title: Epidemiology, clinical features, and resource utilization associated with respiratory syncytial virus in the community and hospital

text: BACKGROUND: The epidemiology, clinical features, and resource utilization of respiratory syncytial virus (RSV) cases in the community and the hospital are not fully characterized. METHODS: We identified individuals of all ages with laboratory‐confirmed RSV from two sources, a community cohort undergoing surveillance for acute respiratory infections (ARIs) and hospitalized patients from the same geographic area of New York City between 2013 and 15. The epidemiology, clinical features, and resource utilization (antibiotic/steroid/ribavirin usage, chest X‐rays, respiratory‐support (continuous positive airway pressure [CPAP], mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), and indicators of disease severity (respiratory‐support, and/or ICU admission or death)) were compared among age groups using univariate and bivariate analyses. RESULTS: In the community cohort (1777 people with 1805 ARIs), 66(3.7%) tested RSV‐positive (3.8% of <1‐year‐olds; 3.8% of adults ≥65); 40.9% were medically attended, and 23.1% reported antibiotic usage. Among 40,461 tests performed on hospital patients, 2.7% were RSV‐positive within ± 2 days of admission (37.3% <1 year old; 17.4% ≥65 years old). Among RSV‐positive hospitalized adults ≥65%, 92.7%, 89.6% and 78.1% received a chest X‐ray, antibiotics and/or steroids respectively, compared with 48.9%, 45.7%, and 48.7% of children <1. Severe illness occurred in 27.0% RSV‐positive hospitalized <1‐year‐olds and 19.8% ≥65‐year‐olds. CONCLUSIONS: Respiratory syncytial virus had a demonstrated impact in the community and hospital. Only 40% of RSV community cases were medically attended. In the hospitalized‐cohort, <1‐ and ≥ 65‐year‐olds accounted for the majority of patients and had similar rates of severe illness. In addition, resource utilization was high in older adults, making both young children and older adults important potential RSV vaccine targets.


title: Tannins: Prospectives and Actual Industrial Applications

text: The origin of tannins, their historical evolution, their different types, and their applications are described. Old and established applications are described, as well as the future applications which are being developed at present and that promise to have an industrial impact in the future. The chemistry of some of these applications is discussed where it is essential to understand the tannins and their derivates role. The essential points of each application, their drawbacks, and their chance of industrial application are briefly discussed. The article presents historical applications of tannins, such as leather, or traditional medicine, and more recent applications.


title: Cellular hnRNP A1 Interacts with Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus and Impairs Viral Replication

text: The nucleocapsid (N) protein is a major structural component of porcine epidemic diarrhea virus (PEDV), which is predicted to be a multifunctional protein in viral replication. Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a cellular protein participating in the splicing of pre-mRNA in the nucleus and translation regulation in the cytoplasm. According to our previous proteomic study about PEDV infection in vivo, hnRNP A1 was thought to be a cellular factor influencing PEDV replication. In this report, PEDV N protein was discovered to colocalize with cellular hnRNP A1 in perinuclear region of PEDV infected cells. Co-immunoprecipitation (CO-IP) results clearly demonstrated that PEDV N protein could bind to human hnRNP A1. Replication of PEDV was inhibited by silencing the expression of hnRNP A1 in CCL-81 cells, suggesting the positive effect of hnRNP A1 on PEDV infection.


title: Recommendations for the Care of Pediatric Orthopaedic Patients During the COVID Pandemic

text: The COVID pandemic has necessitated modifications to pediatric orthopaedic practice to protect patients, families, and healthcare workers and to minimize viral transmission. It is critical to balance the benefits of alterations to current practice to reduce the chances of COVID infection, with the potential long-term impact on patients. Early experiences of the pandemic from orthopaedic surgeons in China, Singapore, and Italy have provided the opportunity to take proactive and preventive measures to protect all involved in pediatric orthopaedic care. These guidelines, based on expert opinion and best available evidence, provide a framework for the management of pediatric orthopaedic patients during the COVID pandemic. General principles include limiting procedures to urgent cases such as traumatic injuries and deferring outpatient visits during the acute phase of the pandemic. Nonsurgical methods should be considered where possible. For patients with developmental or chronic orthopaedic conditions, it may be possible to delay treatment for 2 to 4 months without substantial detrimental long-term impact.


title: HIV protease inhibitor nelfinavir inhibits replication of SARS-associated coronavirus

text: Abstract A novel coronavirus has been identified as an etiological agent of severe acute respiratory syndrome (SARS). To rapidly identify anti-SARS drugs available for clinical use, we screened a set of compounds that included antiviral drugs already in wide use. Here we report that the HIV-1 protease inhibitor, nelfinavir, strongly inhibited replication of the SARS coronavirus (SARS-CoV). Nelfinavir inhibited the cytopathic effect induced by SARS-CoV infection. Expression of viral antigens was much lower in infected cells treated with nelfinavir than in untreated infected cells. Quantitative RT-PCR analysis showed that nelfinavir could decrease the production of virions from Vero cells. Experiments with various timings of drug addition revealed that nelfinavir exerted its effect not at the entry step, but at the post-entry step of SARS-CoV infection. Our results suggest that nelfinavir should be examined clinically for the treatment of SARS and has potential as a good lead compound for designing anti-SARS drugs.


title: Impact of quarantine on the 2003 SARS outbreak: A retrospective modeling study

text: Abstract During the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak, traditional intervention measures such as quarantine and border control were found to be useful in containing the outbreak. We used laboratory verified SARS case data and the detailed quarantine data in Taiwan, where over 150,000 people were quarantined during the 2003 outbreak, to formulate a mathematical model which incorporates Level A quarantine (of potentially exposed contacts of suspected SARS patients) and Level B quarantine (of travelers arriving at borders from SARS affected areas) implemented in Taiwan during the outbreak. We obtain the average case fatality ratio and the daily quarantine rate for the Taiwan outbreak. Model simulations is utilized to show that Level A quarantine prevented approximately 461 additional SARS cases and 62 additional deaths, while the effect of Level B quarantine was comparatively minor, yielding only around 5% reduction of cases and deaths. The combined impact of the two levels of quarantine had reduced the case number and deaths by almost a half. The results demonstrate how modeling can be useful in qualitative evaluation of the impact of traditional intervention measures for newly emerging infectious diseases outbreak when there is inadequate information on the characteristics and clinical features of the new disease—measures which could become particularly important with the looming threat of global flu pandemic possibly caused by a novel mutating flu strain, including that of avian variety.


title: SARS-Coronavirus Protein 6 Conformations Required to Impede Protein Import into the Nucleus

text: The severe acute respiratory syndrome coronavirus (SARS-CoV) genome encodes eight accessory proteins. Accessory protein 6 is a 63-residue amphipathic peptide that accelerates coronavirus infection kinetics in cell culture and in mice. Protein 6 is minimally bifunctional, with an N-terminal lipophilic part implicated in accelerating viral growth and a C-terminal hydrophilic part interfering with general protein import into the nucleus. This interference with nuclear import requires interaction between protein 6 and cellular karyopherins, a process that typically involves nuclear localization signal (NLS) motifs. Here we dissected protein 6 using site-directed mutagenesis and found no evidence for a classical NLS. Furthermore, we found that the C-terminal tail of protein 6 impeded nuclear import only in the context of a lipophilic N-terminus, which could be derived from membrane proteins unrelated to protein 6. These findings are discussed in the context of the proposed protein 6 structure.


title: SARS-CoV-2 infection serology: a useful tool to overcome lockdown?

text: The outbreak of 2019 novel coronavirus disease (Covid-19) caused by SARS-CoV-2 has spread rapidly, inducing a progressive growth in infected patients number. Social isolation (lockdown) has been assessed to prevent and control virus diffusion, leading to a worldwide financial and political crisis. Currently, SARS-CoV-2 RNA detection in nasopharyngeal swab takes place by real-time PCR (RT-qPCR). However, molecular tests can give some false-negative results. In this context, serological assays can be useful to detect IgG/IgM antibodies, to assess the degree of immunization, to trace the contacts, and to support the decision to re-admit people at work. A lot of serological diagnostic kits have been proposed on the market but validation studies have not been published for many of them. The aim of our work was to compare and to evaluate different assays analytical performances (two different immunochromatographic cards, an immunofluorescence chromatographic card, and a chemiluminescence-automated immunoassay) on 43 positive samples with RT-qPCR-confirmed SARS-CoV-2 infection and 40 negative control subjects. Our data display excellent IgG/IgM specificities for all the immunocromatographic card tests (100% IgG and 100% IgM) and for the chemiluminescence-automated assay (100% IgG and 94% IgM); IgG/IgM sensitivities are moderately lower for all methods, probably due to the assay viral antigen’s nature and/or to the detection time of nasopharyngeal swab RT-qPCR, with respect to symptoms onset. Given that sensitivities (around 94% and 84% for IgG and IgM, respectively) implicate false-negative cases and given the lack of effective vaccines or treatments, the only currently available procedure to reduce SARS-CoV-2 transmission is to identify and isolate persons who are contagious. For this reason, we would like to submit a flowchart in which serological tests, integrated with nasopharyngeal swab RT-qPCR, are included to help social and work activities implementation after the pandemic acute phase and to overcome lockdown.


title: Antimicrobial use, drug-resistant infections and COVID-19

text: Coronavirus disease 2019 may have a complex long-term impact on antimicrobial resistance (AMR). Coordinated strategies at the individual, health-care and policy levels are urgently required to inform necessary actions to reduce the potential longer-term impact on AMR and on access to effective antimicrobials.


title: Human Challenge Pilot Study with Cyclospora cayetanensis

text: We describe a pilot study that attempted to infect human volunteers with Cyclospora cayetanensis. Seven healthy volunteers ingested an inoculum of Cyclospora oocysts (approximately 200–49,000 oocysts). The volunteers did not experience symptoms of gastroenteritis, and no oocysts were detected in any stool samples during the 16 weeks volunteers were monitored.


title: Clinical Features of 69 Cases with Coronavirus Disease 2019 in Wuhan, China

text: BACKGROUND: From December 2019 to February 2020, 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China. Related clinical features are needed. METHODS: We reviewed 69 patients who were hospitalized in Union hospital in Wuhan between January 16 to January 29, 2020. All patients were confirmed to be infected with SARS-CoV-2 and the final date of follow-up was February 4, 2020. RESULTS: The median age of 69 enrolled patients was 42.0 years (IQR 35.0-62.0), and 32 patients (46%) were men. The most common symptoms were fever (60[87%]), cough (38[55%]), and fatigue (29[42%]). Most patients received antiviral therapy (66 [98.5%] of 67 patients) and antibiotic therapy (66 [98.5%] of 67 patients). As of February 4, 2020, 18 (26.9%) of 67 patients had been discharged, and five patients had died, with a mortality rate of 7.5%. According to the lowest SpO(2) during admission, cases were divided into the SpO(2)≥90% group (n=55) and the SpO(2)<90% group (n=14). All 5 deaths occurred in the SpO(2)<90% group. Compared with SpO(2)≥90% group, patients of the SpO(2)<90% group were older, and showed more comorbidities and higher plasma levels of IL6, IL10, lactate dehydrogenase, and c reactive protein. Arbidol treatment showed tendency to improve the discharging rate and decrease the mortality rate. CONCLUSIONS: COVID-19 appears to show frequent fever, dry cough, and increase of inflammatory cytokines, and induced a mortality rate of 7.5%. Older patients or those with underlying comorbidities are at higher risk of death.


title: Baculovirus as versatile vectors for protein expression in insect and mammalian cells

text: Today, many thousands of recombinant proteins, ranging from cytosolic enzymes to membrane-bound proteins, have been successfully produced in baculovirus-infected insect cells. Yet, in addition to its value in producing recombinant proteins in insect cells and larvae, this viral vector system continues to evolve in new and unexpected ways. This is exemplified by the development of engineered insect cell lines to mimic mammalian cell glycosylation of expressed proteins, baculovirus display strategies and the application of the virus as a mammalian-cell gene delivery vector. Novel vector design and cell engineering approaches will serve to further enhance the value of baculovirus technology.


title: New Vaccine Design and Delivery Technologies

text: Technological advances in immunology, protein design, and genetic delivery have unlocked new possibilities for vaccine concepts and delivery technologies that were previously inaccessible. These next-generation vaccine design efforts are particularly promising in their potential to provide solutions to challenging targets for which conventional approaches have proven ineffective—for example, a universal influenza vaccine. In this perspective, we discuss emerging approaches to vaccine design and engineering based on recent insights into immunology, structural biology, computational biology, and immunoengineering. We anticipate that these cutting-edge, interdisciplinary approaches will lead to breakthrough vaccine concepts for ever-evolving and (re)emerging influenza viruses, with important ramifications for global public health.


title: When the Dust Settles: Preventing a Mental Health Crisis in COVID-19 Clinicians

text: This essay describes timely and targeted actions that clinicians can take during the COVID-19 pandemic to support fellow clinicians.


title: Current Strategies for Inhibition of Chikungunya Infection

text: Increasing incidences of Chikungunya virus (CHIKV) infection and co-infections with Dengue/Zika virus have highlighted the urgency for CHIKV management. Failure in developing effective vaccines or specific antivirals has fuelled further research. This review discusses updated strategies of CHIKV inhibition and provides possible future directions. In addition, it analyzes advances in CHIKV lifecycle, drug-target development, and potential hits obtained by in silico and experimental methods. Molecules identified with anti-CHIKV properties using traditional/rational drug design and their potential to succeed in subsequent stages of drug development have also been discussed. Possibilities of repurposing existing drugs based on their in vitro findings have also been elucidated. Probable modes of interference of these compounds at various stages of infection, including entry and replication, have been highlighted. The use of host factors as targets to identify antivirals against CHIKV has been addressed. While most of the earlier antivirals were effective in the early phases of the CHIKV life cycle, this review is also focused on drug candidates that are effective at multiple stages of its life cycle. Since most of these antivirals require validation in preclinical and clinical models, the challenges regarding this have been discussed and will provide critical information for further research.


title: Prospective Characterization of Protracted Bacterial Bronchitis in Children

text: Background Prior studies on protracted bacterial bronchitis (PBB) in children have been retrospective or based on small cohorts. As PBB shares common features with other pediatric conditions, further characterization is needed to improve diagnostic accuracy among clinicians. In this study, we aim to further delineate the clinical and laboratory features of PBB in a larger cohort, with a specific focus on concurrent viral detection. Methods Children with and without PBB (control subjects) undergoing flexible bronchoscopy were prospectively recruited. Basic immune function testing and lymphocyte subset analyses were performed. BAL specimens were processed for cellularity and microbiology. Viruses were identified using polymerase chain reaction (PCR) and bacteria were identified via culture. Results The median age of the 104 children (69% male) with PBB was 19 months (interquartile range [IQR], 12-30 mo). Compared with control subjects, children with PBB were more likely to have attended childcare (OR, 8.43; 95% CI, 2.34-30.46). High rates of wheeze were present in both groups, and tracheobronchomalacia was common. Children with PBB had significantly elevated percentages of neutrophils in the lower airways compared with control subjects, and adenovirus was more likely to be detected in BAL specimens in those with PBB (OR, 6.69; 95% CI, 1.50-29.80). Median CD56 and CD16 natural killer (NK) cell levels in blood were elevated for age in children with PBB (0.7 × 109/L; IQR, 0.5-0.9 cells/L). Conclusions Children with PBB are, typically, very young boys with prolonged wet cough and parent-reported wheeze who have attended childcare. Coupled with elevated NK-cell levels, the association between adenovirus and PBB suggests a likely role of viruses in PBB pathogenesis.


title: Cytomegalovirus pneumonia as the first manifestation of severe combined immunodeficiency

text: Severe combined immunodeficiency (SCID) is characterized by the absence of functional T lymphocytes and impairment of adaptive immunity. While heterogeneity of the genetic background in SCID leads to the variability of immune phenotypes, most of affected newborns appear healthy but within the first few months they develop life-threatening opportunistic respiratory or gastrointestinal tract infections. The objective of the study was to define the presenting features and etiology of infections in children with SCID. We retrospectively reviewed five children in whom the diagnosis of SCID had been established in our pediatric immunology clinic over the last 10-year period. A viral respiratory tract infection was the first manifestation of SCID in all the children studied. Cytomegalovirus (CMV) pneumonia was recognized in as many as 4 cases and coronavirus pulmonary infection was diagnosed in one case, whereas Pneumocystis jiroveci was identified as a co-pathogen in one CMV-infected patient. Severe combined immunodeficiency is a pediatric emergency condition and given the significant impact of pulmonary CMV infection in SCID children, establishing an accurate etiological diagnosis is of essential importance in instituting the specific treatment and improving the outcome.


Telemedical education during national emergencies: learning from Kashmir


title: Roles in Cell-to-Cell Fusion of Two Conserved Hydrophobic Regions in the Murine Coronavirus Spike Protein

text: Abstract The spike (S) protein of coronavirus, mouse hepatitis virus (MHV), mediates attachment and fusion during viral entry and cell-to-cell fusion later in infection. By analogy with other viral proteins that induce cell fusion the MHV S protein would be expected to have a hydrophobic stretch of amino acids that serves as a fusion peptide. Sequence analysis suggests that the S protein falls within the group of fusion proteins having internal rather than N-terminal fusion peptides. Based on the features of known viral fusion peptides, we identified two regions (PEP1 and PEP2) of MHV-A59 S2 as possible fusion peptides. Site-directed mutagenesis and anin vitrocell-to-cell fusion assay were used to evaluate the roles of PEP1 and PEP2, as well as a third previously identified putative fusion domain (PEP3) in membrane fusion. Substitution of bulky hydrophobic residues with charged residues within PEP1 affects the fusion activity of the S protein without affecting processing and surface expression. Similar substitutions within PEP2 result in a fusion-negative phenotype; however, these mutant S proteins also exhibit defects in protein processing and surface expression which likely explain the loss of the ability to induce fusion. Thus PEP1 remains a candidate fusion peptide, while PEP2 may play a significant role in the overall structure or oligomerization of the S protein. PEP3 is an unlikely putative fusion peptide since it is not conserved among coronaviruses and nonconservative amino acid substitutions in PEP3 have minimal effects on cell-to-cell fusion.


title: Respiratory viral infections drive chemokine expression and exacerbate the asthmatic response

text: A number of investigations have linked respiratory vial infections and the intensity and subsequent exacerbation of asthma through host response mechanisms. For example, it is likely that the immune-inflammatory response to respiratory syncytial virus can cause a predisposition toward an intense inflammatory reaction associated with asthma, and adenovirus might cause exacerbation of the immune response associated with chronic obstructive pulmonary disease. In each of these situations, the host's immune response plays a critical mechanistic role through the production of certain cytokines and chemokines. Specific aspects of these augmented immune responses are determined by the biology of the virus, the genetic variability of the host, and the cytokine-chemokine phenotype of the involved tissue. For instance, the type 1/type 2 cytokine ratio in the airways during infection with rhinovirus determines how long the viral infection endures. By this same theory, it has been demonstrated that chemokine levels produced during respiratory syncytial virus infection determine host responses to later immune stimuli in the lung, with the potential to augment the asthmatic response. Further research in this area will clarify cytokines, chemokines, or cell targets, which will provide the basis for next-generation therapies.


title: Gut microbial diversity in two insectivorous bats: Insights into the effect of different sampling sources

text: The gut microbiota is now known as a key factor in mammalian physiology and health. Our understanding of the gut microbial communities and their effects on ecology and evolution of their hosts is extremely limited in bats which represent the second largest mammalian order. In the current study, gut microbiota of three sampling sources (small intestine, large intestine, and feces) were characterized in two sympatric and insectivorous bats (Rhinolophus sinicus and Myotis altarium) by high‐throughput sequencing of the V3‐V4 region of the 16S rRNA gene. Combining with published studies, this work reveals that Gammaproteobacteria may be a dominant class in the whole Chiroptera and Fusobacteria is less observed in bats although it has been proven to be dominant in other mammals. Our results reveal that the sampling source influences alpha diversity of the microbial community in both studied species although no significant variations of beta diversity were observed, which support that fecal samples cannot be used as a proxy of the microbiota in other gut regions in wild animals.


title: Chapter 3 Main Groups of Microorganisms of Relevance for Food Safety and Stability General Aspects and Overall Description

text: Abstract Microbiology is important to food safety, production, processing, preservation, and storage. Microbes such as bacteria, molds, and yeasts are employed for the foods production and food ingredients such as production of wine, beer, bakery, and dairy products. On the other hand, the growth and contamination of spoilage and pathogenic microorganisms is considered as one of the main causes to loss of foodstuff nowadays. Although technology, hygienic strategies, and traceability are important factors to prevent and delay microbial growth and contamination, food remains susceptible to spoilage and activity of pathogen microorganisms. Food loss by either spoilage or contaminated food affects food industry and consumers leading to economic losses and increased hospitalization costs. This chapter focuses on general aspects, characteristics, and importance of main microorganisms (bacteria, yeasts, molds, virus, and parasites) involved in food spoilage or contamination: known and recently discovered species; defects and alterations in foodstuff; most common food associated with each foodborne disease; resistance to thermal processing; occurrence in different countries; outbreaks; and associated symptoms.


title: Origin and transmission of Feline coronavirus type I in domestic cats from Northern Italy: a phylogeographic approach

text: Feline coronavirus (FCoV) is responsible, along with an inadequate immune response of the host, for Feline infectious peritonitis (FIP), one of the most frequent and deadly infectious feline disease worldwide. This study analyzed the genetic characteristics of the spike (S) gene of 33 FCoVs circulating in Northern Italy between 2011 and 2015 in cats with or without FIP. In order to reconstruct the most probable places of origin and dispersion of FCoV among Italian cats, a phylogeographic approach was performed based on 106 FCoV S gene partial sequences from cats, including the 33 novel Italian sequences and 73 retrieved from public databases. Only FCoV type I was found in the Italian cats. The estimated mean evolutionary rate of FCoV was 2.4 × 10(-2) subs/site/year (95% HPD: 1.3-3.7 × 10(-2)), confirming the high genetic variability in the circulating strains. All the isolates clustered in a unique highly significant clade that likely originated from USA between the 1950s and the 1970s, confirming the first descriptions of the disease in American cats. Our results suggest that from USA the virus likely entered Germany and thereafter spread to other European countries. Phylogeography showed that sequences segregated mainly by geographical origin. In the 2010s Italian sequences clustered in different subclades, confirming that different strains cocirculate in Italy. Further studies on archival samples and other genetic regions of FCoV are suggested in order to confirm the present results and to reconstruct a more in-depth detailed virus dispersion pattern for the definition of possible control measures.


Comment on: Disposable customized aerosol containment chamber for oral cancer biopsy: A novel technique during COVID‐19 pandemic


title: Genetic Diversity and Evolution of Viral Populations ☆

text: Abstract Population genetic diversity plays a prominent role in viral evolution, pathogenesis, immune escape, and drug resistance. Different mechanisms are responsible for creating and maintaining genetic diversity in viruses, including error-prone replication, repair avoidance, and genome editing, among others. This diversity is subsequently modulated by natural selection and random genetic drift, whose action in turn depends on multiple factors including viral genetic architecture, viral demography, and ecology. Understanding these processes should contribute to the development of more efficient control and treatment strategies against viral pathogens.


title: Lung Ultrasound in Patients with Acute Respiratory Failure Reduces Conventional Imaging and Health Care Provider Exposure to COVID-19

text: Lung ultrasound gained a leading position in the last year as an imaging technique for the assessment and management of patients with acute respiratory failure. In coronavirus disease 2019 (COVID-19), its role may be of further importance because it is performed bedside and may limit chest X-ray and the need for transport to radiology for computed tomography (CT) scan. Since February 21, we progressively turned into a coronavirus-dedicated intensive care unit and applied an ultrasound-based approach to avoid traditional imaging and limit contamination as much as possible. We performed a complete daily examination with lung ultrasound score computation and systematic search of complications (pneumothorax, ventilator-associated pneumonia); on-duty physicians were free to perform CT or chest X-ray when deemed indicated. We compared conventional imaging exams performed in the first 4 wk of the COVID-19 epidemic with those in the same time frame in 2019: there were 84 patients in 2020 and 112 in 2019; 64 and 22 (76.2% vs. 19.6%, p < 0.001) had acute respiratory failure, respectively, of which 55 (85.9%) were COVID-19 in 2020. When COVID-19 patients in 2020 were compared with acute respiratory failure patients in 2019, the median number of chest X-rays was 1.0 (1.0–2.0) versus 3.0 (1.0–4.0) (p = 0.0098); 2 patients 2 (3.6%) versus 7 patients (31.8%) had undergone at least one thoracic CT scan (p = 0.001). A self-imposed ultrasound-based approach reduces the number of chest X-rays and thoracic CT scans in COVID-19 patients compared with patients with standard acute respiratory failure, thus reducing the number of health care providers exposed to possible contamination and sparing personal protective equipment.


Facteurs déclenchant des exacerbations de BPCO


title: Corticosteroid treatment of severe acute respiratory syndrome in Hong Kong

text: Summary Background The patterns of corticosteroids usage in severe acute respiratory syndrome (SARS) and associated treatment outcomes in Hong Kong were studied. Method Patients≥18years old who either had not received corticosteroid or had taken corticosteroids within 14days from symptom onset were included. Patients receiving corticosteroids beyond 15days or other investigational treatment within 21days from symptom onset were excluded. Of 1313 eligible patients, 1287 with major corticosteroid dosage-type combinations were analysed. Results Crude death rate was lower among 1188 steroid-treated patients compared to 99 patients in Group No Steroid (17.0% vs. 28.3%). Among four corticosteroid groups studied, mortality was lowest in the low-dose oral prednisolone (Group P) and high-dose methylprednisolone (Group MP) groups. On multivariate analysis of the corticosteroid groups, independent factors related to death were: corticosteroid group, older age, co-morbidity, worse chest X-ray score, worse respiratory status at Days 8–10 and higher admission white cell count. Again Groups P and MP had significantly lower adjusted odds ratios for death and lower bacterial and fungal culture rates. Despite worse chest X-ray scores and higher cumulative corticosteroid dosages in Group MP compared to Group P, fewer patients required rescue pulsed corticosteroid. Patients on hydrocortisone (Group HC) had the highest positive culture rates. Conclusion We speculate that corticosteroid with higher in-vitro inflammatory potency administered at timing and dosages commensurate with disease severity may be conducive to better outcome from SARS as a consequence of more effective control of immunopathological lung damage.


title: Spatial epidemic dynamics of the COVID-19 outbreak in China

text: Abstract Background On 31 December 2019 an outbreak of COVID-19 in Wuhan, China, was reported. The outbreak spread rapidly to other Chinese cities and multiple countries. This study described the spatio-temporal pattern and measured the spatial association of the early stages of the COVID-19 epidemic in mainland China from 16 January–06 February 2020. Methods This study explored the spatial epidemic dynamics of COVID-19 in mainland China. Moran’s I spatial statistic with various definitions of neighbours was used to conduct a test to determine whether a spatial association of the COVID-19 infections existed. Results The spatial spread of the COVID-19 pandemic in China was observed. The results showed that most of the models, except medical-care-based connection models, indicated a significant spatial association of COVID-19 infections from around 22 January 2020. Conclusions Spatial analysis is of great help in understanding the spread of infectious diseases, and spatial association was the key to the spatial spread during the early stages of the COVID-19 pandemic in mainland China.


Disrupt, Innovate, and Transform in the Era of COVID‐19


title: Natural FCoV infection: cats with FIP exhibit significantly higher viral loads than healthy infected cats

text: Natural feline coronavirus (FCoV) infection has been shown to not only induce intestinal infection with viral shedding, but also systemic infection which either remains without clinical signs or leads to feline infectious peritonitis (FIP). As systemic infection is not the key event in the development of FIP, the question arises as to whether a potential difference in viral load might be of importance. Therefore, the purpose of this study was to quantitatively assess feline coronavirus (FCoV) RNA loads in haemolymphatic tissues of healthy, long-term FCoV-infected cats and cats with FIP. In cats that died from FIP, viral loads were significantly higher, indicating a higher rate of viral replication or a reduced capacity for viral clearance in cats developing and/or suffering from FIP.


title: COVID-19 Monitoring and Response Among U.S. Air Force Basic Military Trainees — Texas, March–April 2020

text: The coronavirus disease 2019 (COVID-19) pandemic has resulted in substantial morbidity and mortality since it was first described in December 2019 (1). Based on epidemiologic data showing spread in congregate settings (2-4), national, state, and local governments instituted significant restrictions on large gatherings to prevent transmission of disease in early March 2020. This and other nonpharmaceutical interventions (NPIs) have shown initial success in slowing the pandemic across the country (5). This report examines the first 7 weeks (March 1-April 18) of implementation of NPIs in Basic Military Training (BMT) at a U.S. Air Force base. In a population of 10,579 trainees, COVID-19 incidence was limited to five cases (47 per 100,000 persons), three of which were in persons who were contacts of the first patient. Transmission of symptomatic COVID-19 was successfully limited using strategies of quarantine, social distancing, early screening of trainees, rapid isolation of persons with suspected cases, and monitored reentry into training for trainees with positive test results after resolution of symptoms.


title: Molecular Mechanism of Functional Ingredients in Barley to Combat Human Chronic Diseases

text: Barley plays an important role in health and civilization of human migration from Africa to Asia, later to Eurasia. We demonstrated the systematic mechanism of functional ingredients in barley to combat chronic diseases, based on PubMed, CNKI, and ISI Web of Science databases from 2004 to 2020. Barley and its extracts are rich in 30 ingredients to combat more than 20 chronic diseases, which include the 14 similar and 9 different chronic diseases between grains and grass, due to the major molecular mechanism of six functional ingredients of barley grass (GABA, flavonoids, SOD, K-Ca, vitamins, and tryptophan) and grains (β-glucans, polyphenols, arabinoxylan, phytosterols, tocols, and resistant starch). The antioxidant activity of barley grass and grain has the same and different functional components. These results support findings that barley grain and its grass are the best functional food, promoting ancient Babylonian and Egyptian civilizations, and further show the depending functional ingredients for diet from Pliocene hominids in Africa and Neanderthals in Europe to modern humans in the world. This review paper not only reveals the formation and action mechanism of barley diet overcoming human chronic diseases, but also provides scientific basis for the development of health products and drugs for the prevention and treatment of human chronic diseases.


title: Structure and dynamics of the core US air travel markets: A basic empirical analysis of domestic passenger demand

text: Abstract The air transportation industry in the US has undergone significant restructuring since 2001. While adjustments in costs have been the focus of the industry, changes in the demand structure have also occurred. This paper analyses the structure and dynamics of the origin and destination of core air travel market demand using 1995–2006 US quarterly time-series data. Despite the industry consolidating its network following the terrorist attacks of 2001, passenger travels in core markets have exhibited strong growth in recent years. This increase was driven mostly by the gains in the larger markets. When segmented by types of markets, super-thin markets are seen to have lost services while other markets gained. A majority of passengers use the thick markets that account for only a small portion of all markets and their demand has continued to grow. Relatively fewer passengers fly in the thin and super-thin markets, but they account for a substantial portion of all markets. Empirical estimates align well with the events and adjustments that have been experienced during the time series we examined.


title: Influenza A☆

text: Abstract The influenza viruses, which contain single-stranded RNA, are classified into three types, A, B, and C and belong to the Orthomyxoviridae family of viruses. Types A and B cause annual epidemics and often pandemics of influenza illness, while type C is a less common disease with fewer symptoms.


title: Functional analysis of Leishmania major cyclophilin

text: A potent immunosuppressive drug cyclosporin A (CsA) is known to inhibit human cell infection by the pathogenic protozoan parasite Leishmania major both in vitro and in vivo. The proposed mechanism of action involves CsA binding to Leishmania major-expressed cyclophilin and subsequent down-regulation of signaling events necessary for establishing productive infection. Recently, we identified a ubiquitously expressed membrane protein, CD147, as a signaling receptor for extracellular cyclophilins in mammalian cells. Here we demonstrate that, while being enzymatically active, the Leishmania cyclophilin, unlike its human homologue, does not interact with CD147 on the cell surface of target cells. CD147 facilitates neither Leishmania binding nor infection. Primary structure and biochemical analyses revealed that the parasite’s cyclophilin is defective in heparan binding, an event required for signaling interaction between CD147 and human cyclophilin. When the heparan-binding motif was reconstituted in Leishmania cyclophilin, it regained the CD147-dependent signaling activity. These results underscore a critical role of cyclophilin-heparan interactions in CD147-mediated signaling events and argue against the role of Leishmania cyclophilin in parasite binding to target cells.


title: SARS-CoV-2 mRNA Vaccine Development Enabled by Prototype Pathogen Preparedness

text: A SARS-CoV-2 vaccine is needed to control the global COVID-19 public health crisis. Atomic-level structures directed the application of prefusion-stabilizing mutations that improved expression and immunogenicity of betacoronavirus spike proteins. Using this established immunogen design, the release of SARS-CoV-2 sequences triggered immediate rapid manufacturing of an mRNA vaccine expressing the prefusion-stabilized SARS-CoV-2 spike trimer (mRNA-1273). Here, we show that mRNA-1273 induces both potent neutralizing antibody and CD8 T cell responses and protects against SARS-CoV-2 infection in lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a Phase 2 clinical trial with a trajectory towards Phase 3 efficacy evaluation.


title: Global Influenza Hospital-based Surveillance Network (GIHSN): results of surveillance of influenza and other respiratory viruses in hospitalised patients in Brazil, 2015

text: BACKGROUND: Influenza-like illness occurs annually worldwide, with peak timing and severity varying seasonally, resulting in significant annual mortality. OBJECTIVES: There were three objectives: (1) to describe the epidemiological and clinical features of hospitalised patients with severe acute respiratory infection caused by influenza and other respiratory viruses (ORVs); (2) to report the influenza seasonality in the region and (3) to correlate findings of influenza circulation and immunisation time in Brazil. PATIENTS/METHODS: This study took place in three Brazilian hospitals located in cities with different climatic conditions (Curitiba (south), Rio de Janeiro (south-east) and Fortaleza (north-east)). Patients presenting with an acute process with indication for admission consisting of a predefined set of conditions potentially associated with recent influenza infection were enrolled. RESULTS: We screened 1666 patients, with 595 meeting the inclusion criteria. Influenza viruses and ORVs were detected in 6.5% and 59% of patients, respectively. Influenza-positive cases fell into the severe spectrum as compared with those with ORVs (30% vs 11%), but without any difference in mortality rates. Epidemiological results revealed variations in the peak time of influenza infections between north-east (Fortaleza) and south (Curitiba) Brazil, basically following the rain period of each region. In north-east Brazil, viral circulation was prevalent in the first 4 months of the year, indicating that the vaccination campaign occurred in a postseasonal period, possibly explaining the low effectiveness. CONCLUSIONS: The active-surveillance model is a valuable tool for investigating respiratory virus impact on hospitalised patients, with influenza-infection monitoring enabling implementation of adequate preventive measures.


title: Treatment of Middle East respiratory syndrome with a combination of lopinavir/ritonavir and interferon-β1b (MIRACLE trial): statistical analysis plan for a recursive two-stage group sequential randomized controlled trial

text: ABSTRACT: The MIRACLE trial (MERS-CoV Infection tReated with A Combination of Lopinavir/ritonavir and intErferon-β1b) investigates the efficacy of a combination therapy of lopinavir/ritonavir and recombinant interferon-β1b provided with standard supportive care, compared to placebo provided with standard supportive care, in hospitalized patients with laboratory-confirmed MERS. The MIRACLE trial is designed as a recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The aim of this article is to describe the statistical analysis plan for the MIRACLE trial. The primary outcome is 90-day mortality. The primary analysis will follow the intention-to-treat principle. The MIRACLE trial is the first randomized controlled trial for MERS treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02845843. Registered on 27 July 2016.


title: Long noncoding RNAs: Novel regulators of virus‐host interactions

text: Long noncoding RNAs (lncRNAs) represent a key class of cellular regulators, involved in the modulation and control of multiple biological processes. Distinct classes of lncRNAs are now known to be induced by host cytokines following viral infections. Current evidence demonstrates that lncRNAs play essential roles at the host‐pathogen interface regulating viral infections by either innate immune responses at various levels including activation of pathogen recognition receptors or by epigenetic, transcriptional, and posttranscriptional effects. We review the newly described mechanisms underlying the interactions between lncRNAs, cytokines, and metabolites differentially expressed following viral infections; we highlight the regulatory networks of host antiviral responses and emphasize the need for interdisciplinary research between lncRNA biology and immunology to deepen understanding of viral pathogenesis.


title: Yellow fever vector live-virus vaccines: West Nile virus vaccine development

text: Abstract By combining molecular-biological techniques with our increased understanding of the effect of gene sequence modification on viral function, yellow fever 17D, a positive-strand RNA virus vaccine, has been manipulated to induce a protective immune response against viruses of the same family (e.g. Japanese encephalitis and dengue viruses). Triggered by the emergence of West Nile virus infections in the New World afflicting humans, horses and birds, the success of this recombinant technology has prompted the rapid development of a live-virus attenuated candidate vaccine against West Nile virus.


Pulmonary Tuberculosis and SARS, China


title: Management of orthopaedic and traumatology patients during the Coronavirus disease (COVID-19) pandemic in northern Italy

text: PURPOSE: This article aims to share northern Italy’s experience in hospital re-organization and management of clinical pathways for traumatic and orthopaedic patients in the early stages of the COVID-19 pandemic. METHODS: Authors collected regional recommendations to re-organize the healthcare system during the initial weeks of the COVID-19 pandemic in March, 2020. The specific protocols implemented in an orthopaedic hospital, selected as a regional hub for minor trauma, are analyzed and described in this article. RESULTS: Two referral centres were identified as the hubs for minor trauma to reduce the risk of overload in general hospitals. These two centres have specific features: an emergency room, specialized orthopaedic surgeons for joint diseases and trauma surgeons on-call 24/7. Patients with trauma without the need for a multi-disciplinary approach or needing non-deferrable elective orthopaedic surgery were moved to these hospitals. Authors report the internal protocols of one of these centres. All elective surgery was stopped, outpatient clinics limited to emergencies and specific pathways, ward and operating theatre dedicated to COVID-19-positive patients were implemented. An oropharyngeal swab was performed in the emergency room for all patients needing to be admitted, and patients were moved to a specific ward with single rooms to wait for the results. Specific courses were organized to demonstrate the correct use of personal protection equipment (PPE). CONCLUSION: The structure of the orthopaedic hubs, and the internal protocols proposed, could help to improve the quality of assistance for patients with musculoskeletal disorders and reduce the risk of overload in general hospitals during the COVID-19 pandemic.


Global health and the US Centers for Disease Control and Prevention


title: Do drones have a realistic place in a pandemic fight for delivering medical supplies in healthcare systems problems?

text: Abstract The advancement of Unmanned Aerial Vehicle (UAV) technology in terms of industrial processes and communication and networking technologies has led to an increase in their use in civil, business, and social applications. Global rules in most countries had previously limited the use of drones to military applications due to their deployment in the open air, drones are likely to be lost, destroyed, or physically hijacked. However, more recently, the presence of COVID-19 has forced the world to present new implementing measures which will also widen the use of drones in civil and commercial and social applications, especially now in the delivery of medicines for medical home care. In the period of requiredpublic isolationas a consequence of the SARS-COV-2 pandemic, thisknowledgehas become one of the principal partners in the fight against the coronavirus. This paper offers a summary of the medical drone manufacturing, with a specific emphasis on its approval by the pharmaceutical sector to solve logistical problems in healthcare during times of sensitive need. We also discuss the numerous challenges to be met in the integration of drones to save our lives and suggest future research directions. The question that arises for this problem, how to optimize delivery medical supplies times in-home health care made up of drones? We conducted a synthesis literature review devoted to the use of UAVs in healthcare with their different aspects. A total of different research made are given to describe the role of UAV in Home healthcare with the presence of SARS-COV-2. We conclude that the drones will be able to optimize the way of eliminating contamination with a very high percentage (through the reduction of human contact) with the increase of the flexibility of the flight (reaching the less accessible regions every hour of the day).


title: The Clinical and Radiological Manifestations in Coronavirus Disease (COVID-19) with Negative Nucleic Acid Results

text: BACKGROUND: COVID-19 was a new emerging disease with high infectiousness. Its diagnosis primarily depended on real time-polymerase chain reaction (RT-PCR) results. This study investigated epidemiological, clinical and radiological characteristics of COVID-19 with negative RT-PCR results before confirmation. METHODS: COVID-19 patients were enrolled and divided into two groups, negative group with negative RT-PCR results before confirmation and positive group with positive results at the first detection. Epidemiological and clinical features were compared. Dynamic chest CT images of negative group were evaluated. RESULT: Nighty-nine laboratory-confirmed COVID-19 including eight patients (8%) with negative RT-PCR results were included. Patients from negative group had similar epidemiological features as the average age (50.25±13.27 y in the negative group and 53.70±16.64 y in the positive group) and gender distribution (males made up 50% of the negative group and 62.6% of the positive group) were comparable. No significant difference of clinical symptoms were observed between the two groups. It was found that fever was the most common symptom for both groups, followed by cough, expectoration, chest distress, fatigue and gastroenterological symptoms. Moreover, ground-glass opacities and consolidations were main manifestations in chest CT of COVID-19 patients with or without confirmed RT-PCR results. CONCLUSIONS: Regardless of initial RT-PCR results, COVID-19 patients had similar epidemiological, clinical and chest CT features. Our study suggested values of early chest CT scan in COVID-19 screening and dynamic significance of radiology in disease monitoring to guide clinical decision.


title: Data and Debriefing Observations on Healthcare Simulation to Prepare for the COVID-19 Pandemic: Healthcare Simulation for COVID-19

text: We report on data and debriefing observations in the context of an immersive simulation conducted to (a) train clinicians and (b) test new protocols and kits, developed in table-top exercises without prior clinical experience to fit anticipated clinical encounters in the setting of the rapidly expanding COVID-19 pandemic. We simulated scenarios with particular relevance for anesthesiology, perioperative and critical care, including (1) cardiac arrest, (2) emergency airway management, (3) tele-instruction for remote guidance and supervision, and (4) transporting an intubated patient. Using a grounded theory approach, three authors (MHA, DLR, EHS) developed emergent themes. First alone and then together, we sought consensus in uncovering overarching themes and constructs from the debriefings. We thus performed an informal qualitative thematic analysis based in a critical realist epistemological position - the understanding that our findings, while real, are affected by situational variables and the observer's perspective.[1,2] We compared data from videos and triangulated the data by member checking. All participants and course instructors volunteered to participate in this educational project and contributed as co-authors to this manuscript. During debriefing, we applied crisis resource management concepts including situation awareness, prioritization of tasks, and clear communication practices, conducting the debriefing with emphasis on current TeamStepps 2.0 terminology and concepts. [3,4] In addition, we re-evaluated formerly familiar processes, as shortcomings of protocols, kits, and interdisciplinary cooperation became apparent. The data provide detailed observations on how immersive simulation and debriefing among peers mitigated the unfamiliarity of individual clinicians and the organization at large with the demands of an unprecedented healthcare crisis. We also observed and report on the anxiety caused by resource constraints, risk to clinicians in the face of limited personal equipment, and the overall uncertainty surrounding COVID-19. We began to summarize, interpret, critique, and discuss our data and debriefing observations in a rapid co-publication in the Journal of Clinical Anesthesia. [Healthcare Simulation to Prepare for the COVID-19 Pandemic][5]


title: Viral-Induced Enhanced Disease Illness

text: Understanding immune responses to viral infections is crucial to progress in the quest for effective infection prevention and control. The host immunity involves various mechanisms to combat viral infections. Under certain circumstances, a viral infection or vaccination may result in a subverted immune system, which may lead to an exacerbated illness. Clinical evidence of enhanced illness by preexisting antibodies from vaccination, infection or maternal passive immunity is available for several viruses and is presumptively proposed for other viruses. Multiple mechanisms have been proposed to explain this phenomenon. It has been confirmed that certain infection- and/or vaccine-induced immunity could exacerbate viral infectivity in Fc receptor- or complement bearing cells- mediated mechanisms. Considering that antibody dependent enhancement (ADE) is a major obstacle in vaccine development, there are continues efforts to understand the underlying mechanisms through identification of the epitopes and antibodies responsible for disease enhancement or protection. This review discusses the recent findings on virally induced ADE, and highlights the potential mechanisms leading to this condition.


title: Palliative Care Integration Project (PCIP) Quality Improvement Strategy Evaluation

text: Abstract This study evaluated the effectiveness of implementation of common assessment tools, collaborative care plans, and symptom management guidelines for cancer patients as a strategy to improve the quality, coordination, and integration of palliative care service across organizations and health care sectors. A pre-post design to measure the impact on symptom management, caregiver burden and satisfaction with care delivery, and service utilization was used. Two cohorts of eligible patients and caregivers completed Edmonton Symptom Assessment Scales, Caregiver Reaction Assessment and FAMCARE Scales and chart audits were conducted. Administrative data from each participating site were examined for utilization trends. Audits of 53 charts preimplementation and 63 postimplementation showed an increase in documentation of pain from 24.5% to 74.6% (P <0.001) of charts. Administrative data showed a decrease in the percentage of patients with at least one emergency room visit from 94.3% to 84.8% (P <0.001), in the percentage of patients with at least one admission to the acute care hospital (P <0.001), and deaths in acute care 43.1%–35.7% (P =0.133). There was minimal change in the intensity of symptoms (P =0.591), and no change in the burden on the caregiver (P =0.086) or caregiver satisfaction with care (P =0.942). This study showed that implementation of common assessment tools, collaborative care plans, and symptom management guidelines across health sectors can result in some increased documentation of symptoms and efficiencies in care. Future projects should consider imbedding a continuous quality improvement methodology and longer timelines into their projects to improve outcomes.


title: Cyclophilin and Viruses: Cyclophilin as a Cofactor for Viral Infection and Possible Anti-Viral Target

text: Cyclophilin (CyP) is a peptidyl prolyl cis/trans isomerase, catalyzing the cis-trans isomerization of proline residues in proteins. CyP plays key roles in several different aspects of cellular physiology including the immune response, transcription, mitochondrial function, cell death, and chemotaxis. In addition to these cellular events, a number of reports demonstrated that CyP plays a critical role in the life cycle of viruses, especially human immunodeficiency virus (HIV) and hepatitis C virus (HCV). These two viruses are significant causes of morbidity and mortality worldwide, but current therapies are often insufficient. CyP may provide a novel therapeutic target for the management and/or cure of these diseases, in particular HCV.


title: Clinical Presentation and Outcomes of Pregnant Women with COVID-19: A Systematic Review and Meta-Analysis

text: INTRODUCTION: Descriptions of coronavirus disease-2019 (COVID-19) have focused on the non-pregnant adult population. This study aims to describe the clinical characteristics and perinatal outcomes of COVID-19 in pregnancy. METHODS: We searched databases from December 2019 to April 30(th), 2020. Eligible studies reported clinical characteristics, radiological findings and/or laboratory testing of pregnant women during infection. Data were pooled across studies using random-effects model. RESULTS: Twenty-four studies (136 women) were included. Most common symptoms were fever (62.9%) and cough (36.8%). Laboratory findings included elevated C-Reactive Protein (57%) and lymphocytopenia (50%). Ground-glass opacity was the most common radiological finding (81.7%). Preterm birth rate was 37.7% and cesarean delivery rate was 76%. There was one maternal death. There were two fetal COVID-19 cases. CONCLUSION: The clinical picture in pregnant women with COVID-19 did not differ from the non-pregnant population, however, the rate of preterm birth and cesarean delivery are considerably higher than international averages.


title: Seroprevalence of Wenzhou virus in China

text: Wenzhou virus (WENV) was first identified in rodents and Asian house shrews in Wenzhou, Zhejiang province, China. However, little is known about the prevalence of WENV infections in humans in China. To determine the threat that WENV may pose to humans, we determine the seroprevalence of WENV in healthy individuals in China in this study. Cross-reactivities of nucleoprotein (NP) were detected between Lymphocytic choriomeningitis virus (LCMV) and WENV using Western blot and ELISA assy. The prevalence of specific IgG antibodies against WENV NP was investigated in different age groups of 830 healthy individuals aged 0–70 years old in China using a competition ELISA assay. The results indicate that WENV and LCMV share cross-reactive epitopes between NPs. The total seroprevalence of WENV in healthy adults was 4.6%, with 3.6% (8/221) for individuals 15–44 years of age, 5.4% (17/317) for individuals 45–59 years of age, and 4.1% (4/98) for older adults over 60. The total seroprevalence of WENV in children under age 15 was 1.5%, with 2.9% (1/34) in children aged 2–5 years, and 2.2% in 5–14 years (2/91). The finding suggests that WENV or WENV-like virus may sporadically infect humans of China.


title: Role of the inflammasome-related cytokines Il-1 and Il-18 during infection with murine coronavirus

text: The inflammasome, a cytosolic protein complex that mediates the processing and secretion of pro-inflammatory cytokines, is one of the first responders during viral infection. The cytokines secreted following inflammasome activation, which include IL-1 and IL-18, regulate cells of both the innate and adaptive immune system, guiding the subsequent immune responses. In this study we used murine coronavirus, mouse hepatitis virus (MHV), infection of the central nervous system and liver to assess of the role of the inflammasome and its related cytokines on pathogenesis and host defense during viral infection. Mice lacking all inflammasome signaling due to the absence of caspase-1 and -11 were more vulnerable to infection, with poor survival and elevated viral replication compared to wild type mice. Mice lacking IL-1 signaling experienced elevated viral replication but similar survival compared to wild type controls. In the absence of IL-18, mice had elevated viral replication and poor survival, and this protective effect of IL-18 was found to be due to promotion of interferon gamma production in αβ T cells. These data suggest that inflammasome signaling is largely protective during murine coronavirus infection, in large part due to the pro-inflammatory effects of IL-18.


title: Detection and Sequence Characterization of the 3′-End of Coronavirus Genomes Harboring the Highly Conserved RNA Motif s2m

text: A remarkably conserved 43-nucleotide-long motif present at the 3′-end of the genomes of several members of the polyadenylated RNA virus families Astroviridae, Coronaviridae, and Picornaviridae can be used for the detection and sequence characterization of the viruses harboring it. The procedure makes use of a primer located in the most conserved core of s2m toward a generic anchored oligo(dT) primer in a semispecific PCR. This strategy allows the sequencing of some 50–100 nucleotides from the 3′-end of the virus genome, representing sufficient sequence information for initiation of further genomic characterization in a rapid amplification of cDNA ends (5′-RACE) and primer walking strategy.


title: IL-27 Is Elevated in Patients With COPD and Patients With Pulmonary TB and Induces Human Bronchial Epithelial Cells to Produce CXCL10

text: Background The role of IL-27 in the pathogenesis of airway inflammatory diseases remains elusive. We, therefore, have studied its concentrations in the sputum and plasma of patients with COPD and patients with pulmonary TB (PTB), and further investigated the mechanism-of-action effects of IL-27 on bronchial epithelial cells in vitro. Methods Human bronchial epithelial cells grown on air-liquid interface culture were activated by IL-27, alone, or in combination with other inflammatory cytokines in the presence or absence of various signaling molecule inhibitors. The expression of CXCL10 was detected by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). The underlying signaling pathways were studied by intracellular staining using flow cytometry, Western blot, ELISA, or siRNA. Results Significantly higher sputum and plasma concentrations of IL-27 were found in patients with COPD (n = 34; P < .01 and P < .001, respectively) or patients with PTB (n = 31; P < .01 and P < .001, respectively) than in healthy control subjects (n = 48). Sputum, but not plasma, IL-27 levels in patients with COPD correlated negatively with FEV1 (r = −0.51, P < .01). Sputum, but not plasma, IL-27 in patients with PTB correlated positively with mycobacterial load in sputum (r = 0.48, P < .05). Further in vitro studies demonstrated that IL-27 could induce gene and protein expression of CXCL10 in bronchial epithelial cells, which was regulated by the activation of the phosphatidylinositol 3-OH kinase (PI3K)-Akt signaling pathway. Conclusions The production of IL-27 is related to the pathogenesis of COPD and PTB, and IL-27 induces the expression of CXCL10 in bronchial epithelial cells through the activation of the PI3K-Akt signaling pathway.


title: A curated transcriptome dataset collection to investigate the blood transcriptional response to viral respiratory tract infection and vaccination.

text: The human immune defense mechanisms and factors associated with good versus poor health outcomes following viral respiratory tract infections (VRTI), as well as correlates of protection following vaccination against respiratory viruses, remain incompletely understood. To shed further light into these mechanisms, a number of systems-scale studies have been conducted to measure transcriptional changes in blood leukocytes of either naturally or experimentally infected individuals, or in individual’s post-vaccination. Here we are making available a public repository, for research investigators for interpretation, a collection of transcriptome datasets obtained from human whole blood and peripheral blood mononuclear cells (PBMC) to investigate the transcriptional responses following viral respiratory tract infection or vaccination against respiratory viruses. In total, Thirty one31 datasets, associated to viral respiratory tract infections and their related vaccination studies, were identified and retrieved from the NCBI Gene Expression Omnibus (GEO) and loaded in a custom web application designed for interactive query and visualization of integrated large-scale data. Quality control checks, using relevant biological markers, were performed. Multiple sample groupings and rank lists were created to facilitate dataset query and interpretation. Via this interface, users can generate web links to customized graphical views, which may be subsequently inserted into manuscripts to report novel findings. The GXB tool enables browsing of a single gene across projects, providing new perspectives on the role of a given molecule across biological systems in the diagnostic and prognostic following VRTI but also in identifying new correlates of protection. This dataset collection is available at: http://vri1.gxbsidra.org/dm3/geneBrowser/list.


title: The lethal sex gap: COVID-19

text: While Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is disrupting lives across the globe for everyone, it has a more devastating impact on the health of older adults, especially that of older men. This pandemic has highlighted the crucial importance of considering an individual’s age and biological sex in the clinic in addition to other confounding diseases (Kuchel, G.A, J Am Geriatr Soc, 67, 203, 2019, Tannenbaum, C., Nature, 575 451-458, 2009) As an interdisciplinary team of scientists in immunology, hematology, genomics, bioinformatics, and geriatrics, we have been studying how age and sex shape the human immune system. Herein we reflect on how our recent findings on the alterations of the immune system in aging might contribute to our current understanding of COVID-19 infection rate and disease risk.


title: Association between insertion/deletion polymorphism in angiotensin-converting enzyme gene and acute lung injury/acute respiratory distress syndrome: a meta-analysis

text: BACKGROUND: A previous meta-analysis reported a positive association between an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene (ACE) and the risk of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Here, we updated this meta-analysis and additionally assessed the association of this polymorphism with ALI/ARDS mortality. METHODS: We searched electronic databases through October 2011 for the terms “angiotensin-converting enzyme gene”, “acute lung injury”, and “acute respiratory distress syndrome,” and reviewed all studies that reported the relationship of the I/D polymorphism in ACE with ALI/ARDS in humans. Seven studies met the inclusion criteria, comprising 532 ALI/ARDS patients, 3032 healthy controls, and 1432 patients without ALI/ARDS. We used three genetic models: the allele, dominant, and recessive models. RESULTS: The ACE I/D polymorphism was not associated with susceptibility to ALI/ARDS for any genetic model. However, the ACE I/D polymorphism was associated with the mortality risk of ALI/ARDS in Asian subjects ( P(allele) < 0.0001, P(dominant) = 0.001, P(recessive) = 0.002). This finding remained significant after correction for multiple comparisons. CONCLUSIONS: There is a possible association between the ACE I/D polymorphism genotype and the mortality risk of ALI/ARDS in Asians.


title: Anthropological Perspectives on the Health Transition

text: The health transition is used to refer to the transitions in morbidity and mortality from infectious to noncommunicable disease, as a consequence of medical interventions and improvements in material conditions of living. Anthropologists and other social scientists have illustrated, however, that epidemiological trends are influenced by cultural, social, and behavioral determinants of health. These factors, with variations in the physical environment, have led to the continued prevalence of infectious disease concurrent with a rise in chronic and degenerative conditions. In this article, I discuss how anthropology has contributed to our understanding of health transitions, using specific diseases, conditions, and contexts to highlight the variable causes, understandings, and responses to such changes.


title: Epidermal growth factor receptor is a co-factor for transmissible gastroenteritis virus entry

text: Abstract Transmissible gastroenteritis virus (TGEV) causes severe diarrhea and high mortality in newborn piglets. It is well established that porcine intestinal epithelium is the target of the TGEV infection, however the mechanism that TGEV invades the host epithelium remains largely unknown. Aminopeptidase N (APN) is a known receptor of TGEV. This study discovered that the extracellular receptor binding domain 1 pertaining to epidermal growth receptor (EGFR) interact with TGEV spike protein. APN and EGFR synergistically promote TGEV invasion. TGEV promotes APN and EGFR clustering early in infection. Furthermore APN and EGFR synergistically stimulate PI3K/AKT as well as MEK/ERK1/2 endocytosis signaling pathways. TGEV entry is via clathrin and caveolin mediated endocytosis in IPEC-J2 cells. TGEV binds with EGFR, and subsequently promotes EGFR internalization by a clathrin-mediated endocytosis pathway. These results show that EGFR is a co-factor of TGEV, and that it plays a synergistic role with APN early in TGEV infection.


COVID-19 infection may increase the risk of parkinsonism – Remember the Spanish flu?


title: Regulation of TGF-β signaling by Smad7

text: Transforming growth factor (TGF)-β is a pleiotropic cytokine regulating a variety of cellular processes such as cell growth, differentiation, apoptosis, migration, cell adhesion, and immune response. In the well-understood classical TGF-β signaling pathway, TGF-β activates Smad signalling via its two cell surface receptors such as TβRII and ALK5/TβRI, leading to Smad-mediated transcriptional regulation. In addition, TGF-β may also activate other signaling pathways like mitogen-activated protein kinase, PI3K, etc. The signaling of TGF-β is finely regulated at different levels. Inhibitory Smads, including Smad6 and Smad7, are key regulators of TGF-β/bone morphogenetic protein (BMP) signaling by negative feedback loops. They can form stable complexes with activated type I receptors and thereby blocking the phosphorylation of R-Smads, or recruit ubiquitin E3 ligases, such as Smurf1/2, resulting in the ubiquitination and degradation of the activated type I receptors. Besides, these inhibitory Smad proteins also inhibit TGF-β/BMP signaling in the nucleus by interacting with transcriptional repressors, such as histone deacetylases, Hoxc-8, and CtBP, or disrupting the formation of the TGF-β-induced functional Smad-DNA complexes. Smad7 is in turn regulated by different stimuli, including TGF-β, IFN-γ, TNF-α as well as ultraviolet and TPA, and mediates the crosstalk between TGF-β and other signaling pathways. Deregulation of Smad7 expression has been associated with various human diseases, such as tissue fibrosis, inflammatory disease as well as carcinogenesis. Overexpression of Smad7 has been shown to antagonize TGF-β-mediated fibrosis, carcinogenesis, and inflammation, suggesting a therapeutic potential of Smad7 to treat these diseases.


title: Composite Structural Motifs of Binding Sites for Delineating Biological Functions of Proteins

text: Most biological processes are described as a series of interactions between proteins and other molecules, and interactions are in turn described in terms of atomic structures. To annotate protein functions as sets of interaction states at atomic resolution, and thereby to better understand the relation between protein interactions and biological functions, we conducted exhaustive all-against-all atomic structure comparisons of all known binding sites for ligands including small molecules, proteins and nucleic acids, and identified recurring elementary motifs. By integrating the elementary motifs associated with each subunit, we defined composite motifs that represent context-dependent combinations of elementary motifs. It is demonstrated that function similarity can be better inferred from composite motif similarity compared to the similarity of protein sequences or of individual binding sites. By integrating the composite motifs associated with each protein function, we define meta-composite motifs each of which is regarded as a time-independent diagrammatic representation of a biological process. It is shown that meta-composite motifs provide richer annotations of biological processes than sequence clusters. The present results serve as a basis for bridging atomic structures to higher-order biological phenomena by classification and integration of binding site structures.


title: Acute viral respiratory infections among children in MERS‐endemic Riyadh, Saudi Arabia, 2012–2013

text: The emergence of the Middle East Respiratory Syndrome (MERS) in Saudi Arabia has intensified focus on Acute Respiratory Infections [ARIs]. This study sought to identify respiratory viruses (RVs) associated with ARIs in children presenting at a tertiary hospital. Children (aged ≤13) presenting with ARI between January 2012 and December 2013 tested for 15 RVs using the Seeplex(R) RV15 kit were retrospectively included. Epidemiological data was retrieved from patient records. Of the 2235 children tested, 61.5% were ≤1 year with a male: female ratio of 3:2. Viruses were detected in 1364 (61.02%) children, 233 (10.4%) having dual infections: these viruses include respiratory syncytial virus (RSV) (24%), human rhinovirus (hRV) (19.7%), adenovirus (5.7%), influenza virus (5.3%), and parainfluenzavirus‐3 (4.6%). Children, aged 9–11 months, were most infected (60.9%). Lower respiratory tract infections (55.4%) were significantly more than upper respiratory tract infection (45.3%) (P < 0.001). Seasonal variation of RV was directly and inversely proportional to relative humidity and temperature, respectively, for non MERS coronaviruses (NL63, 229E, and OC43). The study confirms community‐acquired RV associated with ARI in children and suggests modulating roles for abiotic factors in RV epidemiology. However, community‐based studies are needed to elucidate how these factors locally influence RV epidemiology. J. Med. Virol. 89:195–201, 2017. © 2016 Wiley Periodicals, Inc.


title: Recent strategies and progress in identifying host factors involved in virus replication

text: Viruses are completely dependent on their host cells for the successful production of progeny viruses. At each stage of the viral life cycle an intricate interplay between virus and host takes place with the virus aiming to usurp the host cell for its purposes and the host cell trying to block the intruder from propagation. In recent years these interactions have been studied on a global level by systems biology approaches, such as RNA interference screens, transcriptomic or proteomic methodologies, and exciting new insights into the pathogen–host relationship have been revealed. In this review, we summarize the available data, give examples for important findings from such studies and point out current limitations and potential future directions.


title: Swine Diseases and Disorders

text: Abstract Swine diseases and disorders that are significant in modern, commercial swine production systems are organized by body system; the reader will need to know basic anatomy and physiology. The industry significance, etiology, epidemiology, pathogenesis, clinical signs, postmortem and histpathologic lesions, diagnostic testing, and generic treatment, control, and prevention are described. Diseases of a particular system are summarized in a differential diagnosis table.


title: Utility of the aged BALB/c mouse model to demonstrate prevention and control strategies for Severe Acute Respiratory Syndrome coronavirus (SARS-CoV)

text: The causative agent of Severe Acute Respiratory Syndrome (SARS) was identified as a coronavirus (CoV) following the outbreak of 2002–2003. There are currently no licensed vaccines or treatments for SARS-CoV infections. Potential prevention and control strategies that show promise in vitro must be evaluated in animal models. The aged BALB/c mouse model for SARS supports a high level of viral replication in association with clinical illness and disease that mimics SARS in the elderly. We tested two preventive strategies, vaccination and passive transfer of serum antibody, to determine the extent of protection achieved against SARS-CoV challenge in this model. These approaches were able to achieve or induce antibody titers sufficient to reduce viral load, protect from weight loss, and reduce or eliminate histopathologic changes in the lungs of aged mice. This study validates the utility of the aged BALB/c mouse model for evaluation of the efficacy of vaccines and immunoprophylaxis.


title: Inactivated SARS-CoV vaccine elicits high titers of spike protein-specific antibodies that block receptor binding and virus entry

text: Abstract The only severe acute respiratory syndrome (SARS) vaccine currently being tested in clinical trial consists of inactivated severe acute respiratory syndrome-associate coronavirus (SARS-CoV). However, limited information is available about host immune responses induced by the inactivated SARS vaccine. In this study, we demonstrated that SARS-CoV inactivated by β-propiolactone elicited high titers of antibodies in the immunized mice and rabbits that recognize the spike (S) protein, especially the receptor-binding domain (RBD) in the S1 region. The antisera from the immunized animals efficiently bound to the RBD and blocked binding of RBD to angiotensin-converting enzyme 2, the functional receptor on the susceptible cells for SARS-CoV. With a sensitive and quantitative single-cycle infection assay using pseudovirus bearing the SARS-CoV S protein, we demonstrated that mouse and rabbit antisera significantly inhibited S protein-mediated virus entry with mean 50% inhibitory titers of 1:7393 and 1:2060, respectively. These data suggest that the RBD of S protein is a major neutralization determinant in the inactivated SARS vaccine which can induce potent neutralizing antibodies to block SARS-CoV entry. However, caution should be taken in using the inactivated SARS-CoV as a vaccine since it may also cause harmful immune and/or inflammatory responses.


title: Guide to forensic pathology practice for death cases related to coronavirus disease 2019 (COVID-19) (Trial draft)(‡)

text: Autopsy is of great significance for elucidating the pathological changes, pathogenesis and cause of death of Coronavirus Disease 2019 (COVID-19) and can provide a theoretical basis for scientific and accurate prevention and control of its outbreak. Based on related laws and regulations, such as the Law of the People’s Republic of China on Prevention and Control of Infectious Diseases, clinical manifestations and epidemiological characteristics of COVID-19 and guidelines on the prevention and control of this epidemic, combined with the practical work of forensic pathology examinations, we developed the Guide to Forensic Pathology Practice for Death Cases Related to Coronavirus Disease 2019 (COVID-19) (Trial Draft). This guide describes the background investigation of the death cases, autopsy room requirements, personal prevention and protections, external examinations, autopsy practices and auxiliary examinations, and thus offers a reference for forensic and pathological examination institutions and staff.


title: Fading vision: knowledge translation in the implementation of a public health policy intervention

text: BACKGROUND: In response to several high profile public health crises, public health renewal is underway in Canada. In the province of British Columbia, the Ministry of Health initiated a collaborative evidence-informed process involving a steering committee of representatives from the six health authorities. A Core Functions (CF) Framework was developed, identifying 21 core public health programs. For each core program, an evidence review was conducted and a model core program paper developed. These documents were distributed to health authorities to guide development of their own renewed public health services. The CF implementation was conceptualized as an embedded knowledge translation process. A CF coordinator in each health authority was to facilitate a gap analysis and development of a performance improvement plan for each core program, and post these publically on the health authority website. METHODS: Interviews (n = 19) and focus groups (n = 8) were conducted with a total of 56 managers and front line staff from five health authorities working in the Healthy Living and Sexually Transmitted Infection Prevention core programs. All interviews and focus groups were digitally recorded, transcribed and verified by the project coordinator. Five members of the research team used NVivo 9 to manage data and conducted a thematic analysis. RESULTS: Four main themes emerged concerning implementation of the CF Framework generally, and the two programs specifically. The themes were: ‘you’ve told me what, now tell me how’; ‘the double bind’; ‘but we already do that’; and the ‘selling game.’ Findings demonstrate the original vision of the CF process was lost in the implementation process and many participants were unaware of the CF framework or process. CONCLUSIONS: Results are discussed with respect to a well-known framework on the adoption, assimilation, and implementation of innovations in health services organizations. Despite attempts of the Ministry of Health and the Steering Committee to develop and implement a collaborative, evidence-informed policy intervention, there were several barriers to the realization of the vision for core public health functions implementation, at least in the early stages. In neglecting the implementation process, it seems unlikely that the expected benefits of the public health renewal process will be realized.


title: The enhanced replication of an S-intact PEDV during coinfection with an S1 NTD-del PEDV in piglets

text: Abstract Porcine epidemic diarrhea virus (PEDV) variants having a large deletion in the N-terminal domain of the S1 subunit of spike (S) protein were designated as S1 NTD-del PEDVs. They replicate well in experimentally infected pigs. However, on farms they often co-infect pigs with the PEDV containing an intact S protein (S-intact PEDV). We aimed to characterize viral replication and pathogenesis in neonatal gnotobiotic pigs infected simultaneously with the two types of PEDV using two recombinant PEDVs: icPC22A and its S1 NTD-del form icPC22A-S1Δ197. Additionally, viral replication was compared in Vero and IPEC-DQ cells at the presence of bovine mucin (BM), porcine gastric mucin (PGM), swine bile and bile acids during inoculation. In the pigs coinfected with icPC22A and icPC22A-S1Δ197, icPC22A replicated to a higher peak titer than its infection of pigs without the presence of icPC22A-S1Δ197. The severity of diarrhea and intestinal atrophy were similar between icPC22A and the coinfection groups, but were significantly higher than icPC22A-S1Δ197 group. In Vero and IPEC-DQ cells, certain concentrations of BM, PGM, bile and bile acids increased significantly the infectivity of icPC22A but had no or negative effects on icPC22A-S1Δ197. These results indicated that the replication of the S-intact PEDV was enhanced during coinfection in piglets. This observation may be explained partially by the fact that mucin, bile and bile acids in gastrointestinal tract had facilitating effects on the infection of S-intact PEDV, but no/inhibition effects on S1 NTD-del PEDV.


title: Bilateral pulmonary nodules and acute respiratory failure in a 22-year-old man with dyspnoea and fever

text: Can you diagnose the cause of this man’s bilateral pulmonary nodules and acute respiratory failure? http://ow.ly/NfED30dDBzm


title: Extended model of topological relations between spatial objects in geographic information systems

text: Abstract This paper presents an extended model for describing topological relations between two sets (objects) in geographic information systems (GIS). First, based on the definition of the topological relations between two objects, we uncover a sequence of topological relations between two convex sets. Second, an extended model for topological relations between two sets is proposed based on the new definition. The topological relations between two convex sets are expressed as a sequence of 4×4 matrices, which are the topological properties of Ao ∩Bo, Ao\B, Bo\A, ∂A∩∂B. The model is also extended for handling the properties of the topological relations between two non-convex sets, where the factor of first fundamental group is added to A∪B to handle these complex relations. The results show that the number of topological relations between the two sets is not as simple as finite but infinite and can be approximated by a sequence of matrices.


title: Screening and identification of T helper 1 and linear immunodominant antibody-binding epitopes in spike 1 domain and membrane protein of feline infectious peritonitis virus

text: Abstract Feline infectious peritonitis virus (FIP virus: FIPV) causes a fatal disease in wild and domestic cats. The development of an FIP-preventive vaccine requires an antigen that does not induce antibody-dependent enhancement, and T helper (Th)1 activity plays an important role in protect against FIPV infection. In the present study, we identified synthetic peptides including Th1 and a linear immunodominant antibody-binding epitope in the S1 domain and M protein of FIPV. We also identified peptides that strongly induce Th1 activity from those derived from the structural proteins (S, M, and N proteins) of FIPV based on this and previous studies (Satoh et al. [19]). No Th1 epitope-containing peptide was identified in the peptides derived from the S1 domain of type I FIPV. In contrast, 7 Th1 epitope-containing peptides were identified in the S1 domain of type II FIPV, and no linear immunodominant antibody-binding epitope was contained in any of these peptides. Eleven Th1 epitope-containing peptides common to each serotype were identified in the M protein-derived peptides, and 2 peptides (M-11 and M-12) contained the linear immunodominant antibody-binding epitope. Of the peptides derived from the S, M, and N proteins of FIPV, those that induced significantly stronger Th1 activity than that of the FIPV antigen were rescreened, and 4 peptides were identified. When 3 of these peptides (M-9, I-S2-15, and II-S1-24) were selected and administered with CpG-ODNs to SPF cats, M-9 and II-S1-24 induced Th1 activity. Our results may provide important information for the development of a peptide-based vaccine against FIPV infection.


title: Routes of transmission of influenza A H1N1, SARS CoV, and norovirus in air cabin: Comparative analyses

text: Identifying the exact transmission route(s) of infectious diseases in indoor environments is a crucial step in developing effective intervention strategies. In this study, we proposed a comparative analysis approach and built a model to simulate outbreaks of 3 different in‐flight infections in a similar cabin environment, that is, influenza A H1N1, severe acute respiratory syndrome (SARS) coronavirus (CoV), and norovirus. The simulation results seemed to suggest that the close contact route was probably the most significant route (contributes 70%, 95% confidence interval [CI]: 67%‐72%) in the in‐flight transmission of influenza A H1N1 transmission; as a result, passengers within 2 rows of the index case had a significantly higher infection risk than others in the outbreak (relative risk [RR]: 13.4, 95% CI: 1.5‐121.2, P = .019). For SARS CoV, the airborne, close contact, and fomite routes contributed 21% (95% CI: 19%‐23%), 29% (95% CI: 27%‐31%), and 50% (95% CI: 48%‐53%), respectively. For norovirus, the simulation results suggested that the fomite route played the dominant role (contributes 85%, 95% CI: 83%‐87%) in most cases; as a result, passengers in aisle seats had a significantly higher infection risk than others (RR: 9.5, 95% CI: 1.2‐77.4, P = .022). This work highlighted a method for using observed outbreak data to analyze the roles of different infection transmission routes.


title: Infecciones en el paciente crítico

text: Resumen Introducción Las infecciones son muy frecuentes en los pacientes que se encuentran ingresados en los servicios de medicina intensiva, siendo unas veces motivo de ingreso y en otras la infección se adquiere durante el ingreso. Epidemiologia Las causas más frecuentes de infección adquirida en la comunidad que precisa ingreso en la UCI son las infecciones respiratorias, infecciones urinarias y las infecciones del sistema nervioso central. Dentro de las infecciones adquiridas en la UCI, las asociadas a dispositivos son las más frecuentes. Etiología Los gérmenes más frecuentes en la UCI son los Gram negativos. Etiopatogenia. En el paciente crítico se aúnan factores, haciéndolos especialmente vulnerables a las infecciones. Manifestaciones clínicas Dependerán de la localización de la infección. Diagnóstico Debe ser precoz dada su alta mortalidad. Pronóstico Las infecciones nosocomiales se asocian con un aumento de la mortalidad y la estancia. Tratamiento El retraso en el tratamiento se asocia con un aumento de la mortalidad. Abstract Introduction Infections are very frequent in patients who are admitted to Intensive Care Units, sometimes being a reason for admission and in others the infection is acquired during ICU stay. Epidemiology The most frequent causes of acquired infection in the community that require admission to the ICU are respiratory infections, urinary tract infections and infections of the central nervous system. Among the infections acquired in the ICU, devices-associated infections are the most frequent. Etiology The most frequent in ICU are Gram negative pathogens. Etiopathogenesis In the critical patient, several factors are combined making them especially vulnerable to infections. Clinical manifestations Depends on the location of the infection. Diagnosis It must be early due to its increased mortality. Prognosis Nosocomial infections are associated with an increase in mortality and in the length of stay. Treatment The delay in treatment is associated with an increase in mortality.


title: Babesial infection in the Madagascan flying fox, Pteropus rufus É. Geoffroy, 1803

text: BACKGROUND: Babesiae are erythrocytic protozoans, which infect the red blood cells of vertebrate hosts to cause disease. Previous studies have described potentially pathogenic infections of Babesia vesperuginis in insectivorous bats in Europe, the Americas and Asia. To date, no babesial infections have been documented in the bats of Madagascar, or in any frugivorous bat species worldwide. RESULTS: We used standard microscopy and conventional PCR to identify babesiae in blood from the endemic Madagascan flying fox (Pteropus rufus). Out of 203 P. rufus individuals captured between November 2013 and January 2016 and screened for erythrocytic parasites, nine adult males (4.43%) were infected with babesiae. Phylogenetic analysis of sequences obtained from positive samples indicates that they cluster in the Babesia microti clade, which typically infect felids, rodents, primates, and canids, but are distinct from B. vesperuginis previously described in bats. Statistical analysis of ecological trends in the data suggests that infections were most commonly observed in the rainy season and in older-age individuals. No pathological effects of infection on the host were documented; age-prevalence patterns indicated susceptible-infectious (SI) transmission dynamics characteristic of a non-immunizing persistent infection. CONCLUSIONS: To our knowledge, this study is the first report of any erythrocytic protozoan infecting Madagascan fruit bats and the first record of a babesial infection in a pteropodid fruit bat globally. Given the extent to which fruit bats have been implicated as reservoirs for emerging human pathogens, any new record of their parasite repertoire and transmission dynamics offers notable insights into our understanding of the ecology of emerging pathogens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-019-3300-7) contains supplementary material, which is available to authorized users.


title: Detección de serovares de Salmonella en terneros de crianza artificial de la región lechera Mar y Sierras, Argentina

text: Resumen La salmonelosis es una de las enfermedades bacterianas que afectan el tracto digestivo de los terneros y provocan en ellos diarrea. Con el objetivo de estudiar la prevalencia de los distintos serovares de Salmonella en terneros de crianza artificial y determinar la asociación con signos diarreicos, se realizó un estudio epidemiológico con diseño transversal en la región lechera Mar y Sierras, ubicada en la Provincia de Buenos Aires (Argentina). Mediante hisopado de mucosa rectal, se muestrearon 726 terneros en período de crianza distribuidos en 50 establecimientos lecheros de dicha zona, se incluyeron animales con signos diarreicos y sin estos. Los aislamientos identificados como Salmonella spp. fueron tipificados utilizando antisueros poli- y monovalentes dirigidos contra antígenos somáticos, flagelares y capsulares (Vi). Salmonella spp. se detectó en el 36% de los establecimientos y los serovares hallados fueron S. Mbandaka, S. Anatum, S. Typhimurium, S. Dublin, S. Montevideo, S. Meleagridis, S. Newport, S. Seftemberg, S. subesp.16,7:z1, S. Infantis y S. Give. El 5,5% de los terneros fueron positivos y aquellos terneros con signología diarreica presentaron 5,9 veces más probabilidad de estar infectados con Salmonella spp. que aquellos que no tuvieron signos. La edad de los terneros positivos osciló desde un día hasta 53 días de vida; la mayor frecuencia se detectó al segundo día de nacidos. Se concluye que 11 serovares de Salmonella están presentes en más de un tercio de los establecimientos lecheros de la región lechera Mar y Sierras y que estos serovares mostraron estar asociados a la existencia de signos diarreicos en los terneros, sobre todo a la presencia de moco en las heces. La prevalencia de Salmonella fue mayor en terneros de menos de 21 días de vida. Abstract Salmonellosis in calves is a bacterial disease that affects their digestive tract causing diarrhea. A cross-sectional epidemiological study was carried out with the aim of studying the prevalence of various serovars of Salmonella in calves and their relationship with diarrhea signs. The study was conducted in Mar and Sierras Dairy Basin located in Buenos Aires province, Argentina. Seven hundred and twenty six calves both with diarrhea signs or not were sampled by rectal mucosa swab in 50 dairy farms during the rearing period. Isolates identified as Salmonella spp. were classified using polyvalent and monovalent antisera against somatic, flagellar and capsule antigens (Vi). Salmonella spp. was found in 36% of the farms and serotypes were: S. Mbandaka, S. Anatum, S. Typhimurium, S. Dublin, S. Montevideo, S. Meleagridis, S. Newport, S. Seftemberg, S. subesp. 16,7:z1, S. Infantis, S. Give. A percentage of 5.5% calves was positive and calves showing diarrheal signs were 5.9 times more likely to be infected with Salmonella spp. than those having no signs. The age of positive calves ranged from the first day of life to 53; the second day being the most frequent time. In conclusion, 11 Salmonella serovars were detected in one out of 3dairy farms in Mar and Sierras Dairy Basin, and not only were these serovars associated with diarrhea signs including the presence of mucus in feces, but they were also more prevalent among calves aged up to 21 days.


title: The mechanism of RNA recombination in poliovirus

text: Abstract We have investigated RNA recombination among poliovirus genomes by analyzing both intratypic and intertypic recombinant crosses involving the same defined genetic markers. Sequence analysis of the recombinant junctions of 13 nonsibling intertypic recombinants showed that intertypic RNA recombination is not site-specific, nor does it require extensive homology between the recombining parents at the crossover site. To discriminate between breaking-rejoining and copy choice mechanisms of RNA recombination, we have inhibited the replication of the recombining parents independently and found opposite effects on the frequency of genetic recombination in intratypic crosses. The results strongly support a copy choice mechanism for RNA recombination, in which the viral RNA polymerase switches templates during negative strand synthesis.