title: Murine hepatitis virus nsp4 N258T mutants are not temperature-sensitive

text: Abstract Coronavirus replicase nsp4 is critical for virus-induced membrane modifications. An nsp4 mutant (N258T) of murine hepatitis virus (MHV) has been reported to be temperature-sensitive (ts) and to alter membrane targeting. We engineered and recovered all four possible codon variants of N258T in the cloned MHV-A59 background. All mutant viruses demonstrated impaired replication compared to wildtype MHV, but no nsp4 N258T mutant virus was ts, and all variants colocalized with viral protein markers for replication complexes, but not with markers for mitochondria. This study emphasizes that complete genome sequencing may be necessary, even with directed and confirmed reverse genetic mutants.


title: Virucidal action of sore throat lozenges against respiratory viruses parainfluenza type 3 and cytomegalovirus

text: Abstract Most respiratory tract infections are self-limiting and caused by viruses, and do not warrant antibiotic treatment. Despite this, patients with respiratory tract infections often receive antibiotics, fuelling the rise of antibiotic resistance. Therefore, there is a need to encourage patients to try alternative non-antibiotic therapies, which ideally treat the symptoms and the cause. Lozenges containing amylmetacresol and 2,4-dichlorobenzyl alcohol (AMC/DCBA lozenges) as well as lozenges containing hexylresorcinol have been shown to provide effective symptomatic relief for sore throat. In this study, we investigated whether these lozenges also have virucidal effects in vitro against two viruses associated with respiratory tract infections, parainfluenza virus type 3 and cytomegalovirus. Both viruses were incubated with AMC/DCBA lozenge, placebo lozenge or the active ingredients (AMC/DCBA) as free substances, and parainfluenza virus type 3 was incubated with hexylresorcinol lozenge, placebo lozenge or hexylresorcinol as a free substance. Virucidal effects were observed with the active lozenges and the active ingredients as free substances against both parainfluenza virus type 3 and cytomegalovirus. Mean reductions in viral titre were significantly greater compared with placebo lozenge and peak effects were observed for the shortest incubation time, 1min. These findings suggest that AMC/DCBA lozenge and hexylresorcinol lozenge have the potential to have local antiviral effects in patients with sore throat due to viral respiratory tract infections. Use of such over-the-counter treatments for self-limiting respiratory tract infections may satisfy patients’ desire for an anti-infective medication and reduce the demand for antibiotics.


title: First respiratory transmitted food borne outbreak?

text: Abstract The world is faced with a remarkable coronavirus outbreak with epicentre in Wuhan, China. Altogether 40554 cases have been confirmed globally with novel coronavirus (SARS-CoV-2) until February 10, 2020. Rigorous surveillance in other countries is required to prevent further global expansion of the outbreak, but resolving the exact mechanism of the initial transmission events is crucial. Most initial cases had visited Huanan South Seafood Market in Wuhan selling also various exotic live animals. Based on the limited initial human-to-human transmission and timely clustering of cases in Huanan market among elderly men, coupled with knowledge that coronaviruses are derived from animals and relationship of SARS-CoV-2 to bat coronavirus, zoonotic transmission in the first instance is probable. To target the actions, similar epidemiological actions to human cases are needed with animal or food exposures. According to current information, an exceptionally wide contamination of seafood market might explain the initiation of the SARS-CoV-2 outbreak. Seafood tanks, air contamination by live animals or rodents are possibilities, but sold animals normally come from various sources. The mode of transmission may become clearer in future: usually in outbreak investigations, hindsight is easy, but for now information about the initial source of this outbreak is limited.


title: Modulation of nasopharyngeal innate defenses by viral coinfection predisposes individuals to experimental pneumococcal carriage

text: Increased nasopharyngeal colonization density has been associated with pneumonia. We used experimental human pneumococcal carriage to investigate whether upper respiratory tract viral infection predisposes individuals to carriage. A total of 101 healthy subjects were screened for respiratory virus before pneumococcal intranasal challenge. Virus was associated with increased odds of colonization (75% virus positive became colonized vs. 46% virus-negative subjects; P=0.02). Nasal Factor H (FH) levels were increased in virus-positive subjects and were associated with increased colonization density. Using an in vitro epithelial model we explored the impact of increased mucosal FH in the context of coinfection. Epithelial inflammation and FH binding resulted in increased pneumococcal adherence to the epithelium. Binding was partially blocked by antibodies targeting the FH-binding protein Pneumococcal surface protein C (PspC). PspC epitope mapping revealed individuals lacked antibodies against the FH binding region. We propose that FH binding to PspC in vivo masks this binding site, enabling FH to facilitate pneumococcal/epithelial attachment during viral infection despite the presence of anti-PspC antibodies. We propose that a PspC-based vaccine lacking binding to FH could reduce pneumococcal colonization, and may have enhanced protection in those with underlying viral infection.


title: Epidemiology of Human Respiratory Viruses in Children with Acute Respiratory Tract Infections in Jinan, China

text: The viral etiologies of UTRIs and LTRIs in children in Jinan city were investigated between July 2009 and June 2010. Nasal and throat swabs were collected from 397 children with URTIs and bronchoalveolar lavage fluid specimens were collected from 323 children with LRTIs. RT-PCR/PCR was used to examine all samples for IFV, PIV, RSV, RV, hMPV, HBoV, CoV, ADV, RSV, and EV. Viral pathogens were detected in 47.10% of URTI samples and 66.57% samples, and the incidence of viral coinfection was 5.29% and 21.05%, respectively. IFV was the most common virus in URTIs, with a detection rate of 19.40%, followed by PIV (10.83%), RV (10.58%), and EV (6.30%). For LRTIs, PIV and RV were both detected in 27% of samples, followed by RSV (9.91%), HBoV (8.36%), IFV (5.57%), and hMPV (5.57%). RSV and HBoV were more prevalent in the youngest children of no more than six months. Meanwhile, RV, PIV, and RSV were the most frequent viruses combined with bacterial pathogens in LRTIs. In conclusion, the spectrum of respiratory virus infections in URTIs and LRTIs differed in terms of the most common pathogens, seasonal distribution, and coinfection rate.


title: The past, present, and future of consumer research

text: In this article, we document the evolution of research trends (concepts, methods, and aims) within the field of consumer behavior, from the time of its early development to the present day, as a multidisciplinary area of research within marketing. We describe current changes in retailing and real-world consumption and offer suggestions on how to use observations of consumption phenomena to generate new and interesting consumer behavior research questions. Consumption continues to change with technological advancements and shifts in consumers’ values and goals. We cannot know the exact shape of things to come, but we polled a sample of leading scholars and summarize their predictions on where the field may be headed in the next twenty years.


title: Contrasted patterns of variation and evolutionary convergence at the antiviral OAS1 gene in old world primates

text: The oligoadenylate synthetase 1 (OAS1) enzyme acts as an innate sensor of viral infection and plays a major role in the defense against a wide diversity of viruses. Polymorphisms at OAS1 have been shown to correlate with differential susceptibility to several infections of great public health significance, including hepatitis C virus, SARS coronavirus, and West Nile virus. Population genetics analyses in hominoids have revealed interesting evolutionary patterns. In Central African chimpanzee, OAS1 has evolved under long-term balancing selection, resulting in the persistence of polymorphisms since the origin of hominoids, whereas human populations have acquired and retained OAS1 alleles from Neanderthal and Denisovan origin. We decided to further investigate the evolution of OAS1 in primates by characterizing intra-specific variation in four species commonly used as models in infectious disease research: the rhesus macaque, the cynomolgus macaque, the olive baboon, and the Guinea baboon. In baboons, OAS1 harbors a very low level of variation. In contrast, OAS1 in macaques exhibits a level of polymorphism far greater than the genomic average, which is consistent with the action of balancing selection. The region of the enzyme that directly interacts with viral RNA, the RNA-binding domain, contains a number of polymorphisms likely to affect the RNA-binding affinity of OAS1. This strongly suggests that pathogen-driven balancing selection acting on the RNA-binding domain of OAS1 is maintaining variation at this locus. Interestingly, we found that a number of polymorphisms involved in RNA-binding were shared between macaques and chimpanzees. This represents an unusual case of convergent polymorphism.


Coronavirus-Pandemie: So werden die Leistungen am Patienten vergütet: Wie Sie an das extrabudgetäre Honorar kommen


title: Nsp1 proteins of group I and SARS coronaviruses share structural and functional similarities

text: Abstract The nsp1 protein of the highly pathogenic SARS coronavirus suppresses host protein synthesis, including genes involved in the innate immune system. A bioinformatic analysis revealed that the nsp1 proteins of group I and SARS coronaviruses have similar structures. Nsp1 proteins of group I coronaviruses interacted with host ribosomal 40S subunit and did not inhibit IRF-3 activation. However, synthesis of host immune and non-immune proteins was inhibited by nsp1 proteins at both transcriptional and translational levels, similar to SARS coronavirus nsp1. These results indicate that different coronaviruses might employ the same nsp1 mechanism to antagonize host innate immunity and cell proliferation. However, nsp1 may not be the key determinant of viral pathogenicity, or the factor used by the SARS coronavirus to evade host innate immunity.


Interaction of Biologically-Relevant Peptides with Membrane Model Systems


title: Arthropods as vectors of transmissible diseases in Spain

text: Abstract Different aspects related to globalization together with the great capacity of the arthropod vectors to adapt to a changing world favour the emergence and reemergence of numerous infectious diseases transmitted by them. Diptera (mosquitoes and sandflies), ticks, fleas and lice, among others, cause a wide spectrum of diseases with relevance in public health. Herein, arthropod-borne disease are reviewed, with special emphasis on the existing risk to contract them in Spain according to different parameters, such as the presence of arthropod and the circulation or the possible circulation of the causative agents.


title: Application of Genetically Engineered Pigs in Biomedical Research

text: Progress in genetic engineering over the past few decades has made it possible to develop methods that have led to the production of transgenic animals. The development of transgenesis has created new directions in research and possibilities for its practical application. Generating transgenic animal species is not only aimed towards accelerating traditional breeding programs and improving animal health and the quality of animal products for consumption but can also be used in biomedicine. Animal studies are conducted to develop models used in gene function and regulation research and the genetic determinants of certain human diseases. Another direction of research, described in this review, focuses on the use of transgenic animals as a source of high-quality biopharmaceuticals, such as recombinant proteins. The further aspect discussed is the use of genetically modified animals as a source of cells, tissues, and organs for transplantation into human recipients, i.e., xenotransplantation. Numerous studies have shown that the pig (Sus scrofa domestica) is the most suitable species both as a research model for human diseases and as an optimal organ donor for xenotransplantation. Short pregnancy, short generation interval, and high litter size make the production of transgenic pigs less time-consuming in comparison with other livestock species This review describes genetically modified pigs used for biomedical research and the future challenges and perspectives for the use of the swine animal models.


title: A novel cognitive interpretation of breast cancer thermography with complementary learning fuzzy neural memory structure

text: Abstract Early detection of breast cancer is the key to improve survival rate. Thermogram is a promising front-line screening tool as it is able to warn women of breast cancer up to 10 years in advance. However, analysis and interpretation of thermogram are heavily dependent on the analysts, which may be inconsistent and error-prone. In order to boost the accuracy of preliminary screening using thermogram without incurring additional financial burden, Complementary Learning Fuzzy Neural Network (CLFNN), FALCON-AART is proposed as the Computer-Assisted Intervention (CAI) tool for thermogram analysis. CLFNN is a neuroscience-inspired technique that provides intuitive fuzzy rules, human-like reasoning, and good classification performance. Confluence of thermogram and CLFNN offers a promising tool for fighting breast cancer.


title: 1,2,3,4,6-Penta-O-galloylglucose within Galla Chinensis Inhibits Human LDH-A and Attenuates Cell Proliferation in MDA-MB-231 Breast Cancer Cells

text: A characteristic feature of aggressive malignancy is the overexpression of lactic acid dehydrogenase- (LDH-) A, concomitant to pericellular accumulation of lactate. In a recent high-throughput screening, we identified Rhus chinensis (Mill.) gallnut (RCG) (also known as Galla Chinensis) extract as a potent (IC(50) < 1 µg/mL) inhibitor of human LDH-A (hLDH-A). In this study, through bioactivity guided fractionation of the crude extract, the data demonstrate that penta-1,2,3,4,6-O-galloyl-β-D-glucose (PGG) was a primary constituent responsible for hLDH-A inhibition, present at ~9.95 ± 0.34% dry weight. Theoretical molecular docking studies of hLDH-A indicate that PGG acts through competitive binding at the NADH cofactor site, effects confirmed by functional enzyme studies where the IC(50) = 27.32 nM was reversed with increasing concentration of NADH. Moreover, we confirm protein expression of hLDH-A in MDA-231 human breast carcinoma cells and show that PGG was toxic (LC(50) = 94.18 µM), parallel to attenuated lactic acid production (IC(50) = 97.81 µM). In a 72-hour cell proliferation assay, PGG was found to be a potent cytostatic agent with ability to halt cell division (IC(50) = 1.2 µM) relative to paclitaxel (IC(50) < 100 nM). In summary, these findings demonstrate that PGG is a potent hLDH-A inhibitor with significant capacity to halt proliferation of human breast cancer cells.


title: Generation and Analysis of Novel Plant-Derived Antibody-Based Therapeutic Molecules against West Nile Virus

text: Previously, our group engineered a plant-derived monoclonal antibody (MAb) (pHu-E16) that efficiently treated West Nile virus (WNV) infection in mice. In this study, we developed several pHu-E16 variants to improve its efficacy. These variants included a single-chain variable fragment (scFv) of pHu-E16 fused to the heavy chain (HC) constant domains (C(H) (1-3)) of human IgG (pHu-E16scFv-C(H) (1-3)) and a tetravalent molecule (Tetra pHu-E16) assembled from pHu-E16scFv-C(H) (1-3) with a second pHu-E16scFv fused to the light chain (LC) constant region. pHu-E16scFv-C(H) (1-3) and Tetra pHu-E16 were efficiently expressed and assembled in plants. To assess the impact of differences in N-linked glycosylation on pHu-E16 variant assembly and function, we expressed additional pHu-E16 variants with various combinations of HC and LC components. Our study revealed that proper pairing of HC and LC was essential for the complete N-glycan processing of antibodies in both plant and animal cells. Associated with their distinct N-glycoforms, pHu-E16, pHu-E16scFv-C(H) (1-3) and Tetra pHu-E16 exhibited differential binding to C1q and specific Fcγ receptors (FcγR). Notably, none of the plant-derived Hu-E16 variants showed antibody-dependent enhancement (ADE) activity in CD32A(+) human cells, suggesting the potential of plant-produced antibodies to minimize the adverse effect of ADE. Importantly, all plant-derived MAb variants exhibited at least equivalent in vitro neutralization and in vivo protection in mice compared to mammalian cell-produced Hu-E16. This study demonstrates the capacity of plants to express and assemble a large, complex and functional IgG-like tetravalent mAb variant and also provides insight into the relationship between MAb N-glycosylation, FcγR and C1q binding, and ADE. These new insights may allow the development of safer and cost effective MAb-based therapeutics for flaviviruses, and possibly other pathogens.


UGANDA: Strict Covid‐19 Measures


title: Ellagic Acid, Kaempferol, and Quercetin from Acacia nilotica: Promising Combined Drug With Multiple Mechanisms of Action

text: The pharmacological activity of Acacia nilotica’s phytochemical constituents was confirmed with evidence-based studies, but the determination of exact targets that they bind and the mechanism of action were not done; consequently, we aim to identify the exact targets that are responsible for the pharmacological activity via the computational methods. Furthermore, we aim to predict the pharmacokinetics (ADME) properties and the safety profile in order to identify the best drug candidates. To achieve those goals, various computational methods were used including the ligand-based virtual screening and molecular docking. Moreover, pkCSM and SwissADME web servers were used for the prediction of pharmacokinetics and safety. The total number of the investigated compounds and targets was 25 and 61, respectively. According to the results, the pharmacological activity was attributed to the interaction with essential targets. Ellagic acid, Kaempferol, and Quercetin were the best A. nilotica’s phytochemical constituents that contribute to the therapeutic activities, were non-toxic as well as non-carcinogen. The administration of Ellagic acid, Kaempferol, and Quercetin as combined drug via the novel drug delivery systems will be a valuable therapeutic choice for the treatment of recent diseases attacking the public health including cancer, multidrug-resistant bacterial infections, diabetes mellitus, and chronic inflammatory systemic disease.


title: Equine Coronavirus-Associated Colitis in Horses: A Retrospective Study

text: Abstract Equine coronavirus (ECoV) is a known cause of fever, anorexia, and lethargy in adult horses. Although there are multiple reports of ECoV outbreaks, less is known about the clinical presentation of individual horses during a nonoutbreak situation. The purpose of this study was to describe the clinical presentation of horses diagnosed with ECoV infection that were not associated with an outbreak. Medical records of all horses admitted to Washington State University, Veterinary Teaching Hospital, during an 8-year period were reviewed (2010–2018). The five horses included in this study were older than 1 year of age, were diagnosed with colitis, tested positive for ECoV using real-time polymerase chain reaction, and were negative to other enteric pathogens. Interestingly, 4 of 5 horses had moderate to severe diarrhea, 3 had abnormal large colon ultrasonography, 2 had transient ventricular tachycardia and 2 had clinicopathologic evidence of liver dysfunction. ECoV should be included as a differential diagnosis for individual horses presenting with anorexia, fever, lethargy, and colitis. Early identification of ECoV cases is key to implement appropriate biosecurity measures to prevent the potential spread of this disease.


title: Estimating the effects of asymptomatic and imported patients on COVID‐19 epidemic using mathematical modeling

text: The epidemic of Coronavirus Disease 2019 has been a serious threat to public health worldwide. Data from 23 January to 31 March at Jiangsu and Anhui provinces in China were collected. We developed an adjusted model with two novel features: the asymptomatic population and threshold behavior in recovery. Unbiased parameter estimation identified faithful model fitting. Our model predicted that the epidemic for asymptomatic patients (ASP) was similar in both provinces. The latent periods and outbreak sizes are extremely sensitive to strongly controlled interventions such as isolation and quarantine for both asymptomatic and imported cases. We predicted that ASP serve as a more severe factor with faster outbreaks and larger outbreak sizes compared with imported patients. Therefore, we argued that the currently strict interventions should be continuously implemented, and unraveling the asymptomatic pool is critically important before preventive strategy such as vaccines.


From the Editor's desk


title: Immediate psychological distress in quarantined patients with COVID-19 and its association with peripheral inflammation: a mixed-method study

text: Since the end of 2019, Corona Virus Disease 2019 (COVID-19) has been the cause of a worldwide pandemic. The mental status of patients with COVID-19 who have been quarantined and the interactions between their psychological distress and physiological levels of inflammation have yet to be analyzed. Using a mixed-method triangulation design (QUAN + QUAL), this study investigated and compared the mental status and inflammatory markers of 103 patients who, while hospitalized with mild symptoms, tested positive with COVID-19 and 103 matched controls that were COVID-19 negative. The severity of depression, anxiety, and post-traumatic stress symptoms (PTSS) was measured via an on-line survey. Using a convenience sampling technique, qualitative data were collected until the point of data saturation. In addition, a semi-structured interview was conducted among five patients with COVID-19. Peripheral inflammatory markers were also collected in patients, both at baseline and within ± three days of completing the on-line survey. Results revealed that COVID-19 patients, when compared to non-COVID controls, manifested higher levels of depression (P < 0.001), anxiety (P < 0.001), and post-traumatic stress symptoms (P < 0.001). A gender effect was observed in the score of “Perceived Helplessness”, the subscale of PSS-10, with female patients showing higher scores compared to male patients (Z = 2.56, P = 0.010), female (Z = 2.37, P = 0.018) and male controls (Z = 2.87, P = 0.004). Levels of CRP, a peripheral inflammatory indicator, correlated positively with the PHQ-9 total score (R = .37, P = 0.003, Spearman’s correlation) of patients who presented symptoms of depression. Moreover, the change of CRP level from baseline inversely correlated with the PHQ-9 total score (R = -0.31, P = 0.002), indicative of improvement of depression symptoms. Qualitative analysis revealed similar results with respect to patient reports of negative feelings, including fear, guilt, and helplessness. Stigma and uncertainty of viral disease progression were two main concerns expressed by COVID-19 patients. Our results indicate that significant psychological distress was experienced by hospitalized COVID-19 patients and that levels of depressive features may be related to the inflammation markers in these patients. Thus, we recommend that necessary measures should be provided to address depression and other psychiatric symptoms for COVID-19 patients and attention should be paid to patient perceived stigma and coping strategies when delivering psychological interventions.


title: A SARS-CoV-2 vaccine candidate: In silico cloning and validation

text: SARS-CoV-2 is spreading globally at a rapid pace. To contain its spread and prevent further fatalities, the development of a vaccine against SARS-CoV-2 is an urgent prerequisite. Thus, in this article, by utilizing the in silico approach, a vaccine candidate for SARS-CoV-2 has been proposed. Moreover, the effectiveness and safety measures of our proposed epitopic vaccine candidate have been evaluated by in silico tools and servers (AllerTOP and AllergenFP servers). We observed that the vaccine candidate has no allergenicity and successfully combined with Toll-like receptor (TLR) protein to elicit an inflammatory immune response. Stable, functional mobility of the vaccine-TLR protein binding interface was confirmed by the Normal Mode Analysis. The in silico cloning model demonstrated the efficacy of the construct vaccine along with the identified epitopes against SARS-CoV-2. Taken together, our proposed in silico vaccine candidate has potent efficacy against COVID-19 infection, and successive research work might validate its effectiveness in in vitro and in vivo models.


SARS‐CoV‐2 and the Liver: Considerations in Hepatitis B and Hepatitis C Infections


title: Chapter 27 Sphenisciformes, Gaviiformes, Podicipediformes, Procellariiformes, and Pelecaniformes

text: Abstract Penguins are flightless seabirds with unique anatomy. Although susceptible to a wide range of diseases, aspergillosis and avian malaria dominate captive mortalities, whereas starvation impacts free-ranging colonies. Gastrointestinal foreign bodies, pododermatitis, drug and heavy metal toxicities are relevant in captivity; oil and algal biotoxicities in the wild. Arthropod-borne, pox-, and herpesviruses are significant for captive and free-ranging populations. Important bacterial diseases include salmonellosis, clostridiosis, and the polymicrobial contribution to penguin diphtheria. Free-ranging populations frequently harbor metazoan parasites but avian malaria is the most clinically important parasitic disease. Many Pelecaniformes, Gaviiformes, Podicipediformes, and Procellariiformes are pelagic species that congregate periodically in nesting colonies or during migration. For free-ranging pelagic species, information derives from infrequent opportunistic screening as sentinels of ocean health and pathogen circulation, and mass mortality events. Birds in captive populations, whose life history differs dramatically, are sparsely represented. Nutritional stress, infectious disease, and toxins contribute to morbidity in congregating birds. Adverse anthropogenic influences (population growth, climate change, environmental pollution, and intensive fishing) pose conservation threats.


title: Whither vaccines?

text: Summary Currently used vaccines have had major effects on eliminating common infections, largely by duplicating the immune responses induced by natural infections. Now vaccinology faces more complex problems, such as waning antibody, immunosenescence, evasion of immunity by the pathogen, deviation of immunity by the microbiome, induction of inhibitory responses, and complexity of the antigens required for protection. Fortunately, vaccine development is now incorporating knowledge from immunology, structural biology, systems biology and synthetic chemistry to meet these challenges. In addition, international organisations are developing new funding and licensing pathways for vaccines aimed at pathogens with epidemic potential that emerge from tropical areas.


title: Effects of distribution of infection rate on epidemic models

text: A goal of many epidemic models is to compute the outcome of the epidemics from the observed infected early dynamics. However, often, the total number of infected individuals at the end of the epidemics is much lower than predicted from the early dynamics. This discrepancy is argued to result from human intervention or nonlinear dynamics not incorporated in standard models. We show that when variability in infection rates is included in standard susciptible-infected-susceptible ([Formula: see text]) and susceptible-infected-recovered ([Formula: see text]) models the total number of infected individuals in the late dynamics can be orders lower than predicted from the early dynamics. This discrepancy holds for [Formula: see text] and [Formula: see text] models, where the assumption that all individuals have the same sensitivity is eliminated. In contrast with network models, fixed partnerships are not assumed. We derive a moment closure scheme capturing the distribution of sensitivities. We find that the shape of the sensitivity distribution does not affect [Formula: see text] or the number of infected individuals in the early phases of the epidemics. However, a wide distribution of sensitivities reduces the total number of removed individuals in the [Formula: see text] model and the steady-state infected fraction in the [Formula: see text] model. The difference between the early and late dynamics implies that in order to extrapolate the expected effect of the epidemics from the initial phase of the epidemics, the rate of change in the average infectivity should be computed. These results are supported by a comparison of the theoretical model to the Ebola epidemics and by numerical simulation.


title: Bioinformatic prediction of potential T cell epitopes for SARS-Cov-2

text: To control and prevent the current COVID-19 pandemic, the development of novel vaccines is an emergent issue. In addition, we need to develop tools that can measure/monitor T-cell and B-cell responses to know how our immune system is responding to this deleterious virus. However, little information is currently available about the immune target epitopes of novel coronavirus (SARS-CoV-2) to induce host immune responses. Through a comprehensive bioinformatic screening of potential epitopes derived from the SARS-CoV-2 sequences for HLAs commonly present in the Japanese population, we identified 2013 and 1399 possible peptide epitopes that are likely to have the high affinity (<0.5%- and 2%-rank, respectively) to HLA class I and II molecules, respectively, that may induce CD8(+) and CD4(+) T-cell responses. These epitopes distributed across the structural (spike, envelope, membrane, and nucleocapsid proteins) and the nonstructural proteins (proteins corresponding to six open reading frames); however, we found several regions where high-affinity epitopes were significantly enriched. By comparing the sequences of these predicted T cell epitopes to the other coronaviruses, we identified 781 HLA-class I and 418 HLA-class II epitopes that have high homologies to SARS-CoV. To further select commonly-available epitopes that would be applicable to larger populations, we calculated population coverages based on the allele frequencies of HLA molecules, and found 2 HLA-class I epitopes covering 83.8% of the Japanese population. The findings in the current study provide us valuable information to design widely-available vaccine epitopes against SARS-CoV-2 and also provide the useful information for monitoring T-cell responses.


title: Individual Monitoring and Occupational Dose Record Management in China: History, Current Status and Perspectives

text: This review paper presents an overview of individual monitoring, as well as the national dose register and dose record management of radiation workers in China. Progress has recently been made on the individual monitoring of radiation workers. A critical analysis of current status and problems in individual monitoring is also presented and necessary future research on individual monitoring, such as the monitoring technology in the form of the ring dosimeters and eye lens dosimeters, is suggested.


title: Strong policies control the spread of COVID‐19 in China

text: OBJECTIVE: The coronavirus disease 2019 (COVID‐19) outbroke in Wuhan, Hubei Province, China, affecting more than 200 countries and regions. This study aimed to predict the development of the epidemic with specific interventional policies applied in China and evaluate their effectiveness. METHODS: COVID‐19 data of Hubei Province and the next five most affected provinces were collected from daily case reports of COVID‐19 on the Health Committee official website of these provinces. The number of current cases, defined as the number of confirmed cases minus the number of cured cases and those who have died, was examined in this study. A modified Susceptible‐Exposed‐Infectious‐ Removed (SEIR) model was used to assess the effects of interventional policies on the epidemic. In this study, January 28 was day zero of the model. RESULTS: The results of the modified SEIR model showed that the number of current cases in Hubei and Zhejiang provinces tended to be stabilized after 70 days and after 60 days in the four other provinces. The predicted number of current cases without policy intervention was shown to far exceed that with policy intervention. The estimated number of COVID‐19 cases in Hubei Province with policy intervention was predicted to peak at 51,222, whereas that without policy intervention was predicted to reach 157,721. CONCLUSION: Based on the results of the model, strong interventional policies were found to be vital components of epidemic control. Applying such policies is likely to shorten the duration of the epidemic and reduce the number of new cases. This article is protected by copyright. All rights reserved.


title: Establishment of Vero E6 cell clones persistently infected with severe acute respiratory syndrome coronavirus

text: Abstract Little information is available on persistent infection of severe acute respiratory syndrome (SARS) coronavirus (CoV). In this study, we established persistent infection of SARS-CoV in the Vero E6 cell line. Acute infection of Vero E6 with SARS-CoV produced a lytic infection with characteristic rounding cytopathic effects (CPE) and the production of a large number of infectious particles in the culture fluid within 3 days post-infection. Upon subsequent culturing of the remaining adherent cells, the cells gradually proliferated and recovered normal morphology similar to that of the parental cells, and continued to produce large numbers of infectious viral particles during the observation period of 5 months. Among a total of 87 cell clones obtained from the persistently infected Vero E6, only four cell clones (named #13, #18, #21, and #34) were positive for viral RNA. Clones #13, #18, and #34 shifted to viral RNA-negative during subsequent cultures, while #21 continuously produced infectious particles at a high rate. The SARS-CoV receptor, angiotensin-converting enzyme 2, was almost completely down regulated from the cell surface of persistently infected cells. Western blot analysis as well as electron microscopy indicated that the ratios of spike to nucleocapsid protein in clone #21 as well as its parental persistently infected cells were lower than that in the cells in the acute phase of infection. These Vero E6 cells persistently infected with SARS-CoV may be useful for clarifying the mechanism of the persistent infection and also for elucidating the possible pathophysiologic significance of such long-term maintenance of this virus.


title: Acute Exacerbation of Idiopathic Pulmonary Fibrosis

text: Abstract Acute exacerbation is a major cause of morbidity and mortality in patients with idiopathic pulmonary fibrosis. Although the real nature of it is still not clear and there is no proven effective therapy, progress has been made since the consensus definition and diagnostic criteria were proposed. The trial results of several new innovative therapies in idiopathic pulmonary fibrosis have suggested a potential for benefit in acute exacerbation of idiopathic pulmonary fibrosis, leading to double blind randomized clinical trials in this area. This article reviews the present knowledge on acute exacerbation of idiopathic pulmonary fibrosis, focusing on the triggering factors and treatment.


title: Potential Beneficial Actions of Fucoidan in Brain and Liver Injury, Disease, and Intoxication—Potential Implication of Sirtuins

text: Increased interest in natural antioxidants has brought to light the fucoidans (sulfated polysaccharides present in brown marine algae) as highly valued nutrients as well as effective and safe therapeutics against several diseases. Based on their satisfactory in vitro antioxidant potency, researchers have identified this molecule as an efficient remedy for neuropathological as well as metabolic disorders. Some of this therapeutic activity is accomplished by upregulation of cytoprotective molecular pathways capable of restoring the enzymatic antioxidant activity and normal mitochondrial functions. Sirtuin-3 has been discovered as a key player for achieving the neuroprotective role of fucoidan by managing these pathways, whose ultimate goal is retrieving the entirety of the antioxidant response and preventing apoptosis of neurons, thereby averting neurodegeneration and brain injuries. Another pathway whereby fucoidan exerts neuroprotective capabilities is by interactions with P-selectin on endothelial cells, thereby preventing macrophages from entering the brain proper. Furthermore, beneficial influences of fucoidan have been established in hepatocytes after xenobiotic induced liver injury by decreasing transaminase leakage and autophagy as well as obtaining optimal levels of intracellular fiber, which ultimately prevents fibrosis. The hepatoprotective role of this marine polysaccharide also includes a sirtuin, namely sirtuin-1 overexpression, which alleviates obesity and insulin resistance through suppression of hyperglycemia, reducing inflammation and stimulation of enzymatic antioxidant response. While fucoidan is very effective in animal models for brain injury and neuronal degeneration, in general, it is accepted that fucoidan shows somewhat limited potency in liver. Thus far, it has been used in large doses for treatment of acute liver injuries. Thus, it appears that further optimization of fucoidan derivatives may establish enhanced versatility for treatments of various disorders, in addition to brain injury and disease.


title: EAACI position statement on asthma exacerbations and severe asthma

text: Asthma exacerbations and severe asthma are linked with high morbidity, significant mortality and high treatment costs. Recurrent asthma exacerbations cause a decline in lung function and, in childhood, are linked to development of persistent asthma. This position paper, from the European Academy of Allergy and Clinical Immunology, highlights the shortcomings of current treatment guidelines for patients suffering from frequent asthma exacerbations and those with difficult‐to‐treat asthma and severe treatment‐resistant asthma. It reviews current evidence that supports a call for increased awareness of (i) the seriousness of asthma exacerbations and (ii) the need for novel treatment strategies in specific forms of severe treatment‐resistant asthma. There is strong evidence linking asthma exacerbations with viral airway infection and underlying deficiencies in innate immunity and evidence of a synergism between viral infection and allergic mechanisms in increasing risk of exacerbations. Nonadherence to prescribed medication has been identified as a common clinical problem amongst adults and children with difficult‐to‐control asthma. Appropriate diagnosis, assessment of adherence and other potentially modifiable factors (such as passive or active smoking, ongoing allergen exposure, psychosocial factors) have to be a priority in clinical assessment of all patients with difficult‐to‐control asthma. Further studies with improved designs and new diagnostic tools are needed to properly characterize (i) the pathophysiology and risk of asthma exacerbations, and (ii) the clinical and pathophysiological heterogeneity of severe asthma.


title: Polmoniti nosocomiali acquisite sotto ventilazione meccanica

text: Le polmoniti sono la prima causa di infezione nosocomiale in rianimazione. Le polmoniti nosocomiali acquisite sotto ventilazione meccanica (PNAVM) compaiono dopo almeno 48 ore di ventilazione meccanica invasiva. Il loro meccanismo è multifattoriale, ma predomina la nozione di inalazione che compare dopo una colonizzazione orofaringea, gastrica o tracheale. Il tempo di comparsa permette di classificare queste PNAVM come precoci o tardive a seconda che compaiano prima o dopo il 5° giorno di ventilazione meccanica. La diagnosi può essere aiutata dalla clinica, essenzialmente grazie al punteggio CPIS (Clinical Pulmonary Infection Score), e dal lavaggio broncoalveolare (BAL), che sembra l’esame più utile per la diagnosi microbiologica. La diagnosi differenziale con una pneumopatia non batterica o anche non infettiva (neoplastica, infiammatoria, fibrotica) o la ricerca di un altro focolaio infettivo devono sempre essere discusse in funzione dell’orientamento clinico iniziale o del fallimento della terapia antibiotica. Il ricorso preferenziale alla ventilazione non invasiva, quando possibile, sembra utile per prevenire l’insorgenza di una pneumopatia nosocomiale. La posizione semiseduta del paziente a 30–45° è la sola misura profilattica veramente validata di prevenzione delle PNAVM. Il trattamento curativo delle polmoniti batteriche si basa in genere su una doppia terapia antibiotica. Quest’ultima può essere orientata dai dati di prelievi non invasivi, come le aspirazioni tracheali, realizzate in modo periodico e sistematico. La durata del trattamento è discussa, ma gli ultimi dati sono in favore di una terapia antibiotica relativamente breve, di 8 giorni.


Global infectious diseases—The new norm for the United States?


title: Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review

text: Essential oils are complex mixtures isolated from aromatic plants which may possess antioxidant and anti-inflammatory activities of interest in thye food and cosmetic industries as well as in the human health field. In this work, a review was done on the most recent publications concerning their antioxidant and anti-inflammatory activities. At the same time a survey of the methods generally used for the evaluation of antioxidant activity and some of the mechanisms involved in the anti-inflammatory activities of essential oils are also reported.


title: Managing haematology and oncology patients during the COVID‐19 pandemic: interim consensus guidance

text: INTRODUCTION: A pandemic coronavirus, SARS‐CoV‐2, causes COVID‐19, a potentially life‐threatening respiratory disease. Patients with cancer may have compromised immunity due to their malignancy and/or treatment, and may be at elevated risk of severe COVID‐19. Community transmission of COVID‐19 could overwhelm health care services, compromising delivery of cancer care. This interim consensus guidance provides advice for clinicians managing patients with cancer during the pandemic. MAIN RECOMMENDATIONS: During the COVID‐19 pandemic: In patients with cancer with fever and/or respiratory symptoms, consider causes in addition to COVID‐19, including other infections and therapy‐related pneumonitis. For suspected or confirmed COVID‐19, discuss temporary cessation of cancer therapy with a relevant specialist. Provide information on COVID‐19 for patients and carers. Adopt measures within cancer centres to reduce risk of nosocomial SARS‐CoV‐2 acquisition; support population‐wide social distancing; reduce demand on acute services; ensure adequate staffing; and provide culturally safe care. Measures should be equitable, transparent and proportionate to the COVID‐19 threat. Consider the risks and benefits of modifying cancer therapies due to COVID‐19. Communicate treatment modifications, and review once health service capacity allows. Consider potential impacts of COVID‐19 on the blood supply and availability of stem cell donors. Discuss and document goals of care, and involve palliative care services in contingency planning. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: This interim consensus guidance provides a framework for clinicians managing patients with cancer during the COVID‐19 pandemic. In view of the rapidly changing situation, clinicians must also monitor national, state, local and institutional policies, which will take precedence. ENDORSED BY: Australasian Leukaemia and Lymphoma Group; Australasian Lung Cancer Trials Group; Australian and New Zealand Children's Haematology/Oncology Group; Australia and New Zealand Society of Palliative Medicine; Australasian Society for Infectious Diseases; Bone Marrow Transplantation Society of Australia and New Zealand; Cancer Council Australia; Cancer Nurses Society of Australia; Cancer Society of New Zealand; Clinical Oncology Society of Australia; Haematology Society of Australia and New Zealand; National Centre for Infections in Cancer; New Zealand Cancer Control Agency; New Zealand Society for Oncology; and Palliative Care Australia.


title: The cellular protein nucleolin preferentially binds long-looped G-quadruplex nucleic acids()

text: BACKGROUND: G-quadruplexes (G4s) are four-stranded nucleic acid structures that form in G-rich sequences. Nucleolin (NCL) is a cellular protein reported for its functions upon G4 recognition, such as induction of neurodegenerative diseases, tumor and virus mechanisms activation. We here aimed at defining NCL/G4 binding determinants. METHODS: Electrophoresis mobility shift assay was used to detect NCL/G4 binding; circular dichroism to assess G4 folding, topology and stability; dimethylsulfate footprinting to detect G bases involved in G4 folding. RESULTS: The purified full-length human NCL was initially tested on telomeric G4 target sequences to allow for modulation of loop, conformation, length, G-tract number, stability. G4s in promoter regions with more complex sequences were next employed. We found that NCL binding to G4s heavily relies on G4 loop length, independently of the conformation and oligonucleotide/loop sequence. Low stability G4s are preferred. When alternative G4 conformations are possible, those with longer loops are preferred upon binding to NCL, even if G-tracts need to be spared from G4 folding. CONCLUSIONS: Our data provide insight into how G4s and the associated proteins may control the ON/OFF molecular switch to several pathological processes, including neurodegeneration, tumor and virus activation. Understanding these regulatory determinants is the first step towards the development of targeted therapies. GENERAL SIGNIFICANCE: The indication that NCL binding preferentially stimulates and induces folding of G4s containing long loops suggests NCL ability to modify the overall structure and steric hindrance of the involved nucleic acid regions. This protein-induced modification of the G4 structure may represent a cellular mechanosensor mechanism to molecular signaling and disease pathogenesis. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.


title: Reduction of porcine reproductive and respiratory syndrome virus (PRRSV) infection in swine alveolar macrophages by porcine circovirus 2 (PCV2)-induced interferon-alpha

text: Abstract Two common viral pathogens of swine, namely, porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV), were investigated in regard to their effects on monolayer cultures of swine alveolar macrophages (AMs). The purpose was to identify selected cellular changes and responses potentially associated with the clinical reactions of pigs infected with either or both of these viruses. Measurements included the (1) absolute and relative numbers of infected, viable, and apoptotic cells; (2) distribution of viral antigens; (3) levels of interferon-alpha (IFN-α) and tumor necrosis factor-alpha (TNF-α) produced and their association with the extent of virus-induced cytopathology. Four groups of AMs were studied, including mock-infected, PCV2 alone-infected (PCV2-A), PRRSV alone-infected (PRRSV-A), and PCV2 and PRRSV dually infected (PCV2/PRRSV) groups. The AMs of PCV2-A group had high antigen-containing rate without cell death. There was a marked increase in cell death and apoptosis in PRRSV-A group. However, a lower PRRSV-induced infectious rate, cell death, and apoptosis were seen in PCV2/PRRSV group. High levels of IFN-α production were detected in PCV2-infected groups, but not in mock-infected and PRRSV-A groups. The PRRSV-induced cytopathic effect (CPE) on MARC-145 cells or swine AMs was markedly reduced by pre-incubation of the cells with UV-treated or non-UV-treated supernatants of PCV2-infected AMs. In addition, the reduction in CPE was abolished when the supernatants of PCV2-infected AMs were pre-treated with a mouse anti-recombinant porcine IFN-α antibody. The results suggest that swine AMs were an important reservoir of PCV2; PCV2 infection reduced PRRSV infection and PRRSV-associated CPE in PCV2/PRRSV AMs; the reduction of PRRSV infection in AMs was mediated by IFN-α generated by PCV2 infection. The reduced PRRSV-associated CPE in AMs and increased pro-inflammatory cytokine production may lead to a more severe pneumonic lesion in those dually infected pigs.


title: Construction of recombinant Lactobacillus casei efficiently surface displayed and secreted porcine parvovirus VP2 protein and comparison of the immune responses induced by oral immunization

text: Lactobacillus casei ATCC 393 was selected as a bacterial carrier for the development of mucosal vaccine against porcine parvovirus (PPV) infection. The PPV major structural polypeptide VP2 was used as the model parvovirus antigen. Two inducible expression systems, namely pPG611.1 of the cell-surface expression system and pPG612.1 of the secretion expression system based on the xylose operon promoter were used to express the VP2 protein. The immunogenicity of recombinant strains producing VP2 protein in two cellular locations, cell-surface exposed and secreted, was compared to each other by immunizing mice through the intragastric administration. The two types of constructs were able to induce strong specific immune responses against VP2 via intragastric administration and maximum titres of IgA and IgG were attained on days 46 post oral immunization, while the highest antibody levels were obtained with the strain producing the VP2 protein in extracellular milieu. The induced antibodies demonstrated neutralizing effects on PPV infection.


title: Map location of lactate dehydrogenase-elevating virus (LDV) capsid protein (Vpl) gene

text: Abstract Lactate dehydrogenase-elevating virus (LDV) is currently classified within the Togaviridae family. In an effort to obtain further information on the characteristics of this virus, we have begun to sequence the viral RNA genome and to map the virion structural protein genes. A sequence of 1064 nucleotides, which represents the 3′ terminal end of the genome, was obtained from LDV cDNA clones. A 3′ noncoding region of 80 nucleotides followed by two complete open reading frames (ORFs) were found within this sequence. The two ORFs were in different reading frames and overlapped each other by 11 nucleotides. One ORF encoded a protein of 170 amino acids and the other ORF, located adjacent to the 3′ noncoding region of the viral genome, encoded a 114 amino acid protein. Thirty-three N-terminal residues were sequenced directly from purified LDV capsid protein, Vpi, and this amino acid sequence mapped to the ORF adjacent to the 3′ noncoding region. The presence of overlapping ORFs and the 3′ terminal map position of Vpi indicate that LDV differs significantly from the prototype alpha togaviruses.


title: Photosensitizing potential of tailored magnetite hybrid nanoparticles functionalized with levan and zinc (II) phthalocyanine

text: Abstract Phototherapies, including photodynamic therapy (PDT), have been widely used in the treatment of various diseases, especially for cancer. However, there is still a lack of effective, safe photosensitizers that would be well tolerated by patients. The combination of several methods (like phototherapy and hyperthermia) constitutes a modern therapeutic approach, which demands new materials based on components that are non-toxic without irradiation. Therefore, this study presents the synthesis and properties of novel, advanced nanomaterials in which the advantage features of the magnetic nanoparticles and photoactive compounds were combined. The primary purpose of this work was the synthesis of magnetic nanoparticles coated with biocompatible and antitumor polysaccharide - levan, previously unknown from scientific literature, and the deposition of potent photosensitizer – zinc(II) phthalocyanine on their surface. In order to better characterize the nature of the coating covering the magnetic core, the atomic force microscope analysis, a contact angle measurement, and the mechanical properties of pure levan and its blend with zinc(II) phthalocyanine films were investigated. This magnetic nanomaterial revealed the ability to generate singlet oxygen upon exposure to light. Finally, preliminary toxicity of obtained nanoparticles was tested using the Microtox® test – with and without irradiation.


title: From Orange Juice By-Product in the Food Industry to a Functional Ingredient: Application in the Circular Economy

text: In the orange juice industry, more than 50% of raw material becomes by-products that are rich in active compounds and have high nutritional content. Improved use of these by-products could represent a key strategy for a circular economy. The objective of this study was to produce a flour from orange juice by-product, characterize it, and then apply this flour to produce cookies. Orange by-product flour (OBPF) was characterized in terms of its chemical composition, dietary fiber, phenolic compounds, antioxidant potential, and hygroscopic properties. Subsequently, the effect of substituting wheat flour by OBPF in cookies was evaluated. OBPF presented a very high content of dietary fiber (73.61% dry matter (DM)), minerals (ash = 2.72% DM), and total phenolic compounds (534 ± 30 mg gallic acid equivalent (GAE)/100 g of DM). In general, the properties of cookies were not significantly influenced by using OBPF as a substitution for wheat flour. Sensorial analyses showed that cookies produced with 10% OBPF presented the higher scores. Therefore, OBPF showed interesting characteristics, suggesting its possible use in the development of fiber enriched foods such as cookies; and its production represents a key strategy for the orange juice processing industries towards the application of a circular economy in the food system.


title: Smell and taste disorders during COVID‐19 outbreak: A cross‐sectional study on 355 patients

text: BACKGROUND: As reported by increasing literature, a significant number of patients with SARS‐CoV‐2 infection developed smell/taste disorders. Aim of this study is to determine the prevalence and severity of these symptoms among laboratory‐confirmed SARS‐CoV‐2 patients. Secondary objective is to determine their onset/recovery time. METHODS: This cross‐sectional study was conducted from March 10 to 30, 2020 at Novara University Hospital during the COVID‐19 Italian outbreak. The 355 enrolled patients answered a questionnaire at 14th (or more) days after proven infection. RESULTS: The overall population prevalence of both smell/taste or one of the two disorders was 70%. They were first symptoms in 31 (8,7%) patients. Most patients reported a complete loss that in half of the cases (49.5%) was fully recovered after 14 days, with a median recovery time of 10 days. CONCLUSION: This study confirms a high prevalence of smell/taste disorders in COVID‐19 infection with self‐recovery for half cases after about 2 weeks.


Opportunities for Nursing Science to Advance Patient Care in the Time of COVID‐19: A Palliative Care Perspective


title: Manipulation of Intestinal Antiviral Innate Immunity and Immune Evasion Strategies of Porcine Epidemic Diarrhea Virus

text: Porcine epidemic diarrhea virus (PEDV) infection causes watery diarrhea, dehydration, and high mortality in neonatal pigs, due to its clinical pathogenesis of the intestinal mucosal barrier dysfunction. The host's innate immune system is the first line of defence upon virus invasion of the small intestinal epithelial cells. In turn, the virus has evolved to modulate the host's innate immunity during infection, resulting in pathogen virulence, survival, and the establishment of successful infection. In this review, we gather current knowledge concerning the interplay between PEDV and components of host innate immunity, focusing on the role of cytokines and interferons in intestinal antiviral innate immunity, and the mechanisms underlying the immune evasion strategies of PEDV invasion. Finally, we provide some perspectives on the potential prevention and treatment for PEDV infection.


Second isirv antiviral group conference: overview


Heart failure management during COVID‐19 outbreak in Italy. Telemedicine experience from a heart failure university tertiary referral centre


title: Brief report: International perspectives on the pediatric COVID‐19 experience

text: The 2019 novel coronavirus (SARS‐CoV‐2) is endangering human health worldwide; scarcity of published pediatric cases and current literature and the absence of evidence‐based guidelines necessitate international sharing of experience and personal communication. On 31 March 2020 the International Committee of the American Thoracic Society Pediatrics Assembly recorded an online podcast, during which pediatric pulmonologists worldwide shared their experience on the novel coronavirus disease (COVID‐19) in children. The aim was to share personal experience in organizing pediatric care in different health care settings globally, protecting health care workers, and isolation practices. This manuscript summarizes the common themes of the podcast which centered around three main topics: more benign clinical disease and progression in pediatric cases compared to adults, a strong need for strategies to protect health care workers, and social or economic disparities as a barrier to successful pandemic control.


title: Molecular epidemiology of rubella viruses involved in congenital rubella infections in São Paulo, Brazil, between 1996 and 2009

text: Rubella virus (RV) infection during the early stages of pregnancy can lead to serious birth defects, known as congenital rubella syndrome (CRS). This retrospective study was conducted between 1996 and 2009 with surveillance specimens collected from patients suspected of congenital rubella infection (CRI) and CRS. The clinical samples (nine amminiotic fluid, eight urine, eight blood, one conception product, and one placenta) were sent for viral isolation and genotyping. Twenty‐seven sequences were analysed and four genotypes (1a, 1B, 1G, and 2B) were identified in São Paulo that were involved in congenital infection. To our knowledge, this study is the first report that describes genetic diversity of the circulating rubella strains involved in CRI. J Med. Virol. 85:2034–2041, 2013. © 2013 Wiley Periodicals, Inc.


title: Detection of the nucleocapsid protein of severe acute respiratory syndrome coronavirus in serum: Comparison with results of other viral markers

text: Abstract A capture enzyme-enhanced chemiluminescence immunoassay (ECLIA) based on three specific monoclonal antibodies to detect the nucleocapsid (N) protein of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in the serial serum samples from SARS patients was developed. The anti-SARS-CoV IgG and the viral RNA were also detected in the sera by ELISA and RT-PCR, respectively. During the first 10 days after onset, anti-SARS-CoV IgG, SARS-CoV RNA and the N protein were detected in 21.4, 42.9, and 90% of the patients’ sera, respectively. The detection rate of the N protein during days 11–15 of the disease was still significantly higher than those of anti-SARS-CoV IgG and SARS-CoV RNA. The data demonstrated that detection of the N protein with the capture ECLIA appears to be more useful than detection of other viral makers for rapid diagnosis of SARS in patients.


title: No Effect of a Homeopathic Preparation on Neonatal Calf Diarrhoea in a Randomised Double-Blind, Placebo-Controlled Clinical Trial

text: A double-blind, placebo-controlled clinical trial of a homeopathic treatment of neonatal calf diarrhoea was performed using 44 calves in 12 dairy herds. Calves with spontaneously derived diarrhoea were treated with either the homeopathic remedy Podophyllum (D30) (n = 24) or a placebo (n = 20). No clinically or statistically significant difference between the 2 groups was demonstrated. Calves treated with Podophyllum had an average of 3.1 days of diarrhoea compared with 2.9 days for the placebo group. Depression, inappetence and fever were presented equally in the 2 groups. These results support the widely held opinion that scientific proof for the efficacy of veterinary homeopathy is lacking. In the European Union this implies a considerable risk for animal welfare, since in some countries priority is given to homeopathic treatments in organic farming.


Infection control in countries with limited resources


title: The N-terminal heptad repeat region of reovirus cell attachment protein σ1 is responsible for σ1 oligomer stability and possesses intrinsic oligomerization function

text: Abstract The oligomerization domain of the reovirus cell attachment protein (σ1) was probed using the type 3 reovirus of synthesized in vitro. Trypsin cleaved the α1 protein (49K molecular weight) approximately in the middle and yielded a 26K N-terminal fragment and a 23K C-terminal fragment. Under conditions which allowed for the identification of intact σ1 in the oligomeric form (∼200K) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the N-terminal 26K fragment was found to exist as stable trimers (80K) and, to a less extent, as dimers (54K), whereas the C-terminal fragment remained in the monomeric form. A polypeptide (161 amino acids) containing the N-terminal heptad repeat region synthesized in vitro was capable of forming stable dimers and trimers. Using various criteria, we demonstrated that the stability of the intact σ1 oligomer is conferred mainly by the N-terminal heptad repeat region. Our results are summarized in a model in which individual heptad repeats are held together in a three-stranded α-helical coiled-coil structure via both hydrophobic and electrostatic interactions.


title: The development of vaccines against SARS corona virus in mice and SCID-PBL/hu mice

text: We have investigated to develop novel vaccines against SARS CoV using cDNA constructs encoding the structural antigen; spike protein (S), membrane protein (M), envelope protein (E), or nucleocapsid (N) protein, derived from SARS CoV. Mice vaccinated with SARS-N or -M DNA using pcDNA 3.1(+) plasmid vector showed T cell immune responses (CTL induction and proliferation) against N or M protein, respectively. CTL responses were also detected to SARS DNA-transfected type II alveolar epithelial cells (T7 cell clone), which are thought to be initial target cells for SARS virus infection in human. To determine whether these DNA vaccines could induce T cell immune responses in humans as well as in mice, SCID-PBL/hu mice was immunized with these DNA vaccines. As expected, virus-specific CTL responses and T cell proliferation were induced from human T cells. SARS-N and SARS-M DNA vaccines and SCID-PBL/hu mouse model will be important in the development of protective vaccines.


Monitor sewage to track spread of the coronavirus


title: A 72-Year-Old Woman With Respiratory Failure and Bilateral Ground-Glass Opacities

text: A 72-year-old woman with diabetes mellitus was admitted to our hospital because of dyspnea on exertion. Sputum cytologic evaluation revealed intranuclear inclusion bodies in the cells; we therefore considered viral pneumonia and performed a bronchoscopy. The bronchial washing fluid was positive for immunoperoxidase staining of herpes simplex virus type 1 (HSV1) and HSV1 polymerase chain reaction. The patient was diagnosed as having pneumonia due to HSV1 and was successfully treated with acyclovir.


title: Potential roles of social distancing in mitigating the spread of coronavirus disease 2019 (COVID-19) in South Korea

text: On January 20, 2020, the first COVID-19 case was confirmed in South Korea. After a rapid outbreak, the number of incident cases has been consistently decreasing since early March; this decrease has been widely attributed to its intensive testing. We report here on the likely role of social distancing in reducing transmission in South Korea. Our analysis suggests that transmission may still be persisting in some regions.


title: Nucleocapsid Interacts with NPM1 and Protects it from Proteolytic Cleavage, Enhancing Cell Survival, and is Involved in PEDV Growth

text: Porcine epidemic diarrhea virus (PEDV) replicates in the cytoplasm of infected cells, but its nucleocapsid (N) protein localizes specifically to the nucleolus. The mechanism of nuclear translocation, and whether N protein associates with particular nucleolar components, is unknown. In this study, we confirm that a nucleolar phosphoprotein nucleophosmin (NPM1) interacts and co-localizes with the N protein in the nucleolus. In vitro binding studies indicated that aa 148–294 of N and aa 118–188 of NPM1 were required for binding. Interestingly, N protein importation into the nucleolus is independent of the ability of NPM1 to shuttle between the nucleus and the cytoplasm. Furthermore, overexpression of NPM1 promoted PEDV growth, while knockdown of NPM1 suppressed PEDV growth. In addition, binding of N protein to NPM1 protects it from proteolytic degradation by caspase-3, leading to increased cell survival. Taken together, our studies demonstrate a specific interaction of the N protein with the host cell protein NPM1 in the nucleolus. The results suggest potential linkages among viral strategies for the regulation of cell survival activities, possibly through an interaction of N protein with NPM1 which prevents its proteolytic cleavage and enhances cell survival, thus ultimately promoting the replication of PEDV.


title: Evaluation of multiple ancillary therapies used in combination with an antimicrobial in newly received high-risk calves treated for bovine respiratory disease

text: Ancillary therapy (ANC) is commonly provided in conjunction with an antimicrobial when treating calves for suspected bovine respiratory disease (BRD) in an attempt to improve the response to a suspected BRD challenge. The first experiment evaluated the effects of 3 ANC in combination with an antimicrobial in high-risk calves treated for BRD during a 56-d receiving period. Newly received crossbred steers (n = 516; initial BW = 217 ± 20 kg) were monitored by trained personnel for clinical signs of BRD. Calves that met antimicrobial treatment criteria (n = 320) were then randomly assigned to experimental ANC treatment (80 steers/experimental ANC treatment): intravenous flunixin meglumine injection (NSAID), intranasal viral vaccination (VACC), intramuscular vitamin C injection (VITC), or no ANC (NOAC). Animal served as the experimental unit for all variables except DMI and G:F (pen served as the experimental unit for DMI and G:F). Within calves treated 3 times for BRD, those receiving NOAC had lower (P < 0.01) clinical severity scores (severity scores ranged from 0 to 4 on the basis of observed clinical signs and severity) and heavier (P = 0.01) BW than those receiving NSAID, VACC, or VITC at the time of third treatment. Between the second and third BRD treatments, calves receiving NOAC had decreased (P < 0.01) daily BW loss (−0.13 kg ADG) compared with those receiving NSAID, VACC, or VITC (−1.30, −1.90, and −1.41 kg ADG, respectively). There were no differences in rectal temperature, combined mortalities and removals, or overall performance among the experimental ANC treatments. Overall, morbidity and mortality attributed to BRD across treatments were 66.5% and 13.2%, respectively. After the receiving period, a subset of calves (n = 126) were allocated to finishing pens to evaluate the effects ANC administration on finishing performance, carcass characteristics, and lung scores at harvest. Ultrasound estimates, BW, and visual appraisal were used to target a common physiological end point for each pen of calves. There were no differences among the experimental ANC observed during the finishing period (P ≥ 0.11). In summary, the use of NSAID, VACC, and VITC do not appear to positively impact clinical health and could potentially be detrimental to performance during the receiving period in high-risk calves receiving antimicrobial treatment for suspected BRD.


Quantifying examination distance in ophthalmic assessments


title: A Contemporary Review of Neurological Sequelae of COVID-19

text: Coronavirus 2019 (COVID-19) is currently the center of what has become a public health crisis. While the virus is well-known for its trademark effects on respiratory function, neurological damage has been reported to affect a considerable proportion of severe cases. To characterize the neuro-invasive potential of this disease, a contemporary review of COVID-19 and its neurological sequelae was conducted using the limited, but growing, literature that is available. These neurological squeal are based on the manifestations that the virus has on normal central and peripheral nervous system function. The authors present the virology of the SARS-CoV-2 agent by analyzing its classification as an enveloped, positive-stranded RNA virus. A comprehensive timeline is then presented, indicating the progression of the disease as a public health threat. Furthermore, underlying chronic neurological conditions potentially lead to more adverse cases of COVID-19. SARS-CoV-2 may reach ACE2 receptors on neuronal tissue through mode of the general circulation. The CNS may also be susceptible to an immune response where a “cytokine storm” can manifest into neural injury. Histological evidence is provided, while symptoms such as headache and vertigo are highlighted as CNS manifestations of COVID-19. Treatment of these symptoms is addressed with paracetamol being recommended as a possible, but not conclusive, treatment to some CNS symptoms. The authors then discuss the peripheral nervous system sequelae and COVID's impact on causing chemosensory dysfunction starting with viral attack on olfactory sensory neurons and cells types within the lining of the nose. Histological evidence is also provided while symptoms such as anosmia and ageusia are characterized as PNS manifestations. Possible treatment options for these symptoms are then addressed as a major limitation, as anecdotal, and not conclusive evidence can be made. Finally, preventive measures of the neurological sequelae are addressed using a multidirectional approach. Postmortem examinations of the brains of COVID-19 patients are suggested as being a possible key to formulating new understandings of its neuropathology. Lastly, the authors suggest a more comprehensive neurological follow-up of recovered patients, in order to better characterize the neurological sequelae of this illness.


title: Nurses' willingness to take care of people living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) — does a teaching intervention make a difference?

text: The aim of this study is to describe the impact of an education intervention programme on nurses' willingness to care for HIV-positive people in Lithuania. METHODS: The study utilizes a randomized controlled trial design (RCT). The total sample comprises 185 nurses working in medical, surgical and gynaecological units, and primary health care centres from the same hospital areas in three Lithuanian hospitals. The data were analyzed using SPSS 12.0 and descriptive statistics. FINDINGS: Our educational intervention did not have an impact on the nurses' willingness to take care of people living with HIV (PLHIV), as their level of willingness was high already before the education intervention. CONCLUSIONS: Further research on this issue is needed to try to understand the forces acting on our nursing staff in order to ensure appropriate care for PLHIV.


title: Home and Community-Based Physical Therapist Management of Adults With Post–Intensive Care Syndrome

text: More than 4 million adults survive a stay in the intensive care unit each year, with many experiencing new or worsening physical disability, mental health problems, and/or cognitive impairments, known as the post-intensive care syndrome (PICS). Given the prevalence and magnitude of physical impairments after critical illness, many survivors, including those recovering from COVID-19, could benefit from physical therapist services after hospital discharge. However, due to the relatively recent recognition and characterization of PICS, there may be limited awareness and understanding of PICS among physical therapists practicing in home healthcare and community-based settings. This lack of awareness may lead to inappropriate and/or inadequate rehabilitation service provision. While this perspective article provides information relevant to all physical therapists, it is aimed toward those providing rehabilitation services outside of the acute and post-acute inpatient settings. This article reports the prevalence and clinical presentation of PICS and provides recommendations for physical examination and outcomes measures, plan of care, and intervention strategies. The importance of providing patient and family education, coordinating community resources including referring to other healthcare team members, and community-based rehabilitation service options is emphasized. Finally, this perspective article discusses current challenges for optimizing outcomes for people with PICS and suggests future directions for research and practice.


title: Combining genetic and biochemical approaches to identify functional molecular contact points

text: Protein-protein interactions are required for many viral and cellular functions and are potential targets for novel therapies. Here we detail a series of genetic and biochemical techniques used in combination to find an essential molecular contact point on the duck hepatitis B virus polymerase. These techniques include differential immunoprecipitation, mutagenesis and peptide competition. The strength of these techniques is their ability to identify contact points on intact proteins or protein complexes employing functional assays. This approach can be used to aid identification of putative binding sites on proteins and protein complexes which are resistant to characterization by other methods.


title: Enhanced expression of TGFβ protein in lymphoid organs and lung, but not in serum, of pigs infected with a European field isolate of porcine reproductive and respiratory syndrome virus

text: Abstract Transforming growth factor β (TGFβ) is an immunomodulatory cytokine which is able to modulate the host immune response eliciting an inefficient response against pathogens. In this sense, the role of this cytokine in porcine reproductive and respiratory syndrome (PRRS) has been poorly studied and the reported results are contradictory. Thus, in the present study, the expression of TGFβ was analysed both at tissue (lymphoid organs and lung) and serum level to study its correlation with the expression of PRRS virus (PRRSV). To carry out this study, 32 pigs were inoculated with the European PRRSV field isolate 2982 and sequentially killed from 0dpi to the end of the study (24dpi). Blood and tissue samples were collected to determine the expression of PRRSV and TGFβ. PRRSV was detected in inoculated animals from 3dpi until the end of the study, however TGFβ was not detected in sera from inoculated animals. Contrary, an increase of TGFβ antigen was observed both in the lymphoid organs and in the lung of PRRSV-inoculated pigs when compared with control group. Since TGFβ play a role as an immunomodulatory cytokine of the immune response and also in the differentiation of regulatory T cells (Tregs), the upregulation of the TGFβ at tissue level may play a role in the impairment of the host immune response observed during PRRS, being observed a significant correlation between PRRSV and TGFβ expression at lung level.


title: Coronavirose systémique chez le furet (Mustela putorius) : intérêt de l’analyse histologique et immunohistochimique. À propos de trois cas

text: Résumé Contexte Une nouvelle coronavirose a été décrite chez le furet, notamment en Espagne et aux États-Unis, induite par un Coronavirus du groupe 1, proche du Coronavirus responsable de l’entérite catarrhale enzootique et à l’origine de lésions histologiques similaires à celle de la péritonite infectieuse féline (PIF) dans l’espèce féline. Objectif Démontrer l’origine virale de lésions pyogranulomateuses sévères au sein de tissus lymphoïdes ou viscéraux de trois furets. Méthodes Analyse histologique et immunohistochimique de lésions reçues au laboratoire suite à des autopsies ou des laparotomies exploratrices pratiquées par des vétérinaires. Résultats L’analyse histologique révèle une inflammation pyogranulomateuse multicentrique, touchant préférentiellement les nœuds lymphatiques abdominaux et différents organes abdominaux. L’analyse immunohistochimique permet la mise en évidence d’antigènes viraux de Coronavirus en position intramacrophagique au sein de lésions pyogranulomateuses ganglionnaires. Conclusion Ces trois cas d’inflammation pyogranulomateuse multicentrique sont dus à une coronavirose qui présente de nombreux points de ressemblance avec la PIF. Summary Background A disease resembling feline infectious peritonitis (FIP) has been recognized recently in ferrets, mostly in United States and in Spain. This disease is due to a Group 1 Coronavirus, closely related to the ferret enteric Coronavirus. Objective To demonstrate the viral origin of severe pyogranulomatous lymphoid and visceral lesions in three ferrets. Methods Histopathology and immunohistochemistry of lesions received in our laboratory. Results Severe pyogranulomatous inflammation was observed in the abdominal lymph nodes and in various organs. Positive labelling of Coronavirus antigen was demonstrated in macrophages in the pyogranulomatous lesions by immunohistochemistry. Conclusion The three cases of severe pyogranulomatous disseminated inflammation were due to a Coronavirus, causing a systemic coronavirosis in ferret with a high similarity to FIP.


Letter to the Editor: 'Medical Student Concerns Relating to Neurosurgery Education During COVID-19'


title: Demographic and environmental drivers of metagenomic viral diversity in vampire bats

text: Viruses infect all forms of life and play critical roles as agents of disease, drivers of biochemical cycles and sources of genetic diversity for their hosts. Our understanding of viral diversity derives primarily from comparisons among host species, precluding insight into how intraspecific variation in host ecology affects viral communities or how predictable viral communities are across populations. Here we test spatial, demographic and environmental hypotheses explaining viral richness and community composition across populations of common vampire bats, which occur in diverse habitats of North, Central and South America. We demonstrate marked variation in viral communities that was not consistently predicted by a null model of declining community similarity with increasing spatial or genetic distances separating populations. We also find no evidence that larger bat colonies host greater viral diversity. Instead, viral diversity follows an elevational gradient, is enriched by juvenile‐biased age structure, and declines with local anthropogenic food resources as measured by livestock density. Our results establish the value of linking the modern influx of metagenomic sequence data with comparative ecology, reveal that snapshot views of viral diversity are unlikely to be representative at the species level, and affirm existing ecological theories that link host ecology not only to single pathogen dynamics but also to viral communities.


title: Increased cytokine/chemokines in serum from asthmatic and non-asthmatic patients with viral respiratory infection

text: BACKGROUND: Respiratory viral infections can induce different cytokine/chemokine profiles in lung tissues and have a significant influence on patients with asthma. There is little information about the systemic cytokine status in viral respiratory-infected asthmatic patients compared with non-asthmatic patients. OBJECTIVES: The aim of this study was to determine changes in circulating cytokines (IL-1β, TNF-α, IL-4, IL-5) and chemokines (MCP1: monocyte chemoattractant protein-1 and RANTES: regulated on activation normal T cell expressed and secreted) in patients with an asthmatic versus a non-asthmatic background with respiratory syncytial virus, parainfluenza virus or adenovirus respiratory infection. In addition, human monocyte cultures were incubated with respiratory viruses to determine the cytokine/chemokine profiles. PATIENTS/METHODS: Patients with asthmatic (n = 34) and non-asthmatic (n = 18) history and respiratory infections with respiratory syncytial virus, parainfluenza, and adenovirus were studied. Healthy individuals with similar age and sex (n = 10) were used as controls. Cytokine/chemokine content in blood and culture supernatants was determined by ELISA. Monocytes were isolated by Hystopaque gradient and cocultured with each of the above-mentioned viruses. RESULTS: Similar increased cytokine concentrations were observed in asthmatic and non-asthmatic patients. However, higher concentrations of chemokines were observed in asthmatic patients. Virus-infected monocyte cultures showed similar cytokine/chemokine profiles to those observed in the patients. CONCLUSIONS: Circulating cytokine profiles induced by acute viral lung infection were not related to asthmatic status, except for chemokines that were already increased in the asthmatic status. Monocytes could play an important role in the increased circulating concentration of cytokines found during respiratory viral infections.


title: Impact of intercurrent respiratory infections on lung health in infants born <29 weeks with bronchopulmonary dysplasia

text: OBJECTIVE: Assess the impact of intercurrent respiratory infections in infants <29 weeks gestational age (GA). STUDY DESIGN: A retrospective cohort study of 111 infants born <29 weeks GA, controlling for bronchopulmonary dysplasia (BPD) severity and assessing pulmonary health over the first year of life through oxygen, diuretic and inhaled steroid use. RESULT: Regression analysis showed viral infections increased oxygen use (odds ratio (OR) of 15.5 (confidence interval (CI)=3.4, 71.3)). The trend test showed increasing numbers of viral infections were associated with increased oxygen (OR (95% CI)=6.4 (2.3 to 17.4), P=0.0003), diuretic (OR (95% CI)=2.4 (1.1to 5.2), P=0.02) and inhaled steroid use (OR (95% CI)=2.2 (1.003 to 5.2), P=0.049), whereas bacterial infections were not. CONCLUSION: Viral infections caused more long-term pulmonary morbidity/mortality than bacterial infections on premature lung health, even when controlling for BPD.


title: Virus-binding activity of the truncated C subunit of porcine aminopeptidase N expressed in Escherichia coli

text: Seven overlapping truncated forms of the C subunit of porcine aminopeptidase N (pAPN-C) were expressed in Escherichia coli. By western blotting and ELISA test, all recombinant proteins were recognized by the antibody against native porcine aminopeptidase N. Recombinant proteins, rpAPN-C2 (aa 623–722) and rpAPN-C3 (aa 673–772), had the highest binding activity with swine transmissible gastroenteritis virus among the truncated pAPN-C recombinant proteins. The overlapping region (aa 673–722) between rpAPN-C2 and rpAPN-C3 is indicated to play a key role in viral binding. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10529-011-0795-1) contains supplementary material, which is available to authorized users.


title: Treatment guidance for lung cancer patients during the COVID-19 pandemic

text: Abstract The global COVID-19 pandemic continues to escalate at a rapid pace inundating medical facilities and creating significant challenges globally. The risk of SARS-CoV-2 infection in cancer patients appears to be higher especially as they are more likely to present with an immunocompromised condition, either from the cancer itself or from the treatments they receive. A major consideration in the delivery of cancer care during the pandemic is to balance the risk of patient exposure and infection with the need to provide effective cancer treatment. Many aspects of the SARS-CoV-2 infection remain poorly characterized currently and even less is known about the course of infection in the context of a patient with cancer. As SARS-CoV-2 is highly contagious, the risk of infection directly affects the cancer patient being treated, other cancer patients in close proximity, and health care providers. Infection at any level for patients or providers can cause significant disruption to even the most effective treatment plans. Lung cancer patients, especially those with reduced lung function and cardiopulmonary co-morbidities are more likely to have increased risk and mortality from COVID-19 as one of its common manifestation is as an acute respiratory illness. The purpose of this manuscript is to present a practical multidisciplinary and international overview to assist in treatment for lung cancer patients during this pandemic, with the caveat that evidence is lacking in many areas. It is expected that firmer recommendations can be developed as more evidence becomes available.


title: Infections and coinfections by respiratory human bocavirus during eight seasons in hospitalized children

text: The human bocavirus (hBoV) has been identified in respiratory infections in children in a large number of studies. Despite this, the pathogenic role of the HBoV is under discussion. The main objectives of the study were: to determine the incidence of HBoV in hospitalized children; to describe the main clinical features of the positive children; and to compare the data with those from other viral infections in the same population. A prospective study was performed between 2005 and 2013 including children up to 14‐year old with respiratory infection admitted to the Severo Ochoa Hospital (Spain). Nasopharyngeal aspirates were taken from 3,275 patients and were tested for HBoV and other 15 respiratory viruses by RT‐nested PCR. HBoV was detected in 319 patients (9.9%); 80 cases as a single pathogen, and 239 cases (75%) as coinfections with other viruses. The HBoV was the fourth most common virus detected, behind respiratory syncytial virus (39.8%), rhinovirus (30.6%), and adenovirus (15%). The most common clinical diagnosis, in cases that HBoV was detected as a single pathogen was asthma exacerbation followed by pneumonia. A seasonal distribution was shown, with higher positivity rates in December and January. Children affected by HBoV were older than children infected by other viruses. Differences in terms of clinical diagnosis were found, bronchiolitis diagnosis was lower compared with the other viruses, and HBoV was associated with diagnosis of pneumonia, with increased use of antibiotics (41.8%), and radiographic infiltrates (47%). These findings could suggest a pathogenic role of HBoV in respiratory infections in children under 14 years of age. J. Med. Virol. 88:2052–2058, 2016. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.


title: Poor outcome and prolonged persistence of SARS‐CoV‐2 RNA in COVID‐19 patients with haematological malignancies; King's College Hospital experience

text: Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), emerged at the end of 2019 and caused an infection named COVID‐19 (Guan, Ni et al. 2020). Patients with compromised immune systems are at increased risk of complications but this risk is not precisely defined (Liang, Guan et al. 2020). Although age, gender, comorbidities and ethnicity are risk factors for adverse outcomes (Huang, Wang et al. 2020), various pre‐existing conditions, including haematological cancers, have also been reported to correlate with poor outcomes (Aries, Davies et al. 2020, He, Chen et al. 2020, Malard, Genthon et al. 2020, Martin‐Moro, Marquet et al. 2020, medRxiv 2020)


title: The changes of prevalence and etiology of pediatric pneumonia from National Emergency Department Information System in Korea, between 2007 and 2014

text: PURPOSE: Understanding changes in pathogen and pneumonia prevalence among pediatric pneumonia patients is important for the prevention of infectious diseases. METHODS: We retrospectively analyzed data of children younger than 18 years diagnosed with pneumonia at 117 Emergency Departments in Korea between 2007 and 2014. RESULTS: Over the study period, 329,380 pediatric cases of pneumonia were identified. The most frequent age group was 1–3 years old (48.6%) and the next was less than 12 months of age (17.4%). Based on International Classification of Diseases, 10th revision diagnostic codes, confirmed cases of viral pneumonia comprised 8.4% of all cases, pneumonia due to Mycoplasma pneumoniae comprised 3.8% and confirmed cases of bacterial pneumonia 1.3%. The prevalence of confirmed bacterial pneumonia decreased from 3.07% in 2007 and 4.01% in 2008 to 0.65% in 2014. The yearly rate of pneumococcal pneumonia also decreased from 0.47% in 2007 to 0.08% in 2014. A periodic prevalence of M. pneumoniae pneumonia (MP) was identified. CONCLUSION: The increased number of patients with pneumonia, bacterial pneumonia, pleural effusion, and empyema in 2011 and 2013–2014 resulted from an MP epidemic. We provide evidence that the frequency of confirmed cases of bacterial pneumonia and pneumococcal pneumonia has declined from 2007 to 2014, which can simultaneously reflect the effectiveness of the pneumococcal conjugate vaccine.


title: Comparison of Oral Prednisolone/Paracetamol and Oral Indomethacin/Paracetamol Combination Therapy in the Treatment of Acute Goutlike Arthritis: A Double-Blind, Randomized, Controlled Trial

text: STUDY OBJECTIVE: We compare the analgesic efficacy and adverse effects of oral prednisolone/acetaminophen and oral indomethacin/acetaminophen combination therapy in the treatment of acute goutlike arthritis in patients presenting to an emergency department (ED). METHODS: This is a double-blind, randomized, controlled study in a university hospital emergency department (ED) in the New Territories of Hong Kong. Patients older than 17 years and presenting between February 1, 2003, and June 30, 2004, with a clinical diagnosis of goutlike arthritis were randomized to receive either oral prednisolone/acetaminophen or oral indomethacin/acetaminophen combination therapy. Primary outcome measures were pain scores, time to resolution of symptoms and signs, and adverse effects. Secondary outcome measures were the need for additional acetaminophen and relapse rate. RESULTS: There were 90 patients randomized: 46 patients to the indomethacin group and 44 patients to the prednisolone group. Baseline characteristics, including pain scores, were similar in the 2 groups. Both treatment groups had a similar decrease in pain score in the ED. The mean rate of decrease in pain score with activity for indomethacin was −1.7±1.6 (SD) mm per day and for prednisolone was −2.9±2.0 (SD) mm per day (mean difference 1.2 mm/day; 95% confidence interval 0.4 to 2.0 mm/day; P=.0026). Although these differences were statistically significant, at no time was the difference in mean pain score greater than 13 mm. Therefore, it is unclear whether these differences are clinically significant. The mean total dose of acetaminophen consumed by the prednisolone group was significantly more than in the indomethacin group (mean 10.3 g, range 1 to 21 g versus mean 6.4 g, range 1 to 21 g). Twenty-nine patients in the indomethacin group and 12 patients in the prednisolone group experienced adverse effects (P<.05). The commonest adverse effects in the indomethacin group were nausea, indigestion, epigastric pain, dizziness, and gastrointestinal bleeding (N=5; 11%). None of the patients in the prednisolone group developed gastrointestinal bleeding. The relapse rate for both groups was similar. CONCLUSION: In the treatment of acute goutlike arthritis, oral prednisolone/acetaminophen combination is as effective as oral indomethacin/acetaminophen combination in relieving pain but is associated with fewer adverse effects.


Simple ideas to mitigate the impacts of the COVID-19 epidemic on refugees with chronic diseases


title: Study on the dynamic change law and correlation between CT imaging manifestations and cellular immunity of 2019 novel coronavirus disease

text: PURPOSE: To explore the dynamic changes and correlation between CT imaging manifestations and cellular immunity of COVID-19. MATERIALS AND METHODS: This retrospective review analyzed 23 patients with COVID-19, including 13 males and 10 females aged 27–70 years, with an average age of 48 years. Patients were divided into two groups: group A with 11 critical-severe patients, and group B with 12 common-mild patients. Clinical, laboratory, and radiological data were collected and analyzed. RESULTS: LYM, LYM (%), CD3+, CD4+, and CD8+ decreased, while NEU (%), CRP, and CT scores increased in all patients, WBC in group A increased. In group A, on day 10–12 after disease onset, CT scores and CRP reached the highest point, and day 13–15 LYM, LYM (%) reached the lowest but NEU (%) and WBC reached the highest, CD3+, CD4+ and CD8+ were at the lowest on day 10–15. In group B, on day 7–9, CT scores, NEU (%) and CRP reached the peak, but LYM, LYM (%), CD3+, CD4+ and CD8+ reached the lowest. In all patients, CT scores had a significantly negative correlation with CD3+, CD4+, CD8+, LYM (%), and LYM (p = 0.001, r = − 0.797; p = 0.008, r = − 0.698; p = 0.002, r = − 0.775; p < 0.001, r = − 0.785; p = 0.021, r = − 0.571, respectively), and a significantly positive correlation with WBC and NEU (%) (p < 0.001, r = 0.785; p = 0.003, r = 0.691, respectively). CONCLUSION: Dynamic changes of CT manifestations and cellular immunity of patients with COVID-19 were regular and correlation was high between these two parameters.


Expression and Structural Analysis of Infectious Bronchitis Virus Nucleoprotein


title: Von Kamelen und Krebsforschung: Ungelöste Fragen

text: Die moderne Medizin hat innerhalb der letzten Jahrzehnte große Fortschritte gemacht und viele Wirkstoffe an unerwarteten Orten entdeckt. Eine Forschungsrichtung beschäftigt sich nun mit der Nutzung von Kamelen, die in ihrem natürlichen Habitat schon lange als Lieferant von verschiedensten Heilmitteln gelten.


title: Pediatric Round Pneumonia

text: “Round pneumonia” or “spherical pneumonia” is a well-characterized clinical entity that seems to be less addressed by pediatricians in Taiwan. We herein report the case of a 7-year-old boy who presented with prolonged fever, cough, and chest X-rays showing a well-demarcated round mass measuring 5.9 × 5.6 × 4.3 cm in the left lower lung field, findings which were typical for round pneumonia. The urinary pneumococcal antigen test was positive, and serum anti-Mycoplasma pneumoniae antibody titer measurement using a microparticle agglutination method was 1:160 (+). After oral administration of antibiotics including azithromycin and amoxicillin/clavulanate, which was subsequently replaced by ceftibuten due to moderate diarrhea, the fever subsided 2 days later and the round patch had completely resolved on the 18th day after the diagnosis. Recent evidence suggests treating classical round pneumonia with antibiotics first and waiving unwarranted advanced imaging studies, while alternative etiologies such as abscesses, tuberculosis, nonbacterial infections, congenital malformations, or neoplasms should still be considered in patients with atypical features or poor treatment response.


title: Contact Heterogeneity, Rather Than Transmission Efficiency, Limits the Emergence and Spread of Canine Influenza Virus

text: Host-range shifts in influenza virus are a major risk factor for pandemics. A key question in the study of emerging zoonoses is how the evolution of transmission efficiency interacts with heterogeneity in contact patterns in the new host species, as this interplay influences disease dynamics and prospects for control. Here we use a synergistic mixture of models and data to tease apart the evolutionary and demographic processes controlling a host-range shift in equine H3N8-derived canine influenza virus (CIV). CIV has experienced 15 years of continuous transfer among dogs in the United States, but maintains a patchy distribution, characterized by sporadic short-lived outbreaks coupled with endemic hotspots in large animal shelters. We show that CIV has a high reproductive potential in these facilities (mean R(0) = 3.9) and that these hotspots act as refugia from the sparsely connected majority of the dog population. Intriguingly, CIV has evolved a transmission efficiency that closely matches the minimum required to persist in these refugia, leaving it poised on the extinction/invasion threshold of the host contact network. Corresponding phylogenetic analyses show strong geographic clustering in three US regions, and that the effective reproductive number of the virus (R(e)) in the general dog population is close to 1.0. Our results highlight the critical role of host contact structure in CIV dynamics, and show how host contact networks could shape the evolution of pathogen transmission efficiency. Importantly, efficient control measures could eradicate the virus, in turn minimizing the risk of future sustained transmission among companion dogs that could represent a potential new axis to the human-animal interface for influenza.