niryuu/sni-each-converted huggingface dataset:
Although the rapidly rising transmission trend of COVID-19 in Wuhan has been controlled in late February 2020, the outbreak still caused a global pandemic afterward. Understanding Wuhan's COVID-19 transmission dynamics and the effects of prevention approaches is of significant importance for containing virus global transmission. However, most of the recent studies focused on the early outbreaks without considering improvements in diagnostic capability and effects of prevention measures together, thus the estimated results may only reflect the facts in a given period of time. We constructed a stochastic susceptible-exposed-infected-quarantined-recovered (SEIQR) model, embedding with latent periods under different prevention measures and proportions of documented infections to characterize the Wuhan COVID-19 transmission cross different stages of the outbreak. The epidemiological parameters were estimated using a particle filtering approach. Our model successfully reproduced the dynamics of the Wuhan local epidemic with two peaks on February 4 and February 12 separately. Prevention measures determined the time of reaching the first peak and caused an 87% drop in the R t from 3.09 (95% CI, 2.10 to 3.63) to 0.41 (95% CI, 0.18 to 0.66). An improved diagnostic capability created the second peak and increased the number of documented infections. The proportion of documented infections changed from 23% (95% CI, 20% to 26%) to 37% (95% CI, 33% to 41%) when the detection kits were released after January 26, and later up to 73% (95% CI, 64% to 80%) after the diagnostic criteria were improved.
Output: The impacts of diagnostic capability and prevention measures on transmission dynamics of COVID-19 in Wuhan
The cross-species transmission of viruses from one host species to another is responsible for the majority of emerging infections. However, it is unclear whether some virus families have a greater propensity to jump host species than others. If related viruses have an evolutionary history of co-divergence with their hosts there should be evidence of topological similarities between the virus and host phylogenetic trees, whereas host jumping generates incongruent tree topologies. By analyzing co-phylogenetic processes in 19 virus families and their eukaryotic hosts we provide a quantitative and comparative estimate of the relative frequency of virus-host co-divergence versus cross-species transmission among virus families. Notably, our analysis reveals that cross-species transmission is a near universal feature of the viruses analyzed here, with virus-host co-divergence occurring less frequently and always on a subset of viruses. Despite the overall high topological incongruence among virus and host phylogenies, the Hepadnaviridae, Polyomaviridae, Poxviridae, Papillomaviridae and Adenoviridae, all of which possess double-stranded DNA genomes, exhibited more frequent co-divergence than the other virus families studied here. At the other extreme, the virus and host trees for all the RNA viruses studied here, particularly the Rhabdoviridae and the Picornaviridae, displayed high levels of topological incongruence, indicative of frequent host switching. Overall, we show that cross-species transmission plays a major role in virus evolution, with all the virus families studied here having the potential to jump host species, and that increased sampling will likely reveal more instances of host jumping.
Output: Comparative analysis estimates the relative frequencies of co-divergence and cross- species transmission within viral families
Air cleaning techniques have been applied worldwide with the goal of improving indoor air quality. The effectiveness of applying these techniques varies widely, and pollutant removal efficiency is usually determined in controlled laboratory environments which may not be realized in practice. Some air cleaners are largely ineffective, and some produce harmful by-products. To summarize what is known regarding the effectiveness of fan-driven air cleaning technologies, a state-of-the-art review of the scientific literature was undertaken by a multidisciplinary panel of experts from Europe, North America, and Asia with expertise in air cleaning, aerosol science, medicine, chemistry and ventilation. The effects on health were not examined. Over 26,000 articles were identified in major literature databases; 400 were selected as being relevant based on their titles and abstracts by the first two authors, who further reduced the number of articles to 160 based on the full texts. These articles were reviewed by the panel using predefined inclusion criteria during their first meeting. Additions were also made by the panel. Of these, 133 articles were finally selected for detailed review. Each article was assessed independently by two members of the panel and then judged by the entire panel during a consensus meeting. During this process 59 articles were deemed conclusive and their results were used for final reporting at their second meeting. The conclusions are that: (1) None of the reviewed technologies was able to effectively remove all indoor pollutants and many were found to generate undesirable by-products during operation. (2) Particle filtration and sorption of gaseous pollutants were among the most effective air cleaning technologies, but there is insufficient information regarding long-term performance and proper maintenance. (3) The existing data make it difficult to extract information such as Clean Air Delivery Rate (CADR), which represents a common benchmark for comparing the performance of different air cleaning technologies. (4) To compare and select suitable indoor air cleaning devices, a labeling system accounting for characteristics such as CADR, energy consumption, volume, harmful by-products, and life span is Atmospheric Environment 45 (2011) 4329e4343 necessary. For that purpose, a standard test room and condition should be built and studied. (5) Although there is evidence that some air cleaning technologies improve indoor air quality, further research is needed before any of them can be confidently recommended for use in indoor environments.
Output: Can commonly-used fan-driven air cleaning technologies improve indoor air quality? A literature review
Introduction: Despite the integration of Chinese medicine and biomedicine which has emerged in clinical practice worldwide, a comprehensive development process for clinical practice guidelines (CPG) has up to now been missing. A valid method for the rational use of predictions for herb-drug interaction is a biggest challenge in guideline development process. Methods: This article summarises the development process by reviewing key literature from CPG developers. It focuseson key methods and challenges specific to CPGs for integration by using text mining and bioinformatics to provide a powerful adjunct to CPG development. Results: The guideline development process identified, together with new approaches, incorporates evidence-based methodology and provides better decisions through analysis of uncertain herb-drug interaction. Conclusions: This new process used three basic phases (preparation, development, and finalization) and seven steps providing a set of methodological principles for CPG development intergrating Chinese medicine and biomedicine.
Output: Developing clinical practice guidelines for the integration of Chinese medicine and biomedicine: A new process $
Human behavior has long engaged in collective behavior assembling in crowds. The Christian pilgrimage to the Holy Land has been recorded since the 4th century, while the Hajj, Islam's great pilgrimage, has existed for fourteen centuries, of which a body of literature devoted to the travelogues of the Hajj has been recorded for over ten centuries. Football is a sport played worldwide by more than 1.5 million teams and in 300,000 clubs. Most however play outside of the officially organized sphere: more than 4 percent of the global population plays football, including 270 million amateur players. Assembling for specific events is a uniquely human behavior, though the formal study of crowds did not begin until the mid-Twentieth Century. Today Mass Gathering Medicine focuses on the public health challenges to hosting events attended by a large enough number of people, at a specific site, for a defined period of time, likely to strain both the planning and response to the mass gathering of a community, state, or nation. All of us can recall attending a mass gathering, whether it be watching one's favorite rock group in performance or assembling for religious pilgrimage. Certainly, the event itself is transporting and transforming and the unison of behaviors and activities can be enormously enriching, uplifting and overwhelming, just as much as they may be at times dangerous and high risk. This review seeks to draw contrasts and comparisons between sporting gatherings and religious gatherings with a chief focus on Hajj, among the largest of all mass gatherings today. We will find there are some powerful similarities as well as stark differences. Each bequeaths a legacy which can inform the other and, as we make our observations, we join with you and the legions of other investigators who continue to remain fascinated and enthralled by mass gatherings which are among the most beloved and beholden events of modern humanity.
Output: From the "Madding Crowd" to mass gatherings-religion, sport, culture and public health
publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. braz j infect dis 2 0 1 8;2 2(5):402-411 Pediatric intensive care unit Severe acute respiratory infection (SARI) Child a b s t r a c t Objectives: The role of viral co-detection in children with severe acute respiratory infection is not clear. We described the viral detection profile and its association with clinical characteristics in children admitted to the Pediatric Intensive Care Unit (PICU) during the 2009 influenza A(H1N1) pandemic. Method: Longitudinal observational retrospective study, with patients aged 0-18 years, admitted to 11 PICUs in Rio de Janeiro, with suspected H1N1 infection, from June to November, 2009. The results of respiratory samples which were sent to the Laboratory of Fiocruz/RJ and clinical data extracted from specific forms were analyzed. Results: Of 71 samples, 38% tested positive for H1N1 virus. Of the 63 samples tested for other viruses, 58 were positive: influenza H1N1 (43.1% of positive samples), rhinovirus/enterovirus (41.4%), respiratory syncytial vírus (12.1%), human metapneumovirus (12.1%), adenovirus (6.9%), and bocavirus (3.5%). Viral codetection occured in 22.4% of the cases. H1N1-positive patients were of a higher median age, had higher frequency of fever, cough and tachypnea, and decreased leukometry when compared to H1N1-negative patients. There was no difference in relation to severity outcomes (number of organic dysfunctions, use of mechanical ventilation or amines, hospital/PICU length of stay or death). Comparing the groups with mono-detection and co-dection of any virus, no difference was found regarding the association with any clinical variable. has not yet been completely elucidated.
Output: The Brazilian Journal of INFECTIOUS DISEASES Viral detection profile in children with severe acute respiratory infection
Many pathogens relevant to human disease do not infect other animal species. Therefore, animal models that reconstitute or harbour human tissues are explored as hosts for these. In this review, we will summarize recent advances to utilize mice with human immune system components, reconstituted from hematopoietic progenitor cells in vivo. Such mice can be used to study human pathogens that replicate in leucocytes. In addition to studying the replication of these pathogens, the reconstituted human immune system components can also be analyzed for initiating immune responses and control against these infections. Moreover, these new animal models of human infectious disease should replicate the reactivity of the human immune system to vaccine candidates and, especially, the adjuvants contained in them, more faithfully.
Output: Mice with human immune system components as in vivo models for infections with human pathogens
Viruses have adapted a broad range of unique mechanisms to modulate the cellular translational machinery to ensure viral translation at the expense of cellular protein synthesis. Many of these promote virus-specific translation by use of molecular tags on viral mRNA such as internal ribosome entry sites (IRES) and genome-linked viral proteins (VPg) that bind translation machinery components in unusual ways and promote RNA circularization. This review describes recent advances in understanding some of the mechanisms in which animal virus mRNAs gain an advantage over cellular transcripts, including new structural and biochemical insights into IRES function and novel proteins that function as alternate met-tRNA i met carriers in translation initiation. Comparisons between animal and plant virus mechanisms that promote translation of viral mRNAs are discussed.
Output: Animal virus schemes for translation dominance
A new cell line derived from the kidney of European eel, Anguilla anguilla, has been established and characterized. This cell line, designated as EK (eel kidney), has been maintained in Leibovitz's L-15 supplemented with 10% fetal bovine serum for over 24 months, and subcultured more than 60 times. This cell line consists predominantly of fibroblast-like cells, and can grow at 15-37°C under an optimum temperature of 26°C. The origin of this cell line was confirmed by polymerase chain reaction (PCR) amplification and 18s recombinant (r)RNA sequencing. The chromosome analysis of EK cells at passage 58 revealed an ananeuploid karyotype. The EK cells were successfully transfected with the Pegfp-N1 plasmid, suggesting its potential in genetic studies. The susceptibility test showed a significant cytopathic effect (CPE) in EK cells for Rana grylio virus, and the viral replication was evidenced with quantitative real-time PCR (qRT-PCR) assay. After poly (I:C) stimulation, the expression of the immune-related molecules including interferon regulatory factor-3 (irf3), interferon regulatory factor-7 (irf7) and cytochrome P450 (CYP450) were significantly upregulated in EK cells, while the expression of transforming growth factor (TGF-β) was downregulated. These results suggested the potential of EK cell line as a model in gene engineering, virus identification and environmental toxicology.
Output: Development and characterization of a new cell line derived from European eel Anguilla anguilla kidney
Background The ongoing west Africa Ebola-virus-disease epidemic has disrupted the entire health-care system in aff ected countries. Because of the overlap of symptoms of Ebola virus disease and malaria, the care delivery of malaria is particularly sensitive to the indirect eff ects of the current Ebola-virus-disease epidemic. We therefore characterise malaria case management in the context of the Ebola-virus-disease epidemic and document the eff ect of the Ebolavirus-disease epidemic on malaria case management. Methods We did a cross-sectional survey of public health facilities in Guinea in December, 2014. We selected the four prefectures most aff ected by Ebola virus disease and selected four randomly from prefectures without any reported cases of the disease. 60 health facilities were sampled in Ebola-aff ected and 60 in Ebola-unaff ected prefectures. Study teams abstracted malaria case management indicators from registers for January to November for 2013 and 2014 and interviewed health-care workers. Nationwide weekly surveillance data for suspect malaria cases reported between 2011 and 2014 were analysed independently. Data for malaria indicators in 2014 were compared with previous years. 17 684) antimalarial drugs in surveyed health facilities. In Ebola-aff ected prefectures, 73 of 98 interviewed community health workers were operational (74%, 95% CI 65-83) and 35 of 73 were actively treating malaria cases (48%, 36-60) compared with 106 of 112 (95%, 89-98) and 102 of 106 (96%, 91-99), respectively, in Ebola-unaff ected prefectures. Nationwide, the Ebola-virus-disease epidemic was estimated to have resulted in 74 000 (71 000-77 000) fewer malaria cases seen at health facilities in 2014. Interpretation The reduction in the delivery of malaria care because of the Ebola-virus-disease epidemic threatens malaria control in Guinea. Untreated and inappropriately treated malaria cases lead to excess malaria mortality and more fever cases in the community, impeding the Ebola-virus-disease response.
Output: Eff ect of the Ebola-virus-disease epidemic on malaria case management in Guinea, 2014: a cross-sectional survey of health facilities
Drinking waters are treated for enteric virus via a number of disinfection techniques including chemical oxidants, irradiation, and heat, however the inactivation mechanisms during disinfection remain elusive. Owing to the fact that a number of significant waterborne virus strains are not readily culturable in vitro at this time (e.g. norovirus, hepatitis A), the susceptibility of these viruses to disinfection is largely unknown. An in-depth understanding of the mechanisms involved in virus inactivation would aid in predicting the susceptibility of non-culturable virus strains to disinfection and would foster the development of improved disinfection methods. Recent technological advances in virology research have provided a wealth of information on enteric virus compositions, structures, and biological functions. This knowledge will allow for physical/chemical descriptions of virus inactivation and thus further our understanding of virus disinfection to the most basic mechanistic level.
Output: Virus disinfection mechanisms: the role of virus composition, structure, and function
It is well established that increasing age is associated with a decreased capacity of the immune system to mediate effective immune responses to vaccination and invading pathogens. Because of the inherent limitations of conducting experiments in humans, much of what we have learned is owed to the utility of experimental mouse models of aging. Recent studies performed in the mouse have demonstrated mechanisms responsible for age-related declines in the function of CD4 + and CD8 + cells. This review describes key findings regarding age-related defects in T-cell function and discusses the impact these defects have on vaccine efficacy and immunity.
Output: T-cell immunosenescence: lessons learned from mouse models of aging
The university environment poses a high risk of spreading infectious diseases, particularly the 2009 pandemic influenza H1N1, as it is a mass gathering place for youth. This study aimed to evaluate the predictors of stress symptoms among Chinese university students during the 2009 H1N1 influenza pandemic. Material/Methods: We used a self-reported questionnaire, the PTSD (posttraumatic stress disorder) Checklist-Civilian Version (PCL-C) to evaluate the stress symptoms among Chinese university students from Heilongjiang (n=455), Beijing (n=106), Shanghai (n=419) and Sichuan (n=102). We then analyzed the predictors of stress symptoms.
Output: Predictors of symptoms of posttraumatic stress in Chinese university students during the 2009 H1N1 influenza pandemic
This paper reviews the technical developments in microbiology that led to the discovery of new infectious agents and the effect of these discoveries on establishing proof of causation. In bacteriology, these advances included the light microscope, bacterial stains, bacterial cultures, and the methods used to isolate clones. In virology, they involved the use of filters to separate viruses from bacteria, the electron microscope, the use of laboratory animals, embryonated eggs, tissue cultures to identify or grow the agent, and the recent development of molecular techniques to detect the presence of antigen in tissues. In immunology, they were based on the discovery of antibodies and of the immune response. This paper is dedicated to the late Arthur J. Viseltear, Associate Professor of the History of Medicine and Public Health. He was a dear friend and colleague, and a frequent luncheon companion on the third floor of the Laboratory of Epidemiology and Public Health. There, his wit and wisdom enlivened our conversation on an almost daily basis. His lectures and writing on the history of public health, as well as his personal encouragement of my efforts, were an inspiration to me in my modest writings on certain aspects of this subject. It is an honor to have this opportunity to express my devotion and indebtedness to him in this memorial issue of The Yale Joumal ofBiology and Medicine.
Output: Causation and Disease: Effect of Technology on Postulates of Causation*
Background: Human cytomegalovirus (HCMV) is a virus which has the potential to alter cellular gene expression through multiple mechanisms. Objective: With the application of DNA microarrays, we could monitor the effects of pathogens on host-cell gene expression programmes in great depth and on a broad scale. Methods: Changes in mRNA expression levels of human endothelial-like ECV304 cells following infection with human cytomegalovirus AD169 strain was analyzed by a microarray system comprising 21073 60-mer oligonucleotide probes which represent 18716 human genes or transcripts. Results: The results from cDNA microarray showed that there were 559 differential expressed genes consisted of 471 upregulated genes and 88 down-regulated genes. Real-time qPCR was performed to validate the expression of 6 selected genes (RPS24, MGC8721, SLC27A3, MST4, TRAF2 and LRRC28), and the results of which were consistent with those from the microarray. Among 237 biology processes, 39 biology processes were found to be related significantly to HCMV-infection. The signal transduction is the most significant biological process with the lowest p value (p=0.005) among all biological process which involved in response to HCMV infection. Conclusion: Several of these gene products might play key roles in virus-induced pathogenesis. These findings may help to elucidate the pathogenic mechanisms of HCMV caused diseases.
Output: Global analysis of differential expressed genes in ECV304 Endothelial-like cells infected with human cytomegalovirus
The general enhanced expression of α 1 -antichymotrypsin (ACT), clusterin (CLU), α 1 -antitrypsin (AAT), haptoglobin β-chain (HAP), and leucine rich glycoprotein (LRG) in the sera of patients with epithelial ovarian carcinoma (EOCa) was recently reported. In the present study, we compared the expression of the serum acute-phase proteins (APPs) in the patients according to their stages of cancer. Results: Different altered stage correlative expression of the high abundance serum APPs was demonstrated in sera of the patients studied. While the expression of ACT, HAP and AAT appeared to demonstrate positive correlation with the three initial stages of the cancer, inverse correlation was apparently detected in the expression of LRG and CLU. For patients who were diagnosed with stage IV of the cancer, expression of the serum APPs did not conform to the altered progression changes. Our results highlight the potential prognostic significance of selective high abundance serum APPs in patients with EOCa.
Output: Different altered stage correlative expression of high abundance acute-phase proteins in sera of patients with epithelial ovarian carcinoma
It is an exciting time in the field of microbiology because of the expansion of rapid diagnostic tests. Pathogen testing previously was performed by traditional laboratory methods such as bacterial, fungal, and viral culture or ova and parasite (O&P) examination. Testing could have a slow time to results; some testing lacked sensitivity, and most testing was centralized in the laboratory. Newer advances in pathogen detection assays are now providing rapid results and have greater sensitivity and specificity, and many assays are moving out of the centralized laboratory and to the patient as pointof-care tests. In this review, the authors chose to highlight the currently available US Food and Drug Administration (FDA)-cleared molecular assays for various infectious syndromes relevant to the pediatric population. Although outcome studies in this area are sparse, rapid results may result in decreased time to optimal antimicrobial treatment and improved patient outcomes. Disclosure Statement: E. McElvania is a consultant for Luminex Corporation. M.D. Gonzalez has no disclosures. KEYWORDS Rapid diagnostic assays Group A streptococcus Influenza RSV Syndromic multiplex panels Gastrointestinal panel Respiratory panel Meningitis encephalitis panel Compared with traditional rapid antigen testing, new diagnostics assays for Group A Streptococcus, influenza, and respiratory syncytial virus combine rapid turnaround time with high sensitivity and specificity. There has been a surge in the availability of multiplex syndromic panels that test for a broad range of pathogens associated with a single clinical presentation. Molecular infectious disease testing that was previously performed in microbiology laboratories is now being developed in easy-to-use platforms, which are available at point of care.
Output: New Developments in Rapid Diagnostic Testing for Children
Pneumonia is a serious problem worldwide. We recently demonstrated that innate defense mechanisms of the lung are highly inducible against pneumococcal pneumonia. To determine the breadth of protection conferred by stimulation of lung mucosal innate immunity, and to identify cells and signaling pathways activated by this treatment, mice were treated with an aerosolized bacterial lysate, then challenged with lethal doses of bacterial and fungal pathogens. Mice were highly protected against a broad array of Gram-positive, Gram-negative, and class A bioterror bacterial pathogens, and the fungal pathogen, Aspergillus fumigatus. Protection was associated with rapid pathogen killing within the lungs, and this effect was recapitulated in vitro using a respiratory epithelial cell line. Gene expression analysis of lung tissue showed marked activation of NF-kB, type I and II IFN, and antifungal Card9-Bcl10-Malt1 pathways. Cytokines were the most strongly induced genes, but the inflammatory cytokines TNF and IL-6 were not required for protection. Lung-expressed antimicrobial peptides were also highly up-regulated. Taken together, stimulated innate resistance appears to occur through the activation of multiple host defense signaling pathways in lung epithelial cells, inducing rapid pathogen killing, and conferring broad protection against virulent bacterial and fungal pathogens. Augmentation of innate antimicrobial defenses of the lungs might have therapeutic value for protection of patients with neutropenia or impaired adaptive immunity against opportunistic pneumonia, and for defense of immunocompetent subjects against a bioterror threat or epidemic respiratory infection.
Output: Stimulated Innate Resistance of Lung Epithelium Protects Mice Broadly against Bacteria and Fungi
cally active but which do not bind antibody 259 have been prepared recently; cells transformed by such mutants were not altered morphologically, nor did they show greatly inhibited thymidine incorporation, after injection of antibody 259 26 • It is assumed that while viral oncogenes function without normal control, their mechanism of action is similar to that of related cellular genes. Here we have presented evidence to support this idea in the case of growth factor receptor-like molecules and related oncogenes. It is therefore possible that these data might aid in understanding the way in which cellular genes interact in the control of normal proliferation. Our results indicate that some receptor-like oncogenes depend on ras proteins while some cytoplasmic oncogenes do not. There are, of course, numerous oncogenes which we have not yet tested which might behave differently from those described here. With this limitation in mind and on the basis of our present data, we propose that an important class of proliferative signals are received at the cell surface by receptor molecules such as growth factor receptors, and the c-ras proteins are essential in the transfer of these signals to cytoplasmic effectors having serine kinase activity; the effectors then modify target molecules which are directly involved in initiating a proliferative cycle. Accordingly, if the cytoplasmic effector were mutated such that it functioned without activation, proliferation would continue independently of c-ras proteins. Receptor molecules, on the other hand, would always require c-ras to stimulate proliferation. While our data are consistent with the above scheme, they do not exclude many other possibilities involving multiple metabolic pathways and more complex interactions. For example, we have not reported results with nuclear oncogenes owing to their difficulty in transforming NIH 3T3 cells. The proposed scheme is primarily attractive because of its similarity to the carefully studied mechanism of signal transduction involving cyclic AMP. While it is unlikely that cyclic AMP itself regulates proliferation 27 , G-regulatory proteins with enzymatic similarities to c-ras proteins are involved. These regulatory proteins control signal transduction from cell-surface receptors to cytoplasmic serine kinase effector molecules by regulating adenyl cyclase activity28. While the present study has examined only one aspect of what is likely to be a highly complex system for regulating proliferation, it does provide a means of functionally comparing separate viral oncogenes. Injection of antibody has been used in other studies to characterize the types of molecules responsible for tumour cell proliferation. Like NIH 3T3 cells transformed by mos or raj genes, many tumour cells show no inhibition of proliferation when injected with anti-ras antibody. In this way their proliferation is distinct from that of the normal cell types studied, each of which was efficiently inhibited by the injected antibodyl6.
Output: Viral particles induce Ia antigen expression on astrocytes
Background and objectives. Diagnostic uncertainty over respiratory tract infections (RTIs) in primary care contributes to over-prescribing of antibiotics and drives antibiotic resistance. If symptoms and signs predict respiratory tract microbiology, they could help clinicians target antibiotics to bacterial infection. This study aimed to determine relationships between symptoms and signs in children presenting to primary care and microbes from throat swabs. Methods. Cross-sectional study of children ≥3 months to <16 years presenting with acute cough and RTI, with subset follow-up. Associations and area under receiver operating curve (AUROC) statistics sought between clinical presentation and baseline microbe detection. Microbe prevalence compared between baseline (symptomatic) and follow-up (asymptomatic) visits. Results. At baseline, ≥1 bacteria was detected in 1257/2113 (59.5%) children and ≥1 virus in 894/2127 (42%) children. Clinical presentation was not associated with detection of ≥1 bacteria [AUROC 0.54 (95% CI 0.52-0.56)] or ≥1 virus [0.64 (95% CI 0.61-0.66)]. Individually, only respiratory syncytial virus (RSV) was associated with clinical presentation ]. Prevalence fell between baseline and follow-up; more so in viruses (68% versus 26%, P < 0.001) than bacteria (56% versus 40%, P = 0.01); greatest reductions seen in RSV, influenza B and Haemophilus influenzae. Conclusion. Findings demonstrate that clinical presentation cannot distinguish the presence of bacteria or viruses in the upper respiratory tract. However, individual and overall microbe prevalence was greater when children were unwell than when well, providing some evidence that upper respiratory tract microbes may be the cause or consequence of the illness. If causal, selective microbial point-of-care testing could be beneficial.
Output: Throat swabs in children with respiratory tract infection: associations with clinical presentation and potential targets for point-of-care testing
Concerns about the safety and adequacy of the blood supply have fostered twenty years of research into the so-called "blood substitutes" among them the oxygen carriers based on modified hemoglobin. Although none of these materials has yet been licensed for use in North America or Europe, the results of research and clinical trials have increased our understanding of oxygen delivery and its regulation. In particular, the examination of the basis for the vasoactivity observed with some of the hemoglobin based oxygen carriers has led to the insight that several colligative properties of hemoglobin solutions, such as their diffusion coefficient for oxygen, viscosity and colloid oncotic pressure, are important determinants of efficacy.
Output: What happened to blood substitutes? Qu'est il arrivé aux substituts du sang ?
Acute respiratory distress syndrome (ARDS) is defined by the association of bilateral infiltrates and hypoxaemia following an initial insult. Although a new definition has been recently proposed (Berlin definition), there are various forms of ARDS with potential differences regarding their management (ventilator settings, prone positioning use, corticosteroids). ARDS can be caused by various aetiologies, and the adequate treatment of the responsible cause is crucial to improve the outcome. It is of paramount importance to characterize the mechanisms causing lung injury to optimize both the aetiological treatment and the symptomatic treatment. If there is no obvious cause of ARDS or if a direct lung injury is suspected, bronchoalveolar lavage (BAL) should be strongly considered to identify microorganisms responsible for pneumonia. Blood samples can also help to identify microorganisms and to evaluate biomarkers of infection. If there is no infectious cause of ARDS or no other apparent aetiology is found, second-line examinations should include markers of immunologic diseases. In selected cases, open lung biopsy remains useful to identify the cause of ARDS when all other examinations remain inconclusive. CT scan is fundamental when there is a suspicion of intra-abdominal sepsis and in some cases of pneumonia. Ultrasonography is important not only in evaluating biventricular function but also in identifying pleural effusions and pneumothorax. The definition of ARDS remains clinical and the main objective of the diagnostic workup should be to be focused on identification of its aetiology, especially a treatable infection.
Output: Diagnostic workup for ARDS patients
Uropathogenic E. coli (UPEC), which cause urinary tract infections (UTI), utilize type 1 pili, a chaperone usher pathway (CUP) pilus, to cause UTI and colonize the gut. The pilus rod, comprised of repeating FimA subunits, provides a structural scaffold for displaying the tip adhesin, FimH. We solved the 4.2 Å resolution structure of the type 1 pilus rod using cryo-electron microscopy. Residues forming the interactive surfaces that determine the mechanical properties of the rod were maintained by selection based on a global alignment of fimA sequences. We identified mutations that did not alter pilus production in vitro but reduced the force required to unwind the rod. UPEC expressing these mutant pili were significantly attenuated in bladder infection and intestinal colonization in mice. This study elucidates an unappreciated functional role for the molecular spring-like property of type 1 pilus rods in host-pathogen interactions and carries important implications for other pilus-mediated diseases.
Output: Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions
Acute and chronic inflammatory responses in the lung are associated with the accumulation of large quantities of immune and structural cells undergoing apoptosis, which need to be engulfed by phagocytes in a process called 'efferocytosis'. Apoptotic cell recognition and removal from the lung is mediated predominantly by airway macrophages, though immature dendritic cells and non-professional phagocytes, such as epithelial cells and mesenchymal cells, can also display this function. Efficient clearance of apoptotic cells from the airways is essential for successful resolution of inflammation and the return to lung homeostasis. Disruption of this process leads to secondary necrosis of accumulating apoptotic cells, release of necrotic cell debris and subsequent uncontrolled inflammatory activation of the innate immune system by the released 'damage associated molecular patterns' (DAMPS). To control the duration of the immune response and prevent autoimmune reactions, anti-inflammatory signalling cascades are initiated in the phagocyte upon apoptotic cell uptake, mediated by a range of receptors that recognise specific phospholipids or proteins externalised on, or secreted by, the apoptotic cell. However, prolonged activation of apoptotic cell recognition receptors, such as the family of receptor tyrosine kinases Tyro3, Axl and MerTK (TAM), may delay or prevent inflammatory responses to subsequent infections. In this review, we will discuss recent advances in our This submission is related to Immunopathology of Lung Diseases -Drs
Output: The role of airway macrophages in apoptotic cell clearance following acute and chronic lung inflammation
Picornaviruses form replication complexes in association with membranes in structures called replication organelles. Common themes to emerge from studies of picornavirus replication are the need for cholesterol and phosphatidylinositol 4-phosphate (PI4P). In infected cells, type III phosphatidylinositol 4-kinases (PI4KIIIs) generate elevated levels of PI4P, which is then exchanged for cholesterol at replication organelles. For the enteroviruses, replication organelles form at Golgi membranes in a process that utilizes PI4KIIIb. Other picornaviruses, for example the cardioviruses, are believed to initiate replication at the endoplasmic reticulum and subvert PI4KIIIa to generate PI4P. Here we investigated the role of PI4KIII in foot-and-mouth disease virus (FMDV) replication. Our results showed that, in contrast to the enteroviruses and the cardioviruses, FMDV replication does not require PI4KIII (PI4KIIIa and PI4KIIIb), and PI4P levels do not increase in FMDV-infected cells and PI4P is not seen at replication organelles. These results point to a unique requirement towards lipids at the FMDV replication membranes.
Output: Foot-and-mouth disease virus replicates independently of phosphatidylinositol 4-phosphate and type III phosphatidylinositol 4-kinases
Background: Bovine rotavirus (BRV) is a non-enveloped dsRNA virus that cause neonatal calf diarrhea. Lipid rafts are cholesterol-enrich membrane mircodomains that play a vital role in many cellular processes. In this study, the effect of cellular cholesterol depletion on infection of MA-104 cells with bovine rotavirus was investigated. Results: We demonstrated that cholesterol depletion of the plasma membrane by MβCD had no effect on BRV binding to cells but significantly impaired BRV entry in a dose-dependent manner and the effect was partially reversed by addition of exogenous cholesterol, suggesting the reduction of BRV infection by MβCD was specifically due to cholesterol depletion. Cholesterol depletion after virus entry did not reduce BRV replication, whereas affected virus assembly. Conclusions: Taken together, our results demonstrate that cell membrane cholesterol is essential to BRV infectivity.
Output: Critical role of cellular cholesterol in bovine rotavirus infection
Mathematical models that describe the global spread of infectious diseases such as influenza, severe acute respiratory syndrome (SARS), and tuberculosis (TB) often consider a sample of international airports as a network supporting disease spread. However, there is no consensus on how many cities should be selected or on how to select those cities. Using airport flight data that commercial airlines reported to the Official Airline Guide (OAG) in 2000, we have examined the network characteristics of network samples obtained under different selection rules. In addition, we have examined different size samples based on largest flight volume and largest metropolitan populations. We have shown that although the bias in network characteristics increases with the reduction of the sample size, a relatively small number of areas that includes the largest airports, the largest cities, the most-connected cities, and the most central cities is enough to describe the dynamics of the global spread of influenza. The analysis suggests that a relatively small number of cities (around 200 or 300 out of almost 3000) can capture enough network information to adequately describe the global spread of a disease such as influenza. Weak traffic flows between small airports can contribute to noise and mask other means of spread such as the ground transportation. Citation: Bobashev G, Morris RJ, Goedecke DM (2008) Sampling for Global Epidemic Models and the Topology of an International Airport Network. PLoS ONE 3(9): e3154.
Output: Sampling for Global Epidemic Models and the Topology of an International Airport Network
Background: In the 2003 severe acute respiratory syndrome outbreak, finding viral nucleic acids on hospital surfaces suggested surfaces could play a role in spread in health care environments. Surface disinfection may interrupt transmission, but few data exist on the effectiveness of health care germicides against coronaviruses on surfaces. Methods: The efficacy of health care germicides against 2 surrogate coronaviruses, mouse hepatitis virus (MHV) and transmissible gastroenteritis virus (TGEV), was tested using the quantitative carrier method on stainless steel surfaces. Germicides were o-phenylphenol/ p-tertiary amylphenol) (a phenolic), 70% ethanol, 1:100 sodium hypochlorite, ortho-phthalaldehyde (OPA), instant hand sanitizer (62% ethanol), and hand sanitizing spray (71% ethanol). Results: After 1-minute contact time, for TGEV, there was a log 10 reduction factor of 3.2 for 70% ethanol, 2.0 for phenolic, 2.3 for OPA, 0.35 for 1:100 hypochlorite, 4.0 for 62% ethanol, and 3.5 for 71% ethanol. For MHV, log 10 reduction factors were 3.9 for 70% ethanol, 1.3 for phenolic, 1.7 for OPA, 0.62 for 1:100 hypochlorite, 2.7 for 62% ethanol, and 2.0 for 71% ethanol. Conclusion: Only ethanol reduced infectivity of the 2 coronaviruses by .3-log 10 after 1 minute. Germicides must be chosen carefully to ensure they are effective against viruses such as severe acute respiratory syndrome coronavirus.
Output: Inactivation of surrogate coronaviruses on hard surfaces by health care germicides
With the mapping of the human genome comes the ability to identify genes of interest in specific diseases and the pathways involved therein. Laboratory technology has evolved in parallel, providing us with the ability to assay thousands of these genes at once, a technique known as microarray analysis. The main question that this type of technology raises is how we can apply this powerful technology to clinical medicine. Recently, advances in data analysis, as well as standardization of the technology, have allowed us to examine this question, and indeed a few clinical trials currently being performed include microarrays as part of their protocol. In this review we outline the microarray technique and describe these types of studies in further detail.
Output: Gene Expression Profiling: From Microarrays to Medicine
Background: The pteropine orthoreovirus (PRV) was isolated from monkey (Macaca fascicularis) faecal samples collected from human-inhabited areas in Lopburi Province, Thailand. These samples were initially obtained to survey for the presence of hepatitis E virus (HEV). Results: Two virus isolates were retrieved by virus culture of 55 monkey faecal samples. Liquid chromatographytandem mass spectrometry (LC-MS/MS) was successfully used to identify the viruses as the segmented dsRNA orthoreovirus. Phylogenetic analysis of the Lopburi orthoreovirus whole-genomes revealed relationships with the well-characterised PRVs Pulau (segment L1), Cangyuan (segments L2, M3 and S3), Melaka (segments L3 and M2), Kampar (segments M1 and S2) and Sikamat (segments S1 and S4) of Southeast Asia and China with nucleotide sequence identities of 93.5-98.9%. RT-PCR showed that PRV was detected in 10.9% (6/55) and HEV was detected in 25.5% (14/55) of the monkey faecal samples. Conclusions: PRV was isolated from monkey faeces for the first time in Thailand via viral culture and LC-MS/MS. The genetic diversity of the virus genome segments suggested a re-assortment within the PRV species group. The overall findings emphasise that monkey faeces can be sources of zoonotic viruses, including PRV and HEV, and suggest the need for active virus surveillance in areas of human and monkey co-habitation to prevent and control emerging zoonotic diseases in the future.
Output: Mass spectrometry-based identification and whole-genome characterisation of the first pteropine orthoreovirus isolated from monkey faeces in Thailand
Background: Although sub-Saharan Africa (SSA) is particularly affected by sickle cell disease (SCD), there is dearth of research on this topic in the region, specifically targeting the magnitude of SCD-related complications. We therefore conducted this study to determine the burden of acute chest syndrome (ACS) and describe its clinical and therapeutic aspects among SCD children in Cameroon, a SSA country. Methods: This was a retrospective study carried-out from September 2013 to June 2014 at the SCD unit of the Mother and Child Centre of the Chantal Biya Foundation, a pediatric reference centre in Yaoundé, Cameroon. We enrolled all SCD children with confirmed diagnosis of ACS, and recorded their clinical presentation at admission along with their evolution during hospitalization. Results: Twenty one cases of ACS were identified during the study period, from 338 hospitalizations of children with SCD. Ages ranged from 11 months to 16 years with a mean (standard deviation) of 5.5 (3.4) years, and a male/ female sex ratio of 3.2/1. We noticed relatively low levels of HbF, from 6.4 to 21.9 % with a mean of 14.6 % (6.0 %). The three main symptoms at admission were fever (90.5 %), cough (81 %) and chest pains (28.6 %). Two patients (9.5 %) developed ACS 2 days after admission. The mean values of leukocytes, neutrophils, serum CRP, serum LDH and hemoglobin were respectively 32479.4 (17862.3)/mm 3 , 23476 (11543.7)/mm 3 , 228.2 (132.6) mg/l, 3452.3 (2916.3) IU/l and 6.5 (1.2) g/dl. The main localizations of radiological alveolar consolidations were the lower lobes (90.5 %). Treatment associated broad-spectrum antibiotics (100 %), hydration (100 %), analgesics (43.2 %), whole blood transfusion (66.7 %), and oxygen supplementation (33.3 %). Blood transfusion significantly improved hemoglobin level (p = 0.039). The duration of hospitalization, the mean of which was 6.8 (3.1) days, was influenced by none of the tested variables (all p values > 0.05). Conclusion: ACS is frequent among SCD children in our milieu. Its etiologies seem to be multifactorial. Patients' parents should be educated to recognize early signs and symptoms of the disease, and consult rapidly. Additionally, clinicians must be trained to diagnose ACS, and manage it promptly and efficiently to avoid its related catastrophic consequences.
Output: The Acute Chest Syndrome in Cameroonian children living with sickle cell disease