title: Lower Respiratory Tract Virus Findings in Mechanically Ventilated Patients With Severe Community-Acquired Pneumonia

text: Background. The role of viral infections in the etiology of severe community-acquired pneumonia (SCAP) was prospectively evaluated from 2008 to 2012 at a university-level intensive care unit. Methods. Clinical data and microbiological tests were assessed: blood cultures, urine pneumococcal and legionella antigens, Mycoplasma pneumoniae and Chlamydia pneumoniae antibodies from paired serums, and respiratory virus detection by multiplex, real-time polymerase chain reaction (PCR) from nasopharyngeal swabs and lower tracheal specimens via intubation tube. Results. Of 49 mechanically ventilated SCAP patients (21 men and 28 women; median age, 54 years), the etiology was identified in 45 cases (92%). There were 21 pure bacterial infections (43%), 5 probably pure viral infections (10%), and 19 mixed bacterial–viral infections (39%), resulting in viral etiology in 24 patients (49%). Of 26 viruses, 21 (81%) were detected from bronchial specimens and 5 (19%) from nasopharyngeal swabs. Rhinovirus (15 cases, 58%) and adenovirus (4 cases, 15%) were the most common viral findings. The bacterial–viral etiology group had the highest peak C-reactive protein levels (median, 356 [25th–75th percentiles, 294–416], P = .05), whereas patients with probably viral etiology had the lowest peak procalcitonin levels (1.7 [25th–75th percentiles, 1.6–1.7]). The clinical characteristics of pure bacterial and mixed bacterial–viral etiologies were comparable. Hospital stay was longest among the bacterial group (17 vs 14 days; P = .02). Conclusions. Viral findings were demonstrated in almost half of the SCAP patients. Clinical characteristics were similar between the pure bacterial and mixed bacterial–viral infections groups. The frequency of viral detection depends on the availability of PCR techniques and lower respiratory specimens.


Role of anaesthesiologists during the coronavirus disease 2019 outbreak in China


docid: tltteovy

title: Point of Care Ultrasound in Critically Ill Patients- Assessing Value in an Ever-changing Environment


title: Diabetes increases the mortality of patients with COVID-19: a meta-analysis

text: AIMS: Nowadays, the ongoing pandemic of COVID-19 caused by the novel coronavirus Syndrome-Coronavirus-2 (SARS-CoV-2) is an emerging, rapidly evolving situation. Complications such as hypertension, diabetes, COPD, cardiovascular disease, and cerebrovascular disease are major risk factors for patients with COVID-19. METHODS: No meta-analysis has explored if or not diabetes related to mortality of patients with COVID-19. Therefore, this meta-analysis first aims to explore the possible clinical mortality between diabetes and COVID-19, analyze if diabetes patients infected with SARS-CoV-2 are exposed to the worst clinical prognostic risk, and to evaluate the reliability of the evidence. RESULTS: Our results showed a close relationship between diabetes and mortality of COVID-19, with a pooled OR of 1.75 (95% CI 1.31–2.36; P = 0.0002). The pooled data were calculated with the fixed effects model (FEM) as no heterogeneity appeared in the studies. Sensitivity analysis showed that after omitting any single study or converting a random effect model to FEM, the main results still held. CONCLUSIONS: Our meta-analysis showed that diabetes increases the mortality of patients with COVID-19. These results indicated the disturbance of blood glucose in the COVID-19 patients. More importantly, this meta-analysis grades the reliability of evidence for further basic and clinical research into the diabetes dysfunction in COVID-19 patients.


title: SARS-CoV-2 and Male Infertility: Possible Multifaceted Pathology

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease 2019 (COVID-19) has been declared a pandemic by the World Health Organization (WHO) on 11th March 2020. Bulk of research on this virus are carried out to unveil its multivariate pathology. Surprisingly, men are reportedly more vulnerable to COVID-19 even with higher fatality rate compared to women. Thus, it is crucial to determine whether SARS-CoV-2 infection can even affect male fertility as an immediate or long-term consequence of the disease. Among the discrete data available, an important finding is that angiotensin converting enzymes 2 (ACE2) receptor, that aids the SARS-CoV-2 entry into host cells, is profoundly expressed in testicular cells. In addition, the endogenous androgen milieu and its receptors are associated with ACE2 activation reflecting that enhanced testosterone levels may trigger the pathogenesis of COVID-19. In contrary, hypogonadism has also been reported in the acute phase of some COVID-19 cases. Moreover, SARS-CoV-2 infection-induced uncontrolled inflammatory responses may lead to systemic oxidative stress (OS), whose severe disruptive effects on testicular functions are well-documented. This article aims to precisely present the possible impact of COVID-19 on male reproductive functions, and to highlight the speculations that need in-depth research for the exact underlying mechanisms how COVID-19 is associated with men’s health and fertility.


Safety of Ibuprofen in Patients With COVID-19 Causal or Confounded?


title: The REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) Study. Rationale and Design

text: There is broad interest in improved methods to generate robust evidence regarding best practice, especially in settings where patient conditions are heterogenous and require multiple concomitant therapies. Here, we present the rationale and design of a large, international trial that combines features of adaptive platform trials with pragmatic point-of-care trials to determine best treatment strategies for patients admitted to an intensive care unit with severe community-acquired pneumonia. The trial uses a novel design, entitled “a randomized embedded multifactorial adaptive platform.” The design has five key features: 1) randomization, allowing robust causal inference; 2) embedding of study procedures into routine care processes, facilitating enrollment, trial efficiency, and generalizability; 3) a multifactorial statistical model comparing multiple interventions across multiple patient subgroups; 4) response-adaptive randomization with preferential assignment to those interventions that appear most favorable; and 5) a platform structured to permit continuous, potentially perpetual enrollment beyond the evaluation of the initial treatments. The trial randomizes patients to multiple interventions within four treatment domains: antibiotics, antiviral therapy for influenza, host immunomodulation with extended macrolide therapy, and alternative corticosteroid regimens, representing 240 treatment regimens. The trial generates estimates of superiority, inferiority, and equivalence between regimens on the primary outcome of 90-day mortality, stratified by presence or absence of concomitant shock and proven or suspected influenza infection. The trial will also compare ventilatory and oxygenation strategies, and has capacity to address additional questions rapidly during pandemic respiratory infections. As of January 2020, REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) was approved and enrolling patients in 52 intensive care units in 13 countries on 3 continents. In February, it transitioned into pandemic mode with several design adaptations for coronavirus disease 2019. Lessons learned from the design and conduct of this trial should aid in dissemination of similar platform initiatives in other disease areas. Clinical trial registered with www.clinicaltrials.gov (NCT02735707).


title: The final size of a SARS epidemic model without quarantine

text: Abstract In this article, we present the continuing work on a SARS model without quarantine by Hsu and Hsieh [Sze-Bi Hsu, Ying-Hen Hsieh, Modeling intervention measures and severity-dependent public response during severe acute respiratory syndrome outbreak, SIAM J. Appl. Math. 66 (2006) 627–647]. An “acting basic reproductive number” ψ is used to predict the final size of the susceptible population. We find the relation among the final susceptible population size S ∞ , the initial susceptible population S 0 , and ψ. If ψ > 1 , the disease will prevail and the final size of the susceptible, S ∞ , becomes zero; therefore, everyone in the population will be infected eventually. If ψ < 1 , the disease dies out, and then S ∞ > 0 which means part of the population will never be infected. Also, when S ∞ > 0 , S ∞ is increasing with respect to the initial susceptible population S 0 , and decreasing with respect to the acting basic reproductive number ψ.


title: The major histocompatibility complex in Old World camelids and low polymorphism of its class II genes

text: BACKGROUND: The Major Histocompatibility Complex (MHC) is a genomic region containing genes with crucial roles in immune responses. MHC class I and class II genes encode antigen-presenting molecules expressed on the cell surface. To counteract the high variability of pathogens, the MHC evolved into a region of considerable heterogeneity in its organization, number and extent of polymorphism. Studies of MHCs in different model species contribute to our understanding of mechanisms of immunity, diseases and their evolution. Camels are economically important domestic animals and interesting biomodels. Three species of Old World camels have been recognized: the dromedary (Camelus dromedarius), Bactrian camel (Camelus bactrianus) and the wild camel (Camelus ferus). Despite their importance, little is known about the MHC genomic region, its organization and diversity in camels. The objectives of this study were to identify, map and characterize the MHC region of Old World camelids, with special attention to genetic variation at selected class MHC II loci. RESULTS: Physical mapping located the MHC region to the chromosome 20 in Camelus dromedarius. Cytogenetic and comparative analyses of whole genome sequences showed that the order of the three major sub-regions is “Centromere - Class II – Class III – Class I”. DRA, DRB, DQA and DQB exon 2 sequences encoding the antigen binding site of the corresponding class II antigen presenting molecules showed high degree of sequence similarity and extensive allele sharing across the three species. Unexpectedly low extent of polymorphism with low numbers of alleles and haplotypes was observed in all species, despite different geographic origins of the camels analyzed. The DRA locus was found to be polymorphic, with three alleles shared by all three species. DRA and DQA sequences retrieved from ancient DNA samples of Camelus dromedarius suggested that additional polymorphism might exist. CONCLUSIONS: This study provided evidence that camels possess an MHC comparable to other mammalian species in terms of its genomic localization, organization and sequence similarity. We described ancient variation at the DRA locus, monomorphic in most species. The extent of molecular diversity of MHC class II genes seems to be substantially lower in Old World camels than in other mammalian species. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2500-1) contains supplementary material, which is available to authorized users.


title: L’analyse virologique des aspirations nasopharyngées reflète-t-elle l’infection respiratoire basse chez l’enfant ? Étude en PCR multiplex

text: Résumé Les infections respiratoires sont un problème de santé publique. Leur cause en est majoritairement virale chez le jeune enfant. La mise au point de techniques de détection par biologie moléculaire a permis d’en élargir le spectre virologique. L’objectif de notre travail est d’évaluer la corrélation entre les résultats des prélèvements effectués par aspiration rhinopharyngée et par lavage bronchoalvéolaire. Trente enfants présentant une symptomatologie d’infection respiratoire basse ont ainsi été prélevés aux deux sites au cours d’une même séance. Les échantillons ont été analysés par Polymerase chain reaction (PCR) virale multiplex (xTAG™RVP). Une corrélation forte est retrouvée entre la positivité de la PCR virale dans les voies respiratoires hautes et basses (p =0,0002). Le virus le plus fréquemment isolé est l’entéro-rhinovirus. Ces résultats confirment que l’infection virale touche l’appareil respiratoire de façon diffuse, et suggèrent que le prélèvement par aspiration rhinopharyngée suffit au diagnostic virologique d’une infection respiratoire virale basse chez l’enfant immunocompétent. Abstract Respiratory tract infections are frequent in young children and are related to viruses in most cases. Multiplex Polymerase chain reaction (PCR) based techniques are valuable tools for describing the spectrum of such viruses. The goal of this study was to assess the correlation of virus detection in samples obtained by nasopharyngeal aspiration and by bronchoalveolar lavage. Both samples were taken at the same time in 30 children with lower respiratory tract infection, and were analyzed by multiplex virus PCR (xTAG™RVP). A strong correlation has been found (P =0.0002) and the most frequently isolated virus was the entero-rhinovirus spp. These results strengthen the opinion that viruses colonize both the upper and lower respiratory tract. Nasopharyngeal samples should be sufficient to the diagnosis of lower respiratory tract viral infection in immuno-competent children.


Cytokine profiles of suction pulmonary secretions from children infected with pandemic influenza A(H1N1) 2009


title: Safety during crisis: Rapid on‐site evaluation at the time of COVID‐19 pandemic

text: The COVID‐19 pandemic is posing a worldwide challenge to control and contain. SARS‐CoV‐2 is a highly infectious virus. Health care providers at the front lines are at high risk of getting the infection and the risk applies also to laboratory personnel as they deal with specimens that might be contaminated with infectious materiel. Cytopathology teams specifically are at high risk of dealing with contaminated material because of patients encounter during fine‐needle aspiration biopsies or Rapid On‐Site Evaluation (ROSE) for adequacy. In our article, we discuss alternative safer staining methods to the widely used Diff–Quick stain that can be utilized for ROSE to decrease the risk of viral exposure during the current COVID‐19 pandemic.


title: Coronavirus disease 2019 in renal transplant recipients: report of two cases

text: Coronavirus disease 2019 (COVID‐19) has been a pandemic worldwide. The data about COVID‐19 in renal transplant recipient is deficiency. Herein we report two COVID‐19 cases in renal transplant recipients. Both cases were discharged following a treatment regimen including discontinued immunosuppressant and low‐dose methylprednisolone‐based therapy. There were no signs of rejection during the treatment. These successfully treated cases can provide helpful information about the management of COVID‐19 in renal transplant recipients.


title: Clinical implications of and lessons learnt from external assessment of Mers-CoV diagnostics

text: With the emergence of new viral infections, it is necessary to set up new target-specific assays, based on existing molecular techniques such as real-time PCR, as quickly as possible. Without these diagnostic tools, the geographical spread of new infections, follow-up of the disease outbreak and analysis of the pathogenesis of the disease are not possible. Therefore, the genomic information of the emerging pathogen, diagnostic protocols and standards allowing quality control need to be available in a few days. This can only be implemented with good quality experienced laboratories having suitable infrastructure to establish in-house assays. Even though these molecular tools are available quickly, challenges still remain with what sample types to select for a proper diagnostic value.


title: Environmental and Intrinsic Correlates of Stress in Free-Ranging Wolves

text: BACKGROUND: When confronted with a stressor, animals react with several physiological and behavioral responses. Although sustained or repeated stress can result in severe deleterious physiological effects, the causes of stress in free-ranging animals are yet poorly documented. In our study, we aimed at identifying the main factors affecting stress levels in free-ranging wolves (Canis lupus). METHODOLOGY/PRINCIPAL FINDINGS: We used fecal cortisol metabolites (FCM) as an index of stress, after validating the method for its application in wolves. We analyzed a total of 450 fecal samples from eleven wolf packs belonging to three protected populations, in Italy (Abruzzo), France (Mercantour), and the United States (Yellowstone). We collected samples during two consecutive winters in each study area. We found no relationship between FCM concentrations and age, sex or social status of individuals. At the group level, our results suggest that breeding pair permanency and the loss of pack members through processes different from dispersal may importantly impact stress levels in wolves. We measured higher FCM levels in comparatively small packs living in sympatry with a population of free-ranging dogs. Lastly, our results indicate that FCM concentrations are associated with endoparasitic infections of individuals. CONCLUSIONS/SIGNIFICANCE: In social mammals sharing strong bonds among group members, the death of one or several members of the group most likely induces important stress in the remainder of the social unit. The potential impact of social and territorial stability on stress levels should be further investigated in free-ranging populations, especially in highly social and in territorial species. As persistent or repeated stressors may facilitate or induce pathologies and physiological alterations that can affect survival and fitness, we advocate considering the potential impact of anthropogenic causes of stress in management and conservation programs regarding wolves and other wildlife.


title: A novel glycoprotein D-specific monoclonal antibody neutralizes herpes simplex virus

text: Abstract The worldwide prevalence of herpes simplex virus (HSV) and the shortage of efficient vaccines and novel therapeutic strategies against HSV are widely global concerns. The abundance on the virion and the major stimulus for the virus-neutralizing antibodies makes gD a predominant candidate for cure of HSV infection. In this study, we generated a monoclonal antibody (mAb), termed m27f, targeting to glycoprotein D (gD) of HSV-2, which also has cross-reactivity against HSV-1 gD. It has a high level of neutralizing activity against both HSV-1 and HSV-2, and binds to a highly conserved region (residues 292–297) within the pro-fusion domain of gD. It can effectively block HSV cell-to-cell spread in vitro. The pre- or post-attachment neutralization assay and syncytium formation inhibition assay revealed that m27f neutralizes HSV at the post-binding stage. Moreover, therapeutic administration of m27f completely prevented infection-related mortality of mice challenged with a lethal dose of HSV-2. Our newly identified epitope for the neutralizing antibody would facilitate studies of gD-based HSV entry or vaccine design, and m27f itself demonstrated a high potential for adaptation as a protective or therapeutic drug against HSV.


title: Syndactyly in a litter of cats

text: In this case report, we describe the clinical and radiographic features of a litter of kittens affected with complex syndactyly. We also provide guidelines for the diagnosis, possible treatment and prevention of propagation of this condition. This is the first report of syndactyly in a litter of kittens and syndactyly affecting both the pectoral and pelvic limbs.


A pandemic in prisons


docid: efraixvg

title: 978. Production of SARS Coronavirus-Like Particles That Bind Host Cells and Serve as Vaccine Antigen


title: Feline and canine coronaviruses are released from the basolateral side of polarized epithelial LLC-PK1 cells expressing the recombinant feline aminopeptidase-N cDNA

text: In this study feline (FECV and FIPV) and canine (CCoV) coronavirus entry into and release from polarized porcine epithelial LLC-PK1 cells, stably expressing the recombinant feline aminopeptidase-N cDNA, were investigated. Virus entry appeared to occur preferentially through the apical membrane, similar to the entry of the related porcine coronavirus transmissible gastroenteritis virus (TGEV) into these cells. However, whereas TGEV is released apically, feline and canine coronaviruses were found to be released from the basolateral side of the epithelial cells. These observations indicate that local infections as caused by TGEV, FECV and CCoV do not strictly correlate with apical release, as suggested by earlier work.


Hematopoietic stem cell transplantation from an infected SARS-CoV2 donor sibling


docid: wzxcrwea

title: Sequencing identifies multiple, early introductions of SARS-CoV2 to New York City Region

text: Effective public response to a pandemic relies upon accurate measurement of the extent and dynamics of an outbreak. Viral genome sequencing has emerged as a powerful approach to link seemingly unrelated cases, and large-scale sequencing surveillance can inform on critical epidemiological parameters. Here, we report the analysis of 236 SARS-CoV2 sequences from cases in the New York City metropolitan area during the initial stages of the 2020 COVID-19 outbreak. The majority of cases throughout the region had no recent travel history or known exposure, and genetically linked cases were spread throughout the region. Comparison to global viral sequences showed that the majority were most related to cases from Europe. Our data are consistent with numerous seed transmissions from multiple sources and a prolonged period of unrecognized community spreading. This work highlights the complementary role of real-time genomic surveillance in addition to traditional epidemiological indicators.


ICU beds: less is more? No


title: In-silico immune cell deconvolution of the airway proteomes of infants with pneumonia reveals a link between reduced airway eosinophils and an increased risk of mortality

text: Rationale Pneumonia is a leading cause of mortality in infants and young children. The immune responses in the airway that are associated with mortality are poorly understood. Studies of the cellular immunology of the infant airway have traditionally been hindered by the limited sample volumes available from the young, frail children who are admitted to hospital with pneumonia. This is further compounded by the relatively low frequencies of certain immune cell phenotypes that are thought to be critical to the clinical outcome of infection. To address this, we developed a novel in-silico deconvolution method for inferring the frequencies of immune cell phenotypes in the airway of children with different survival outcomes using proteomic data. Methods Using high-resolution mass spectrometry, we identified > 1,000 proteins expressed in the airways of children who were admitted to hospital with clinical pneumonia. 61 of these children were discharged from hospital and survived for more than 365 days after discharge, while 19 died during admission. We used unsupervised learning by random forest to derive protein classification markers that could be used to deconvolve individual immune cell phenotypes. We applied these phenotype-specific signatures to high-resolution mass spectrometry-based proteomic data obtained from airway samples collected at admission from infants and children who were discharged from hospital and survived for at least one year as well as those who died from pneumonia during the course of admission. Main Results We identified protein classification markers for 33 immune cell phenotypes. Eosinophil-associated protein markers were significantly elevated in airway secretions obtained from pneumonia survivors and were downregulated in children who subsequently died. To confirm these results, we analyzed clinical parameters from >10,000 children who had been admitted with pneumonia in the previous 10 years. The results of this retrospective analysis mirrored airway deconvolution data and showed that survivors had significantly elevated eosinophils at admission compared to fatal cases of pneumonia. Conclusions Airway eosinophils appear to be a critical immune cell phenotype for pneumonia survival in infants and young children.


title: SARS Transmission and Hospital Containment

text: An outbreak of severe acute respiratory syndrome (SARS) was detected in Singapore at the beginning of March 2003. The outbreak, initiated by a traveler to Hong Kong in late February 2003, led to sequential spread of SARS to three major acute care hospitals in Singapore. The critical factor in containing this outbreak was early detection and complete assessment of movements and follow-up of patients, healthcare workers, and visitors who were contacts. Visitor records were important in helping identify exposed persons who could carry the infection into the community. In the three hospital outbreaks, three different containment strategies were used to contain spread of infection: closing an entire hospital, removing all potentially infected persons to a dedicated SARS hospital, and managing exposed persons in place. On the basis of this experience, if a nosocomial outbreak is detected late, a hospital may need to be closed in order to contain spread of the disease. Outbreaks detected early can be managed by either removing all exposed persons to a designated location or isolating and managing them in place.


title: The psychological impact of the COVID-19 epidemic on college students in China

text: Abstract A COVID-19 epidemic has been spreading in China and other parts of the world since December 2019. The epidemic has brought not only the risk of death from infection but also unbearable psychological pressure. We sampled college students from Changzhi medical college by using cluster sampling. They responded to a questionnaire packet that included the 7-item Generalized Anxiety Disorder Scale (GAD-7) and those inquiring the participants’ basic information. We received 7,143 responses. Results indicated that 0.9% of the respondents were experiencing severe anxiety, 2.7% moderate anxiety, and 21.3% mild anxiety. Moreover, living in urban areas (OR = 0.810, 95% CI = 0.709 - 0.925), family income stability (OR = 0.726, 95% CI = 0.645 - 0.817) and living with parents (OR = 0.752, 95% CI = 0.596 - 0.950) were protective factors against anxiety. Moreover, having relatives or acquaintances infected with COVID-19 was a risk factor for increasing the anxiety of college students (OR = 3.007, 95% CI = 2.377 - 3.804). Results of correlation analysis indicated that economic effects, and effects on daily life, as well as delays in academic activities, were positively associated with anxiety symptoms (P < .001). However, social support was negatively correlated with the level of anxiety (P < .001). It is suggested that the mental health of college students should be monitored during epidemics.


title: Synthesis, biological evaluation and molecular modeling of novel azaspiro dihydrotriazines as influenza virus inhibitors targeting the host factor dihydrofolate reductase (DHFR)

text: Recently we identified cycloguanil-like dihydrotriazine derivatives, which provided host-factor directed antiviral activity against influenza viruses and respiratory syncytial virus (RSV), by targeting the human dihydrofolate reductase (hDHFR) enzyme. In this context we deemed interesting to further investigate the structure activity relationship (SAR) of our first series of cycloguanil-like dihydrotriazines, designing two novel azaspiro dihydrotriazine scaffolds. The present study allowed the exploration of the potential chemical space, around these new scaffolds, that are well tolerated for maintaining the antiviral effect by means of interaction with the hDHFR enzyme. The new derivatives confirmed their inhibitory profile against influenza viruses, especially type B. In particular, the two best compounds shared potent antiviral activity (4: EC(50) = 0.29 μM; 6: EC(50) = 0.19 μM), which was comparable to that of zanamivir (EC(50) = 0.14 μM), and better than that of ribavirin (EC(50) = 3.2 μM). In addition, these two compounds proved to be also effective against RSV (4: EC(50) = 0.40 μM, SI ≥ 250; 6: EC(50) = 1.8 μM, SI ≥ 56), surpassing the potency and selectivity index (SI) of ribavirin (EC(50) = 5.8 μM, SI > 43). By a perspective of these results, the above adequately substituted azaspiro dihydrotriazines may represent valuable hit compounds worthy of further structural optimization to develop improved host DHFR-directed antiviral agents.


title: Immune recovery following bronchiolitis is linked to a drop in cytokine and LTC4 levels

text: BACKGROUND: Bronchiolitis is the main cause of hospitalization of children younger than 1 year; however, the immune mechanism of bronchiolitis is not completely understood. The aim of this study was to analyze the recovery of immune response after a bronchiolitis episode. METHODS: Forty-nine infants hospitalized with bronchiolitis diagnosis were enrolled. Nasopharyngeal aspirates (NPAs) were processed. Twenty-seven pro-inflammatory biomarkers linked to innate immunity, inflammation, and epithelial damage, as well as nitrites and lipid mediators, were evaluated in the NPA supernatant by ELISA (enzyme-linked immunosorbent assay) and Luminex. Also, 11 genes were analyzed in NPA cells by quantitative PCR. RESULTS: A widespread statistically significant decline of multiple pro-inflammatory parameters and cytokines were detected in the recovery period after respiratory infection: interferon-α2 (IFNα2), IFNγ, interleukin-10 (IL-10), IL-1β, IL-8, IFN-γ-inducible protein-10, vascular endothelial growth factor, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α (MIP-1α), and MIP-1β. Supporting these results, a decreased nuclear factor-κB gene expression was observed (P = 0.0116). A significant diminution of cysteinyl leukotriene C4 (LTC4) soluble levels (P = 0.0319) and cyclooxygenase-2 (COX-2) gene expression were observed in the recovery sample. In children classified by post-bronchiolitis wheezing, LTC4 remains elevated in the NPA supernatant. CONCLUSIONS: After bronchiolitis, cytokines and biomarkers linked to innate immune response in NPA decrease significantly in the recovery period accompanied by a drop in LTC4 levels; however, this reduction was lower in infants with post-bronchiolitis wheezing.


title: Bat Flight and Zoonotic Viruses

text: Bats are sources of high viral diversity and high-profile zoonotic viruses worldwide. Although apparently not pathogenic in their reservoir hosts, some viruses from bats severely affect other mammals, including humans. Examples include severe acute respiratory syndrome coronaviruses, Ebola and Marburg viruses, and Nipah and Hendra viruses. Factors underlying high viral diversity in bats are the subject of speculation. We hypothesize that flight, a factor common to all bats but to no other mammals, provides an intensive selective force for coexistence with viral parasites through a daily cycle that elevates metabolism and body temperature analogous to the febrile response in other mammals. On an evolutionary scale, this host–virus interaction might have resulted in the large diversity of zoonotic viruses in bats, possibly through bat viruses adapting to be more tolerant of the fever response and less virulent to their natural hosts.


title: Association between viral seasonality and meteorological factors

text: Numerous viruses can cause upper respiratory tract infections. They often precede serious lower respiratory tract infections. Each virus has a seasonal pattern, with peaks in activity in different seasons. We examined the effects of daily local meteorological data (temperature, relative humidity, “humidity-range” and dew point) from Edinburgh, Scotland on the seasonal variations in viral transmission. We identified the seasonality of rhinovirus, adenovirus, influenza A and B viruses, human parainfluenza viruses 1–3 (HPIV), respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) from the 52060 respiratory samples tested between 2009 and 2015 and then confirmed the same by a generalised linear model. We also investigated the relationship between meteorological factors and viral seasonality. Non-enveloped viruses were present throughout the year. Following logistic regression adenovirus, influenza viruses A, B, RSV and HMPV preferred low temperatures; RSV and influenza A virus preferred a narrow “humidity-range” and HPIV type 3 preferred the season with lower humidity. A change (i.e. increase or decrease) in specific meteorological factors is associated with an increase in activity of specific viruses at certain times of the year.


title: Oncofertility and COVID-19—cancer does not wait

text: The current pandemic due to the coronavirus disease 2019 (COVID-19) outbreak has forced physicians to review their current clinical practice and guidelines. Although elective procedures using assisted reproductive technologies (ART) should be preferably canceled or postponed at this time, this does not always apply to urgent procedures such as those in patients with cancer. A complete oncofertility counseling balancing the benefits and risks of undergoing fertility preservation before commencing gonadotoxic therapies (chemotherapy and/or radiotherapy) should also be provided during the COVID-19 outbreak. This article briefly highlights what patients, oncologists and fertility specialists need to keep in mind during oncofertility counseling at the time of the COVID-19 outbreak.


title: Epidemiological characteristics and phylogenic analysis of human respiratory syncytial virus in patients with respiratory infections during 2011–2016 in southern China

text: Abstract Background Human respiratory syncytial virus (RSV) is one of the most important pathogens that cause acute respiratory infections in children and immunocompromised adults. This work was conducted to understand the epidemiological and phylogenetic features of RSV in southern China during 2011–2016. Methods A total of 16 024 nasopharyngeal swabs were collected from patients with respiratory infections in 14 hospitals, and screened for RSV and seven other respiratory viruses using real-time PCR. Six hundred and twenty-three RSV-positive samples from 13 hospitals were further analyzed for subtypes. G gene sequencing and phylogenetic analysis were performed based on 46 RSV-A and 15 RSV-B strains. Results RSV was detected in 9.5% of the 16 024 specimens, the highest among the eight respiratory viruses screened. Most of these specimens came from inpatients and children under 3 years of age. The incidence of RSV-A (9.4%) was higher than that of RSV-B (4.4%) in children (<15 years), but not in adults (0.64% vs. 0.58%). A 2-year RSV-A dominance followed by a 1-year RSV-B dominance pattern was found. The co-detection rate of RSV was 25.1%. The main prevalent genotypes were NA1, ON1, and BA9. The prevalent RSV-A genotype in 2011–2012 was NA1, close to Chongqing and Brazil, but a new Hong Kong ON1 genotype was introduced and became the prevalent genotype in Guangzhou in 2014–2015. Deduced amino acid sequence analysis confirmed the ongoing evolution and a high selection pressure of RSV-A and B strains, especially in RSV-A ON1 and NA1 genotypes. Conclusions This study demonstrated the molecular epidemiological characteristics of RSV in patients with respiratory infections in southern China.


title: Overlapping CD8+ and CD4+ T-cell epitopes identification for the progression of epitope-based peptide vaccine from nucleocapsid and glycoprotein of emerging Rift Valley fever virus using immunoinformatics approach

text: Abstract Rift Valley fever virus (RVFV) is an emergent arthropod-borne zoonotic infectious viral pathogen which causes fatal diseases in the humans and ruminants. Currently, no effective and licensed vaccine is available for the prevention of RVFV infection in endemic as well as in non-endemic regions. So, an immunoinformatics-driven genome-wide screening approach was performed for the identification of overlapping CD8+ and CD4+ T-cell epitopes and also linear B-cell epitopes from the conserved sequences of the nucleocapsid (N) and glycoprotein (G) of RVFV. We identified overlapping 99.39% conserved 1 CD8+ T-cell epitope (MMHPSFAGM) from N protein and 100% conserved 7 epitopes (AVFALAPVV, LAVFALAPV, FALAPVVFA, VFALAPVVF, IAMTVLPAL, FFDWFSGLM, and FLLIYLGRT) from G protein and also identified IL-4 and IFN-γ induced (99.39% conserved) 1 N protein CD4+ T-cell epitope (HMMHPSFAGMVDPSL) and 100% conserved 5 G protein CD4+ T-cell epitopes (LPALAVFALAPVVFA, PALAVFALAPVVFAE, GIAMTVLPALAVFAL, GSWNFFDWFSGLMSW, and FFLLIYLGRTGLSKM). The overlapping CD8+ and CD4+ T-cell epitopes were bound with most conserved HLA-C*12:03 and HLA-DRB1*01:01, respectively with the high binding affinity (kcal/mol). The combined population coverage analysis revealed that the allele frequencies of these epitopes are high in endemic and non-endemic regions. Besides, we found 100% conserved and non-allergenic 2 decamer B-cell epitopes, GVCEVGVQAL and RVFNCIDWVH of G protein had the sequence similarity with the nonamer CD8+ T-cell epitopes, VCEVGVQAL and RVFNCIDWV, respectively. Consequently, these epitopes may be used for the development of epitope-based peptide vaccine against emerging RVFV. However, in vivo and in vitro experiments are required for their efficient use as a vaccine.


title: The viral RNA capping machinery as a target for antiviral drugs

text: Abstract Most viruses modify their genomic and mRNA 5′-ends with the addition of an RNA cap, allowing efficient mRNA translation, limiting degradation by cellular 5′–3′ exonucleases, and avoiding its recognition as foreign RNA by the host cell. Viral RNA caps can be synthesized or acquired through the use of a capping machinery which exhibits a significant diversity in organization, structure and mechanism relative to that of their cellular host. Therefore, viral RNA capping has emerged as an interesting field for antiviral drug design. Here, we review the different pathways and mechanisms used to produce viral mRNA 5′-caps, and present current structures, mechanisms, and inhibitors known to act on viral RNA capping.


title: Donut-shaped fingerprint in homologous polypeptide relationships—A topological feature related to pathogenic structural changes in conformational disease

text: Abstract Features of homologous relationship of proteins can provide us a general picture of protein universe, assist protein design and analysis, and further our comprehension of the evolution of organisms. Here we carried out a study of the evolution of protein molecules by investigating homologous relationships among residue segments. The motive was to identify detailed topological features of homologous relationships for short residue segments in the whole protein universe. Based on the data of a large number of non-redundant proteins, the universe of non-membrane polypeptide was analyzed by considering both residue mutations and structural conservation. By connecting homologous segments with edges, we obtained a homologous relationship network of the whole universe of short residue segments, which we named the graph of polypeptide relationships (GPR). Since the network is extremely complicated for topological transitions, to obtain an in-depth understanding, only subgraphs composed of vital nodes of the GPR were analyzed. Such analysis of vital subgraphs of the GPR revealed a donut-shaped fingerprint. Utilization of this topological feature revealed the switch sites (where the beginning of exposure of previously hidden “hot spots” of fibril-forming happens, in consequence a further opportunity for protein aggregation is provided; 188–202) of the conformational conversion of the normal α -helix-rich prion protein PrP C to the β -sheet-rich PrP Sc that is thought to be responsible for a group of fatal neurodegenerative diseases, transmissible spongiform encephalopathies. Efforts in analyzing other proteins related to various conformational diseases are also introduced.


title: Glial Cell Lines: An Overview

text: The importance and essential functions of glial cells in the nervous system are now beginning to be understood and appreciated. Glial cell lines have been instrumental in the elucidation of many of these properties. In this Overview, the origin and properties of most of the existing cell lines for the major glial types: oligodendroglia, astroglia, microglia and Schwann cells, are documented. Particular emphasis is given to the culture conditions for each cell line and the degree to which the line can differentiate in vitro and in vivo. The major molecular markers for each glial cell lines are indicated. Finally, methods by which the glial cell lines have been developed are noted and the future directions of glial cell line research are discussed.


title: Computer-Based Blood Donor Screening: A Status Report

text: There is a substantial literature suggesting that computer-assisted interviewing has advantages over face-to-face and written self-administration of interviews in venues eliciting sensitive information similar to that sought in blood donor history screening. We review some of the recent developments in blood donor history screening, the evidence suggesting that automated interviews should be useful, and the experience to date using computer interviews for blood donation. These data suggest that automated computer-assisted interviewing increases the elicitation of behaviors associated with the risk of transfusion-transmissible infection in donors, improves donor and staff satisfaction, and reduces errors and omissions that frequently accompany traditional interviewing methods. Food and Drug Administration–cleared systems for computer-assisted self-interview of blood donors are briefly described.


title: How the SARS vaccine effort can learn from HIV—speeding towards the future, learning from the past

text: A remarkable collaborative effort coordinated by the severe acute respiratory syndrome (SARS) team at WHO resulted in discovery of the etiologic agent of severe acute respiratory syndrome less than 2 months after the announcement of global alert. The development of a vaccine to prevent SARS should be pursued with the same urgency and cooperative spirit, as SARS is highly lethal and, if not controlled during the first few generations of transmission, is likely to become endemic in regions of the world where health-care infrastructure is underdeveloped and epidemiological control measures are weak. The scientific community already learned many important lessons from HIV vaccine development; these should be heeded. For example, consideration should be given to the development of a vaccine that will protect across regional strains of SARS, as the newly emergent coronavirus SARS-coronavirus (SARS-CoV) is proving to be variable and may be mutating in response to immune pressure. SARS-specific research reagents should also be collected and shared. These would include SARS peptides, adjuvants, DNA vaccine vectors and clinical grade viral vectors. Rapidly developing a collaborative approach to developing a SARS vaccine that will be both effective and safe is the only way to go. This article reviews parallels between HIV and SARS and proposes an approach that would accelerate the development of a SARS vaccine.


title: Risques connus et impact de mesures prises sur ces risques en transfusion sanguine

text: Résumé Sur la base évidente, d’une part, de l’existence de risques (de différentes natures) en transfusion sanguine et, d’autre part, de l’attente d’une transfusion sans « vice » ni risque, trois niveaux de sécurisation ont pu être proposés ces dernières années : une politique d’analyse de risques généralisée ; des procédures de maîtrise des risques ; une politique généralisée de qualité. Ces constructions sécuritaires ont néanmoins des impacts multidirectionnels, sur les organisations, les coûts et l’économie en général, la disponibilité des produits, et – in fine – possiblement sur l’éthique. Ce sont ces points qui sont analysés dans le présent essai, ainsi que la place éventuelle dans ces dispositifs des procédés d’inactivation/réduction de pathogènes. Abstract Transfusion is indeed associated with risks that are diverse in nature. Besides, the society expects a risk- and vice-exempt transfusion. During the recent past years, there have been three levels of safety implementation in transfusion: a generalized risk assessment policy; a mastering of processes; standard quality engineering. However, these safety measures have impacts in several ways, such as management and organization, inventory, economics and possibly ethics. All these issues are addressed in the present essay as well as the possible effect of pathogen reduction procedures.


title: Effect of social distancing on COVID-19 incidence and mortality in the US

text: Social distancing policies were implemented in most US states as a containment strategy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The effectiveness of these policy interventions on morbidity and mortality remains unknown. Our analysis examined the associations between statewide policies and objective measures of social distancing, and objective social distancing and COVID-19 incidence and mortality. We used nationwide, de-identified smartphone GPS data to estimate county-level social distancing. COVID-19 incidence and mortality data were from the Johns Hopkins Coronavirus Resource Center. Generalized linear mixed models were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the association between objective social distancing and COVID-19 incidence and mortality. Stay-at-home orders were associated with a 35% increase in social distancing. Higher social distancing was associated with a 29% reduction in COVID-19 incidence (adjusted IRR 0.71; 95% CI 0.57–0.87) and a 35% reduction in COVID-19 mortality (adjusted IRR 0.65; 95% CI 0.55–0.76). These findings provide evidence to inform ongoing national discussions on the effectiveness of these public health measures and the potential implications of returning to normal social activity.


title: Immune-Mediated Damage Completes the Parabola: Cryptococcus neoformans Pathogenesis Can Reflect the Outcome of a Weak or Strong Immune Response

text: Cryptococcosis occurs most frequently in immunocompromised individuals. This has led to the prevailing view that this disease is the result of weak immune responses that cannot control the fungus. However, increasingly, clinical and experimental studies have revealed that the host immune response can contribute to cryptococcal pathogenesis, including the recent study of L. M. Neal et al. (mBio 8:e01415-17, 2017, https://doi.org/10.1128/mBio.01415-17) that reports that CD4(+) T cells mediate tissue damage in experimental murine cryptococcosis. This finding has fundamental implications for our understanding of the pathogenesis of cryptococcal disease; it helps explain why immunotherapy has been largely unsuccessful in treatment and provides insight into the paradoxical observation that HIV-associated cryptococcosis may have a better prognosis than cryptococcosis in those with no known immune impairment. The demonstration that host-mediated damage can drive cryptococcal disease provides proof of concept that the parabola put forth in the damage-response framework has the flexibility to depict complex and changing outcomes of host-microbe interaction.


title: A Systematic Review of CT Chest in COVID‐19 Diagnosis and its Potential Application in a Surgical Setting

text: AIM: To investigate the sensitivity and utility of computed tomography (CT) of the chest in diagnosing active Coronavirus 2019 (COVID‐19) infection, and its potential application to the surgical setting. METHODS: A literature review was conducted using Google Scholar® and MEDLINE®/PubMed® to identify current available evidence regarding the sensitivity of CT chest in comparison to RT‐PCR for diagnosis of COVID‐19 positive patients. GRADE criteria and the QUADAS 2 tool was used to assess the level of evidence. RESULTS: A total of 20 articles were identified that addressed the question of sensitivity of CT for diagnosis of COVID‐19 positive symptomatic and asymptomatic patients. Overall sensitivity of CT scan ranged from 57%‐100% for symptomatic and 46%‐100% for asymptomatic COVID‐19 patients, while that of RT‐PCR ranged from 39%‐89%. CT chest was a better diagnostic modality and capable of detecting active infection earlier in the time course of infection than RT‐PCR in symptomatic patients. In asymptomatic patients, disease prevalence seems to play a role in the positive predictive value. Minimal evidence exists regarding the sensitivity of CT in patients who are asymptomatic. CONCLUSIONS: In surgical patients, CT Chest should be considered as an important adjunct for detection of COVID‐19 infection in patients who are symptomatic with negative RT‐PCR prior to any operation. For surgical patients who are asymptomatic, there is insufficient evidence to recommend routine preoperative CT Chest for COVID‐19 screening.


Response to Martin-Moreno et al. (2014) Surgical mask or no mask for health workers not a defensible position for Ebola


title: Self-Replicating RNA

text: Self-replicating RNA derived from the genomes of positive strand RNA viruses represents a powerful tool for both molecular studies on virus biology and approaches to novel safe and effective vaccines. The following chapter summarizes the principles how such RNAs can be established and used for design of vaccines. Due to the large variety of strategies needed to circumvent specific pitfalls in the design of such constructs the technical details of the experiments are not described here but can be found in the cited literature.


title: Human respiratory syncytial virus (hRSV) RNA quantification in nasopharyngeal secretions identifies the hRSV etiologic role in acute respiratory tract infections of hospitalized infants

text: Abstract Background Human respiratory syncytial virus (hRSV) detection in nasopharyngeal aspirates (NPAs) from infants with acute respiratory tract infection (ARTI) does not prove the hRSV etiology of the current ARTI episode. HRSV RNA quantification may help in affording this issue. Objectives hRSV was detected by quantitative reverse transcription-PCR in NPAs taken upon admission to hospital and, whenever possible, at discharge and subsequent medical visits. Study design Prospective study, including 63 infants affected by either hRSV upper or lower ARTI. Results Based on the kinetics of viral load, hRSV etiology was identified in 25 infants in whom hRSV load dropped from 2.5×106 upon admission (presence of respiratory symptoms) to 7.5×102 RNAcopies/ml NPA upon discharge (absence of symptoms) after a median time of 5 days, and in 19 infants, in whom hRSV load was determined at admission only, in association with clinical symptoms (2.4×106 copies/ml). Furthermore, low levels of hRSV RNA (<1×105 copies/ml NPA) identified 14 patients with non-hRSV ARTI. Finally, in 14 infants with hRSV coinfections or sequential infections, hRSV quantification defined the hRSV role in the current ARTI episode. Conclusions hRSV RNA quantification is critical in defining the hRSV role in respiratory infections.


title: Activation of influenza viruses by proteases from host cells and bacteria in the human airway epithelium

text: Influenza is an acute infection of the respiratory tract, which affects each year millions of people. Influenza virus infection is initiated by the surface glycoprotein hemagglutinin (HA) through receptor binding and fusion of viral and endosomal membranes. HA is synthesized as a precursor protein and requires cleavage by host cell proteases to gain its fusion capacity. Although cleavage of HA is crucial for virus infectivity, little was known about relevant proteases in the human airways for a long time. Recent progress in the identification and characterization of HA-activating host cell proteases has been considerable however and supports the idea of targeting HA cleavage as a novel approach for influenza treatment. Interestingly, certain bacteria have been demonstrated to support HA activation either by secreting proteases that cleave HA or due to activation of cellular proteases and thereby may contribute to virus spread and enhanced pathogenicity. In this review, we give an overview on activation of influenza viruses by proteases from host cells and bacteria with the main focus on recent progress on HA cleavage by proteases HAT and TMPRSS2 in the human airway epithelium. In addition, we outline investigations of HA-activating proteases as potential drug targets for influenza treatment.


El coronavirus causante del síndrome respiratorio de Oriente Medio


title: Equine arteritis virus is delivered to an acidic compartment of host cells via clathrin-dependent endocytosis

text: Abstract Equine arteritis virus (EAV) is an enveloped, positive-stranded RNA virus belonging to the family Arteriviridae. Infection by EAV requires the release of the viral genome by fusion with the respective target membrane of the host cell. We have investigated the entry pathway of EAV into Baby Hamster Kindey cells (BHK). Infection of cells assessed by the plaque reduction assay was strongly inhibited by substances which interfere with clathrin-dependent endocytosis and by lysosomotropic compounds. Furthermore, infection of BHK cells was suppressed when clathrin-dependent endocytosis was inhibited by expression of antisense RNA of the clathrin-heavy chain before infection. These results strongly suggest that EAV is taken up via clathrin-dependent endocytosis and is delivered to acidic endosomal compartments.


docid: vncjvjoa

title: A Surveillance System to Reduce Transmission of Pandemic H1N1 (2009) Influenza in a 2600-Bed Medical Center

text: BACKGROUND: Concerns have been raised about how the transmission of emerging infectious diseases from patients to healthcare workers (HCWs) and vice versa could be recognized and prevented in a timely manner. An effective strategy to block transmission of pandemic H1N1 (2009) influenza in HCWs is important. METHODOLOGY/PRINCIPAL FINDINGS: An infection control program was implemented to survey and prevent nosocomial outbreaks of H1N1 (2009) influenza at a 2,600-bed, tertiary-care academic hospital. In total, 4,963 employees at Kaohsiung Chang Gung Memorial Hospital recorded their temperature and received online education on control practices for influenza infections. Administration records provided vaccination records and occupational characteristics of all HCWs. Early recognition of a pandemic H1N1 (2009) influenza case was followed by a semi-structured questionnaire to analyze possible routes of patient contact, household contact, or unspecified contact. Surveillance spanned August 1, 2009 to January 31, 2010; 51 HCWs were confirmed to have novel H1N1 (2009) influenza by quantitative real-time reverse transcription polymerase chain reaction. Prevalence of patient contact, household contact, or unspecified contact infection was 13.7% (7/51), 13.7% (7/51), and 72.5% (37/51), respectively. The prevalence of the novel H1N1 infection was significantly lower among vaccinated HCWs than among unvaccinated HCWs (p<0.001). Higher viral loads in throat swabs were found in HCWs with patient and household contact infection than in those with unspecified contact infection (4.15 vs. 3.53 copies/mL, log(10), p = 0.035). CONCLUSION: A surveillance system with daily temperature recordings and online education for HCWs is important for a low attack rate of H1N1 (2009) influenza transmission before H1N1 (2009) influenza vaccination is available, and the attack rate is further decreased after mass vaccination. Unspecified contact infection rates were significantly higher than that of patient contact and household contact infection, highlighting the need for public education of influenza transmission in addition to hospital infection control.


title: Urban Governance for a Sustainable Future

text: Cities have the potential to lead the way to a cleaner, greener, more inclusive future, but this cannot be achieved without effective leadership and governance. Here, we ask experts to reflect upon the governance challenges on the way to a sustainable urban world.


title: Strengthening the Detection of and Early Response to Public Health Emergencies: Lessons from the West African Ebola Epidemic

text: Mark Siedner and colleagues reflect on the early response to the Ebola epidemic and lessons that can be learned for future epidemics.


title: The global burden of premature mortality due to the Middle East respiratory syndrome (MERS) using standard expected years of life lost, 2012 to 2019

text: BACKGROUND: It has been 8 years since the first case of Middle East respiratory syndrome coronavirus (MERS-CoV) was reported in Saudi Arabia and the disease is still being reported in 27 countries; however, there is no international study to estimate the overall burden related of this emerging infectious disease. The present study was conducted to assess the burden of premature mortality due to Middle East respiratory syndrome (MERS) worldwide. METHODS: In this retrospective analysis, we have utilized publicly available data from the WHO website related to 1789 MERS patients reported between September 23, 2012 and May 17, 2019. To calculate the standard expected years of life lost (SEYLL), life expectancy at birth was set according to the 2000 global burden of disease study on levels 25 and 26 of West model life tables from Coale-Demeny at 82.5 and 80 years for females and males, respectively. RESULTS: Overall, the total SEYLL in males and females was 10,702 and 3817.5 years, respectively. The MERS patients within the age range of 30–59 year-olds had the highest SEYLL (8305.5 years) in comparison to the patients within the age groups 0–29 (SEYLL = 3744.5 years) and ≥ 60 years (SEYLL = 2466.5 years). The total SEYLL in all age groups in 2012, 2013, 2014, 2015, 2016, 2017, 2018, and 2019 were 71.5, 2006.5, 3162, 4425.5, 1809.5, 878, 1257.5 and 909 years, respectively. The most SEYLL related to MERS-CoV infection was in the early four years of the onset of the pandemic (2012 to 2015) and in the last four years of the MERS-CoV pandemic (216 to 2019), a significant reduction was observed in the SEYLL related to MERS-CoV infection in the MERS patients. CONCLUSION: We believe that the findings of this study will shed light about the burden of premature mortality due to MERS infection in the world and the results may provide necessary information for policy-makers to prevent, control, and make a quick response to the outbreak of MERS-CoV disease.


title: Improving vaccine-induced immunity: Can Baseline Predict Outcome?

text: Abstract Immune signatures measured at baseline and immediately prior to vaccination, may predict the immune response to vaccination. Such pre-vaccine assessment might allow not only population-based, but also more personalized vaccination strategies (‘precision vaccination’). If baseline immune signatures are predictive, the underlying mechanism they reflect may also determine vaccination outcome. Thus, baseline signatures might contribute to identifying interventional targets to be modulated prior to vaccination in order to improve vaccination responses. This concept has the potential to transform vaccination strategies and usher in a new approach to improve global health.


title: Molecular epidemiology of canine parvovirus type 2 in Vietnam from November 2016 to February 2018

text: BACKGROUND: Canine parvovirus type 2 (CPV-2) was first identified in the late 1970s; it causes intestinal hemorrhage with severe bloody diarrhea in kennels and dog shelters worldwide. Since its emergence, CPV-2 has been replaced with new genetic variants (CPV-2a, CPV-2b, and CPV-2c). Currently, information about the genotype prevalence of CPV-2 in Vietnam is limited. In the present study, we investigated the genotype prevalence and distribution of CPV-2 in the three regions of Vietnam. METHODS: Rectal swabs were collected from 260 dogs with suspected CPV-2 infection from northern, central, and southern Vietnam from November 2016 to February 2018. All samples were identified as parvovirus positive by real-time PCR, and further genotyping was performed using a SimpleProbe® real-time PCR assay. RESULTS: Of the 260 Vietnamese CPV-2 isolates, 6 isolates (2.31%) were identified as CPV-2a, 251 isolates (96.54%) were identified as CPV-2c and 3 isolates (1.15%) were untypable using the SimpleProbe® real-time PCR assay. In northern Vietnam, the percentages of CPV-2a and CPV-2c were 2.97% (3/101) and 97.3% (98/101), respectively. In central Vietnam, the percentages of CPV-2a and CPV-2c were 1.11% (1/90) and 98.89% (89/90), respectively. In southern Vietnam, the percentages of CPV-2a and CPV-2c were 3.03% (2/66) and 96.97% (64/66), respectively. CPV-2b was not observed in this study. The VP2 genes of CPV-2c in Vietnam are more genetically similar to those of CPV-2c strains in China and Taiwan than to those of prototype CPV-2c strains (FJ222821) or the first Vietnamese CPV-2c (AB120727). CONCLUSION: The present study provides evidence that CPV-2c is the most prevalent variant in Vietnam. Phylogenetic analysis demonstrated that the recent Vietnamese CPV-2c isolates share a common evolutionary origin with Asian CPV-2c strains. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-019-1159-z) contains supplementary material, which is available to authorized users.


title: Why Do We Feel Sick When Infected—Can Altruism Play a Role?

text: When we contract an infection, we typically feel sick and behave accordingly. Symptoms of sickness behavior (SB) include anorexia, hypersomnia, depression, and reduced social interactions. SB affects species spanning from arthropods to vertebrates, is triggered nonspecifically by viruses, bacteria, and parasites, and is orchestrated by a complex network of cytokines and neuroendocrine pathways; clearly, it has been naturally selected. Nonetheless, SB seems evolutionarily costly: it promotes starvation and predation and reduces reproductive opportunities. How could SB persist? Former explanations focused on individual fitness, invoking improved resistance to pathogens. Could prevention of disease transmission, propagating in populations through kin selection, also contribute to SB?


docid: hsowmxan

title: Influence of the containment on the epidemiology of maxillo-facial emergencies during the covid-19 pandemic. Why no more cellulites of odontogenic origin?


title: Better To Be Safe than “Sarry”: Preparing for Severe Acute Respiratory Syndrome

text: Abstract ISSUE: The emergence of Severe Acute Respiratory Syndrome (SARS) in 2003 challenged the world of infection control. During the SARS epidemic, Toronto was included as a travel location in the SARS definition. The lack of preparedness at our facility became evident in June 2003, when a patient was admitted with a fever, infiltrates, and recent travel to Toronto. This admission revealed many failure modes in our system for identifying and containing SARS. Twenty-one healthcare workers (HCWs) had unprotected exposure to the suspected case. As a result, the HCWs were screened prior to reporting to work for the 10 days following their exposure. Improper handling of lab specimens delayed testing. The case eventually was ruled out as a SARS case. PROJECT: A multidisciplinary team was formed to conduct a root-cause analysis (RCA) of the potential SARS exposure. Several process failures were identified, from admission through specimen handling. The team recognized that the frequency of admitting a SARS patient was low; however, the potential health threat was high. Rather than conduct additional educational sessions, a SARS Toolkit was developed for the hospital units. The kit contained step-by-step instructions, visuals, and a notification list. The kit's built-in forcing functions were designed to move the process along, but not to rely on HCWs memory. The new process was tested in a mock SARS admission drill. Only administration and the RCA team knew about the drill. The drill was completed in 3 hours. RESULTS: The kit was activated immediately and key departments, including infection control, were notified. Personal protective equipment was obtained and the patient was placed in the proper isolation. Laboratory specimens were processed and handled appropriately. HCW exposure did not occur. The kit assisted in preventing exposures while allowing for patient care. A debriefing followed the drill and included all HCWs involved, administration, and the RCA team. The mock patient was able to provide additional information regarding objects with potential fomite contamination that were brought out of the room. LESSONS LEARNED: Preparedness for events that may or may not occur challenged us to create a process that would succeed. Overall, the kit proved its worth with well-defined instructions for communication. At any time, it could easily be updated. It was identified that some signage needed clarification, and changes were made to the kit. The kit has since been adopted by our system hospitals.


title: A reverse genetics system for avian coronavirus infectious bronchitis virus based on targeted RNA recombination

text: BACKGROUND: Avian coronavirus infectious bronchitis virus (IBV) is a respiratory pathogen of chickens that causes severe economic losses in the poultry industry worldwide. Major advances in the study of the molecular biology of IBV have resulted from the development of reverse genetics systems for the highly attenuated, cell culture-adapted, IBV strain Beaudette. However, most IBV strains, amongst them virulent field isolates, can only be propagated in embryonated chicken eggs, and not in continuous cell lines. METHODS: We established a reverse genetics system for the IBV strain H52, based on targeted RNA recombination in a two-step process. First, a genomic and a chimeric synthetic, modified IBV RNA were co-transfected into non-susceptible cells to generate a recombinant chimeric murinized (m) IBV intermediate (mIBV). Herein, the genomic part coding for the spike glycoprotein ectodomain was replaced by that of the coronavirus mouse hepatitis virus (MHV), allowing for the selection and propagation of recombinant mIBV in murine cells. In the second step, mIBV was used as the recipient. To this end a recombination with synthetic RNA comprising the 3′-end of the IBV genome was performed by introducing the complete IBV spike gene, allowing for the rescue and selection of candidate recombinants in embryonated chicken eggs. RESULTS: Targeted RNA recombination allowed for the modification of the 3′-end of the IBV genome, encoding all structural and accessory genes. A wild-type recombinant IBV was constructed, containing several synonymous marker mutations. The in ovo growth kinetics and in vivo characteristics of the recombinant virus were similar to those of the parental IBV strain H52. CONCLUSIONS: Targeted RNA recombination allows for the generation of recombinant IBV strains that are not able to infect and propagate in continuous cell lines. The ability to introduce specific mutations holds promise for the development of rationally designed live-attenuated IBV vaccines and for studies into the biology of IBV in general. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-017-0775-8) contains supplementary material, which is available to authorized users.


title: Highlighting Clinical Metagenomics for Enhanced Diagnostic Decision-making: A Step Towards Wider Implementation

text: Clinical metagenomics (CMg) is the discipline that refers to the sequencing of all nucleic acid material present within a clinical specimen with the intent to recover clinically relevant microbial information. From a diagnostic perspective, next-generation sequencing (NGS) offers the ability to rapidly identify putative pathogens and predict their antimicrobial resistance profiles to optimize targeted treatment regimens. Since the introduction of metagenomics nearly a decade ago, numerous reports have described successful applications in an increasing variety of biological specimens, such as respiratory secretions, cerebrospinal fluid, stool, blood and tissue. Considerable advancements in sequencing and computational technologies in recent years have made CMg a promising tool in clinical microbiology laboratories. Moreover, costs per sample and turnaround time from specimen receipt to clinical management continue to decrease, making the prospect of CMg more feasible. Many difficulties, however, are associated with CMg and warrant further improvements such as the informatics infrastructure and analytical pipelines. Thus, the current review focuses on comprehensively assessing applications of CMg for diagnostic and subtyping purposes.


title: The Antiviral and Antitumor Effects of Defective Interfering Particles/Genomes and Their Mechanisms

text: Defective interfering particles (DIPs), derived naturally from viral particles, are not able to replicate on their own. Several studies indicate that DIPs exert antiviral effects via multiple mechanisms. DIPs are able to activate immune responses and suppress virus replication cycles, such as competing for viral replication products, impeding the packaging, release and invasion of viruses. Other studies show that DIPs can be used as a vaccine against viral infection. Moreover, DIPs/DI genomes display antitumor effects by inducing tumor cell apoptosis and promoting dendritic cell maturation. With genetic modified techniques, it is possible to improve its safety against both viruses and tumors. In this review, a comprehensive discussion on the effects exerted by DIPs is provided. We further highlight the clinical significance of DIPs and propose that DIPs can open up a new platform for antiviral and antitumor therapies.


title: Spinal anesthesia after intraoperative cardiac arrest during general anesthesia in an infant

text: Although generally safe and effective, severe perioperative complications, including cardiac arrest, may occur during general anesthesia in infants. With the emergence of evidence that specific anesthetic agents may affect future neurocognitive outcomes, there has been an increased focus on alternatives to general anesthesia, including spinal anesthesia. We present a case of cardiac arrest during general anesthesia in an infant who required urologic surgery. During the subsequent anesthetic care, spinal anesthesia was offered as an alternative to general anesthesia. The risks of severe perioperative complications during general anesthesia are reviewed, etiologic factors for such events are presented, and the use of spinal anesthesia as an alternative to general anesthesia is discussed.


title: A 68-Year-Old Lung Transplant Recipient With Shortness of Breath, Weight Loss, and Abnormal Chest CT

text: Case Presentation A 68-year-old man presented to our ED with shortness of breath, weakness, and a 25-lb unintentional weight loss. He had undergone bilateral lung transplantation (cytomegalovirus [CMV]: donor+, recipient+; Epstein-Barr virus: donor+; recipient+) for idiopathic pulmonary fibrosis (IPF) 18 months prior. His posttransplant course was fairly unremarkable until 1 month earlier, when he was admitted for breathlessness and weakness. CT of the chest during that admission revealed mild intralobular and interlobular septal thickening. A bronchoscopy with BAL and transbronchial biopsies did not show acute cellular rejection, but the BAL fluid was positive for coronavirus. His cortisol level was undetectable; he was diagnosed with adrenal insufficiency and fludrocortisone was initiated. He was taking prednisone, tacrolimus, and everolimus for immunosuppression and valganciclovir, itraconazole, and trimethoprim-sulfamethoxazole for antimicrobial prophylaxis. His 25-lb weight loss occurred over the span of just one month.


title: Predicting RNA-Protein Interactions Using Only Sequence Information

text: BACKGROUND: RNA-protein interactions (RPIs) play important roles in a wide variety of cellular processes, ranging from transcriptional and post-transcriptional regulation of gene expression to host defense against pathogens. High throughput experiments to identify RNA-protein interactions are beginning to provide valuable information about the complexity of RNA-protein interaction networks, but are expensive and time consuming. Hence, there is a need for reliable computational methods for predicting RNA-protein interactions. RESULTS: We propose RPISeq, a family of classifiers for predicting RNA-protein interactions using only sequence information. Given the sequences of an RNA and a protein as input, RPIseq predicts whether or not the RNA-protein pair interact. The RNA sequence is encoded as a normalized vector of its ribonucleotide 4-mer composition, and the protein sequence is encoded as a normalized vector of its 3-mer composition, based on a 7-letter reduced alphabet representation. Two variants of RPISeq are presented: RPISeq-SVM, which uses a Support Vector Machine (SVM) classifier and RPISeq-RF, which uses a Random Forest classifier. On two non-redundant benchmark datasets extracted from the Protein-RNA Interface Database (PRIDB), RPISeq achieved an AUC (Area Under the Receiver Operating Characteristic (ROC) curve) of 0.96 and 0.92. On a third dataset containing only mRNA-protein interactions, the performance of RPISeq was competitive with that of a published method that requires information regarding many different features (e.g., mRNA half-life, GO annotations) of the putative RNA and protein partners. In addition, RPISeq classifiers trained using the PRIDB data correctly predicted the majority (57-99%) of non-coding RNA-protein interactions in NPInter-derived networks from E. coli, S. cerevisiae, D. melanogaster, M. musculus, and H. sapiens. CONCLUSIONS: Our experiments with RPISeq demonstrate that RNA-protein interactions can be reliably predicted using only sequence-derived information. RPISeq offers an inexpensive method for computational construction of RNA-protein interaction networks, and should provide useful insights into the function of non-coding RNAs. RPISeq is freely available as a web-based server at http://pridb.gdcb.iastate.edu/RPISeq/.


title: Evaluating the Combined Effectiveness of Influenza Control Strategies and Human Preventive Behavior

text: Control strategies enforced by health agencies are a major type of practice to contain influenza outbreaks. Another type of practice is the voluntary preventive behavior of individuals, such as receiving vaccination, taking antiviral drugs, and wearing face masks. These two types of practices take effects concurrently in influenza containment, but little attention has been paid to their combined effectiveness. This article estimates this combined effectiveness using established simulation models in the urbanized area of Buffalo, NY, USA. Three control strategies are investigated, including: Targeted Antiviral Prophylaxis (TAP), workplace/school closure, community travel restriction, as well as the combination of the three. All control strategies are simulated with and without regard to individual preventive behavior, and the resulting effectiveness are compared. The simulation outcomes suggest that weaker control strategies could suffice to contain influenza epidemics, because individuals voluntarily adopt preventive behavior, rendering these weaker strategies more effective than would otherwise have been expected. The preventive behavior of individuals could save medical resources for control strategies and avoid unnecessary socio-economic interruptions. This research adds a human behavioral dimension into the simulation of control strategies and offers new insights into disease containment. Health policy makers are recommended to review current control strategies and comprehend preventive behavior patterns of local populations before making decisions on influenza containment.


title: CT image visual quantitative evaluation and clinical classification of coronavirus disease (COVID-19)

text: OBJECTIVES: To explore the relationship between the imaging manifestations and clinical classification of COVID-19. METHODS: We conducted a retrospective single-center study on patients with COVID-19 from Jan. 18, 2020 to Feb. 7, 2020 in Zhuhai, China. Patients were divided into 3 types based on Chinese guideline: mild (patients with minimal symptoms and negative CT findings), common, and severe-critical (patients with positive CT findings and different extent of clinical manifestations). CT visual quantitative evaluation was based on summing up the acute lung inflammatory lesions involving each lobe, which was scored as 0 (0%), 1 (1–25%), 2 (26–50%), 3 (51–75%), or 4 (76–100%), respectively. The total severity score (TSS) was reached by summing the five lobe scores. The consistency of two observers was evaluated. The TSS was compared with the clinical classification. ROC was used to test the diagnosis ability of TSS for severe-critical type. RESULTS: This study included 78 patients, 38 males and 40 females. There were 24 mild (30.8%), 46 common (59.0%), and 8 severe-critical (10.2%) cases, respectively. The median TSS of severe-critical-type group was significantly higher than common type (p < 0.001). The ICC value of the two observers was 0.976 (95% CI 0.962–0.985). ROC analysis showed the area under the curve (AUC) of TSS for diagnosing severe-critical type was 0.918. The TSS cutoff of 7.5 had 82.6% sensitivity and 100% specificity. CONCLUSIONS: The proportion of clinical mild-type patients with COVID-19 was relatively high; CT was not suitable for independent screening tool. The CT visual quantitative analysis has high consistency and can reflect the clinical classification of COVID-19. KEY POINTS: • CT visual quantitative evaluation has high consistency (ICC value of 0.976) among the observers. The median TSS of severe-critical type group was significantly higher than common type (p < 0.001). • ROC analysis showed the area under the curve (AUC) of TSS for diagnosing severe-critical type was 0.918 (95% CI 0.843–0.994). The TSS cutoff of 7.5 had 82.6% sensitivity and 100% specificity. • The proportion of confirmed COVID-19 patients with normal chest CT was relatively high (30.8%); CT was not a suitable screening modality


title: Prevalence of Chemosensory Dysfunction in COVID-19 Patients: A Systematic Review and Meta-analysis Reveals Significant Ethnic Differences

text: A significant fraction of people who test positive for COVID-19 have chemosensory deficits. However, the reported prevalence of these deficits in smell and/or taste varies widely, and the reason for the differences between studies is unclear. We determined the pooled prevalence of such chemosensory deficits in a systematic review. We searched the COVID-19 portfolio of the National Institutes of Health for all studies that reported the prevalence of smell and/or taste deficits in patients diagnosed with COVID-19. Forty-two studies reporting on 23,353 patients qualified and were subjected to a systematic review and meta-analysis. Estimated random prevalence of olfactory dysfunction was 38.5%, of taste dysfunction was 30.4% and of overall chemosensory dysfunction was 50.2%. We examined the effects of age, disease severity, and ethnicity on chemosensory dysfunction. The effect of age did not reach significance, but anosmia/hypogeusia decreased with disease severity, and ethnicity was highly significant: Caucasians had a 3-6 times higher prevalence of chemosensory deficits than East Asians. The finding of ethnic differences points to genetic, ethnicity-specific differences of the virus-binding entry proteins in the olfactory epithelium and taste buds as the most likely explanation, with major implications for infectivity, diagnosis and management of the COVID-19 pandemic.


Risk Exposure to Coronavirus Disease 2019 in Pregnant Healthcare Workers


title: A Systems Biology Approach to Infectious Disease Research: Innovating the Pathogen-Host Research Paradigm

text: The twentieth century was marked by extraordinary advances in our understanding of microbes and infectious disease, but pandemics remain, food and waterborne illnesses are frequent, multidrug-resistant microbes are on the rise, and the needed drugs and vaccines have not been developed. The scientific approaches of the past—including the intense focus on individual genes and proteins typical of molecular biology—have not been sufficient to address these challenges. The first decade of the twenty-first century has seen remarkable innovations in technology and computational methods. These new tools provide nearly comprehensive views of complex biological systems and can provide a correspondingly deeper understanding of pathogen-host interactions. To take full advantage of these innovations, the National Institute of Allergy and Infectious Diseases recently initiated the Systems Biology Program for Infectious Disease Research. As participants of the Systems Biology Program, we think that the time is at hand to redefine the pathogen-host research paradigm.


No Reduction of ST-segment Elevation Myocardial Infarction Admission in Taiwan During Coronavirus Pandemic


title: New episode of Middle East Respiratory Syndrome Coronavirus outbreak in Saudi Arabia: an emerging public health threat

text: • Middle East respiratory syndrome coronavirus (MERS-CoV) is resurgent in Saudi Arabia. • Intercontinental travel facilitates the spread of MERS-CoV infection to other global locations. • Improved vigilance is imperative to curb the dissemination of infection. • Discovery of an effective therapy and prophylaxis is a public health priority.


title: Potent and selective inhibition of SARS coronavirus replication by aurintricarboxylic acid

text: Abstract The severe acute respiratory syndrome virus (SARS) is a coronavirus that instigated regional epidemics in Canada and several Asian countries in 2003. The newly identified SARS coronavirus (SARS-CoV) can be transmitted among humans and cause severe or even fatal illnesses. As preventive vaccine development takes years to complete and adverse reactions have been reported to some veterinary coronaviral vaccines, anti-viral compounds must be relentlessly pursued. In this study, we analyzed the effect of aurintricarboxylic acid (ATA) on SARS-CoV replication in cell culture, and found that ATA could drastically inhibit SARS-CoV replication, with viral production being 1000-fold less than that in the untreated control. Importantly, when compared with IFNs α and β, viral production was inhibited by more than 1000-fold as compared with the untreated control. In addition, when compared with IFNs α and β, ATA was approximately 10 times more potent than IFN α and 100 times more than interferon β at their highest concentrations reported in the literature previously. Our data indicated that ATA should be considered as a candidate anti-SARS compound for future clinical evaluation.


title: Epidemiology, etiology, x-ray features, importance of co-infections and clinical features of viral pneumonia in developing countries

text: Pneumonia is still the number one killer of young children globally, accounting for 18% of mortality in children under 5 years of age. An estimated 120 million new cases of pneumonia occur globally each year. In developing countries, management and prevention efforts against pneumonia have traditionally focused on bacterial pathogens. More recently however, viral pathogens have gained attention as a result of improved diagnostic methods, such as polymerase chain reaction, outbreaks of severe disease caused by emerging pathogens, discovery of new respiratory viruses as well as the decrease in bacterial pneumonia as a consequence of the introduction of highly effective conjugate vaccines. Although the epidemiology, etiology and clinical characterization of viral infections are being studied extensively in the developed world, little data are available from low- and middle-income countries. In this paper, we review the epidemiology, etiology, clinical and radiological features of viral pneumonia in developing countries.


title: Virus glycosylation: role in virulence and immune interactions

text: The study of N-linked glycosylation as it relates to virus biology has become an area of intense interest in recent years due to its ability to impart various advantages to virus survival and virulence. HIV and influenza, two clear threats to human health, have been shown to rely on expression of specific oligosaccharides to evade detection by the host immune system. Additionally, other viruses such as Hendra, SARS-CoV, influenza, hepatitis and West Nile rely on N-linked glycosylation for crucial functions such as entry into host cells, proteolytic processing and protein trafficking. This review focuses on recent findings on the importance of glycosylation to viral virulence and immune evasion for several prominent human pathogens.


title: The case of Complement activation in COVID-19 multiorgan impact

text: The novel coronavirus disease COVID-19 originates in the lungs, but may extend to other organs, causing, in severe cases, multiorgan damage, including cardiac injury and acute kidney injury. In severe cases, the presence of kidney injury is associated with increased risk of death, highlighting the relevance of this organ as a target of SARS-CoV-2 infection. COVID-19-associated tissue injury is not primarily mediated by viral infection, but rather is a result of the inflammatory host immune response, which drives hypercytokinemia and aggressive inflammation that affect lung parenchymal cells, diminishing oxygen uptake but also endothelial cells, resulting in endotheliitis and thrombotic events and intravascular coagulation. The complement system represents the first response of the host immune system to SARS-CoV-2 infection, but there is growing evidence that unrestrained activation of complement induced by the virus in the lungs and other organs plays a major role in acute and chronic inflammation, endothelial cell dysfunction, thrombus formation and intravascular coagulation, and ultimately contributes to multiple organ failure and death. In this review we will discuss the relative role of the different complement activation products in the pathogenesis of COVID-19-associated tissue inflammation and thrombosis and propose the hypothesis that blockade of the terminal complement pathway may represent a potential therapeutic option for the prevention and treatment of lung and multi-organ damage.


title: Hepatitis Virus in Long-Fingered Bats, Myanmar

text: During an analysis of the virome of bats from Myanmar, a large number of reads were annotated to orthohepadnaviruses. We present the full genome sequence and a morphological analysis of an orthohepadnavirus circulating in bats. This virus is substantially different from currently known members of the genus Orthohepadnavirus and represents a new species.


title: Structural biology in antiviral drug discovery

text: Structural biology has emerged during the last thirty years as a powerful tool for rational drug discovery. Crystal structures of biological targets alone and in complex with ligands and inhibitors provide essential insights into the mechanisms of actions of enzymes, their conformational changes upon ligand binding, the architectures and interactions of binding pockets. Structure-based methods such as crystallographic fragment screening represent nowadays invaluable instruments for the identification of new biologically active compounds. In this context, three-dimensional protein structures have played essential roles for the understanding of the activity and for the design of novel antiviral agents against several different viruses. In this review, the evolution in the resolution of viral structures is analysed, along with the role of crystal structures in the discovery and optimisation of new antivirals.


title: A novel group of rhinoviruses is associated with asthma hospitalizations

text: Background Although recent studies have identified new group C human rhinoviruses (HRVCs), their spectrum of pediatric disease is unknown. Objective We sought to determine the presentation and burden of disease caused by HRVCs among young hospitalized children. Methods We conducted prospective population-based surveillance in 2 US counties among children less than 5 years of age hospitalized with acute respiratory illness or fever from October 2001 through September 2003. Nasal/throat swabs were obtained and tested for HRVs, as determined by means of RT-PCR and then characterized by means of partial sequencing. Results Of 1052 children enrolled and tested during the 2-year period, 167 (16%) had HRVs detected. Of 147 samples successfully sequenced, 64 were group A HRVs, 6 were group B HRVs, and 77 were HRVCs. Children with HRVCs were significantly more likely than those with group A HRVs to have underlying high-risk conditions, such as asthma (42% vs 23%, P = .023) and to have had a discharge diagnosis of asthma (55% vs 36%, P = .022). Conclusions Overall, HRVCs were detected in 7% of children hospitalized for fever or respiratory conditions and constituted almost half of all rhinovirus-associated hospitalizations, suggesting that this novel group causes a substantial burden of pediatric disease.


title: Clinical presentation and outcome of severe acute respiratory syndrome in dialysis patients

text: Abstract There was a major outbreak of severe acute respiratory syndrome (SARS) affecting more than 300 patients occurring in a private housing estate in Hong Kong, in which an infected renal patient was suspected to be the primary source. It is unknown whether renal patients would represent a distinct group of patients who share some characteristics that could predispose them to have higher infectivity. In this context, we have encountered 4 dialysis patients contracting SARS in a minor outbreak, which involved 11 patients and 4 health care workers, in a medical ward of a regional hospital. Of these 4 dialysis patients, 1 patient was receiving hemodialysis while the other 3 patients were on continuous ambulatory peritoneal dialysis. Fever and radiological changes were their dominant presenting features. All were having positive results for SARS-associated coronavirus ribonucleic acid by reverse transcriptase-polymerase chain reaction performed on their nasopharyngeal aspirates or stool samples. It appeared that treatment with high-dose intravenous ribavirin and corticosteroids could only resolve the fever, but it could not stop the disease progression. All 4 patients developed respiratory failure requiring mechanical ventilation on days 9 through 12. At the end, all of the patients died from sudden cardiac arrest, which was associated with acute myocardial infarction in 2 cases. From this small case series, it appeared that dialysis patients might have an aggressive clinical course and poor outcome after contracting SARS. However, a large-scale study is required to further examine this issue, and further investigation into the immunologic abnormalities associated with the uremic state in this group of patients is also warranted.


title: Wind-induced natural ventilation of re-entrant bays in a high-rise building

text: Abstract This paper reports a systematic computational study of wind-induced natural ventilation and pollutant transport of re-entrant bays on a total of 30 generic building models of different building heights and with bays of different dimensions. Mean wind flow around each building model and wind-induced flow inside re-entrant bays are computed. To determine the ventilation efficiency of the bay, the computed flow field is used to disperse a scalar pollutant initially occupying the entire bay at a uniform concentration. The subsequent time decay of pollutant concentration inside the bay is studied and the ventilation efficiency is quantified by the retention time. The results show that wind-induced flow inside the bay, especially on the building side face, is complex and highly three-dimensional. Air exchange rates through the roof opening and vertical side opening are analyzed for each bay and their relationship to the ventilation efficiency is discussed. The bays on the building side faces are much worse ventilated than those on the windward or leeward building face. The deeper the side bay, the worse is the air exchange and ventilation. The building height is found to have a governing effect on the ventilation of the windward and leeward re-entrant bays.


title: The Image of Disease in Religious, Medical–Astrological and Social Discourses: Old Polish Literature as an Example of Early Modern European Mentality

text: Today, the world is struggling with a coronavirus epidemic. People explain differently the causes and sense of this disease. Old Polish literature about diseases is representative for European thought in the modern era. The problem of the disease appears in old Polish literature in various discourses. The three most important are religious, medical–astrological and social discourse. In this article, I discuss basic paradigms of thinking connected with these discourses and the relationship between them. In the religious discourse, it is God who decides about health and illness. The pathological state of the organism can be both a trial and a punishment for the sinner. The medical and astrological discourse is based on ancient medicine, medieval medicine and astrology. It assumes a close dependence of human health on the balance of the fluids in the body and on the planetary system. The social discourse is dominated by epidemics of infectious diseases. It is a collection of advices for organizing a society during a pandemic.


title: Feminist Ethics and Women Leaders: From Difference to Intercorporeality

text: This paper problematises the ways women’s leadership has been understood in relation to male leadership rather than on its own terms. Focusing specifically on ethical leadership, we challenge and politicise the symbolic status of women in leadership by considering the practice of New Zealand Prime Minister Jacinda Ardern. In so doing, we demonstrate how leadership ethics based on feminised ideals such as care and empathy are problematic in their typecasting of women as being simply the other to men. We apply different strategies of mimesis for developing feminist leadership ethics that does not derive from the masculine. This offers a radical vision for leadership that liberates the feminine and women’s subjectivities from the masculine order. It also offers a practical project for changing women’s working lives through relationality, intercorporeality, collective agency and ethical openness with the desire for fundamental political transformation in the ways in which women can lead.


title: History of Virology

text: Abstract The history of virology can be traced as the personalities involved have described their concepts and published their experimental results. Although infections we now know as, e.g., rabies, yellow fever, smallpox, etc. were clinically evident in early human history, the initial isolation of individual viruses and their assignment to specific diseases did not occur until about 1898, 120 years ago, a proverbial drop in the bucket of time. Just one lifetime ago, Peter Medawar, awarded the Nobel Prize in Medicine and Physiology in 1960, defined viruses as a piece of nucleic acid surrounded by bad news.


title: Knocking down barriers: advances in siRNA delivery

text: In the 10 years that have passed since the Nobel prize-winning discovery of RNA interference (RNAi), billions of dollars have been invested in the therapeutic application of gene silencing in humans. Today, there are promising data from ongoing clinical trials for the treatment of age-related macular degeneration and respiratory syncytial virus. Despite these early successes, however, the widespread use of RNAi therapeutics for disease prevention and treatment requires the development of clinically suitable, safe and effective drug delivery vehicles. Here, we provide an update on the progress of RNAi therapeutics and highlight novel synthetic materials for the encapsulation and intracellular delivery of nucleic acids.


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title: Technological opportunity discovery for technological convergence based on the prediction of technology knowledge flow in a citation network

text: Abstract As technological convergence has recently become a mainstream innovation trend, technological opportunities need to be explored in heterogeneous technology fields. Most of the previous convergence studies have taken a retrospective view in measuring the degree of convergence and monitoring the converging trends. This paper proposes a quantitative future-oriented approach to technological opportunity discovery for convergence using patent information. In a future-oriented approach, technological opportunities for convergence are suggested by predicting potential technological knowledge flows (TKFs) between heterogeneous fields. The potential TKFs are predicted by a link prediction method in a directed network, which is suggested in this paper to represent the direction of the predicted TKFs by adapting the concept of bibliographic coupling and edge-betweenness centrality. Converging technological opportunities are proposed as incremental and radical technological opportunities by extracting the potential increased knowledge flow links and emerging knowledge flow links. Moreover, the direction and themes of the predicted potential TKFs are provided as technological opportunities for convergence. As an illustration of the proposed method, the technological opportunities between biotechnology (BT) and information technology (IT) are explored. Firms and researchers can use the proposed method to seek out new technological opportunities from various technologies so that R&D policymakers can plan new R&D projects on technological convergence.


Assessment of wheezing frequency and viral etiology on childhood and adolescent asthma risk