCIF, and did not neutralize TGEV. Comparison of CCIF antibody titers of MAbs to the virulent and attenuated strains of TGEV indicated that differences existed in titers of most E 2 and all N-specific MAbs, with titers consistently higher against virulent TGEV (homologous strain). Hyperimmune antisera prepared in gnotobiotic pigs against the attenuated, virulent and a recent isolate ofTGEV immunoprecipitated the 3 major structural proteins of both the attenuated and virulent TGEV strains. Relative mot. wt. differences in the E 1 and E 2 proteins between the two virus strains were revealed using either the hyperimmune pig sera or MAbs. In addition to the 48 K N protein, a 44 K protein was coimmunoprecipitated by the hyperimmune sera and MAbs, but mainly from lysates of attenuated TGEV.
Output: Monoclonal antibodies to a virulent strain of transmissible gastroenteritis virus: comparison of reactivity with virulent and attenuated virus
Objective. To describe the rapid development and implementation of an innovative emergency medical services (EMS) command, control, and tracking system to mitigate the risk of iatrogenic spread of severe acute respiratory syndrome (SARS) among health care facilities, health care workers, and patients in Ontario, Canada, as a result of interfacility patient transfers. Methods. A working group of stakeholders in health care and transport medicine developed and implemented a medically based command, control, and tracking center for all interfacility (including acute and long-term care) patient transfers in Ontario, Canada. Development and implementation took place in three distinct but overlapping phases: needs assessment, design and implementation, and expansion and ongoing operations. Results. The needs assessment, design, and implementation were completed in less than 48 hours using existing EMS infrastructure and personnel. The center was successfully handling more than 500 requests for interfacility patient transfer per day within 36 hours of operation and more than 1,100 requests per day within two weeks. Expansion into a new physical space enables 40 staff to process up to 1,500 requests per day. There was no reported spread of SARS resulting from interfacility patient transfers since the center began operation on April 1, 2003, and anecdotal evidence demonstrates it identified up to 13 new SARS cases. The center continues to operate as a part of Ontario's commitment as a result of diligence in transport medicine and infection control, even though no new cases of SARS were reported since June 12, 2003. Further study is needed to determine its overall efficacy at risk mitigation.
Output: AN EMERGENCY MEDICAL SERVICES TRANSFER AUTHORIZATION CENTER IN RESPONSE TO THE TORONTO SEVERE ACUTE RESPIRATORY SYNDROME OUTBREAK