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48mtdwuv | Vorpal: A novel RNA virus feature-extraction algorithm demonstrated through interpretable genotype-to-phenotype linear models | In the analysis of genomic sequence data, so-called “alignment free” approaches are often selected for their relative speed compared to alignment-based approaches, especially in the application of distance comparisons and taxonomic classification1,2,3,4. These methods are typically reliant on excising K-length substrings of the input sequence, called K-mers5. In the context of machine learning, K-mer based feature vectors have been used in applications ranging from amplicon sequencing classification to predictive modeling for antimicrobial resistance genes6,7,8. This can be seen as an analogy of the “bag-of-words” model successfully employed in natural language processing and computer vision for document and image classification9,10. Feature extraction techniques from natural language processing have previously been analogized to genomics data11; however, the “bag-of-words” approach is brittle in the RNA virus space due to the high intersequence variance and the exact matching requirement of K-mers. To reconcile the simplicity of “bag-of-words” methods with the complications presented by the intrinsic variance of RNA virus space, a method to resolve the fragility of extracted K-mers in a way that faithfully reflects an underlying biological phenomenon was devised. Our algorithm, Vorpal, allows the construction of interpretable linear models with clustered, representative ‘degenerate’ K-mers as the input vector and, through regularization, sparse predictors of binary phenotypes as the output. Here, we demonstrate the utility of Vorpal by identifying nucleotide-level genomic motif predictors for binary phenotypes in three separate RNA virus clades; human pathogen vs. non-human pathogen in Orthocoronavirinae, hemorrhagic fever causing vs. non-hemorrhagic fever causing in Ebolavirus, and human-host vs. non-human host in Influenza A. The capacity of this approach for in silico identification of hypotheses which can be validated by direct experimentation, as well as identification of genomic targets for preemptive biosurveillance of emerging viruses, is discussed. The code is available for download at https://github.com/mriglobal/vorpal. |
dvkcof3x | Orientierungshilfen in der Corona-Krise – Die Ad-hoc-Empfehlung des Deutschen Ethikrats und die Klinisch-ethischen Empfehlungen von sieben Fachgesellschaften aus der Medizin | |
2787pt96 | Differentiate or die: reconstructing market(place) economies | |
1vjdvp8q | Blocking drug-induced autophagy with chloroquine in HCT-116 colon cancer cells enhances DC maturation and T cell responses induced by tumor cell lysate | Abstract Autophagy is an important mechanism for tumor escape, allowing tumor cells to recover from the damage induced by chemotherapy, radiation therapy, and immunotherapy and contributing to the development of resistance. The pharmacological inhibition of autophagy contributes to increase the efficacy of antineoplastic agents. Exposing tumor cells to low concentrations of select autophagy-inducing antineoplastic agents increases their immunogenicity and enhances their ability to stimulate dendritic cell (DC) maturation. We tested whether the application of an autophagy-inhibiting agent, chloroquine (CQ), in combination with low concentrations of 5-fluorouracil (5-FU) increases the ability of tumor cells to induce DC maturation. DCs sensitized with the lysate of HCT-116 cells previously exposed to such a combination enhanced the DC maturation/activation ability. These matured DCs also increased the allogeneic responsiveness of both CD4+ and CD8+ T cells, which showed a greater proliferative response than those from DCs sensitized with control lysates. The T cells expanded in such cocultures were CD69+ and PD-1- and produced higher levels of IFN-γ and lower levels of IL-10, consistent with the preferential activation of Th1 cells. Cocultures of autologous DCs and lymphocytes improved the generation of cytotoxic T lymphocytes, as assessed by the expression of CD107a, perforin, and granzyme B. The drug combination increased the expression of genes related to the CEACAM family (BECN1, ATGs, MAPLC3B, ULK1, SQSTM1) and tumor suppressors (PCBP1). Furthermore, the decreased expression of genes related to metastasis and tumor progression (BNIP3, BNIP3L, FOSL2, HES1, LAMB3, LOXL2, NDRG1, P4HA1, PIK3R2) was noted. The combination of 5-FU and CQ increases the ability of tumor cells to drive DC maturation and enhances the ability of DCs to stimulate T cell responses. |
udqu5jub | Advances in MALDI Mass Spectrometry in Clinical Diagnostic Applications | The concept of matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) was first reported in 1985. Since then, MALDI MS technologies have been evolving, and successfully used in genome, proteome, metabolome, and clinical diagnostic research. These technologies are high-throughput and sensitive. Emerging evidence has shown that they are not only useful in qualitative and quantitative analyses of proteins, but also of other types of biomolecules, such as DNA, glycans, and metabolites. Recently, parallel fragmentation monitoring (PFM), which is a method comparable to selected reaction monitoring, has been reported. This highlights the potentials of MALDI-TOF/TOF tandem MS in quantification of metabolites. Here we critically review the applications of the major MALDI MS technologies, including MALDI-TOF MS, MALDI-TOF/TOF MS, SALDI-TOF MS, MALDI-QqQ MS, and SELDI-TOF MS, to the discovery and quantification of disease biomarkers in biological specimens, especially those in plasma/serum specimens. Using SELDI-TOF MS as an example, the presence of systemic bias in biomarker discovery studies employing MALDI-TOF MS and its possible solutions are also discussed in this chapter. The concepts of MALDI, SALDI, SELDI, and PFM are complementary to each other. Theoretically, all these technologies can be combined, leading to the next generation of the MALDI MS technologies. Real applications of MALDI MS technologies in clinical diagnostics should be forthcoming. |
3ov501xx | A Survey on Deep Transfer Learning and Edge Computing for Mitigating the COVID-19 Pandemic | Abstract Global Health sometimes faces pandemics as are currently facing COVID-19 disease. The spreading and infection factors of this disease are very high. A huge number of people from most of the countries are infected within four months from its first report of appearance and it keeps spreading. The required systems are not ready up to some stages for any pandemic; therefore, mitigation with existing capacity becomes necessary. On the other hand, modern-era largely depends on Artificial Intelligence(AI) including Data Science, and Deep Learning(DL) is one of the current flag-bearer of these techniques. It could use to mitigate COVID-19 like pandemics in terms of stop spread, diagnosis of the disease, drug & vaccine discovery, treatment, and many more. But this DL requires large datasets as well as powerful computing resources. A shortage of reliable datasets of a running pandemic is a common phenomenon. So, Deep Transfer Learning(DTL) would be effective as it learns from one task and could work on another task. In addition, Edge Devices(ED) such as IoT, Webcam, Drone, Intelligent Medical Equipment, Robot, etc. are very useful in a pandemic situation. These types of equipment make the infrastructures sophisticated and automated which helps to cope with an outbreak. But these are equipped with low computing resources, so, applying DL is also a bit challenging; therefore, DTL also would be effective there. This article scholarly studies the potentiality and challenges of these issues. It has described relevant technical backgrounds and reviews of the related recent state-of-the-art. This article also draws a pipeline of DTL over Edge Computing as a future scope to assist the mitigation of any pandemic. |
ejbhpf0w | cis-acting genomic elements and trans-acting proteins involved in the assembly of RNA viruses | Abstract There is now considerable evidence that a specific site (or sites) in the genome of an RNA virus interacts with a viral protein to initiate the assembly of the virus ribonucleoprotein or nucleocapsid. We describe the progress that has been made in defining these elements for a number of different viruses: the togavirus, Sindbis virus; the coronavirus, mouse hepatitis virus; influenza A virus; several retroviruses; and the hepadnavirus, hepatitis B virus. The importance of cis-acting elements in packaging has been established for all of these viruses. For Sindbis virus, specificity in the binding of the RNA element to a region of the viral capsid protein in vitro has also been demonstrated. |
wg5y75y1 | An efficient RNA‐cleaving DNA enzyme can specifically target the 5′‐untranslated region of severe acute respiratory syndrome associated coronavirus (SARS‐CoV) | BACKGROUND: The worldwide epidemic of severe acute respiratory syndrome (SARS) in 2003 was caused by a novel coronavirus called SARS‐CoV. We report the use of DNAzyme (catalytic DNA) to target the 5′‐untranslated region (5′UTR) of a highly conserved fragment in the SARS genome as an approach to suppression of SARS‐CoV replication. A mono‐DNA enzyme (Dz‐104) possessing the 10–23 catalytic motif was synthesized and tested both in vitro and in cell culture. MATERIALS AND METHODS: SARS‐CoV total RNA was isolated, extracted from the SARS‐CoV‐WHU strain and converted into cDNA. We designed a RNA‐cleaving 10–23 DNAzyme targeting at the loop region of the 5′UTR of SARS‐CoV. The designed DNAzyme, Dz‐104, and its mutant version, Dz‐104 (mut), as a control consist of 9 + 9 arm sequences with a 10–23 catalytic core. In vitro cleavage was performed using an in vitro transcribed 5′UTR RNA substrate. A vector containing a fused 5′UTR and enhanced green fluorescent protein (eGFP) was co‐transfected with the DNAzyme into E6 cells and the cells expressing eGFP were visualized with fluorescence microscopy and analyzed by fluorescence‐activated cell sorting (FACS). RESULTS AND CONCLUSIONS: Our results demonstrated that this DNAzyme could efficiently cleave the SARS‐CoV RNA substrate in vitro and inhibit the expression of the SARS‐CoV 5′UTR‐eGFP fusion RNA in mammalian cells. This work presents a model system to rapidly screen effective DNAzymes targeting SARS and provides a basis for potential therapeutic use of DNA enzymes to combat the SARS infection. Copyright © 2007 John Wiley & Sons, Ltd. |
ikqsty4y | Dissection of SARS Coronavirus Spike Protein into Discrete Folded Fragments | Abstract The spike protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) mediates cell fusion by binding to target cell surface receptors. This paper reports a simple method for dissecting the viral protein and for searching for foldable fragments in a random but systematic manner. The method involves digestion by DNase I to generate a pool of short DNA segments, followed by an additional step of reassembly of these segments to produce a library of DNA fragments with random ends but controllable lengths. To rapidly screen for discrete folded polypeptide fragments, the reassembled gene fragments were further cloned into a vector as N-terminal fusions to a folding reporter gene which was a variant of green fluorescent protein. Two foldable fragments were identified for the SARS-CoV spike protein, which coincide with various anti-SARS peptides derived from the hepated repeat (HR) region 2 of the spike protein. The method should be applicable to other viral proteins to isolate antigen or vaccine candidates, thus providing an alternative to the full-length proteins (subunits) or linear short peptides. |
j5evawo4 | Communicable Disease and Health Protection Quarterly Review: April to June 2004 | |
lj3092mw | Population Based Cohort Study for Pediatric Infectious Diseases Research in Vietnam | A population-based cohort study on pediatric infectious diseases was established at Khanh Hoa Province, central Vietnam in 2006, to determine the etiology and risk factors for severe pediatric infectious diseases (SPID) such as acute respiratory infection (ARI), diarrhea and dengue which are the major causes of under 5 mortality. A population census survey was conducted in Nha-Trang and Ninh-Hoa to collect demographic, social-behavioral data and disease burden on SPID. The study site covered a population of 353,525 residing in 75,826 households with 24,781 children less than 5 years. Hospital databases from two hospitals covering the region were obtained. Linking the census and hospital databases, we were able to investigate on a variety of SPID such as environmental tobacco smoking exposure and increased risked of pediatric pneumonia hospitalization, population density, water supply and risk of dengue fever and animal livestock and risk of hospitalized diarrhea. To determine incidence, viral etiology and risk factors for pediatric ARI/pneumonia, we setup a population based prospective hospitalized Pediatric ARI surveillance at Khanh Hoa General Hospital, Nha-Trang in February 2007. The study has revealed RSV, rhinovirus and influenza A as major viral pathogens, role of multiple viral infection and its interaction with bacteria in the development of pneumonia. In addition, we are also conducting a birth cohort study to investigate the incidence of congenital infection and its impact on physical-neurological development, and role of host genetic polymorphism on SPID hospitalization in Vietnam. Population mobility, high cost of regular census update and low mortality are the challenges. |
fenhvgs6 | Bringing it together | An in-depth look at membrane fusion—a process essential for communication within and between cells—is presented in this issue of Nature Structural & Molecular Biology. |
1qc72ovc | Specific mutations in H5N1 mainly impact the magnitude and velocity of the host response in mice | BACKGROUND: Influenza infection causes respiratory disease that can lead to death. The complex interplay between virus-encoded and host-specific pathogenicity regulators – and the relative contributions of each toward viral pathogenicity – is not well-understood. RESULTS: By analyzing a collection of lung samples from mice infected by A/Vietnam/1203/2004 (H5N1; VN1203), we characterized a signature of transcripts and proteins associated with the kinetics of the host response. Using a new geometrical representation method and two criteria, we show that inoculation concentrations and four specific mutations in VN1203 mainly impact the magnitude and velocity of the host response kinetics, rather than specific sets of up- and down- regulated genes. We observed analogous kinetic effects using lung samples from mice infected with A/California/04/2009 (H1N1), and we show that these effects correlate with morbidity and viral titer. CONCLUSIONS: We have demonstrated the importance of the kinetics of the host response to H5N1 pathogenesis and its relationship with clinical disease severity and virus replication. These kinetic properties imply that time-matched comparisons of ‘omics profiles to viral infections give limited views to differentiate host-responses. Moreover, these results demonstrate that a fast activation of the host-response at the earliest time points post-infection is critical for protective mechanisms against fast replicating viruses. |
3gv6469y | Social big data: Recent achievements and new challenges | Abstract Big data has become an important issue for a large number of research areas such as data mining, machine learning, computational intelligence, information fusion, the semantic Web, and social networks. The rise of different big data frameworks such as Apache Hadoop and, more recently, Spark, for massive data processing based on the MapReduce paradigm has allowed for the efficient utilisation of data mining methods and machine learning algorithms in different domains. A number of libraries such as Mahout and SparkMLib have been designed to develop new efficient applications based on machine learning algorithms. The combination of big data technologies and traditional machine learning algorithms has generated new and interesting challenges in other areas as social media and social networks. These new challenges are focused mainly on problems such as data processing, data storage, data representation, and how data can be used for pattern mining, analysing user behaviours, and visualizing and tracking data, among others. In this paper, we present a revision of the new methodologies that is designed to allow for efficient data mining and information fusion from social media and of the new applications and frameworks that are currently appearing under the “umbrella” of the social networks, social media and big data paradigms. |
smxer3tk | Clonal Spread of a Unique Strain of Macrolide-Resistant Mycoplasma Pneumoniae Within a Single Family in Italy | Macrolide-resistant Mycoplasma pneumoniae (MR-MP) is an increasing problem worldwide. This study describes the clonal spread of a unique strain of MR-MP within a single family. On January 23, 2015, nasopharyngeal swabs and sputum samples were collected from the index case (a 9-year-old girl) in southern Italy. The patient had pneumonia and was initially treated with clarithromycin. MR-MP infection was suspected due to prolonged symptoms despite appropriate antibiotic therapy. Two further cases of pneumonia occurred in relatives (a 7-year-old cousin and the 36-year-old mother of the index case); therefore, respiratory samples were also collected from other family members. Sequence analysis identified mutations associated with resistance to macrolides. Both P1 major adhesion protein typing and multiple loci variable-number tandem repeat analysis (MLVA) typing were performed to assess the relatedness of the strains. The index case, the cousin, the mother, and another 4 family members (twin siblings of the index case, a 3-year-old cousin, and the grandmother) were positive for MR-MP. All strains harbored the mutation A2063G, had the same P1 subtype (1), and were MLVA (7/4/5/7/2) type Z. In addition, the index case's aunt (31 years of age and the probable source of infection) harbored an M pneumoniae strain with the same molecular profile; however, this strain was susceptible to macrolides. This cluster of MR-MP infection/carriage caused by a clonal strain suggests a high transmission rate within this family and highlights the need for increased awareness among clinicians regarding the circulation of MR-MP. Novel strategies for the treatment and prevention of M pneumoniae infections are required. |
0gkonrzw | Viral Membrane Channels: Role and Function in the Virus Life Cycle | Viroporins are small, hydrophobic trans-membrane viral proteins that oligomerize to form hydrophilic pores in the host cell membranes. These proteins are crucial for the pathogenicity and replication of viruses as they aid in various stages of the viral life cycle, from genome uncoating to viral release. In addition, the ion channel activity of viroporin causes disruption in the cellular ion homeostasis, in particular the calcium ion. Fluctuation in the calcium level triggers the activation of the host defensive programmed cell death pathways as well as the inflammasome, which in turn are being subverted for the viruses’ replication benefits. This review article summarizes recent developments in the functional investigation of viroporins from various viruses and their contributions to viral replication and virulence. |
gu91cact | Isolation and Characterization of a Phaseolus vulgaris Trypsin Inhibitor with Antiproliferative Activity on Leukemia and Lymphoma Cells | A 17.5-kDa trypsin inhibitor was purified from Phaseolus vulgaris cv. “gold bean” with an isolation protocol including ion exchange chromatography on DEAE-cellulose (Diethylaminoethyl-cellulose), affinity chromatography on Affi-gel blue gel, ion exchange chromatography on SP-sepharose (Sulfopropyl-sepharose), and gel filtration by FPLC (Fast protein liquid chromatography) on Superdex 75. It dose-dependently inhibited trypsin with an IC(50) value of 0.4 μM, and this activity was reduced in the presence of dithiothreitol in a dose- and time-dependent manner, signifying the importance of the disulfide linkage to the activity. It inhibited [methyl-(3)H] thymidine incorporation by leukemia L1210 cells and lymphoma MBL2 cells with an IC(50) value of 2.3 μM and 2.5 μM, respectively. The inhibitor had no effect on fungal growth and the activities of various viral enzymes when tested up to 100 μM. |
h3fls1oz | Coronavirus disease 2019 and ophthalmologists: introducing a simple protective shield for slitlamp biomicroscopic examination | |
q7fit39i | Glucocorticosteroid in Treatment of Severe Pneumonia | Airway diseases such as pneumonia constitute a major health burden on a global scale; untreated pneumonia may develop to severe pneumonia and consequently lead to to fatal episodes of mortality and morbidity. The balance between inflammatory mediators is key for the outcome of the pulmonary infection; elimination of invading pathogen was marked by the release of cytokines and other inflammatory mediators from alveolar macrophages and glucocorticoid steroids (GCs) acting on the inflammatory component. Treatments of severe pneumonia with GCs have been developing for years with inconclusive results. In many cases GCs have been administered empirically without clinical evidence. Recent studies assess beneficial impact on treatment of severe pneumonia by suggesting specific dosage, period of administration, and tapered dosage. |
a49yg45g | Face shields for infection control: A review | Face shields are personal protective equipment devices that are used by many workers (e.g., medical, dental, veterinary) for protection of the facial area and associated mucous membranes (eyes, nose, mouth) from splashes, sprays, and spatter of body fluids. Face shields are generally not used alone, but in conjunction with other protective equipment and are therefore classified as adjunctive personal protective equipment. Although there are millions of potential users of face shields, guidelines for their use vary between governmental agencies and professional societies and little research is available regarding their efficacy. |
h20t25ck | Enhancing Laboratory Response Network Capacity in South Korea | Laboratory Response Network (LRN) laboratories help protect populations from biological and chemical public health threats. We examined the role of LRN biological laboratories in enhancing capacity to detect and respond to public health infectious disease emergencies in South Korea. The model for responding to infectious disease emergencies leverages standardized laboratory testing procedures, a repository of standardized testing reagents, laboratory testing cooperation among hospital sentinel laboratories and reference laboratories, and maintenance of a trained workforce through traditional and on-demand training. Cooperation among all network stakeholders helps ensure that laboratory response is an integrated part of the national response. The added laboratory testing capacity provided by the US Centers for Disease Control and Prevention LRN assets helps protect persons who reside in South Korea, US military personnel and civilians in South Korea, and those who reside in the continental United States. |
m3cb8yij | Manifestations of blood coagulation and its relation to clinical outcomes in severe COVID‐19 patients: Retrospective analysis | INTRODUCTION: Characteristics of blood coagulation and its relation to clinical outcomes in COVID‐19 patients are still rarely reported. We aimed to investigate the blood coagulation function and its influences on clinical outcomes of patients with syndrome coronavirus 2 (SARS‐CoV‐2) infection. METHODS: A total of 71 severe patients with confirmed SARS‐CoV‐2 infection who were treated in Wuhan First Hospital from February 12 to March 20, 2020, were enrolled. The blood coagulation data in these patients and in 61 healthy controls were collected. The patients with COVID‐19 were divided into two groups: the aggravated group and the nonaggravated group, respectively, basing on whether the patients' conditions turned to critically ill or not after admission. RESULTS: Compared with healthy controls, patients with COVID‐19 had significant performances with coagulation dysfunction, including dramatically elevated values of FIB, PT, APTT, INR, FDP, and D‐Dimers but markedly reduced AT value (P < .05). Importantly, more noteworthy coagulation disorders similar to the differences between patients and controls were found in the aggravated patients with conditions deterioration after admission than those in the nonaggravated patients without conditions deterioration (P < .05). Moreover, the aggravated patients possessed a longer hospital stay and a higher mortality compared with the nonaggravated patients (P < .001). The coagulation parameters of COVID‐19 patients were widely and closely related to the indexes of liver function and inflammation (P < .05), indicating the coagulation dysfunction of these patients may be caused by liver injury and inflammatory storm. CONCLUSION: Severe patients with SARS‐CoV‐2 infection often possess coagulation dysfunction on admission. A certain correlation exists in coagulation disorder and adverse clinical outcome among severe COVID‐19 patients. |
hl96i9kd | Reply to: Endonasal drilling may be employed safely in the COVID‐19 era | |
ixz6t7gb | Age, inflammation and disease location are critical determinants of intestinal expression of SARS-CoV-2 receptor ACE2 and TMPRSS2 in inflammatory bowel disease. | |
6ryglxwx | Ketogenic diet therapy provision in the COVID-19 pandemic: Dual-center experience and recommendations | Abstract The current coronavirus-19 pandemic has changed dramatically how neurologists care for children and adults with epilepsy. Stay-at-home orders and resistance to hospitalizations by patients have led epileptologists to engage in telemedicine and re-evaluate how to provide elective services. Ketogenic diet therapy is often started in the hospital, with families educated in hospital-based classes, but this is difficult to do in this current pandemic. At our two academic centers, both our pediatric and adult epilepsy diet centers have had to quickly consider alternative methods to both start and maintain ketogenic diet therapy. This paper provides several examples of how ketogenic diet therapy can be provided to patients in unique ways, along with recommendations from other experts and patients learned over the past few months. |
i9tzr13z | Modeling pathogenesis of emergent and pre-emergent human coronaviruses in mice | The emergence of highly pathogenic human coronaviruses (hCoVs) in the last two decades has illuminated their potential to cause high morbidity and mortality in human populations and disrupt global economies. Global pandemic concerns stem from their high mortality rates, capacity for human-to-human spread by respiratory transmission, and complete lack of approved therapeutic countermeasures. Limiting disease may require the development of virus-directed and host-directed therapeutic strategies due to the acute etiology of hCoV infections. Therefore, understanding how hCoV–host interactions cause pathogenic outcomes relies upon mammalian models that closely recapitulate the pathogenesis of hCoVs in humans. Pragmatism has largely been the driving force underpinning mice as highly effective mammalian models for elucidating hCoV–host interactions that govern pathogenesis. Notably, tractable mouse genetics combined with hCoV reverse genetic systems has afforded the concomitant manipulation of virus and host genetics to evaluate virus–host interaction networks in disease. In addition to assessing etiologies of known hCoVs, mouse models have clinically predictive value as tools to appraise potential disease phenotypes associated with pre-emergent CoVs. Knowledge of CoV pathogenic potential before it crosses the species barrier into the human population provides a highly desirable preclinical platform for addressing global pathogen preparedness, an overarching directive of the World Health Organization. Although we recognize that results obtained in robust mouse models require evaluation in non-human primates, we focus this review on the current state of hCoV mouse models, their use as tractable complex genetic organisms for untangling complex hCoV–host interactions, and as pathogenesis models for preclinical evaluation of novel therapeutic interventions. |
doxdnptd | ABPP and Host–Virus Interactions | Successful viral infection, as well as any resultant antiviral response, relies on numerous sequential interactions between host and viral factors. These interactions can take the form of affinity-based interactions between viral and host macromolecules or active, enzyme-based interactions, consisting both of direct enzyme activity performed by viral enzymes and indirect modulation of the activity of the host cell’s enzymes via viral interference. This activity has the potential to transform the local microenvironment to the benefit or detriment of both the virus and the host, favouring either the continuation of the viral life cycle or the host’s antiviral response. Comprehensive characterisation of enzymatic activity during viral infection is therefore necessary for the understanding of virally induced diseases. Activity-based protein profiling techniques have been established as effective and practicable tools with which to interrogate the regulation of enzymes’ catalytic activity and the roles played by these enzymes in various cell processes. This paper will review the contributions of these techniques in characterising the roles of both host and viral enzymes during viral infection in humans. |
486j76e1 | HOW LONG WILL MY MOUSE LIVE? MACHINE LEARNING APPROACHES FOR PREDICTION OF MOUSE LIFESPAN | Prediction of individual lifespan based upon characteristics evaluated at middle-age represents a challenging objective for aging research. In this study, we used machine learning algorithms to construct models that predict lifespan in a stock of genetically heterogeneous mice. Lifespan-prediction accuracy of 22 algorithms was evaluated using a cross-validation approach, in which models were trained and tested with distinct subsets of data. Using a combination of body weight and T-cell subset measures evaluated before two years of age, we show that the lifespan quartile to which an individual mouse belongs can be predicted with an accuracy of 35.3% (± 0.10%). This result provides a new benchmark for the development of lifespan-predictive models, but improvement can be expected through identification of new predictor variables and development of computational approaches. Future work in this direction can provide tools for aging research and will shed light on associations between phenotypic traits and longevity. |
15yhf955 | Beta-cyclodextrin derivatives as carriers to enhance the antiviral activity of an antisense oligonucleotide directed toward a coronavirus intergenic consensus sequence | The ability of cyclodextrins to enhance the antiviral activity of a phosphodiester oligodeoxynucleotide has been investigated. Aff18-mer oligodeoxynucleotide complementary to the initiation region of the mRNA coding for the spike protein and containing the intergenic consensus sequence of an enteric coronavirus has been tested for antiviral action against virus growth in human adenocarcinoma cells. The phosphodiester oligodeoxynucleotide only showed a limited effect on virus growth rate (from 12 to 34% viral inhibition in cells treated with 7.5 to 25 μM oligodeoxynucleotide, respectively, at a multiplicity of infection of 0.1 infectious particle per cell). In the same conditions, the phosphorothioate analogue exhibited stronger antiviral activity, the inhibition increased from 56 to 90%. The inhibitory effect of this analogue was antisense and sequence-specific. Northern blot analysis showed that the sequence-dependent mechanism of action appears to be the inhibition of mRNA transcription. We conclude that the coronavirus intergenic consensus sequence is a good target for an antisense oligonucleotide antiviral action. The properties of the phosphodiester oligonucleotide was improved after its complexation with cyclodextrins. The most important increase of the antiviral activity (90% inhibition) was obtained with only 7.5 μM oligonucleotide complexed to a cyclodextrin derivative, 6-deoxy-6-S-β-D-galactopyranosyl-6-thio-cyclomaltoheptaose in a molar ratio of 1:100. These studies suggest that the use of cyclodextrin derivatives as carrier for phosphodiester oligonucleotides delivery may be an effective method for increasing the therapeutic potential of these compounds in viral infections. |
sjp2c6xo | A Facile Synthesis of Deaza-Analogues of the Bisindole Marine Alkaloid Topsentin | A series of substituted ethyl 1-[(tert-butoxycarbonyl)amino]-2-methyl-5-(1-methyl-1H-indol-3-yl)-4-[(1-methyl-1H-indol-3-yl)carbonyl]-1H-pyrrole-3-carboxylates were prepared in excellent yields (82-98%) by one-pot reactions between β-dicarbonyl compounds 12a–e and 1,2-diaza-1,3-diene (DD) 13. Derivatives 10a,c–e, deazaanalogues of the bis-indole alkaloid topsentin, screened by the National Cancer Institute (Bethesda, MD, USA) in the in vitro one dose primary anticancer assay against a panel of about 60 human tumor cell lines, showed no significant activity, with the exception of compound 9e, which showed moderate activity against the HOP-92 cell line of the non small cell lung cancer sub-panel and the SNB-75 cell line of the CNS sub-panel. |
0j0nbm9k | Use of amantadine in a patient with SARS‐CoV‐2 | A 57-year old man with cold symptoms and muscle pain, with elevated blood glucose of 200mg/dL, was prescribed paracetamol (500mg every 6 hours) and naproxen (550mg daily for 5 days) and continued to take 850mg of metformin twice a day for the treatment of 10-year-old type 2 diabetes. Due to a persistent cough, 500 mg of azithromycin was added for three days, but the symptoms continued, and he had to go to his community hospital, where he got a pharyngeal exudate, to do a real-time PCR test for SARS-Cov-2 which was positive. This article is protected by copyright. All rights reserved. |
u8cu0mop | Experiencing Community in a Covid Surge | As I organize a pile of ethics consult chart notes in New York City in mid‐April 2020, I look at the ten cases that I have co‐consulted on recently. Nine of the patients were found to be Covid positive. The reasons for the consults are mostly familiar—surrogate decision‐making, informed refusal of treatment, goals of care, defining futility. But the context is unfamiliar and unsettling. Bioethicists are in pandemic mode, dusting off and revising triage plans. Patients and potential patients are fearful—of the disease itself and of the amplification of health disparities and inequities. There is so much to contemplate, but as I go through my cases, I worry about disability, about biases and racist stereotypes. In this pandemic, historically marginalized communities are at risk of further disenfranchisement. |
y47p1c15 | Ambient bioaerosol distribution and associated health risks at a high traffic density junction at Dehradun city, India | Traffic junctions are one of the crowded places where commuters are at high risk of developing respiratory infections, due to their greater exposure to airborne and human transmitted microbial pathogens. An airborne bioaerosol assessment study was carried out at a high traffic density junction focusing on their concentration, contribution in respirable particulate matter (PM), and factors influencing the distribution and microbial diversity. Andersen six-stage viable cascade impactor and a wide-range aerosol spectrometer were used for microbial and particulate matter measurements, respectively. Statistical analysis was conducted to evaluate the relationship between bioaerosol concentration, vehicular count, PM concentration, and meteorological parameters. The mean bacteria concentration (1962.95 ± 651.85 CFU/m(3)) was significantly different than fungi (1118.95 ± 428.34 CFU/m(3)) (p < 0.05). The temporal distribution showed maximum concentration for bacteria and fungi during monsoon and postmonsoon seasons, respectively. In terms of bioaerosol loading, a considerable fraction of fungi (3.25%) and bacteria (5.65%) contributed to the total airborne PM. Most abundant bioaerosols were Aspergillus (27.58%), Penicillium (23%), and Cladosporium (14.05%) (fungi), and Micrococcus (25.73%), Staphylococcus (17.98%), and Bacillus (13.8%) (bacteria). Traffic-induced roadside soil resuspension and microbial aerosolizations from the human body were identified as the chief sources of bioaerosol emissions. The risk of lower respiratory tract infections caused by anthroponotic (human transmitted) transfer of bacterial pathogens is very high. The results of the study can be used to trace sources of microbial mediated communicable diseases, and to recommend appropriate safety measures to avoid pathogenic bioaerosol exposure. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10661-020-8158-9) contains supplementary material, which is available to authorized users. |
613aftc1 | Establishment of a transgenic mouse model with liver-specific expression of secretory immunoglobulin D | Mutation of mevalonate kinase (MVK) is thought to account for most cases of hyperimmunoglobulinemia D syndrome (HIDS) with recurrent fever. However, its mechanism and the relationship between elevated serum immunoglobulin D (IgD) and the clinical features of HIDS are unclear. In this study, we generated by fusion PCR a vector to express high levels of chimeric secretory IgD (csIgD) specifically in the liver. We then generated seven founder lines of transgenic mice by co-microinjection, and verified them using genomic PCR and Southern blotting. We detected the expression of csIgD by reverse transcription PCR, quantitative PCR, western blotting, and enzyme-linked immunosorbent assays. We demonstrated that csIgD could be specifically and stably expressed in the liver. We used flow cytometry to show that overexpression of csIgD in the bone marrow and spleen cells had no effect on B cell development. Morphologic and anatomical observation of the transgenic mice revealed skin damage, hepatosplenomegaly, and nephromegaly in some transgenic mice; in these mice, pathological sections showed high levels of cell necrosis and protein-like sediments in the liver, spleen, and kidney. We demonstrated that the genomic insertion sites of the transgenes did not disrupt the MVK gene on mouse chromosome 5. This transgenic mouse will be useful to explore the pathogenesis of HIDS. |
1j9hw0c6 | Effect of 13 week magnetic field exposures on DMBA-initiated mammary gland carcinomas in female Sprague–Dawley rats | Several studies suggest that exposure to 50 Hz magnetic fields may promote chemically induced breast cancer in rats. Groups of 100 female Sprague–Dawley rats were initiated with four weekly 5 mg gavage doses of 7,12-dimethylbenz[a]anthracene (DMBA) starting at 50 days of age. After the first weekly DMBA administration, exposure to ambient fields (sham exposed), 50 Hz magnetic fields at either 1 or 5 G field intensity or 60 Hz fields at 1 G for 18.5 h/day, 7 days/week was initiated. Exposure continued for 13 weeks. A vehicle control group without DMBA was included. In a second study, using lower doses of DMBA, groups of 100 female Sprague–Dawley rats were initiated with four weekly doses of 2 mg of DMBA starting at 50 days of age followed, after the first weekly DMBA administration, by exposure to ambient fields (sham exposed) or 50 Hz magnetic fields at either 1 or 5 G field intensity for 18.5 h/day, 7 days/week for 13 weeks. Rats were weighed and palpated weekly for the presence of tumors. There was no effect of magnetic field exposure on body weight gains or on the time of appearance of mammary tumors in either study. At the end of 13 weeks, the animals were killed and the mammary tumors counted and measured. Mammary gland masses found grossly were examined histologically. In the first 13 week study, the mammary gland carcinoma incidences were 92, 86, 96 and 96% for the DMBA controls, 1 G, 50 Hz, 5 G, 50 Hz and 1 G, 60 Hz groups, respectively. The total numbers of carcinomas were 691, 528 (P < 0.05, decrease), 561 and 692 for the DMBA controls, 1 G, 50 Hz, 5 G, 50 Hz and 1 G, 60 Hz groups, respectively. In study 2, the mammary gland carcinoma incidences were 43, 48 and 38% for the DMBA controls, 1 G, 50 Hz and 5 G, 50 Hz groups, respectively. The total numbers of carcinomas were 102, 90 and 79 for the DMBA controls, 1 G, 50 Hz and 5 G, 50 Hz groups, respectively. There was no effect of magnetic field exposure on tumor size either by in-life palpation or by measurement at necropsy in either study. There was no evidence that 50 or 60 Hz magnetic fields promoted breast cancer in these studies in female rats. These studies do not support the hypothesis that magnetic field exposure promotes breast cancer in this DMBA rat model. |
o3dvpdfl | A generalized purpuric eruption with histopathologic features of leucocytoclastic vasculitis in a patient severely ill with COVID‐19 | A 59‐year‐old man was admitted to hospital for a severe respiratory failure and then intubated due to worsening of his respiratory condition. During his hospital stay, he received multiple empirical broad spectrum antibiotics (cefepime, piperacillin/tazobactam, linezolid, gentamicin and meropenem plus amikacin). The patient had no known history of drug allergies. A test to detect SARS‐CoV‐2 by real‐time reverse‐transcription‐polymerase‐chain‐reaction (RT‐PCR) assay of a throat swab was positive. Blood cell count showed severe eosinophilia (from 1,3 to 4.60 x 10) that decreased abruptly to 0.47 x 10 after introduction of methylprednisolone 1 mg/kg/day. On day 35 post admission, while on therapy only with corticosteroids, he developed a symmetrically distributed maculopapular purpuric exanthema on the face, trunk and extremities (Fig.1 a,b). Mucous membranes were spared. |
uzge50xu | Montelukast Reduces Serum Levels of Eosinophil-Derived Neurotoxin in Preschool Asthma | PURPOSE: Several markers for eosinophilic inflammation have been proposed to predict response to asthma treatment. However, definitive criteria for treatment decisions have not yet been established. We investigate a potentially useful relatively non-invasive biomarker, eosinophil-derived neurotoxin (EDN), to predict favorable responses to budesonide or montelukast, common treatment for children with asthma. METHODS: Young children (1 to 6 years old) were enrolled in this randomized, parallel, 2-group, open-label trial. Criteria for eligibility included: 1) being symptomatic during the run-in period; and 2) having a serum EDN (sEDN) level ≥ 53 ng/mL, with positive specific immunoglobulin E to house dust mite. Eligible patients were randomly placed into 2 groups: the BIS group received budesonide inhalation suspension (BIS) 0.5 mg once daily; the MONT group received montelukast 4 mg once daily. Ineligible patients were invited to receive montelukast 4 mg once daily (OBS group). Treatment period was 12 weeks. RESULTS: Asthma control days increased significantly in the BIS and MONT groups (P < 0.000) over the 12-week study period. There was no significant change in sEDN in the BIS group but there was a significant decrease in the MONT group (P < 0.000). Patients in the OBS group with high EDN levels (< 53 ng/mL) showed a significant decrease due to MONT treatment (P = 0.023). Rescue medication usage significantly decreased in the BIS and MONT groups (P < 0.000). CONCLUSIONS: EDN is a useful relatively non-invasive biomarker for predicting responses to montelukast and budesonide treatment of preschool children with beta2-agonist responsive recurrent wheeze and multiple-trigger wheeze (Trial registry at UMIN Clinical Trials Registry, UMIN000008335). |
rb7ex6vw | Update on Canine and Feline Blood Donor Screening for Blood‐Borne Pathogens | An update on the 2005 American College of Veterinary Internal Medicine (ACVIM) Consensus Statement on blood donor infectious disease screening was presented at the 2015 ACVIM Forum in Indianapolis, Indiana, followed by panel and audience discussion. The updated consensus statement is presented below. The consensus statement aims to provide guidance on appropriate blood‐borne pathogen testing for canine and feline blood donors in North America. |
anvi0pef | Professor Wolfgang Wagner, the President of ISPN (2018–2019) | |
moyln4am | COVID-19 and the difficulty of inferring epidemiological parameters from clinical data – Authors' reply | |
l3rq1er3 | Blood clots and TAM receptor signalling in COVID-19 pathogenesis | We suggest that the exuberant blood clotting and immune hyper-reaction seen in patients with COVID-19 may be exacerbated by depletion of the same regulator. This agent is protein S, which is both an anticoagulant in the blood coagulation cascade and an activating ligand for the immunosuppressive TAM family of receptor tyrosine kinases. |
dnxkzi3j | Potential of immunomodulatory host defense peptides as novel anti-infectives | A fundamentally new strategy for the treatment of infectious disease is the modulation of host immune responses to enhance clearance of infectious agents and reduce tissue damage due to inflammation. Antimicrobial host defense peptides have been investigated for their potential as a new class of antimicrobial drugs. Recently their immunomodulatory activities have begun to be appreciated. Modulation of innate immunity by synthetic variants of host defense peptides, called innate defense regulators (IDRs), is protective without direct antimicrobial action. We discuss the potential and current limitations in exploiting the immunomodulatory activity of IDRs as a novel anti-infective pathway. IDRs show significant promise and current research is uncovering mechanistic information that will aid in the future development of IDRs for clinical use. |
72zu3mna | Buffalo: Mediterranean Region ☆ | Abstract The buffaloes reared in the Mediterranean region are the Asian buffalo or water buffalo, that is, Bubalus bubalis. This species includes two types: (1) the river type, with 50 chromosomes, with an adult male weighing between 450 and 1000kg and with an annual milk production of 1000–3000kg; and (2) the swamp type, with 48 chromosomes, with an adult male weighing between 325 and 450kg and with an annual milk production of up to 600kg. The river buffalo is reared mainly for milk, whereas the swamp buffalo is reared mainly for draught. Only 3% of the world buffalo population is reared in the Mediterranean region. Significant numbers of buffaloes are at present found only in Italy, Romania, Egypt, Turkey, Azerbaijan, Iraq and Iran. In all these countries, buffaloes represent only a very small portion of total livestock, except in Egypt, where buffaloes are more numerous than cattle. Because of the strong market demand for buffalo cheese, the number of buffaloes has increased in Italy and there is a preference for buffalo dairy products compared to cows' milk products in a few countries. Major morphological differences between the buffalo populations of different countries include (1) the variable size, ranging between a minimum of 280 and 300kg liveweight for adult females and males, respectively, in Egypt to a maximum of 900 and 1000kg in Iraq, the most frequent weights being 600 and 800kg; (2) the shape of the horns; and (3) the coat color, from dark gray and dark brown to black, showing white spots in some cases. |
9alqngxk | Coronavirus Pandemic and Worries during Pregnancy; a Letter to Editor | |
c2vc2yya | Human Metapneumovirus: Etiological Agent of Severe Acute Respiratory Infections in Hospitalized and Deceased Patients with a Negative Diagnosis of Influenza | Human metapneumovirus (HMPV) is one of the four major viral pathogens associated with acute respiratory tract infections (ARI) and creates a substantial burden of disease, particularly in young children (<5 years) and older individuals (≥65 years). The objective of this study was to determine the epidemiological behavior of HMPV in Mexico. This retrospective study was conducted over a nine-year period and used 7283 influenza-negative respiratory samples from hospitalized and deceased patients who presented Severe Acute Respiratory Infection (SARI). The samples were processed with the help of qualitative multiplex RT-PCR for simultaneous detection of 14 respiratory viruses (xTAG(®) RVP FAST v2). 40.8% of the samples were positive for respiratory viruses, mainly rhinovirus/enterovirus (47.6%), respiratory syncytial virus (15.9%), HMPV (11.1%) and parainfluenza virus (8.9%). Other respiratory viruses and co-infections accounted for 16.5%. HMPV infects all age groups, but the most affected group was infants between 29 days and 9 years of age (65.6%) and adults who are 40 years and older (25.7%). HMPV circulates every year from November to April, and the highest circulation was observed in late winter. The results of this study aim to raise awareness among clinicians about the high epidemiological impact of HMPV in young children and older individuals in order to reduce the economic burden in terms of health care costs. |
8bq3hd64 | Facial Abrikosoff tumour: The role of the dermatologist during COVID‐19 pandemic | |
5a03euc0 | A dynamic mathematical test of international property securities bubbles and crashes | Abstract This study investigates property securities bubbles and crashes by using a dynamic mathematical methodology developed from the previous research (Watanabe et al. 2007a, b [31,32]). The improved model is used to detect the bubble and crash periods in five international countries/cities (namely, United States, United Kingdom, Japan, Hong Kong and Singapore) from Jan, 2000 to Oct, 2008. By this model definition, we are able to detect the beginning of each bubble period even before it bursts. Meanwhile, the empirical results show that most of property securities markets experienced bubble periods between 2003 and 2007, and crashes happened in Apr 2008 triggered by the Subprime Mortgage Crisis of US. In contrast, Japan suffered the shortest bubble period and no evidence has documented the existence of crash there. |
wpwwetrs | COVID-19 distresses the depressed while schizophrenic patients are unimpressed: a study on psychiatric inpatients | |
0msnzoua | Spatiotemporal pattern of COVID-19 and government response in South Korea (as of May 31, 2020) | Abstract Objectives The aim of this study is to assess how COVID-19 clustered across districts in South Korea and to assess whether the pattern and duration of clusters changed following the country’s containment strategy. Methods We conducted spatiotemporal analysis of COVID-19 daily confirmed cases by 250 districts in South Korea from January 20 to May 31, 2020, obtained from the Korea Centers for Disease Control and Prevention and each provincial website. Global Moran’s I statistic was used for spatial autocorrelation analysis and retrospective space-time scan statistic was used to analyze spatiotemporal clusters of COVID-19. Results The geographical distribution showed strong spatial autocorrelation, with a global Moran’s I coefficient of 0.784 (p = 0.0001). Twelve statistically significant spatiotemporal clusters were identified by space-time scan statistic using a discrete Poisson model. The spatial pattern of clusters changed and the duration of clusters became shorter over time. Conclusions Results indicate that South Korea’s containment strategy of COVID-19 was highly effective in both early detection and mitigation, with recent clusters being small in size and duration. Lessons from South Korea should spark a discussion on epidemic response. |
4kuxua6s | Bereit: Von der Normalstation zur Covid-19-Überwachungsstation | |
c51lfwd6 | Inhaled Hydroxychloroquine to Improve Efficacy and Reduce Harm in the Treatment of COVID-19 | Current formulations and dose regimens of hydroxychloroquine (HCQ) put patients at risk of harm. An analysis of clinical trials registered on ClinicalTrials.gov revealed that this may continue as many studies combine HCQ with agents that prolong the QT interval. Further, almost all of the trials registered do not consider dosage adjustment in the elderly, a patient population most likely to require HCQ treatment. Here we describe an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma and discuss how this approach may reduce side-effects and improve efficacy. As this simple formulation progressed to phase II studies, safety data can be used to immediately enable phase II trials in COVID-19. |
au24l9vs | First report of group A rotavirus and bovine coronavirus associated with neonatal calf diarrhea in the northwest of Argentina | Group A rotavirus (RVA) and bovine coronavirus (BCoV) are the two main viral enteropathogens associated with neonatal calf diarrhea. The aim of the present survey was to investigate the epidemiology and the role of RVA and BCoV in the presentation of dairy and beef calf diarrhea in Lerma Valley of Salta province, within the Northwest region of Argentina. Stool samples of calves with or without diarrhea younger than 2 months of age were collected from 19 dairy farms and 20 beef farms between the years 2014 and 2016. Stool samples were screened for RVA and BCoV detection by ELISA. Heminested multiplex RT-PCR was used for RVA typing and RT-PCR to confirm BCoV. Positive samples were submitted to sequencing analysis. Bovine RVA and BCoV were circulating in 63% (12/19) and 10.52% (2/19) of the dairy farms, respectively, where 9.5% (46/484) of the calves were positives to RVA and 0.4% (2/484) to BCoV. In beef herds, RVA was detected in 40% (8/20) of the farms and in 6.75% (21/311) of the calves, without positives cases of BCoV. Molecular analysis showed that in dairy farms, G6P[11] and G10P[11] were the prevalent RVA strains, while in beef farms, G10P[11] was the prevalent. The main finding was the detection for the first time of a G15P[11] causing diarrhea in beef calves of Argentina that represents a new alert to be consider for future vaccine updates. Analysis of detected BCoV showed that it is related to the other circulating strains of Argentina. |
nly4gqxq | Three-Dimensional Architecture and Biogenesis of Membrane Structures Associated with Hepatitis C Virus Replication | All positive strand RNA viruses are known to replicate their genomes in close association with intracellular membranes. In case of the hepatitis C virus (HCV), a member of the family Flaviviridae, infected cells contain accumulations of vesicles forming a membranous web (MW) that is thought to be the site of viral RNA replication. However, little is known about the biogenesis and three-dimensional structure of the MW. In this study we used a combination of immunofluorescence- and electron microscopy (EM)-based methods to analyze the membranous structures induced by HCV in infected cells. We found that the MW is derived primarily from the endoplasmic reticulum (ER) and contains markers of rough ER as well as markers of early and late endosomes, COP vesicles, mitochondria and lipid droplets (LDs). The main constituents of the MW are single and double membrane vesicles (DMVs). The latter predominate and the kinetic of their appearance correlates with kinetics of viral RNA replication. DMVs are induced primarily by NS5A whereas NS4B induces single membrane vesicles arguing that MW formation requires the concerted action of several HCV replicase proteins. Three-dimensional reconstructions identify DMVs as protrusions from the ER membrane into the cytosol, frequently connected to the ER membrane via a neck-like structure. In addition, late in infection multi-membrane vesicles become evident, presumably as a result of a stress-induced reaction. Thus, the morphology of the membranous rearrangements induced in HCV-infected cells resemble those of the unrelated picorna-, corona- and arteriviruses, but are clearly distinct from those of the closely related flaviviruses. These results reveal unexpected similarities between HCV and distantly related positive-strand RNA viruses presumably reflecting similarities in cellular pathways exploited by these viruses to establish their membranous replication factories. |
n6obg4yc | COVID-19: My Perspective | |
wisaamn7 | Temporal patterns of charcoal burning suicides among the working age population in Hong Kong SAR: the influence of economic activity status and sex | BACKGROUND: Charcoal burning in a sealed room has recently emerged as the second most common suicide means in Hong Kong, causing approximately 200 deaths each year. As charcoal burning suicide victims have a unique sociodemographic profile (i.e., predominantly economically active men), they may commit suicide at specific times. However, little is known about the temporal patterns of charcoal burning suicides. METHODS: Suicide data from 2001 to 2008 on victims of usual working age (20–59) were obtained from the registered death files of the Census and Statistics Department of Hong Kong. A total of 1649 cases of charcoal burning suicide were analyzed using a two-step procedure, which first examined the temporal asymmetries in the incidence of suicide, and second investigated whether these asymmetries were influenced by sex and/or economic activity status. Poisson regression analyses were employed to model the monthly and daily patterns of suicide by economic activity status and sex. RESULTS: Our findings revealed pronounced monthly and daily temporal variations in the pattern of charcoal burning suicides in Hong Kong. Consistent with previous findings on overall suicide deaths, there was an overall spring peak in April, and Monday was the common high risk day for all groups. Although sex determined the pattern of variation in charcoal burning suicides, the magnitude of the variation was influenced by the economic activity status of the victims. CONCLUSION: The traditional classification of suicide methods as either violent or nonviolent tends to elide the temporal variations of specific methods. The interaction between sex and economic activity status observed in the present study indicates that sex should be taken into consideration when investigating the influence of economic activity status on temporal variations of suicide. This finding also suggests that suicide prevention efforts should be both time- and subgroup-specific. |
deuytbml | Viruses and atypical bacteria associated with asthma exacerbations in hospitalized children | OBJECTIVES AND WORKING HYPOTHESIS: To evaluate the prevalence of respiratory viruses Mycoplasma pneumoniae and Chlamydophila pneumoniae and gain insight into their seasonal circulation pattern in children with acute asthma exacerbations in a temperate southern hemisphere region. STUDY DESIGN: Patients hospitalized between 3 months and 16 years of age were included in a 1‐year prospective, observational, cross‐sectional study. Respiratory secretions were collected and the presence of different viruses and atypical bacteria analyzed by immunofluorescence and polymerase chain reaction. RESULTS: Two hundred nine patients (118 females) aged (mean ± SD) 4.4 ± 4 years were included. A potential causative agent was detected in 78% of the patients. The most frequently detected viruses were respiratory syncytial virus (HRSV) (n = 85; 40%) and rhinovirus (HRV) (n = 52; 24.5%); M. pneumoniae and C. pneumoniae were detected in 4.5% and 2% of the cases, respectively. Patients with HRSV (vs. HRV) were hospitalized for a longer time (6.7 vs. 5.2 days, P = 0.012), required more days of oxygen supply (5.1 vs. 3.4, P = 0.005), had a longer duration of the exacerbation before hospitalization (3.6 vs. 1.9 days, P = 0.001) and were younger (3.7 vs. 5.1 years, P = 0.012). Three peaks of admissions were observed. A first peak (early autumn) caused by HRV, a second peak (winter) caused mainly by HRSV and a third one (spring), caused by HRSV, an increase in HMPV together with a second outbreak of HRV. CONCLUSIONS: Children with an acute asthma exacerbation presented a high prevalence of respiratory viruses. Most hospitalizations corresponded to seasonal increases in prevalence of HRV and HRSV. Pediatr Pulmonol. 2010; 45:619–625. © 2010 Wiley‐Liss, Inc. |
ag5hq426 | Vaccinia Virus Protein C6 Is a Virulence Factor that Binds TBK-1 Adaptor Proteins and Inhibits Activation of IRF3 and IRF7 | Recognition of viruses by pattern recognition receptors (PRRs) causes interferon-β (IFN-β) induction, a key event in the anti-viral innate immune response, and also a target of viral immune evasion. Here the vaccinia virus (VACV) protein C6 is identified as an inhibitor of PRR-induced IFN-β expression by a functional screen of select VACV open reading frames expressed individually in mammalian cells. C6 is a member of a family of Bcl-2-like poxvirus proteins, many of which have been shown to inhibit innate immune signalling pathways. PRRs activate both NF-κB and IFN regulatory factors (IRFs) to activate the IFN-β promoter induction. Data presented here show that C6 inhibits IRF3 activation and translocation into the nucleus, but does not inhibit NF-κB activation. C6 inhibits IRF3 and IRF7 activation downstream of the kinases TANK binding kinase 1 (TBK1) and IκB kinase-ε (IKKε), which phosphorylate and activate these IRFs. However, C6 does not inhibit TBK1- and IKKε-independent IRF7 activation or the induction of promoters by constitutively active forms of IRF3 or IRF7, indicating that C6 acts at the level of the TBK1/IKKε complex. Consistent with this notion, C6 immunoprecipitated with the TBK1 complex scaffold proteins TANK, SINTBAD and NAP1. C6 is expressed early during infection and is present in both nucleus and cytoplasm. Mutant viruses in which the C6L gene is deleted, or mutated so that the C6 protein is not expressed, replicated normally in cell culture but were attenuated in two in vivo models of infection compared to wild type and revertant controls. Thus C6 contributes to VACV virulence and might do so via the inhibition of PRR-induced activation of IRF3 and IRF7. |
g6j79d6v | Host gene targets for novel influenza therapies elucidated by high-throughput RNA interference screens | Influenza virus encodes only 11 viral proteins but replicates in a broad range of avian and mammalian species by exploiting host cell functions. Genome-wide RNA interference (RNAi) has proven to be a powerful tool for identifying the host molecules that participate in each step of virus replication. Meta-analysis of findings from genome-wide RNAi screens has shown influenza virus to be dependent on functional nodes in host cell pathways, requiring a wide variety of molecules and cellular proteins for replication. Because rapid evolution of the influenza A viruses persistently complicates the effectiveness of vaccines and therapeutics, a further understanding of the complex host cell pathways coopted by influenza virus for replication may provide new targets and strategies for antiviral therapy. RNAi genome screening technologies together with bioinformatics can provide the ability to rapidly identify specific host factors involved in resistance and susceptibility to influenza virus, allowing for novel disease intervention strategies.—Meliopoulos, V. A., Andersen, L. E., Birrer, K. F., Simpson, K. J., Lowenthal, J. W., Bean, A. G. D., Stambas, J., Stewart, C. R., Tompkins, S. M., van Beusechem, V. W., Fraser, I., Mhlanga, M., Barichievy, S., Smith, Q., Leake, D., Karpilow, J., Buck, A., Jona, G., Tripp, R. A. Host gene targets for novel influenza therapies elucidated by high-throughput RNA interference screens. |
o035r1pj | Universal health coverage in ‘One ASEAN’: are migrants included? | BACKGROUND: As the Association of South East Asian Nations (ASEAN) gears toward full regional integration by 2015, the cross-border mobility of workers and citizens at large is expected to further intensify in the coming years. While ASEAN member countries have already signed the Declaration on the Protection and Promotion of the Rights of Migrant Workers, the health rights of migrants still need to be addressed, especially with ongoing universal health coverage (UHC) reforms in most ASEAN countries. This paper seeks to examine the inclusion of migrants in the UHC systems of five ASEAN countries which exhibit diverse migration profiles and are currently undergoing varying stages of UHC development. DESIGN: A scoping review of current migration trends and policies as well as ongoing UHC developments and migrant inclusion in UHC in Indonesia, Malaysia, Philippines, Singapore, and Thailand was conducted. RESULTS: In general, all five countries, whether receiving or sending, have schemes that cover migrants to varying extents. Thailand even allows undocumented migrants to opt into its Compulsory Migrant Health Insurance scheme, while Malaysia and Singapore are still yet to consider including migrants in their government-run UHC systems. In terms of predominantly sending countries, the Philippines's social health insurance provides outbound migrants with portable insurance yet with limited benefits, while Indonesia still needs to strengthen the implementation of its compulsory migrant insurance which has a health insurance component. Overall, the five ASEAN countries continue to face implementation challenges, and will need to improve on their UHC design in order to ensure genuine inclusion of migrants, including undocumented migrants. However, such reforms will require strong political decisions from agencies outside the health sector that govern migration and labor policies. Furthermore, countries must engage in multilateral and bilateral dialogue as they redefine UHC beyond the basis of citizenship and reimagine UHC systems that transcend national borders. CONCLUSIONS: By enhancing migrant coverage, ASEAN countries can make UHC systems truly ‘universal’. Migrant inclusion in UHC is a human rights imperative, and it is in ASEAN's best interest to protect the health of migrants as it pursues the path toward collective social progress and regional economic prosperity. |
n593kh7u | A comparison of the sensitivity and specificity of sialodacryoadenitis virus, Parker's rat coronavirus, and mouse hepatitis virus-infected cells as a source of antigen for the detection of antibody to rat coronaviruses | Sialodacryoadenitis virus (SDAV) and Parker's rat coronavirus (PRC) are two recognized viral strains which cause spontaneous disease in the laboratory rat. Currently there is no recognized practical procedure which will accurately differentiate infections with these strains. Using SDAV- and PRC-infected L-2 cells as the source of antigen, and sera from rats collected post inoculation with either of these viral strains, the indirect fluorescent antibody (IFA) procedure was used to determine whether antibody titers could be used to differentiate infections from the homologous and heterologous virus. There was no detectable difference in the sensitivity or specificity of these systems in detecting antibody to the homologous or heterologous virus. Thus there was no evidence that SDAV- and PRC-infected cells would serve to differentiate antibody to the homologous virus using the IFA technique. In addition, antibody titers were similar when mouse hepatitis virus (MHV)-infected cells were used as the source of antigen for the IFA technique. However, using MHV or SDAV-infected cells as the source of antigen, there was a significant difference in antibody titers to the homologous virus detected using the immunoenzyme technique. |
fvo2jyh7 | WhatsApp supported language teacher development: A case study in the Zataari refugee camp | This paper explores the possibilities and challenges of using the social media tool WhatsApp to support language teacher development in the Zataari refugee camp in Jordan. It takes a sociocultural perspective on teacher development where WhatsApp is a mediating tool in the broader sociocultural landscape. A thematic analysis of the postings and exchanges from the WhatsApp group revealed three main uses of the WhatsApp chat: for interpersonal interactions, for professional development, and for organisational purposes. The analysis suggests the WhatsApp group contributed to the teachers’ English language knowledge, provided a platform for them to share and discuss issues related to the challenges of their particular context, enabled them to contribute to the development of some teaching materials and begin to address some of the issues they had in a meaningful way. It also raises issues of participation, access, equity and sustainability. We conclude by suggesting there is good potential for the use of social media tools such as WhatsApp for teacher development in challenging contexts, despite the contextual constraints observed and described. While this specific case involves language teachers, the general findings can potentially be applied to any teacher education or training context where access to training or education might be curtailed for a number of reasons, including the most recent changes enforced by the global COVID-19 pandemic. |
gl2gbqi9 | Estimates of Outbreak Risk from New Introductions of Ebola with Immediate and Delayed Transmission Control | While the ongoing Ebola outbreak continues in the West Africa countries of Guinea, Sierra Leone, and Liberia, health officials elsewhere prepare for new introductions of Ebola from infected evacuees or travelers. We analyzed transmission data from patients (i.e., evacuees, international travelers, and those with locally acquired illness) in countries other than the 3 with continuing Ebola epidemics and quantitatively assessed the outbreak risk from new introductions by using different assumptions for transmission control (i.e., immediate and delayed). Results showed that, even in countries that can quickly limit expected number of transmissions per case to <1, the probability that a single introduction will lead to a substantial number of transmissions is not negligible, particularly if transmission variability is high. Identifying incoming infected travelers before symptom onset can decrease worst-case outbreak sizes more than reducing transmissions from patients with locally acquired cases, but performing both actions can have a synergistic effect. |
8z9k5u5r | Recommendation about the perioperative prevention of infection to healthcare workers and the anesthesia management of children with SARS-CoV-2 infection | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread widely and persistently over 100 countries. New challenges have occurred in the perioperative management of airway and anesthesia in children diagnosed with SARS-CoV-2 infection. According to current publications and to our own experiences in anesthesia management for cases with SARS-CoV-2 suspected, we reviewed concerns about the perioperative prevention of SARS-CoV-2 to medical staff and the anesthesia strategy to the patient. |
1yhxnvoh | Analysis of codon usage patterns in Hirudinaria manillensis reveals a preference for GC-ending codons caused by dominant selection constraints | BACKGROUND: Hirudinaria manillensis is an ephemeral, blood-sucking ectoparasite, possessing anticoagulant capacities with potential medical applications. Analysis of codon usage patterns would contribute to our understanding of the evolutionary mechanisms and genetic architecture of H. manillensis, which in turn would provide insight into the characteristics of other leeches. We analysed codon usage and related indices using 18,000 coding sequences (CDSs) retrieved from H. manillensis RNA-Seq data. RESULTS: We identified four highly preferred codons in H. manillensis that have G/C-endings. Points generated in an effective number of codons (ENC) plot distributed below the standard curve and the slope of a neutrality plot was less than 1. Highly expressed CDSs had lower ENC content and higher GC content than weakly expressed CDSs. Principal component analysis conducted on relative synonymous codon usage (RSCU) values divided CDSs according to GC content and divided codons according to ending bases. Moreover, by determining codon usage, we found that the majority of blood-diet related genes have undergone less adaptive evolution in H. manillensis, except for those with homologous sequences in the host species. CONCLUSIONS: Codon usage in H. manillensis had an overall preference toward C-endings and indicated that codon usage patterns are mediated by differential expression, GC content, and biological function. Although mutation pressure effects were also notable, the majority of genetic evolution in H. manillensis was driven by natural selection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-4937-x) contains supplementary material, which is available to authorized users. |
z3pd339v | Traffic Control Bundling Is Essential for Protecting Healthcare Workers and Controlling the 2014 Ebola Epidemic | |
96jn13r1 | High prevalence of asymptomatic COVID-19 in hemodialysis: Daily learning during first month of COVID-19 pandemic | Abstract Dialysis patients are at risk for SARS-CoV-2 infection and possibly with more complications than other individuals; however, the information available is scarce. The objective of the present work is to describe the experience during the first month of the SARS-CoV-2 pandemic in a hemodialysis (HD) unit from a hospital in Madrid serving the 2nd district with the highest incidence of COVID-19 (almost 1,000 patients in 100,000 inhabitants). The information presented includes the actions carried out, the incidence of COVID-19 in HD patients and in health personnel, clinical characteristics and the result of a screening of all patients from the HD unit. At the beginning, we had 90 HD patients: 37 (41.1%) had COVID-19, of which 17 (45.9%) were diagnosed by symptoms detected in the triage or during the HD session, and 15 (40.5%) were diagnosed in a subsequent screening of patients in whom the diagnostic test by PCR-SARS-CoV-2 had not been done previously. The most frequent symptom was fever, 50% presented lymphopenia and in 18.4% the O2 saturation was <95%. Hospital admission was required in 16 patients (43.2%) and 6 died (16.2%). We found that contagion was clustered in turns of HD sessions and also in patients using collective transportation. Out of the 44 staff personnel, 15 (34%) presented compatible symptoms and 4 (9%) had SARS-CoV-2 diagnosed by PCR performed by the personnel health service, 9 (20%) required some transitory sick leave (TSL) and 5 were considered probable cases of Covid-19. Conclusions We detected a high prevalence of COVID-19 with a high percentage being diagnosed by screening and therefore it is necessary to be proactive in the diagnosis to stop the pandemic. Most patients positive for COVID-19 are being managed on an outpatient basis, although severe cases may occur and the mortality so far is 16.2%. Regarding the staff, 20% have required TSL in relation to COVID-19. |
ufazj34c | Potential Neuroinvasive Pathways of SARS‐CoV‐2: Deciphering the Spectrum of Neurological Deficit Seen in Coronavirus Disease 2019 (COVID‐19) | COVID‐19 was declared a global pandemic on March 11, 2020. Scientists and clinicians must acknowledge that Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) has the potential to attack the human body in multiple ways simultaneously and exploit any weaknesses of its host. A multipronged attack could potentially explain the severity and extensive variety of signs and symptoms observed in patients with COVID‐19. Understanding the diverse tactics of this virus to infect the human body is both critical and incredibly complex. Although patients diagnosed with COVID‐19 have primarily presented with pulmonary involvement, viral invasion, and injury to diverse end organs is also prevalent and well documented in these patients, but has been largely unheeded. Human organs known for Angiotensin‐Converting Enzyme 2 (ACE2) expression including the gastrointestinal tract, kidneys, heart, adrenals, brain, and testicles are examples of extra‐pulmonary tissues with confirmed invasion by SARS‐CoV‐2. Initial multiple organ involvement may present with vague signs and symptoms to alert healthcare professionals early in the course of COVID‐19. Another example of an ongoing, yet neglected element of the syndromic features of COVID‐19, are the reported findings of loss of smell, altered taste, ataxia, headache, dizziness, and loss of consciousness, which suggest a potential for neural involvement. In this review, we further deliberate on the neuroinvasive potential of SARS‐CoV‐2, the neurologic symptomology observed in COVID‐19, the host‐virus interaction, possible routes of SARS‐CoV‐2 to invade the central nervous system (CNS), other neurologic considerations for patients with COVID‐19, and a collective call to action. This article is protected by copyright. All rights reserved. |
284yyvzr | Comparing the performance of 3 bioaerosol samplers for influenza virus | Abstract Respiratory viral diseases can be spread when a virus-containing particle (droplet) from one individual is aerosolized and subsequently comes into either direct or indirect contact with another individual. Increasing numbers of studies are examining the occupational risk to healthcare workers due to proximity to patients. Selecting the appropriate air sampling method is a critical factor in assuring the analytical performance characteristics of a clinical study. The objective of this study was to compare the physical collection efficiency and virus collection efficiency of a 5mL compact SKC BioSampler®, a gelatin filter, and a glass fiber filter, in a laboratory setting. The gelatin filter and the glass fiber filter were housed in a home-made filter holder. Submersion (with vortexing and subsequent centrifugation) was used for the gelatin and glass fiber filters. Swabbing method was also tested to retrieve the viruses from the glass fiber filter. Experiments were conducted using the H1N1 influenza A virus A/Puerto Rico/8/1934 (IAV-PR8), and viral recovery was determined using culture and commercial real-time-PCR (BioFire and Xpert). An atomizer was used to aerosolize a solution of influenza virus in PBS for measurement, and two Scanning Mobility Particle Sizers were used to determine particle size distributions. The SKC BioSampler demonstrated a U-shaped physical collection efficiency, lowest for particles around 30–50nm, and highest at 10nm and 300–350nm within the size range examined. The physical collection efficiency of the gelatin filter was strongly influenced by air flow and time: a stable collection across all particle sizes was only observed at 2L/min for the 9min sampling time, otherwise, degradation of the filter was observed. The glass fiber filter demonstrated the highest physical collection efficiency (100% for all sizes) of all tested samplers, however, its overall virus recovery efficiency fared the worst (too low to quantify). The highest viral collection efficiencies for the SKC BioSampler and gelatin filter were 5% and 1.5%, respectively. Overall, the SKC BioSampler outperformed the filters. It is important to consider the total concentration of viruses entering the sampler when interpreting the results. |
s5lailkp | IL-6 Inhibitors in the Treatment of Serious COVID-19: A Promising Therapy? | At present, there are no proven agents for treatment of coronavirus disease (COVID-19). The available evidence has not allowed guidelines to clearly recommend any drugs outside the context of clinical trials. The novel coronavirus SARS-CoV-2 that causes COVID-19 invokes a hyperinflammatory state driven by multiple cells and mediators like interleukin (IL)-1, IL-6, IL-12, and IL-18, tumor necrosis factor alpha (TNFα), etc. Considering the proven role of cytokine dysregulation in causing this hyperinflammation in the lungs with IL-6 being a key driver, particularly in seriously ill COVID-19 patients, it is crucial to further explore selective cytokine blockade with drugs like the IL-6 inhibitors tocilizumab, sarilumab, and siltuximab. These targeted monoclonal antibodies can dampen the downstream IL-6 signaling pathways, which can lead to decreased cell proliferation, differentiation, oxidative stress, exudation, and improve clinical outcomes in patients with evident features of cytokine-driven inflammation like persistent fever, dyspnea and elevated markers. Preliminary evidence has come for tocilizumab from some small studies, and interim analysis of a randomized controlled trial; the latter also being available for sarilumab. International guidelines do include IL-6 inhibitors as one of the options available for severe or critically ill patients. There has been increased interest in evaluating these drugs with a series of clinical trials being registered and conducted in different countries. The level of investigation though perhaps needs to be further intensified as there is a need to focus on therapeutic options that can prove to be ‘life-saving’ as the number of COVID-19 fatalities worldwide keeps increasing alarmingly. IL-6 inhibitors could be one such treatment option, with generation of more evidence and completion of a larger number of systematic studies. |
z5d0qh87 | SARS‐CoV‐2–associated Guillain‐Barré syndrome with dysautonomia | |
gzkfy70s | Utility of Tracheostomy in Patients With COVID‐19 and Other Special Considerations | INTRODUCTION: Patients who become severely ill from coronavirus disease 2019 (COVID‐19) have a high likelihood of needing prolonged intubation, making tracheostomy a likely consideration. The infectious nature of COVID‐19 poses an additional risk of transmission to healthcare workers that should be taken into consideration. METHODS: We explore current literature and recommendations for tracheostomy in patients with COVID‐19 and look back at previous data from severe acute respiratory syndrome coronavirus 1 (SARS‐CoV‐1), the virus responsible for the SARS outbreak of 2003. RESULTS: Given the severity and clinical uncertainty of patients with COVID‐19 and the increased risk of transmission to clinicians, careful consideration should be taken prior to performing tracheostomy. If tracheostomy is performed, we recommend a bedside approach to limit exposure time and number of exposed personnel. Bronchoscopy use with a percutaneous approach should be limited in order to decrease viral exposure. CONCLUSION: Thorough preprocedural planning, use of experienced personnel, enhanced personal protective equipment where available, and a thoughtful anesthesia approach are instrumental in maximizing positive patient outcomes while successfully protecting the safety of healthcare personnel. Laryngoscope, 2020 |
97qg757x | Frequent Detection of Respiratory Viruses in Adult Recipients of Stem Cell Transplants with the Use of Real-Time Polymerase Chain Reaction, Compared with Viral Culture | Background. Respiratory virus infections have been recognized as important causes of severe pneumonia in patients who have undergone stem cell transplantation (SCT). Reported incidences of respiratory virus infection in adult SCT recipients vary in the literature from 3.5% to 36% when determined by viral culture. However, a more sensitive method to assess the presence of respiratory viruses in the lower airways may be important for delineation of the true incidence of respiratory virus—associated pneumonia and may be essential for guidance on implementation of antiviral therapy and prevention or limitation of nosocomial spread of infection with respiratory viruses. Methods. To determine the incidence and severity of respiratory tract illness (RTI) and to assess the diagnostic value of real-time reverse-transcriptase polymerase chain reaction (RT-PCR) versus viral culture, 72 SCT recipients were monitored during a 6-month period. Results. A respiratory virus was detected in 21% of episodes of RTI by viral culture and in 63% of RTI episodes by real-time RT-PCR (P < .0001). In lower respiratory tract illness, real-time RT-PCR was much more sensitive than viral culture for detection of respiratory virus (73% vs. 9%; P = .008). The mortality rate for patients with respiratory virus—associated lower respiratory tract illness (25%) was similar to rates reported elsewhere. Respiratory viruses (predominantly rhinovirus) were detected by real-time RT-PCR in 9% of samples obtained from symptom-free SCT recipients at predetermined times by real-time RT-PCR and by viral culture in 1% (P < .0001), indicating that asymptomatic shedding of respiratory viruses also occurs. Conclusion. We conclude that, although asymptomatic shedding of respiratory virus occurs, respiratory viruses are frequent causes of RTI in SCT recipients. |
5hbsceqk | Utility of an immunocytochemical assay using aqueous humor in the diagnosis of feline infectious peritonitis | OBJECTIVE: In cats suffering from feline infectious peritonitis (FIP) without effusion, antemortem diagnosis is challenging. Uveitis is common in these cats. It was the aim of this study to evaluate sensitivity and specificity of an immunocytochemical assay (ICC) in aqueous humor of cats suspected of having FIP. ANIMALS STUDIED: The study included 26 cats with immunohistochemically confirmed FIP and 12 control cats for which FIP was suspected due to similar clinical or laboratory changes, but which suffered from other diseases confirmed via histopathology. PROCEDURES: All aqueous humor samples were collected postmortem by paracentesis. ICC was carried out as avidin–biotin complex method. Sensitivity, specificity, and the overall accuracy including 95% confidence intervals (95% CI) were calculated. RESULTS: Immunocytochemistry was positive in 16 of 25 cats with FIP and 2 of 11 control cats (one cat with lymphoma, one with pulmonary adenocarcinoma). Aqueous humor samples of one cat with FIP and of one control cat were excluded from statistical analysis. Sensitivity was 64.0% (95% CI: 42.5–82.0); specificity 81.8% (95% CI: 48.2–97.7); and overall accuracy 69.4% (95% CI: 51.9–83.7). CONCLUSIONS: As false‐positive results occurred and specificity is most important in the diagnosis of FIP, the diagnostic utility of ICC in aqueous humor is limited. Further studies are required to clarify the origin of false‐positive ICC results. |
ihc0an83 | Management of Hepatocellular Cancer in the time of SARS‐CoV‐2 | As COVID‐19 the disease caused by SARS‐CoV‐2 continues to have a profound impact on global health, there have been a number of guidelines recently published addressing the management of patients with liver disease during the COVID‐19 pandemic including the recently published EASL‐ESCMID Position Paper, guidelines issued by the International Liver Cancer Association and the American Association for the Study of Liver Diseases (1‐3). All publications present a sound discussion regarding the challenges face by both patients and clinicians alike in the management of chronic liver disease in the setting of this ongoing pandemic. |
nedbi9aq | Increased frequency of porcine epidemic diarrhea virus shedding and lesions in suckling pigs compared to nursery pigs and protective immunity in nursery pigs after homologous re-challenge | Porcine epidemic diarrhea virus (PEDV) causes enteric disease in pigs and spreads rapidly after entering naïve pig populations. The objectives were to (1) compare the disease course following inoculation with PEDV isolate US/Colorado/2013 in naïve 10 day and 8 week-old pigs, and (2) contrast the naïve response to homologous challenge in 8 week-old pigs. Pigs were randomly assigned into group 1 (n = 40, no PEDV exposure), group 2 (n = 43, PEDV inoculation at 10 days of age) and group 3 (n = 48, PEDV inoculation at 8 weeks of age). Thirty-three group 2 pigs received a homologous challenge at 8 weeks of age. Following primary or secondary inoculation, 3–10 pigs were euthanized at days post-inoculation (dpi) 1, 2, 3, 7 or 14. Clinical signs were more pronounced in 10 day-old pigs compared to 8 week-old pigs at dpi 2 and 3, a higher number of 10 day-old pigs shed PEDV RNA in feces compared to 8 week-old pigs. Typical severe atrophic enteritis of PEDV infection was observed at dpi 3 in both age groups, and at dpi 4 and 14 fecal shedding patterns were also similar. While both age groups had seroconverted to PEDV by dpi 14, IgG levels were higher in 8 week-old pigs. PEDV IgA antibodies were detected in feces of approximately 50% of the pigs at dpi 44. In homologous challenged pigs, no clinical signs or lesions were found, and PEDV fecal shedding was restricted to less than 10% of the pigs indicating the existence of homologous protection 44 days after initial PEDV exposure. |
ycyoxt02 | A Role for Neutrophils in Viral Respiratory Disease | Neutrophils are immune cells that are well known to be present during many types of lung diseases associated with acute respiratory distress syndrome (ARDS) and may contribute to acute lung injury. Neutrophils are poorly studied with respect to viral infection, and specifically to respiratory viral disease. Influenza A virus (IAV) infection is the cause of a respiratory disease that poses a significant global public health concern. Influenza disease presents as a relatively mild and self-limiting although highly pathogenic forms exist. Neutrophils increase in the respiratory tract during infection with mild seasonal IAV, moderate and severe epidemic IAV infection, and emerging highly pathogenic avian influenza (HPAI). During severe influenza pneumonia and HPAI infection, the number of neutrophils in the lower respiratory tract is correlated with disease severity. Thus, comparative analyses of the relationship between IAV infection and neutrophils provide insights into the relative contribution of host and viral factors that contribute to disease severity. Herein, we review the contribution of neutrophils to IAV disease pathogenesis and to other respiratory virus infections. |
6hdk8801 | A Pneumonia Case Associated with Type 2 Polio Vaccine Strains | |
2ypbpqtf | Short‐term Skin Reactions Following Use of N95 Respirators and Medical Masks | |
57urt8no | Immune mechanisms in inflammatory polyneuropathy | |
9pb2eqoa | A cluster randomised trial of cloth masks compared with medical masks in healthcare workers | OBJECTIVE: The aim of this study was to compare the efficacy of cloth masks to medical masks in hospital healthcare workers (HCWs). The null hypothesis is that there is no difference between medical masks and cloth masks. SETTING: 14 secondary-level/tertiary-level hospitals in Hanoi, Vietnam. PARTICIPANTS: 1607 hospital HCWs aged ≥18 years working full-time in selected high-risk wards. INTERVENTION: Hospital wards were randomised to: medical masks, cloth masks or a control group (usual practice, which included mask wearing). Participants used the mask on every shift for 4 consecutive weeks. MAIN OUTCOME MEASURE: Clinical respiratory illness (CRI), influenza-like illness (ILI) and laboratory-confirmed respiratory virus infection. RESULTS: The rates of all infection outcomes were highest in the cloth mask arm, with the rate of ILI statistically significantly higher in the cloth mask arm (relative risk (RR)=13.00, 95% CI 1.69 to 100.07) compared with the medical mask arm. Cloth masks also had significantly higher rates of ILI compared with the control arm. An analysis by mask use showed ILI (RR=6.64, 95% CI 1.45 to 28.65) and laboratory-confirmed virus (RR=1.72, 95% CI 1.01 to 2.94) were significantly higher in the cloth masks group compared with the medical masks group. Penetration of cloth masks by particles was almost 97% and medical masks 44%. CONCLUSIONS: This study is the first RCT of cloth masks, and the results caution against the use of cloth masks. This is an important finding to inform occupational health and safety. Moisture retention, reuse of cloth masks and poor filtration may result in increased risk of infection. Further research is needed to inform the widespread use of cloth masks globally. However, as a precautionary measure, cloth masks should not be recommended for HCWs, particularly in high-risk situations, and guidelines need to be updated. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry: ACTRN12610000887077. |
662arlyb | CORONAVIRUS AND RADIOLOGY. CONSIDERATIONS ON THE CRISIS | |
ml24b7tb | El diagnostico COVID-19 a través de la imagen | |
ptdgqjb4 | Mechanical Risks of Ventilator Sharing in the COVID-19 Era: a Simulation- Based Study | |
145kwny3 | Surface plasmon resonance applications in clinical analysis | In the last 20 years, surface plasmon resonance (SPR) and its advancement with imaging (SPRi) emerged as a suitable and reliable platform in clinical analysis for label-free, sensitive, and real-time monitoring of biomolecular interactions. Thus, we report in this review the state of the art of clinical target detection with SPR-based biosensors in complex matrices (e.g., serum, saliva, blood, and urine) as well as in standard solution when innovative approaches or advanced instrumentations were employed for improved detection. The principles of SPR-based biosensors are summarized first, focusing on the physical properties of the transducer, on the assays design, on the immobilization chemistry, and on new trends for implementing system analytical performances (e.g., coupling with nanoparticles (NPs). Then we critically review the detection of analytes of interest in molecular diagnostics, such as hormones (relevant also for anti-doping control) and biomarkers of interest in inflammatory, cancer, and heart failure diseases. Antibody detection is reported in relation to immune disorder diagnostics. Subsequently, nucleic acid targets are considered for revealing genetic diseases (e.g., point mutation and single nucleotides polymorphism, SNPs) as well as new emerging clinical markers (microRNA) and for pathogen detection. Finally, examples of pathogen detection by immunosensing were also analyzed. A parallel comparison with the reference methods was duly made, indicating the progress brought about by SPR technologies in clinical routine analysis. |
0vke9lch | Apoptosis induced in vivo by new type gosling viral enteritis virus | In this study, apoptosis was induced by new type gosling viral enteritis virus (NGVEV) in experimentally infected goslings is reported in detail for the first time. After 3-day-old goslings were orally inoculated with a NGVEV-CN strain suspension, the time course of NGVEV effects on apoptotic morphological changes of the internal tissues was evaluated. These changes were observed by histological analysis with light microscopy and ultrastructural analysis with transmission electron microscopy. DNA fragmentation was assessed with a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay and DNA ladder analysis. A series of characteristic apoptotic morphological changes including chromatin condensation and margination, cytoplasmic shrinkage, plasma membrane blebbing, and formation of apoptotic bodies were noted. Apoptosis was readily observed in the lymphoid and gastrointestinal organs, and sporadically occurred in other organs after 3 days post-infection (PI). The presence and quantity of TUNEL-positive cells increased with infection time until 9 days PI. DNA extracted from the NGVEV-infected gosling cells displayed characteristic 180~200 bp ladders. Apoptotic cells were ubiquitously distributed, especially among lymphocytes, macrophages, monocytes, and epithelial and intestinal cells. Necrosis was subsequently detected during the late NGVEV-infection phase, which was characterized by cell swelling, plasma membrane collapse, and rapidly lysis. Our results suggested that apoptosis may play an important role in the pathogenesis of NGVE disease. |
ja8nxc82 | COVID-19 et Insuffisance rénale aigue en réanimation | Résumé L’atteinte rénale est une complication fréquemment rencontrée chez les patients hospitalisés en unité de soins intensifs pour syndrome de détresse respiratoire aigüe (SDRA) du à la COVID-19. Sa prévalence semble différente à travers le monde. Plusieurs mécanismes physiopathologiques sont impliqués, parmi lesquelles une hypoperfusion rénale liée à la ventilation mécanique, au sepsis et à l’orage cytokinique, ainsi qu’une toxicité directe du virus sur les cellules tubulaires proximales et les podocytes, médiée par les récepteurs de conversion de l’angiotensine 2 (ACE 2) et les protéases TMPRSS. Le recours à l’épuration extra rénale (EER) est de l’ordre de 20% chez les patients de réanimation. La dialyse est rendue difficile par l’état d’hypercoagulabilité des patients atteints du SARS-Cov2, qui provoque des thromboses précoces du filtre. Summary Renal impairment is a common complication in patients hospitalized in intensive care unit for acute respiratory distress syndrome (ARDS) due to COVID-19 infection. However, the prevalence of SARS-covid2 kidney injury is difficult to estimate worldwide. Several pathophysiological mechanisms are involved; including decreased renal perfusion related to mechanical ventilation, sepsis and cytokines release, as well as direct virus toxicity on proximal tubular cells and podocytes, mediated by angiotensin 2 conversion receptors (ACE 2) and TMPRSS proteases. More than 20% of ICU COVID-19 patients require extra renal replacement therapy (ERT) for acute renal failure that is made difficult by the hypercoagulable state of these patients, responsible for filter thrombosis. |
fmsa7ket | Exploring the Major Factors Influencing Consumer Selection of Travel Agencies in a Regional Setting | The research reported in this article explores why consumers choose to book their travel arrangements with travel agencies in regional settings. Consumers can now access online bookings for airlines, accommodation, transportation, sightseeing tours and other related products, so why do they still go to travel agencies for reservations? This article identifies the attributes consumers seek in a travel agency or consultant and determines the relative importance of these in their selection process. The research was conducted in two stages. The first stage was a series of in-depth interviews with 10 travel agency users and three travel consultants. The second stage was a mail-out survey of 400 users of travel agencies in the Darling Downs area of Queensland, Australia. Despite its regionality, the region is a significant consumer of travel with approximately eight agencies in the city of Toowoomba alone. The in-depth interviews highlighted the need to de-emphasise two particular agency attributes, agency promotion and adequate brochure provision, from the research questions and replace these with parking and travel reward programs as factors worthy of investigation. Survey results revealed that there were 12 significant attributes impacting on consumer selection and, of these, the most important were the knowledge and experience of consultants, and the helpfulness and friendliness of consultants. Of particular note was that these attributes related to the consultant and not the agency per se. Travel reward programs were seen as the least influential in this research. |
urwpow4n | Spillover and pandemic properties of zoonotic viruses with high host plasticity | Most human infectious diseases, especially recently emerging pathogens, originate from animals, and ongoing disease transmission from animals to people presents a significant global health burden. Recognition of the epidemiologic circumstances involved in zoonotic spillover, amplification, and spread of diseases is essential for prioritizing surveillance and predicting future disease emergence risk. We examine the animal hosts and transmission mechanisms involved in spillover of zoonotic viruses to date, and discover that viruses with high host plasticity (i.e. taxonomically and ecologically diverse host range) were more likely to amplify viral spillover by secondary human-to-human transmission and have broader geographic spread. Viruses transmitted to humans during practices that facilitate mixing of diverse animal species had significantly higher host plasticity. Our findings suggest that animal-to-human spillover of new viruses that are capable of infecting diverse host species signal emerging disease events with higher pandemic potential in that these viruses are more likely to amplify by human-to-human transmission with spread on a global scale. |
84etaikv | Predictive value of C-reactive protein for the diagnosis of meningitis in febrile infants under 3 months of age in the emergency department | BACKGROUND: Fever is a common cause of pediatric consultation in the emergency department. However, identifying the source of infection in many febrile infants is challenging because of insufficient presentation of signs and symptoms. Meningitis is a critical cause of fever in infants, and its diagnosis is confirmed invasively by lumbar puncture. This study aimed to evaluate potential laboratory markers for meningitis in febrile infants. METHODS: We retrospectively analyzed infants aged <3 months who visited the emergency department of our hospital between May 2012 and May 2017 because of fever of unknown etiology. Clinical information and laboratory data were evaluated. Receiver operating characteristic (ROC) curves were constructed. RESULTS: In total, 145 febrile infants aged <3 months who underwent lumbar punctures were evaluated retrospectively. The mean C-reactive protein (CRP) level was significantly higher in the meningitis group than in the non-meningitis group, whereas the mean white blood cell count or absolute neutrophil count (ANC) did not significantly differ between groups. The area under the ROC curve (AUC) for CRP was 0.779 (95% confidence interval [CI], 0.701–0.858). The AUC for the leukocyte count was 0.455 (95% CI, 0.360–0.550) and that for ANC was 0.453 (95% CI, 0.359–0.547). The CRP cut-off value of 10 mg/L was optimal for identifying possible meningitis. CONCLUSION: CRP has an intrinsic predictive value for meningitis in febrile infants aged <3 months. Despite its invasiveness, a lumbar puncture may be recommended to diagnose meningitis in young, febrile infants with a CRP level >10 mg/L. |
voem879q | Structure‐Based Design and Synthesis of Highly Potent SARS‐CoV 3CL Protease Inhibitors | In a successful example of lead optimization by computer modeling prediction, computational technology was used to optimize a lead inhibitor (TL‐3) of the SARS‐CoV 3CL protease. A novel C (2)‐symmetric diol (1) was then designed and synthesized, and displayed higher affinity than the original lead compound by one order of magnitude in its inhibition constant (0.6→0.073 μm). We believe that this approach has provided a platform for further lead optimization.[Image: see text] |
h1afpc9x | Role of Human Polyomaviruses in Respiratory Tract Disease in Young Children | KI virus was detected in respiratory secretions of 8/367 (2.2%) symptomatic and 0/96 asymptomatic children (p = 0.215). WU virus was detected in 26/367 (7.1%) symptomatic and 6/96 (6.3%) asymptomatic children (p = 1.00). These human polyomaviruses may not independently cause respiratory tract disease in young children. |
mq6qjs2s | Mechanisms and evidence of vertical transmission of infections in pregnancy including SARS‐CoV‐2 | There remain unanswered questions concerning mother‐to‐child‐transmission (MTCT) of SARS‐CoV‐2. Despite reports of neonatal COVID‐19, SARS‐CoV‐2 has not been consistently isolated in perinatal samples thus, definitive proof of transplacental infection is still lacking. To address these questions, we assessed investigative tools used to confirm maternal‐fetal infection and known protective mechanisms of the placental barrier that prevent transplacental pathogen migration. Forty studies of COVID‐19 pregnancies reviewed suggest a lack of consensus on diagnostic strategy for congenital infection. While RT‐PCR of neonatal swabs was universally performed, a wide range of clinical samples was screened including vaginal secretions (22.5%), amniotic fluid (35%), breast milk (22.5%) and umbilical cord blood. Neonatal COVID‐19 was reported in eight studies, two of which were based on the detection of SARS‐CoV‐2 IgM in neonatal blood. Histological examination demonstrated sparse viral particles, vascular malperfusion and inflammation in the placenta from pregnant women with COVID‐19. The paucity of placental co‐expression of ACE‐2 and TMPRSS2, two receptors involved in cytoplasmic entry of SARS‐CoV‐2, may explain its relative insensitivity to transplacental infection. Viral interactions may utilise membrane receptors other than ACE‐2 thus, tissue susceptibility may be broader than currently known. Further spatial‐temporal studies are needed to determine the true potential for transplacental migration. This article is protected by copyright. All rights reserved. |
0jnj3usw | Ion Channels Formed by SARS Coronavirus Envelope Protein: Lipid Regulation of Conductance and Selectivity | |
p9bdjni9 | Gammaherpesviral Gene Expression and Virion Composition Are Broadly Controlled by Accelerated mRNA Degradation | Lytic gammaherpesvirus infection restricts host gene expression by promoting widespread degradation of cytoplasmic mRNA through the activity of the viral endonuclease SOX. Though generally assumed to be selective for cellular transcripts, the extent to which SOX impacts viral mRNA stability has remained unknown. We addressed this issue using the model murine gammaherpesvirus MHV68 and, unexpectedly, found that all stages of viral gene expression are controlled through mRNA degradation. Using both comprehensive RNA expression profiling and half-life studies we reveal that the levels of the majority of viral mRNAs but not noncoding RNAs are tempered by MHV68 SOX (muSOX) activity. The targeting of viral mRNA by muSOX is functionally significant, as it impacts intracellular viral protein abundance and progeny virion composition. In the absence of muSOX-imposed gene expression control the viral particles display increased cell surface binding and entry as well as enhanced immediate early gene expression. These phenotypes culminate in a viral replication defect in multiple cell types as well as in vivo, highlighting the importance of maintaining the appropriate balance of viral RNA during gammaherpesviral infection. This is the first example of a virus that fails to broadly discriminate between cellular and viral transcripts during host shutoff and instead uses the targeting of viral messages to fine-tune overall gene expression. |
jc97qxm9 | Letter to the Editor Regarding: “An Imperative Need for Research on the Role of Environmental Factors in Transmission of Novel Coronavirus (COVID-19)” —Secondhand and Thirdhand Smoke As Potential Sources of COVID-19 | |
strhszpd | Current advancements and potential strategies in the development of MERS-CoV vaccines | Middle East respiratory syndrome (MERS) is a newly emerging infectious disease caused by a novel coronavirus, MERS-coronavirus (MERS-CoV), a new member in the lineage C of β-coronavirus (β-CoV). The increased human cases and high mortality rate of MERS-CoV infection make it essential to develop safe and effective vaccines. In this review, the current advancements and potential strategies in the development of MERS vaccines, particularly subunit vaccines based on MERS-CoV spike (S) protein and its receptor-binding domain (RBD), are discussed. How to improve the efficacy of subunit vaccines through novel adjuvant formulations and routes of administration as well as currently available animal models for evaluating the in vivo efficacy of MERS-CoV vaccines are also addressed. Overall, these strategies may have important implications for the development of effective and safe vaccines for MERS-CoV in the future. |
euxtklwq | Meta‐analysis of chest CT features of patients with COVID‐19 pneumonia | The objective of this paper is to perform a meta‐analysis regarding the chest computed tomography (CT) manifestations of coronavirus disease‐2019 (COVID‐19) pneumonia patients. PubMed, Embase, and Cochrane Library databases were searched from 1 December 2019 to 1 May 2020 using the keywords of “COVID‐19 virus,” “the 2019 novel coronavirus,” “novel coronavirus,” and “COVID‐19.” Studies that evaluated the CT manifestations of common and severe COVID‐19 pneumonia were included. Among the 9736 searched results, 15 articles describing 1453 common patients and 697 severe patients met the inclusion criteria. Based on the CT images, the common patients were less frequent to exhibit consolidation (odds ratio [OR] = 0.31), pleural effusion (OR = 0.19), lymphadenopathy (OR = 0.17), crazy‐paving pattern (OR = 0.22), interlobular septal thickening (OR = 0.27), reticulation (OR = 0.20), traction bronchiectasis (OR = 0.40) with over two lobes involved (OR = 0.07) and central distribution (OR = 0.18) while more frequent to bear unilateral pneumonia (OR = 4.65) involving one lobe (OR = 13.84) or two lobes (OR = 6.95) when compared with severe patients. Other CT features including ground‐glass opacities (P = .404), air bronchogram (P = .070), nodule (P = .093), bronchial wall thickening (P = .15), subpleural band (P = .983), vascular enlargement (P = .207), and peripheral distribution (P = .668) did not have a significant association with the severity of the disease. No publication bias among the selected studies was suggested (Harbord's tests, P > .05 for all.) We obtained reliable estimates of the chest CT manifestations of COVID‐19 pneumonia patients, which might provide an important clue for the diagnosis and classification of COVID‐19 pneumonia. |
t9nx7a7b | Antibody responses to respiratory coronavirus infections of cattle during shipping fever pathogenesis | Antibody responses against respiratory bovine coronavirus (RBCV) infections were monitored in cattle from the onset of a naturally occurring severe shipping fever (SF) epizootic to complete recovery of affected cattle or fatal outcomes. The infection with RBCV was detected in nasal secretions of 86 cattle, and 81 of them developed acute respiratory tract disease, including fatal pneumonia. Cattle nasally shedding RBCV at the beginning of the epizootic experienced characteristic primary immune responses with specific antibodies for hemagglutinin-esterase (HE) and spike (S) glycoproteins. Virus shedding in nasal secretions of the majority of the cattle ceased between days 7 and 14 with the appearance of HE- and S-specific antibodies. Nasal samples and lung tissues from 9 of the 10 fatal cases had high titers of RBCV, but these cattle had only IgM responses to RBCV infections. Cattle remaining negative in RBCV isolation tests entered this epizootic with antibodies against HE and S. Protection against respiratory tract disease was apparently associated with high level of opsonic and virus-neutralizing IgG2. The HE and S glycoproteins were recognized earliest by the bovine immune system while the N protein induced antibody responses during the later stage of initial infection and the early stage of reinfection. The membrane (M) glycoprotein was the least immunogenic of the major viral structural proteins. |
vbdb0x3m | 28 New and Emerging Infections of the Lung | Abstract In this era of rapid globalization and frequent travel, emerging viral infections have gained an immense potential to spread at an unprecedented speed and scale compared with the past. This poses a significant challenge to coordinated international efforts in global surveillance and infection control. Significantly, respiratory viral infections, spread mostly via droplet transmission, are extremely contagious and have caused significant morbidity and mortality during outbreaks in the last decade. Molecular diagnostics via reverse transcriptase polymerase chain reaction (RT-PCR) have been key in the rapid diagnosis of most of these viral infections. However, a high index of suspicion and early institution of appropriate isolation measures remain as the mainstay in the control and containment of the spread of these viral infections. Although treatment for most of the viral infections remains supportive, efficacious antiviral agents against influenza infections exist. The infections discussed in this chapter include those first described in the 2000s: Middle East respiratory syndrome coronavirus (MERS-CoV) and metapneumovirus and rhinovirus C as well as those that have been described in the past but have reemerged in the last decade in outbreaks resulting in significant morbidity and mortality, including adenovirus, influenza virus, and enterovirus D68 (EV-D68). |
9cblzv98 | Identification of potential inhibitors of SARS-COV-2 endoribonuclease (EndoU) from FDA approved drugs: a drug repurposing approach to find therapeutics for COVID-19 | SARS-CoV-2 is causative agent of COVID-19, which is responsible for severe social and economic disruption globally. Lack of vaccine or antiviral drug with clinical efficacy suggested that drug repurposing approach may provide a quick therapeutic solution to COVID-19. Nonstructural protein-15 (NSP15) encodes for an uridylate-specific endoribonuclease (EndoU) enzyme, essential for virus life cycle and an attractive target for drug development. We have performed in silico based virtual screening of FDA approved compounds targeting EndoU in search of COVID-19 drugs from commercially available approved molecules. Two drugs Glisoxepide and Idarubicin used for treatment for diabetes and leukemia, respectively, were selected as stronger binder of EndoU. Both the drugs bound to the active site of the viral endonuclease by forming attractive intermolecular interactions with catalytically essential amino acid residues, His235, His250, and Lys290. Molecular dynamics simulation studies showed stable conformation dynamics upon drugs binding to endoU. The binding free energies for Glisoxepide and Idarubicin were calculated to be –141 ± 11 and –136 ± 16 kJ/mol, respectively. The IC(50) were predicted to be 9.2 µM and 30 µM for Glisoxepide and Idarubicin, respectively. Comparative structural analysis showed the stronger binding of EndoU to Glisoxepide and Idarubicin than to uridine monophosphate (UMP). Surface area calculations showed buried are of 361.8Å(2) by Glisoxepide which is almost double of the area occupied by UMP suggesting stronger binding of the drug than the ribonucleotide. However, further studies on these drugs for evaluation of their clinical efficacy and dose formulations may be required, which may provide a quick therapeutic option to treat COVID-19. Communicated by Ramaswamy H. Sarma |