title: The termini of VSV DI particle RNAs are sufficient to signal RNA encapsidation, replication, and budding to generate infectious particles

text: Abstract Infectious defective interfering (DI) particles of the negative-stranded RNA virus vesicular stomatitis virus (VSV) havebeen recovered from negative-sense transcripts of a plasmid that contains a full-length cDNA derived from the DI-T particle genome. In order to determine the cis-acting sequences necessary for RNA replication, encapsidation, and budding and to approximate the minimal size of RNA that can be packaged into infectious particles, we constructed a series of internal deletions in the DI cDNA to generate plasmids that could be transcribed to yield RNAs which ranged in size from 2209 nucleotides down to 102 nucleotides. All the deletion plasmids retained at least 36 nucleotides from the 5′-terminus and 51 nucleotides from the 3′-terminus of the DI genome. In cells expressing the five VSV proteins, the deleted DI RNAs were examined for their ability to be encapsidated, to replicate, and to bud to produce infectious DI particles. An RNA as small as 191 nucleotides, which contained 46 nucleotides from the 5′-end and 145 nucleotides from the 3′-end of the DI genome was encapsidated, replicated, and budded at least as efficiently as the full-length wild-type DI RNA. In contrast, a 102-nucleotide RNA that contained only the 51 nucleotides from the 5′-end of the DI RNA and its perfect 51-nucleotide complement at the 3′-end replicated poorly and failed to bud infectious DI particles. However, an RNA with an insertion of 1499-nucleotide “stuffer” sequences of non-VSV origin between the two 51-nucleotide complementary termini not only replicated but also budded infectious particles. These data show that the signals necessary for RNA encapsidation, replication, and packaging into infectious DI particles are contained within the 5′-terminal 36 nucleotides and the 3′-terminal 51 nucleotides of the DI RNA genome. Furthermore, the results show that a heterologous sequence can be replicated and packaged into infectious particles if it is flanked by the DI RNA termini.


title: The ABCD study: understanding the development of risk for mental and physical health outcomes

text: Following in the footsteps of other large “population neuroscience” studies, the Adolescent Brain Cognitive Development℠ (ABCD) study is the largest in the U.S. assessing brain development. The study is examining approximately 11,875 youth from 21 sites from age 9 to 10 for approximately ten years into young adulthood. The ABCD Study® has completed recruitment for the baseline sample generally using a multi-stage probability sample including a stratified random sample of schools. The dataset has a wealth of measured attributes of youths and their environment, including neuroimaging, cognitive, biospecimen, behavioral, youth self-report and parent self-report metrics, and environmental measures. The initial goal of the ABCD Study was to examine risk and resiliency factors associated with the development of substance use, but the project has expanded far beyond this initial set of questions and will also greatly inform our understanding of the contributions of biospecimens (e.g., pubertal hormones), neural alterations, and environmental factors to the development of both healthy behavior and brain function as well as risk for poor mental and physical outcomes. This review outlines how the ABCD Study was designed to elucidate factors associated with the development of negative mental and physical health outcomes and will provide a selective overview of results emerging from the ABCD Study. Such emerging data includes initial validation of new instruments, important new information about the prevalence and correlates of mental health challenges in middle childhood, and promising data regarding neural correlates of both healthy and disordered behavior. In addition, we will discuss the challenges and opportunities to understanding both healthy development and the emergence of risk from ABCD Study data. Finally, we will overview the future directions of this large undertaking and the ways in which it will shape our understanding of the development of risk for poor mental and physical health outcomes.


title: COVID‐19 cardiac involvement in a 38‐day old infant

text: The spectrum of clinical manifestations of coronavirus disease 2019 in children is yet to be fully elucidated. We report the case of an infant who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and developed mild cardiovascular inflammation, a novelty for patients of very young age, that contributes to defining the puzzling nature of this disease in pediatric patients. The potential cardiovascular involvement of SARS‐CoV‐2 in children should always be taken into account.


title: siRNA-containing liposomes modified with polyarginine effectively silence the targeted gene

text: Abstract Development of RNA interference (RNAi) technology utilizing the short interfering RNA sequences (siRNA) based ‘targeted’ therapeutics has focused on creating methods for delivering siRNAs to cells and for enhancing siRNA stability in vitro and in vivo. Here, we describe a novel approach for siRNA cellular delivery using siRNA encapsulated into liposomes additionally bearing arginine octamer (R8) molecules attached to their outer surface (R8-liposomes). The R8-liposomal human double minute gene 2 (HDM2)-siRNA demonstrated a significant stability against degradation in the blood serum (siRNA-loaded R8-liposomes remained intact even after 24-h incubation), and higher transfection efficiency into all three tested lung tumor cell lines. siRNA delivery successfully proceeds in the presence of plasma proteins, and R8-liposomes demonstrate low non-specific toxicity. The mechanism of action of R8-liposome-encapsulated siRNA is associated with the RNAi-mediated degradation of the target mRNA. siRNA in R8-liposomes effectively inhibited the targeted gene and significantly reduced the proliferation of cancer cells. The approach offers the potential for siRNA delivery for various in vitro and in vivo applications.


title: Building upon current knowledge and techniques of indoor microbiology to construct the next era of theory into microorganisms, health, and the built environment

text: In the constructed habitat in which we spend up to 90% of our time, architectural design influences occupants’ behavioral patterns, interactions with objects, surfaces, rituals, the outside environment, and each other. Within this built environment, human behavior and building design contribute to the accrual and dispersal of microorganisms; it is a collection of fomites that transfer microorganisms; reservoirs that collect biomass; structures that induce human or air movement patterns; and space types that encourage proximity or isolation between humans whose personal microbial clouds disperse cells into buildings. There have been recent calls to incorporate building microbiology into occupant health and exposure research and standards, yet the built environment is largely viewed as a repository for microorganisms which are to be eliminated, instead of a habitat which is inexorably linked to the microbial influences of building inhabitants. Health sectors have re-evaluated the role of microorganisms in health, incorporating microorganisms into prevention and treatment protocols, yet no paradigm shift has occurred with respect to microbiology of the built environment, despite calls to do so. Technological and logistical constraints often preclude our ability to link health outcomes to indoor microbiology, yet sufficient study exists to inform the theory and implementation of the next era of research and intervention in the built environment. This review presents built environment characteristics in relation to human health and disease, explores some of the current experimental strategies and interventions which explore health in the built environment, and discusses an emerging model for fostering indoor microbiology rather than fearing it.


title: Dermoscopy features of COVID‐19‐related chilblains in children and adolescents

text: Chilblains are skin condition frequently seen by physicians worldwide during the COVID‐19 outbreak. We attended 22 children and adolescents with chilblains during the outbreak peak of COVID‐19 in Madrid. The clinicopathologic and laboratory features of these patients have been reported. We describe herein the dermoscopic findings. Approval from the institutional Ethics Committee and Board was obtained. Standard informed consents were obtained for recording images in all patients.


title: Older Adults’ Strategies for Obtaining Medication Refills in Hypothetical Scenarios in the Face of COVID-19 Risk

text: Abstract Objective To identify whether older adults would avoid going to the pharmacy (e.g., by restricting medications or requesting delivery) due to the risk of COVID-19. Our secondary objectives were to determine which types of medications older adults may be more likely to restrict and to determine factors that influence these decisions. Design Cross-sectional survey experiment in which participants read 6 scenarios, each stating they had a three-day supply of a particular medication remaining. Setting and participants National web-based survey distributed to 1,457 U.S. adults 65 years and older by Dynata during March 25 – April 1, 2020. Outcome measures Participants reported whether they would go to a pharmacy, have a medication delivered, or restrict use of each medication. They reported their perceptions and experiences with COVID-19, health risk factors, preferences for more or less care (Medical Maximizer-Minimizer), medication attitudes (Beliefs about Medicines Questionnaire), health literacy, prescription insurance status, and demographics. Results Most participants (84%) were told to shelter in place, but only 12% reported attempting to obtain extra medications. Participants most often reported that they would go to the pharmacy to obtain each medication (range tramadol 48.9% to insulin 64.9%), except for zolpidem which they were most likely to restrict (45.4%). Participants who reported risk factors for COVID-19 (beyond age) were just as likely to go to the pharmacy as those without. In multinomial logistic regression analyses, women and the oldest participants were more likely to seek delivery of medications. Restricting medications was most common for 2 symptom-focused medications (tramadol and zolpidem), and both demographic factors (e.g., gender) and beliefs (e.g., medical maximizing-minimizing preferences) were associated with such decisions. Conclusion Many older adults intend to continue to go to the pharmacy to obtain their medications during a pandemic, even those who have health conditions that further increase their risk from COVID-19.


title: Cathepsins B and L activate Ebola but not Marburg virus glycoproteins for efficient entry into cell lines and macrophages independent of TMPRSS2 expression

text: Abstract Ebola (EBOV) and Marburg virus (MARV) cause severe hemorrhagic fever. The host cell proteases cathepsin B and L activate the Zaire ebolavirus glycoprotein (GP) for cellular entry and constitute potential targets for antiviral intervention. However, it is unclear if different EBOV species and MARV equally depend on cathepsin B/L activity for infection of cell lines and macrophages, important viral target cells. Here, we show that cathepsin B/L inhibitors markedly reduce 293T cell infection driven by the GPs of all EBOV species, independent of the type II transmembrane serine protease TMPRSS2, which cleaved but failed to activate EBOV-GPs. Similarly, a cathepsin B/L inhibitor blocked macrophage infection mediated by different EBOV-GPs. In contrast, MARV-GP-driven entry exhibited little dependence on cathepsin B/L activity. Still, MARV-GP-mediated entry was efficiently blocked by leupeptin. These results suggest that cathepsins B/L promote entry of EBOV while MARV might employ so far unidentified proteases for GP activation.


title: A biologically inspired immunization strategy for network epidemiology

text: Abstract Well-known immunization strategies, based on degree centrality, betweenness centrality, or closeness centrality, either neglect the structural significance of a node or require global information about the network. We propose a biologically inspired immunization strategy that circumvents both of these problems by considering the number of links of a focal node and the way the neighbors are connected among themselves. The strategy thus measures the dependence of the neighbors on the focal node, identifying the ability of this node to spread the disease. Nodes with the highest ability in the network are the first to be immunized. To test the performance of our method, we conduct numerical simulations on several computer-generated and empirical networks, using the susceptible-infected-recovered (SIR) model. The results show that the proposed strategy largely outperforms the existing well-known strategies.


title: To alert coinfection of COVID-19 and dengue virus in developing countries in the dengue-endemic area

text: Coronavirus disease 2019 (CoVID-19) is a new outbreak infectious disease caused by SARS-CoV-2, which was originated from Wuhan in China and has now spread to the whole world. At the meantime, dengue was endemic in the Southeast Asia and South America, and a part of the patients shared the same symptoms, so, we write this paper to alert the clinicians to distinguish these two diseases.


title: Encephalomyocarditis virus is potentially derived from eastern bent-wing bats living in East Asian countries

text: Abstract Bats are reservoir hosts of many zoonotic viruses and identification of viruses that they carry is important. This study aimed to use high throughput screening to identify the viruses in fecal guano of Taiwanese insectivorous bats caves in order to obtain more information on bat-derived pathogenic viruses in East Asia. Guano samples were collected from two caves in Taiwan, pooled, and then subjected to Multiplex PCR-based next generation sequencing for viral identification. Subsequently, encephalomyocarditis virus (EMCV) sequence was detected and confirmed by reverse transcription PCR. EMCV is considered as rodent virus and thus, animal species identification through cytochrome oxidase I (COI) barcoding was further done to identify the viral source. Finally, determination of distribution and verification of the presence of EMCV in guano obtained from Japanese and South Korean caves was also done. We concluded that the guano collected was not contaminated with the excrement of rodents which were reported and presumed to live in Taiwan. Also, EMCV genome fragments were found in guanos of Japanese and South Korean caves. It is possible that the eastern bent-wing bat (Miniopterus fuliginosus) is one of the natural hosts of EMCV in East Asia.


title: Microorganisms Causing Community-Acquired Acute Bronchitis: The Role of Bacterial Infection

text: BACKGROUND: Although acute bronchitis is quite common, there is relatively limited information regarding the microorganisms that are involved in this illness. METHODS: We performed a prospective study of acute bronchitis at 31 hospitals and clinics in Korea from July 2011 to June 2012. Sputum specimens were collected for polymerase chain reaction (PCR) and culture of microorganisms. RESULTS: Of the 811 enrolled patients, 291 had acceptable sputum specimens that were included for analysis of the etiologic distribution. With multiplex PCR testing, viruses were identified in 36.1% (105/291), most commonly rhinovirus (25.8%) and coronavirus (3.8%). Typical bacteria were isolated in 126/291 (43.3%) patients. Among these patients Haemophilus influenzae (n = 39) and Streptococcus pneumoniae (n = 30) were isolated most commonly; atypical bacteria were identified in 44 (15.1%) patients. Bacteria-only, virus-only, and mixed infections (bacteria plus virus) accounted for 36.7% (98/291), 17.2% (50/291), and 18.9% (55/291) of infections, respectively. In particular, 52.4% of patients with viral infection had a concurrent bacterial infection, and rhinovirus was the most common virus in mixed infections (40/55). Additionally, infections with typical bacteria were more common in patients with chronic lung disease (p = 0.029), and typical bacterial infections showed a trend towards a higher prevalence with older age (p = 0.001). CONCLUSIONS: Bacteria were associated with almost half of community-acquired acute bronchitis cases. Additional studies are required to further illuminate the role of bacteria and to identify patient groups most likely to benefit from antibiotic treatment.


title: Curing a viral infection by targeting the host: The example of cyclophilin inhibitors

text: Every step of the viral life cycle is dependent on the host, which potentially can be explored for antiviral targets. Historically, however, drug discovery has focused mainly on viral targets, because of their perceived specificity. Efforts to pursue host targets have been largely hampered by concern over potential on-target toxicity, the lack of predictive cell culture and animal models, and the complexity of host–virus interactions. On the other hand, there are distinct advantages of targeting the host, such as creating a high barrier to resistance, providing broad coverage of different genotypes/serotypes and possibly even multiple viruses, and expanding the list of potential targets, when druggable viral targets are limited. Taking hepatitis C virus (HCV) as the example, there are more than 20 inhibitors of the viral protease, polymerase and NS5A protein currently in advanced clinical testing. However, resistance has become a main challenge with these direct-acting antivirals, because HCV, an RNA virus, is notoriously prone to mutation, and a single mutation in the viral target may prevent the binding of an inhibitor, and rendering it ineffective. Host cyclophilin inhibitors have shown promising effects both in vitro and in patients to prevent the emergence of resistance and to cure HCV infection, either alone or in combination with other agents. They are also capable of blocking the replication of a number of other viral pathogens. While the road to developing host-targeting antivirals has been less traveled, and significant challenges remain, delivering the most effective antiviral regimen, which may comprise inhibitors of both host and viral targets, should be well worth the effort.


title: Crafting Jobs for Occupational Satisfaction and Innovation among Manufacturing Workers Facing the COVID-19 Crisis

text: China’s manufacturing employees are confronted with unprecedent occupational and innovation challenges caused by the ongoing COVID-19 crisis coupled with the pressure of being replaced by digital technologies. To gain a better understanding of the rising occupational uncertainty during this critical time, based on the job demands-resources (JD-R) theory, we examined the associations of employees’ job crafting behaviors (JCB) with their occupational satisfaction and innovation workplace behavior (IWB), as well as the mediating effect of work engagement on the above relationships. The final usable data were obtained from the formal survey of 311 employees of six manufacturing companies that have returned to work amid COVID-19. Structural equation modelling was adopted to analyze the data. Results show that employees’ JCB strengthens their occupational satisfaction and IWB via work engagement. Theoretically, our research enriches the existing body of knowledge about JCB from a cross-disciplinary angle integrating the perspectives of career and psychology. Practically, we offer valuable first-hand evidence about how manufacturing employees conducted JCB to re-orient their careers and to innovate in the face of the high unemployment situation.


title: SGTA: A New Player in the Molecular Co-Chaperone Game

text: Small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) is a steroid receptor molecular co-chaperone that may substantially influence hormone action and, consequently, hormone-mediated carcinogenesis. To date, published studies describe SGTA as a protein that is potentially critical in a range of biological processes, including viral infection, cell division, mitosis, and cell cycle checkpoint activation. SGTA interacts with the molecular chaperones, heat shock protein 70 (HSP70) and HSP90, and with steroid receptor complexes, including those containing the androgen receptor. Steroid receptors are critical for maintaining cell growth and differentiation in hormonally regulated tissues, such as male and female reproductive tissues, and also play a role in disease states involving these tissues. There is growing evidence that, through its interactions with chaperones and steroid receptors, SGTA may be a key player in the pathogenesis of hormonally influenced disease states, including prostate cancer and polycystic ovary syndrome. Research into the function of SGTA has been conducted in several model organisms and cell types, with these studies showing that SGTA functionality is cell-specific and tissue-specific. However, very few studies have been replicated in multiple cell types or experimental systems. Although a broad range of functions have been attributed to SGTA, there is a serious lack of mechanistic information to describe how SGTA acts. In this review, published evidence linking SGTA with hormonally regulated disease states is summarized and discussed, highlighting the need for future research to more clearly define the biological function(s) of this potentially important co-chaperone. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12672-013-0151-0) contains supplementary material, which is available to authorized users.


title: Full-length genome sequences of porcine epidemic diarrhoea virus strain CV777; Use of NGS to analyse genomic and sub-genomic RNAs

text: Porcine epidemic diarrhoea virus, strain CV777, was initially characterized in 1978 as the causative agent of a disease first identified in the UK in 1971. This coronavirus has been widely distributed among laboratories and has been passaged both within pigs and in cell culture. To determine the variability between different stocks of the PEDV strain CV777, sequencing of the full-length genome (ca. 28kb) has been performed in 6 different laboratories, using different protocols. Not surprisingly, each of the different full genome sequences were distinct from each other and from the reference sequence (Accession number AF353511) but they are >99% identical. Unique and shared differences between sequences were identified. The coding region for the surface-exposed spike protein showed the highest proportion of variability including both point mutations and small deletions. The predicted expression of the ORF3 gene product was more dramatically affected in three different variants of this virus through either loss of the initiation codon or gain of a premature termination codon. The genome of one isolate had a substantially rearranged 5´-terminal sequence. This rearrangement was validated through the analysis of sub-genomic mRNAs from infected cells. It is clearly important to know the features of the specific sample of CV777 being used for experimental studies.


title: Diagnostic yield of bronchoalveolar lavage in immunocompromised children with malignant and non‐malignant disorders

text: BACKGROUND: The diagnostic yield of bronchoalveolar lavage (BAL) in the Immunocompromised pediatric population has ranged from 28% to 68%. We hypothesized that the diagnostic yield of BALs would be higher in more recent years due to new diagnostic assays. METHODS: A retrospective case series was performed among immunocompromised children ≤18 years old who underwent BALs from 2001 to 2012, to assess the yield of microbiologic diagnostic studies and to determine the impact of BAL findings on antimicrobial management. RESULTS: In all, 123 subjects underwent 174 BALs (mean age 9.9 years). Underlying diagnoses included both malignant (n = 79) and non‐malignant (n = 44) disorders, and 75 (61.0%) subjects were hematopoietic stem cell transplant (HSCT) recipients. Fifty‐four (31.0%) of 174 BAL were positive for ≥1 potential pathogen (n = 58 microorganisms). The diagnostic yield of BALs performed from 2001 to 2006 versus2007–2012 was similar (40.5% vs. 26.6%, respectively, P = 0.07). Most subjects (86.2%) were on ≥1 antimicrobial at the time of BAL. Most (65.8%) negative BALs were associated with narrowing antimicrobial therapy, while most (74.1%) positive BALs were associated with continuing or changing to targeted antimicrobial therapy. CONCLUSIONS: In this study population, the diagnostic yield of BAL was similar to that previously described and unchanged in more recent years. Both negative and positive BALs were associated with changes in antimicrobial management. SUMMARY: A 10‐year retrospective review of bronchoalveolar lavage in 123 immunocompromised children determined that the rate of isolation of potential pathogens was 31% in this population. The majority of BAL was associated with a change in antimicrobial therapy. Pediatr Pulmonol. 2017;52:820–826. © 2017 Wiley Periodicals, Inc.


title: Transcriptomics analysis reveals candidate genes and pathways for susceptibility or resistance to Singapore grouper iridovirus in orange-spotted grouper (Epinephelus coioides)

text: Abstract In this study, the transcriptional response of grouper to Singapore grouper iridovirus (SGIV) stimulation was characterized using RNA sequencing. Transcriptome sequencing of three test groups in the grouper was performed using the Illumina MiSeq platform. The three test groups were a control group, which was injected with PBS buffer; a high-susceptible (HS) group, which died shortly after the SGIV injection; and a high-resistance (HR) group, which survived the SGIV injection. In total, 38,253 unigenes were generated. When the HS group was compared with the control group, 885 unigenes were upregulated and 487 unigenes were downregulated. When the HR and control groups were compared, 1114 unigenes were upregulated and 420 were downregulated, and when the HR and HS groups were compared, 1010 unigenes were upregulated and 375 were downregulated. In the KEGG analysis, two immune-related pathways, the p53 and peroxisome proliferator-activated receptor pathways, were detected with highly significant enrichment. In addition, 7465 microsatellites and 22,1569 candidate single nucleotide polymorphisms were identified from our transcriptome data. The results suggested several pathways that are associated with traits of disease susceptibility or disease resistance, and provided extensive information about novel gene sequences, gene expression profiles, and genetic markers. This may contribute to vaccine research and a breeding program against SGIV infection in grouper.


Testing Dilemmas: Post negative, positive SARS-CoV-2 RT-PCR – is it a reinfection?


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title: Environmental triggers and avoidance in the management of asthma

text: Identifying asthma triggers forms the basis of environmental secondary prevention. These triggers may be allergenic or nonallergenic. Allergenic triggers include indoor allergens, such as house dust mites (HDMs), molds, pets, cockroaches, and rodents, and outdoor allergens, such as pollens and molds. Clinical observations provide support for the role of HDM exposure as a trigger, although avoidance studies provide conflicting results. Molds and their metabolic products are now considered to be triggers of asthma attacks. Pets, dogs, and especially cats can undoubtedly trigger asthmatic symptoms in sensitized subjects. Avoidance is difficult and rarely adhered to by families. Cockroach allergens contribute to asthma morbidity, and avoidance strategies can lead to clinical benefit. Mouse allergens are mostly found in inner-city dwellings, but their implication in asthma morbidity is debated. In the outdoors, pollens can induce seasonal asthma in sensitized individuals. Avoidance relies on preventing pollens from getting into the house and on minimizing seasonal outdoor exposure. Outdoor molds may lead to severe asthma exacerbations. Nonallergenic triggers include viral infections, active and passive smoking, meteorological changes, occupational exposures, and other triggers that are less commonly involved. Viral infection is the main asthma trigger in children. Active smoking is associated with higher asthma morbidity, and smoking cessation interventions should be personalized. Passive smoking is also a risk factor for asthma exacerbation. The implementation of public smoking bans has led to a reduction in the hospitalization of asthmatic children. Air pollution levels have been linked with asthmatic symptoms, a decrease in lung function, and increased emergency room visits and hospitalizations. Since avoidance is not easy to achieve, clean air policies remain the most effective strategy. Indoor air is also affected by air pollutants, such as cigarette smoke and volatile organic compounds generated by building and cleaning materials. Occupational exposures include work-exacerbated asthma and work-related asthma.


title: The Cucumber leaf spot virus p25 auxiliary replicase protein binds and modifies the endoplasmic reticulum via N-terminal transmembrane domains

text: Abstract Cucumber leaf spot virus (CLSV) is a member of the Aureusvirus genus, family Tombusviridae. The auxiliary replicase of Tombusvirids has been found to localize to endoplasmic reticulum (ER), peroxisomes or mitochondria; however, localization of the auxiliary replicase of aureusviruses has not been determined. We have found that the auxiliary replicase of CLSV (p25) fused to GFP colocalizes with ER and that three predicted transmembrane domains (TMDs) at the N-terminus of p25 are sufficient for targeting, although the second and third TMDs play the most prominent roles. Confocal analysis of CLSV infected 16C plants shows that the ER becomes modified including the formation of punctae at connections between ER tubules and in association with the nucleus. Ultrastructural analysis shows that the cytoplasm contains numerous vesicles which are also found between the perinuclear ER and nuclear membrane. It is proposed that these vesicles correspond to modified ER used as sites for CLSV replication.


title: Clariant extends oxygen scavengers range; agrees sale of masterbatches business

text: A new oxygen-scavenging additive masterbatch has been added to Clariant's Mevopur range of medical-grade materials for pharmaceutical packaging and medical devices. According to the company, Mevopur ProTect provides effective protection against oxygen (O2) degradation for drugs and nutraceuticals stored in polyethylene terephthalate (PET) bottles, even in a transparent monolayer construction, thereby ensuring the requisite shelf-life for such products. The new masterbatch concentrate was introduced at the Paris Pharmapack Europe event in February.


title: Outbreak of Human Parainfluenza Virus Type 1 in a Kindergarten from China, 2018

text: Objective We reported an outbreak of human parainfluenza virus type 1 (HPIV1) in a kindergarten and explored the genetic characteristics of HPIV1 hemagglutinin-neuraminidase (HN) and fusion (F) genes to provide more evidence about HPIV1 outbreaks. Methods Suspected cases were the children with an influenza-like illness during June 20 to 26, 2018. Nasopharyngeal swabs were collected and screened to determine the presence of respiratory pathogens by real-time fluorescent quantitative polymerase chain reaction. The HN and F gene sequences of HPIV-positive samples were further amplified and sequenced to confirm the HPIV genotype and identify genetic characteristics. A phylogenetic tree, based on the HN and F genes, was reconstructed by maximum likelihood method. Results Fourteen children in the outbreak were diagnosed as upper respiratory tract infection. The most common symptom was cough (10/14), followed by rhinorrhea (5/14), sore throat (4/14), headache (1/14), and abdominal pain (1/14). Eight patients were positive for HPIV1 and negative for other pathogens. Phylogenetic tree demonstrated that the eight strains from the year 2018 in our study located in the clade 2.3. Two specific substitutions (N333S and I509M) in the amino acids of the F protein and two substitutions (V19A and L436I) in the HN protein were different from other strains in the clade 2. Conclusion HPIV1 was attributed to the outbreak, which may be related to the genetic variations of HPIV1.


title: Comparison of intestinal gene expression in Atlantic cod (Gadus morhua) fed standard fish meal or soybean meal by means of suppression subtractive hybridization and real-time PCR

text: Abstract Gene expression was studied in Atlantic cod fed two different diets, fish meal (FM) and dehulled and extracted soybean meal (SBM). RNA was isolated from the distal part of the mid-intestine of Atlantic cod and suppression subtractive hybridization (SSH) was employed to screen for genes that showed changes in expression in response to the two dietary treatments. We made a cDNA subtracted library, isolated and sequenced 192 clones. Identification of 157 clones was predicted by BLAST. Most of the clones were previously unidentified in cod. Expression of 12 selected clones was further studied by quantitative PCR. Expression of four clones showing similarity to aminopeptidase N, transcobalamin I precursor, cytochrome P450 3A40, and ras-related nuclear protein was significantly up regulated in intestine of cod fed SBM compared to cod fed FM. A trend towards up regulation of a clone with similarity to fatty acid binding protein in SBM-fed cod was also observed. No significant differences in expression were observed for: transmembrane 4 superfamily protein member, polypeptide N-acetylgalactosaminyltransferase, glutathione peroxidase, peroxiredoxin 4, SEC61, F-BOX, and 14-3-3.


docid: apbrwqwj

title: Comparison of oral, intravenous, and subcutaneous fluid therapy for resuscitation of calves with diarrhea

text: ABSTRACT Neonatal diarrhea remains the primary cause of mortality in dairy calves around the world, and optimal treatment protocols are needed. The main goals of therapy are to restore hydration and electrolyte concentrations, correct strong ion (metabolic) acidemia, and provide nutritional support. Administration of oral electrolyte solutions (OES) has long been the primary method used to treat neonatal diarrhea in humans and calves because OES are capable of addressing each of the primary goals of therapy. In calves with moderate dehydration, we hypothesized that oral electrolytes would be as good as or better than small volumes of intravenous (IV) or subcutaneous (SC) fluids. Therefore, the main goal of this study was to compare the ability of a commercially available oral electrolyte solution (OES) administered alone or in combination with hypertonic saline with small volumes of IV or SC fluid therapy to resuscitate calves with diarrhea. Thirty-three Holstein calves from 5 to 14 d of age were utilized in this clinical trial. Diarrhea and dehydration were induced by adding sucrose to the milk replacer. In addition, hydrochlorothiazide and spironolactone were given orally and furosemide intramuscularly. Depression status, clinical hydration scores, fecal consistency, and body weight were recorded at regular intervals. Treatment began when calves had severe diarrhea and had a decrease in plasma volume of at least 10%. Calves were randomly assigned to 1 of 4 treatment groups of 8 to 9 calves per group: (1) OES; (2) OES with hypertonic saline (4 mL/kg, IV); (3) IV fluids (lactated Ringer's, 2 L); or (4) SC fluids (lactated Ringer's, 2 L). Treatments were given at 0 and 12 h. Changes in plasma volume, blood pH, electrolyte levels, and physical examination scores were determined before therapy and again at 1, 2, 4, 8, and 12 h after each treatment. All 4 treatments were ultimately successful in improving hydration as well as increasing blood pH; however, animals in both groups that received OES had much faster resuscitation than those in either the IV or SC fluid group. In conclusion, oral electrolyte products remain the gold standard for resuscitating diarrheic calves with moderate dehydration and acidemia and will likely perform better than small volumes of IV lactated Ringer's solution. Subcutaneous fluids by themselves are a poor treatment option and should be only be used as supportive therapy following the initial correction of hypovolemia and metabolic acidosis.


title: Beyond receptors and signaling: epigenetic factors in the regulation of innate immunity

text: The interaction of innate immune cells with pathogens leads to changes in gene expression that elicit our body’s first line of defense against infection. Although signaling pathways and transcription factors have a central role, it is becoming increasingly clear that epigenetic factors, in the form of DNA or histone modifications, as well as noncoding RNAs, are critical for generating the necessary cell lineage as well as context-specific gene expression in diverse innate immune cell types. Much of the epigenetic landscape is set during cellular differentiation; however, pathogens and other environmental triggers also induce changes in histone modifications that can either promote tolerance or ‘train’ innate immune cells for a more robust antigen-independent secondary response. Here we review the important contribution of epigenetic factors to the initiation, maintenance and training of innate immune responses. In addition, we explore how pathogens have hijacked these mechanisms for their benefit and the potential of small molecules targeting chromatin machinery as a way to boost or subdue the innate immune response in disease.


title: Targeting the Adipose Tissue in COVID‐19

text: The WHO considers non-communicable diseases (NCDs), such as obesity, a major risk factor for becoming seriously ill with 2019 novel coronavirus (COVID-19) (1). A study by the UK Intensive Care National Audit and Research Centre indicates that two thirds of people who developed serious or fatal COVID-19-related complications were overweight or obese (2). The report includes data from all COVID-19 admissions in intensive care units in the UK until midnight, March 19, 2020. The study shows that almost 72 % of those in critical care units are either overweight or with obesity suggesting the impact of obesity in seriously ill COVID-19 patients.


title: Detection of viral, Chlamydia pneumoniae and Mycoplasma pneumoniae infections in exacerbations of asthma in children

text: Abstract Background: A high frequency of virus infections has been recently pointed out in the exacerbations of asthma in children. Objectives: To confirm this, using conventional and molecular detection methods, and expanding the study to younger children. Study design: One hundred and thirty-two nasal aspirates from 75 children hospitalized for a severe attack of asthma were studied (32 infants, mean age 9.1 months; and 43 children, mean age 5.6 years). According to the virus, a viral isolation technique, immunofluorescence assays (IFA) or both were used for the detection of rhinovirus, enterovirus, respiratory syncytial (RS) virus, adenovirus, coronavirus 229E, influenza and parainfluenza virus. Polymerase chain reaction (PCR) assays were used for the detection of rhinovirus, enterovirus, RS virus, adenovirus, coronavirus 229E and OC43, Chlamydia pneumoniae and Mycoplasma pneumoniae. Results: Using IFA and viral isolation techniques, viruses were detected in 33.3% of cases, and by PCR techniques, nucleic acid sequences of virus, Chlamydia pneumoniae and Mycoplasma pneumoniae were obtained in 71.9% of cases. The combination of conventional and molecular techniques detects 81.8% of positive samples. Two organisms were identified in the same nasal sample in 20.4% of the cases. The percentage of detections was higher (85.9%) in the younger group than in the other (77%). The most frequently detected agents were rhinovirus (46.9%) and RS virus (21.2%). Using PCR rather than conventional techniques, the detection rates were increased 5.8- and 1.6-fold in rhinovirus and RS virus infections, respectively. The detection levels of the other organisms are as follows: 9.8, 5.1, 4.5, 4.5, 4.5, 3.7, and 2.2% for enterovirus, influenza virus, Chlamydia pneumoniae, adenovirus, coronavirus, parainfluenza virus, and Mycoplasma pneumoniae, respectively. Conclusion: These results confirm the previously reported high frequency of rhinovirus detection in asthmatic exacerbations in children. They also point out the frequency of RS virus detection, and emphasize the fact that PCR assays may be necessary to diagnose respiratory infections in asthma.


title: Creosote bush lignans for human disease treatment and prevention: Perspectives on combination therapy

text: Abstract The medicinal properties of the most successful plant in the deserts of the western hemisphere, the creosote bush (Larrea tridentata), are evidenced by the long traditional usage of the plants by the Native Americans Indian tribes in Southwestern North America and the Amerindians from South America. The plant is rich in simple bisphenyl lignans and tricyclic lignans known as cyclolignans. These compounds are responsible for many of the pharmacological activities of extracts of the plants. Some of these activities, namely antiherpes, antioxidant, antifungal, and anti-inflammatory, were known a century ago. Only recently have further studies revealed other crucial activities of the same plant molecules as powerful agents against human immunodeficiency virus, human papillomavirus, cancer, neurodegenerative diseases, and symptoms of aging. Molecular mechanisms underlying the antiviral and anticancer activities have been elucidated and involve the inhibition of SP1 dependent gene transcription. This review summarizes the recent findings on creosote bush lignans. We introduce the concept of a cocktail of safe well-characterized natural products from the creosote bush that would represent a bridge between oriental herbal medicines and Western drug-based therapies.


title: The Pandemic: Lessons for Bioethics?

text: Seeking useful ways to respond to the Covid‐19 pandemic, bioethicists have been tempted to claim for themselves what Alasdair MacIntyre characterized in After Virtue as the moral fiction of managerial expertise. They have been eager to offer a wide range of policy prescriptions, presenting themselves as bureaucratic managers and suggesting an expertise that bioethics may not in fact be able to offer. This was evident, for example, in the petition published by The Hastings Center in March 2020. The pandemic could foster a more hopeful future for bioethics if it were to focus attention less on policy decisions that belong to all citizens and more on some of the most basic moral questions that life presents and with which bioethics has always dealt—including, surely, the virtues needed in order to live well in a time of pandemic.


title: Travel Surveillance and Genomics Uncover a Hidden Zika Outbreak during the Waning Epidemic

text: Summary The Zika epidemic in the Americas has challenged surveillance and control. As the epidemic appears to be waning, it is unclear whether transmission is still ongoing, which is exacerbated by discrepancies in reporting. To uncover locations with lingering outbreaks, we investigated travel-associated Zika cases to identify transmission not captured by reporting. We uncovered an unreported outbreak in Cuba during 2017, a year after peak transmission in neighboring islands. By sequencing Zika virus, we show that the establishment of the virus was delayed by a year and that the ensuing outbreak was sparked by long-lived lineages of Zika virus from other Caribbean islands. Our data suggest that, although mosquito control in Cuba may initially have been effective at mitigating Zika virus transmission, such measures need to be maintained to be effective. Our study highlights how Zika virus may still be “silently” spreading and provides a framework for understanding outbreak dynamics. Video Abstract


title: Treatment options for COVID-19: the reality and challenges

text: Abstract An outbreak related to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019. An extremely high potential for dissemination resulted in the global coronavirus disease 2019 (COVID-19) pandemic in 2020. Despite the worsening trends of COVID-19, no drugs are validated to have significant efficacy in clinical treatment of COVID-19 patients in large-scale studies. Remdesivir is considered the most promising antiviral agent; it works by inhibiting the activity of RNA-dependent RNA polymerase (RdRp). A large-scale study investigating the clinical efficacy of remdesivir (200 mg on day 1, followed by 100 mg once daily) is on-going. The other excellent anti-influenza RdRp inhibitor favipiravir is also being clinically evaluated for its efficacy in COVID-19 patients. The protease inhibitor lopinavir/ritonavir (LPV/RTV) alone is not shown to provide better antiviral efficacy than standard care. However, the regimen of LPV/RTV plus ribavirin was shown to be effective against SARS-CoV in vitro. Another promising alternative is hydroxychloroquine (200 mg thrice daily) plus azithromycin (500 mg on day 1, followed by 250 mg once daily on day 2-5), which showed excellent clinical efficacy on Chinese COVID-19 patients and anti-SARS-CoV-2 potency in vitro. The roles of teicoplanin (which inhibits the viral genome exposure in cytoplasm) and monoclonal and polyclonal antibodies in the treatment of SARS-CoV-2 are under investigation. Avoiding the prescription of non-steroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors, or angiotensin II type I receptor blockers is advised for COVID-19 patients.


Extreme Engineering: Polarization in Product Development and Manufacturing


title: Perinatal viral infections

text: In comparison to older children and adults, neonates are immunologically incompetent. They are susceptible to infections caused by a variety of microorganisms, including bacteria, fungi and viruses. These infectious agents may be acquired by neonates either prenatally, during the intrapartum period or postnatally. The purpose of this review is to emphasize the potential impact of viral infections contracted by neonates at the time of delivery or within the neonatal period. The viruses reviewed include the herpes group of viruses (cytomegalo-virus, herpes simplex viruses and varicella-zoster virus), type B hepatitis virus, human immunodeficiency virus, respiratory viruses, enteroviruses, rotavirus and human papilloma virus. For each virus the potential sources and incidence of the infection, the common manifestations of the illness, and possible means of prevention and therapy are discussed. Although infections caused by bacteria tend to be more clinically dramatic and more immediately life-threatening, it is emphasized that infections caused by viruses are common and associated with substantial long-term morbidity. Perinatal viral infections need to be recognized as early in life as possible so that their natural history can be more completely defined and any possible intervention made.


title: Growth behavior of bovine herpesvirus-1 in permissive and semi-permissive cells

text: Abstract Bovine herpesvirus-1 (BHV-1) can replicate well in bovine-derived cell lines such as Madin Darby bovine kidney (MDBK) but grows poorly in hamster lung (HmLu-1). Virus replication, DNA synthesis, and immediate-early gene expression are severely restricted in HmLu-1. We compared adsorption and penetration of BHV-1 in permissive MDBK and semi-permissive HmLu-1 cells. At a low multiplicity of infection, BHV-1 attached to permissive MDBK cells twice as much as to HmLu-1. The presence of heparin inhibited the attachment of BHV-1 to MDBK cells by about 60%, but over 90% of the attachment was inhibited in HmLu-1. To investigate the penetration of BHV-1, we performed the quantitative measurement of viral DNA by quantitative competitive (QC)PCR in infected cells. In MDBK cells, virions attached to the cell surface, penetrated into the cells and were transported to the nucleus. However in HmLu-1, only a small fraction of the virions attached to the cell surface were allowed to penetrate. Our results indicated that the replication of BHV-1 in semi-permissive HmLu-1 was not dramatically restricted at one certain point but at some various stages including adsorption and penetration.


title: Changing trends and serotype distribution of Shigella species in Beijing from 1994 to 2010

text: Shigella species are a common cause of acute diarrheal disease in China. In this study, we characterized the changing trends and serotype distribution of Shigella species in Beijing from 1994 to 2010. A total of 5999 Shigella strains were isolated and serotyped from the 302nd Hospital in Beijing. The annual number of Shigella isolates reached a peak (n = 1192; 19.84%) in 1996 and then decreased annually, reaching the lowest point (n = 24; 0.41%) in 2010. S. flexneri 2a and S. sonnei were the most frequently isolated Shigella, with their respective isolates making up 53.3% and 27.6% of the total. Isolates of S. flexneri 4c, 4a, and x made up 3% respectively of the total isolates. Significant decreases in percentage of S. flexneri over time were observed. S. sonnei surpassed S. flexneri 2a as the predominant serotype in 2000. Most isolates were recovered from July to September; 13.6% of the isolates were recovered from children aged 0 to 5 years, and 16% were recovered from those aged 21 to 25 years. S. flexneri 2a and 5 were recovered mostly from males (33.41%, p < 0.001; and 0.46%, p < 0.001%; respectively), whereas S. flexneri 2b and 6, and S. sonnei were most often isolated from females. Continuous monitoring of Shigella showed that all 4 species and 27 serotypes were present in Beijing, China, during the study period. The emergence of S. sonnei and the overall decreasing isolation rate of Shigella in Beijing can potentially aid in the development of vaccine and control strategies for shigellosis in the city.


title: Viral etiologies of lower respiratory tract infections among Egyptian children under five years of age

text: BACKGROUND: Lower respiratory tract infections (LRTI) are responsible for a considerable number of deaths among children, particularly in developing countries. In Egypt and the Middle East region, there is a lack of data regarding the viral causes of LRTI. In this study, we aimed to identify the relative prevalence of various respiratory viruses that contribute to LRTIs in young children. Although, nucleic acid-based methods have gained importance as a sensitive tool to determine the viral infections, their use is limited because of their prohibitive cost in low-income countries. Therefore, we applied three different laboratory methods, and presented the different virus prevalence patterns detected by each method. METHODS: We collected nasopharyngeal aspirate samples, demographic data and, clinical data from 450 children under five years of age who presented with LRTI at Abou El Reesh hospital in Cairo during a one-year period. To identify the viral causes of the LRTI we used direct fluorescence assay, real-time reverse-transcriptase polymerase chain reaction (rt-RT-PCR), and shell vial culture. We tested for eight major respiratory viruses. RESULTS: Two hundred sixty-nine patients (59.9%) had a viral infection, among which 10.8% had a co-infection with two or more viruses. By all three methods, respiratory syncytial virus (RSV) was the most predominant, and parainfluenza virus type 2 (HPIV-2), influenza B virus (FLUBV) were the least predominant. Other viral prevalence patterns differed according to the detection method used. The distribution of various viruses among different age groups and seasonal distribution of the viruses were also determined. CONCLUSIONS: RSV and human adenovirus were the most common respiratory viruses detected by rt-RT-PCR. Co-infections were found to be frequent among children and the vast majority of co-infections were detected by nucleic acid-based detection assays.


title: Laboratory testing of SARS‐CoV, MERS‐CoV, and SARS‐CoV‐2 (2019‐nCoV): Current status, challenges, and countermeasures

text: Emerging and reemerging infectious diseases are global public concerns. With the outbreak of unknown pneumonia in Wuhan, China in December 2019, a new coronavirus, SARS‐CoV‐2 has been attracting tremendous attention. Rapid and accurate laboratory testing of SARS‐CoV‐2 is essential for early discovery, early reporting, early quarantine, early treatment, and cutting off epidemic transmission. The genome structure, transmission, and pathogenesis of SARS‐CoV‐2 are basically similar to SARS‐CoV and MERS‐CoV, the other two beta‐CoVs of medical importance. During the SARS‐CoV and MERS‐CoV epidemics, a variety of molecular and serological diagnostic assays were established and should be referred to for SARS‐CoV‐2. In this review, by summarizing the articles and guidelines about specimen collection, nucleic acid tests (NAT) and serological tests for SARS‐CoV, MERS‐CoV, and SARS‐CoV‐2, several suggestions are put forward to improve the laboratory testing of SARS‐CoV‐2. In summary, for NAT: collecting stool and blood samples at later periods of illness to improve the positive rate if lower respiratory tract specimens are unavailable; increasing template volume to raise the sensitivity of detection; putting samples in reagents containing guanidine salt to inactivate virus as well as protect RNA; setting proper positive, negative and inhibition controls to ensure high‐quality results; simultaneously amplifying human RNase P gene to avoid false‐negative results. For antibody test, diverse assays targeting different antigens, and collecting paired samples are needed.


title: Interactions between cyclodextrins and cellular components: Towards greener medical applications?

text: In the field of host–guest chemistry, some of the most widely used hosts are probably cyclodextrins (CDs). As CDs are able to increase the water solubility of numerous drugs by inclusion into their hydrophobic cavity, they have been widespread used to develop numerous pharmaceutical formulations. Nevertheless, CDs are also able to interact with endogenous substances that originate from an organism, tissue or cell. These interactions can be useful for a vast array of topics including cholesterol manipulation, treatment of Alzheimer’s disease, control of pathogens, etc. In addition, the use of natural CDs offers the great advantage of avoiding or reducing the use of common petroleum-sourced drugs. In this paper, the general features and applications of CDs have been reviewed as well as their interactions with isolated biomolecules leading to the formation of inclusion or exclusion complexes. Finally, some potential medical applications are highlighted throughout several examples.


title: Inflammatory Mediators in the Mesenteric Lymph Nodes, Site of a Possible Intermediate Phase in the Immune Response to Feline Coronavirus and the Pathogenesis of Feline Infectious Peritonitis?

text: Summary Feline infectious peritonitis (FIP) is an almost invariably fatal feline coronavirus (FCoV)-induced disease thought to arise from a combination of viral mutations and an overexuberant immune response. Natural initial enteric FCoV infection may remain subclinical, or result in mild enteric signs or the development of FIP; cats may also carry the virus systemically with no adverse effect. This study screened mesenteric lymph nodes (MLNs), the presumed first site of FCoV spread from the intestine regardless of viraemia, for changes in the transcription of a panel of innate immune response mediators in response to systemic FCoV infection and with FIP, aiming to identify key pathways triggered by FCoV. Cats with and without FIP, the latter with and without FCoV infection in the MLN, were compared. Higher expression levels in FIP were found for toll-like receptors (TLRs) 2, 4 and 8. These are part of the first line of defence and suggest a response to both viral structural proteins and viral nucleic acid. Expression of genes encoding inflammatory cytokines and chemokines, including interleukin (IL)-1β, IL-6, IL-15, tumour necrosis factor (TNF)-α, CXCL10, CCL8, interferon (IFN)-α, IFN-β and IFN-γ, was higher in cats with FIP, consistent with inflammatory pathway activation. Expression of genes encoding transcription factors STAT1 and 2, regulating signalling pathways, particularly of the interferons, was also higher. Among cats without FIP, there were few differences between virus-positive and virus-negative MLNs; however, TLR9 and STAT2 expression were higher with infection, suggesting a direct viral effect. The study provides evidence for TLR involvement in the response to FCoV. This could open up new avenues for therapeutic approaches.


COVID‐19: we must not forget about Indigenous health and equity


Changes in the Clinical Practice of Ophthalmology during the Coronavirus Disease 2019 (COVID-19) Outbreak: an Experience from Daegu, Korea


title: The first case of the 2015 Korean Middle East Respiratory Syndrome outbreak

text: This study reviewed problems in the prevention of outbreak and spread of Middle East Respiratory Syndrome (MERS) and aimed to provide assistance in establishing policies to prevent and manage future outbreaks of novel infectious diseases of foreign origin via in-depth epidemiological investigation of the patient who initiated the MERS outbreak in Korea, 2015. Personal and phone interviews were conducted with the patient and his guardians, and his activities in Saudi Arabia were investigated with the help of the Saudi Arabian Ministry of Health. Clinical courses and test results were confirmed from the medical records. The patient visited 4 medical facilities and contacted 742 people between May 11, 2015, at symptom onset, and May 20, at admission to the National Medical Center; 28 people were infected and diagnosed with MERS thereafter. Valuable lessons learned included: (1) epidemiological knowledge on the MERS transmission pattern and medical knowledge on its clinical course; (2) improvement of epidemiological investigative methods via closed-circuit television, global positioning system tracking, and review of Health Insurance Review and Assessment Service records; (3) problems revealed in the existing preventive techniques, including early determination of the various people contacted; (4) experiences with preventive methods used for the first time in Korea, including cohort quarantine; (5) reconsideration of the management systems for infectious disease outbreaks across the country, such as this case, at the levels of central government, local government, and the public; (6) reconsideration of hospital infectious disease management systems, culture involving patient visitation, and emergency room environments.


A call for precision in COVID-linked case reporting- a crucial step more important now than ever


title: Biosafety considerations for attenuated measles virus vectors used in virotherapy and vaccination

text: Attenuated measles virus (MV) is one of the most effective and safe vaccines available, making it attractive candidate vector to prevent infectious diseases. Attenuated MV have acquired the ability to use the complement regulator CD46 as a major receptor to mediate virus entry and intercellular fusion. Therefore, attenuated MV strains preferentially infect and destroy a wide variety of cancer cells making them also attractive oncolytic vectors. The use of recombinant MV vector has to comply with various regulatory requirements, particularly relating to the assessment of potential risks for human health and the environment. The present article highlights the main characteristics of MV and recombinant MV vectors used for vaccination and virotherapy and discusses these features from a biosafety point of view.


title: The Search for a Practical Approach to Emerging Diseases: The Case of Severe Acute Respiratory Syndrome (SARS)

text: The plague, which the Board of Health had feared might enter with the German troops into the Milanese, had entered it indeed, as is well known; and it is likewise well known, that it paused not here, but invaded and ravaged a great part of Italy. (A. Manzoni, The Bethrothed, 1826)


title: Cell-Membrane-Mimicking Nanodecoys against Infectious Diseases

text: [Image: see text] Infectious diseases are a leading cause of mortality worldwide, with viruses and bacteria in particular having enormous impacts on global healthcare. One major challenge in combatting such diseases is a lack of effective drugs or specific treatments. In addition, drug resistance to currently available therapeutics and adverse effects caused by long-term overuse are both serious public health issues. A promising treatment strategy is to employ cell-membrane mimics as decoys to trap and to detain the pathogens. In this Perspective, we briefly review the infection mechanisms adopted by different pathogens at the cellular membrane interface and highlight the applications of cell-membrane-mimicking nanodecoys for systemic protection against infectious diseases. We also discuss the implication of nanodecoy–pathogen complexes in the development of vaccines. We anticipate this Perspective will provide new insights on design and development of advanced materials against emerging infectious diseases.


title: Subcellular location and topology of severe acute respiratory syndrome coronavirus envelope protein

text: Abstract Severe acute respiratory syndrome (SARS) coronavirus (CoV) envelope (E) protein is a transmembrane protein. Several subcellular locations and topological conformations of E protein have been proposed. To identify the correct ones, polyclonal and monoclonal antibodies specific for the amino or the carboxy terminus of E protein, respectively, were generated. E protein was mainly found in the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) of cells transfected with a plasmid encoding E protein or infected with SARS-CoV. No evidence of E protein presence in the plasma membrane was found by using immunofluorescence, immunoelectron microscopy and cell surface protein labeling. In addition, measurement of plasma membrane voltage gated ion channel activity by whole-cell patch clamp suggested that E protein was not present in the plasma membrane. A topological conformation in which SARS-CoV E protein amino terminus is oriented towards the lumen of intracellular membranes and carboxy terminus faces cell cytoplasm is proposed.


Off‐target ACE2 ligands: Possible therapeutic option for CoVid‐19?


The Tipping Point of Medical Technology: Implications for the Postpandemic Era


title: Antibiotics for bronchiectasis exacerbations in children: rationale and study protocol for a randomised placebo-controlled trial

text: BACKGROUND: Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous settings globally, high quality evidence to inform management is scarce. It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations, but not all practitioners agree. Inadequately treated exacerbations may risk lung function deterioration. Our study tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are superior to placebo at improving resolution rates of respiratory exacerbations by day 14 in children with bronchiectasis unrelated to cystic fibrosis. METHODS: We are conducting a bronchiectasis exacerbation study (BEST), which is a multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel group trial, in five centres (Brisbane, Perth, Darwin, Melbourne, Auckland). In the component of BEST presented here, 189 children fulfilling inclusion criteria are randomised (allocation-concealed) to receive amoxicillin-clavulanic acid (22.5 mg/kg twice daily) with placebo-azithromycin; azithromycin (5 mg/kg daily) with placebo-amoxicillin-clavulanic acid; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days. Clinical data and a paediatric cough-specific quality of life score are obtained at baseline, at the start and resolution of exacerbations, and at day 14. In most children, blood and deep nasal swabs are also collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 14. The main secondary outcome is the paediatric cough-specific quality of life score. Other outcomes are time to next exacerbation; requirement for hospitalisation; duration of exacerbation; and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood markers will also be reported. DISCUSSION: Effective, evidence-based management of exacerbations in people with bronchiectasis is clinically important. Yet, there are few randomised controlled trials (RCTs) in the neglected area of non-cystic fibrosis bronchiectasis. Indeed, no published RCTs addressing the treatment of bronchiectasis exacerbations in children exist. Our multicentre, double-blind RCT is designed to determine if azithromycin and amoxicillin-clavulanic acid, compared with placebo, improve symptom resolution on day 14 in children with acute respiratory exacerbations. Our planned assessment of the predictors of antibiotic response, the role of antibiotic-resistant respiratory pathogens, and whether early treatment with antibiotics affects duration and time to the next exacerbation, are also all novel. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR) number ACTRN12612000011886.


title: COVID-19: Current Trends in Invitro Diagnostics

text: The novel coronavirus SARS-CoV-2 is the seventh known species of coronavirus, infectious to human beings. The pandemic COVID-19 spread all over the world with an unprecedented spreading rate after its first appearance in Wuhan, China. As a novel viral disease there in no antiviral treatment or vaccine for the COVID-19. At present, the early detection and the quarantine of infected patients are the ways to stop the spreading of the disease. This review will discuss about the current invitro diagnostic methods used worldwide for the early and accurate diagnosis of COVID-19. Currently the nucleic acid based polymerase chain reaction is used as the reliable diagnostic platform and antigen/antibody detection immunoassays are playing the role of screening tests for early detection and prognosis in COVID-19 treatment.


title: The pandemic under siege: A view from the Gaza Strip

text: In this article I argue that while the COVID-19 outbreak is at its early stages in the Gaza Strip, the Palestinian coastal enclave is particularly vulnerable to its effects – not least due to the multiplicity of existing development challenges that have resulted from an ongoing Israeli and Egyptian-imposed blockade. With the economy at a standstill, the Palestinian governing authority has limited financial resources to (re)build key sanitation, hygiene, waste treatment and water supply infrastructure. These (infrastructural) inadequacies, while already a public health concern before the onset of the pandemic, now renders Gaza particularly vulnerable to the spread of viruses and diseases. Additionally, the limited movement of goods because of the siege has led to an acute shortage of medical supplies and equipment that are essential for combating a pandemic. Nonetheless, the COVID-19 outbreak is also “unique” in that it presents Gaza with a crisis that has little to do with the hostilities that define the politics of Israel-Palestine. Yet, the potential of a widespread outbreak also lays bare to the development challenges that Gaza faces as a result of the conflict. This, I conclude, provides an opportunity for the donor community to, under pretext of combating the pandemic, remedy some of the consequences of the conflict and siege without having to contend with the (political) stigma of doing so.


title: Alternative divalent cations (Zn(2+), Co(2+), and Mn(2+)) are not mutagenic at conditions optimal for HIV-1 reverse transcriptase activity

text: BACKGROUND: Fidelity of DNA polymerases can be influenced by cation co-factors. Physiologically, Mg(2+) is used as a co-factor by HIV reverse transcriptase (RT) to perform catalysis; however, alternative cations including Mn(2+), Co(2+), and Zn(2+) can also support catalysis. Although Zn(2+) supports DNA synthesis, it inhibits HIV RT by significantly modifying RT catalysis. Zn(2+) is currently being investigated as a component of novel treatment options against HIV and we wanted to investigate the fidelity of RT with Zn(2+). METHODS: We used PCR-based and plasmid-based alpha complementation assays as well as steady-state misinsertion and misincorporation assays to examine the fidelity of RT with Mn(2+), Co(2+), and Zn(2+). RESULTS: The fidelity of DNA synthesis by HIV-1 RT was approximately 2.5 fold greater in Zn(2+) when compared to Mg(2+) at cation conditions optimized for nucleotide catalysis. Consistent with this, RT extended primers with mismatched 3′ nucleotides poorly and inserted incorrect nucleotides less efficiently using Zn(2+) than Mg(2+). In agreement with previous literature, we observed that Mn(2+) and Co(2+) dramatically decreased the fidelity of RT at highly elevated concentrations (6 mM). However, surprisingly, the fidelity of HIV RT with Mn(2+) and Co(2+) remained similar to Mg(2+) at lower concentrations that are optimal for catalysis. CONCLUSION: This study shows that Zn(2+), at optimal extension conditions, increases the fidelity of HIV-1 RT and challenges the notion that alternative cations capable of supporting polymerase catalysis are inherently mutagenic.


title: Elevated hepatic DPP4 activity promotes insulin resistance and non-alcoholic fatty liver disease

text: OBJECTIVE: Increased hepatic expression of dipeptidyl peptidase 4 (DPP4) is associated with non-alcoholic fatty liver disease (NAFLD). Whether this is causative for the development of NAFLD is not yet clarified. Here we investigate the effect of hepatic DPP4 overexpression on the development of liver steatosis in a mouse model of diet-induced obesity. METHODS: Plasma DPP4 activity of subjects with or without NAFLD was analyzed. Wild-type (WT) and liver-specific Dpp4 transgenic mice (Dpp4-Liv-Tg) were fed a high-fat diet and characterized for body weight, body composition, hepatic fat content and insulin sensitivity. In vitro experiments on HepG2 cells and primary mouse hepatocytes were conducted to validate cell autonomous effects of DPP4 on lipid storage and insulin sensitivity. RESULTS: Subjects suffering from insulin resistance and NAFLD show an increased plasma DPP4 activity when compared to healthy controls. Analysis of Dpp4-Liv-Tg mice revealed elevated systemic DPP4 activity and diminished active GLP-1 levels. They furthermore show increased body weight, fat mass, adipose tissue inflammation, hepatic steatosis, liver damage and hypercholesterolemia. These effects were accompanied by increased expression of PPARγ and CD36 as well as severe insulin resistance in the liver. In agreement, treatment of HepG2 cells and primary hepatocytes with physiological concentrations of DPP4 resulted in impaired insulin sensitivity independent of lipid content. CONCLUSIONS: Our results give evidence that elevated expression of DPP4 in the liver promotes NAFLD and insulin resistance. This is linked to reduced levels of active GLP-1, but also to auto- and paracrine effects of DPP4 on hepatic insulin signaling.


title: Novel Variation in the N Protein of Avian Infectious Bronchitis Virus

text: Abstract The nucleocapsid protein of coronaviruses has been considered highly conserved, showing greater than 94% conservation within strains of a given species. We determined the nucleotide sequence of the N gene and the 3′ untranslated region (UTR) of eight naturally occurring strains of IBV which differed in pathogenicity and tissue tropism. In pairwise comparisons, the deduced amino acid sequences of N of five strains Vic S, N1/62, N9/74, N2/75, and V5/90 (group I) shared 92.3–98.8% identity. The three strains N1/88, Q3/88, and V18/91 (group II) shared 85.8–89.2% identity with each other, but only 60.0–63.3% identity with viruses of group I. Amino acid substitutions, deletions, and insertions occurred throughout the N protein and involved regions previously identified as being conserved. Despite the considerable variation observed between the two virus groups, all N proteins contained a high proportion of basic residues, 80% of which were conserved in position. In addition, all strains contained approximately 30 serine residues of which 10 were conserved, the majority occurring between positions 168 and 194. As for all other coronaviruses, the region between positions 92 and 103 was highly conserved. Hence, a large number of amino acid changes can be tolerated within the N protein without affecting its integrity or functioning. The 3′ UTR immediately downstream from the N gene was highly heterogeneous with extensive deletions occurring in the group II strains.


Signals of T(h)2 immune response from COVID-19 patients requiring intensive care


title: COVID-19 Guidance for Triage of Operations for Thoracic Malignancies: A Consensus Statement from Thoracic Surgery Outcomes Research Network

text: Abstract The extraordinary demands of managing the COVID-19 pandemic has disrupted the world’s ability to care for patients with thoracic malignancies. As a hospital’s COVID-19 population increases and hospital resources are depleted, the ability to provide surgical care is progressively restricted - forcing surgeons to prioritize among their cancer populations. Representatives from multiple cancer, surgical and research organizations have come together to provide a guide for triaging patients with thoracic malignancies, as the impact of COVID-19 evolves as each hospital.


title: Interim report on the A/H1N1 influenza virus pandemic in Marseille, France, April-November 2009

text: Abstract We report here the results of a 7-month survey of the influenza A/H1N1 pandemic in the Virology laboratory of the public hospitals of Marseille (April–November 2009). In total, 8 587 samples were analysed during this period, of which 1 974 (23%) were positive for the novel influenza variant. The analysis of results obtained using rapid influenza diagnostic tests (RIDTs) revealed a global sensitivity of 49.4% (vs. molecular qRT-PCR detection), strongly correlated with age groups (varying from 30% to 58% for patients >40 age and <10, respectively), indicating that RIDTs can be helpful in accelerating the management of suspected cases. Epidemiological analysis showed that the winter influenza wave began in October in Marseille (i.e. 2 to 3 months earlier than usual seasonal influenza outbreaks) and that the majority of autochthonous cases were observed in patients younger than 20 years old, with a low number of cases in patients over 60 years old. In November 2009, 22.2% (167/754) of patients with a laboratory diagnosis of influenza A/H1N1 infection were hospitalized, of which 9% (15/167) were admitted to an intensive care unit (ICU). Patients in the extreme age groups (>40 years old and <1) were significantly more often hospitalized than others, and 2.4% of hospitalized patients died. During the last 3 weeks of the period, the average number of bed-days attributable to H1N1sw-positive patients was 31.4, of which 5.9 were in ICUs.


title: Use of a novel virus detection assay to identify coronavirus HKU1 in the lungs of a hematopoietic stem cell transplant recipient with fatal pneumonia

text: A 38-year-old patient with systemic lupus erythematosus presented with pulmonary infiltrates and hypoxemia for several months following immunodepleting autologous hematopoietic stem cell transplantation. She was treated for influenza, which was isolated repeatedly from ororpharynx and bronchoalveolar lavage fluids, and later empirically for lupus pneumonitis, but expired 6 months after transplant. Autopsy findings failed to show influenza in the lungs or lupus pneumonitis. A novel generic PCR-based assay using degenerate primers identified human coronavirus HKU1 RNA in bronchoalveolar lavage fluid at autopsy. Coronavirus was confirmed by virus-specific PCRs of lung tissue at autopsy. Electron microscopy showed viral particles consistent with coronavirus HKU1 in lung tissue both at autopsy and from a previous biopsy. While human coronavirus HKU1 infection is not usually severe, in highly immunocompromised patients, it can be associated with fatal pneumonia.


title: Isolation and phylogenetic analysis of porcine deltacoronavirus from pigs with diarrhoea in Hebei province, China

text: Porcine deltacoronavirus (PDCoV) is a recently identified coronavirus in the genus Deltacoronavirus that can cause enteric disease with clinical signs including diarrhoea, vomiting, dehydration and mortality in neonatal piglets. Although evidence of the prevalence of PDCoV in China is accumulating, little published information about Chinese PDCoV isolates is available. In this study, we investigated the presence of PDCoV in 49 faecal/intestinal samples from piglets with diarrhoea on different farms in Hebei province. Five samples (10.2%) were positive for PDCoV, but no coinfection of PDCoV with other enteropathogens was observed. A PDCoV strain named HB‐BD was successfully isolated from the intestinal contents of a diarrhoeic piglet and serially propagated in swine testicular (ST) cells for >40 passages. The complete genome of the HB‐BD strain was sequenced and analysed. Genomic analysis showed that the HB‐BD strain had a closer relationship with Chinese strains than those from other countries and was grouped within the Chinese PDCoV cluster. The results of this study will be valuable for further research of PDCoV genetic evolution and development of effective diagnostic reagents, assays and potential vaccines against newly emerged PDCoV strains.


title: COVID‐19 and Dermatology: A Comprehensive Guide for Dermatologists

text: As of the 11(th) of March, the world health organization (WHO) declared Coronavirus disease‐2019 (COVID‐19) as a pandemic disease caused by SARS‐CoV‐2 (previously known as 2019‐nCOV) (1,2). By the 19(th) of April, 2,241,778 confirmed patients were reported worldwide with 152,552 COVID‐19 related deaths (3). The COVID‐19 pandemic represents the most serious health crisis facing the modern world resulting in unprecedented efforts to contain this pandemic and its consequences (1).


title: Experimental infection of dogs with a feline endogenous retrovirus RD-114

text: BACKGROUND: The feline endogenous retrovirus RD114 is contained in the genome of cats. The virus may contaminate live canine vaccines based on cultured feline cells. The in vivo infectivity, acute and subacute pathogenicity, and viral proliferation of the RD114 virus were evaluated by experimental infection of dogs. METHODS: Nine specific pathogen free dogs were divided into three groups, with each group consisting of one female and two male dogs. Dogs were subcutaneously inoculated in the neck with either 1 ml RD114 stock virus (group A), inactivated RD114 virus suspension (group B), or cell culture medium (group C) as a negative control. To assess blood cell counts and biochemical properties, blood samples from each group were collected 5 days before inoculation, just prior to inoculation, and 1, 3, 7 and 10 days post-inoculation. RESULT: During the experimental period of 51 days, none of the dogs inoculated with RD114 virus showed any clinical signs, significant increases in rectal temperature or abnormal blood biochemical characteristics including C-reactive protein when compared with the negative controls. We were not able to re-isolate the RD114 virus from buffy coat cells of group A dogs. Additionally, we could not detect RD114 provirus in the genomic DNA isolated from peripheral blood leukocytes, lymph node, spleen and sternal bone marrow cells. CONCLUSIONS: Signs of RD114 virus proliferation were not found after subcutaneous infection of dogs. Although the potential risk caused by infection with RD114 virus in dogs could not be assessed in this study, we suspect that RD114 virus has little or no virulence in dogs.


Inhibitors of Peptidyl Proline Isomerases As Antivirals in Hepatitis C and Other Viruses


title: 148. Acute bipolar disorder depression is associated with immune activation

text: Recent studies indicate that immune activation may be an important component of the pathogenesis of bipolar disorder. The study sample consists of 40 patients admitted to the hospital with a diagnosis of acute bipolar depression. Blood samples were drawn at 3 time points: at time of hospital admission, during the acute hospital stay, and at a six month follow-up. Inflammatory markers were measured including C-reactive protein (CRP), Pentraxin 3 (PTX3), and antibodies to infectious agents. The markers in the bipolar depressed patients were studied over the 3 time points and also compared to those in other groups: 60 hospitalized for acute mania; 69 with recent onset psychosis; 246 with multi-episode schizophrenia; 98 with bipolar disorder not selected for mania or depression; and 222 non-psychiatric controls. The bipolar depressed patients had elevated levels of CRP at all 3 time points. The bipolar depressed patients also had elevated levels of PTX3 at hospital admission which were reduced during the hospital stay and at follow-up. The bipolar depressed group also had elevated levels of antibodies to the nucleocapsid protein of the SARS strain of coronavirus, while elevated levels of these antibodies were not found in the other groups. Our study indicates that bipolar disorder depression is associated with immune activation, particularly during acute exacerbations. These findings may lead to the development of new methods of prevention and treatment.


title: Impact of the COronaVIrus Disease 2019 lockdown on hand and upper limb emergencies: experience of a referred university trauma hand centre in Paris, France centre in Paris, France

text: PURPOSE: The lockdown imposed in France to cope with the COronaVIrus Disease 2019 (COVID-19) outbreak has led to major changes in the lifestyle of French citizens. The aim of our study was to study its impact on activity related to emergencies in hand and upper limb trauma in comparison to the same reference period in 2019. MATERIAL AND METHODS: All consecutive patients consulting for upper limb injury requiring urgent care at Georges-Pompidou European Hospital (HEGP), France, during the lockdown period (case group) and the equivalent period in 2019 (control group) were included. In each group, the type of accident, the anatomical location of the injury, and the treatment were reported and compared. RESULTS: Two hundred seventy-five patients were included in the case group in comparison to 784 patients in the control group. We observed a two-third decrease in the rate of upper limb emergencies (− 64.9%) in particular a drastic drop in the rate of road, work, and leisure accidents (10.4% vs 14.3%, p = 0.1151; 10.0% vs 22.6%, p < 0.0001; 13.1% vs 30.8%, p < 0.0001, respectively), and a clear increase in domestic accidents (66.5% vs 32.3%, p < 0.0001). The aetiologies were more dominated by lacerations of soft tissues (48.4%, vs 38.3%, p = 0.0034) and infections (8.7% vs 5.1%, p = 0.0299) with an increase in the indications for surgical management (51.2% vs 36.9%, p < 0.0001). Conversely, we observed fewer consultations for joint injuries (20.7% vs 30.7%, p = 0.0015) and fractures (22.2% vs 25.9%, p = 0.2210). CONCLUSION: The lockdown imposed in France has changes the etiologies and the management of hand and upper limb emergencies.


Epithelial Expression of HLA Class II Molecules: A New Pathogenic Factor in Organ‐Specific Autoimmunity


title: Imaging Axonal Degeneration and Repair in Preclinical Animal Models of Multiple Sclerosis

text: Multiple sclerosis (MS) is a central nervous system (CNS) disease characterized by chronic neuroinflammation, demyelination, and axonal damage. Infiltration of activated lymphocytes and myeloid cells are thought to be primarily responsible for white matter damage and axonopathy. Over time, this neurologic damage manifests clinically as debilitating motor and cognitive symptoms. Existing MS therapies focus on symptom relief and delay of disease progression through reduction of neuroinflammation. However, long-term strategies to remyelinate, protect, or regenerate axons have remained elusive, posing a challenge to treating progressive forms of MS. Preclinical mouse models and techniques, such as immunohistochemistry, flow cytometry, and genomic and proteomic analysis have provided advances in our understanding of discrete time-points of pathology following disease induction. More recently, in vivo and in situ two-photon (2P) microscopy has made it possible to visualize continuous real-time cellular behavior and structural changes occurring within the CNS during neuropathology. Research utilizing 2P imaging to study axonopathy in neuroinflammatory demyelinating disease has focused on five areas: (1) axonal morphologic changes, (2) organelle transport and health, (3) relationship to inflammation, (4) neuronal excitotoxicity, and (5) regenerative therapies. 2P imaging may also be used to identify novel therapeutic targets via identification and clarification of dynamic cellular and molecular mechanisms of axonal regeneration and remyelination. Here, we review tools that have made 2P accessible for imaging neuropathologies and advances in our understanding of axonal degeneration and repair in preclinical models of demyelinating diseases.


title: SARS‐CoV, Mers‐CoV and Covid‐19:what differences from a dermatological viewpoint?

text: Over the past two decades, 3 zoonotic global coronavirus outbreaks have occurred: 1. SARS starting in 2002 in China due to SARS‐CoV; 2. MERS starting in 2012 in Saudi Arabia due to MERS‐CoV; 3. Covid‐19 due to SARS‐CoV‐2 starting in 2019 in Wuhan, China (1). Both beta‐coronaviruses, SARS‐CoV and MERS‐CoV caused a severe disease in most infected people.


title: Groundwater Pollution

text: This chapter starts with the presentation of the history of one of the most natural disaster caused by groundwater pollution (Love Canal). The derivation of the mathematical model describing the transport of pollution via groundwater is presented in detail with the derivation of the exact solution. Statistical techniques for sensitivity and uncertainties analysis of parameters associated to the transport model are presented. Some techniques for groundwater remediation are listed.


NEI Corp launches UV-resistant coating used to disinfect coronavirus


title: Mapping of three antigenic sites on the haemagglutinin-neuraminidase protein of Newcastle disease virus

text: Abstract Nine neutralizing monoclonal antibodies (MAbs), each of which react with the haemagglutinin-neuraminidase (HN) glycoprotein of the Beaudette C strain of Newcastle disease virus (NDV), have been used in competitive binding assays to delineate three non-overlapping antigenic sites A, B and C. Epitopes within these sites have been identified on the basis of cross-reactivity of MAb-resistant mutants against the panel of MAbs, determined by plaque assays and Western blotting. Site A contains three non-overlapping epitopes (A1, A2 and A3). A1 is the only linear epitope; all remaining epitopes are conformational. MAbs which react with epitopes A2 and A3 inhibit neuraminidase activity (NA) when assayed with neuraminlactose. Site B contains three partially overlapping epitopes (B1, B2 and B3) and site C is represented by a single epitope (C1). HN gene sequence analysis of MAb-resistant mutants showed that they each had only single amino acid substitutions which range from amino acid residues 347–460 for site A, 284–325 for site B, and at 481 for the Cl epitope. The apparent molecular mass of the HN glycoprotein of one mutant was increased from 72 to 75 kDa. This correlates well with the creation of an additional potential glycosylation site in this mutant from Asn-Ser-Pro(325) to Asn-Ser-Ser(325).


title: COVID‐19 suspicion and diagnosis: are we still chasing epidemiological criteria?

text: Italy was the second nation after China to be most involved into the COVID‐19 outbreak. From the beginning, much attention has been attributed to the importance of epidemiological criteria (such as previous contact with confirmed COVID‐19 cases, recent journey across China or the northern Italian regions) in order to assess a suspected patient for SARS‐CoV‐2 infection. Despite this, by now evidences do exist about the possibly huge reservoir of asymptomatic patients and its underestimated ability to spread the infection. Thus, we do believe that when an infectious disease has a big ratio of asymptomatic cases, as for COVID‐19, it is simply not safe to rely on epidemiological criteria and we briefly discuss this issue throughout the few new evidences there are about. This article is protected by copyright. All rights reserved.


title: Influence of a propionic acid feed additive on performance of turkey poults with experimentally induced poult enteritis and mortality syndrome

text: Abstract Poult enteritis and mortality syndrome (PEMS) has multiple etiological agents associated with its occurrence, including two viruses and at least three Escherichia coli isolates. Myco Curb (MC) contains organic acids and is used as a feed additive to inhibit growth of many bacteria and toxin-producing molds but not viruses. Studies evaluating the influence of MC on BW, feed conversion, and mortality indicate that turkey poults tolerate MC at 1.25% but not 2.50%, but higher MC content in feed provides greater suppression of growth of bacterial isolates commonly associated with PEMS. In two PEMS experiments, 1.25% MC was blended into poult starter feed and was maintained in the feed for the duration of the 3-wk experiments. In these experiments, 1-d-old commercial poults were placed into battery brooders and were given turkey starter feed and water ad libitum. At 6 d posthatch, PEMS-designated poults were given a 1-mL oral gavage of a 10% suspension of feces from PEMS-infected poults. BW depression due to PEMS was not alleviated by MC, although there was less variation in mean BW of the MC-fed poults, and there was a highly significant reduction in mortality (68% in PEMS-exposed with MC vs. 32.5% in PEMS-exposed without MC). The reduction in mortality in the MC-fed poults was attributed to decreased bacterial content of the gut and to maintenance of packed cell volume and hemoglobin content. It was concluded that MC might be a potential nutritional intervention during PEMS.


title: Retention and retrieval in the endoplasmic reticulum and the Golgi apparatus

text: Abstract Resident proteins of the exocytic pathway contain at least two types of information in their primary sequence for determining their subcellular location. The first type of information is found at the carboxyl terminus of soluble proteins of the endoplasmic reticulum (ER) and in the cytoplasmic domain of some ER and Golgi membrane proteins. It acts as a retrieval signal, returning proteins that have left the compartment in which they reside. The second type of information has been found in the membrane-spanning domain of several ER and Golgi proteins and, though the mechanism by which it operates is still unclear, it acts as a retention signal, keeping the protein at a particular location within the organelle. The presence of both a retrieval signal and a retention signal in a trans-Golgi network resident protein suggests that more than one mechanism operates to ensure correct localization of resident proteins along the exocytic pathway.


title: Influenza A virus infection increases IgE production and airway responsiveness in aerosolized antigen-exposed mice

text: Abstract Background: Respiratory viral infection is known clinically to promote sensitization to antigen inhalation and the development of asthma. Objective: The purpose of this investigation was to determine whether influenza type A virus infection enhances inhalation sensitization and increases airway responsiveness in mice. Methods: Mice were infected by intranasal inoculation with influenza A viruses (strains: H1 N1 and H3 N2 ) or PBS. Animals were exposed to aerosols of ovalbumin on day 3. Two weeks after ovalbumin sensitization, mice were challenged with ovalbumin aerosols; 24 hours later, airway responsiveness (AR) to inhaled methacholine, levels of ovalbumin-specific IgE, and bronchoalveolar lavage fluid (BALF) were examined. Results: Neither influenza A virus (H1 N1 nor H3 N2 ) alone nor ovalbumin sensitization alone caused changes in AR or IgE. However, ovalbumin sensitization after inoculation with either influenza A virus increased AR and levels of ovalbumin-specific IgE. On BALF-cell analysis, ovalbumin sensitization after inoculation with influenza virus A increased the number of lymphocytes but not the number of eosinophils. No difference in AR or IgE levels was observed between the 2 strains of influenza A viruses. Immmunostaining of BALF cells showed an increase in T cells, especially CD8+ cells, with ovalbumin sensitization after inoculation with influenza virus A. Conclusion: Infection by influenza A virus enhances sensitization to inhaled antigens and airway responsiveness in mice by means of mechanisms including CD8+ cells and antigen-specific IgE. (J Allergy Clin Immunol 1998;102:732-40.)


title: The evidence base of primary research in public health emergency preparedness: a scoping review and stakeholder consultation

text: BACKGROUND: Effective public health emergency preparedness and response systems are important in mitigating the impact of all-hazards emergencies on population health. The evidence base for public health emergency preparedness (PHEP) is weak, however, and previous reviews have noted a substantial proportion of anecdotal event reports. To investigate the body of research excluding the anecdotal reports and better understand primary and analytical research for PHEP, a scoping review was conducted with two objectives: first, to develop a thematic map focused on primary research; and second, to use this map to inform and guide an understanding of knowledge gaps relevant to research and practice in PHEP. METHODS: A scoping review was conducted based on established methodology. Multiple databases of indexed and grey literature were searched based on concepts of public health, emergency, emergency management/preparedness and evaluation/evidence. Inclusion and exclusion criteria were applied iteratively. Primary research studies that were evidence-based or evaluative in nature were included in the final group of selected studies. Thematic analysis was conducted for this group. Stakeholder consultation was undertaken for the purpose of validating themes and identifying knowledge gaps. To accomplish this, a purposive sample of researchers and practicing professionals in PHEP or closely related fields was asked to complete an online survey and participate in an in-person meeting. Final themes and knowledge gaps were synthesized after stakeholder consultation. RESULTS: Database searching yielded 3015 citations and article selection resulted in a final group of 58 articles. A list of ten themes from this group of articles was disseminated to stakeholders with the survey questions. Survey findings resulted in four cross-cutting themes and twelve stand-alone themes. Several key knowledge gaps were identified in the following themes: attitudes and beliefs; collaboration and system integration; communication; quality improvement and performance standards; and resilience. Resilience emerged as both a gap and a cross-cutting theme. Additional cross-cutting themes included equity, gender considerations, and high risk or at-risk populations. CONCLUSIONS: In this scoping review of the literature enhanced by stakeholder consultation, key themes and knowledge gaps in the PHEP evidence base were identified which can be used to inform future practice-oriented research in PHEP. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-015-1750-1) contains supplementary material, which is available to authorized users.


title: Effects of feeding pregnant beef cows selenium-enriched alfalfa hay on selenium status and antibody titers in their newborn calves

text: In newborn dairy calves, it has been demonstrated that supranutritional maternal and colostral Se supplementation using Se yeast or sodium selenite, respectively, improves passive transfer of IgG. In beef cattle, agronomic biofortification with Se is a more practical alternative for Se supplementation, whereby the Se concentration of hay is increased through the use of Se-containing fertilizer amendments. It has been previously demonstrated that agronomic Se biofortification is an effective strategy to improve immunity and performance in Se-replete weaned beef calves. The objective of this experiment was to determine the effects of feeding beef cows Se-enriched alfalfa (Medicago sativa) hay during the last 8 to 12 wk of gestation on passive transfer of antibodies to calves. At 10 wk ± 16 d before calving, 45 cows were assigned to 1 of 3 treatment groups with 3 pens (5 cows/pen) per treatment: Control cows were fed non-Se-fortified alfalfa hay plus a mineral supplement containing 120 mg/kg Se from sodium selenite, Med-Se cows were fed alfalfa hay fertilized with 45.0 g Se/ha as sodium selenate, and High-Se cows were fed alfalfa hay fertilized with 89.9 g Se/ha as sodium selenate; both the Med-Se and the High-Se groups received mineral supplement without added Se. Colostrum and whole blood (WB) were collected from cows at calving, and WB was collected from calves within 2 h of calving and at 12, 24, 36, and 48 h of age. Concentrations of IgG1 and J-5 Escherichia coli antibody in cow colostrum and calf serum were quantified using ELISA procedures. Selenium concentrations linearly increased in WB (P < 0.001) and colostrum (P < 0.001) of cows and in WB of newborn calves (P < 0.001) with increasing Se concentration in alfalfa hay. Colostrum concentrations of IgG1 (P = 0.03) were increased in cows fed Se-biofortified alfalfa hay, but J-5 E. coli antibody (P = 0.43) concentrations were not. Calf serum IgG1 (P = 0.43) and J-5 E. coli antibody (P = 0.44) concentrations during the first 48 h of age were not affected by prior Se treatment of cows. These data suggest that feeding Se-biofortified alfalfa hay promotes the accumulation of Se and antibodies in colostrum but does not affect short-term serum antibody concentrations in calves.