title: Containing Emerging Epidemics: a Quantitative Comparison of Quarantine and Symptom Monitoring

text: Strategies for containing an emerging infectious disease outbreak must be non-pharmaceutical when drugs or vaccines for the pathogen do not yet exist or are unavailable. The success of these non-pharmaceutical strategies will depend not only on the effectiveness of quarantine or other isolation measures but also on the epidemiological characteristics of the infection. However, there is currently no systematic framework to assess the relationship between different containment strategies and the natural history and epidemiological dynamics of the pathogen. Here, we compare the effectiveness of quarantine and symptom monitoring, implemented via contact tracing, in controlling epidemics using an agent-based branching model. We examine the relationship between epidemic containment and the disease dynamics of symptoms and infectiousness for seven case study diseases with diverse natural histories including Ebola, Influenza A, and Severe Acute Respiratory Syndrome (SARS). We show that the comparative effectiveness of symptom monitoring and quarantine depends critically on the natural history of the infectious disease, its inherent transmissibility, and the intervention feasibility in the particular healthcare setting. The benefit of quarantine over symptom monitoring is generally maximized for fast-course diseases, but we show the conditions under which symptom monitoring alone can control certain outbreaks. This quantitative framework can guide policy-makers on how best to use non-pharmaceutical interventions to contain emerging outbreaks and prioritize research during an outbreak of a novel pathogen. Quarantine and symptom monitoring of contacts with suspected exposure to an infectious disease are key interventions for the control of emerging epidemics; however, there does not yet exist a quantitative framework for comparing the control performance of each. Here, we use a mathematical model of seven case study diseases to show how the choice of intervention is influenced by the natural history of the infectious disease, its inherent transmissibility, and the intervention feasibility in the particular healthcare setting. We use this information to identify the most important characteristics of the disease and setting that need to be characterized for an emerging pathogen in order to make an informed decision between quarantine and symptom monitoring.


title: Gender differences in the perceptions of common cold symptoms

text: Abstract Higher rates of reported morbidity among women are sometimes attributed to lower thresholds among women for experiencing and reporting symptoms. Gender differences in the perception of signs and symptoms of minor illness were examined on data from the MRC Common Cold Unit. Volunteers assessed the presence and severity of colds at the end of their stay in the Unit, using the same two measures as a trained clinical observer (all ratings were double blind). Even after adjustment for other variables, men were significantly more likely to ‘over-rate’ their symptoms in comparison with the clinical observer than were women. These data, and recent analyses from elsewhere, suggest that rather than artefactually exaggerating gender differences in morbidity, differing thresholds for perceiving and reporting symptoms may produce underestimates of gender differences in morbidity.


title: Chapter 2 Sialoglycans and genetically engineered plants

text: Abstract Plants express N-glycosylation pathways and produce N-glycosylated proteins but differ from the mammalian-type proteins. Therefore attempts are made to design and engineer plant glycosylation pathways that can produce mammalian-type glycosylated moieties so that large quantities of biopharmaceuticals compatible to the human body can be produced. Most of the studies of plant expression systems for molecular farming have been conducted on Nicotiana sp. and genetic engineering and molecular biology tools have enabled the generation of glycoengineered plant for human use in the production of therapeutic recombinant proteins. We have discussed in this chapter the advances of glycoengineering in plants with special reference to the reconstruction of silaylation pathways in plants and the latest application in the production of antibody and therapeutics in plants.


title: SARS – My personal battle

text: Summary It isn’t every day that a doctor becomes a patient. It is more peculiar when it occurs with an unknown mysterious epidemic respiratory illness that kills. Severe acute respiratory syndrome (SARS) gripped the world in 2003, spreading via air-links and throwing the global economy into disarray. As a practicing physician in Singapore, one of the first countries affected, I describe my first-hand account of my battle with this illness, how I acquired this illness in Singapore, and eventually quarantine in Frankfurt am Main, Germany.


title: Biological and genetic analysis of a bovine-like coronavirus isolated from water buffalo (Bubalus bubalis) calves

text: Abstract We describe the isolation, biological and genetic characterization of a host-range variant of bovine coronavirus (BCoV) detected in water buffalo (Bubalus bubalis). By conventional and real-time RT-PCR assays, the virus was demonstrated in the intestinal contents of two 20-day-old buffalo calves dead of a severe form of enteritis and in the feces of additional 17 buffalo calves with diarrhea. Virus isolation, hemagglutination and receptor-destroying enzyme activity showed that the buffalo coronavirus (BuCoV) is closely related to BCoV but possesses some different biological properties. Sequence and phylogenetic analyses of the 3′ end (9.6 kb) of the BuCoV RNA revealed a genomic organization typical of group 2 coronaviruses. Moreover, the genetic distance between BuCoV and BCoV was proven to be the same or even higher than the distance between other ruminant coronaviruses and BCoV. In conclusion, our data support the existence of a host-range variant of BCoV associated with enteritis in buffaloes.


title: Human metapneumovirus and human bocavirus associated with respiratory infection in Apulian population

text: Abstract We have studied the occurrence of hBoV, hMPV and InfA-B in an Apulian population with respiratory tract infections. During influenza season 2008–2009, 116 oropharingeal swabs were collected from patients affected by Influenza-Like Illness (ILI). The PCR products of hMPV M and HBoV NP-1 genes were sequenced. 78 out of 116 samples were positive for at least one respiratory virus; hBoV was detected in 53, hMPV in 22 and InfA-B in 41 out of 116 swabs. A high rate of hBoV infection in adult (18.9%) and elderly (26.4%) subjects was found. The co-infection rate was higher for hMPV (18/22 cases, 81.8%) compared to hBoV (26/53 cases, 49.1%), and InfA-B (25/41 cases, 61.0%). Co-infections were common in children. hBoV positive samples shared a high level of genetic similarity with the hBoV1 genotype, and hMPV positive samples clustered with A2 subgroup. Our results suggest that hBoV and hMPV play a role in ILI.


title: Disease Overview of the Urinary Tract in Exotic Companion Mammals and Tips on Clinical Management

text: Diseases of the urinary tract are reviewed, covering infectious (bacterial, viral, parasitic), degenerative, congenital, metabolic, nutritional, neoplastic, obstructive, and toxic causes. Some clinical presentations and diagnostic procedures are described for ferrets, rabbits, guinea pigs, hamsters, mice, rats, chinchillas, hedgehogs, and sugar gliders, as well as therapies.


title: Presence and molecular characterisation of Giardia and Cryptosporidium in alpacas (Vicugna pacos) from Peru

text: Abstract The presence of Giardia and Cryptosporidium was investigated in 274 faecal samples of alpacas (Vicugna pacos) from 12 herds from Peru by immunofluorescence microscopy and PCR amplification and sequencing of fragments of the ssu-rRNA and β-giardin genes from Giardia spp., as well as the ssu-rRNA gene from Cryptosporidium spp. A total of 137 samples (50.0%) were positive for Giardia spp., and 12 samples (4.4%) for Cryptosporidium spp. In ten samples (3.6%), co-infection by both pathogens was found. Herd prevalence was found to be 91.7% (11/12 herds) for Giardia and 58.3% (7/12 herds) for Cryptosporidium. Regarding the age of the animals, although Giardia was detected in animals as young as 1 week, the prevalence increased with age, reaching 80% by 8 weeks. Similarly, the highest percentage of Cryptosporidium detection (20%) was also found in the 8 week-old group. By PCR, 92 of the 274 analysed samples were positive for Giardia. Sequencing of the amplicons showed the existence of Giardia duodenalis assemblage A in 67 samples; G. duodenalis assemblage E in 24 samples; and inconsistent results between the two molecular markers used in a further sample. Cryptosporidium was only detected by PCR in 3 of the 274 samples; Cryptosporidium parvum was identified in two samples and Cryptosporidium ubiquitum in one sample. This study is the first performing molecular characterisation of both parasites in Peruvian alpacas, and the first report of C. ubiquitum in this host. The identification of G. duodenalis assemblage A, C. parvum and C. ubiquitum, suggests that zoonotic transmission of these enteropathogens between alpacas and humans is possible.


title: Sequence Analysis of the Nucleocapsid Protein Gene of Rat Coronavirus SDAV-681

text: Abstract The nucleotide sequence of the 3′-end of the genomic RNA of sialodacryoadenitis virus strain 681 (SDAV-681) was determined. A large open reading frame encoding a 454-amino-acid protein was identified as the nucleocapsid protein (N) gene, since the predicted protein is similar in size, chemical properties, and amino acid sequence to the N proteins of other coronaviruses. The amino acid variance of the N proteins between SDAV and mouse hepatitis virus (MHV) is not markedly different from that among MHV strains. A high degree of genetic relatedness between SDAV and MHV was revealed in the intergenic and 3′-noncoding sequences as well as in the N gene.


title: Detection of airborne viruses using electro-aerodynamic deposition and a field-effect transistor

text: We report a technique for the detection of aerosolized viruses. Conventional field-effect-transistor (FET)-based techniques use solution-based processes, thus require antibody binding to the detection region of the FET prior to the supply of the analyte. With the method described here, virus–antibody-bound particles are delivered to the FET during detection; therefore, neither a pre-treatment antibody binding step on the FET channel nor washing process for virus–antibody-binding are necessary. Our method is based on the concept that virus–antibody-bound particles are larger than the virus or antibody alone, and thus have larger charge numbers following aerosol charging. When these particles are charged by negative ions and electro-aerodynamically deposited on a substrate, there exists a location on the substrate where neither lone virus nor antibody particles land, and where only virus–antibody-bound particles are deposited. If this location coincides with the channel of the FET, the resulting variation in the current can be used to indicate the existence of a virus. By aerosolizing a mixed solution of the virus and the antibody, only the virus–antibody-bound particles were transported to the swCNT-FET, and the electric current in the swCNT-FET decreased to 30% of that measured with no deposited particles.


Update on COVID‐19 Effects in Dermatology Specialty


title: IgY - turning the page toward passive immunization in COVID-19 infection (Review)

text: The world is facing one of the major outbreaks of viral infection of the modern history, however, as vaccine development workflow is still tedious and can not control the infection spreading, researchers are turning to passive immunization as a good and quick alternative to treat and contain the spreading. Within passive immunization domain, raising specific immunoglobulin (Ig)Y against acute respiratory tract infection has been developing for more than 20 years. Far from being an obsolete chapter we will revise the IgY-technology as a new frontier for research and clinic. A wide range of IgY applications has been effectively confirmed in both human and animal health. The molecular particularities of IgY give them functional advantages recommending them as good candidates in this endeavor. Obtaining specific IgY is sustained by reliable and nature friendly methodology as an alternative for mammalian antibodies. The aria of application is continuously enlarging from bacterial and viral infections to tumor biology. Specific anti-viral IgY were previously tested in several designs, thus its worth pointing out that in the actual COVID-19 pandemic context, respiratory infections need an enlarged arsenal of therapeutic approaches and clearly the roles of IgY should be exploited in depth.


title: Assessment of Adenovirus Infection in Adult Lung Transplant Recipients Using Molecular Surveillance

text: Background Little is known about adenovirus infections in adult lung transplant recipients. Because the virus can establish latency, re-activation may be relatively common after transplantation. Methods We assessed adenovirus infection in 80 adult lung transplant recipients. Adenovirus polymerase chain reaction (real-time PCR assay; limit of detection ∼25 copies/ml plasma) was done on plasma samples collected at regular intervals until 1 year post-transplant. Results Adenovirus DNA was detected in 18 of 80 patients (22.5%) and in 19 of 595 (3.4%) plasma samples up to 12 months post-transplant. Median time to detection of viremia was 134 days post-transplant (range 1 to 370 days). Median viral load was 180 copies/ml plasma (range 50 to 360 copies/ml). Symptoms were evaluated at the time of adenovirus detection: 14 of 18 (78%) patients were asymptomatic; 4 of 18 (22%) patients had otherwise unexplained febrile/flu-like illness that resolved spontaneously. Adenovirus was not found to be a trigger for acute rejection. No detrimental effect on pulmonary function was seen immediately after adenovirus infection. Conclusions Adenovirus viremia is common in adult lung transplant recipients. In contrast to findings on adenoviral pneumonitis in lung transplant recipients, isolated episodes of low-level viremia are self-limited and do not trigger acute rejection or a decline in pulmonary function.


title: The C-terminal tail of the gp41 transmembrane envelope glycoprotein of HIV-1 clades A, B, C, and D may exist in two conformations: an analysis of sequence, structure, and function

text: Abstract In addition to the major ectodomain, the gp41 transmembrane glycoprotein of HIV-1 is now known to have a minor ectodomain that is part of the long C-terminal tail. Both ectodomains are highly antigenic, carry neutralizing and non-neutralizing epitopes, and are involved in virus-mediated fusion activity. However, data have so far been biologically based, and derived solely from T cell line-adapted (TCLA), B clade viruses. Here we have carried out sequence and theoretically based structural analyses of 357 gp41 C-terminal sequences of mainly primary isolates of HIV-1 clades A, B, C, and D. Data show that all these viruses have the potential to form a tail loop structure (the minor ectodomain) supported by three, β-sheet, membrane-spanning domains (MSDs). This means that the first (N-terminal) tyrosine-based sorting signal of the gp41 tail is situated outside the cell membrane and is non-functional, and that gp41 that reaches the cell surface may be recycled back into the cytoplasm through the activity of the second tyrosine-sorting signal. However, we suggest that only a minority of cell-associated gp41 molecules – those destined for incorporation into virions – has 3 MSDs and the minor ectodomain. Most intracellular gp41 has the conventional single MSD, no minor ectodomain, a functional first tyrosine-based sorting signal, and in line with current thinking is degraded intracellularly. The gp41 structural diversity suggested here can be viewed as an evolutionary strategy to minimize HIV-1 envelope glycoprotein expression on the cell surface, and hence possible cytotoxicity and immune attack on the infected cell.


title: Establishing an oncocardiology service

text: Oncocardiology is an emerging field in cardiovascular healthcare. Besides establishing surveillance and follow-up strategies for cancer patients, it will be essential to set up specialized oncocardiology services. However, there is a lack of clinical studies to give evidence-based recommendations regarding cardiological diagnostic and therapeutic approaches for cancer patients. An oncocardiology service is a patient-centered structure that aims to integrate research and interdisciplinary patient care to bridge this gap. We discuss the current challenges in developing an oncocardiology service and review the literature on this topic. We further provide an overview of the essential diagnostic tools and upcoming ethical issues to be considered in the management of oncology patients.


title: Interferon-Inducible Transmembrane Protein 3 Genetic Variant rs12252 and Influenza Susceptibility and Severity: A Meta-Analysis

text: BACKGROUND: The pandemic influenza A (H1N1) pdm09 virus, avian influenza A (H5N1) virus, and influenza A (H7N9) virus induced severe morbidity and mortality throughout the world. Previous studies suggested a close association between the interferon-induced transmembrane protein-3 (IFITM3) genetic variant rs12252 and influenza. Here, we explored the correlation between the rs12252 and influenza susceptibility and severity using meta-analysis. METHODS: Relevant studies published before May 22, 2014 were retrieved from PubMed, ISI web of knowledge, EBSCO, and Cochrane central register of controlled trials databases. Association between rs12252 and influenza susceptibility and severity were determined using statistical analysis of odds ratios (ORs). RESULTS: A total of four studies consisting of 445 cases and 4180 controls were included in our analysis. Generally, there is increased risk of influenza in subjects carrying rs12252 in the recessive model (CC vs. CT+TT: OR = 2.35, 95% CI: 1.49-3.70, P<0.001), the dominant model (CC+CT vs. TT: OR=1.60, 95% CI: 1.18–2.22, P=0.003), the homozygote comparison (CC vs. TT: OR=4.11, 95% CI: 2.15–7.84, P<0.001), and the allele contrast (C vs. T: OR=1.67, 95% CI: 1.32–2.13, P<0.001). Stratification analysis of ethnicity and severity revealed a significant increase in influenza susceptibility by IFITM3-SNP rs12252 among both Asian and Caucasian population. SNP rs12252 shows significant impact on severe infections (P<0.05), but not on mild influenza. Besides, our result also associated rs12252 with influenza severity (severe vs. mild: OR=2.37, 95% CI: 1.32–4.25, P=0.004), (severe vs. control: OR=2.70, 95% CI: 1.85–3.94, P<0.001). CONCLUSION: Our meta-analysis suggests a significant association between a minor IFITM3 allele (SNP rs12252-C) with severe influenza susceptibility, but not in mild influenza subjects, in both UK Caucasians and Han Chinese population. The rs12252-C allele causes a 23.7% higher chance of infection and also constitutes a risk factor for more severe influenza.


title: Epilepsy and COVID-19: Associations and important considerations

text: Abstract Coronavirus disease 2019 (COVID-19) outbreak, which initially occurred in Wuhan, China in late 2019, is now rapidly spreading globally. Epilepsy, a disease characterized by a spontaneous recurrence of unprovoked seizures, is a common chronic neurological condition. Associations between epilepsy and COVID-19 have not been reported. Here, we discuss the important considerations for epilepsy patients by reviewing known facts of COVID-19 and suggestions from medical societies associated with epilepsy, as well as inferences from past experiences of infectious diseases. We discuss the risk of COVID-19 for epilepsy patients, the effect of COVID-19 on epilepsy patients, and the importance of maintaining seizure control. We also consider suggestions for epilepsy monitoring units or surgery, what caregivers should know, and the importance of public awareness. The effect of COVID-19 on individuals with epilepsy remains unclear due to the lack of enough evidence. Clinicians and researchers need to share case information, continue investigations, and provide known facts to epilepsy patients and their families.


title: Association between short-term exposure to air pollution and COVID-19 infection: Evidence from China

text: Abstract The novel coronavirus pneumonia, namely COVID-19, has become a global public health problem. Previous studies have found that air pollution is a risk factor for respiratory infection by carrying microorganisms and affecting body's immunity. This study aimed to explore the relationship between ambient air pollutants and the infection caused by the novel coronavirus. Daily confirmed cases, air pollution concentration and meteorological variables in 120 cities were obtained from January 23, 2020 to February 29, 2020 in China. We applied a generalized additive model to investigate the associations of six air pollutants (PM2.5, PM10, SO2, CO, NO2 and O3) with COVID-19 confirmed cases. We observed significantly positive associations of PM2.5, PM10, NO2 and O3 in the last two weeks with newly COVID-19 confirmed cases. A 10-μg/m3 increase (lag0–14) in PM2.5, PM10, NO2, and O3 was associated with a 2.24% (95% CI: 1.02 to 3.46), 1.76% (95% CI: 0.89 to 2.63), 6.94% (95% CI: 2.38 to 11.51), and 4.76% (95% CI: 1.99 to 7.52) increase in the daily counts of confirmed cases, respectively. However, a 10-μg/m3 increase (lag0–14) in SO2 was associated with a 7.79% decrease (95% CI: −14.57 to −1.01) in COVID-19 confirmed cases. Our results indicate that there is a significant relationship between air pollution and COVID-19 infection, which could partially explain the effect of national lockdown and provide implications for the control and prevention of this novel disease.


title: The 17th Rocky Mountain Virology Association Meeting

text: Since 2000, scientists and students from the greater Rocky Mountain region, along with invited speakers, both national and international, have gathered at the Mountain Campus of Colorado State University to discuss their area of study, present recent findings, establish or strengthen collaborations, and mentor the next generation of virologists and prionologists through formal presentations and informal discussions concerning science, grantsmanship and network development. This year, approximately 100 people attended the 17th annual Rocky Mountain Virology Association meeting, that began with a keynote presentation, and featured 29 oral and 35 poster presentations covering RNA and DNA viruses, prions, virus-host interactions and guides to successful mentorship. Since the keynote address focused on the structure and function of Zika and related flaviviruses, a special session was held to discuss RNA control. The secluded meeting at the foot of the Colorado Rocky Mountains gave ample time for in-depth discussions amid the peak of fall colors in the aspen groves while the random bear provided excitement. On behalf of the Rocky Mountain Virology Association, this report summarizes the >50 reports.


title: Longitudinal active sampling for respiratory viral infections across age groups

text: BACKGROUND: Respiratory viral infections are a major cause of morbidity and mortality worldwide. However, their characterization is incomplete because prevalence estimates are based on syndromic surveillance data. Here, we address this shortcoming through the analysis of infection rates among individuals tested regularly for respiratory viral infections, irrespective of their symptoms. METHODS: We carried out longitudinal sampling and analysis among 214 individuals enrolled at multiple New York City locations from fall 2016 to spring 2018. We combined personal information with weekly nasal swab collection to investigate the prevalence of 18 respiratory viruses among different age groups and to assess risk factors associated with infection susceptibility. RESULTS: 17.5% of samples were positive for respiratory viruses. Some viruses circulated predominantly during winter, whereas others were found year round. Rhinovirus and coronavirus were most frequently detected. Children registered the highest positivity rates, and adults with daily contacts with children experienced significantly more infections than their counterparts without children. CONCLUSION: Respiratory viral infections are widespread among the general population with the majority of individuals presenting multiple infections per year. The observations identify children as the principal source of respiratory infections. These findings motivate further active surveillance and analysis of differences in pathogenicity among respiratory viruses.


title: DNA Vaccine

text: Abstract The DNA vaccine has proven to be one of the most promising applications in the field of gene therapy. Due to its unique ability to readily induce humoral as well as cellular immune responses, it attracted great interest when the concept was first confirmed in the early 1990s. After thousands of articles related to the DNA vaccine were published, scientists began to realize that although the DNA vaccine is very effective in small animal models, its effectiveness in recent clinical trails is rather disappointing. Therefore, current effort has been shifted to understanding the different performance of the DNA vaccine in mouse and large animal models and on how to transfer the success of the DNA vaccine in small animals to large animals and humans.


title: Arguments pour une possible transmission par voie aérienne du SARS-CoV-2 dans la crise COVID-19

text: Résumé La connaissance des modes de transmission du SARS-CoV-2 est un élément fondamental dans l’élaboration des stratégies de prévention en santé au travail et en santé publique dans le cadre de la gestion de crise du Covid-19. Le SARS-CoV-2 est retrouvé dans les voies aériennes des patients, y compris asymptomatiques. Les données récentes de la littérature suggèrent un risque de transmission du SARS-CoV-2 par voie aérienne qui a probablement été sous-estimé, notamment via des aérosols générés par la toux ou les éternuements, mais aussi plus simplement la parole et la respiration, et donc la composition est majoritairement le fait de particules dont le diamètre est inférieur ou égal à 1 µm. Des données préliminaires montrent la présence d’ARN viral dans l’air et sur des surfaces distantes des patients sources. Cependant, il est important de noter que la détection de matériel génétique viral par RT-PCR ne signifie pas que le virus soit vivant et infectant. En fonction de données sur la quantification du pouvoir infectant des aérosols de petite taille et si l’hypothèse d’une telle transmission était confirmée, les indications de port des protections respiratoires de type FFP2 mériteraient d’être élargies, notamment en milieu de soin. Abstract Understanding routes of transmission of SARS-CoV-2 is a key element in establishing both occupational health and public health guidelines in the Covid-19 management. SARS-CoV-2 is found in patients’ airways, including for asymptomatic ones. Available data suggest a underestimated risk of air transmission of SARS-CoV-2 when an infected individual coughs or sneezes, but also when he speaks or simply breezes, the majority of emitted particles being smaller than 1 μm. Preliminary data indicate the presence of viral RNA in air samples and on surfaces far from source patients. However, it is important to note that the detection of viral genetic material by RT-PCR does not mean that the virus is alive or infectious. According to data on the quantification of the infective power of such aerosol with small size particles and if such air transmission was confirmed, a larger use of N95 respirators should be promoted particularly in health care units.


title: Cell receptor-independent infection by a neurotropic murine coronavirus

text: Abstract The cellular receptors for a coronavirus, mouse hepatitis virus (MHV), have been recently identified as one or more members of the carcinoembryonic antigen (CEA) family. The neurotropic JHM strain of MHV (MHV-JHM) possesses a highly fusogenic surface (S) glycoprotein. This protein is now shown to promote the spread of MHV into cells lacking the specific CEA-related MHV receptor. Resistant cells are recruited into MHV-induced syncytium with consequent production of progeny virus. Cell-to-cell spread of virus via membrane fusion without the requirement for specific cell surface receptor offers a novel way for virus to spread within infected hosts.


title: Aetiology of Balkan nephropathy: A reapprisal after 30 years

text: Balkan nephropathy (BN) has been a complete aetiological puzzle for many years. Intense research produced many controversial results, but also helped some clues to be traced. Thus, it became rather obvious that the disease is caused by environmental factors (though it may be, to some extent, genetically controlled). Among live agents, slow viruses are the only (and theoretically very attractive) possible cause of both BN and urothelial tumours, which occur frequently in BN endemic areas. Apart from occasional visualization of virus-like particles, other evidence supporting this hypothesis has been lacking. The role of biological products, particularly fungal toxins, needs to be further defined. An excess of any heavy metal or radioactive substance as a cause of BN is very unlikely indeed; however, a deficiency of a bio-essential element could not be ruled out. Many epidemiological data indicate that water might be a transmitter of the agent(s). A wide range of ions and minerals have been incriminated, but up to now most of the studies have provided negative or inconclusive results. Organic compounds in well water have never been sufficiently considered. Another ignored area are unstable and, particularly, photosensitive substances. Fertilizers, pesticides, analgesics, local herbs and teas have no causal relation to BN.


title: Development of clinical care guidelines for faculty and residents in the era of COVID‐19

text: BACKGROUND: The global COVID‐19 pandemic brings new challenges to otolaryngology resident education. Surgical volume and clinic visits are curtailed, personal protective equipment for operating room participation is restricted, and the risk of COVID‐19 disease transmission during heretofore routine patient care is the new norm. METHODS: We describe a small‐team “cohorting” protocol including guidelines for faculty and resident in common clinical scenarios with attention paid to the risk of common otolaryngologic procedures. RESULTS: A rotating small‐team approach was implemented at each clinical site, limiting interaction between department members but providing comprehensive coverage. Faculty were involved at the earliest phase of clinical interactions. Guidelines delineated faculty and resident roles based on risk stratification by patient COVID status and anticipated procedures. Special consideration was given to high‐risk procedures such as endoscopy and tracheotomy. CONCLUSIONS: A small‐team‐based approach with guidelines for faculty/resident roles may mitigate risk while optimizing patient care and maximizing education.


docid: jnbnvaop

title: ICTV and the Virology Division News


title: Factors Influencing the Diagnosis and Treatment of Latent Tuberculosis among Contacts in Congregated Settings in Korea

text: BACKGROUND: This study aimed to compare the indicators (the rates of diagnosis, need for treatment, treatment initiation, and treatment completion) of management of latent tuberculosis infection (LTBI) in contacts and to identify the impact of active tuberculosis (TB) index case characteristics on the exposed population in congregated settings, such as schools, workplaces, and medical institutes. METHODS: The data of 8,648 clusters in the TB epidemiological investigation database between 2013 and 2016 were extracted and analyzed to evaluate the indicators and perform multilevel logistic regression (MLR) analyses to identify the factors affecting each indicator. RESULTS: The rates of total LTBI diagnosis, need for treatment, treatment initiation, and treatment completion were 15.2%, 10.2%, 69.4%, and 76.6%, respectively. After adjusting for other factors on MLR, the probability of diagnosis and need for treatment of latent TB in contacts was higher in most types of facilities than in schools. Conversely, treatment completion rates in these facilities were lower. Notably, the correctional institutions showed the highest odds ratio (OR) relative to school for LTBI diagnosis (OR, 6.37) and need for treatment (OR, 4.49) and the lowest OR for treatment completion (OR, 0.10). CONCLUSION: This study provided evidence for the implementation of latent TB control policies in congregated settings.


title: Human adenovirus replication and persistence in hypertrophic adenoids and palatine tonsils in children

text: The role of human adenovirus (HAdV) infection in different acute diseases, such as febrile exudative tonsillitis, conjunctivitis, and pharyngoconjunctival fever is well established. However, the relationships, if any, of HAdV persistence and reactivation in the development of the chronic adenotonsillar disease is not fully understood. The present paper reports a 3‐year cross‐sectional hospital‐based study aimed at detecting and quantifying HAdV DNA and mRNA of the HAdV hexon gene in adenoid and palatine tonsil tissues and nasopharyngeal secretions (NPS) from patients with adenotonsillar hypertrophy or recurrent adenotonsillitis. HAdV C, B, and E were detectable in nearly 50% of the patients, with no association with the severity of airway obstruction, nor with the presence of recurrent tonsillitis, sleep apnea or otitis media with effusion (OME). Despite the higher rates of respiratory viral coinfections in patients with HAdV, the presence of other viruses, including DNA and RNA viruses, had no association with HAdV replication or shedding in secretions. Higher HAdV loads in adenoids showed a significant positive correlation with the presence of sleep apnea and the absence of OME. Although this study indicates that a significant proportion (~85%) of individuals with chronic adenotonsillar diseases have persistent nonproductive HAdV infection, including those by HAdV C, B, and E, epithelial and subepithelial cells in tonsils seem to be critical for HAdV C production and shedding in NPS in some patients, since viral antigen was detected in these regions by immunohistochemistry in four patients, all of which were also positive for HAdV mRNA detection.


title: Autophagy in immunity and inflammation

text: Autophagy is an essential, homeostatic process by which cells break down their own components. Perhaps the most primordial function of this lysosomal degradation pathway is adaptation to nutrient deprivation. However, in complex multicellular organisms, the core molecular machinery of autophagy — the 'autophagy proteins' — orchestrates diverse aspects of cellular and organismal responses to other dangerous stimuli such as infection. Recent developments reveal a crucial role for the autophagy pathway and proteins in immunity and inflammation. They balance the beneficial and detrimental effects of immunity and inflammation, and thereby may protect against infectious, autoimmune and inflammatory diseases.


title: Severe community-acquired pneumonia caused by adenovirus type 11 in immunocompetent adults in Beijing

text: Abstract Background Severe community-acquired pneumonia (CAP) due to human adenoviruses (HAdVs) in immunocompetent adults has raised concerns. Objective To describe the clinical, laboratorial, and radiological characteristics of adenovirus pneumonia and detect the type and diversity of human adenoviruses that caused acute respiratory distress syndrome (ARDS) in Beijing. Study design An etiological study of adult community-acquired pneumonia was carried out prospectively at Beijing Chao-Yang Hospital. A total of 18 cases with laboratory-confirmed adenovirus infections in 487 cases with CAP were observed clinically. The viral type and phylogenetic analysis were tested by polymerase chain reaction (PCR). Results Patients with adenovirus pneumonia typically reported flu-like symptoms. Some of them developed shortness of breath or severe dyspnea on 6 days after disease onset. The patients with ARDS usually present dyspnea, higher level of serum muscle enzymes and bilateral, mutilobal consolidation and patchy/ground-glass opacities. HAdVs type was detected in 17 samples and all of them belonged to species B (HAdV-11, 7, 3 and 14). Among them, HAdV-11 was most frequently (10/17), followed by HAdV-7 (5/17). Phylogenetic analysis of the partial penton nucleotide confirmed a close relationship with stains circulating in the Beijing region. Conclusions Our identification of severe respiratory illness due to adenovirus, especially type 11 may highlight the need for rapid diagnosis and improved surveillance, which may assist with targeted development of antiviral agents or type-specific vaccines.


title: Sino-Australian University Partnership in Health Management Education

text: This paper outlines a successful partnership program between La Trobe University in Melbourne Australia, and Harbin Medical University in Harbin, China. These two universities have been collaborating for more than 15 years to provide a comprehensive Master of Health Administration program that adapts the Australian curriculum to meet the rapidly increasing need for qualified health services managers throughout China. This paper describes the mechanisms by which the joint programs were developed and how the two universities work together in partnership to continually improve the program components and outcomes, taking into account the significant differences in context and cultures. Since 2001, La Trobe University has enrolled about 1000 Chinese health services managers, with 721 completing a Master's degree, who are now having increasing influence on the reforms of the Chinese health care system. The partnership has enriched Australian knowledge of Chinese culture and values, as well as the Chinese health system and health policies, as evidenced by the large volume of joint publications. The profession of health management has been substantially strengthened in China, and working together, Chinese and Australian academics have had demonstrated impact on enhancing the reforms of the Chinese public health system. Further studies, with sufficient funds for data collection, are needed to evaluate the long-term impacts of transnational programs on academic and health system development in China.


docid: cxktdaws

title: MFM Guidance for COVID-19

text: The World Health Organization (WHO) has declared COVID-19 a global pandemic. Healthcare providers should prepare internal guidelines covering all aspect of the organization in order to have their unit ready as soon as possible. This document addresses the current COVID-19 pandemic for maternal-fetal medicine (MFM) practitioners. The goals the guidelines put forth here are two fold- first to reduce patient risk through healthcare exposure, understanding that asymptomatic health systems/healthcare providers may become the most common vector for transmission, and second to reduce the public health burden of COVID-19 transmission throughout the general population. Box 1 outlines general guidance to prevent spread of COVID-19 and protect our obstetric patients. Section 1 outlines suggested modifications of outpatient obstetrical (prenatal) visits. Section 2 details suggested scheduling of obstetrical ultrasound. Section 3 reviews suggested modification of nonstress tests (NST) and biophysical profiles (BPP). Section 4 reviews suggested visitor policy for obstetric outpatient office. Section 5 discusses the role of trainees and medical education in the setting of a pandemic. These are suggestions, which can be adapted to local needs and capabilities. Guidance is changing rapidly, so please continue to watch for updates.


title: Estimating the economic impact of pandemic influenza: An application of the computable general equilibrium model to the UK

text: Abstract There is concern regarding the impact that a global infectious disease pandemic might have, especially the economic impact in the current financial climate. However, preparedness planning concentrates more upon population health and maintaining a functioning health sector than on the wider economic impact. We developed a single country Computable General Equilibrium model to estimate the economic impact of pandemic influenza (PI) and associated policies. While the context for this development was the United Kingdom, there are lessons to be drawn for application of this methodology, as well as indicative results, to other contexts. Disease scenarios were constructed from an epidemiological model which estimated case fatality rates (mild, moderate and severe) as 0.06%, 0.18% and 0.35%. A clinical attack rate of 35% was also used to produce influenza scenarios, together with preparedness policies, including antivirals and school closure, and the possible prophylactic absence of workers. UK cost estimates (in Sterling) are presented, together with relative percentage impacts applicable to similar large economies. Percentage/cost estimates suggest PI would reduce GDP by 0.3% (£3.5bn), 0.4% (£5bn) and 0.6% (£7.4bn) respectively for the three disease scenarios. However, the impact of PI itself is smaller than disease mitigation policies: combining school closure with prophylactic absenteeism yields percentage/cost effects of 1.1% (£14.7bn), 1.3% (£16.3bn) and 1.4% (£18.5bn) respectively for the three scenarios. Sensitivity analysis shows little variability with changes in disease parameters but notable changes with variations in school closure and prophylactic absenteeism. The most severe sensitivity scenario results in a 2.9% (£37.4bn), 3.2% (£41.4bn) and 3.7% (£47.5bn) loss to GDP respectively for the three scenarios.


title: Excess all-cause mortality during the COVID-19 pandemic in Europe – preliminary pooled estimates from the EuroMOMO network, March to April 2020

text: A remarkable excess mortality has coincided with the COVID-19 pandemic in Europe. We present preliminary pooled estimates of all-cause mortality for 24 European countries/federal states participating in the European monitoring of excess mortality for public health action (EuroMOMO) network, for the period March–April 2020. Excess mortality particularly affected ≥ 65 year olds (91% of all excess deaths), but also 45–64 (8%) and 15–44 year olds (1%). No excess mortality was observed in 0–14 year olds.


title: Alteration of amino acid 101 within capsid protein VP-1 changes the pathogenicity of Theiler's murine encephalomyelitis virus

text: Chronic Theiler's murine encephalomyelitis virus infection of susceptible mice is an animal model for human demyelinating diseases. Previously we described an altered and diminished pattern of central nervous system disease in immunocompetent SJL/J mice infected with a variant virus. This variant virus H7A6-2 was selected with a neutralizing mAb recognizing the capsid protein VP-1 of Theiler's virus. Here we characterize the variant virus by ELISA and neutralization assays and by sequencing selected regions of the viral RNA genome and relate the alteration to disease. The variant virus contains one single point mutation within a neutralizing epitope of VP- 1. This nucleotide change lead to an amino acid replacement at amino acid 101 of VP-1, a threonine (wild type) to an isoleucine (variant). Model building based on sequence alignments and the known structure of the related Mengo virus indicates that the altered amino acid is located in an exposed loop on the surface of the virus at the periphery of a site that has been proposed to be the receptor binding site. The results of ELISA, neutralization assay, and direct RNA sequencing provide for the first time an opportunity to precisely map an important structural determinant of neurovirulence.


title: A Potent, Broad-Spectrum Antiviral Agent that Targets Viral Membranes

text: Commentary on Wolf, M.C.; Freiberg, A.N.; Zhang, T.; Akyol-Ataman, Z.; Grock, A.; Hong, P.W.; Li, J.; Watson, N.F.; Fang, A.Q.; Aguilar, H.C.; et al. A broad-spectrum antiviral targeting entry of enveloped viruses. Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 3157–3162.


Convalescent plasma from COVID 19 patients enhances intensive care unit survival rate. A preliminary report


title: A Multigene Approach for Comparing Genealogy of Betacoronavirus from Cattle and Horses

text: Gastroenteritis is one of the leading causes of morbidity and mortality among young and newborn animals and is often caused by multiple intestinal infections, with rotavirus and bovine coronavirus (BCoV) being the main viral causes in cattle. Given that BCoV is better studied than equine coronaviruses and given the possibility of interspecies transmission of these viruses, this research was designed to compare the partial sequences of the spike glycoprotein (S), hemagglutinin-esterase protein (HE), and nucleoprotein (N) genes from coronaviruses from adult cattle with winter dysentery, calves with neonatal diarrhea, and horses. To achieve this, eleven fecal samples from dairy cows with winter dysentery, three from calves, and two from horses, all from Brazil, were analysed. It could be concluded that the enteric BCoV genealogy from newborn and adult cattle is directly associated with geographic distribution patterns, when S and HE genes are taken into account. A less-resolved genealogy exists for the HE and N genes in cattle, with a trend for an age-related segregation pattern. The coronavirus strains from horses revealed Betacoronavirus sequences indistinguishable from those found in cattle, a fact previously unknown.


title: Virome heterogeneity and connectivity in waterfowl and shorebird communities

text: Models of host-microbe dynamics typically assume a single-host population infected by a single pathogen. In reality, many hosts form multi-species aggregations and may be infected with an assemblage of pathogens. We used a meta-transcriptomic approach to characterize the viromes of nine avian species in the Anseriformes (ducks) and Charadriiformes (shorebirds). This revealed the presence of 27 viral species, of which 24 were novel, including double-stranded RNA viruses (Picobirnaviridae and Reoviridae), single-stranded RNA viruses (Astroviridae, Caliciviridae, Picornaviridae), a retro-transcribing DNA virus (Hepadnaviridae), and a single-stranded DNA virus (Parvoviridae). These viruses comprise multi-host generalist viruses and those that are host-specific, indicative of both virome connectivity and heterogeneity. Virome connectivity was apparent in two well described multi-host virus species (avian coronavirus and influenza A virus) and a novel Rotavirus species that were shared among some Anseriform species, while heterogeneity was reflected in the absence of viruses shared between Anseriformes and Charadriiformes. Notably, within avian host families there was no significant relationship between either host taxonomy or foraging ecology and virome composition, although Anseriform species positive for influenza A virus harboured more additional viruses than those negative for influenza virus. Overall, we demonstrate complex virome structures across host species that co-exist in multi-species aggregations.


title: Clinical Pharmacology Considerations for Developing Small‐Molecule Treatments for COVID‐19

text: Numerous drugs are being investigated for the treatment of COVID‐19, including antivirals and therapies targeting complications related to COVID‐19. The clinical presentation of COVID‐19 varies from mild fever, cough, and dyspnea in the early stages of disease to severe complications such as acute respiratory distress syndrome, systemic hyperinflammation, and sepsis. A thorough understanding of the disease pathogenesis and the disease complications is essential to developing effective therapies to treat this potentially life‐threatening disease. This review offers key clinical pharmacology considerations involved in the development of small molecules for the treatment of COVID‐19. They are based on the major observed disease complications that impact drug absorption, distribution, metabolism, and elimination. We also address considerations regarding potential drug interactions, alternative routes and methods of administration, and dosing in patients on hemodialysis.


title: Regulation of Innate Immune Responses by Bovine Herpesvirus 1 and Infected Cell Protein 0 (bICP0)

text: Bovine herpesvirus 1 (BoHV-1) infected cell protein 0 (bICP0) is an important transcriptional regulatory protein that stimulates productive infection. In transient transfection assays, bICP0 also inhibits interferon dependent transcription. bICP0 can induce degradation of interferon stimulatory factor 3 (IRF3), a cellular transcription factor that is crucial for activating beta interferon (IFN-β) promoter activity. Recent studies also concluded that interactions between bICP0 and IRF7 inhibit trans-activation of IFN-β promoter activity. The C3HC4 zinc RING (really important new gene) finger located near the amino terminus of bICP0 is important for all known functions of bICP0. A recombinant virus that contains a single amino acid change in a well conserved cysteine residue of the C3HC4 zinc RING finger of bICP0 grows poorly in cultured cells, and does not reactivate from latency in cattle confirming that the C3HC4 zinc RING finger is crucial for viral growth and pathogenesis. A bICP0 deletion mutant does not induce plaques in permissive cells, but induces autophagy in a cell type dependent manner. In summary, the ability of bICP0 to stimulate productive infection, and repress IFN dependent transcription plays a crucial role in the BoHV-1 infection cycle.


title: Prevention and Treatment of Infectious Complications After Solid Organ Transplantation in Children

text: Effective prevention, diagnosis, and treatment of infectious diseases after transplantation are key factors contributing to the success of organ transplantation. Most transplant patients experience different kinds of infections during the first year after transplantation. Children are at particular risk of developing some types of infections by virtue of lack of immunity although they may be at risk for other types due the effect of immunosuppressive regimens necessary to prevent rejection. Direct consequences of infections result in syndromes such as mononucleosis, pneumonia, gastroenteritis, hepatitis, among other entities. Indirect consequences are mediated through cytokines, chemokines, and growth factors elaborated by the transplant recipient in response to microbial replication and invasion, which contribute to the net state of immunosuppression among other effects. This review summarizes the major infections that occur after pediatric organ transplantation, highlighting the current treatment and prevention strategies, based on the available data and/or consensus.


Letter to the Editor in response to “COVID-19: desperate times call for desperate measures”


Novel insights into the genetics of early human development: PGT as a catalyst for reform


title: Favipiravir, an anti-influenza drug against life-threatening RNA virus infections

text: Abstract Favipiravir has been developed as an anti-influenza drug and licensed as an anti-influenza drug in Japan. Additionally, favipiravir is being stockpiled for 2 million people as a countermeasure for novel influenza strains. This drug functions as a chain terminator at the site of incorporation of the viral RNA and reduces the viral load. Favipiravir cures all mice in a lethal influenza infection model, while oseltamivir fails to cure the animals. Thus, favipiravir contributes to curing animals with lethal infection. In addition to influenza, favipiravir has a broad spectrum of anti-RNA virus activities in vitro and efficacies in animal models with lethal RNA viruses and has been used for treatment of human infection with life-threatening Ebola virus, Lassa virus, rabies, and severe fever with thrombocytopenia syndrome. The best feature of favipiravir as an antiviral agent is the apparent lack of generation of favipiravir-resistant viruses. Favipiravir alone maintains its therapeutic efficacy from the first to the last patient in an influenza pandemic or an epidemic lethal RNA virus infection. Favipiravir is expected to be an important therapeutic agent for severe influenza, the next pandemic influenza strain, and other severe RNA virus infections for which standard treatments are not available.


title: Bats as reservoirs of severe emerging infectious diseases

text: Abstract In recent years severe infectious diseases have been constantly emerging, causing panic in the world. Now we know that many of these terrible diseases are caused by viruses originated from bats (Table 1), such as Ebola virus, Marburg, SARS coronavirus (SARS-CoV), MERS coronavirus (MERS-CoV), Nipah virus (NiV) and Hendra virus (HeV). These viruses have co-evolved with bats due to bats’ special social, biological and immunological features. Although bats are not in close contact with humans, spillover of viruses from bats to intermediate animal hosts, such as horses, pigs, civets, or non-human primates, is thought to be the most likely mode to cause human infection. Humans may also become infected with viruses through aerosol by intruding into bat roosting caves or via direct contact with bats, such as catching bats or been bitten by bats.


title: Duck karyopherin α4 (duKPNA4) is involved in type I interferon expression and the antiviral response against Japanese encephalitis virus

text: Abstract Karyopherin α4 (KPNA4) is an adaptor molecule that mediates type I interferon (IFN) production by facilitating the nuclear translocation of IFN transcription factors. Here, we cloned the duck KPNA4 (duKPNA4) gene and analyzed its involvement in type I IFN expression as well as antiviral response against Japanese encephalitis virus (JEV). The full-length duKPNA4 gene encoded a 520-amino acid protein that shared 97.3–98.7% sequence similarity with its orthologues in chickens, humans and mice. The duKPNA4 was extensively expressed in various duck tissues at the mRNA level. Analysis of the subcellular localization of duKPNA4 by immunofluorescence assays indicated that the duKPNA4 was primarily distributed in both the cytoplasm and nucleus in primary duck embryonic fibroblasts (DEFs). However, it translocated from the cytoplasm to the nucleus in response to poly(I:C) stimulation or JEV infection. The duKPNA4 interacted with duck IFN regulatory factor 7 and facilitated its nuclear translocation, thereby up-regulating the expression of IFN-α and IFN-β in DEFs in the presence of poly(I:C) stimulation. Exogenous expression of duKPNA4 significantly elevated the expression of IFN-α and IFN-β induced by JEV infection and inhibited JEV replication in DEFs. These data demonstrate the importance of duKPNA4 in type I IFN signaling as well as the antiviral response against JEV replication.


title: One misdated sequence of rabbit hemorrhagic disease virus prevents accurate estimation of its nucleotide substitution rate

text: BACKGROUND: The literature is ripe with phylogenetic estimates of nucleotide substitution rates, especially of measurably evolving species such as RNA viruses. However, it is not known how robust these rate estimates are to inaccuracies in the data, particularly in sampling dates that are used for molecular clock calibration. Here we report on the rate of evolution of the emerging pathogen Rabbit hemorrhagic disease virus (RHDV), which has significantly different rates of evolution for the same outer capsid (VP60) gene published in the literature. In an attempt to reconcile the conflicting data and further elucidate details of RHDV ’s evolutionary history, we undertook fresh Bayesian analyses and employed jackknife control methods to produce robust substitution rate and time to most recent common ancestor (TMRCA) estimates for RHDV based on the VP60 and RNA-dependent RNA polymerase genes. RESULTS: Through these control methods, we were able to identify a single misdated taxon, a passaged lab strain used for vaccine production, which was responsible for depressing the RHDV capsid gene’s rate of evolution by 65%. Without this isolate, the polymerase and the capsid protein genes had nearly identical rates of evolution: 1.90x10(-3) nucleotide substitutions/site/year, ns/s/y, (95% highest probability density (HPD) 1.25x10(-3)-2.55x10(-3)) and 1.91x10(-3) ns/s/y (95% HPD 1.50x10(-3)-2.34x10(-3)), respectively. CONCLUSIONS: After excluding the misdated taxon, both genes support a significantly higher substitution rate as well as a relatively recent emergence of RHDV, and obviate the need for previously hypothesized decades of unobserved diversification of the virus. The control methods show that using even one misdated taxon in a large dataset can significantly skew estimates of evolutionary parameters and suggest that it is better practice to use smaller datasets composed of taxa with unequivocal isolation dates. These jackknife controls would be useful for future tip-calibrated rate analyses that include taxa with ambiguous dates of isolation.


title: Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS‐CoV‐2 infection

text: OBJECTIVE: This study aimed to assess the presence of novel coronavirus in tears and conjunctival secretions of SARS–CoV‐2‐infected patients. METHODS: A prospective interventional case series study was performed, and 30 confirmed novel coronavirus pneumonia (NCP) patients were selected at the First Affiliated Hospital of Zhejiang University from 26 January 2020 to 9 February 2020. At an interval of 2 to 3 days, tear and conjunctival secretions were collected twice with disposable sampling swabs for reverse‐transcription polymerase chain reaction (RT‐PCR) assay. RESULTS: Twenty‐one common‐type and nine severe‐type NCP patients were enrolled. Two samples of tear and conjunctival secretions were obtained from the only one patient with conjunctivitis yielded positive RT‐PCR results. Fifty‐eight samples from other patents were all negative. CONCLUSION: We speculate that SARS‐CoV‐2 may be detected in the tears and conjunctival secretions in NCP patients with conjunctivitis.


title: Commercial exchanges instead of air pollution as possible origin of COVID-19 initial diffusion phase in Italy: more efforts are necessary to address interdisciplinary research

text: This communication aims to advocate a more coordinate activity mainly between medical and environmental scientists to clarify some confusing information related to airborne diffusion mechanisms of COVID-19. In this frame it is suggested that parameters other than environmental pollution (accounting for pollution-to human transmission mechanisms), as for example parameters involving commercial exchanges (accounting for human-to human transmission mechanisms), should be considered to better justify the difference in the initial diffusion of virus in Italy.


Emergency management, mitigation for COVID‐19 and the importance of preparedness for future outbreaks


title: Impact of Multiplex Polymerase Chain Reaction Testing for Respiratory Pathogens on Healthcare Resource Utilization for Pediatric Inpatients

text: OBJECTIVE: To assess whether multiplex polymerase chain reaction (mPCR) vs. non-MPCR testing impacts the use of antibiotics, chest radiographs, and isolation precautions. STUDY DESIGN: We retrospectively compared use of antibiotics, chest radiographs, and isolation precautions for patients <18 years old (excluding neonates) hospitalized at a tertiary referral center tested for respiratory pathogens in the emergency department or during the first 2 hospital days, during two periods: June 2010–June 2012 (non-MPCR group) vs. October 2012-May 2014 (MPCR group). RESULTS: Subjects (n=2430) in the MPCR group were older, had more complex chronic conditions, and were admitted to the PICU more often compared with the non-MPCR (n=2349) group. Subjects in the MPCR group had more positive tests (42.4% vs. 14.4%, p<0.01), received fewer days of antibiotics (4 vs. 5 median antibiotic days, p<0.01), fewer chest radiographs performed, (59% vs. 78%, p<0.01), and were placed in isolation longer (20 vs. 0 median isolation-hours, p<0.01) compared with the non-MPCR group. In multivariable regression, patients tested with MPCR were less likely to receive antibiotics for ≥2 days (OR 0.5, 95% CI 0.5-0.6), chest radiographs at admission (OR 0.4, 95% CI 0.3-0.4), and more likely to be in isolation for ≥2 days (OR 2.4, 95% CI 2.1-2.8 compared with the non- MPCR group. CONCLUSIONS: Use of MPCR testing for respiratory viruses among hospitalized patients was significantly associated with decreased healthcare resource utilization, including decreased use of antibiotics and chest radiographs, and increased use of isolation precautions.


docid: vtjsigod

title: Novel coronavirus infection during the 2019–2020 epidemic: preparing intensive care units—the experience in Sichuan Province, China


154. Severe Acute Respiratory Syndrome Coronavirus-Like Particles (SARS-CoVLPs) Stimulate Human Monocyte-Derived Dendritic Cell Activity and Induce Antibody Response in Mouse Model


Letter to the Editor: “Our Response to Covid-19 as Endocrinologists and Diabetologists”


title: The Genomic Signature of Population Reconnection Following Isolation: From Theory to HIV

text: Ease of worldwide travel provides increased opportunities for organisms not only to colonize new environments but also to encounter related but diverged populations. Such events of reconnection and secondary contact of previously isolated populations are widely observed at different time scales. For example, during the quaternary glaciation, sea water level fluctuations caused temporal isolation of populations, often to be followed by secondary contact. At shorter time scales, population isolation and reconnection of viruses are commonly observed, and such events are often associated with epidemics and pandemics. Here, using coalescent theory and simulations, we describe the temporal impact of population reconnection after isolation on nucleotide differences and the site frequency spectrum, as well as common summary statistics of DNA variation. We identify robust genomic signatures of population reconnection after isolation. We utilize our development to infer the recent evolutionary history of human immunodeficiency virus 1 (HIV-1) in Asia and South America, successfully retrieving the successive HIV subtype colonization events in these regions. Our analysis reveals that divergent HIV-1 subtype populations are currently admixing in these regions, suggesting that HIV-1 may be undergoing a process of homogenization, contrary to popular belief.


Can imaging impact the coronavirus pandemic?


title: Predicting virus emergence amid evolutionary noise

text: The study of virus disease emergence, whether it can be predicted and how it might be prevented, has become a major research topic in biomedicine. Here we show that efforts to predict disease emergence commonly conflate fundamentally different evolutionary and epidemiological time scales, and are likely to fail because of the enormous number of unsampled viruses that could conceivably emerge in humans. Although we know much about the patterns and processes of virus evolution on evolutionary time scales as depicted in family-scale phylogenetic trees, these data have little predictive power to reveal the short-term microevolutionary processes that underpin cross-species transmission and emergence. Truly understanding disease emergence therefore requires a new mechanistic and integrated view of the factors that allow or prevent viruses spreading in novel hosts. We present such a view, suggesting that both ecological and genetic aspects of virus emergence can be placed within a simple population genetic framework, which in turn highlights the importance of host population size and density in determining whether emergence will be successful. Despite this framework, we conclude that a more practical solution to preventing and containing the successful emergence of new diseases entails ongoing virological surveillance at the human–animal interface and regions of ecological disturbance.


title: Drive-Through Testing: A Unique, Efficient Method of Collecting Large Volume of Specimens During the SARS-CoV-2 (COVID-19) Pandemic

text: The World Health Organization declared COVID-19 a global pandemic in March 2020. A major challenge in this worldwide pandemic has been efficient and effective large-scale testing for the disease. In this communication, we discuss lessons learned in the set up and function of a locally organized drive-through testing facility.


title: A clinical, histopathological and laboratory study of 19 consecutive Italian paediatric patients with chilblain‐like lesions: lights and shadows on the relationship with COVID‐19 infection

text: BACKGROUND: Acral chilblain‐like lesions are being increasingly reported during COVID‐19 pandemic. However, only few patients proved positivity for SARS‐CoV‐2 infection. The relationship between this skin manifestation and COVID‐19 infection has not been clarified yet. OBJECTIVE: To thoroughly characterize a prospective group of patients with chilblain‐like lesions, and to investigate the possible relationship with SARS‐CoV‐2 infection. METHODS: Following informed consent, patients underwent: (i) clinical evaluation, (ii) RT‐PCR and serology testing for SARS‐CoV‐2, (iii) digital videocapillaroscopy of finger‐ and toe‐nailfolds, (iv) blood testing to screen for autoimmune diseases and coagulation anomalies, and (v) skin biopsy for histopathology, direct immunofluorescence, and, in selected cases, electron microscopy. RESULTS: Nineteen patients, all adolescents (mean age: 14 years), were recruited. 11/19 (58%) of them and/or their cohabitants reported flu‐like symptoms one to two months prior to skin manifestation onset. Lesions were localized to toes and also heels and soles. Videocapillarcosopy showed pericapillary oedema, dilated and abnormal capillaries, and microhemorrhages both in finger and toe in the majority of patients. Major pathological findings included: epidermal basal layer vacuolation, papillary dermis oedema and erythrocyte extravasation, perivascular and perieccrine dermal lymphocytic infiltrate, and mucin deposition in the dermis and hypodermis; dermal vessel thrombi were observed in 2 cases. Blood exams were normal. Nasopharyngeal swab for SARS‐CoV‐2 and IgG serology for SARS‐CoV‐2 nucleocapsid protein were negative. Importantly, IgA serology for S1 domain of SARS‐CoV‐2 spike protein was positive in 6 patients and borderline in 3. CONCLUSIONS: Chilblain‐like lesions during COVID‐19 pandemic have specific epidemiologic, clinical, capillaroscopic and histopathological characteristics, which distinguish them from idiopathic perniosis. Though we could not formally prove SARS‐CoV‐2 infection in our patients, history data and the detection of anti‐SARS‐COV‐2 IgA strongly suggest a relationship between skin lesions and COVID‐19. Further investigations on the mechanisms of SARS‐CoV‐2 infection in children and pathogenesis of chilblain‐like lesions are warranted.


docid: xqowfmzz

title: A dynamic modeling tool for estimating healthcare demand from the COVID19 epidemic and evaluating population-wide interventions

text: OBJECTIVES: Public health officials need tools to assist with anticipating the healthcare resources required to confront the SARS-COV-2 pandemic. We built a modeling tool to aid practicing public health officials with estimating healthcare demand from the pandemic in their jurisdictions and to evaluate the potential impacts of population-wide social-distancing interventions. METHODS: The tool uses a SEIR compartmental model to project the pandemic’s local spread. Users input case counts, healthcare resources, and select intervention strategies to evaluate. Outputs include the number of infections and deaths with and without intervention, and the demand for hospital and critical care beds and ventilators relative to existing capacity. We illustrate the tool using data from three regions of Chile. RESULTS: Our scenarios indicate a surge in COVID-19 patients could overwhelm Chilean hospitals by June, peaking in July or August at 6 to 50 times the current supply of beds and ventilators. A lockdown strategy or combination of case isolation, home quarantine, social distancing of individuals >70 years, and telework interventions may keep treatment demand below capacity. CONCLUSIONS: Aggressive interventions can avert substantial morbidity and mortality from COVID-19. Our tool permits rapid evaluation of locally-applicable policy scenarios and updating of results as new data become available.


title: Feline immune system

text: Abstract Immunological features of feline lymphocytes, immunoglobulins, monocytes/macrophages, cytokines, major histocompatibility complex and delayed-type hypersensitivity are reviewed. Attention is given to the comparison of the feline immune system with the immune systems of humans and other animals. Also presented is information on the modification of feline immunity by pathogens.


title: Impact of the COVID-19 pandemic on patients with pre-existing anxiety disorders attending secondary care

text: OBJECTIVES: To examine the psychological and social impact of the COVID-19 pandemic on patients with established anxiety disorders during a period of stringent mandated social restrictions. METHODS: Semi-structured interviews were conducted with 30 individuals attending the Galway-Roscommon Mental Health Services with an International Classification of Diseases diagnosis of an anxiety disorder to determine the impact of the COVID-19 restrictions on anxiety and mood symptoms, social and occupational functioning and quality of life. RESULTS: Twelve (40.0%) participants described COVID-19 restrictions as having a deleterious impact on their anxiety symptoms. Likert scale measurements noted that the greatest impact of COVID-19 related to social functioning (mean = 4.5, SD = 2.9), with a modest deleterious effect on anxiety symptoms noted (mean = 3.8, SD = 2.9). Clinician rated data noted that 8 (26.7%) participants had disimproved and 14 (46.7%) participants had improved since their previous clinical review, prior to commencement of COVID-19 restrictions. Conditions associated with no ‘trigger’, such as generalised anxiety disorder, demonstrated a non-significant increase in anxiety symptoms compared to conditions with a ‘trigger’, such as obsessive compulsive disorder. Psychiatric or physical comorbidity did not substantially impact on symptomatology secondary to COVID-19 mandated restrictions. CONCLUSIONS: The psychological and social impact of COVID-19 restrictions on individuals with pre-existing anxiety disorders has been modest with only minimal increases in symptomatology or social impairment noted.


title: Telemedicine Barriers and Challenges for Persons with Disabilities: Covid-19 and Beyond

text: The Covid-19 pandemic has forced a rapid adoption of telemedicine over traditional in-person visits due to social restrictions. While telemedicine improves access and reduces barriers to healthcare access for many, several barriers and challenges remain for persons with disabilities, and novel challenges have been exposed, many of which may persist long-term. The challenges and barriers that need to be systematically addressed include: Infrastructure and access barriers, operational challenges, regulatory barriers, communication barriers and legislative barriers. Persons with disabilities are a vulnerable population and little attention has been placed on their healthcare access during the pandemic. Access and communication during a healthcare encounter are important mediators of outcomes for persons with disabilities. Significant, long-term changes in technological, regulatory, and legislative infrastructure and custom solutions to unique patient and health system needs are required to address these barriers going forward in order to improve healthcare access and outcomes for persons with disabilities.


Reflecting on the future of infection prevention and control: Are we waiting or creating?


title: Canine Isosporosis – Epidemiology of Field and Experimental Infections

text: Isospora spp. are the causative agents of canine isosporosis. Of the 3590 diagnostic samples from Austrian dogs (≤2 years old), 8.7% contained Isospora oocysts, 78% of which from dogs up to 4 months of age. Non‐haemorrhagic and haemorrhagic diarrhoea were significantly more prevalent in Isospora‐infected animals than in coccidia‐negative ones. Twelve of 15 litters from a large commercial dog breeding unit (examined from the third to the 10th week of life) also excreted Isospora (average prevalence: 36.4%) in intensities from 333 to 35 000 oocysts per gram of faeces (opg). In experimental trials 26 3‐week‐old Beagle puppies were infected with low (600–6000), medium (10 000) or high (20 000) dose of Isospora ohioensis‐group or Isospora canis field isolates. Additionally 21 puppies were infected as above and treated with a symmetrical triazintrione. Parasitological and clinical parameters were examined. The two Isospora species differed significantly concerning intensity and duration of excretion. The pre‐patent period was 6–7 days for I. ohioensis and 10–12 days for I. canis. The latter species showed significantly longer excretion and higher opg. This was not influenced by simultaneous infections with both species. Individual patterns of faecal consistency were very variable, irrespective of the infection dose. Treatment significantly reduced both the intensity and the duration of oocysts excretion as well as diarrhoea in comparison with the infected, untreated group and thus proved to be effective against coccidiosis in experimental infections.


title: Rapid asymptomatic transmission of COVID-19 during the incubation period demonstrating strong infectivity in a cluster of youngsters aged 16-23 years outside Wuhan and characteristics of young patients with COVID-19: A prospective contact-tracing study

text: Summary Background The outbreak of coronavirus-disease-2019 (COVID-19) has rapidly spread to many places outside Wuhan. Previous studies on COVID-19 mostly included older hospitalized-adults. Little information on infectivity among and characteristics of youngsters with COVID-19 is available. Methods A cluster of 22 close-contacts of a 22-year-old male (Patient-Index) including youngsters with laboratory-confirmed COVID-19 and hospitalized close-contacts testing negative for severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) in Anhui Province, China was prospectively-traced. Results Since January 23, 2020, we enrolled a cluster of eight youngsters with COVID-19 (median age [range], 22 [16–23] years; six males) originating from Patient-Index returning from Wuhan to Hefei on January 19. Patient-Index visited his 16-year-old female cousin in the evening on his return, and met 15 previous classmates in a get-together on January 21. He reported being totally asymptomatic and were described by all his contacts as healthy on January 19-21. His very first symptoms were itchy eyes and fever developed at noon and in the afternoon on January 22, respectively. Seven youngsters (his cousin and six classmates) became infected with COVID-19 after a-few-hour-contact with Patient-Index. None of the patients and contacts had visited Wuhan (except Patient-Index), or had any exposure to wet-markets, wild-animals, or medical-institutes within three months. For affected youngsters, the median incubation-period was 2 days (range, 1–4). The median serial-interval was 1 day (range, 0–4). Half or more of the eight COVID-19-infected youngsters had fever, cough, sputum production, nasal congestion, and fatigue on admission. All patients had mild conditions. Six patients developed pneumonia (all mild; one bilateral) on admission. As of February 20, four patients were discharged. Conclusions SARS-CoV-2-infection presented strong infectivity during the incubation-period with rapid transmission in this cluster of youngsters outside Wuhan. COVID-19 developed in these youngsters had fast onset and various nonspecific atypical manifestations, and were much milder than in older patients as previously reported.


Recovery of Non-Urgent Surgery – Operation Backlog and Proposals for a Restart


Will warmer spring weather slow down the rate of spread?


title: Echoes of 2009 H1N1 Influenza Pandemic in the COVID Pandemic

text: Abstract The severe acute respiratory syndrome–related coronavirus-2 (SARS-CoV2) pandemic that has engulfed the globe has had incredible effects on health care systems and economic activity. Social distancing and school closures have played a central role in public health efforts to counter the coronavirus disease 2019 (COVID)-19 pandemic. The most recent global pandemic prior to COVID-19 was the 2009 pandemic, hemagglutinin type 1 and neuraminidase type 1 (H1N1) influenza. The course of events in 2009 offer some rich lessons that could be applied to the current COVID-19 pandemic. This commentary highlights some of the most relevant points and a discussion of possible outcomes of the COVID-19 pandemic. © 2020 Elsevier Inc.


Psychosis: A Presentation of COVID-19?


Myasthenia gravis: Antigen presentation by thymoma epithelial cells


title: Effects of Atypical Infections with Mycoplasma and Chlamydia on Asthma

text: Mycoplasma pneumoniae and Chlamydophila pneumoniae are atypical bacteria that are frequently found in patients with asthma. A definitive diagnosis of infection is often difficult to obtain because of limitations with sampling and detection. Numerous animal studies have outlined mechanisms by which these infections may promote allergic lung inflammation and airway remodeling. In addition, there is mounting evidence from human studies suggesting that atypical bacterial infections contribute to asthma exacerbations, chronic asthma, and disease severity. The role of antimicrobials directed against atypical bacteria in asthma is still under investigation.


title: Disease Associated with Equine Coronavirus Infection and High Case Fatality Rate

text: BACKGROUND: Equine coronavirus (ECoV) is associated with clinical disease in adult horses. Outbreaks are associated with a low case fatality rate and a small number of animals with signs of encephalopathic disease are described. OBJECTIVES: The aim of this study is to describe the epidemiological and clinical features of two outbreaks of ECoV infection that were associated with an high case fatality rate. ANIMALS: 14 miniature horses and 1 miniature donkey testing fecal positive for ECoV from two related disease outbreaks. METHODS: Retrospective study describing the epidemiological findings, clinicopathological findings, and fecal viral load from affected horses. RESULTS: In EcoV positive horses, 27% (4/15) of the animals died or were euthanized. Severe hyperammonemia (677 μmol/L, reference range ≤60 μmol/L) was identified in one animal with signs of encephalopathic disease that subsequently died. Fecal viral load (ECoV genome equivalents per gram of feces) was significantly higher in the nonsurvivors compared to animals that survived (P = .02). CONCLUSIONS AND CLINICAL IMPORTANCE: Equine coronavirus had a higher case fatality rate in this group of miniature horses than previously reported in other outbreaks of varying breeds. Hyperammonemia could contribute to signs of encephalopathic disease, and the fecal viral load might be of prognostic value in affected horses.


title: Natural killer cells in host defense against veterinary pathogens

text: Abstract Natural Killer (NK) cells constitute a major subset of innate lymphoid cells that do not express the T- and B-cell receptors and play an important role in antimicrobial defense. NK cells not only induce early and rapid innate immune responses, but also communicate with dendritic cells to shape the adaptive immunity, thus bridging innate and adaptive immunity. Although the functional biology of NK cells is well-documented in a variety of infections in humans and mice, their role in protecting domestic animals from infectious agents is only beginning to be understood. In this article, we summarize the current state of knowledge about the contribution of NK cells in pathogen defense in domestic animals, especially cattle and pigs. Understanding the immunobiology of NK cells will translate into strategies to manipulate these cells for preventive and therapeutic purposes.


title: The Role of the Global Health Development/Eastern Mediterranean Public Health Network and the Eastern Mediterranean Field Epidemiology Training Programs in Preparedness for COVID-19

text: The World Health Organization (WHO) declared the current COVID-19 a public health emergency of international concern on January 30, 2020. Countries in the Eastern Mediterranean Region (EMR) have a high vulnerability and variable capacity to respond to outbreaks. Many of these countries addressed the need for increasing capacity in the areas of surveillance and rapid response to public health threats. Moreover, countries addressed the need for communication strategies that direct the public to actions for self- and community protection. This viewpoint article aims to highlight the contribution of the Global Health Development (GHD)/Eastern Mediterranean Public Health Network (EMPHNET) and the EMR’s Field Epidemiology Training Program (FETPs) to prepare for and respond to the current COVID-19 threat. GHD/EMPHNET has the scientific expertise to contribute to elevating the level of country alert and preparedness in the EMR and to provide technical support through health promotion, training and training materials, guidelines, coordination, and communication. The FETPs are currently actively participating in surveillance and screening at the ports of entry, development of communication materials and guidelines, and sharing information to health professionals and the public. However, some countries remain ill-equipped, have poor diagnostic capacity, and are in need of further capacity development in response to public health threats. It is essential that GHD/EMPHNET and FETPs continue building the capacity to respond to COVID-19 and intensify support for preparedness and response to public health emergencies.


title: An analytic framework to develop policies for testing, prevention, and treatment of two-stage contagious diseases

text: In this paper we consider healthcare policy issues for trading off resources in testing, prevention, and cure of two-stage contagious diseases. An individual that has contracted the two-stage contagious disease will initially show no symptoms of the disease but is capable of spreading it. If the initial stages are not detected which could lead to complications eventually, then symptoms start appearing in the latter stage when it would be necessary to perform expensive treatment. Under a constrained budget situation, policymakers are faced with the decision of how to allocate budget for prevention (via vaccinations), subsidizing treatment, and examination to detect the presence of initial stages of the contagious disease. These decisions need to be performed in each period of a given time horizon. To aid this decision-making exercise, we formulate a stochastic dynamic optimal control problem with feedback which can be modeled as a Markov decision process (MDP). However, solving the MDP is computationally intractable due to the large state space as the embedded stochastic network cannot be decomposed. Hence we propose an asymptotically optimal solution based on a fluid model of the dynamics in the stochastic network. We heuristically fine-tune the asymptotically optimal solution for the non-asymptotic case, and test it extensively for several numerical cases. In particular we investigate the effect of budget, length of planning horizon, type of disease, population size, and ratio of costs on the policy for budget allocation.


title: Coronaviral hypothetical and structural proteins were found in the intestinal surface enterocytes and pneumocytes of severe acute respiratory syndrome (SARS)

text: Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease that haunted the world from November 2002 to July 2003. Little is known about the biology and pathophysiology of the novel coronavirus that causes SARS. The tissue and cellular distributions of coronaviral hypothetical and structural proteins in SARS were investigated. Antibodies against the hypothetical (SARS 3a, 3b, 6, 7a and 9b) and structural proteins (envelope, membrane, nucleocapsid and spike) of the coronavirus were generated from predicted antigenic epitopes of each protein. The presence of these proteins were first verified in coronavirus-infected Vero E6 tissue culture model. Immunohistochemical studies on different human tissues, including a cohort of nine autopsies, two liver biopsies and intestinal biopsies of SARS patients, further confirmed the existence of coronaviral hypothetical and structural proteins in the cytoplasm of pneumocytes and small intestinal surface enterocytes in SARS patients. With this vast array of antibodies, no signal was observed in other cell types including those organs in which reverse transcriptase-polymerase chain reactions were reported to be positive. Structural proteins and the functionally undefined hypothetical proteins were expressed in coronavirus-infected cells with distinct expression pattern in different organs in SARS patients. These antipeptide antibodies can be useful for the diagnosis of SARS at the tissue level.


title: Complications cardiaques du Covid-19 en réanimation

text: Résumé L’infection à SARS-CoV2, responsable de détresse respiratoire aigue grave est déclarée pandémie mondiale par l’OMS à partir du 11 mars 2020. Si les manifestations pulmonaires sont le plus souvent au premier plan, des complications cardiovasculaires ont été observées et associées à un plus mauvais pronostic. L'enzyme ACE2 intrinsèquement impliquée dans la physiologique de la fonction cardiaque et dans le développement de l'hypertension et du diabète a été identifiée comme un récepteur fonctionnel du SARS-CoV-2. Il est difficile préciser les mécanismes des atteintes cardiaques car ils sont probablement multiples : atteinte myocardique directe du SARS-CoV-2 responsable de myocardites virales ; atteinte secondaire à l’état d’inflammation systémique exacerbé avec l’hypoxémie responsable de souffrance myocardique. Par ailleurs, les traitements à l’étude dans cette maladie provoquent des modifications de l’électrocardiogramme avec un allongement du segment QT. Les dosages des marqueurs cardiaques sont nécessaires si une souffrance myocardique est suspectée ainsi qu’une surveillance échographique. Les atteintes cardiaques augmentant la morbidité post hospitalière, la stratification du risque avec l’IRM cardiaque et le suivi prolongé des patients semblent nécessaires. Summary The World Health Organization declared the SARS-CoV-2 infection causing severe acute respiratory distress a global pandemic in March 2020. While respiratory features are commonly at the forefront of the disease, cardiovascular complications have been observed and associated with a poorer prognosis. The ACE2 enzyme intrinsically involved in the physiology of cardiac function and in the development of hypertension and diabetes has been identified as a functional receptor for SARS-CoV-2. It is difficult to highlight the precise mechanisms of cardiac damage because of its possible multiple implications, through direct damage from SARS-CoV-2 responsible for viral myocarditis or indirect damage from the state of exacerbated systemic inflammation associated with hypoxaemia. The treatments of the disease, may also induce adverse effects such as an increase in QT segment duration. Measurements of cardiac biomarkers are required if myocardial damage is suspected and are part of a panel of arguments confronted with clinical features, ultrasonic monitoring and electrocardiogram. As the cardiac disorders increase post-hospital morbidity, risk stratification with cardiac MRI and prolonged follow-up are required.


Viral Infections of the Central Nervous System: Pathogenesis to Therapeutics


title: Elevated levels of vitamin D and deficiency of mannose binding lectin in dengue hemorrhagic fever

text: BACKGROUND: Altered plasma concentrations of vitamin D and mannose binding lectin (MBL), components of innate immunity, have been shown to be associated with the pathogenesis of viral infections. The objective of the present study was to find out whether plasma concentrations of MBL and vitamin D are different in patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). THE RESULTS: The plasma concentrations of vitamin D and MBL were assessed in 48 DF cases, 45 DHF cases and 20 apparently healthy controls using ELISA based methods. Vitamin D concentrations were found to be higher among both DF and DHF cases as compared to healthy controls (P < 0.005 and P < 0.001). Vitamin D concentrations were not different between DF and DHF cases. When the dengue cases were classified into primary and secondary infections, secondary DHF cases had significantly higher concentrations of vitamin D as compared to secondary DF cases (P < 0.050). MBL concentrations were not significantly different between healthy controls and dengue cases. MBL concentrations were observed to be lower in DHF cases as compared to DF cases (P < 0.050). Although MBL levels were not different DF and DHF cases based on immune status, the percentage of primary DHF cases (50%) having MBL levels lower than 500 ng/ml were less compared to primary DF cases (P = 0.038). CONCLUSIONS: The present study suggests that higher concentrations of vitamin D might be associated with secondary DHF while deficiency of MBL may be associated with primary DHF.


title: Dengue Hemorrhagic Fever in Infants: Research Opportunities Ignored

text: The age distribution of cases of dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) in infants under the age of 1 year are reported from Bangkok, Thailand, and for the first time for Ho Chi Minh City, Vietnam; Yangon, Myanmar; and Surabaya, Indonesia. The four dengue viruses were isolated from Thai infants, all of whom were having a primary dengue infection. Progress studying the immunologically distinct infant DHF/DSS has been limited; most contemporary research has centered on DHF/DSS accompanying secondary dengue infections. In designing research results obtained in studies on a congruent animal model, feline infectious peritonitis virus (FIPV) infections of kittens born to FIPV-immune queens should be considered. Research challenges presented by infant DHF/DSS are discussed.


title: Chronic renal failure in Sri Lanka caused by elevated dietary cadmium: Trojan horse of the green revolution

text: Abstract The endemic of chronic renal failure (CRF) emerged in 2002 in the farming provinces of Sri Lanka. An estimate of dietary cadmium intake was between 15 and 28μg/kg body weight per week. The mean urinary cadmium in patients diagnosed with stage 5 kidney failure was 7.6μg/g creatinine and 11.6μg/g for asymptomatic persons. The agrochemical triple superphosphate (TSP) fertilizer containing 23.5–71.7mgCd/kg was the source of cadmium added to soils. Mean Cd content in cultivated vs. uncultivated soils in Anuradhapura district was 0.02±0.01 vs. 0.11±0.19mg/kg while in Polonnaruwa district, it was 0.005±0.004 vs. 0.016±0.005mg/kg. Prior to the Green Revolution, the amount of fertilizer used in rice cultivation in 1970 was 32,000 metric tons (Mts) rising to 74,000Mts in 1975. Up to 68.9Mts of Cd could have entered into the rice-cascade reservoir environment from TSP use since 1973. Diversion of the Mahaweli River in 1970–1980 further increased cadmium input. Cadmium transfer from Upper Mahaweli water to Polgolla was 72.13kg/day. Cadmium content of the sediments from reservoirs collecting cadmium from irrigated TSP fertilized crop fields (rice and vegetables) was 1.8–2.4mg/kg.


title: Cis-acting RNA elements in human and animal plus-strand RNA viruses

text: The RNA genomes of plus-strand RNA viruses have the ability to form secondary and higher-order structures that contribute to their stability and to their participation in inter- and intramolecular interactions. Those structures that are functionally important are called cis-acting RNA elements because their functions cannot be complemented in trans. They can be involved not only in RNA/RNA interactions but also in binding of viral and cellular proteins during the complex processes of translation, RNA replication and encapsidation. Most viral cis-acting RNA elements are located in the highly structured 5′- and 3′-nontranslated regions of the genomes but sometimes they also extend into the adjacent coding sequences. In addition, some cis-acting RNA elements are embedded within the coding sequences far away from the genomic ends. Although the functional importance of many of these structures have been confirmed by genetic and biochemical analyses their precise roles are not yet fully understood. In this review we have summarized what is known about cis-acting RNA elements in nine families of human and animal plus-strand RNA viruses with an emphasis on the most thoroughly characterized virus families, the Picornaviridae and Flaviviridae.


title: Common commercial cosmetic products induce arthritis in the DA rat.

text: Many different agents, including mineral oil and silicone, have the capacity to act as immunological adjuvants, i.e., they can contribute to the activation of the immune system. Some adjuvants, including mineral oil, are known to induce arthritis in certain strains of rats after intradermal injection or percutaneous application. The aim of this study was to determine if common commercial cosmetic products containing mineral oil could induce arthritis in the highly susceptible DA (Dark Agouti) rat. Intradermal injection of five out of eight assayed cosmetic products without further additives resulted in arthritis with synovitis. One of the products induced a very aggressive arthritis, which had declined after 5-9 weeks. When this product was also assayed for arthritogenicity upon percutaneous administration, it induced a mild and transient arthritis in 5 out of 10 DA rats, whereas control animals showed no clinical signs of joint involvement. No arthritic reaction was seen in rats after peroral feeding with the most arthritogenic product or by intravaginal application of Freund's adjuvants. Silicone gel implants in DA rats did not cause arthritis. We conclude that mineral oils included in common commercially available products retain their adjuvant properties and are arthritogenic in the presently investigated arthritis-prone rat strain. There is yet no evidence that mineral oils present in cosmetics may contribute to arthritis in humans, but we suggest that this question should be subject to further investigation.


title: NCBI Viral Genomes Resource

text: Recent technological innovations have ignited an explosion in virus genome sequencing that promises to fundamentally alter our understanding of viral biology and profoundly impact public health policy. Yet, any potential benefits from the billowing cloud of next generation sequence data hinge upon well implemented reference resources that facilitate the identification of sequences, aid in the assembly of sequence reads and provide reference annotation sources. The NCBI Viral Genomes Resource is a reference resource designed to bring order to this sequence shockwave and improve usability of viral sequence data. The resource can be accessed at http://www.ncbi.nlm.nih.gov/genome/viruses/ and catalogs all publicly available virus genome sequences and curates reference genome sequences. As the number of genome sequences has grown, so too have the difficulties in annotating and maintaining reference sequences. The rapid expansion of the viral sequence universe has forced a recalibration of the data model to better provide extant sequence representation and enhanced reference sequence products to serve the needs of the various viral communities. This, in turn, has placed increased emphasis on leveraging the knowledge of individual scientific communities to identify important viral sequences and develop well annotated reference virus genome sets.


Crisis Sanitaria COVID-19: el papel de un cirujano


title: Comment on Matricardi PM et al.: The first, holistic immunological model of COVID‐19: implications for prevention, diagnosis, and public health measures

text: We read with great interest the review article by Matricardi and colleagues [1] depicting mechanisms of disease for COVID‐19 and analyzing both viral and host factors influencing its course. We particularly agree with Authors on the pivotal role of innate immunity in the very early phase of disease, being crucial for the subsequent evolution. Most known weapons of innate immune system are represented by natural antibodies, non‐specific antimicrobial proteins, interferons, cytokines and cellular elements (i.e. natural killer cells).[1] However, innate immunity could be influenced by other, still underrecognized, factors.


title: Post‐translational regulation of antiviral innate signaling

text: The innate immune system initiates immune responses by pattern‐recognition receptors (PRR). Virus‐derived nucleic acids are sensed by the retinoic acid‐inducible gene I (RIG‐I)‐like receptor (RLR) family and the toll‐like receptor (TLR) family as well as the DNA sensor cyclic GMP‐AMP (cGAMP) synthase (cGAS). These receptors activate IRF3/7 and NF‐κB signaling pathways to induce the expression of type I interferons (IFNs) and other cytokines firing antiviral responses within the cell. However, to achieve a favorable outcome for the host, a balanced production of IFNs and activation of antiviral responses is required. Post‐translational modifications (PTMs), such as the covalent linkage of functional groups to amino acid chains, are crucial for this immune homeostasis in antiviral responses. Canonical PTMs including phosphorylation and ubiquitination have been extensively studied and other PTMs such as methylation, acetylation, SUMOylation, ADP‐ribosylation and glutamylation are being increasingly implicated in antiviral innate immunity. Here we summarize our recent understanding of the most important PTMs regulating the antiviral innate immune response, and their role in virus‐related immune pathogenesis.