title: Porcine deltacoronavirus (PDCoV) infection suppresses RIG-I-mediated interferon-β production

text: Abstract Porcine deltacoronavirus (PDCoV), an emerging animal coronavirus causing enteric disease in pigs, belongs to the newly identified Deltacoronavirus genus in the Coronaviridae family. Although extensive studies have been carried out to investigate the regulation of interferon (IFN) responses by alphacoronaviruses, betacoronaviruses, and gammacoronaviruses, little is known about this process during deltacoronavirus infection. In this study, we found that PDCoV infection fails to induce, and even remarkably inhibits, Sendai virus- or poly(I: C)-induced IFN-β production by impeding the activation of transcription factors NF-κB and IRF3. We also found that PDCoV infection significantly suppresses the activation of IFN-β promoter stimulated by IRF3 or its upstream molecules (RIG-I, MDA5, IPS-1, TBK1, IKKε) in the RIG-I signaling pathway, but does not counteract its activation by the constitutively active mutant of IRF3 (IRF3–5D). Taken together, our results demonstrate that PDCoV infection suppresses RIG-I-mediated IFN signaling pathway, providing a better understanding of the PDCoV immune evasion strategy.


title: Interactions between M protein and other structural proteins of severe, acute respiratory syndrome-associated coronavirus

text: Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) structural proteins (S, E, M, and NC) localize in different subcellular positions when expressed individually. However, SARS-CoV M protein is co-localized almost entirely with S, E, or NC protein when co-expressed in the cells. On the other hand, only partial co-localization was observed when S and E, S and NC, or E and NC were co-expressed in the cells. Interactions between SARS-CoV M and other structural proteins but not interactions between S and E, S and NC, or E and NC were further demonstrated by co-immunoprecipitation assay. These results indicate that SARS-CoV M protein, similar to the M proteins of other coronaviruses, plays a pivotal role in virus assembly. The cytoplasmic C-terminus domain of SARS-CoV M protein was responsible for binding to NC protein. Multiple regions of M protein interacted with E and S proteins. A model for the interactions between SARS-CoV M protein and other structural proteins is proposed. This study helps us better understand protein-protein interactions during viral assembly of SARS-CoV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11373-008-9278-3) contains supplementary material, which is available to authorized users.


Herbs that might be effective for the management of COVID-19: A bioinformatics analysis on anti-tyrosine kinase property


title: Cyclodextrins in non-viral gene delivery

text: Abstract Cyclodextrins (CDs) are naturally occurring cyclic oligosaccharides. They consist of (α-1,4)-linked glucose units, and possess a basket-shaped topology with an “inner–outer” amphiphilic character. Over the years, substantial efforts have been undertaken to investigate the possible use of CDs in drug delivery and controlled drug release, yet the potential of CDs in gene delivery has received comparatively less discussion in the literature. In this article, we will first discuss the properties of CDs for gene delivery, followed by a synopsis of the use of CDs in development and modification of non-viral gene carriers. Finally, areas that are noteworthy in CD-based gene delivery will be highlighted for future research. Due to the application prospects of CDs, it is anticipated that CDs will continue to emerge as an important tool for vector development, and will play significant roles in facilitating non-viral gene delivery in the forthcoming decades.


title: Extraordinary GU-rich single-strand RNA identified from SARS coronavirus contributes an excessive innate immune response

text: Abstract A dangerous cytokine storm occurs in the SARS involving in immune disorder, but many aspects of the pathogenetic mechanism remain obscure since its outbreak. To deeply reveal the interaction of host and SARS-CoV, based on the basic structural feature of pathogen-associated molecular pattern, we created a new bioinformatics method for searching potential pathogenic molecules and identified a set of SARS-CoV specific GU-rich ssRNA fragments with a high-density distribution in the genome. In vitro experiments, the result showed the representative SARS-CoV ssRNAs had powerful immunostimulatory activities to induce considerable level of pro-inflammatory cytokine TNF-a, IL-6 and IL-12 release via the TLR7 and TLR8, almost 2-fold higher than the strong stimulatory ssRNA40 that was found previously from other virus. Moreover, SARS-CoV ssRNA was able to cause acute lung injury in mice with a high mortality rate in vivo experiment. It suggests that SARS-CoV specific GU-rich ssRNA plays a very important role in the cytokine storm associated with a dysregulation of the innate immunity. This study not only presents new evidence about the immunopathologic damage caused by overactive inflammation during the SARS-CoV infection, but also provides a useful clue for a new therapeutic strategy.


title: Factors preventing materno-fetal transmission of SARS-CoV-2

text: Although many pregnant women have been infected by coronavirus, the presence of intrauterine vertical transmission has not been conclusively reported yet. What prevents this highly contagious virus from reaching the fetus? Is it only the presence of a strong placental barrier, or is it the natural absence of the some receptor that the viruses use for transmission? We, therefore, need to comprehensively understand the mechanism of action of the mammalian epithelial barriers located in two different organs with functional similarity. The barriers selected as potential targets by SARS-CoV-2 are the alveolo-capillary barrier (ACB), and the syncytio-capillary barrier (SCB). Caveolae are omega-shaped structures located on the cell membrane. They consist of caveolin-1 protein (Cav-1) and are involved in the internalisation of some viruses. By activating leukocytes and nuclear factor-κB, Cav-1 initiates inflammatory reactions. The presence of more than one Cav-1 binding sites on coronavirus is an important finding supporting the possible relationship between SARS-CoV-2-mediated lung injury. While the ACB cells express Cav-1 there is no caveolin expression in syncytiotrophoblasts. In this short review, we will try to explain our hypothesis that the lack of caveolin expression in the SCB is one of the most important physiological mechanisms that prevents vertical transmission of SARS-CoV-2. Since the physiological Cav-1 deficiency appears to prevent acute cell damage treatment algorithms could potentially be developed to block this pathway in the non-pregnant population affected by SARS-CoV-2.


title: Chronic obstructive pulmonary disease

text: Summary Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities. The main cause is smoking tobacco, but other factors have been identified. Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli. The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both. Comorbidities include ischaemic heart disease, diabetes, and lung cancer. Bronchodilators constitute the mainstay of treatment: β2 agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids). Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification. Future research should be directed towards the development of agents that notably affect the course of disease.


title: Bilio-pancreatic endoscopy during COVID-19 pandemic

text: On 31 December 2019, the WHO China Country Office was informed of cases of pneumonia of unknown etiology detected in Wuhan (Hubei Province of China). In January 2020, a new coronavirus named SARS-CoV2 was isolated and, since that time, SARS-CoV2 related disease (COVID-19) rapidly spread all over the world becoming pandemic in March 2020. The COVID-19 outbreak dramatically affected the public-health and the health-care facilities organization. Bilio-pancreatic endoscopy is considered a high-risk procedure for cross-contamination and, even though it is not directly involved in COVID-19 diagnosis and management, its reorganization is crucial to guarantee high standards of care minimizing the risk of SARS-CoV2 transmission among patients and health-care providers. Bilio-pancreatic endoscopic procedures often require a short physical distance between the endoscopist and the patient for a long period of time, a frequent exchange of devices, the involvement of a large number of personnel, the use of complex endoscopes difficult to reprocess. On this basis, endoscopic units should take precautions with adjusted management of bilio-pancreatic endoscopy. The aim of this article is to discuss the approach to bilio-pancreatic endoscopy in the COVID-19 era with focus on diagnostic algorithms, indications, management of the endoscopic room, proper use of Personal Protective Equipment and correct reprocessing of instrumentation.


title: Treatment, outcomes and costs of asthma exacerbations in Chilean children: a prospective multicenter observational study

text: Abstract Objective To describe potential regional variations in therapies for severe asthma exacerbations in Chilean children and estimate the associated health expenditures. Methods Observational prospective cohort study in 14 hospitals over a one-year period. Children five years of age or older were eligible for inclusion. Days with oxygen supply and pharmacological treatments received were recorded from the clinical chart. A basic asthma hospitalization basket was defined in order to estimate the average hospitalization cost for a single patient. Six months after discharge, new visits to the Emergency Room (ER), use of systemic corticosteroids and adherence to the controller treatment were evaluated. Results 396 patients were enrolled. Patients from the public health system and from the north zone received significantly more days of oxygen, systemic corticosteroids and antibiotics. Great heterogeneity in antibiotic use among the participating hospitals was found, from 0 to 92.3% (ICC 0.34, 95% CI 0.16–0.52). The use of aminophylline, magnesium sulfate and ketamine varied from 0 to 36.4% between the different Pediatric Intensive Care Units (ICC 0.353, 95% CI 0.010–0.608). The average cost per inpatient was of $1910 USD. 290 patients (73.2%) completed the follow-up six months after discharge. 76 patients (26.2%) were not receiving any controller treatment and nearly a fourth had new ER visits and use of systemic corticosteroids due to new asthma exacerbations. Conclusions Considerable practice variation in asthma exacerbations treatment was found among the participating hospitals, highlighting the poor outcome of many patients after hospital discharge, with an important health cost.


La Dermatología Española en la era del COVID-19


title: The journey of remdesivir: from Ebola to COVID-19

text: Countries around the world are currently fighting the coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a betacoronavirus, belonging to the same genus as severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV. Currently, there are no proven antiviral therapies for COVID-19. Numerous clinical trials have been initiated to identify an effective treatment. One leading candidate is remdesivir (GS-5734), a broad-spectrum antiviral that was initially developed for the treatment of Ebola virus (EBOV). Although remdesivir performed well in preclinical studies, it did not meet efficacy endpoints in a randomized trial conducted during an Ebola outbreak. Remdesivir holds promise for treating COVID-19 based on in vitro activity against SARS-CoV-2, uncontrolled clinical reports, and limited data from randomized trials. Overall, current data are insufficient to judge the efficacy of remdesivir for COVID-19, and the results of additional randomized studies are eagerly anticipated. In this narrative review, we provide an overview of Ebola and coronavirus outbreaks. We then summarize preclinical and clinical studies of remdesivir for Ebola and COVID-19.


title: Comparison of FilmArray Respiratory Panel and laboratory-developed real-time reverse transcription–polymerase chain reaction assays for respiratory virus detection

text: Abstract The FilmArray Respiratory Panel (Idaho Technology) is a highly multiplexed respiratory virus real-time polymerase chain reaction (PCR) assay. Eighty-four respiratory viruses identified by laboratory-developed real-time reverse transcription–PCR assays (LDA) or by viral cultures were mixed and tested by FilmArray to assess its performance. FilmArray identified 72 (90%) of 80 viruses also detected by LDA. Six of the 8 viruses not detected by FilmArray had PCR cycle threshold values >35. Compared to LDA, FilmArray showed comparable sensitivity when used to test serial dilutions of virus mixtures and good agreement with negative samples. With the use of 1 FilmArray instrument, 7 clinical samples could be analyzed and reported in an 8-h shift compared to 20 using LDA and 1 real-time detection instrument. While the FilmArray was rapid and easy to use, its low throughput and qualitative results may be a disadvantage in some clinical settings.


title: Molecular characteristic and pathogenicity analysis of a virulent recombinant avain infectious bronchitis virus isolated in China

text: ABSTRACT A virulent infectious bronchitis virus (IBV), designated as CK/CH/GD/QY16 (referred as QY16), was isolated from a diseased chicken farm in Guangdong province, China, in 2016. The complete genome of the strain was sequenced and analyzed. The results show that the genome of QY16 consists of 27,670 nucleotides, excluding poly (A) tail, and that its genome organization is 5’ UTR-1a-1b-S-3a-3b-E-M-4b-4c-5a-5b-N-6b-3’ UTR-poly (A) tail. Sequence comparison among QY16 and other IBV strains was conducted and its results demonstrate that the S1 gene of QY16 has the highest nucleotide sequence identity with that of 4/91, and the other part of its genome is highly similar to that of YX10. The results of the phylogenic analysis show that the entire genome of QY16 and most of the QY16 genes are located in the same cluster as those of YX10, except for the S1 gene which is located in the same cluster with that of 4/91. It has been further confirmed by the RDP and SimPlot analysis that QY16 is a recombinant strain deriving from YX10 (as the major parental sequence) and 4/91 (as the minor parental sequence), and that the recombination occurs in a region which includes the 3’-terminal 1b sequence (85 nt) and the 5’-terminal S1 protein gene sequence (1,466 nt). The results of the vaccination-challenge test suggest that QY16 is a nephropathogenic strain of IBV and that the vaccine strains–H120 and 4/91—cannot provide effective protection against it. These results indicate that the continuing evolution of IBV strains by genetic drift and genetic recombination may lead to IBV outbreaks even among the vaccinated chickens in China.


title: Need for integrative thinking to fight against emerging infectious diseases. Proceedings of the 5th seminar on emerging infectious diseases, March 22, 2016 – current trends and proposals

text: Abstract We present here the proceedings of the 5th seminar on emerging infectious diseases, held in Paris on March 22nd, 2016, with seven priority proposals that can be outlined as follows: encourage research on the prediction, screening and early detection of new risks of infection; develop research and surveillance concerning transmission of pathogens between animals and humans, with their reinforcement in particular in intertropical areas (“hot-spots”) via public support; pursue aid development and support in these areas of prevention and training for local health personnel, and foster risk awareness in the population; ensure adapted patient care in order to promote adherence to treatment and to epidemic propagation reduction measures; develop greater awareness and better education among politicians and healthcare providers, in order to ensure more adapted response to new types of crises; modify the logic of governance, drawing from all available modes of communication and incorporating new information-sharing tools; develop economic research on the fight against emerging infectious diseases, taking into account specific driving factors in order to create a balance between preventive and curative approaches.


title: Distancing Bonus Or Downscaling Loss? The Changing Livelihood of Us Online Workers in Times of COVID‐19

text: We draw on data from the Online Labour Index and interviews with freelancers in the United States securing work on online platforms, to illuminate effects of the COVID‐19 pandemic. The pandemic's global economic upheaval is shuttering shops and offices. Those able to do so are now working remotely from their homes. They join workers who have always been working remotely: freelancers who earn some or all of their income from projects secured via online labour platforms. Data allow us to sketch a first picture of how the initial months of the COVID‐19 pandemic have affected the livelihoods of online freelancers. The data shows online labour demand falling rapidly in early March 2020, but with an equally rapid recovery. We also find significant differences between countries and occupations. Data from interviews make clear jobs are increasingly scarce even as more people are creating profiles and seeking freelance work online.


title: Prevalence of enteric viruses among hospital patients with AIDS in Kinshasa, Zaire

text: Abstract Diarrhoea is the most common manifestation of acquired immunodeficiency syndrome (AIDS) in Africa. Numerous parasitic or bacterial agents have been implicated, but a pathogen-specific aetiology has not been found. Enteric viruses (i.e., rotavirus, small round structured viruses, coronavirus, and adenovirus) were detected by enzyme-linked immunosorbent assay or electron microscopy in faecal specimens of 17% of 198 consecutive adult admissions to a general medical ward of an urban hospital in Kinshasa, Zaire. Overall, 57% of patients were seropositive for infection with human immunodeficiency virus (HIV) 1; of these, 50% were classified as World Health Organization Aids stage IV. The prevalence of enteric viruses in stool specimens did not differ significantly between patients with and without HIV infection, and was not associated with acute or chronic diarrhoea, or constitutional symptoms. However, a trend (P = 0·14) towards greater frequency of virus in stools from patients in the lower 3 quintiles of the CD4/CD8 T cell ratio was seen. This trend approached statistical significance (P = 0·07) with stratification by HIV infection. Although we found no evidence in this population to support a major pathogenic role for these viruses alone in the enteropathy of AIDS, increased viral shedding was weakly associated with immunodeficiency.


title: Effect of TLR agonist on infections bronchitis virus replication and cytokine expression in embryonated chicken eggs

text: Abstract Avian infectious bronchitis (IB) is an acute, highly infectious and contagious viral disease of chickens caused by avian infectious bronchitis virus (IBV) belonging to the genus Coronavirus and family Coronaviridae. It can affect all age groups of birds. The toll-like receptors (TLRs) are a major class of innate immune pattern recognition receptors that have a key role in immune response and defense against various infections.The TLRs are essential for initiation of innate immune responses and in the development of adaptive immune responses. An in ovo model was employed to study the antiviral activity of TLR ligands (Pam3CSK4, LPS and CpG ODN) on replication of IBV. It was hypothesized that optimum dose and specific timing of TLR ligands may reduce viral load of IBV in specific pathogen free (SPF) embryonated chicken eggs (ECEs). Further, the mechanism involved in the TLR-mediated antiviral response in chorioallantoic membrane (CAM) of ECEs was investigated. The ECEs of 9–11 days old were treated with different doses (high, intermediate and low) of TLR-2 (Pam3CSK4), TLR-4 (LPS) and TLR-21 (CpG ODN) ligands. In addition, to know the timing of TLR ligand treatment, six time intervals were analyzed viz. 36, 24 and 12 h prior to infection, time of infection (co-administration of TLR ligands and avian IBV) and 12 and 24 h post-IBV infection. For studying the relative expression of immuno-stimulatory genes (IFN-α, IFN-β, IFN-γ, IL-1β, iNOS and OAS) in CAM, TLR ligands were administered through intra-allantoicroute and CAM were collected at 4, 8 and 16 h post treatment. The results demonstrated that intermediate dose of all the three TLR ligands significantly reduced virus titers and used in the present study. However, the LPS reduced virus titer pre- and post-IBV infection but Pam3CSK4 and CpG ODN reduced only pre-IBV infection. Further analysis showed that TLR ligands induced IFN-γ, IL-1β and IFN stimulated genes viz. iNOS and OAS genes in CAM. The present study pointed towards the novel opportunities for rational design of LPS as immuno-stimulatory agent in chickens with reference to IBV. It may be speculated that in ovo administration of these TLR ligands may enhance resistance against viral infection in neonatal chicken and may contribute towards the development of more effective and safer vaccines including in ovo vaccines.


title: Intracerebral delivery of small interfering RNAs (siRNAs) using adenoviral vector protects mice against lethal peripheral rabies challenge

text: Abstract To investigate the potential of RNA interference (RNAi) as antiviral agent against rabies, two small interfering RNAs (siRNAs) targeting rabies virus (RABV) nucleoprotein (N) and polymerase (L) genes were designed and evaluated. Both siRNAs knockdown or silenced the target RABV genes as evaluated in a plasmid based transient expression model. For efficient delivery, adenoviruses expressing the siRNAs were constructed and antiviral potential of the delivered siRNAs was investigated in BHK-21 cells. When cells treated with adenoviruses expressing siRNAs were challenged with RABV, there was 88.35±2.4% and 41.52±9.3% reduction in RABV multiplication in infected cells with siRNAs targeting RABV-N and L genes, respectively. Relative quantification of RABV transcripts using real-time PCR revealed knockdown of both RABV-N and L gene transcripts, however, significant reduction was observed only with adenovirus expressing siRNA against RABV-N. When mice treated intracerebrally with adenoviruses expressing siRNAs were challenged peripherally with lethal RABV by the intramuscular route in masseter muscle, there was 66.6% and 33.3% protection with adenoviruses expressing siRNAs against RABV-N and L genes, respectively. These results demonstrated that adenovirus expressing siRNA against RABV-N efficiently inhibited the RABV multiplication both, in vitro and in vivo and conferred significant protection against lethal RABV challenge. This supported the hypothesis that RNAi, based on siRNA targeting RABV-N gene can prevent RABV infection and holds the potential of RNAi as an approach to prevent rabies infection.


title: RNA granules: the good, the bad and the ugly

text: Processing bodies (PBs) and Stress granules (SGs) are the founding members of a new class of RNA granules, known as mRNA silencing foci, as they harbor transcripts circumstantially excluded from the translationally active pool. PBs and SGs are able to release mRNAs thus allowing their translation. PBs are constitutive, but respond to stimuli that affect mRNA translation and decay, whereas SGs are specifically induced upon cellular stress, which triggers a global translational silencing by several pathways, including phosphorylation of the key translation initiation factor elF2alpha, and tRNA cleavage among others. PBs and SGs with different composition may coexist in a single cell. These macromolecular aggregates are highly conserved through evolution, from unicellular organisms to vertebrate neurons. Their dynamics is regulated by several signaling pathways, and depends on microfilaments and microtubules, and the cognate molecular motors myosin, dynein, and kinesin. SGs share features with aggresomes and related aggregates of unfolded proteins frequently present in neurodegenerative diseases, and may play a role in the pathology. Virus infections may induce or impair SG formation. Besides being important for mRNA regulation upon stress, SGs modulate the signaling balancing apoptosis and cell survival. Finally, the formation of nuclear stress bodies (nSBs), which share components with SGs, and the assembly of additional cytosolic aggregates containing RNA—the UV granules and the Ire1 foci—, all them induced by specific cell damage factors, contribute to cell survival.


title: Pathogenesis and Diagnostic Approaches of Avian Infectious Bronchitis

text: Infectious bronchitis (IB) is one of the major economically important poultry diseases distributed worldwide. It is caused by infectious bronchitis virus (IBV) and affects both galliform and nongalliform birds. Its economic impact includes decreased egg production and poor egg quality in layers, stunted growth, poor carcass weight, and mortality in broiler chickens. Although primarily affecting the respiratory tract, IBV demonstrates a wide range of tissues tropism, including the renal and reproductive systems. Thus, disease outcome may be influenced by the organ or tissue involved as well as pathotypes or strain of the infecting virus. Knowledge on the epidemiology of the prevalent IBV strains in a particular region is therefore important to guide control and preventions. Meanwhile previous diagnostic methods such as serology and virus isolations are less sensitive and time consuming, respectively; current methods, such as reverse transcription polymerase chain reaction (RT-PCR), Restriction Fragment Length Polymorphism (RFLP), and sequencing, offer highly sensitive, rapid, and accurate diagnostic results, thus enabling the genotyping of new viral strains within the shortest possible time. This review discusses aspects on pathogenesis and diagnostic methods for IBV infection.


title: Epidemiological characteristics of pulmonary tuberculosis in Shandong, China, 2005–2017: A retrospective study

text: This study aimed to analyze the epidemiology of pulmonary tuberculosis (PTB) and gained insight into the future TB control plan in China. We extracted epidemiological, clinical, and geographic data from TB prevention and control institutions in 6 cities of Shandong province, China, during 2005 to 2017. Among 224,480 diagnosed PTB, rural residents accounted for 93%, smear-positive PTB 52%, and new cases 92%. The incidence rate of overall PTB declined from 40.8 to 26.25 per 100,000 during 2005 to 2017. Except smear-negative PTB (7.57–19.87 per 100,000), the incidence of smear-positive PTB and all that stratified by age, sex, and treatment history decreased. With 80% reduction, the incidence of smear-positive PTB (6.38 per 100,000) and relapse cases (1.01 per 100,000) were already very low in 2017. With persistent efforts to combat TB, the disease burden had shifted from smear-positive PTB to smear-negative PTB. While new cases need continuous attention, further reducing the incidence of smear-negative PTB and elderly patients may have a greater impact on future TB control.


title: How Might AI and Chest Imaging Help Unravel COVID-19’s Mysteries?

text: Artificial intelligence (AI) has the potential to expand the role of chest imaging in COVID-19 beyond diagnosis to enable risk stratification, treatment monitoring, and discovery of novel therapeutic targets. AI’s power to generate models from large volumes of information – fusing molecular, clinical, epidemiological, and imaging data – may accelerate solutions to detect, contain, and treat COVID-19.


Italian Radiology's response to the COVID-19 outbreak


title: Construction and genetic analysis of murine hepatitis virus strain A59 Nsp16 temperature sensitive mutant and the revertant virus

text: Coronaviruses (CoVs) are generally associated with respiratory and enteric infections and have long been recognized as important pathogens of livestock and companion animals. Mouse hepatitis virus (MHV) is a widely studied model system for Coronavirus replication and pathogenesis. In this study, we created a MHV-A59 temperature sensitive (ts) mutant Wu”-ts18(cd) using the recombinant vaccinia reverse genetics system. Virus replication assay in 17C1-1 cells showed the plaque phenotype and replication characterization of constructed Wu”-ts18(cd) were indistinguishable from the reported ts mutant Wu”-ts18. Then we cultured the ts mutant Wu”-ts18(cd) at non-permissive temperature 39.5°C, which “forced” the ts recombinant virus to use second-site mutation to revert from a ts to a non-ts phenotype. Sequence analysis showed most of the revertants had the same single amino acid mutation at Nsp16 position 43. The single amino acid mutation at Nsp16 position 76 or position 130 could also revert the ts mutant Wu”-ts18 (cd) to non-ts phenotype, an additional independent mutation in Nsp13 position 115 played an important role on plaque size. The results provided us with genetic information on the functional determinants of Nsp16. This allowed us to build up a more reasonable model of CoVs replication-transcription complex.


title: New technology and clinical applications of nanomedicine: Highlights of the second annual meeting of the American Academy of Nanomedicine (Part I)

text: Abstract The Second Annual Meeting of the American Academy of Nanomedicine (AANM) was held at the National Acadmy of Science Building in Washinton, DC, September 9–10, 2006. The program included two Nobel Prize Laureate Lectures, two Keynote Lectures, and 123 invited outstanding State-in-Art lectures presenting in 23 special concurrent symposia. In addition, there were 22 poster presentations in the meeting addressing different areas in nanomedicine research. All of the presenters at the meeting are outstanding investigators and researchers in the field. The Second Annual Meeting of the AANM was a great success. The meeting provides investigators from different world areas a forum and an opportunity for discussion. We believe that nanomedicine research will develop rapidly in the future. The AANM invites basic and clinical researchers from the world to join this exciting research.


title: Een groene herstart van patiënt aardbol?

text: Klimaatverandering is de grootste bedreiging voor de volksgezondheid op aarde in de 21(e) eeuw. Zo luidt de conclusie van een internationale groep wetenschappers die onderzoek heeft gedaan naar de effecten van de klimaatverandering op de gezondheid van de wereldbevolking. Er zijn steeds meer voorbeelden dat klimaatverandering en gezondheid niet los van elkaar staan.


title: A minor groove binder probe real-time PCR assay for discrimination between type 2-based vaccines and field strains of canine parvovirus

text: A minor groove binder (MGB) probe assay was developed to discriminate between type 2-based vaccines and field strains of canine parvovirus (CPV). Considering that most of the CPV vaccines contain the old type 2, no longer circulating in canine population, two MGB probes specific for CPV-2 and the antigenic variants (types 2a, 2b and 2c), respectively, were labeled with different fluorophores. The MGB probe assay was able to discriminate correctly between the old type and the variants, with a detection limit of 10(1) DNA copies and a good reproducibility. Quantitation of the viral DNA loads was accurate, as demonstrated by comparing the CPV DNA titres to those calculated by means of the TaqMan assay recognising all CPV types. This assay will ensure resolution of most diagnostic problems in dogs showing CPV disease shortly after CPV vaccination, although it does not discriminate between field strains and type 2b-based vaccines, recently licensed to market in some countries.


title: Importance of Viral Disease in Dairy Cow Fertility

text: Abstract Many viral diseases are endemic in cattle populations worldwide. The ability of many viruses to cross the placenta and cause abortions and fetal malformations is well understood. There is also significant evidence that viral infections have additional actions in dairy cows, which are reflected in reduced conception rates. These effects are, however, highly dependent on the time at which an individual animal first contracts the disease and are less easy to quantify. This paper reviews the evidence relating to five viruses that can affect fertility, together with their potential mechanisms of action. Acute infection with non-cytopathic bovine viral diarrhea virus (BVDV) in mid-gestation increases abortion rates or causes the birth of persistently infected calves. BVDV infections closer to the time of breeding can have direct effects on the ovaries and uterine endometrium, which cause estrous cycle irregularities and early embryo mortality. Fertility may also be reduced by BVDV-induced immunosuppression, which increases the susceptibility to bacterial infections. Bovine herpesvirus (BHV)-1 is most common in pre-pubertal heifers, and can slow their growth, delay breeding, and increase the age at first calving. Previously infected animals subsequently show reduced fertility. Although this may be associated with lung damage, ovarian lesions have also been reported. Both BHV-1 and BHV-4 remain latent in the host following initial infection and may be reactivated later by stress, for example associated with calving and early lactation. While BHV-4 infection alone may not reduce fertility, it appears to act as a co-factor with established bacterial pathogens such as Escherichia coli and Trueperella pyogenes to promote the development of endometritis and delay uterine repair mechanisms after calving. Both Schmallenberg virus (SBV) and bluetongue virus (BTV) are transmitted by insect vectors and lead to increased abortion rates and congenital malformations. BTV-8 also impairs the development of hatched blastocysts; furthermore, infection around the time of breeding with either virus appears to reduce conception rates. Although the reductions in conception rates are often difficult to quantify, they are nevertheless sufficient to cause economic losses, which help to justify the benefits of vaccination and eradication schemes.


title: The α(1,2)-mannosidase I inhibitor 1-deoxymannojirimycin potentiates the antiviral activity of carbohydrate-binding agents against wild-type and mutant HIV-1 strains containing glycan deletions in gp120

text: Abstract Exposure of carbohydrate-binding agents (CBAs) (i.e. the mannose-specific plant lectins Hippeastrum hybrid agglutinin and Galanthus nivalis agglutinin) to HIV-1 progressively select for mutant HIV-1 strains that contain N-glycan deletions in their envelope gp120. This results in resistance of the mutant virus strains to the CBAs. Exposure of such mutant virus strains to the α(1,2)-mannosidase I inhibitor 1-deoxymannojirimycin (DMJ) results in an enhanced suppression of mutant virus-induced cytopathicity in CEM cell cultures. Moreover, when combined with CBAs at concentrations that showed poor if any suppression of mutant virus replication as single drugs, a synergistic antiviral activity of DMJ was observed. These observations argue for a combined exposure of CBAs and glycosylation inhibitors such as DMJ to HIV to afford a more pronounced suppression of virus replication, prior to, or during, CBA resistance development.


title: Formation and activity of covalent conjugates of poliovirus and ligands binding to cell surface structures

text: Abstract Disulfide-linked conjugates of poliovirus with streptavidin or concanavalin A were formed and the binding of the conjugates to mouse L cells that lack natural poliovirus receptors was studied. The conjugate with streptavidin was specifically bound to biotinylated L cells, but not to unmodified L cells. The conjugate with conA was bound to L cells in the absence of, but not in the presence of α-methyl mannoside. Incubation of L cells with bound conjugates did not produce virus, although the conjugates were highly infectious in HeLa cells, containing natural poliovirus receptors. This suggests that the artificially bound virus was unable to penetrate the L cells and start replication. The possibility that binding of the virus to the natural receptor is required for efficient infection is discussed.


title: Early experience with convalescent plasma as immunotherapy for COVID‐19 in China: Knowns and unknowns

text: BACKGROUND AND OBJECTIVES: In the absence of a vaccine or specific drug treatment options for coronavirus disease (COVID‐19), attention has been shifted in China to the possible therapeutic use of convalescent plasma. COVID‐19 convalescent plasma (CCP) is currently under investigation. We summarized clinical studies and other research data available as of May 5, 2020, on CCP therapy according to the Clinical Treatment Guideline of COVID‐19 Convalescent Plasma in China, as well as clinical experience at the First Affiliated Hospital of Zhejiang University, as part of a comprehensive anti‐epidemic strategy. MATERIALS AND METHODS: As of May 5, 2020, when the epidemic was well‐controlled in China, healthcare databases and sources of English literature relating to convalescent plasma were searched and reviewed. Sources of clinical and methodological heterogeneity were identified. RESULTS: As of May 5, 2020, up to 2,000 samples of CCP had been collected across China and administered to 700 COVID‐19 patients. From donors, 200–400 mL of plasma were collected at each donation, with antibody titers >1:160. We identified three clinical studies for COVID‐19 in China. Analyses showed a statistically significant improvement in clinical outcomes compared with untreated cases (P<0.001). No adverse effects were reported. CONCLUSION: From initial studies, convalescent plasma therapy appears effective and safe for COVID‐19. However, there is clearly a need for well‐designed RCTs (randomized controlled trials) or other formal studies to further evaluate the efficacy and any potential adverse effects of CCP.


title: Lobar Distribution of COVID-19 Pneumonia Based on Chest Computed Tomography Findings; A Retrospective Study

text: INTRODUCTION: Computed tomography (CT) imaging has quickly found its place as a beneficial tool in the detection of coronavirus disease 2019 (COVID-19). To date, only a few studies have reported the distribution of lung lesions by segment. This study aimed to evaluate the lobar and segmental distribution of COVID-19 pneumonia based on patients’ chest CT scan. METHODS: This was a retrospective study performed on 63 Iranian adult patients with a final diagnosis of COVID-19. All patients had undergone chest CT scan on admission. Demographic data and imaging profile, including segmental distribution, were evaluated. Moreover, a scoring scale was designed to assess the severity of ground-glass opacification (GGO). The relationship of GGO score with age, sex, and symptoms at presentation was investigated. RESULTS: Among included patients, mean age of patients was 54.2 ±14.9 (range: 26 - 81) years old and 60.3% were male. Overall, the right lower lobe (87.3%) and the left lower lobe (85.7%) were more frequently involved. Specifically, predominant involvement was seen in the posterior segment of the left lower lobe (82.5%). The most common findings were peripheral GGO and consolidation, which were observed in 92.1% and 42.9% of patients, respectively. According to the self-designed GGO scoring scale, about half of the patients presented with mild GGO on admission. GGO score was found to be equally distributed among different sex and age categories; however, the presence of dyspnea on admission was significantly associated with a higher GGO score (p= 0.022). Cavitation, reticulation, calcification, bronchiectasis, tree-in-bud appearance and nodules were not identified in any of the cases. CONCLUSION: COVID-19 mainly affects the lower lobes of the lungs. GGO and consolidation in the lung periphery is the imaging hallmark in patients with COVID-19 infection. Absence of bronchiectasis, solitary nodules, cavitation, calcifications, tree-in-bud appearance, and reversed halo-sign indicates that these features are not common findings, at least in the earlier stages.


title: Predicting mortality due to SARS-CoV-2: A mechanistic score relating obesity and diabetes to COVID-19 outcomes in Mexico

text: BACKGROUND: The SARS-CoV-2 outbreak poses challenge to healthcare systems due to high complication rates in patients with cardiometabolic diseases. Here, we identify risk factors and propose a clinical score to predict COVID-19 lethality, including specific factors for diabetes and obesity and its role in improving risk prediction. METHODS: We obtained data of confirmed and negative COVID-19 cases and their demographic and health characteristics from the General Directorate of Epidemiology of Mexican Ministry of Health. We investigated specific risk factors associated to COVID-19 positivity and mortality and explored the impact of diabetes and obesity on modifying COVID-19 related lethality. Finally, we built a clinical score to predict COVID-19 lethality. RESULTS: Among 177,133 subjects at May 18(th), 2020, we observed 51,633 subjects with SARS-CoV-2 and 5,332 deaths. Risk factors for lethality in COVID-19 include early-onset diabetes, obesity, COPD, advanced age, hypertension, immunosuppression, and CKD; we observed that obesity mediates 49.5% of the effect of diabetes on COVID-19 lethality. Early-onset diabetes conferred an increased risk of hospitalization and obesity conferred an increased risk for ICU admission and intubation. Our predictive score for COVID-19 lethality included age ≥65 years, diabetes, early-onset diabetes, obesity, age <40 years, CKD, hypertension, and immunosuppression and significantly discriminates lethal from non-lethal COVID-19 cases (c-statistic=0.823). RESULTS: Here, we propose a mechanistic approach to evaluate risk for complications and lethality attributable to COVID-19 considering the effect of obesity and diabetes in Mexico. Our score offers a clinical tool for quick determination of high-risk susceptibility patients in a first contact scenario.


title: Correlation between climate indicators and COVID-19 pandemic in New York, USA

text: Abstract This study analyzed the association between COVID-19 and climate indicators in New York City, USA. We used secondary published data from New York city health services and National weather service, USA. The climate indicators included in the study are average temperature, minimum temperature, maximum temperature, rainfall, average humidity, wind speed, and air quality. Kendall and Spearman rank correlation tests were chosen for data analysis. We find that average temperature, minimum temperature, and air quality were significantly associated with the COVID-19 pandemic. The findings of this study will help World Health Organization and health regulators such as Center for Disease Control (CDC) to combat COVID-19 in New York and the rest of the world.


title: Systems Biology Approaches to Disease Marker Discovery

text: Our understanding of human disease and potential therapeutics is improving rapidly. In order to take advantage of these developments it is important to be able to identify disease markers. Many new high-throughput genomics and proteomics technologies are being implemented to identify candidate disease markers. These technologies include protein microarrays, next-generation DNA sequencing and mass spectrometry platforms. Such methods are particularly important for elucidating the repertoire of molecular markers in the genome, transcriptome, proteome and metabolome of patients with diseases such as cancer, autoimmune diseases, and viral infections, resulting from the disruption of many biological pathways. These new technologies have identified many potential disease markers. These markers are expected to be valuable to achieve the promise of truly personalized medicine.


LA REHABILITACIÓN EN LOS TIEMPOS DEL COVID-19


title: Vascular disrupting agent DMXAA enhances the antitumor effects generated by therapeutic HPV DNA vaccines

text: Antigen-specific immunotherapy using DNA vaccines has emerged as an attractive approach for the control of tumors. Another novel cancer therapy involves the employment of the vascular disrupting agent, 5,6-dimethylxanthenone-4-acetic acid (DMXAA). In the current study, we aimed to test the combination of DMXAA treatment with human papillomavirus type 16 (HPV-16) E7 DNA vaccination to enhance the antitumor effects and E7-specific CD8+ T cell immune responses in treated mice. We determined that treatment with DMXAA generates significant therapeutic effects against TC-1 tumors but does not enhance the antigen-specific immune responses in tumor bearing mice. We then found that combination of DMXAA treatment with E7 DNA vaccination generates potent antitumor effects and E7-specific CD8+ T cell immune responses in the splenocytes of tumor bearing mice. Furthermore, the DMXAA-mediated enhancement or suppression of E7-specific CD8+ T cell immune responses generated by CRT/E7 DNA vaccination was found to be dependent on the time of administration of DMXAA and was also applicable to other antigen-specific vaccines. In addition, we determined that inducible nitric oxide synthase (iNOS) plays a role in the immune suppression caused by DMXAA administration before DNA vaccination. Our study has significant implications for future clinical translation.


title: Clinical trials for coronavirus disease 2019: What is being evaluated and what is not

text: Since the report of the first case of coronavirus disease 2019 (COVID-19) in China in late December 2019, there have been 204 610 cases worldwide as of 18 March, 2020. As part of the response to this outbreak, there has been an impressive amount of research undertaken to better characterize the disease and to evaluate therapeutic options. By March 12, 2020, there are more than 382 studies registered in the clinical trials databases addressing COVID-19 including more than 80 randomized controlled trials.


title: Porcine epidemic diarrhoea virus: a comprehensive review of molecular epidemiology, diagnosis, and vaccines

text: The porcine epidemic diarrhoea virus (PEDV), a member of the Coronaviridae family, causes acute diarrhoea and dehydration in pigs. Although it was first identified in Europe, it has become increasingly problematic in many Asian countries, including Korea, China, Japan, the Philippines, and Thailand. The economic impacts of the PEDV are substantial, given that it results in significant morbidity and mortality in neonatal piglets and is associated with increased costs related to vaccination and disinfection. Recently, progress has been made in understanding the molecular epidemiology of PEDV, thereby leading to the development of new vaccines. In the current review, we first describe the molecular and genetic characteristics of the PEDV. Then we discuss its molecular epidemiology and diagnosis, what vaccines are available, and how PEDV can be treated.


title: COVID-19, Fiscal Federalism and Provincial Debt: Have We Reached a Critical Juncture?

text: In 2019, Canada's gross subnational debt to GDP was well over 40 per cent, easily the highest in the world (see Figure 1). This level will only grow as the provinces grapple with the pandemic and its fiscal effects. Some believe surging provincial debts have brought Canadian federalism to a critical juncture: they have greatly increased the odds of federal measures to stabilize provincial finances. This article assesses this claim. The cleanest and most balanced path to fiscal sustainability is a combination of enhanced federal transfers, which would bolster provincial fiscal capacity, and national fiscal rules, which would constrain provincial borrowing. But the former is unlikely to restore sustainability on its own, and the latter would require a severe provincial debt crisis, which Canada's existing fiscal federal structures can avoid. COVID-19 has increased the odds of certain reforms, and it is difficult to predict their long-run effects. But any obvious paths to fiscal sustainability remain hidden.


title: Reviewing Chandipura: A Vesiculovirus in Human Epidemics

text: Chandipura virus, a member of the rhabdoviridae family and vesiculovirus genera, has recently emerged as human pathogen that is associated with a number of outbreaks in different parts of India. Although, the virus closely resembles with the prototype vesiculovirus, Vesicular Stomatitis Virus, it could be readily distinguished by its ability to infect humans. Studies on Chandipura virus while shed light into distinct stages of viral infection; it may also allow us to identify potential drug targets for antiviral therapy. In this review, we have summarized our current understanding of Chandipura virus life cycle at the molecular detail with particular interest in viral RNA metabolisms, namely transcription, replication and packaging of viral RNA into nucleocapsid structure. Contemporary research on otherwise extensively studied family member Vesicular Stomatitis Virus has also been addressed to present a more comprehensive picture of vesiculovirus life cycle. Finally, we reveal examples of protein economy in Chandipura virus life-cycle whereby each viral protein has evolved complexity to perform multiple tasks.


title: What’s New With the Old Coronaviruses?

text: Coronaviruses contribute to the burden of respiratory diseases in children, frequently manifesting in upper respiratory symptoms considered to be part of the “common cold.” Recent epidemics of novel coronaviruses recognized in the 21st century have highlighted issues of zoonotic origins of transmissible respiratory viruses and potential transmission, disease, and mortality related to these viruses. In this review, we discuss what is known about the virology, epidemiology, and disease associated with pediatric infection with the common community-acquired human coronaviruses, including species 229E, OC43, NL63, and HKU1, and the coronaviruses responsible for past world-wide epidemics due to severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus.


title: Critical paths in a metapopulation model of H1N1: Efficiently delaying influenza spreading through flight cancellation

text: Disease spreading through human travel networks has been a topic of great interest in recent years, as witnessed during outbreaks of influenza A (H1N1) or SARS pandemics. One way to stop spreading over the airline network are travel restrictions for major airports or network hubs based on the total number of passengers of an airport. Here, we test alternative strategies using edge removal, cancelling targeted flight connections rather than restricting traffic for network hubs, for controlling spreading over the airline network. We employ a SEIR metapopulation model that takes into account the population of cities, simulates infection within cities and across the network of the top 500 airports, and tests different flight cancellation methods for limiting the course of infection. The time required to spread an infection globally, as simulated by a stochastic global spreading model was used to rank the candidate control strategies. The model includes both local spreading dynamics at the level of populations and long-range connectivity obtained from real global airline travel data. Simulated spreading in this network showed that spreading infected 37% less individuals after cancelling a quarter of flight connections between cities, as selected by betweenness centrality. The alternative strategy of closing down whole airports causing the same number of cancelled connections only reduced infections by 18%. In conclusion, selecting highly ranked single connections between cities for cancellation was more effective, resulting in fewer individuals infected with influenza, compared to shutting down whole airports. It is also a more efficient strategy, affecting fewer passengers while producing the same reduction in infections. The network of connections between the top 500 airports is available under the resources link on our website http://www.biological-networks.org.


title: Management of infection control and radiological protection in diagnostic radiology examination of COVID-19 cases

text: Since the COVID-19 outbreak, diagnostic imaging has been providing valuable radiological support for disease diagnosis and prognosis prediction. Radiological staff, especially radiographers working on the front line in the battle against the COVID-19 outbreak. They are in direct contact with the patients, bearing the responsibility and pressure of both the infection prevention and control and the radiation protection. A number of relevant professionals and experts reached a consensus, which clarifies the detailed implementing rules with respective to infection control and protection of the radiation workers, disinfection of diagnostic radiology equipment and workplace, and radiological protection. The aim is to further normalize the clinical procedures of radiological staff, reduce the infection risk, especially the radiation risk to medics and patients.


title: Natural ventilation for reducing airborne infection in hospitals

text: Abstract High ventilation rate is shown to be effective for reducing cross-infection risk of airborne diseases in hospitals and isolation rooms. Natural ventilation can deliver much higher ventilation rate than mechanical ventilation in an energy-efficient manner. This paper reports a field measurement of naturally ventilated hospital wards in Hong Kong and presents a possibility of using natural ventilation for infection control in hospital wards. Our measurements showed that natural ventilation could achieve high ventilation rates especially when both the windows and the doors were open in a ward. The highest ventilation rate recorded in our study was 69.0 ACH. The airflow pattern and the airflow direction were found to be unstable in some measurements with large openings. Mechanical fans were installed in a ward window to create a negative pressure difference. Measurements showed that the negative pressure difference was negligible with large openings but the overall airflow was controlled in the expected direction. When all the openings were closed and the exhaust fans were turned on, a reasonable negative pressure was created although the air temperature was uncontrolled. The high ventilation rate provided by natural ventilation can reduce cross-infection of airborne diseases, and thus it is recommended for consideration of use in appropriate hospital wards for infection control. Our results also demonstrated a possibility of converting an existing ward using natural ventilation to a temporary isolation room through installing mechanical exhaust fans.


title: Mixing ratio optimization for functional complex extracts of Rhodiola crenulata, Panax quinquefolius, and Astragalus membranaceus using mixture design and verification of immune functional efficacy in animal models

text: Abstract We aimed to identify the optimum mixing ratio for various ingredients to obtain complex extracts with high extract yields and immune-enhancing activity in animals. The extract yield and amounts of nitric oxide (NO) and interleukin (IL)-6 were set to maximum for modeling predictions. The predicted optimum values for the mixing ratio were 49.5% for Rhodiola crenulata, 26.1% for Astragalus membranaceus, and 24.4% for Panax quinquefolius, and the predicted response values were 31.5% yield, 13.4% NO production, and 6.1% IL-6 production; actual values were 35.3% yield, 14.7% NO, and 6.6% IL-6. The optimum mixing ratio extract (OMRE) was used for the animal experiments. Treating mice with OMRE at 200 mg/kg produced significant increases in spleen indexes and T-cell/B-cell proliferation. OMRE treatment increased IL-10 and IL-6 production in concanavalin A- and lipopolysaccharide-induced T- and B- lymphocytes, respectively. These results provide a basis for the development of functional extracts and drinks.


Pertinent roles of African higher institutions in the COVID‐19 pandemic response: The University of Ilorin, Ilorin, Nigeria; An African Model


title: Taking down covid-19

text: Thousands of people are searching for coronavirus treatments. Which are most promising and when will we have them, asks Carrie Arnold


title: Planning and provision of ECMO services for severe ARDS during the COVID-19 pandemic and other outbreaks of emerging infectious diseases

text: Summary WHO interim guidelines recommend offering extracorporeal membrane oxygenation (ECMO) to eligible patients with acute respiratory distress syndrome (ARDS) related to coronavirus disease 2019 (COVID-19). The number of patients with COVID-19 infection who might develop severe ARDS that is refractory to maximal medical management and require this level of support is currently unknown. Available evidence from similar patient populations suggests that carefully selected patients with severe ARDS who do not benefit from conventional treatment might be successfully supported with venovenous ECMO. The need for ECMO is relatively low and its use is mostly restricted to specialised centres globally. Providing complex therapies such as ECMO during outbreaks of emerging infectious diseases has unique challenges. Careful planning, judicious resource allocation, and training of personnel to provide complex therapeutic interventions while adhering to strict infection control measures are all crucial components of an ECMO action plan. ECMO can be initiated in specialist centres, or patients can receive ECMO during transportation from a centre that is not specialised for this procedure to an expert ECMO centre. Ensuring that systems enable safe and coordinated movement of critically ill patients, staff, and equipment is important to improve ECMO access. ECMO preparedness for the COVID-19 pandemic is important in view of the high transmission rate of the virus and respiratory-related mortality.


COVID-19 in a pediatric heart transplant recipient: Emergence of Donor Specific Antibodies


title: Immunogenicity of Candidate MERS-CoV DNA Vaccines Based on the Spike Protein

text: MERS-coronavirus is a novel zoonotic pathogen which spread rapidly to >25 countries since 2012. Its apparent endemicity and the wide spread of its reservoir host (dromedary camels) in the Arabian Peninsula highlight the ongoing public health threat of this virus. Therefore, development of effective prophylactic vaccine needs to be urgently explored given that there are no approved prophylactics or therapeutics for humans or animals to date. Different vaccine candidates have been investigated but serious safety concerns remain over protein or full-length spike (S) protein-based vaccines. Here, we investigated the immunogenicity of naked DNA vaccines expressing different fragments of MERS-CoV S protein in mice. We found that plasmids expressing full-length (pS) or S1-subunit (pS1) could induce significant levels of S1-specific antibodies (Abs) but with distinct IgG isotype patterns. Specifically, pS1 immunization elicited a balanced Th1/Th2 response and generally higher levels of all IgG isotypes compared to pS vaccination. Interestingly, only mice immunized with pS1 demonstrated significant S1-specific cellular immune response. Importantly, both constructs induced cross-neutralizing Abs against multiple strains of human and camel origins. These results indicate that vaccines expressing S1-subunit of the MERS-CoV S protein could represent a potential vaccine candidate without the possible safety concerns associated with full-length protein-based vaccines.


title: Transferrin receptor 1 in the zoonosis and pathogenesis of New World hemorrhagic fever arenaviruses

text: At least five New World arenaviruses cause severe human hemorrhagic fevers. These viruses are transmitted to humans through contact with their respective South American rodent hosts. Each uses human transferrin receptor 1 (TfR1) as its obligate receptor. Accidental similarities between human TfR1 and TfR1 orthologs of arenviral host species enable zoonoses, whereas mice and rats are not infectable because they lack these TfR1 determinants of infection. All pathogenic New World arenaviruses bind to a common region of the apical domain of TfR1. The ability of a New World arenavirus to use human TfR1 is absolutely predictive of its ability to cause hemorrhagic fevers in humans. Non-pathogenic arenaviruses, closely related to hemorrhagic fever arenaviruses, cannot utilize human TfR1 but efficiently enter cells through TfR1 orthologs of their native rodent hosts. Mutagenesis studies suggest that minor changes in the entry glycoproteins of these non-pathogenic viruses may allow human transmission. TfR1 is upregulated as a result of iron sequestration during the acute phase response to infection, and the severity of disease may result from amplification of viral replication during this response.


title: Operational strategies of a trauma hub in early coronavirus disease 2019 pandemic

text: PURPOSE: The “Spedali Civili”, one of the largest hospitals in the Italian region most affected by SARS-CoV-2 infection, is managing a large number of traumatic injuries. The objective of this article is to share our operational protocols to deliver an appropriate hospital trauma care in the context of the COVID-19 pandemic. METHODS: We changed our work shifts, in consideration of the high number of patients; colleagues from smaller hospitals in the area joined us to increase the number of surgeons available. Thanks to the collaboration between orthopaedists, anaesthesiologists, and nurses, we created a flow chart and separate routes (in the emergency room, in the wards, and in the operating rooms) to optimize patient management. Our protocols allow us to always provide healthcare professionals with the correct personal protective equipment for the task they are performing. RESULTS: Our strategies proved to be practical and feasible. Having a well thought plan helped us to provide for the most robust response possible. We have not yet been able to study the effectiveness of our protocols, and our recommendations may not be applicable to all healthcare facilities. Nonetheless, sharing our early experience can help other institutions conducting and adapting such plans more quickly. CONCLUSIONS: Having a clear strategy during the COVID-19 pandemic kept our systems resilient and effective and allowed us to provide high-quality trauma care. We offer this approach for other institutions to adopt and adapt to their local setting.


title: Mutational analysis of the “slippery-sequence” component of a coronavirus ribosomal frameshifting signal

text: Abstract The ribosomal frameshift signal in the genomic RNA of the coronavirus IBV is composed of two elements, a heptanucleotide “slippery-sequence” and a downstream RNA pseudoknot. We have investigated the kinds of slippery sequence that can function at the IBV frameshift site by analysing the frameshifting properties of a series of slippery-sequence mutants. We firstly confirmed that the site of frameshifting in IBV was at the heptanucleotide stretch UUUAAAC, and then used our knowledge of the pseudoknot structure and a suitable reporter gene to prepare an expression construct that allowed both the magnitude and direction of ribosomal frameshifting to be determined for candidate slippery sequences. Our results show that in almost all of the sequences tested, frameshifting is strictly into the −1 reading frame. Monotonous runs of nucleotides, however, gave detectable levels of a −2 +1 frameshift product, and U stretches in particular gave significant levels (2% to 21%). Preliminary evidence suggests that the RNA pseudoknot may play a role in influencing frameshift direction. The spectrum of slip-sequences tested in this analysis included all those known or suspected to be utilized in vivo. Our results indicate that triplets of A, C, G and U are functional when decoded in the ribosomal P-site following slippage ( XXX YYYN) although C triplets were the least effective. In the A-site (XXY YYY N), triplets of C and G were non-functional. The identity of the nucleotide at position 7 of the slippery sequence (XXXYYY N ) was found to be a critical determinant of frameshift efficiency and we show that a hierarchy of frameshifting exists for A-site codons. These observations lead us to suggest that ribosomal frameshifting at a particular site is determined, at least in part, by the strength of the interaction of normal cellular tRNAs with the A-site codon and does not necessarily involve specialized “shifty” tRNAs.


title: Methods for the discovery of emerging pathogens

text: Abstract Recently, there has been a steady increase in the number of recognized pathogenic microorganisms, specifically bacteria. The development of genetic technologies, MALDI-TOF mass spectrometry and new culturing techniques has significantly widened the repertoire of known microorganisms and therefore pathogenic microorganisms. The repertoire of infectious agents has been studied in various environments including water, soil, pets, livestock, wildlife and arthropods. Using different methods, many known pathogens can be identified in these samples; therefore, the impact of emergent pathogens on humans can be examined and novel pathogens can be identified. In this special issue, we discuss the identification of emerging pathogens in the environment and animals.


title: Prolonged viral shedding in feces of pediatric patients with coronavirus disease 2019

text: Abstract Objective To determine the dynamic changes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in respiratory and fecal specimens in children with coronavirus disease 2019 (COVID-19). Methods From January 17, 2020 to February 23, 2020, three paediatric cases of COVID-19 were reported in Qingdao, Shandong Province, China. Epidemiological, clinical, laboratory, and radiological characteristics and treatment data were collected. Patients were followed up to March 10, 2020, and dynamic profiles of nucleic acid testing results in throat swabs and fecal specimens were closely monitored. Results Clearance of SARS-CoV-2 in respiratory tract occurred within two weeks after abatement of fever, whereas viral RNA remained detectable in stools of pediatric patients for longer than 4 weeks. Two children had fecal SARS-CoV-2 undetectable 20 days after throat swabs showing negative, while that of another child lagged behind for 8 days. Conclusions SARS-CoV-2 may exist in children's gastrointestinal tract for a longer time than respiratory system. Persistent shedding of SARS-CoV-2 in stools of infected children raises the possibility that the virus might be transmitted through contaminated fomites. Massive efforts should be made at all levels to prevent spreading of the infection among children after reopening of kindergartens and schools.


title: Smell and Taste Dysfunction in Patients With COVID-19: A Systematic Review and Meta-analysis

text: Abstract Objective To estimate the prevalence of olfactory and gustatory dysfunctions (OGDs) among patients infected with novel coronavirus disease 2019 (COVID-19). Patients and Methods A systematic review was conducted by searching MEDLINE, EMBASE, and the preprint server MedRxiv until 11 May 2020 using the terms ‘anosmia’ or ‘hyposmia’ or ‘dysosmia’ or ‘olfactory dysfunction’ or ‘olfaction disorder’ or ‘smell dysfunction’ or ‘ageusia’ or ‘hypogeusia’ or ‘dysgeusia’ or ‘taste dysfunction’ or ‘gustatory dysfunction’ or ‘neurological’ and ‘COVID-19’ or ‘2019 novel coronavirus’ or ‘2019-nCoV’ or ‘SARS-CoV-2’. References of included studies were also manually screened. Only studies involving diagnostic-confirmed patients with COVID-19 were included. Random-effects meta-analysis was performed. Results A total of twenty-four studies with data from 8438 test-confirmed COVID-19 patients from thirteen countries were included. The pooled proportion of patients presenting with olfactory and gustatory dysfunctions was 41.0% (95% confidence interval [CI] 28.5% to 53.9) and 38.2% (95% CI 24.0 to 53.6%), respectively. Increasing mean age correlated with lower prevalence of olfactory (coefficient = -0.076; p=.02) and gustatory (coefficient = -0.073; p=.03) dysfunctions. There was a higher prevalence of olfactory dysfunctions with the use of objective measurements compared to self-reports (coefficient = 2.33; p=.01). No significant moderation of the prevalence of OGDs by gender was observed. Conclusion There is a high prevalence of OGDs among patients infected with COVID-19. Routine screening for these conditions could contribute to improved case detection in the ongoing COVID-19 pandemic. However, to better inform population screening measures, further studies are needed to establish causality.


title: Chapter 7 Environmental and Safety Issues With Nanoparticles

text: Abstract Because nanoparticles have superior surface activity and can be applied to the production of particles with various functions, they are extremely important for the future development of sophisticated material technologies. On the other hand, this superior activity of nanoparticles is a cause of trouble from the perspective of safety and does not always have a positive influence on the environment. Attention must also be paid to impact on health. Nevertheless, all technologies have negative aspects, and overcoming these kinds of problems, we will be able to utilize the superior characteristics of nanoparticles for practical purposes. To achieve this goal, it is necessary to fully understand the influence of nanoparticles on the environment and the relevant safety issues.


title: DEA allows buprenorphine inductions based on telephone only

text: Last week, the Drug Enforcement Administration (DEA) said opioid treatment programs (OTPs) and Drug Addiction Treatment Act (DATA)–waived prescribers can treat new patients with buprenorphine based on a telephone call only. The Controlled Substances Act (CSA), enforced by the DEA, requires all new patients being treated with controlled substances to have an in‐person — or, for now, telemedicine — physical exam. Now, however, because of the coexisting COVID‐19 pandemic and opioid overdose crisis, the DEA has dropped this requirement. This follows the decision of the Substance Abuse and Mental Health Services Administration (SAMHSA) to allow exemptions from the OTP take‐home regulations allowing stable patients to be given 14 or 28 days of methadone doses, instead of coming in more frequently (see DEA, SAMHSA relax OTP/OBOT regulations due to COVID‐19, ADAW March 23, https://onlinelibrary.wiley.com/doi/10.1002/adaw.32664).


title: Mobile Virology Research and Diagnostic Laboratory (MVRDL: BSL-3) for COVID-19 Screening, Virus Culturing and Vaccine Development

text: In order to prevent spread of COVID-19, World Health Organization (WHO) has specified that measures such as cleaning hands regularly with alcohol-based hand sanitizer or washing with soap and water, avoiding touching nose, eyes, mouth and social distancing should be followed by people. Another important measure for containing spread is by Testing–Testing and Testing. To conduct real-time reverse transcription polymerase chain reaction (rRT-PCR) test for diagnosing COVID-19. Possibility to test up to 2000 samples per day. For virus culturing for drug screening, convalescent plasma-derived therapy. To aid in the development of vaccine and development of diagnostic kits.


title: American Society for Transplantation and Cellular Therapy Pharmacy Special Interest Group Position Statement on Pharmacy Practice Management and Clinical Management for COVID-19 in Hematopoietic Cell Transplant and Cellular Therapy Patients in the United States

text: Abstract The coronavirus-19 (COVID-19) pandemic poses a significant risk to patients undergoing hematopoietic stem cell transplant or cellular therapy. The American Society for Transplantation and Cellular Therapy Pharmacy Special Interest Group Steering Committee aims to provide pharmacy practice management recommendations for how to transition clinical hematopoietic stem cell transplant (HCT) or cellular therapy pharmacy services utilizing telemedicine capabilities in the inpatient and outpatient setting to maintain an equivalent level of clinical practice but minimizing viral spread in a high risk, immunocompromised population. Additionally, the Steering Committee offers clinical management recommendations for COVID-19 in HCT and cellular therapy patients based on the rapidly developing literature. As the therapeutic and supportive care interventions for COVID-19 increase, collaboration with clinical pharmacy providers is critical to ensure safe administration in HCT patients. Attention to drug-drug interactions (DDI) and toxicity, particularly QTc prolongation, warrants close cardiac monitoring and potential cessation of concomitant QTc prolonging agents. Expanded indications for hydroxychloroquine and tocilizumab have already shown potential stress to usual supply chain. Detailed prescribing algorithms, decision pathways and specific patient population stock may be necessary. The COVID-19 pandemic has challenged every member of the healthcare team and we must continue to remain vigilant in providing pharmacy clinical services to one of the most high-risk patient populations and remain committed to providing compassionate and safe care for patients receiving HCT and cellular therapies.


Absence of Middle East respiratory syndrome coronavirus in Bactrian camels in the West Inner Mongolia Autonomous Region of China: surveillance study results from July 2015


title: Telehealth Home Support During COVID-19 Confinement for Community-Dwelling Older Adults With Mild Cognitive Impairment or Mild Dementia: Survey Study

text: BACKGROUND: The public health emergency of coronavirus disease (COVID-19) is rapidly evolving worldwide; some countries, including Spain, have implemented restrictive measures. Populations that are vulnerable to this outbreak and its physical and mental health effects include community-dwelling older adults with mild cognitive impairment or mild dementia. Telehealth is a potential tool to deliver health care and decrease exposure risk. OBJECTIVE: The aims of this study were to explore the impact of confinement on the health and well-being of community-dwelling older adults with mild cognitive impairment or mild dementia, to provide television-based and telephone-based health and social support, and to study the effects of a television-based assistive integrated technology, TV-AssistDem (TeleVision-based ASSistive Integrated Service to supporT European adults living with mild DEMentia or mild cognitive impairment). METHODS: A telephone-based survey was administered in Spain to 93 participants in the TV-AssistDem clinical trial from March 25 to April 6, 2020. RESULTS: Of the respondents, 60/93 (65%) were women. The mean age was 73.34 (SD 6.07), and 69/93 (74%) lived accompanied. Lockdown measures forced 17/93 respondents (18%) to change their living arrangements. Health status was found to be optimal in 89/93 respondents (96%), with no COVID-19 symptoms. Grocery and pharmacy outings were performed by family members of 68/93 participants (73%); 57 (61%) reported overall well-being, and 65 (70%) maintained their sleep quality. However, participants living alone reported greater negative feelings and more sleeping problems. Regarding leisure activities, 53/93 respondents (57%) took walks, 32 (35%) played memory games, 55 (60%) watched television, and 91 (98%) telephoned relatives. 58/93 (64%) respondents reported accessing moderate or too much COVID-19 information, 89 (97%) received it from television, and 56 (62%) stated that their understanding of the information was extreme. 39/93 (39%) respondents had contacted health and social services, while 29 (31%) requested information regarding these services during the telephone call. There were no significant differences in health and well-being between the intervention and control groups. Respondents with TV-AssistDem performed more memory exercises (24/93, 52% vs 8/93, 17.4%; P<.001) than control respondents. CONCLUSIONS: Our findings suggest that during COVID-19 confinement, the physical and mental health and well-being was optimal for the majority of our vulnerable population. However, those living alone reported greater negative psychological effects and sleeping problems. Measures adopted to address the negative experiences of confinement included keeping informed about the situation, accessing health and social services, having a support network that prevents risk of exposure to COVID-19 and guarantees food and medical supplies, a daily routine with maintained sleeping habits and leisure activities, staying physically and mentally active with cognitive stimulation exercises, and ensuring social connectedness using technology. Television sets were preferred technological devices to access COVID-19 information, watch television as a recreational activity, and perform memory exercises as an intellectual activity. Television-based telehealth support using TV-AssistDem demonstrated potential for cognitive stimulation. TRIAL REGISTRATION: ClinicalTrials.gov NCT03653234; https://clinicaltrials.gov/ct2/show/NCT03653234


title: Legionella community-acquired pneumonia (CAP) presenting with spontaneous bilateral pneumothoraces

text: Legionnaires' disease is a common cause of non-zoonotic atypical community-acquired pneumonia (CAP). Legionnaires' disease has varied manifestations but may be diagnosed clinically on the basis of its characteristic pattern of extra-organ involvement. In a patient with non-zoonotic CAP, the clinical and laboratory features in a patient with CAP pointing to the diagnosis of Legionnaires' disease include relative bradycardia, mental confusion/ encephalopathy, loose stools/diarrhea, abdominal pain, mild/transient increases in serum transaminases, decreased serum phosphorous, a highly elevated C-reactive protein (CRP), elevated creatinine phosphokinase (CPK), highly elevated serum ferritin levels, or microscopic hematuria. The radiologic manifestations of Legionnaires' disease are varied and no radiographic appearance is pathopneumonic. Patchy infiltrates in Legionnaires' disease are symmetrical and rapidly progressive even on appropriate anti-Legionella antimicrobial therapy. Spontaneous unilateral pneumothorax is a rare radiographic manifestation of Legionnaires' disease. We present a case of a young male who is presenting clinical finding was that of spontaneous bilateral pneumothoraces due to Legionella CAP. We believe this is the first reported case of Legionnaires' disease presenting as spontaneous bilateral pneumothoraces. Clinicians should be aware of the protean radiological manifestations of Legionnaires' disease. In patients presenting with CAP and unilateral or bilateral spontaneous pneumothorax, clinicians should have Legionnaires' disease in the differential diagnosis.


title: Plan de contingencia para los servicios de medicina intensiva frente a la pandemia COVID-19♦

text: Resumen En enero de 2020 China identificó un nuevo virus de la familia de los Coronaviridae como causante de varios casos de neumonía de origen desconocido. Inicialmente confinado a la ciudad de Wuhan, se extendió posteriormente fuera de las fronteras chinas. En España, el primer caso se declaró el 31 de enero de 2020. El 11 de marzo, la Organización Mundial de la Salud declaró el brote de coronavirus como pandemia. El 16 de marzo había 139 países afectados. Ante esta situación, las Sociedades Científicas SEMICYUC y SEEIUC han decidido la elaboración de este plan de contingencia para dar respuesta a las necesidades que conllevará esta nueva enfermedad. Se pretende estimar la magnitud del problema e identificar las necesidades asistenciales, de recursos humanos y materiales, de manera que los servicios de medicina intensiva del país tengan una herramienta que les permita una planificación óptima y realista con que responder a la pandemia. Abstract In January 2020, the Chinese authorities identified a new virus of the Coronaviridae family as the cause of several cases of pneumonia of unknown aetiology. The outbreak was initially confined to Wuhan City, but then spread outside Chinese borders. On 31 January 2020, the first case was declared in Spain. On 11 March 2020, The World Health Organization (WHO) declared the coronavirus outbreak a pandemic. On 16 March 2020, there were 139 countries affected. In this situation, the Scientific Societies SEMICYUC and SEEIUC, have decided to draw up this Contingency Plan to guide the response of the Intensive Care Services. The objectives of this plan are to estimate the magnitude of the problem and identify the necessary human and material resources. This is to provide the Spanish Intensive Medicine Services with a tool to programme optimal response strategies.


title: Knowledge, Attitudes, Impact, and Anxiety Regarding COVID-19 Infection Among the Public in China

text: Objectives: Sufficient knowledge and positive attitudes are crucial to the prevention of COVID-19. However, little is known about public awareness and attitudes regarding COVID-19 in China. The impact of COVID-19 on the societal well-being and anxiety levels of the public has never been documented. The aim of this study was to survey the knowledge, attitudes, impact, and anxiety levels of the people of China in relation to the COVID-19 outbreak. Method: A cross-sectional population survey using an online questionnaire was undertaken between Jan 24 and Feb 24, 2020. The study participants were residents of mainland China over the age of 18 years. The attitude items in this study measured the perceived threat of COVID-19 based on the Health Belief Model. Anxiety was measured with the State-Trait Anxiety Inventory (STAI), a self-reported questionnaire that measure both state (STAI-S), and trait anxiety (STAI-T) Results: A total of 2,446 completed responses were received. The mean and standard deviation (SD) for the total knowledge score was 20.3 (SD ± 2.9) out of a possible score of 23. The social disruption and household economic impact were notable, particularly in provinces with higher cumulative confirmed cases. The majority of responses indicated a low perceived susceptibility of being infected (86.7% [95%CI 85.4–88.1]), with a fair proportion of respondents perceiving a higher severity (62.9% [95% CI 61.0–64.8]). The mean total impact score was 9.9 (SD ± 3.8) out of a possible score of 15. The mean score for STAI-S was 48.7 (SD ± 10.8), whereas the mean STAI-T score was 45.7 (SD ± 8.5). By demographics, women reported significantly higher odds for higher levels of both STAI-S (OR = 1.67) and STAI-T (OR = 1.30) compared to men. People of a younger age were also more likely to experience higher STAI-S and STAI-T. Higher perceived susceptibility and severity and impact were strong predictors of higher levels of STAI-S and STAI-T. Conclusion: Our findings can assist in tailoring public communication to change people's knowledge and attitudes. The present study also underlined the importance of the promotion of mental health during infectious disease outbreaks to help in moderating the perceived threat, social and household economic impact, targeting the vulnerable segment of the population.


title: The Coronavirus Replicase

text: Coronavirus genome replication and transcription take place at cytoplasmic membranes and involve coordinated processes of both continuous and discontinuous RNA synthesis that are mediated by the viral replicase, a huge protein complex encoded by the 20-kb replicase gene. The replicase complex is believed to be comprised of up to 16 viral subunits and a number of cellular proteins. Besides RNA-dependent RNA polymerase, RNA helicase, and protease activities, which are common to RNA viruses, the coronavirus replicase was recently predicted to employ a variety of RNA processing enzymes that are not (or extremely rarely) found in other RNA viruses and include putative sequence-specific endoribonuclease, 3′-to-5′ exoribonuclease, 2′-O-ribose methyltransferase, ADP ribose 1′-phosphatase and, in a subset of group 2 coronaviruses, cyclic phosphodiesterase activities. This chapter reviews (1) the organization of the coronavirus replicase gene, (2) the proteolytic processing of the replicase by viral proteases, (3) the available functional and structural information on individual subunits of the replicase, such as proteases, RNA helicase, and the RNA-dependent RNA polymerase, and (4) the subcellular localization of coronavirus proteins involved in RNA synthesis. Although many molecular details of the coronavirus life cycle remain to be investigated, the available information suggests that these viruses and their distant nidovirus relatives employ a unique collection of enzymatic activities and other protein functions to synthesize a set of 5′-leader-containing subgenomic mRNAs and to replicate the largest RNA virus genomes currently known.


title: Genome Wide Association Identifies PPFIA1 as a Candidate Gene for Acute Lung Injury Risk Following Major Trauma

text: Acute Lung Injury (ALI) is a syndrome with high associated mortality characterized by severe hypoxemia and pulmonary infiltrates in patients with critical illness. We conducted the first investigation to use the genome wide association (GWA) approach to identify putative risk variants for ALI. Genome wide genotyping was performed using the Illumina Human Quad 610 BeadChip. We performed a two-stage GWA study followed by a third stage of functional characterization. In the discovery phase (Phase 1), we compared 600 European American trauma-associated ALI cases with 2266 European American population-based controls. We carried forward the top 1% of single nucleotide polymorphisms (SNPs) at p<0.01 to a replication phase (Phase 2) comprised of a nested case-control design sample of 212 trauma-associated ALI cases and 283 at-risk trauma non-ALI controls from ongoing cohort studies. SNPs that replicated at the 0.05 level in Phase 2 were subject to functional validation (Phase 3) using expression quantitative trait loci (eQTL) analyses in stimulated B-lymphoblastoid cell lines (B-LCL) in family trios. 159 SNPs from the discovery phase replicated in Phase 2, including loci with prior evidence for a role in ALI pathogenesis. Functional evaluation of these replicated SNPs revealed rs471931 on 11q13.3 to exert a cis-regulatory effect on mRNA expression in the PPFIA1 gene (p = 0.0021). PPFIA1 encodes liprin alpha, a protein involved in cell adhesion, integrin expression, and cell-matrix interactions. This study supports the feasibility of future multi-center GWA investigations of ALI risk, and identifies PPFIA1 as a potential functional candidate ALI risk gene for future research.


title: Tuberculosis and pneumonia in HIV-infected children: an overview

text: Pneumonia remains the most common cause of hospitalization and the most important cause of death in young children. In high human immunodeficiency virus (HIV)-burden settings, HIV-infected children carry a high burden of lower respiratory tract infection from common respiratory viruses, bacteria and Mycobacterium tuberculosis. In addition, Pneumocystis jirovecii and cytomegalovirus are important opportunistic pathogens. As the vertical transmission risk of HIV decreases and access to antiretroviral therapy increases, the epidemiology of these infections is changing, but HIV-infected infants and children still carry a disproportionate burden of these infections. There is also increasing recognition of the impact of in utero exposure to HIV on the general health of exposed but uninfected infants. The reasons for this increased risk are not limited to socioeconomic status or adverse environmental conditions—there is emerging evidence that these HIV-exposed but uninfected infants may have particular immune deficits that could increase their vulnerability to respiratory pathogens. We discuss the impact of tuberculosis and other lower respiratory tract infections on the health of HIV-infected infants and children.


title: First Confirmed Cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection in the United States, Updated Information on the Epidemiology of MERS-CoV Infection, and Guidance for the Public, Clinicians, and Public Health Authorities — May 2014

text: Since mid-March 2014, the frequency with which cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection have been reported has increased, with the majority of recent cases reported from Saudi Arabia and United Arab Emirates (UAE). In addition, the frequency with which travel-associated MERS cases have been reported and the number of countries that have reported them to the World Health Organization (WHO) have also increased. The first case of MERS in the United States, identified in a traveler recently returned from Saudi Arabia, was reported to CDC by the Indiana State Department of Health on May 1, 2014, and confirmed by CDC on May 2. A second imported case of MERS in the United States, identified in a traveler from Saudi Arabia having no connection with the first case, was reported to CDC by the Florida Department of Health on May 11, 2014. The purpose of this report is to alert clinicians, health officials, and others to increase awareness of the need to consider MERS-CoV infection in persons who have recently traveled from countries in or near the Arabian Peninsula. This report summarizes recent epidemiologic information, provides preliminary descriptions of the cases reported from Indiana and Florida, and updates CDC guidance about patient evaluation, home care and isolation, specimen collection, and travel as of May 13, 2014.


title: Single-Stranded DNA Aptamers against Pathogens and Toxins: Identification and Biosensing Applications

text: Molecular recognition elements (MREs) can be short sequences of single-stranded DNA, RNA, small peptides, or antibody fragments. They can bind to user-defined targets with high affinity and specificity. There has been an increasing interest in the identification and application of nucleic acid molecular recognition elements, commonly known as aptamers, since they were first described in 1990 by the Gold and Szostak laboratories. A large number of target specific nucleic acids MREs and their applications are currently in the literature. This review first describes the general methodologies used in identifying single-stranded DNA (ssDNA) aptamers. It then summarizes advancements in the identification and biosensing application of ssDNA aptamers specific for bacteria, viruses, their associated molecules, and selected chemical toxins. Lastly, an overview of the basic principles of ssDNA aptamer-based biosensors is discussed.


title: Généralités sur l'infection du système nerveux par les virus

text: Summary Study of nervous system viral diseases is not limited to descriptions of the topography of the infection in man : it also includes studies of animal models which can help in the understanding of the physiopathology of the diseases. It is unlikely than all viruses which can infect nervous tissues are known, and new human viruses have been discovered by Neurologists. Analysis of the route of viral penetration into the brain, and of differing cell susceptibility can help our understanding of disease. Pathological modalities, other than acute infection, have been recently described. Slow virus infections can result from an atypical relationship between the virus and the cell, or the infected cell and the immunological response of the host, as well as from infection by a new category of unconventional agents which nervertheless share some common properties with known viruses.


title: Drug adherence and the incidence of coronary heart disease- and stroke-specific mortality among 218,047 patients newly prescribed an antihypertensive medication: A five-year cohort study

text: Abstract Background Randomized trials have shown that optimal adherence to antihypertensive agents could protect against cardiovascular diseases, but whether adherence reduces cardiovascular deaths in community settings has not been explored so fully. This study evaluates the association between antihypertensive adherence and cardiovascular (coronary heart disease and stroke) mortality in the primary care settings. Methods From a territory-wide database in Hong Kong, we included all patients who were prescribed their first-ever antihypertensive agents in the years between 2001 and 2005 from the public healthcare sector. All patients were followed up for five years, and assigned as having poor (Proportion of Days Covered [PDC]<40%), intermediate (40–79%), and high (≥80%) adherence to antihypertensive agents. The association between antihypertensive adherence and cardiovascular mortality was evaluated by using the Cox proportional hazard models. Results From a total of 218,047 eligible patients, 3825 patients (1.75%) died of cardiovascular disease within five years after having received their first-ever antihypertensive agents. The proportions of patients having poor, intermediate, and high medication adherence were 32.9%, 12.1%, and 55.0%, respectively. Higher adherence levels at PDC 40%–79% (HR=0.46, 95% C.I. 0.41–0.52, p<0.001) and ≥80% (HR=0.91, 95% C.I. 0.85–0.98, p=0.012) were significantly less likely to be associated with mortality than the poor adherence (PDC0.040) group. Conclusions Better antihypertensive adherence was associated with lower cardiovascular mortality. This highlights the need to promote adherence through strategies which have been proved to be effective in clinical settings.


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title: A new method of assessing aerosolized bacteria generated during orthodontic debonding procedures

text: Introduction The main objective of this study was to assess the efficacy of a new and innovative method of harvesting bacteria that are aerosolized during orthodontic debonding. Additionally, the protection efficacy of several commercially available masks from such aerosols was assessed in a pilot study. Methods Twenty-six subjects were debonded during aerosol sampling, by using an innovative collection system to harvest bonding dust liberated during debonding. Dark-field microscopy, gram-stain microscopy, and chemical identification were used to determine speciation of the collected aerosol from 23 subjects. Three additional subjects were used to test 3 commercial dental or protective masks to determine whether they provide effective protection from the aerosol. Results Twenty-one species of oral bacteria were identified by the new sampling technique. Two of the 3 masks that were tested offered no protection against the aerosolized bacteria. Conclusions A new and effective method for collecting airborne bacteria is presented. Some conventional dental masks offer no protection from aerosolized organisms liberated during debonding procedures. Further assessment of mask efficacy is ongoing.


title: Structural and functional characterisation of ferret interleukin-2

text: Abstract While the ferret is a valuable animal model for a number of human viral infections, such as influenza, Hendra and Nipah, evaluating the cellular immune response following infection has been hampered by the lack of a number of species-specific immunological reagents. Interleukin 2 (IL-2) is one such key cytokine. Ferret recombinant IL-2 incorporating a C-terminal histidine tag was expressed and purified and the three-dimensional structure solved and refined at 1.89 Å by X-ray crystallography, which represents the highest resolution and first non-human IL-2 structure. While ferret IL-2 displays the classic cytokine fold of the four-helix bundle structure, conformational flexibility was observed at the second helix and its neighbouring region in the bundle, which may result in the disruption of the spatial arrangement of residues involved in receptor binding interactions, implicating subtle differences between ferret and human IL-2 when initiating biological functions. Ferret recombinant IL-2 stimulated the proliferation of ferret lymph node cells and induced the expression of mRNA for IFN-γ and Granzyme A.


title: An enhanced beam search algorithm for the Shortest Common Supersequence Problem

text: Abstract The Shortest Common Supersequence Problem asks to obtain a shortest string that is a supersequence of every member of a given set of strings. It has applications, among others, in data compression and oligonucleotide microarray production. The problem is NP-hard, and the existing exact solutions are impractical for large instances. In this paper, a new beam search algorithm is proposed for the problem, which employs a probabilistic heuristic and uses the dominance property to further prune the search space. The proposed algorithm is compared with three recent algorithms proposed for the problem on both random and biological sequences, outperforming them all by quickly providing solutions of higher average quality in all the experimental cases. The Java source and binary files of the proposed IBS_SCS algorithm and our implementation of the DR algorithm and all the random and real datasets used in this paper are freely available upon request.