niryuu/sni-each-converted huggingface dataset:
Coronaviruses are a large group of enveloped, single-stranded positive-sense RNA viruses that infect a wide range of avian and mammalian species, including humans. The emergence of deadly human coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV) have bolstered research in these viral and often zoonotic pathogens. While coronavirus cell and tissue tropism, host range, and pathogenesis are initially controlled by interactions between the spike envelope glycoprotein and host cell receptor, it is becoming increasingly apparent that proteolytic activation of spike by host cell proteases also plays a critical role. Coronavirus spike proteins are the main determinant of entry as they possess both receptor binding and fusion functions. Whereas binding to the host cell receptor is an essential first step in establishing infection, the proteolytic activation step is often critical for the fusion function of spike, as it allows for controlled release of the fusion peptide into target cellular membranes. Coronaviruses have evolved multiple strategies for proteolytic activation of spike, and a large number of host proteases have been shown to proteolytically process the spike protein. These include, but are not limited to, endosomal cathepsins, cell surface transmembrane protease/serine (TMPRSS) proteases, furin, and trypsin. This review focuses on the diversity of strategies coronaviruses have evolved to proteolytically activate their fusion protein during spike protein biosynthesis and the critical entry step of their life cycle, and highlights important findings on how proteolytic activation of coronavirus spike influences tissue and cell tropism, host range and pathogenicity.
Output: Host cell proteases: Critical determinants of coronavirus tropism and pathogenesis
Background. Bronchiolitis is associated with a greater risk of developing recurrent wheezing, but with currently available tools, it is impossible to know which infants with bronchiolitis will develop this condition. This preliminary prospective study aimed to assess whether urine metabolomic analysis can be used to identify children with bronchiolitis who are at risk of developing recurrent wheezing. Methods. Fifty-two infants <1 year old treated in the emergency department at University Hospital of Padova for acute bronchiolitis were enrolled (77% tested positive for respiratory syncytial virus [RSV]). Follow-up visits were conducted for 2 years after the episode of bronchiolitis. Untargeted metabolomic analyses based on mass spectrometry were performed on urine samples collected from infants with acute bronchiolitis. Data modeling was based on univariate and multivariate data analyses. Results. We distinguished children with and those without postbronchiolitis recurrent wheeze, defined as ≥3 episodes of physician-diagnosed wheezing. Pathway overrepresentation analysis pointed to a major involvement of the citric acid cycle (P < .001) and some amino acids (lysine, cysteine, and methionine; P ≤ .015) in differentiating between these 2 groups of children. Conclusion. This is the first study showing that metabolomic profiling of urine specimens from infants with bronchiolitis can be used to identify children at increased risk of developing recurrent wheezing.
Output: The Journal of Infectious Diseases Metabolomic Profiling of Infants With Recurrent Wheezing After Bronchiolitis
Promoting global health security as an international priority is a challenge; the US Centers for Disease Control and Prevention (CDC) in its Global Health Security Agenda has articulated the importance of accelerating progress toward a world safe and secure from infectious disease threats. The goals are to (1) prevent and reduce the likelihood of outbreaks-natural, accidental, or intentional; (2) detect threats early to save lives; and (3) respond rapidly and effectively using multisectoral, international coordination and communication. Foundational to this agenda is the World Health Organization (WHO) Revised International Health Regulations (IHR) of 2005, which provide the legal framework for countries to strengthen their health systems in order to be able to respond to any public health emergency of international concern. This article proposes leveraging the distributed structure of the US-managed Laboratory Response Network for Biological Threats Preparedness (LRN-B) to develop the core capacity of laboratory testing and to fulfill the laboratorystrengthening component of the Global Health Security Agenda. The LRN model offers an effective mechanism to detect and respond to public health emergencies of international concern. Chris N. Mangal, MPH, is
Output: Leveraging the Laboratory Response Network Model for the Global Health Security Agenda
Drawing on the lessons learned from previous disaster and disease outbreak studies over the past two decades, in the following article we review research related to social psychological assessment of community attitudes, knowledge, and beliefs associated with the recent Ebola outbreak and other public health threats, and discuss the use of this information to assist in future disaster planning and crisis communications. Psychologists, physicians, and others in the healthcare field need to be aware of these developments and involved with preparations related to mitigating the psychological impact of Ebola disease outbreaks among different populations, as well as other potential public health threats in the future.
Output: Assessing Community Reactions to Ebola Virus Disease and Other Disasters: Using Social Psychological Research to Enhance Public Health and Disaster Communications
Previous reports on the spread of bovine virus diarrhoea virus (BVDV) from animals primarily infected with the agent are contradictory. In this study, the possibility of transmission of BVDV from calves simultaneously subjected to acute BVDV and bovine coronavirus (BCV) infection was investigated. Ten calves were inoculated intranasally with BVDV Type 1. Each of the 10 calves was then randomly allocated to one of two groups. In each group there were four additional calves, resulting in five infected and four susceptible calves per group. Virulent BCV was actively introduced in one of the groups by means of a transmitter calf. Two calves, susceptible to both BVDV and BCV, were kept in a separate group, as controls. All ten calves actively inoculated with BVDV became infected as shown by seroconversions, and six of them also shed the virus in nasal secretions. However, none of the other eight calves in the two groups (four in each) seroconverted to this agent. In contrast, it proved impossible to prevent the spread of BCV infection between the experimental groups and consequently all 20 study calves became infected with the virus. Following infection, BCV was detected in nasal secretions and in faeces of the calves and, after three weeks in the study, all had seroconverted to this virus. All calves, including the controls, showed at least one of the following clinical signs during days 3±15 after the trial started: fever (!40 C), depressed general condition, diarrhoea, and cough. The study showed that BVDV primarily infected cattle, even when co-infected with an enteric and respiratory pathogen, are inefficient transmitters of BVDV. This finding supports the principle of the Scandinavian BVDV control programmes that elimination of BVDV infection from cattle populations can be achieved by identifying and removing persistently infected (PI) animals, i.e. that long-term circulation of the virus without the presence of PI animals is highly unlikely.
Output: Failure to Spread Bovine Virus Diarrhoea Virus Infection from Primarily Infected Calves Despite Concurrent Infection with Bovine Coronavirus
Objective: The emerging and recent 2014 Ebola Virus Disease (EVD) outbreaks rang the bell to call upon efforts from globe to assist resource-constrained countries to strengthen public health surveillance system for early response. Malawi adopted the Integrated Disease Surveillance and Response (IDSR) strategy to develop its national surveillance system since 2002 and revised its guideline to fulfill the International Health Regulation (IHR) requirements in 2014. This study aimed to understand the state of IDSR implementation and differences between guideline and practice for future disease surveillance system strengthening. Methods: This was a mixed-method observational study. Quantitative data were to analyze completeness and timeliness of surveillance system performance from national District Health Information System 2 (DHIS2). Qualitative data were collected through interviews with 29 frontline health service providers from the selected district and key informants of the IDSR system implementation and administration at district and national levels. Findings: The current IDSR system showed relatively good completeness (76.4%) but poor timeliness (41.5%) of total expected monthly reports nationwide and zero weekly reports. The challenges of IDSR implementation revealed through qualitative data included lack of supervision, inadequate resources for training and difficulty to implement weekly report due to overwhelming paperwork at frontline health services. Conclusions: The differences between IDSR technical guideline and actual practice were huge. The developing information technology infrastructure in Malawi and emerging mobile health (mHealth) technology can be opportunities for the country to overcome these challenges and improve surveillance system to have better timeliness for the outbreaks and unusual events detection.
Output: Title: Integrated Disease Surveillance and Response (IDSR) in Malawi: Implementation Gaps and Challenges for Timely Alert Submit journal: PLoS ONE
Autophagy is a cellular process that catabolizes cytoplasmic components and maintains energy homeostasis. As a stress response, the autophagy machinery interconnects a wide range of cellular pathways, enhancing the spread of certain pathogens while limiting others, and has become a highly active research area over the past several years. Independent laboratories have recently reported that autophagy vesicles accumulate in hepatitis C virus (HCV) infected cells and that autophagy proteins can function as proviral factors required for HCV replication. In this review, we summarize what is currently known about the interplay between autophagy and HCV and the possible mechanisms whereby autophagy proteins might favor HCV propagation.
Output: Impact of the Autophagy Machinery on Hepatitis C Virus Infection
Introduction Viral acute respiratory infections (ARIs) cause substantial child morbidity. Sensitive molecularbased assays aid virus detection, but the clinical significance of positive tests remains uncertain as some viruses may be found in both acutely ill and healthy children. We describe disease-pathogen associations of respiratory viruses and quantify virus-specific attributable risk of ARIs in healthy children during the first 2 years of life. Methods One hundred fifty-eight term newborn babies in Brisbane, Australia, were recruited progressively into a longitudinal, community-based, birth cohort study conducted between September 2010 and October 2014. A daily tick-box diary captured predefined respiratory symptoms from birth until their second birthday. Weekly parent-collected nasal swabs were batch-tested for 17 respiratory viruses by PCR assays, allowing calculation of virus-specific attributable fractions in the exposed (AFE) to determine the proportion of virus-positive children whose ARI symptoms could be attributed to that particular virus. Results Of 8100 nasal swabs analysed, 2646 (32.7%) were virus-positive (275 virus codetections, 3.4%), with human rhinoviruses accounting for 2058/2646 (77.8%) positive swabs. Viruses were detected in 1154/1530 (75.4%) ARI episodes and in 984/4308 (22.8%) swabs from asymptomatic periods. Respiratory syncytial virus (AFE: 68% (95% CI 45% to 82%)) and human metapneumovirus (AFE: 69% (95% CI 43% to 83%)) were strongly associated with higher risk of lower respiratory symptoms. Discussion The strong association of respiratory syncytial virus and human metapneumovirus with ARIs and lower respiratory symptoms in young children managed within the community indicates successful development of vaccines against these two viruses should provide substantial health benefits.
Output: Viruses causing lower respiratory symptoms in young children: findings from the ORChID birth cohort Respiratory infection
Recent advances in nucleic acid diagnostic technologies have revolutionized microbiology by facilitating rapid, sensitive pathogen surveillance and differential diagnosis of infectious diseases. With the expansion and dissemination of genomic sequencing technology scientists are discovering new microbes at an accelerating pace. In this article we review recent progress in the fi eld of pathogen surveillance and discovery with a specifi c focus on applications in the fi eld of laboratory animal research. We discuss the challenges in proving a causal relationship between the presence of a candidate organism and disease. We also discuss the strengths and limitations of various assay platforms and describe a staged strategy for viral diagnostics. To illustrate the complexity of pursuing pathogen discovery research, we include examples from our own work that are intended to provide insights into the process that led to the selection of particular strategies.
Output: Microbe Hunting in Laboratory Animal Research
Background: The novel corona virus SARS-CoV-2 (COVID-19) can infect healthcare workers. We developed an institutional algorithm to protect operating room team members during the COVID-19 pandemic and rationally conserve personal protective equipment (PPE). Study Design: An interventional platform (operating room, interventional suites, and endoscopy) PPE taskforce was convened by the hospital and medical school leadership and tasked with developing a common algorithm for PPE use, to be used throughout the interventional platform. In conjunction with our infection disease experts, we developed our guidelines based upon potential patterns of spread, risk of exposure and conservation of PPE. A decision tree algorithm describing our institutional guidelines for precautions for operating room team members was created. This algorithm is based on urgency of operation, anticipated viral burden at the surgical site, opportunity for a procedure to aerosolize virus, and likelihood a patient could be infected based on symptoms and testing. Conclusion: Despite COVID-19 being a new threat, we have shown that by developing an easyto-follow decision tree algorithm for the interventional platform teams, we can ensure optimal healthcare worker safety.
Output: Journal Pre-proof Precautions for Operating Room Team Members during the COVID-19 Pandemic Precautions for Operating Room Team Members during the COVID-19 Pandemic
was performed with RdRpSeq-Fwd (similar to the first round) and RdRpSeq-Rnest primer by using MyFi ™ Mix Kit (Bioline, USA) according to the following parameters: 95 °C for 1 min, followed by 35 cycles at 95 °C for 15 seconds, 56 °C for 15 seconds, 72 °C for 20 seconds, and 2 min at 72 °C for terminal elongation[5]. The resulted amplicons were separated by gel electrophoresis, and the DNA fragments were excised, purified and subjected to sequencing in both directions. The obtained sequences were verified by basic local alignment search tool. As for the amplification of complete N gene region, cDNA was synthesized by using SuperScript III First Strand Synthesis System for RT-PCR (Invitrogen, USA) with NR2 primer (Table 1). Two microliters of the generated cDNA was subjected to one round of PCR cycle by using MyFi ™ Mix Kit (Bioline, USA) with NF1 and NR2 (Table 1) primers following the parameters: 95 °C for 1 min followed by 25 cycles at 95 °C for 15 seconds, 52 °C for 15 seconds and 72 °C for 30 seconds and terminal elongation at 72 °C for 5 min. Then, 0.5 μL of the resulted PCR amplicon was further subjected to the second round PCR following the abovementioned parameters. The resulted PCR product was separated by gel electrophoresis while the DNA fragment was excised, purified and subjected to sequencing by using NF1, NR1, NF2, NR2 and N350R primers. The obtained sequences were analyzed by using ChromasPro version 1.7.4 (Technelysium Pty Ltd, Australia). Multiple sequence alignment was performed by using Clustal X (version 2.0.11) with 44 human-derived (including the Malaysian case; MyH010414; GenBank accession No: KP769415) and 3 camel-derived MERS-CoV sequences[6]. Maximum likelihood analysis was conducted by using Molecular Evolutionary Genetics Analysis 6.06[7]. The evolutionary history was computed by using Tamura-Nei model with 1 000 replicates of bootstrap analysis. Extracted RNA from combination of throat and nasal swabs from the case was detected positive both in rRT-PCR and conventional RT-PCR for partial RdRp and N gene. The cycle threshold values for upE, ORF1a and ORF1b were 28.19, 29.16 and 33.36, respectively. Amplification of partial RdRp and N gene regions resulted in DNA fragment of ~240 bp and ~310 bp, respectively (data not shown). Initial sequencing result of these fragments showed highly identical nucleotide sequence (99%) to MERS-CoV strain Jeddah_1_2013 (KJ556336.1), further confirming the MERS-CoV infection. JX869059/Human/Jeddah/HCoV EMC/2012 KC776174/Human/Jordan/Jordan N3/2012 Clade A 0.0005 67 63 63 63 66 50 62 Clade B Figure 1. Phylogenetic analysis of N gene region of Malaysia MERS-CoV case together with 3 camel-derived and 43 human-derived MERS-CoV sequences from 2012-2014. Red diamond: Malaysian case; Blank diamond: sequences from the camel-derived MERS-CoV.
Output: Nucleocapsid gene analysis from an imported case of Middle East respiratory syndrome coronavirus, Malaysia Asian Pacific Journal of Tropical Disease
Background: Caveolae are involved in diverse cellular functions such as signal transduction, cholesterol homeostasis, endo-and transcytosis, and also may serve as entry sites for microorganisms. Hence, their occurrence in epithelium of the airways might be expected but, nonetheless, has not yet been examined. Methods: Western blotting, real-time quantitative PCR analysis of abraded tracheal epithelium and laser-assisted microdissection combined with subsequent mRNA analysis were used to examine the expression of cav-1 and cav-2, two major caveolar coat proteins, in rat tracheal epithelium. Fluorescence immunohistochemistry was performed to locate caveolae and cav-1 and -2 in the airway epithelium of rats, mice and humans. Electron-microscopic analysis was used for the identification of caveolae. CLSM-FRET analysis determined the interaction of cav-1α and cav-2 in situ. Western blotting and laser-assisted microdissection identified protein and transcripts, respectively, of cav-1 and cav-2 in airway epithelium. Real-time quantitative RT-PCR analysis of abraded tracheal epithelium revealed a higher expression of cav-2 than of cav-1. Immunoreactivities for cav-1 and for cav-2 were co-localized in the cell membrane of the basal cells and basolaterally in the ciliated epithelial cells of large airways of rat and human. However, no labeling for cav-1 or cav-2 was observed in the epithelial cells of small bronchi. Using conventional double-labeling indirect immunofluorescence combined with CLSM-FRET analysis, we detected an association of cav-1α and -2 in epithelial cells. The presence of caveolae was confirmed by electron microscopy. In contrast to human and rat, cav-1-immunoreactivity and caveolae were confined to basal cells in mice. Epithelial caveolae were absent in cav-1-deficient mice, implicating a requirement of this caveolar protein in epithelial caveolae formation. These results show that caveolae and caveolins are integral membrane components in basal and ciliated epithelial cells, indicating a crucial role in these cell types. In addition to their physiological role, they may be involved in airway infection.
Output: Respiratory Research Caveolin-1 and -2 in airway epithelium: expression and in situ association as detected by FRET-CLSM
Foxp3 + regulatory T (Treg) cells limit inflammatory responses and maintain immune homeostasis. Although comprised of several phenotypically and functionally distinct subsets, the differentiation of specialized Treg cell populations within the periphery is poorly characterized. We demonstrate that the development of T-bet + Treg cells that potently inhibit T helper 1 (Th1) cell responses was dependent on the transcription factor STAT1 and occurred directly in response to interferon-g produced by effector T cells. Additionally, delayed induction of the IL-12Rb2 receptor component after STAT1 activation helped ensure that Treg cells do not readily complete STAT4-dependent Th1 cell development and lose their ability to suppress effector T cell proliferation. Thus, we define a pathway of abortive Th1 cell development that results in the specialization of peripheral Treg cells and demonstrate that impaired expression of a single cytokine receptor helps maintain Treg cell-suppressive function in the context of inflammatory Th1 cell responses. Immunity
Output: Article T-bet + Treg Cells Undergo Abortive Th1 Cell Differentiation due to Impaired Expression of IL-12 Receptor b2
Global health has become an increasingly important focus of education, research, and clinical service in North American universities and academic health centers. Today there are at least 49 academically based global health programs in the United States and Canada, as compared with only one in 1999. A new academic society, the Consortium of Universities for Global Health, was established in 2008 and has grown significantly. This sharp expansion reflects convergence of 3 factors: (1) rapidly growing student and faculty interest in global health; (2) growing realizationpowerfully catalyzed by the acquired immune deficiency syndrome epidemic, the emergence of other new infections, climate change, and globalization-that health problems are interconnected, cross national borders, and are global in nature; and (3) rapid expansion in resources for global health. This article examines the evolution of the concept of global health and describes the driving forces that have accelerated interest in the field. It traces the development of global health programs in academic health centers in the United States. It presents a blueprint for a new schoolwide global health program at Mount Sinai School of Medicine. The mission of that program, Mount Sinai Global Health, is to enhance global health as an academic field of study within the Mount Sinai community and to improve the health of people around the world. Mount Sinai Global Health is uniting and building synergies among strong, existing global health programs within Mount Sinai; it is training the next generation of physicians and health scientists to be leaders in global health; it is making novel discoveries that translate into blueprints for improving health worldwide; and it builds on Mount Sinai's long and proud tradition of providing medical and surgical care in places where need is great and resources few. academic health center; Consortium of Universities for Global Health; global health; Global Health Training Center; Mount Sinai "Academic medicine must take more responsibility for global health." Lancet, October 9, 2010, cover
Output: New Academic Partnerships in Global Health: Innovations at Mount Sinai School of Medicine NIH Public Access Author Manuscript
Sore throat is common in primary healthcare. Aetiological studies have focused on the presence of a limited number of pathogens. The aim of the present study was to investigate the presence of a wide range of bacteria and viruses, including Fusobacterium necrophorum, in patients with pharyngotonsillitis and in asymptomatic controls. A prospective case control study was performed in primary healthcare in Kronoberg County, Sweden. Patients (n = 220) aged 15 to 45 years with a suspected acute pharyngotonsillitis, and controls (n = 128), were included. Nasopharyngeal and throat swabs were analysed for β-hemolytic streptococci, F. necrophorum, Mycoplasma pneumoniae, and Chlamydophila pneumoniae, and 13 respiratory viruses. Serum samples were analysed for antibodies to Epstein-Barr virus. The patient history and symptoms, including Centor score, were analysed in relation to pathogens. In 155/220 (70.5%) of the patients, as compared to 26/128 (20.3%) of the controls (p <0.001), at least one microorganism was found. Group A streptococci, F. necrophorum, and influenza B virus were the three most common findings, and all significantly more common in patients than in controls (p <0.001, p 0.001, and p 0.002, respectively). Patients with F. necrophorum only (n = 14) displayed a lower Centor score than patients with Group A streptococcus only (n = 46), but a higher score than patients with influenza B, other viruses, or no potential pathogen (Kruskal-Wallis p <0.001). A pathogen was detected in 70% of the patients, displaying a wide range of pathogens contributing to the aetiology of pharyngotonsillitis. This study supports F. necrophorum as one of the pathogens to be considered in the aetiology of pharyngotonsillitis. Clinical Microbiology and Infection
Output: The aetiology of pharyngotonsillitis in adolescents and adults - Fusobacterium necrophorum is commonly found
Studying spatio-temporal evolution of epidemics can uncover important aspects of interaction among people, infectious diseases, and the environment, providing useful insights and modeling support to facilitate public health response and possibly prevention measures. This paper presents an empirical spatio-temporal analysis of epidemiological data concerning 2321 SARS-infected patients in Beijing in 2003. We mapped the SARS morbidity data with the spatial data resolution at the level of street and township. Two smoothing methods, Bayesian adjustment and spatial smoothing, were applied to identify the spatial risks and spatial transmission trends. Furthermore, we explored various spatial patterns and spatio-temporal evolution of Beijing 2003 SARS epidemic using spatial statistics such as Moran's I and LISA. Part of this study is targeted at evaluating the effectiveness of public health control measures implemented during the SARS epidemic. The main findings are as follows. (1) The diffusion speed of SARS in the northwest-southeast direction is weaker than that in northeast-southwest direction. (2) SARS's spread risk is positively spatially associated and the strength of this spatial association has experienced changes from weak to strong and then back to weak during the lifetime of the Beijing SARS epidemic. (3) Two spatial clusters of disease cases are identified: one in the city center and the other in the eastern suburban area. These two clusters followed different evolutionary paths but interacted with each other as well. (4) Although the government missed the opportunity to contain the early outbreak of SARS in March 2003, the response strategies implemented after the mid of April were effective. These response measures not only controlled the growth of the disease cases, but also mitigated the spatial diffusion. severe acute respiratory syndrome (SARS), Beijing, morbidity rate, spatial analysis, spatio-temporal evolution, control measures Citation:
Output: Spatio-temporal evolution of Beijing
Monocytes/macrophages are central mediators of inflammation and immunity and therefore of major interest in the study of immunosenescence. In healthy adult cats, monocytes have been shown to constitutively transcribe pro-and anti-inflammatory cytokines. However, in order to characterize the effect of age, feline monocyte functions were examined for changes in cytokine transcription levels in early stages of immunosenescence. For this purpose, isolated, short-term cultured monocytes from barrier-maintained adult cats of different ages (15 mo to 10 yr) were examined for transcription of IL-1b, IL-6, IL-10, IL-12 p40 and TNF-a by real-time PCR. Transcription levels of cytokines varied and were generally highest for IL-1b. For IL-1b, IL-6 and IL-12 p40, both young and old cats exhibited highest levels. The age association was significant. TNF-a appeared to be transcribed at similar levels over the examination period, whereas IL-10 tended to decline with age but without any statistical significant differences. The observed age association of the constitutive transcription of some cytokines indicates a drop in monocyte activities from youth to middle age, which is then followed by a (progressive) increase with increasing age. This provides evidence that monocytes are in part responsible for the pro-inflammatory status observed with ageing. q 2005 Elsevier Inc. All rights reserved.
Output: Age-related dynamics of constitutive cytokine transcription levels of feline monocytes
SARS-coronavirus (SARS-CoV) replication and transcription are mediated by a replication/transcription complex (RTC) of which virus-encoded, non-structural proteins (nsps) are the primary constituents. The 16 SARS-CoV nsps are produced by autoprocessing of two large precursor polyproteins. The RTC is believed to be associated with characteristic virus-induced double-membrane structures in the cytoplasm of SARS-CoV-infected cells. To investigate the link between these structures and viral RNA synthesis, and to dissect RTC organization and function, we isolated active RTCs from infected cells and used them to develop the first robust assay for their in vitro activity. The synthesis of genomic RNA and all eight subgenomic mRNAs was faithfully reproduced by the RTC in this in vitro system. Mainly positive-strand RNAs were synthesized and protein synthesis was not required for RTC activity in vitro. All RTC activity, enzymatic and putative membrane-spanning nsps, and viral RNA cosedimented with heavy membrane structures. Furthermore, the pelleted RTC required the addition of a cytoplasmic host factor for reconstitution of its in vitro activity. Newly synthesized subgenomic RNA appeared to be released, while genomic RNA remained predominantly associated with the RTC-containing fraction. RTC activity was destroyed by detergent treatment, suggesting an important role for membranes. The RTC appeared to be protected by membranes, as newly synthesized viral RNA and several replicase/transcriptase subunits were protease-and nucleaseresistant and became susceptible to degradation only upon addition of a non-ionic detergent. Our data establish a vital functional dependence of SARS-CoV RNA synthesis on virus-induced membrane structures.
Output: SARS-Coronavirus Replication/Transcription Complexes Are Membrane-Protected and Need a Host Factor for Activity In Vitro
To investigate a cluster of Middle East respiratory syndrome (MERS) cases in a women-only dormitory in Riyadh, Saudi Arabia, in October 2015, we collected epidemiologic information, nasopharyngeal/oropharyngeal swab samples, and blood samples from 828 residents during November 2015 and December 2015-January 2016. We found confirmed infection for 19 (8 by reverse transcription PCR and 11 by serologic testing). Infection attack rates varied (2.7%-32.3%) by dormitory building. No deaths occurred. Independent risk factors for infection were direct contact with a confirmed case-patient and sharing a room with a confirmed case-patient; a protective factor was having an air conditioner in the bedroom. For 9 women from whom a second serum sample was collected, antibodies remained detectable at titers >1:20 by pseudoparticle neutralization tests (n = 8) and 90% plaque-reduction neutralization tests (n = 2). In closed high-contact settings, MERS coronavirus was highly infectious and pathogenicity was relatively low.
Output: EID podcast Tuberculosis Surveillance and Control in Puerto Rico
Before 1945, Streptococcus pneumoniae caused more than 90% of cases of pneumonia in adults. After 1950, the proportion of pneumonia caused by pneumococcus began to decline. Pneumococcus has continued to decline; at present, this organism is identified in fewer than fewer10%-15% of cases. This proportion is higher in Europe, a finding likely related to differences in vaccination practices and smoking. Gram-negative bacilli, Staphylococcus aureus, Chlamydia, Mycoplasma, and Legionella are each identified in 2%-5% of patients with pneumonia who require hospitalization. Viruses are found in 25% of patients, up to one-third of these have bacterial coinfection. Recent studies fail to identify a causative organism in more than 50% of cases, which remains the most important challenge to understanding lower respiratory infection. Our findings have important implications for antibiotic stewardship and should be considered as new policies for empiric pneumonia management are developed.
Output: Clinical Infectious Diseases Evolving Understanding of the Causes of Pneumonia in Adults, With Special Attention to the Role of Pneumococcus
Hajj is a unique gathering with Mecca and Kaaba being spiritually important to many faiths across the globe, especially Muslims. This is because of the proclamation of the prophet's father, Ibrahaam, when he called all mankind to perform Hajj. That is why all Muslims on Earth feel that they have to visit Mecca and Kaaba on a specific date and time, and that is the reason this small location hosts one of the largest human gatherings in the world. Hajj is one of the five pillars of Islam that every financially and physically able Muslim must perform once in his/her lifetime. For 14 centuries countless millions of Muslim men and women from the four corners of the earth have undertaken pilgrimage to Mecca. In conclusion this review article confirm that Hajj is oldest and largest mass gathering in all mankind and there is some issues influence the health response such as size of gathering. diversity of population, climate and health facilities around hajj site, also we discuss the infectious and non infectious related illness in hajj and their prevention methods.
Output: Health response to Hajj mass gathering from emergency perspective, narrative review
Adults over 65 years of age are more vulnerable to infectious disease and show poor responses to vaccination relative to those under 50. A complex set of age-related changes in the immune system is believed to be largely responsible for these defects. These changes, collectively termed immune senescence, encompass alterations in both the innate and adaptive immune systems, in the microenvironments where immune cells develop or reside, and in soluble factors that guide immune homeostasis and function. While age-related changes in primary lymphoid organs (bone marrow, and, in particular, the thymus, which involutes in the first third of life) have been long appreciated, changes affecting aging secondary lymphoid organs, and, in particular, aging lymph nodes (LNs) have been less well characterized. Over the last 20 years, LN stromal cells have emerged as key players in maintaining LN morphology and immune homeostasis, as well as in coordinating immune responses to pathogens. Here, we review recent progress in understanding the contributions of LN stromal cells to immune senescence. We discuss approaches to understand the mechanisms behind the decline in LN stromal cells and conclude by considering potential strategies to rejuvenate aging LN stroma to improve immune homeostasis, immune responses, and vaccine efficacy in the elderly.
Output: a section of the journal Frontiers in Immunology Functional and Homeostatic impact of Age-Related Changes in Lymph node Stroma
Oligodendroglial cell death is a frequent phenomenon of many neurological diseases, e.g. in demyelinating diseases such as multiple sclerosis (MS). The underlying mechanisms are largely unknown. Here, we demonstrate that in the toxic demyelination cuprizone model, oligodendroglial cell death and downregulation of myelin genes start days after initiation of the cuprizone diet and weeks before demyelination is obvious. In earlybut not in laterstages, dying oligodendrocytes express activated caspase 3, suggesting a switch from classical apoptotic pathways to caspase 3-independent mechanisms during the course of the cuprizone diet. The expression level of FAS in the corpus callosum, a cell death receptor crucial for oligodendroglial cell death in experimental autoimmune encephalomyelitis (EAE), correlates with the expression of activated caspase 3 in oligodendrocytes. However, mice lacking FAS in oligodendrocytes are not protected against cuprizone-induced oligodendroglial cell death, showing that FAS is dispensable for oligodendroglial cell death in the cuprizone model.
Output: In toxic demyelination oligodendroglial cell death occurs early and is FAS independent
Background: There is limited evidence to support the use of facemasks in preventing infection for primary care professionals. Negative effects on communication has been suggested when the physician wears a facemask. As communication skills and doctor patient relationship are essential to primary care consultations, the effects of doctor's facemask wearing were explored. Method: A randomised controlled study was conducted in primary care to explore the effects of doctors wearing facemasks on patients' perception of doctors' empathy, patient enablement and patient satisfaction. Primary care doctors were randomized to mask wearing and non mask wearing clinical consultations in public primary care clinics in Hong Kong. Patients' views were gathered using the Consultation and Relational Empathy (CARE) Measure, Patient Enablement Instrument (PEI) and an overall satisfaction rating scale. The effects of face mask wearing were investigated using multilevel (hierarchical) modelling. Results: 1,030 patients were randomised to doctor-mask wearing consultations (n = 514) and non mask wearing consultations (n = 516). A significant and negative effect was found in the patients' perception of the doctors' empathy (CARE score reduction −0.98, p-value = 0.04). In the more established doctor-patient relationship, the effect of doctors' mask wearing was more pronounced (CARE score reduction −5.67, p-value = 0.03). Conclusion: This study demonstrates that when doctors wearing a facemask during consultations, this has a significant negative impact on the patient's perceived empathy and diminish the positive effects of relational continuity. Consideration should be taken in planning appropriate use of facemasks in infectious disease policy for primary care and other healthcare professionals at a national, local or practice level.
Output: Effect of facemasks on empathy and relational continuity: a randomised controlled trial in primary care
xMAP technology is applicable for high-throughput, multiplex and simultaneous detection of different analytes within a single complex sample. xMAP multiplex assays are currently available in various nucleic acid and immunoassay formats, enabling simultaneous detection and typing of pathogenic viruses, bacteria, parasites and fungi and also antigen or antibody interception. As an open architecture platform, the xMAP technology is beneficial to end users and therefore it is used in various pharmaceutical, clinical and research laboratories. The main aim of this review is to summarize the latest findings and applications in the field of pathogen detection using microsphere-based multiplex assays.
Output: xMAP Technology: Applications in Detection of Pathogens
Introduction: Cryptococcosis is a ubiquitous opportunistic fungal disease caused by Cryptococcus neoformans var. grubii. It has high global morbidity and mortality among HIV patients and none-HIV carriers with 99% and 95% respectively. Furthermore, the increasing prevalence of undesired toxicity profile of antifungal, multi-drug resistant organism, and the scarcity of FDA authorized vaccines, where the hallmark in the present days. This study was undertaken to design a reliable multi-epitope peptide vaccine against highly conserved immunodominant heat shock 70KDa protein of Cryptococcus neoformans var. grubii that covers a considerable digit of the world population through implementing computational vaccinology approach. Materials and Methods: A total of 38 Sequences of Cryptococcus neoformans var. grubii's heat shock 70KDa protein were retrieved from NCBI protein database. Different prediction tools were used to analyze the aforementioned protein at Immune Epitope Database (IEDB) to discriminate the most promising Tcell and B-cell epitopes. Then the proposed epitopes were subjected to Population coverage analysis tool to compute global population's coverage. Finally, the projected epitopes were ranked based on their scores and binding modes through using Moe 2007 program. Keywords: Multi-epitope peptide vaccine, Computational vaccinology, Cryptococcus neoformans var. grubii, Cryptococcosis, in silico vaccine, Heat shock 70KDa protein (Hsp70).
Output: Computational vaccinology approach: Designing an efficient multi-epitope peptide vaccine against Cryptococcus neoformans var. grubii's heat shock 70KDa protein
Cytotoxic CD8+ T-cell immunosurveillance for intracellular pathogens, such as viruses, is controlled by classical major histocompatibility complex (MHC) class Ia molecules, and ideally, these antiviral T-cell populations are defined by the specific peptide and restricting MHC allele. Surprisingly, despite the utility of the cat in modeling human viral immunity, little is known about the Feline Leukocyte Antigen class I complex (FLAI). Only a few coding sequences with uncertain locus origin and expression patterns have been reported. Of 19 class I genes, 3 loci -FLAI-E, -H and -K -are predicted to encode classical molecules, and our objective was to evaluate their status by analyzing polymorphisms and tissue expression. Using locus-specific, PCR-based genotyping, we amplified 33 FLAI-E, -H, and -K alleles from 12 cats of various breeds, identifying, for the first time, alleles across 3 distinct loci in a feline species. Alleles shared the expected polymorphic and invariant sites in the 1/ 2 domains, and full-length cDNA clones possessed all characteristic class Ia exons. Alleles could be assigned to a specific locus with reasonable confidence, although there was evidence of potentially confounding interlocus recombination between FLAI-E and -K. Only FLAI-E, -H and -K-origin alleles were amplified from cDNAs of multiple tissue types. We also defined hypervariable regions across these genes, which permitted the assignment of names to both novel and established alleles. As predicted, FLAI-E, -H, and -K fulfill the major criteria of class Ia genes. These data represent a necessary prerequisite for studying epitope-specific antiviral CD8+ T-cell responses in cats.
Output: Polymorphisms and Tissue Expression of the Feline Leukocyte Antigen Class I Loci FLAI-E, -H and -K
Les pneumonies infectieuses aiguës constituent un problème de santé publique important, car elles sont une cause majeure de morbidité et de mortalité chez l'adulte. Si les données cliniques et radiographiques permettent le plus souvent de faire le diagnostic de pneumonie infectieuse, le diagnostic étiologique est plus difficile. En effet, de nombreux agents pathogènes peuvent être responsables de pneumonie et la réaction du parenchyme pulmonaire est peu variée, d'où la faible spécificité des lésions radiologiques observées en dehors de quelques cas particuliers. C'est pourquoi la compréhension des mécanismes physiopathologiques permet d'expliquer certains aspects radiologiques. De même, la connaissance des bases anatomocliniques et radiologiques autorise la reconnaissance de trois aspects radiographiques principaux. Quant à l'appréciation des contextes épidémiologique et immunitaire, ils peuvent permettre également d'approcher le germe en cause. Abstract The acute infectious pneumonia constitute a problem of public health because they are one cause of great morbidity and mortality in adult. If the clinical and radiological information allow often to achieve the diagnosis of infectious pneumonia, the etiologic diagnosis is more difficult. Indeed, numerous pathogen germs are responsible of pneumonia and the reaction of lung is not very various, this explain the low specificity of radiological imaging, except for few characteristic cases. That's why the understanding of physiopathologic mechanisms allow to explain some special cases. In the same way, the knowledge of anatomical and radiological understanding allow the acknowledgment of three main radiographic appearance. As for the evaluation of epidemiological and immune contexte, they can allow to recognize the concern germ.
Output: Imagerie moderne des pneumonies infectieuses aiguës Modern imaging of acute infectious pneumonia
Respiratory tract infections rank second as causes of adult and paediatric morbidity and mortality worldwide. Respiratory tract infections are caused by many diff erent bacteria (including mycobacteria) and viruses, and rapid detection of pathogens in individual cases is crucial in achieving the best clinical management, public health surveillance, and control outcomes. Further challenges in improving management outcomes for respiratory tract infections exist: rapid identifi cation of drug resistant pathogens; more widespread surveillance of infections, locally and internationally; and global responses to infections with pandemic potential. Developments in genome amplifi cation have led to the discovery of several new respiratory pathogens, and sensitive PCR methods for the diagnostic work-up of these are available. Advances in technology have allowed for development of single and multiplexed PCR techniques that provide rapid detection of respiratory viruses in clinical specimens. Microarraybased multiplexing and nucleic-acid-based deep-sequencing methods allow simultaneous detection of pathogen nucleic acid and multiple antibiotic resistance, providing further hope in revolutionising rapid point of care respiratory tract infection diagnostics.
Output: Emerging respiratory tract infections 4 Rapid point of care diagnostic tests for viral and bacterial respiratory tract infections-needs, advances, and future prospects
undergo RNA recombination at a very high frequency. To understand the mechanism of recombination in murine coronavirus, we have performed RNA sequencing of viral genomic RNA to determine the precise sites of recombination in a series of recombinants which have crossovers within the gene encoding the peplomer protein. We found that all of the recombination sites are clustered within a region of 278 nucleotides in the 5'-half of the gene. This region in which all of the crossovers occurred represents a small fraction of the distance between the two selection markers used for the isolation of these recombinant viruses. This result suggests that this region may be a preferred site for RNA recombination. The crossover sites are located within and immediately adjacent to a hypervariable area of the gene. This area has undergone deletions of varying sizes in several virus strains which have been passaged either in viva or in vitro. These results suggest that a similar RNA structure may be involved in the occurrence of both recombination and deletion events. o 199OAcademic PWSS, I~C.
Output: A Clustering of RNA Recombination Sites Adjacent to a Hypervariable Region of the Peplomer Gene of Murine Coronavirus
While autophagy has been shown to act as an anti-viral defense, the Picornaviridae avoid and, in many cases, subvert this pathway to promote their own replication. Evidence indicates that some picornaviruses hijack autophagy in order to induce autophagosome-like membrane structures for genomic RNA replication. Expression of picornavirus proteins can specifically induce the machinery of autophagy, although the mechanisms by which the viruses employ autophagy appear to differ. Many picornaviruses up-regulate autophagy in order to promote viral replication while some members of the family also inhibit degradation by autolysosomes. Here we explore the unusual relationship of this medically important family of viruses with a degradative mechanism of innate immunity.
Output: Picornavirus Subversion of the Autophagy Pathway