title: Chapter 2 Anatomical Uniqueness of the Mucosal Immune System (GALT, NALT, iBALT) for the Induction and Regulation of Mucosal Immunity and Tolerance

text: Abstract Mucosal surfaces lining the lung and the gut are constantly exposed to environmental antigens, commensal organisms, and pathogens. Consequently, the host’s immune system devotes enormous resources to the defense of these tissues. Although mucosal immune responses must be sufficiently strong to eliminate pathogens, they must also have mechanisms to prevent excessive inflammation and initiate epithelial repair. Importantly, mucosal immune responses are initiated and regulated by a variety of mucosal lymphoid tissues, collectively known as mucosa-associated lymphoid tissue (MALT). This chapter describes the unique developmental, architectural, and functional features of the MALT and how those features facilitate the local immune response at each site.


title: Exotic Viral Diseases: A Global Guide Stephen A. Berger Charles H. Calisher

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title: Inhibition of white spot syndrome virus in Litopenaeus vannamei shrimp by sequence-specific siRNA

text: Abstract RNA interference (RNAi) is a sequence-specific, post-transcriptional process of mRNA degradation. Here, we described specific silencing of five white spot syndrome virus (WSSV) genes in Litopenaeus vannamei in vivo with sequence-specific siRNAs. These genes included DNA polymerase (dnapol), ribonucleotide reductase small subunit (rr2), thymidine kinase and thymidylate kinase (tk-tmk), vp24 and vp28. At 6 days post-challenged, the relative survival rates of shrimp injected with siDNApol, siRR2, siTK-TMK, siVP24 and siVP28 (siRNAs for dnapol, rr2, tk-tmk, vp24 and vp28 genes) reached 50%, 50%, 66%, 33% and 33%, respectively. Specific siRNAs of the five WSSV genes could result in suppression of the target genes and a significant reduction in the viral proliferation. In negative controls, sequence-independent siRNA (mutant siRNA) could not inhibit expression of these five genes or viral replication. Consequently, injection of sequence-dependent siRNA could induce anti-WSSV activity in shrimp. These results suggest that siRNA can suppress WSSV efficiently in shrimp, and it may provide a potential approach to the therapy of aquaculture viral disease.


title: Structural and mutational analysis of the interaction between the Middle-East respiratory syndrome coronavirus (MERS-CoV) papain-like protease and human ubiquitin

text: The papain-like protease (PL(pro)) of Middle-East respiratory syndrome coronavirus (MERS-CoV) has proteolytic, deubiquitinating, and deISGylating activities. The latter two are involved in the suppression of the antiviral innate immune response of the host cell. To contribute to an understanding of this process, we present here the X-ray crystal structure of a complex between MERS-CoV PL(pro) and human ubiquitin (Ub) that is devoid of any covalent linkage between the two proteins. Five regions of the PL(pro) bind to two areas of the Ub. The C-terminal five residues of Ub, RLRGG, are similar to the P5–P1 residues of the polyprotein substrates of the PL(pro) and are responsible for the major part of the interaction between the two macromolecules. Through sitedirected mutagenesis, we demonstrate that conserved Asp165 and non-conserved Asp164 are important for the catalytic activities of MERS-CoV PL(pro). The enzyme appears not to be optimized for catalytic efficiency; thus, replacement of Phe269 by Tyr leads to increased peptidolytic and deubiquitinating activities. Ubiquitin binding by MERS-CoV PL(pro) involves remarkable differences compared to the corresponding complex with SARS-CoV PL(pro). The structure and the mutational study help understand common and unique features of the deubiquitinating activity of MERS-CoV PL(pro). ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s12250-016-3742-4 and is accessible for authorized users.


title: Neurologic Characteristics in Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis

text: Importance: Coronavirus disease 2019 (COVID-19) is a newly emerging infectious disease that has caused a global pandemic. The presenting symptoms are mainly respiratory symptom, yet studies have reported nervous system involvement in the disease. A systematic review and meta-analysis of these studies are required to understanding the neurologic characteristic of the disease and help physicians with early diagnosis and management. Objective: To conduct a systematic review and meta-analysis on the neurologic characteristics in patients with COVID-19. Evidence Review: Authors conducted a literature search through PubMed from January 1st, 2020 to April 8th, 2020. Furthermore, the authors added additional sources by reviewing related references. Studies presenting the neurologic features of COVID-19 patients in their data were included. Case reports and case series were also included in this review. The quality of the studies was assessed based on the Oxford Center for Evidence-Based Medicine guidelines. Selected studies were included in the meta-analysis of proportion and the heterogeneity test. Finding: From 280 identified studies, 33 were eligible, with 7,559 participants included. Most of the included studies were from China (29 [88%]). Muscle injury or myalgia was the most common (19.2%, 95%CI 15.4–23.2%) neurologic symptom of COVID-19, followed by headache (10.9%, 95%CI 8.62–13.51%); dizziness (8.7%, 95%CI 5.02–13.43%); nausea with or without vomiting (4.6%, 95%CI 3.17–6.27%); concurrent cerebrovascular disease (4.4%, 95%CI 1.92–7.91%); and impaired consciousness (3.8%, 95%CI 0.16–12.04%). Underlying cerebrovascular disease was found in 8.5% (95%CI 4.5–13.5%) of the studies. Conclusion: Neurologic findings vary from non-specific to specific symptoms in COVID-19 patients. Some severe symptoms or diseases can present in the later stage of the disease. Physicians should be aware of the presence of neurologic signs and symptoms as a chief complaint of COVID-19, in order to improve management and prevent a worsening outcome of the patients.


title: Treatment strategy for gastrointestinal tumor under the outbreak of novel coronavirus pneumonia in China

text: The outbreak of the novel coronavirus pneumonia (NCP) has become a public health emergency in China. Chinese authorities and health agencies had devoted great efforts to control this disease. As surgeons specialized in the treatment of gastrointestinal tumors, we should always be aware of the prevention for NCP and incorporate this awareness into every detail of clinical practice. For the patients with gastrointestinal tumors, pre-admission screening should be done in order to rule out NCP. Real-time RT-PCR panel and chest CT scan should be conducted for patients with fever (>37.3℃), travel history to Hubei Province within 14 days, or contact history with residents from Wuhan district within 14 days. Prevention measures for both medical staffs and the screen-negative admitted patients should also be enhanced because false negative is possible. Medical instruments should be properly discarded or disinfected according to standardized procedures established by the local center for disease control and prevention (CDC). Surgical operation should be reduced at a minimal level to prevent cross infection in this special period.Surgical intervention for benign tumor should be postponed. For malignant tumor, multidisciplinary therapy (MDT) is recommended and non-surgical anti-tumor therapy should be selected with higher priority. Neoadjuvant therapy is highly recommended for gastrointestinal cancer at advanced stages that meet the indications of NCCN guideline (gastric cancer T stage ≥ 2/rectal cancer T stage ≥ 3/unresectable colon cancer). Gastric or esophagogastricjunction (EGJ) malignant tumor with obstruction can be managed with gastric tube decompression or stent placement to relieve the symptoms. Transnasal enteral feeding tube intubation/percutaneous endoscopic gastrostomy could be adopted to ensure enteral nutrition supply. For colorectal malignancy with simple intestinal obstruction, stent placement can achieve a high success rate, which not only helps avoid emergency surgery, but also creates a better condition for subsequent surgery. Transcatheter arterial embolization for hemostasis is an alternative choice for gastrointestinal tumor with bleeding. However, emergency operation still must be performed for patients with acute uncontrolled bleeding, obstruction or after other alternative treatment measures fail. All cases with suspicious or confirmed with NCP must be reported to the local CDC department. All invasive intervention must be performed in a designated isolation area. Tertiary prevention measure must be adopted for all anesthetists with additional face mask or medical goggle protection to prevent respiratory droplet transmission. Preventive enterostomy is preferable in lower digestive tract surgery. Thoroughly disinfecting the operating room after surgery is necessary. Fever after surgery must be carefully differentiated whether it's caused by post-surgery abdominal infection/inflammation or NCP. Single-room isolation and related examinations should be performed according to the standard procedures. We believe that with the unprecedentedly joint efforts of doctors and patients, we will eventually win this war against NCP.


Public Health Literacy for Lawyers


title: Experimental co-infection of infectious bronchitis and low pathogenic avian influenza H9N2 viruses in commercial broiler chickens

text: Abstract In this study, commercial broilers were experimentally infected with single (classical IBV, variant IBV or AIV-H9N2) or mixed AIV-H9N2 with classical, variant or vaccine strains of IBV. Birds were monitored for clinical and pathological outcomes and virus shedding for 10days post infection (DPI). Clinical signs were limited to the respiratory tract in all challenged groups and varied from mild to moderate mouth breathing to severe respiratory signs with snorting sound and extended head. Mortalities were only recorded in mixed AIV-H9N2/variant IBV challenge group. AIV-H9N2 challenge caused tracheal petechial hemorrhage that progressed to tracheal congestion and caseation. In mixed AIV-H9N2/IBV vaccine challenge, severe tracheitis with bronchial cast formation was observed. In mixed AIV-H9N2/variant IBV challenge severe congestion of the tracheal mucosa and excessive exudates with a tendency to form tubular casts were observed. Kidney ureate deposition was only observed in variant IBV challenge group. Histopathologically, tracheal congestion, severe degeneration, and deciliation were noticed in all groups of mixed infection. Interestingly, hemorrhage and atrophy were observed in thymus gland of birds challenged with single AIV-H9N2 or mixed AIV-H9N2/IBV. There was no difference in the tracheal shedding level of variant IBV between single and mixed infected groups while classical IBV shedding increased in mixed infection group. Interestingly, the AIV-H9N2 showed constantly high shedding titers till 7DPI with variant or vaccine IBV co-infection. In conclusion, co-infection of IBV and AIV-H9N2 induced severe clinical outcome and high mortality. Also, IBV co-infection increased the shedding of AIV-H9N2 in experimentally infected birds.


China's shift in HIV/AIDS policy marks turnaround on health


title: Novel Viruses, Zoonotic Infections, and Travel Health

text: Novel viruses and zoonotic infections pose global health risks.


title: Simultaneous detection and differentiation of canine parvovirus and feline parvovirus by high resolution melting analysis

text: BACKGROUND: Canine parvovirus (CPV) and feline parvovirus (FPV) are causative agents of diarrhea in dogs and cats, which manifests as depression, vomiting, fever, loss of appetite, leucopenia, and diarrhea in young animals. CPV and FPV can single or mixed infect cats and cause disease. To diagnose sick animals effectively, an effective virus diagnostic and genome typing method with high sensitivity and specificity is required. RESULTS: In this study, a conserved segment containing one SNP A4408C of parvovirus was used for real-time PCR amplification. Subsequently, data were auto-analyzed and plotted using Applied Biosystems® High Resolution Melt Software v3.1. Results showed that CPV and FPV can be detected simultaneously in a single PCR reaction. No cross-reactions were observed with canine adenovirus, canine coronavirus, and canine distemper virus. The assay had a detection limit of 4.2 genome copies of CPV and FPV. A total of 80 clinical samples were subjected to this assay, as well as to conventional PCR-sequence assay and virus isolation. Results showed that the percentage of agreement of the assay and other methods are high. CONCLUSIONS: In short, we have developed a diagnostic test for the accurate detection and differentiation of CPV and FPV in fecal samples, which is also cost effective.


title: COVID-19 and the Fears of Italian Senior Citizens

text: Italy has been hit very hard by the severe acute respiratory syndrome—coronavirus-2 (SARS-CoV-2) pandemic. This brief report highlights some of the peculiarities manifested by its older adult population, with particular reference to those living in nursing institutions and at home. Mortality data (as of 26 April) are reported, together with reactions to forced isolation, loneliness, and fear of contracting the disease, which represent big challenges for all, especially for frail elderly people.


title: Adherence to Universal Travel Screening in the Emergency Department During Epidemic Ebola Virus Disease

text: Abstract Background During the 2014 West African Ebola Virus Disease (EVD) outbreak, the U.S. Centers for Disease Control and Prevention recommended that all emergency department (ED) patients undergo travel screening for risk factors of importing EVD. Objectives We sought to determine the overall adherence rate to the recommended travel screening protocol and to identify factors associated with nonadherence to the protocol. Methods We conducted a multicenter, retrospective analysis of adherence to the travel screening program in an academic hospital and three affiliated community hospitals. A regression model identified patient and hospital factors associated with nonadherence. Results Of the 147,062 patients included for analysis, 93.7% (n = 137,834) had travel screenings completed. We identified several characteristics of patients that were most likely to be missed by the screening protocol—patients with low English proficiency, patients who arrive via ambulance or helicopter, and patients with more severe illness or injury based on initial triage acuity. Conclusions These findings should be used to improve adherence to the travel screening protocol for future emerging infectious disease threats.


title: RNA-GPS Predicts SARS-CoV-2 RNA Localization to Host Mitochondria and Nucleolus

text: The SARS-CoV-2 coronavirus is driving a global pandemic, but its biological mechanisms are less well understood. SARS-CoV-2 is an RNA virus whose multiple genomic and subgenomic RNA (sgRNA) transcripts hijack the host cell’s machinery, located across distinct cytotopic locations. Subcellular localization of its viral RNA could play important roles in viral replication and host antiviral immune response. Here we perform computational modeling of SARS-CoV-2 viral RNA localization across eight subcellular neighborhoods. We compare hundreds of SARS-CoV-2 genomes to the human transcriptome and other coronaviruses and perform systematic sub-sequence analyses to identify the responsible signals. Using state-of-the-art machine learning models, we predict that the SARS-CoV-2 RNA genome and all sgRNAs are enriched in the host mitochondrial matrix and nucleolus. The 5’ and 3’ viral untranslated regions possess the strongest and most distinct localization signals. We discuss the mitochondrial localization signal in relation to the formation of double-membrane vesicles, a critical stage in the coronavirus life cycle. Our computational analysis serves as a hypothesis generation tool to suggest models for SARS-CoV-2 biology and inform experimental efforts to combat the virus.


CD24Fc protects against viral pneumonia in simian immunodeficiency virus-infected Chinese rhesus monkeys


title: Humanized Mouse Models of Epstein-Barr Virus Infection and Associated Diseases

text: Epstein-Barr virus (EBV) is a ubiquitous herpesvirus infecting more than 90% of the adult population of the world. EBV is associated with a variety of diseases including infectious mononucleosis, lymphoproliferative diseases, malignancies such as Burkitt lymphoma and nasopharyngeal carcinoma, and autoimmune diseases including rheumatoid arthritis (RA). EBV in nature infects only humans, but in an experimental setting, a limited species of new-world monkeys can be infected with the virus. Small animal models, suitable for evaluation of novel therapeutics and vaccines, have not been available. Humanized mice, defined here as mice harboring functioning human immune system components, are easily infected with EBV that targets cells of the hematoimmune system. Furthermore, humanized mice can mount both cellular and humoral immune responses to EBV. Thus, many aspects of human EBV infection, including associated diseases (e.g., lymphoproliferative disease, hemophagocytic lymphohistiocytosis and erosive arthritis resembling RA), latent infection, and T-cell-mediated and humoral immune responses have been successfully reproduced in humanized mice. Here we summarize recent achievements in the field of humanized mouse models of EBV infection and show how they have been utilized to analyze EBV pathogenesis and normal and aberrant human immune responses to the virus.


title: Infectious disease emergence and global change: thinking systemically in a shrinking world

text: BACKGROUND: Concern intensifying that emerging infectious diseases and global environmental changes that could generate major future human pandemics. METHOD: A focused literature review was undertaken, partly informed by a forthcoming report on environment, agriculture and infectious diseases of poverty, facilitated by the Special Programme for Tropical Diseases. RESULTS: More than ten categories of infectious disease emergence exist, but none formally analyse past, current or future burden of disease. Other evidence suggests that the dominant public health concern focuses on two informal groupings. Most important is the perceived threat of newly recognised infections, especially viruses that arise or are newly discovered in developing countries that originate in species exotic to developed countries, such as non-human primates, bats and rodents. These pathogens may be transmitted by insects or bats, or via direct human contact with bushmeat. The second group is new strains of influenza arising from intensively farmed chickens or pigs, or emerging from Asian “wet markets” where several bird species have close contact. Both forms appear justified because of two great pandemics: HIV/AIDS (which appears to have originated from bushmeat hunting in Africa before emerging globally) and Spanish influenza, which killed up to 2.5% of the human population around the end of World War I. Insufficiently appreciated is the contribution of the milieu which appeared to facilitate the high disease burden in these pandemics. Additionally, excess anxiety over emerging infectious diseases diverts attention from issues of greater public health importance, especially: (i) existing (including neglected) infectious diseases and (ii) the changing milieu that is eroding the determinants of immunity and public health, caused by adverse global environmental changes, including climate change and other components of stressed life and civilisation-supporting systems. CONCLUSIONS: The focus on novel pathogens and minor forms of anti-microbial resistance in emerging disease literature is unjustified by their burden of disease, actual and potential, and diverts attention from far more important health problems and determinants. There is insufficient understanding of systemic factors that promote pandemics. Adverse global change could generate circumstances conducive to future pandemics with a high burden of disease, arising via anti-microbial and insecticidal resistance, under-nutrition, conflict, and public health breakdown.


mBio Addresses the Pause in Gain-of-Function (GOF) Experiments Involving Pathogens with Pandemic Potential (PPP)


title: In vitro and in vivo Safety Evaluation of Nephure(TM)

text: Nephure(TM) is a proprietary oxalate decarboxylase (OxDC) enzyme being developed as a food ingredient. In this study, the safety of Nephure(TM) was evaluated in a bacterial mutagenicity assay and in a sub-chronic (13-week) oral toxicity study in rats. Nephure(TM) did not show any mutagenic properties in the mutagenicity assay. In the 13-week sub-chronic oral toxicity study in which 10 Sprague Dawley rats per sex were administered 0, 118, 235 and 475 mg/kg bw/day (8260, 16450 and 33,250 Units/kg bw/day, respectively) of Nephure(TM) by gavage, male and female rats did not show any test article-related clinical observations or effects on body weight, body weight gain, food consumption, food efficiency, ophthalmology, functional observational battery parameters or motor activity. Furthermore, there were no changes in coagulation, clinical chemistry, urinalysis or hematology parameters, macroscopic/microscopic findings or organ weights that could be attributed to the test article. Based on these results, Nephure(TM) was not mutagenic and the no-adverse-effect level (NOAEL) in the 13-week study was determined to be 475 mg/kg bw/day (33,250 Units/kg bw/day). Evaluation of the estimated consumption of Nephure(TM), generation of the metabolite formate, and the current safety studies resulted in a conclusion of a tolerable upper limit of 3450 Units of OxDC activity/day (57.5 Units activity/kg bw/day), when Nephure(TM) is added to food to decrease dietary oxalate.


title: Endogenous endophthalmitis caused by Enterococcus faecalis in a cat

text: A three‐year‐old male neutered domestic shorthair cat was presented for loss of vision associated with hyperthermia, lethargy and anorexia. Ophthalmic examination revealed a bilateral panuveitis. Cytological examination of aqueous and vitreous humours was performed and revealed a suppurative inflammation associated with numerous cocci. Enterococcus faecalis was identified by bacterial culture from aqueous and vitreous humour. No primary infection site was identified. Active uveitis resolved after systemic antibiotic therapy, but the vision loss was permanent. To the authors’ knowledge, this is the first reported case of endogenous bacterial endophthalmitis secondary to E. faecalis infection in a cat.


title: Eukaryotic initiation factor 4A (eIF4A) during viral infections

text: The helicase eIF4A is part of the cellular eIF4F translation initiation complex. The main functions of eIF4A are to remove secondary complex structures within the 5′-untranslated region and to displace proteins attached to mRNA. As intracellular parasites, viruses regulate the processes involved in protein synthesis, and different mechanisms related to controlling translation factors, such as eIF4A, have been found. The inhibitors of this factor are currently known; these substances could be used in the near future as part of antiviral pharmacological therapies in instances of replication cycles in which eIF4A is required. In this review, the particularities of how some viruses make use of this initiation factor to synthesize their proteins are discussed.


title: Separation and Quantification of Four Main Chiral Glucosinolates in Radix Isatidis and Its Granules Using High-Performance Liquid Chromatography/Diode Array Detector Coupled with Circular Dichroism Detection

text: As chemical drugs, separation and quantification of the specific enantiomer from the chiral compounds in herbal medicines are becoming more important. To clarify the chemical characterization of chiral glucosinolates—the antiviral active ingredients of Radix Isatidis, an optimized efficient method of HPLC-UV-CD was developed to simultaneously separate and quantify the four main chiral glucosinolates: progoitrin, epiprogoitrin, and R,S-goitrin. The first step was to determine progoitrin, epiprogoitrin, and R,S-goitrin using HPLC-UV, and then determine the R-goitrin and S-goitrin by coupling with CD detection. Subsequently, through the linear relations between anisotropy factor (g factor) and the percent optical purity of R-goitrin, the contents of R-goitrin and S-goitrin from the R,S-goitrin mixture were calculated separately. Furthermore, the chemical composition features of the four chiral glucosinolates in 37 samples from crude drugs, decoction pieces, and granules of R. Isatidis were conducted. The total content of the four glucosinolates was obviously higher in crude drugs, and the variance character of each glucosinolate contents was different. In summary, the accurate measurement method reported here allows for better control of the internal quality of R. Isatidis and its granules and provides a powerful approach for the analysis of other chiral components in traditional Chinese medicines.


title: Treatment of respiratory virus infections

text: Abstract Respiratory viral infections (RVIs) can be associated with a wide range of clinical manifestations ranging from self-limited upper respiratory tract infections to more devastating conditions, such as pneumonia. RVIs constitute the most frequent reason for medical consultations in the world and they have a considerable impact on quality of life and productivity. Therefore, the prevention and control of RVIs remain major clinical goals. Currently, there are approximately 200 known respiratory viruses that can be grouped into one family of DNA viruses (Adenoviridae) and four families of RNA viruses (Orthomyxoviridae, Paramyxoviridae, Picornaviridae and Coronaviridae). In this paper, we review the major respiratory viruses that cause disesases in humans, with an emphasis on current treatment options.


title: An updated TaqMan real-time PCR for canine and feline parvoviruses

text: Abstract Canine parvovirus type 2 (CPV-2) emerged in late 1970s from the feline panleukopenia virus (FPLV) and developed, since then, into novel genetic and antigenic variants (CPV-2a, -2b and -2c). Canine and feline parvoviruses cause an acute enteric disease in their hosts, with high level of viral shedding. In this study, a quantitative TaqMan PCR for detection and quantitation of canine and feline parvoviruses in serum and fecal samples was developed. The primers were designed based upon the entire GenBank content for CPV and FPLV. A standard curve was generated, and validation tests were performed using 10-fold serial dilutions of CPV-2 virus in CPV/FPLV-negative feces and CPV/FPLV-negative serum samples. As a result, the 100% detection limit of the PCR was 18 copies of the viral genome per μl of serum and fecal sample. All canine parvovirus types as well as FPLV were detected. In conclusion, the real-time PCR represents an upgraded and useful tool to identify and quantify canine and feline parvoviruses in different sample matrices.


title: Rapid metagenomic characterization of a case of imported COVID-19 in Cambodia

text: Rapid production and publication of pathogen genome sequences during emerging disease outbreaks provide crucial public health information. In resource-limited settings, especially near an outbreak epicenter, conventional deep sequencing or bioinformatics are often challenging. Here we successfully used metagenomic next generation sequencing on an iSeq100 Illumina platform paired with an open-source bioinformatics pipeline to quickly characterize Cambodia’s first case of COVID-2019.


title: Discovery of Hepatitis C Virus NS3 Helicase Inhibitors by a Multiplexed, High‐Throughput Helicase Activity Assay Based on Graphene Oxide

text: Ein einfaches Testsystem auf der Basis von Graphenoxid (GO) ermöglicht das Screening selektiver Inhibitoren einer Helicase des Hepatitis‐C‐Virus (HCV) zusammen mit Inhibitoren eines SARS‐Coronavirus (SARS‐CoV) (siehe Schema). In einem einzelnen Screen wurden fünf hochselektive Inhibitoren der HCV‐Helicase gefunden, die ortholog zur SARS‐CoV‐Helicase sind. Einige dieser Treffer wurden mit dem gleichen GO‐Assay validiert.[Image: see text]


title: Cerebrovascular Accident in a Pediatric Patient Presenting With Influenza

text: Abstract Background Acute ischemic stroke (AIS) in pediatric populations accounts for more than half of pediatric strokes and is associated with significant morbidity and mortality. Pediatric AIS can present with nonspecific symptoms or symptoms that mimic alternate pathology. Case Report A 4-month-old female presented to the emergency department for fever, decreased oral intake, and “limp” appearance after antibiotic administration. She was febrile, tachypneic, and hypoxic. Her skin was mottled with 3-s capillary refill, her anterior fontanelle was tense, and she had mute Babinski reflex bilaterally but was moving all extremities. The patient was hyponatremic, thrombocytopenic, and tested positive for influenza A. A computed tomography scan of the brain revealed an acute infarction involving the right frontal, parietal, temporal, and occipital lobes in addition to hyperdensities concerning for thrombosed cortical veins. The patient was transferred for specialty evaluation and was discharged 2 weeks later on levetiracetam. Why Should an Emergency Physician be Aware of This? Pediatric AIS can present with nonspecific symptoms that mimic alternate pathology. A high level of suspicion is needed so as not to miss the diagnosis of pediatric AIS in the emergency department. A thorough neurologic assessment is warranted, and subtle abnormalities should be investigated further.


title: Exploring possible mechanisms for COVID‐19 induced thrombocytopenia: Unanswered questions

text: We read with enthusiasm the recent article by Tang et al. entitled "Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia," which is a retrospective analysis of the coagulation profile of 183 patients admitted with pneumonia secondary to the 2019-nCoV (COVID-19).1 This article deals with a timely topic and brings up important points that need to be interrogated in future studies.


title: Sendai virus intra-host population dynamics and host immunocompetence influence viral virulence during in vivo passage

text: In vivo serial passage of non-pathogenic viruses has been shown to lead to increased viral virulence, and although the precise mechanism(s) are not clear, it is known that both host and viral factors are associated with increased pathogenicity. Under- or overnutrition leads to a decreased or dysregulated immune response and can increase viral mutant spectrum diversity and virulence. The objective of this study was to identify the role of viral mutant spectra dynamics and host immunocompetence in the development of pathogenicity during in vivo passage. Because the nutritional status of the host has been shown to affect the development of viral virulence, the diet of animal model reflected two extremes of diets which exist in the global population, malnutrition and obesity. Sendai virus was serially passaged in groups of mice with differing nutritional status followed by transmission of the passaged virus to a second host species, guinea pigs. Viral population dynamics were characterized using deep sequence analysis and computational modeling. Histopathology, viral titer and cytokine assays were used to characterize viral virulence. Viral virulence increased with passage and the virulent phenotype persisted upon passage to a second host species. Additionally, nutritional status of mice during passage influenced the phenotype. Sequencing revealed the presence of several non-synonymous changes in the consensus sequence associated with passage, a majority of which occurred in the hemagglutinin-neuraminidase and polymerase genes, as well as the presence of persistent high frequency variants in the viral population. In particular, an N1124D change in the consensus sequences of the polymerase gene was detected by passage 10 in a majority of the animals. In vivo comparison of an 1124D plaque isolate to a clone with 1124N genotype indicated that 1124D was associated with increased virulence.


title: Transcriptome Analysis Reveals the Mechanism Underlying the Production of a High Quantity of Chlorogenic Acid in Young Leaves of Lonicera macranthoides Hand.-Mazz

text: Lonicera macranthoides Hand.-Mazz (L. macranthoides) is a medicinal herb that is widely distributed in southern China. The biosynthetic and metabolic pathways for a core secondary metabolite in L. macranthoides, chlorogenic acid (CGA), have been elucidated in many species. However, the mechanisms of CGA biosynthesis and the related gene regulatory network in L. macranthoides are still not well understood. In this study, CGA content was quantified by high performance liquid chromatography (HPLC), and CGA levels differed significantly among three tissues; specifically, the CGA content in young leaves (YL) was greater than that in young stems (YS), which was greater than that in mature flowers (MF). Transcriptome analysis of L. macranthoides yielded a total of 53,533,014 clean reads (average length 90 bp) and 76,453 unigenes (average length 703 bp). A total of 3,767 unigenes were involved in biosynthesis pathways of secondary metabolites. Of these unigenes, 80 were possibly related to CGA biosynthesis. Furthermore, differentially expressed genes (DEGs) were screened in different tissues including YL, MF and YS. In these tissues, 24 DEGs were found to be associated with CGA biosynthesis, including six phenylalanine ammonia lyase (PAL) genes, six 4-coumarate coenzyme A ligase (4CL) genes, four cinnamate 4-Hydroxylase (C4H) genes, seven hydroxycinnamoyl transferase/hydroxycinnamoyl-CoA quinate transferase HCT/HQT genes and one coumarate 3-hydroxylase (C3H) gene.These results further the understanding of CGA biosynthesis and the related regulatory network in L. macranthoides.


When Home is Not a Safe Place: Impacts of Social Distancing Directives on Women Living with HIV


Impact of Covid 19 pandemic on obsessive compulsive and related disorder patients‐ Psychodermatological perspectives


title: A Molecular Docking Study Repurposes FDA Approved Iron Oxide Nanoparticles to Treat and Control COVID-19 Infection

text: COVID-19, is a disease resulting from the SARS-CoV-2 global pandemic. Due to the current global emergency and the length of time required to develop specific antiviral agent(s) and a vaccine for SARS-CoV-2, the world health organization (WHO) adopted the strategy of repurposing existing medications to treat COVID-19. Iron oxide nanoparticles (IONPs) were previously approved by the US food and drug administration (FDA) for anemia treatment and studies have also demonstrated its antiviral activity in vitro. Therefore, we performed a docking study to explore the interaction of IONPs (Fe(2)O(3) and Fe(3)O(4)) with the spike protein receptor binding domain (S1-RBD) of SARS-CoV-2 that is required for virus attachment to the host cell receptors. A similar docking analysis was also performed with hepatitis C virus (HCV) glycoproteins E1 and E2. These studies revealed that both Fe(2)O(3) and Fe(3)O(4) interacted efficiently with the SARS-CoV-2 S1-RBD and to HCV glycoproteins, E1 and E2. Fe(3)O(4) formed a more stable complex with S1-RBD whereas Fe(2)O(3) favored HCV E1 and E2. These interactions of IONPs are expected to be associated with viral proteins conformational changes and hence, viral inactivation. Therefore, we recommend FDA-approved-IONPs to proceed for COVID-19 treatment clinical trials.


title: Phylogenetic and antigenic analysis of avian infectious bronchitis virus in southwestern China, 2012–2016

text: Abstract The aim of this study was to decipher the molecular epidemiological and antigenic characteristics of infectious bronchitis virus strains (IBVs) isolated in recent years in southwestern China. A total of 24 field strains were isolated from diseased chickens between 2012 and 2016. Phylogenetic analysis based on S1 nucleotide sequences showed that 16 of the 24 isolates were clustered into four distinct genotypes: QX (37.5%), TW (16.7%, TWI and TWII), Mass (8.3%), and J2 (4.2%). The QX genotype was still the prevalent genotype in southwestern China. Recombination analysis of the S1 subunit gene showed that eight of the 24 field strains were recombinant variants that originated from field strains and vaccine strains. A new potential recombination hotspot [ATTTT(T/A)] was identified, implying that recombination events may become more and more common. The antigenicity of ten IBVs, including seven field strains and commonly used vaccine strains, were assayed with a viral cross-neutralization assay in chicken embryonated kidney cells (CEK). The results showed that the ten IBVs could be divided into four serotypes (Massachusetts, 793B, Sczy3, and SCYB). Sczy3 and 793B were the predominant serotypes. Six of the seven field isolates (all except for cK/CH/SCYB/140913) cross-reacted well with anti-sera against other field strains. In conclusion, the genetic and antigenic features of IBVs from southwestern China in recent years have changed when compared to the previous reports. The results could provide a reference for vaccine development and the prevention of infectious bronchitis in southwestern China.


title: Looking out for myself: Exploring the relationship between conspiracy mentality, perceived personal risk, and COVID‐19 prevention measures

text: OBJECTIVES: This research examined how conspiracy mentality may affect compliance with preventive health measures necessary to fight the COVID‐19 pandemic, and the underlying motivations to comply. DESIGN AND METHOD: We conducted two cross‐sectional studies (Study 1 N = 762, Study 2 N = 229) on a French population, measuring conspiracy mentality, compliance with preventive health measures, and perceived risks related to COVID‐19. We also measured motivations to comply with preventive measures in Study 2. RESULTS: We show that people high in conspiracy mentality are likely to engage in non‐normative prevention behaviours (Study 1), but are less willing to comply with extreme preventive behaviours that are government‐driven (Study 2). However, we demonstrate that a perceived risk to oneself (risk of death) and a motivation to protect oneself can act as a suppressor: Conspiracy mentality is linked with an increase in the perception of risk to oneself, which, in turn, is associated with normative compliance. We also find that perceived risk of death explains the relationship between conspiracy mentality and non‐normative prevention behaviours. CONCLUSIONS: Our studies showcase how people high in conspiracy theorizing may (dis)engage with prevention behaviours, but that perceived risk and motivation to protect oneself could increase these individuals’ compliance.


title: Field strain feline coronaviruses with small deletions in ORF7b associated with both enteric infection and feline infectious peritonitis

text: Feline coronavirus (FCoV) varies greatly from causing subclinical or mild enteric infections to fatal feline infectious peritonitis (FIP). The open reading frame (ORF) 7b of FCoV has been speculated to play a determining role in virulence as deletions were found to be associated with avirulent viruses. To further clarify the correlation between this gene and FIP, clinical samples from 20 cats that had succumbed to wet-type FIP and 20 clinically healthy FCoV-infected cats were analysed. The ORF7b from the peritoneal/pleural effusions of FIP cats and from the rectal swabs of healthy cats was amplified. Of the 40 FCoVs analysed, 32 were found to have an intact 7b gene whereas eight showed deletions of either three or 12 nucleotides. Surprisingly, among the eight viruses with deletions, three were from FIP diseased cats. These results show that deletions in the ORF7b gene are not constrained to low pathogenicity/enteric biotypes but also associated with pathogenicity/FIP biotypes of FCoV.


title: Cutaneous lesions associated with coronavirus-induced vasculitis in a cat with feline infectious peritonitis and concurrent feline immunodeficiency virus infection

text: This report describes a clinical case of feline infectious peritonitis (FIP) with multisystemic involvement, including multiple nodular cutaneous lesions, in a cat that was co-infected with feline coronavirus and feline immunodeficiency virus. The skin lesions were caused by a pyogranulomatous-necrotising dermal phlebitis and periphlebitis. Immunohistology demonstrated the presence of coronavirus antigen in macrophages within these lesions. The pathogenesis of FIP involves a viral associated, disseminated phlebitis and periphlebitis which can arise at many sites. Target organs frequently include the eyes, abdominal organs, pleural and peritoneal membranes, and central nervous tissues, but cutaneous lesions have not previously been reported.


title: Lessons learned: Optimization of a murine small bowel resection model

text: BACKGROUND/PURPOSE: Central to the use of murine models of disease is the ability to derive reproducible data. The purpose of this study was to determine factors contributing to variability in our murine model of small bowel resection (SBR). METHODS: Male C57Bl/6 mice were randomized to sham or 50% SBR. The effect of housing type (pathogen-free versus standard housing), nutrition (reconstituted powder versus tube feeding formulation), and correlates of intestinal morphology with gene expression changes were investigated Multiple linear regression modeling or one-way ANOVA was used for data analysis. RESULTS: Pathogen-free mice had significantly shorter ileal villi at baseline and demonstrated greater villus growth after SBR compared to mice housed in standard rooms. Food type did not affect adaptation. Gene expression changes were more consistent and significant in isolated crypt cells that demonstrated adaptive growth when compared with crypts that did not deepen after SBR. CONCLUSION: Maintenance of mice in pathogen-free conditions and restricting gene expression analysis to individual animals exhibiting morphologic adaptation enhances sensitivity and specificity of data derived from this model. These refinements will minimize experimental variability and lead to improved understanding of the complex process of intestinal adaptation.


title: Immunosuppression drug‐related and clinical manifestation of Coronavirus disease 2019: A therapeutical hypothesis

text: We read with interest the article of Guillen et al. 1 . Here, the authors described the management of a kidney transplanted patient infected by SARS-CoV-2 that causes novel Coronavirus disease 2019 (COVID-19). The authors stated that immunosuppressed patients might present with atypical clinical manifestation (fever, diarrhea, fatigue) without respiratory symptoms. Also Li and colleagues 2 reported SARS-CoV-2 infection in two solid organ transplanted patients. The two heart transplanted patients presented with variable severity of COVID-19 (one mild and another with more severe manifestations requiring a prolonged hospitalization), however, both survived the event.


title: As MERS spreads, frustration at lack of info grows

text: There are signs that the new coronavirus that emerged in the Arabian peninsula last year is spreading among people that have had no known contact with an infected source


title: Genomes of the Mouse Collaborative Cross

text: The Collaborative Cross (CC) is a multiparent panel of recombinant inbred (RI) mouse strains derived from eight founder laboratory strains. RI panels are popular because of their long-term genetic stability, which enhances reproducibility and integration of data collected across time and conditions. Characterization of their genomes can be a community effort, reducing the burden on individual users. Here we present the genomes of the CC strains using two complementary approaches as a resource to improve power and interpretation of genetic experiments. Our study also provides a cautionary tale regarding the limitations imposed by such basic biological processes as mutation and selection. A distinct advantage of inbred panels is that genotyping only needs to be performed on the panel, not on each individual mouse. The initial CC genome data were haplotype reconstructions based on dense genotyping of the most recent common ancestors (MRCAs) of each strain followed by imputation from the genome sequence of the corresponding founder inbred strain. The MRCA resource captured segregating regions in strains that were not fully inbred, but it had limited resolution in the transition regions between founder haplotypes, and there was uncertainty about founder assignment in regions of limited diversity. Here we report the whole genome sequence of 69 CC strains generated by paired-end short reads at 30× coverage of a single male per strain. Sequencing leads to a substantial improvement in the fine structure and completeness of the genomes of the CC. Both MRCAs and sequenced samples show a significant reduction in the genome-wide haplotype frequencies from two wild-derived strains, CAST/EiJ and PWK/PhJ. In addition, analysis of the evolution of the patterns of heterozygosity indicates that selection against three wild-derived founder strains played a significant role in shaping the genomes of the CC. The sequencing resource provides the first description of tens of thousands of new genetic variants introduced by mutation and drift in the CC genomes. We estimate that new SNP mutations are accumulating in each CC strain at a rate of 2.4 ± 0.4 per gigabase per generation. The fixation of new mutations by genetic drift has introduced thousands of new variants into the CC strains. The majority of these mutations are novel compared to currently sequenced laboratory stocks and wild mice, and some are predicted to alter gene function. Approximately one-third of the CC inbred strains have acquired large deletions (>10 kb) many of which overlap known coding genes and functional elements. The sequence of these mice is a critical resource to CC users, increases threefold the number of mouse inbred strain genomes available publicly, and provides insight into the effect of mutation and drift on common resources.


title: Comparison of a laboratory-developed RT-PCR and the CDC RT-PCR protocol with rapid immunodiagnostic testing during the 2009 H1N1 influenza A pandemic

text: Abstract We evaluated the performance of a laboratory-developed multiplex real-time reverse transcription-PCR assay (LDT rRT-PCR), the Centers for Disease Control and Prevention (CDC) 2009 H1N1 rRT-PCR protocol using the LightCycler 480 II, the multiplex xTAG Respiratory Virus Panel (xTAG RVP), and rapid immunodiagnostic testing (RIDT) using the BinaxNOW Influenza A & B to detect 2009 H1N1 with 426 nasopharyngeal swab specimens during the 2009 H1N1 pandemic. The specificity of the methods tested was ≥98%, and the individual test sensitivities were RIDT at 42.3% [95% confidence interval (CI), 31.4–54.0], LDT rRT-PCR at 98.9% (95% CI, 92.9–99.9), CDC 2009 H1N1 rRT-PCR at 78.2% (95% CI, 67.8–86.0), and xTAG RVP at 93.1% (95% CI, 85.0–97.2). A negative RIDT result should not be used to make decisions with respect to treatment or infection prevention. rRT-PCR is the preferred first-line diagnostic test for detecting 2009 H1N1 influenza A.


title: Application of National Aerosol Facility (NAF) in Designing of a Ventilation System for Isolation Rooms to Minimize Interpersonal Exposure of Sneezing/Coughing

text: With the outbreak of pandemic COVID-19, protection of public and health workers has become a national priority. In this regard, it is desirable to study the coughing- and sneezing-generated pathogen aerosols, its dispersion and transportation in isolation rooms, clinics, confined spaces and other general public places to evolve efficient ventilation system along with suitable protective measures to limit the spread of the virus. The present paper describes the overall experimental scheme supported with computational fluid dynamics evaluation to address this problem for evolution of optimal ventilation system using the National Aerosol Facility at IIT Kanpur set up in collaboration with BARC Trombay. The outcome of this study is aimed to evolve a national standard for optimum isolation rooms that would provide adequate protection to health workers.


LEVEN TIJDENS COVID-19


title: Blood Component Recalls and Market Withdrawals: Frequency, Reasons, and Management in the United States

text: Abstract In a previous article, we reviewed the management of blood component recalls and withdrawals (G. Ramsey. Transfusion Med Rev 2004;18:36–45). Since then, US rates of recall and biological product deviation for blood components have improved significantly, particularly with regard to reduced recalls for donor infectious disease risks or testing. However, analysis of the current data from the US Food and Drug Administration suggests that 1 (0.4%) in 250 blood components is involved in market withdrawals and quarantines, with 1 in 5800 components formally recalled. Most of these units, unfortunately, had already have been transfused. The US Food and Drug Administration has issued several recent guidances that address transfusion service actions for dealing with specific infectious disease problems. This present article updates our 2004 recommendations as to when to notify physicians about transfused nonconforming blood components.


title: Genome-wide Prediction of microRNAs in Zika virus Genomes Reveals Possible Interactions with Human Genes Involved in the Nervous System Development

text: Zika virus (ZIKV) is a member of the family Flaviviridae. In 2015, ZIKV triggered a large epidemic in Brazil and spread across Latin America. In November of that year, the Brazilian Ministry of Health reported a 20-fold increase in cases of neonatal microcephaly, which corresponds geographically and temporally to the ZIKV outbreak. ZIKV was isolated from the brain tissue of a fetus diagnosed with microcephaly, and recent studies in mice models revealed that ZIKV infection may cause brain defects by influencing brain cell developments. Unfortunately, the mechanisms by which ZIKV alters neurophysiological development remain unknown. MicroRNAs (miRNAs) are small noncoding RNAs that regulate post-transcriptional gene expression by translational repression. In order to gain insight into the possible role of ZIKV-mediated miRNA signaling dysfunction in brain-tissue development, we computationally predicted new miRNAs encoded by the ZIKV genome and their effective hybridization with transcripts from human genes previously shown to be involved in microcephalia. The results of these studies suggest a possible role of these miRNAs on the expression of human genes associated with this disease. Besides, a new ZIKV miRNA was predicted in the 3’stem loop (3’ SL) of the 3’untranslated region (3’UTR) of the ZIKV genome, suggesting the role of the 3’UTR of flaviviruses as a source of miRNAs.


title: Sensitive and rapid detection of Zika virus by loop-mediated isothermal amplification

text: Zika virus (ZIKV) is a mosquito-borne flavivirus, which is a pathogen affecting humans in Africa, Asia, and America. It is necessary to detect ZIKV with a rapid and sensitive molecular method to guide timely treatment. In this study, a loop-mediated isothermal amplification (LAMP) assay was described, which is an attractive option as a fast, sensitive, and specific method for ZIKV detection using the NS5 protein coding region and the envelope protein (EP) coding region as target sequences. Two different techniques, a calcein/Mn(2+) complex chromogenic method and real-time turbidity monitoring, were employed. The specificity and sensitivity of the LAMP assay were determined. The assay’s detection limit was 0.5 × 10(−9) pmol/µl DNA for NS5 protein coding region and 1.12 × 10(−11) pmol/µl DNA for E coding region, respectively, which is a 100-fold increase in sensitivity compared with real-time reverse transcription-polymerase chain reaction (RT-PCR) and conventional PCR. All 12 non-ZIKA respiratory pathogens tested were negative for LAMP detection, indicating the high specificity of the primers for ZIKV. In conclusion, a visual detection LAMP assay was developed, which could be a useful tool for primary quarantine purposes and clinical screening, especially in situations where resources are poor and in point-of-care tests.


title: Genome Organization of Canada Goose Coronavirus, A Novel Species Identified in a Mass Die-off of Canada Geese

text: The complete genome of a novel coronavirus was sequenced directly from the cloacal swab of a Canada goose that perished in a die-off of Canada and Snow geese in Cambridge Bay, Nunavut, Canada. Comparative genomics and phylogenetic analysis indicate it is a new species of Gammacoronavirus, as it falls below the threshold of 90% amino acid similarity in the protein domains used to demarcate Coronaviridae. Additional features that distinguish the genome of Canada goose coronavirus include 6 novel ORFs, a partial duplication of the 4 gene and a presumptive change in the proteolytic processing of polyproteins 1a and 1ab.


The Transmembrane Domain of the Infectious Bronchitis Virus E Protein is Required for Efficient Virus Release


title: Detection of Alphacoronavirus vRNA in the Feces of Brazilian Free-Tailed Bats (Tadarida brasiliensis) from a Colony in Florida, USA

text: Bats are natural reservoirs of coronaviruses and other viruses with zoonotic potential. Florida has indigenous non-migratory populations of Brazilian free-tailed bats (Tadarida brasiliensis) that mostly roost in colonies in artificial structures. Unlike their counterparts in Brazil and Mexico, the viruses harbored by the Florida bats have been underexplored. We report the detection of an alphacoronavirus RNA-dependent RNA polymerase (RdRp) gene sequence in the feces of two of 19 different T. brasiliensis that were capture/release bats that had been evaluated for overall health. The RdRp sequence is similar but not identical to previously detected sequences in the feces of two different species of bats (T. brasiliensis and Molossus molossus) in Brazil. In common with the experience of others doing similar work, attempts to isolate the virus in cell cultures were unsuccessful. We surmise that this and highly related alphacoronavirus are carried by Brazilian free-tailed bats living in a wide eco-spatial region. As various coronaviruses (CoVs) that affect humans emerged from bats, our study raises the question whether CoVs such as the one detected in our work are yet-to-be-detected pathogens of humans and animals other than bats.


title: Human Metapneumovirus: A New Player among Respiratory Viruses

text: The human metapneumovirus (hMPV) is a newly described member of the Paramyxoviridae family belonging to the Metapneumovirus genus. Since its initial description in 2001, hMPV has been reported in most parts of the world and isolated from the respiratory tract of subjects from all age groups. Despite the fact that prospective and case-control studies have been limited, the epidemiology and clinical manifestations associated with hMPV have been found to be reminiscent of those of the human respiratory syncytial virus, with most severe respiratory tract infections occurring in infants, elderly subjects, and immunocompromised hosts. Additional research is needed to define the pathogenesis of this viral infection and the host's specific immune response.


title: Isolation of Virus from a SARS Patient and Genome-wide Analysis of Genetic Mutations Related to Pathogenesis and Epidemiology from 47 SARS-CoV Isolates

text: Severe acute respiratory syndrome (SARS) caused by SARS-associated coronavirus (SARS-CoV) is a fatal disease. Prevention of future outbreaks is essential and requires understanding pathogenesis and evolution of the virus. We have isolated a SARS-CoV in China and analyzed 47 SARS-CoV genomes with the aims to reveal the evolution trends of the virus and provide insights into understanding pathogenesis and SARS epidemic. Specimen from a SARS patient was inoculated into cell culture. The presence of SARS-CoV was determined by RT-PCR and confirmed by electron microscopy. Virus was isolated followed by the determination of its genome sequences, which were then analyzed by comparing with other 46 SARS-CoV genomes. Genetic mutations with potential implications to pathogenesis and the epidemic were characterized. This viral genome consists of 29,728 nucleotides with overall organization in agreement with that of published isolates. A total of 348 positions were mutated on 47 viral genomes. Among them 22 had mutations in more than three genomes. Hot spots of nucleotide variations and unique trends of mutations were identified on the viral genomes. Mutation rates were different from gene to gene and were correlated well with periodical or geographic characteristics of the epidemic.


title: Gastroenteritis and respiratory infection outbreaks in French nursing homes from 2007 to 2018: Morbidity and all-cause lethality according to the individual characteristics of residents

text: BACKGROUND: Gastroenteritis (GE) and respiratory tract infection (RTI) outbreaks are a significant issue in nursing homes. This study aimed to describe GE and RTI outbreaks with infection and all-cause lethality rates according to the individual characteristics of nursing home residents. METHODS: Clinical and virological surveillance were conducted (2007 to 2018). Virus stratifications for the analysis were: outbreaks with positive norovirus or influenza identifications (respectively NoV+ or Flu+), episodes with no NoV or influenza identification or testing (respectively NoV- or Flu-). Associations between individual variables (sex, age, length of stay (LOS), autonomy status) and infection and lethality rates were tested with univariate and Mantel-Haenszel (MH) methods. RESULTS: 61 GE outbreaks and 76 RTI oubreaks (total 137 outbreaks) were recorded involving respectively 4309 and 5862 residents. In univariate analysis, higher infection rates and age were associated in NoV+, NoV-, and Flu+ contexts, and lower infection rates were associated with longer stays (NoV+ and NoV-). In MH stratified analysis (virus, sex (female/male)) adjusted for LOS (<4 or ≥4 years), the odds of being infected remained significant among older residents (≥86 years): NoV+/male (Odds ratio (OR(MH)): 1.64, 95% confidence interval (CI): 1.16–2.30) and Flu+/female and male (respectively OR(MH): 1.50, CI: 1.27–1.79 and 1.73, CI: 1.28–2.33). In univariate analysis, lower autonomy status (NoV+, Flu+ and Flu-) and increased age (Flu+) were associated with higher lethality. In MH adjusted analysis, significant OR(age) adjusted for autonomy was: Flu+/ ≥86 years compared with <86 years, 1.97 (1.19–3.25) and OR(autonomy) adjusted for age for the more autonomous group (compared with the less autonomous group) was: Flu+, 0.41 (0.24–0.69); Flu-, 0.42 (0.20, 0.90). CONCLUSION: The residents of nursing homes are increasingly elderly and dependent. The specific infection and lethality risks according to these two factors indicate that surveillance and infection control measures are essential and of high priority.


title: COVID-19 and ENT Surgery

text: ABSTRACT In Otorhinolaryngology - Head and Neck Surgery, clinical examination and invasive procedures on the respiratory tract and on airway-connected cavities such as paranasal sinuses and the middle ear expose people to direct transmission of SARS-CoV-2 by inhalation or ocular projection of contaminated droplets, and to indirect transmission by contact with contaminated hands, objects or surfaces. Estimating an R0 of Covid-19 at around 3 justified postponing non-urgent face-to-face consultations and expanding the use of teleconsultation in order to limit the risks of SARS-CoV-2 infection of patients or health workers and comply with the lockdown. The health authority recommends cancellation of all medical or surgical activities which are not urgent as long as this does not involve a loss of chance for the patient. The purpose of this cancellation is to significantly increase critical care capacity, prioritize the reception of patients with Covid-19, prioritize the allocation of staff and provision of the equipment necessary for their medical or surgical management, and contribute to the smooth running of downstream critical care within their establishment. Another goal is to reduce the risks of patient contamination within healthcare facilities. This document provides guidance on how to proceed with and adapt ENT surgery in the current pandemic context, as well as on the management of postponed operations. This best practice advice must of course be adapted in each region according to the development of the epidemic and pre-existing arrangements. Their local application can only be decided within the framework of collaboration between the ENT teams, the operational hygiene units and all the other specialties concerned.


title: Testing for COVID-19: willful ignorance or selfless behavior?

text: Widespread testing is key to controlling the spread of COVID-19. But should we worry about self-selection bias in the testing? The recent literature on willful ignorance says we should – people often avoid health information. In the context of COVID-19, such willful ignorance can bias testing data. Furthermore, willful ignorance often arises when selfish wants conflict with social benefits, which might be particularly likely for potential ‘super-spreaders’ – people with many social interactions – given people who test positive are urged to self-isolate for two weeks. We design a survey in which participants (n = 897) choose whether to take a costless COVID-19 test. We find that 70% would take a test. Surprisingly, the people most likely to widely spread COVID-19 – the extraverts, others who meet more people in their daily lives and younger people – are the most willing to take a test. People's ability to financially or emotionally sustain self-isolation does not matter to their decision. We conclude that people are selfless in their decision to test for COVID-19. Our results are encouraging – they imply that COVOD-19 testing may succeed in targeting those who generate the largest social benefits from self-isolation if infected, which strengthens the case for widespread testing.


title: The impact of food safety events on the value of food-related firms: An event study approach

text: Food safety events threaten not only consumers’ health, but also the value of associated firms. While previous studies examined the impact of food safety events on consumer demand for products, little attention has been paid to the impact on the market value of firms. Using the event study method (ESM), this study investigated abnormal returns (ARs) and cumulative abnormal returns (CARs) of firms associated with 40 food safety events over the past 25 years in the U.S. The results of this study demonstrated the magnitude and duration of the impact of food safety events on firm value. Moreover, firm-specific factors (past history and firm size) and situational factor (media attention) were found to influence the magnitude of the impact. This study contributes to the hospitality literature by extending the knowledge of the impact of food safety events and its practical implications for effective crisis management strategies for food-related firms.


Ignaz Semmelweis—Handwashing Invention and COVID-19


title: Morbillivirus vaccines: Recent successes and future hopes

text: The impact of morbilliviruses on both human and animal populations is well documented in the history of mankind. Indeed, prior to the development of vaccines for these diseases, morbilliviruses plagued both humans and their livestock that were heavily relied upon for food and motor power within communities. Measles virus (MeV) was responsible for the death of millions of people annually across the world and those fortunate enough to escape the disease often faced starvation where their livestock had died following infection with rinderpest virus (RPV) or peste des petits ruminants virus (PPRV). Canine distemper virus has affected dog populations for centuries and in the past few decades appears to have jumped species, now causing disease in a number of non-canid species, some of which are been pushed to the brink of extinction by the virus. During the age of vaccination, the introduction and successful application of vaccines against rinderpest and measles has led to the eradication of the former and the greater control of the latter. Vaccines against PPR and canine distemper have also been generated; however, the diseases still pose a threat to susceptible species. Here we review the currently available vaccines against these four morbilliviruses and discuss the prospects for the development of new generation vaccines.


title: Altered Pathogenesis of a Mutant of the Murine Coronavirus MHV-A59 Is Associated with a Q159L Amino Acid Substitution in the Spike Protein

text: Abstract C12, an attenuated, fusion delayed, very weakly hepatotropic mutant of mouse hepatitis virus strain A59 (MHV-A59) has been further characterized. We have previously shown that C12 has two amino acid substitutions relative to wild type virus in the spike protein, Q159L (within a region of S1 shown to bind to viral receptor in anin vitroassay) and H716D (in the proteolytic cleavage recognition site). We have sequenced the rest of the 31-kb genome of C12 and compared it to wild type virus. Only three additional amino acids substitutions were found, all encoded within the replicase gene. Analysis of C12in vivoin C57Bl/6 mice has shown that despite the fact that this virus replicates in the brain to titers at least as high as wild type and causes acute encephalitis similar to wild type, this virus causes a minimal level of demyelination and only at very high levels of virus inoculation. Thus acute encephalitis is not sufficient for the induction of demyelination by MHV-A59. Analysis of mutants isolated at earlier times from the same persistently infected glial cell culture as C12, as well as mutants isolated from a second independent culture of persistently infected glial cells, suggests that both the weakly demyelinating and the weakly hepatotropic phenotypes of C12 are associated with the Q159L amino acid substitution.


title: A survey on the impact of the COVID‐19 pandemic on motility and functional investigations in Europe and considerations for recommencing activities in the early recovery phase

text: BACKGROUND: The COVID‐19 pandemic, declared by WHO on March 13(th) 2020, had a major global impact on the health care system and services. In the acute phase, the presence of the SARS‐CoV‐2 virus in the aerodigestive tract limited activities in the gastroenterology clinic and procedures to emergencies only. Motility and function testing was interrupted and as we enter the recovery phase, restarting these procedures requires a safety‐focused approach with adequate infection prevention for patients and healthcare professionals. METHODS: We summarized knowledge on the presence of the SARS‐CoV‐2 virus in the aerodigestive tract and the risk of spread with motility and functional testing. We surveyed 39 European centers documenting how the pandemic affected activities and which measures they are considering for restarting these measurements. We propose recommendations based on current knowledge as applied in our center. RESULTS: Positioning of catheters for gastrointestinal motility tests carries a concern for aerosol‐borne infection of health care workers. The risk is low with breath tests. The surveyed centers stopped almost all motility and function tests from the second half of March. The speed of restarting and the safety measures taken varied highly. CONCLUSIONS AND INFERENCES: Based on these findings, we provided recommendations and practical relevant information for motility and function test procedures in the COVID‐19 pandemic era, to guarantee a high‐quality patient care with adequate infection prevention.


title: Computational investigation on Andrographis paniculata phytochemicals to evaluate their potency against SARS-CoV-2 in comparison to known antiviral compounds in drug trials

text: The outbreak due to SARS-CoV-2 (or Covid-19) is spreading alarmingly and number of deaths due to infection is aggressively increasing every day. Due to the rapid human to human transmission of Covid-19, we are in need to find a potent drug at the earliest by ruling-out the traditional time-consuming approach of drug development. This is only possible if we use reliable computational approaches for screening compounds from chemical space or by drug repurposing or by finding the phytochemicals and nutraceuticals from plants as they can be immediately used without the need for carrying out drug-trials to test safety and efficacy. A number of plant products were routinely suggested as drugs in traditional Indian and Chinese medicine. Here using molecular docking approach, and combined molecular dynamics and MM-GBSA based free energy calculations approach, we study the potency of the four selected phytochemicals namely andrographolide (AGP1), 14-deoxy 11,12-didehydro andrographolide (AGP2), neoandrographolide (AGP3) and 14-deoxy andrographolide (AGP4) from A. paniculata plant against the four key targets including three non-structural proteins (3 L main protease (3CLpro), Papain-like proteinase (PLpro) and RNA-directed RNA polymerase (RdRp)) and a structural protein (spike protein (S)) of the virus which are responsible for replication, transcription and host cell recognition. The therapeutic potential of the selected phytochemicals against Covid-19 were also evaluated in comparison with a few commercially available drugs. The binding free energy data suggest that AGP3 could be used as a cost-effective drug-analog for treating covid-19 infection in developing countries. Communicated by Ramaswamy H. Sarma


Osteoporotic Fractures in the Time of COVID‐19


title: Liver injury in COVID‐19: diagnosis and associated factors – authors' reply

text: As coronavirus disease 2019 (COVID‐19) is a new, emerging infectious disease, guidance or consensus on liver injury are lacking(2). The definition of COVID‐19 associated liver injury in our manuscript was as alanine transaminase (ALT), aspartate aminotransferase (AST) or bilirubin above the upper limit of normal (ULN), which were 50 U/L, 40 U/L, and 26 μmol/l respectively. The abnormal test results of ALT, AST and total bilirubin at baseline data were defined as liver injury in our manuscript.


title: Modulation of immunity and inflammatory gene expression in buffalo (Bubalus bubalis) with some digestive disorders

text: So far, there has been scarce information about the status of immunoglobulins (Ig) and the gene expression of inflammatory cytokines in buffaloes showing digestive troubles. The purpose of the present study was to explore the modulation of gene expression of some immune-inflammatory markers in buffaloes suffered from various digestive disorders. For this reason, 50 native breed water buffaloes were studied. Forty of these buffaloes showed various symptoms of digestive disorders and were allocated into 4 groups of equal sizes (group 1: uncategorized stomatitis; group 2: acute traumatic reticuloperitonitis [TRR]; group 3: acute rumen impaction; and group 4: undifferentiated enteritis). Ten apparently healthy buffaloes were randomly selected and considered as a control group. RNA was firstly extracted from the whole blood then a reverse transcription kits was used to convert the RNA to cDNA. Real-time PCR was used to measure the expression of mRNAs of interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor (TNF)-α, IgG, and IgA, while glyceraldehyde-3-phosphate dehydrogenase (GAPDH) used as an internal reference. The results of real-time PCR revealed a significant (P ≤ 0.05) upregulation of the gene expression of IL-1β, IL-6, IL-10, and TNF-α in blood of diseased buffaloes compared with those of controls. Animals showing acute TRP had peak values of both IL-6 and IL-10; while those exhibiting enteritis and rumen impaction had the highest values of IL-1β and TNF-α, respectively. The results of qPCR also revealed a significant (P ≤ 0.05) downregulation of both IgG and IgA gene expression in blood of all diseased buffaloes compared with controls. The lowest values of both genes were recorded in buffaloes showing acute TRP. The results herein suggest that the tested genes could have a pivotal role in the pathophysiologic mechanism of the underlying diseases.


title: Phosphatidylserine’s role in Ebola’s inflammatory cytokine storm and hemorrhagic consumptive coagulopathy and the therapeutic potential of annexin V

text: Abstract The phosphatidylserine (PS) molecule is present in cell membranes where it is actively kept on their inner leaflets but when cells are damaged it moves to the surface and become a signal for their removal, the platform upon which the coagulation cascade takes place and a ligand that activates a feedback cycle of inflammatory cytokine secretion and initiates the wakeup call for the innate immune response. These are physiologic responses to PS but the Ebola virus displays PS molecules on its membrane’s surface and the huge numbers of viruses cause a pathologic inflammatory cytokine storm and a hemorrhagic consumptive coagulopathy. Annexin V is an innate molecule that can cloak membrane displayed PS and prevents its Th1 cell’s inflammatory cytokine generation and cascade thrombin generation. The hypothesis presented is that its administration will cloak PS and prevent Ebola’s consumptive coagulopathy and its cytokine storm.


title: Sex and gender differences in the outcome of patients with COVID‐19

text: The SARS-CoV-2 pandemic is a new wave of emerging infections that the world is struggling with. There are many unanswered questions in this regard, including Gender-specific outcome in COVID-19. Gender and age are major risk factors for SARS-CoV-2 infection. In addition to the effect of these factors on the prevalence of SARS-CoV-2, the clinical outcome varies according to both of them. This article is protected by copyright. All rights reserved.


Telemedicina, telementorización y evaluación telemática en Cirugía. ¿Es su momento después de la COVID-19?


title: Exogenous lipoid pneumonia in children: A systematic review

text: Abstract Objectives To describe the clinical-radiological-pathological characteristics and treatment outcomes of children with suspected exogenous lipoid pneumonia (ELP). Design Systematic review. We searched electronic databases and reference lists published between 1967 and 2018, restricted to non-accidental cases. Results Forty-four studies including 489 participants aged 1 day to 17 years from 13 countries were included. Cultural, medical, and behavioural rationale for oil-use was described. The clinical-radiological presentation varied widely. Diagnostic certainty was deemed highest if ELP was confirmed on bronchoalveolar lavage/frozen section lung biopsy with documented extracellular lipid on cytological staining and/or fat analysis. Non-tuberculous mycobacteria infection was identified in six studies: Mycobacterium fortuitum/chelonei, Mycobacterium smegmatis and Mycobacterium abscessus. Treatment comprised supportive therapy, corticosteroids, stopping oil, therapeutic lung-lavage and surgical resection. Outcomes were reported inconsistently. Conclusion Paediatric ELP resulting from cultural and medical practices continues to be described globally. Preventive interventions, standardized reporting, and treatment efficacy studies for cases not averted, are lacking. Protocol registration: PROSPERO CRD42017068313.


Letter to the Editor: “Clinical characteristics and outcomes of patients undergoing surgeries during the incubation period of COVID-19 infection”


title: Estimation of the impact of providing outpatients with information about SARS infection control on their intention of outpatient visit

text: Abstract To examine the effect of provision of information about the infection control in the specific infection disease treatment unit in a city hospital on the outpatient’s intention of outpatient service use, respondents who underwent outpatient medical care at the hospital (N = 821) were asked whether or not they intended to continue the outpatient visit at the hospital if a severe acute respiratory syndrome (SARS) patient was admitted to the unit. Although 56% of respondents replied that they could continue to visit the department if a SARS patient was admitted to the unit in the hospital before they read the information, the proportion of those who intended to continue outpatient care significantly increased by 15% after they read it. The logistic regression analyses revealed that respondents who had frequently visited the outpatient department (P < 0.001), those who felt relieved by reading the information about the unit (P < 0.001), and those who did not worry about nosocomial SARS infection inside the hospital (P < 0.001) were significantly more likely to reply that they would continue outpatient visits. We estimated that admission of a SARS patient to the unit would result in a 20% decrease in the cumulative total number of outpatients in the hospital during a 180-day interval after admission of a SARS patient to the unit, and the cumulative total number of outpatients increased by 7% after they read the information. This study suggests that providing outpatients with appropriate information about SARS infection control in the hospital had a statistically significant and substantial impact on the outpatients’ intention to continue outpatient visits at the hospital.


title: Zoledronic acid sequential therapy could avoid disadvantages due to the discontinuation of less than 3-year denosumab treatment

text: INTRODUCTION: Rapid descent in bone mineral density (BMD) and ascent in bone turnover marker (BTM) occur within the short period following denosumab (Dmab) discontinuation. In addition, the incidence of vertebral fracture also rises within the short period. The purpose of this study is to investigate the effects of sequential therapy using zoledronic acid (ZOL) on any adverse events after Dmab discontinuation. MATERIALS AND METHODS: This study was a multicenter retrospective observational study, and the subjects were osteoporosis patients who visited our institutions between 2013 and 2018. We performed sequential therapy using ZOL for 30 patients who had difficulty continuing Dmab, due to physical or social reasons, and investigated the fracture incidence and BMD/BTM changes at 4 time points (at the start of Dmab, the start of ZOL, 6 months after ZOL and 12 months after ZOL). RESULTS: No new vertebral/nonvertebral fractures were observed at each time point after switching from Dmab to ZOL in any of the 30 patients. The BMD/BTM changes were evaluated in 18 of the 30 cases, since all data of lumbar/femoral neck BMDs and TRACP-5b at 4 time points was only available in 18 cases. BMDs significantly increased at each time point compared with that at the start of Dmab. Serum TRACP-5b significantly decreased at each time point compared with that at the start of Dmab. CONCLUSION: It was suggested that sequential therapy using ZOL could suppress the decrease of BMD, and increase of BTM, if the period of Dmab administration was less than 3 years. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00774-020-01126-w) contains supplementary material, which is available to authorized users.


title: FDA Perspectives on Diagnostic Device Clinical Studies for Respiratory Infections

text: Two pathways are described for submission to FDA for clearance of a diagnostic device: a Premarket Application (PMA), which can lead to approval of a diagnostic device, and a Premarket Notification, which can lead to clearance. The latter is often called a 510(k), named for the statute providing for this path. Recent FDA clearance of molecular-based multiplex panels represents the beginning of a new era for the diagnosis of respiratory infections. The ability to test for multiple pathogens simultaneously, accompanied by the increasing availability of molecular-based assays for newly recognized respiratory pathogens will likely have a major impact on patient care, drug development, and public health epidemiology. We provide a general overview of how FDA evaluates new diagnostics for respiratory tract infections and the agency’s expectations for sponsors developing new tests in this area.


title: Core components for effective infection prevention and control programmes: new WHO evidence-based recommendations

text: Health care-associated infections (HAI) are a major public health problem with a significant impact on morbidity, mortality and quality of life. They represent also an important economic burden to health systems worldwide. However, a large proportion of HAI are preventable through effective infection prevention and control (IPC) measures. Improvements in IPC at the national and facility level are critical for the successful containment of antimicrobial resistance and the prevention of HAI, including outbreaks of highly transmissible diseases through high quality care within the context of universal health coverage. Given the limited availability of IPC evidence-based guidance and standards, the World Health Organization (WHO) decided to prioritize the development of global recommendations on the core components of effective IPC programmes both at the national and acute health care facility level, based on systematic literature reviews and expert consensus. The aim of the guideline development process was to identify the evidence and evaluate its quality, consider patient values and preferences, resource implications, and the feasibility and acceptability of the recommendations. As a result, 11 recommendations and three good practice statements are presented here, including a summary of the supporting evidence, and form the substance of a new WHO IPC guideline. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13756-016-0149-9) contains supplementary material, which is available to authorized users.


Kongresse des BDI


title: The Globalisation of Cardiology and Cardiovascular Diseases in the World–Society—A Case Study with a Special Focus on Heart Failure

text: While there has been a shift of attention in global health towards non-communicable diseases, we still know little about the social mechanisms that have allowed these diseases to emerge as topics of global concern. We employ a sociological approach to globalisation in order to reconstruct how cardiology, with our special focus being on heart failure research, has become global, and thereby placed cardiovascular diseases on the agenda of global health. Following sociological theories of world–society and world–polity, we identify a number of preconditions that had to be met so that the globalisation of cardiology could set in. Amongst them were technological innovations, the emergence of an organisational infrastructure on the national level, the appearance of cardiological journals, and an internationally standardised nomenclature. More recently, new drugs and treatment strategies, new specialist journals, and new international standards allowed the subspeciality of heart failure to globalise. Our findings are based on the history and sociology of cardiology, and on our analysis of a broad range of other documents, including scientific articles, guidelines, and policy documents. Additionally, our analysis included two datasets, one containing information on national cardiac societies, and the other containing data on publication output in cardiology.


title: Biosafety and biosecurity

text: Abstract With the profound changes in the international security situation, the progression of globalization, and the continuous advancement of biotechnology, the risks and challenges posed by major infectious diseases and bioterrorism to the international community are also increasing. Biosafety, therefore, presents new opportunities for international cooperation and global governance. The world has become more integrated and now shares a common destiny in terms of biosafety. In the face of the current risks and challenges, the international community must work together to avert threats, advance mutual interests, and safeguard global biosecurity. In the context of the current situation regarding biosafety and biosecurity, we conducted the present analysis, and present here some appropriate countermeasures.


Early Defervescence and SARS Recovery


title: Role of animal movement and indirect contact among farms in transmission of porcine epidemic diarrhea virus

text: Abstract Epidemiological models of the spread of pathogens in livestock populations primarily focus on direct contact between farms based on animal movement data, and in some cases, local spatial spread based on proximity between premises. The roles of other types of indirect contact among farms is rarely accounted for. In addition, data on animal movements is seldom available in the United States. However, the spread of porcine epidemic diarrhea virus (PEDv) in U.S. swine represents one of the best documented emergences of a highly infectious pathogen in the U.S. livestock industry, providing an opportunity to parameterize models of pathogen spread via direct and indirect transmission mechanisms in swine. Using observed data on pig movements during the initial phase of the PEDv epidemic, we developed a network-based and spatially explicit epidemiological model that simulates the spread of PEDv via both indirect and direct movement-related contact in order to answer unresolved questions concerning factors facilitating between-farm transmission. By modifying the likelihood of each transmission mechanism and fitting this model to observed epidemiological dynamics, our results suggest that between-farm transmission was primarily driven by direct mechanisms related to animal movement and indirect mechanisms related to local spatial spread based on geographic proximity. However, other forms of indirect transmission among farms, including contact via contaminated vehicles and feed, were responsible for high consequence transmission events resulting in the introduction of the virus into new geographic areas. This research is among the first reports of farm-level animal movements in the U.S. swine industry and, to our knowledge, represents the first epidemiological model of commercial U.S. swine using actual data on farm-level animal movement.


title: RIG-I Enhanced Interferon Independent Apoptosis upon Junin Virus Infection

text: Junin virus (JUNV) is the etiological agent of Argentine hemorrhagic fever (AHF), a human disease with a high case-fatality rate. It is widely accepted that arenaviral infections, including JUNV infections, are generally non-cytopathic. In contrast, here we demonstrated apoptosis induction in human lung epithelial carcinoma (A549), human hepatocarcinoma and Vero cells upon infection with the attenuated Candid#1 strain of, JUNV as determined by phosphatidylserine (PS) translocation, Caspase 3 (CASP3) activation, Poly (ADP-ribose) polymerase (PARP) cleavage and/or chromosomal DNA fragmentation. Moreover, as determined by DNA fragmentation, we found that the pathogenic Romero strain of JUNV was less cytopathic than Candid#1 in human hepatocarcinoma and Vero, but more apoptotic in A549 and Vero E6 cells. Additionally, we found that JUNV-induced apoptosis was enhanced by RIG-I signaling. Consistent with the previously reported role of RIG-I like helicase (RLH) signaling in initiating programmed cell death, we showed that cell death or DNA fragmentation of Candid#1-infected A549 cells was decreased upon siRNA or shRNA silencing of components of RIG-I pathway in spite of increased virus production. Similarly, we observed decreased DNA fragmentation in JUNV-infected human hepatocarcinoma cells deficient for RIG-I when compared with that of RIG-I-competent cells. In addition, DNA fragmentation detected upon Candid#1 infection of type I interferon (IFN)-deficient Vero cells suggested a type I IFN-independent mechanism of apoptosis induction in response to JUNV. Our work demonstrated for the first time apoptosis induction in various cells of mammalian origin in response to JUNV infection and partial mechanism of this cell death.


title: Metagenomic analysis of a sample from a patient with respiratory tract infection reveals the presence of a γ-papillomavirus

text: Previously unknown or unexpected pathogens may be responsible for that proportion of respiratory diseases in which a causative agent cannot be identified. The application of broad-spectrum, sequence independent virus discovery techniques may be useful to reduce this proportion and widen our knowledge about respiratory pathogens. Thanks to the availability of high-throughput sequencing (HTS) technology, it became today possible to detect viruses which are present at a very low load, but the clinical relevance of those viruses must be investigated. In this study we used VIDISCA-454, a restriction enzyme based virus discovery method that utilizes Roche 454 HTS system, on a nasal swab collected from a subject with respiratory complaints. A γ-papillomavirus was detected (complete genome: 7142 bp) and its role in disease was investigated. Respiratory samples collected both during the acute phase of the illness and 2 weeks after full recovery contained the virus. The patient presented antibodies directed against the virus but there was no difference between IgG levels in blood samples collected during the acute phase and 2 weeks after full recovery. We therefore concluded that the detected γ-papillomavirus is unlikely to be the causative agent of the respiratory complaints and its presence in the nose of the patient is not related to the disease. Although HTS based virus discovery techniques proved their great potential as a tool to clarify the etiology of some infectious diseases, the obtained information must be subjected to cautious interpretations. This study underlines the crucial importance of performing careful investigations on viruses identified when applying sensitive virus discovery techniques, since the mere identification of a virus and its presence in a clinical sample are not satisfactory proofs to establish a causative link with a disease.


title: Enhancing immunity in viral infections, with special emphasis on COVID-19: A review

text: Abstract Background and aims Balanced nutrition which can help in maintaining immunity is essential for prevention and management of viral infections. While data regarding nutrition in coronavirus infection (COVID-19) are not available, in this review, we aimed to evaluated evidence from previous clinical trials that evaluated nutrition-based interventions for viral diseases (with special emphasis on respiratory infections), and summaries our observations. Methods A systematic search strategy was employed using keywords to search the literature in 3 key medical databases: PubMed®, Web of Science® and SciVerse Scopus®. Studies were considered eligible if they were controlled trials in humans, measuring immunological parameters, on viral and respiratory infections. Clinical trials on vitamins, minerals, nutraceuticals and probiotics were included. Results total of 640 records were identified initially and 22 studies were included from other sources. After excluding duplicates and articles that did not meet the inclusion criteria, 43 studies were obtained (vitamins: 13; minerals: 8; nutraceuticals: 18 and probiotics: 4). Among vitamins, A and D showed a potential benefit, especially in deficient populations. Among trace elements, selenium and zinc have also shown favourable immune-modulatory effects in viral respiratory infections. Several nutraceuticals and probiotics may have some role in enhancing immune functions. Micronutrients may be beneficial in nutritionally depleted elderly population. Conclusions We summaries possible benefits of some vitamins, trace elements, nutraceuticals and and probiotics. Nutrition principles based on these data could be useful in possible prevention and management of COVID-19


title: A cost-effective and efficacious method of pinworm treatment for large colonies of mice

text: Rodent pinworm infestations are common in modern animal facilities, and treatments to eradicate these nematodes are often costly and labor-intensive. The authors describe a method they developed to treat rodents with ivermectin using the automatic watering system available at their facility. This delivery method proved an efficacious and cost-effective means of eradicating Aspiculuris tetraptera from a large colony of mice. The system might also be used to provide other orally administered agents to mice and other species.


title: Double etched porous silicon nanowire arrays for impedance sensing of influenza viruses

text: Abstract We report new sensing element based on double-etched porous silicon (DEPSi) for sensitive detection of influenza viruses (H1N1). The proposed structure provided efficient penetration of virions into sensitive layer and trapping of them. Adsorption of the viruses led to significant shift of resonant frequency of DEPSi coupled with a coil, measured by impedance spectrometer. The detection limit of virions was lower than 100 TCID50. The results can be used for invention of H1N1 sensor, which provide rapid, label-free and low-cost detection of influenza.


title: Chapter Two Pathogen and Particle Associations in Wastewater Significance and Implications for Treatment and Disinfection Processes

text: Abstract Disinfection guidelines exist for pathogen inactivation in potable water and recycled water, but wastewater with high numbers of particles can be more difficult to disinfect, making compliance with the guidelines problematic. Disinfection guidelines specify that drinking water with turbidity ≥1 Nephelometric Turbidity Units (NTU) is not suitable for disinfection and therefore not fit for purpose. Treated wastewater typically has higher concentrations of particles (1–10NTU for secondary treated effluent). Two processes widely used for disinfecting wastewater are chlorination and ultraviolet radiation. In both cases, particles in wastewater can interfere with disinfection and can significantly increase treatment costs by increasing operational expenditure (chemical demand, power consumption) or infrastructure costs by requiring additional treatment processes to achieve the required levels of pathogen inactivation. Many microorganisms (viruses, bacteria, protozoans) associate with particles, which can allow them to survive disinfection processes and cause a health hazard. Improved understanding of this association will enable development of cost-effective treatment, which will become increasingly important as indirect and direct potable reuse of wastewater becomes more widespread in both developed and developing countries. This review provides an overview of wastewater and associated treatment processes, the pathogens in wastewater, the nature of particles in wastewater and how they interact with pathogens, and how particles can impact disinfection processes.


title: Follow-up chest radiographic findings in patients with MERS-CoV after recovery

text: PURPOSE: To evaluate the follow-up chest radiographic findings in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) who were discharged from the hospital following improved clinical symptoms. MATERIALS AND METHODS: Thirty-six consecutive patients (9 men, 27 women; age range 21–73 years, mean ± SD 42.5 ± 14.5 years) with confirmed MERS-CoV underwent follow-up chest radiographs after recovery from MERS-CoV. The 36 chest radiographs were obtained at 32 to 230 days with a median follow-up of 43 days. The reviewers systemically evaluated the follow-up chest radiographs from 36 patients for lung parenchymal, airway, pleural, hilar and mediastinal abnormalities. Lung parenchyma and airways were assessed for consolidation, ground-glass opacity (GGO), nodular opacity and reticular opacity (i.e., fibrosis). Follow-up chest radiographs were also evaluated for pleural thickening, pleural effusion, pneumothorax and lymphadenopathy. Patients were categorized into two groups: group 1 (no evidence of lung fibrosis) and group 2 (chest radiographic evidence of lung fibrosis) for comparative analysis. Patient demographics, length of ventilations days, number of intensive care unit (ICU) admission days, chest radiographic score, chest radiographic deterioration pattern (Types 1-4) and peak lactate dehydrogenase level were compared between the two groups using the student t-test, Mann-Whitney U test and Fisher's exact test. RESULTS: Follow-up chest radiographs were normal in 23 out of 36 (64%) patients. Among the patients with abnormal chest radiographs (13/36, 36%), the following were found: lung fibrosis in 12 (33%) patients GGO in 2 (5.5%) patients, and pleural thickening in 2 (5.5%) patients. Patients with lung fibrosis had significantly greater number of ICU admission days (19 ± 8.7 days; P value = 0.001), older age (50.6 ± 12.6 years; P value = 0.02), higher chest radiographic scores [10 (0-15.3); P value = 0.04] and higher peak lactate dehydrogenase levels (315-370 U/L; P value = 0.001) when compared to patients without lung fibrosis. CONCLUSION: Lung fibrosis may develop in a substantial number of patients who have recovered from Middle East respiratory syndrome coronavirus (MERS-CoV). Significantly greater number of ICU admission days, older age, higher chest radiographic scores, chest radiographic deterioration patterns and peak lactate dehydrogenase levels were noted in the patients with lung fibrosis on follow-up chest radiographs after recovery from MERS-CoV.