title: Covid-19 growth rate analysis: application of a low-complexity tool for understanding and comparing epidemic curves

text: INTRODUCTION: The acceleration of new cases is important for the characterization and comparison of epidemic curves. The objective of this study was to quantify the acceleration of daily confirmed cases and death curves using the polynomial interpolation method. METHODS: Covid-19 epidemic curves from Brazil, Germany, the United States, and Russia were obtained. We calculated the instantaneous acceleration of the curve using the first derivative of the representative polynomial. RESULTS: The acceleration for all curves was obtained. CONCLUSIONS: Incorporating acceleration into an analysis of the Covid-19 time series may enable a better understanding of the epidemiological situation.


title: Kidney Infarction in Patients With COVID-19

text: Coronavirus disease 2019 (COVID-19) is a contagious, life-threatening infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent findings indicate an increased risk of acute kidney injury during COVID-19. The pathophysiological mechanisms leading to acute kidney injury in COVID-19 are unclear, but may include direct cytopathic effects of the virus on kidney tubular and endothelial cells, indirect damage caused by virus-induced cytokine release, and kidney hypoperfusion due to a restrictive fluid strategy. In this case-report we propose an additional pathophysiological mechanism. We describe two cases in which patients with COVID-19 developed a decrease in kidney function due to kidney infarction. These patients did not have atrial fibrillation. One of these patients was treated with therapeutic doses of low molecular weight heparin, whereafter no further deterioration of kidney function was observed. Our findings implicate that the differential diagnosis of acute kidney injury in COVID-19 patients should include kidney infarction, which may have important preventive and therapeutic implications.


title: PI3K/Akt/p53 pathway inhibits reovirus infection

text: Abstract Viral infections activate many host signaling pathways, including the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which has recently attracted considerable interest due to its central role in modulating virus replication. This study demonstrated that the sero-type 3 reovirus strain Masked Palm Civet/China/2004 (MPC/04) could transiently activate the PI3K/Akt pathway in A549 cells at earlier time points of infection. The blockage of PI3K/Akt activation increased viral RNA synthesis and yield. The role of the downstream effectors MDM2/p53 of PI3K/Akt in regulating reovirus replication was further analyzed. We found that during reovirus infection, the level of phosphorylated MDM2 (p-MDM2) was increased and the expression of p53 was reduced. In addition, the blockage of PI3K/Akt by Ly294002 or knockdown of Akt by siRNA reduced the level of p-MDM2 and increased the level of p53. Both indicated that the downstream effectors MDM2/p53 of PI3K/Akt were activated. Pre-treatment with Nutlin, which can destroy MDM2 and p53 cross-talk and increase the expression of p53 RNA and protein, dose-dependently enhanced reovirus replication. Additionally, the overexpression of p53 alone also supported reovirus replication, and knockdown of p53 significantly inhibited viral replication. This study demonstrates that PI3K/Akt/p53 activated by mammalian reovirus can serve as a pathway for inhibiting virus replication/infection, yet the precise mechanism of this process remains under further investigation.


title: Understand potential legal implications of pandemic's economic impact on athletics

text: The numerous public health measures that were implemented as a result of the COVID‐19 pandemic and the subsequent impact on the nation's economy have created a new world of emergency planning at every educational institution and within every athletics department. Between the money that had to be returned for room and board and/or tuition reimbursements; the decline in or disappearance of digital rights payments, ticket sales, donations, and corporate sponsorships; the cancellation of March Madness, and the loss of many other revenue streams, the economic vise‐grip created by COVID‐19 tightened quickly and dramatically. Within the public sector, a future reduction in legislative appropriations in various states for higher education is likewise being discussed.


title: SARS: Epidemiology, Clinical Presentation, Management, and Infection Control Measures

text: Severe acute respiratory syndrome (SARS) is a recently recognized febrile respiratory illness that first appeared in southern China in November 2002, has since spread to several countries, and has resulted in more than 8000 cases and more than 750 deaths. The disease has been etiologically linked to a novel coronavirus that has been named the SARS-associated coronavirus. It appears to be spread primarily by large droplet transmission. There is no specific therapy, and management consists of supportive care. This article summarizes currently available information regarding the epidemiology, clinical features, etiologic agent, and modes of transmission of the disease, as well as infection control measures appropriate to contain SARS.


title: Modified vaccinia virus Ankara as a vaccine against feline coronavirus: immunogenicity and efficacy

text: Abstract Feline infectious peritonitis virus (FIPV) is a coronavirus that induces a fatal systemic disease mediated by an inappropriate immune response. Most previous vaccination attempts against FIPV were unsuccessful because IgG antibodies against the surface protein enhance the infection. However, two studies have shown that poxvirus vectors (vaccinia WR and canarypox) expressing only the FIPV membrane (M) protein can elicit a partially protective immunity which is supposed to be cell-mediated (Virology 181 (1991) 327; International patent WO 97/20054 (1997)). In our study, we report the construction of another poxvirus, the modified vaccinia virus Ankara (MVA), as an expression vector for the FIPV M protein. In this vector, the M gene has been inserted downstream a strong early/late promoter, whereas the two previously described poxviruses expressed the M protein during their early stage only. The immunogenicity of the recombinant MVA-M was evaluated in the murine model which revealed an effect of the vector on the Th1/Th2 balance. The vaccine was then tested in cats to evaluate its efficacy in an FIPV 79-1146 challenge. Vaccinated kittens developed FIPV-specific antibodies after immunization, however, none of them was protected against FIPV. Our results suggest a crucial role for the type of poxviral promoter that must be used to induce an effective immune response against FIPV.


title: Major cluster of pediatric “ true ” primary chilblains during the COVID‐19 pandemic: a consequence of lifestyle changes due to lockdown

text: BACKGROUND: Over the last months, during the COVID‐19 pandemic, a growing number of chilblain‐like lesions was reported mainly in children, rarely in young adults. The relationship with SARS‐CoV‐2 infection was postulated, often without any laboratory, instrumental or clinical confirmation. The disclosure of information about chilblain‐like lesions as a COVID‐19 manifestation in social media has created concern in children’s families and pediatricians OBJECTIVES: to verify whether the chilblain‐like lesions were caused by SARS‐CoV‐2 infection. METHODS: prospective study on a case series including children who presented with acral lesions at the Pediatric Dermatology Outpatient and Pediatric Emergency Unit of the University of Bologna, from April 1 to April 30, 2020. We reported demographical, laboratory and clinical features, history of close contact with COVID‐19 patients, presence of similar skin lesions in other family members, precipitating and risk factors for chilblain onset. RESULTS: We evaluated 8 patients (5 females, 3 males) aged between 11 and 15 years. We excluded acute or previous SARS‐CoV‐2 infection with RT‐PCR nasopharyngeal swab, serum antibody levels using chemiluminescent immunoassays. Other acute infections causing purpuric lesions at the extremities were negative in all patients. Skin lesion biopsy for histological and immunohistochemical evaluation was made in two cases and was consistent with chilblain. PCR‐assay on skin lesion biopsy for Parvovirus B19, Mycoplasma pneumoniae and SARS‐CoV‐2 was performed in a patient and resulted negative. We identified common precipitating and risk factors: physical (cold and wet extremities, low BMI), cold and wet indoor and outdoor environment, behaviors, habits, lifestyle. We therefore reached a diagnosis of primary chilblains. CONCLUSIONS: During the COVID‐19 pandemic, a “cluster” of primary chilblains developed in predisposed subjects, mainly teenagers, due to to cold exposure in the lockdown period. Laboratory findings support our hypothesis, although it is also possible that an unknown infectious trigger may have contributed to the pathogenesis.


title: Complete Genome of Avian coronavirus Vaccine Strains Ma5 and BR-I

text: Avian coronavirus (AvCoV) is a ubiquitous multiple-serotype pathogen of poultry, and its control is mainly based on the use of vaccines. We report here the previously unknown full genomes of the Ma5 (27,652 nucleotides [nt]) and BR-I (27,618 nt) AvCoV vaccine strains of the GI-1 (Massachusetts) and GI-11 (Brazil) types.


title: Connecting clusters of COVID-19: an epidemiological and serological investigation

text: Summary Background Elucidation of the chain of disease transmission and identification of the source of coronavirus disease 2019 (COVID-19) infections are crucial for effective disease containment. We describe an epidemiological investigation that, with use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assays, established links between three clusters of COVID-19. Methods In Singapore, active case-finding and contact tracing were undertaken for all COVID-19 cases. Diagnosis for acute disease was confirmed with RT-PCR testing. When epidemiological information suggested that people might have been nodes of disease transmission but had recovered from illness, SARS-CoV-2 IgG serology testing was used to establish past infection. Findings Three clusters of COVID-19, comprising 28 locally transmitted cases, were identified in Singapore; these clusters were from two churches (Church A and Church B) and a family gathering. The clusters in Church A and Church B were linked by an individual from Church A (A2), who transmitted SARS-CoV-2 infection to the primary case from Church B (F1) at a family gathering they both attended on Jan 25, 2020. All cases were confirmed by RT-PCR testing because they had active disease, except for A2, who at the time of testing had recovered from their illness and tested negative. This individual was eventually diagnosed with past infection by serological testing. ELISA assays showed an optical density of more than 1·4 for SARS-CoV-2 nucleoprotein and receptor binding domain antigens in titres up to 1/400, and viral neutralisation was noted in titres up to 1/320. Interpretation Development and application of a serological assay has helped to establish connections between COVID-19 clusters in Singapore. Serological testing can have a crucial role in identifying convalescent cases or people with milder disease who might have been missed by other surveillance methods. Funding National Research Foundation (Singapore), National Natural Science Foundation (China), and National Medical Research Council (Singapore).


title: Proteomics of Bronchoalveolar Lavage Fluid Reveals a Lung Oxidative Stress Response in Murine Herpesvirus-68 Infection

text: Murine herpesvirus-68 (MHV-68) productively infects mouse lungs, exhibiting a complex pathology characteristic of both acute viral infections and chronic respiratory diseases. We sought to discover proteins differentially expressed in bronchoalveolar lavage (BAL) from mice infected with MHV-68. Mice were infected intranasally with MHV-68. After nine days, as the lytic phase of infection resolved, differential BAL proteins were identified by two-dimensional (2D) electrophoresis and mass spectrometry. Of 23 unique proteins, acute phase proteins, vitamin A transport, and oxidative stress response factors Pdx6 and EC-SOD (Sod3) were enriched. Correspondingly, iNOS2 was induced in lung tissue by seven days post-infection. Oxidative stress was partly a direct result of MHV-68 infection, as reactive oxygen species (ROS) were induced in cultured murine NIH3T3 fibroblasts and human lung A549 cells infected with MHV-68. Finally, mice infected with a recombinant MHV-68 co-expressing inflammatory cytokine murine interleukin 6 (IL6) showed exacerbated oxidative stress and soluble type I collagen characteristic of tissue recovery. Thus, oxidative stress appears to be a salient feature of MHV-68 pathogenesis, in part caused by lytic replication of the virus and IL6. Proteins and small molecules in lung oxidative stress networks therefore may provide new therapeutic targets to ameliorate respiratory virus infections.


title: Lipoteichoic acid from Staphylococcus aureus exacerbates respiratory disease in porcine respiratory coronavirus-infected pigs

text: The objective of this study was to assess if lipoteichoic acid (LTA), produced by Staphylococcus aureus, exacerbates respiratory disease in porcine respiratory coronavirus (PRCV)-infected pigs, as has previously been shown with lipopolysaccharide. Piglets were inoculated with PRCV and 24 h later with S. aureus LTA. Clinical signs, lung virus titres, inflammatory cells and cytokines in bronchoalveolar lavage fluid (BALF) were compared with those of animals in PRCV- and LTA- inoculated control groups. All PRCV-LTA inoculated pigs except one developed severe respiratory disease, whereas clinical signs in the control groups were minimal or absent. Virus titres and grossly visible pulmonary lesions were similar in the PRCV-LTA- and PRCV-inoculated groups and were not detected in the LTA-group. Neutrophil percentages in BALF were higher in the PRCV-LTA than in the PRCV group. There was no significant difference in interferon (IFN)-γ, interleukin (IL)-1, IL-6, IL-12/IL-23 and tumour necrosis factor (TNF)-α concentrations in BALF between the PRCV-LTA and PRCV groups, but levels of IL-6, IL-12/IL-23 and IFN-γ were higher in the PRCV-LTA-inoculated than in the LTA-inoculated controls. The findings suggest that the experimentally-induced respiratory disease was not mediated by cytokine over-production, but rather reflected the concerted action of particular cytokine interactions and/or as yet unidentified mediators. This is the first in vivo study to report the synergistic interaction between a virus and LTA in enhancing the severity of respiratory disease in the pig. Given that Gram-positive bacteria, capable of producing LTA, are commonly found in pig accommodation, the role of this compound in the development of the porcine respiratory disease complex requires further investigation.


title: Preferential loss of Th17 cells is associated with CD4 T cell activation in patients with 2009 pandemic H1N1 swine-origin influenza A infection

text: Abstract Very limited evidence has been reported on host T cell responses to the pandemic H1N1 swine-origin influenza A virus (S-OIV) infection in humans. Therefore, we investigated the proportions of peripheral T cell subsets and analyzed the relationship of T helper subset changes with T cell activation during this infection. We found that these S-OIV-infected patients exhibited rapid lymphopenia, T cell activation and preferential loss of Th17 subset at the early stage of acute infection. Statistical analysis indicated that CD4 depletion and loss of Th17 cells, rather than Th1 or Treg cells, were correlated with CD4 T cell activation. More importantly, up-regulated IFN-α likely contributed to the functional loss of Th17 cells. Thus, rapidly generalized lymphopenia, preferential loss of Th17 population and T cell activation presented as characteristics of the early immune response in S-OIV-infected patients. These findings, therefore, may be helpful for an earlier diagnosis and further studies of immune pathogenesis of S-OIV infection.


title: Comparison of phenotypic and genotypic diagnosis of acute human bocavirus 1 infection in children

text: Abstract Background Diagnosis of human bocavirus 1 (HBoV1) has been based on qualitative PCRs detecting HBoV1 DNA or detection of HBoV1 mRNA. Objective This study aims to assess whether a rapid and automated HBoV1 antigen test is suitable for diagnosis of acute HBoV1 infection. Study design HBoV1 antigen detection has been compared with quantitative HBoV1 DNA PCR and HBoV1 mRNA RT-PCR. Results and conclusion We conclude that HBoV1 antigen detection has higher clinical specificity and positive predictive value than HBoV1 DNA qualitative PCRs, yet a lower sensitivity than HBoV1 mRNA detection. Additionally, HBoV1 antigen detection is beneficial in its rapidity and availability as a point-of-care test.


title: An evaluation of porcine epidemic diarrhea virus survival in individual feed ingredients in the presence or absence of a liquid antimicrobial

text: BACKGROUND: Contaminated complete feed and porcine plasma are risk factors for PEDV introduction to farms and a liquid antimicrobial has been proven useful for reducing risk. This study provides information on the survivability of PEDV across common swine feed ingredients in the presence or absence of the liquid antimicrobial. RESULTS: Eighteen ingredients commonly included in commercial swine diets were selected, including 3 grain sources (corn, soybean meal (SBM), dried distillers grains with solubles (DDGS)), 5 porcine by-products (spray-dried plasma, purified plasma, intestinal mucosa, meat and bone meal and red blood cells (RBCs)), 3 vitamin/trace mineral (VTM) mixes (sow, nursery, finishing), 2 fat sources (choice white grease and soy oil), 3 synthetic amino acids (lysine HCL, D/L methionine, threonine), as well as limestone and dry choline chloride. Complete feed and stock PEDV served as controls. Thirty grams of each ingredient were inoculated with 2 mL PEDV. A matched set of samples were treated with the formaldehyde-based liquid antimicrobial SalCURB® (LA). All samples (n = 320) were stored outdoors under winter time ambient conditions for 30 days. Samples were submitted on 1, 7, 14 and 30 days post-inoculation (DPI) and tested by PCR and virus isolation (VI). All VI-negative samples were tested by swine bioassay. Viable PEDV was detected by VI or swine bioassay at 1, 7, 14 and 30 DPI from SBM, DDGS, meat & bone meal, RBCs, lysine HCL, D/L methionine, choice white grease, choline chloride, complete feed and stock virus control and at 7 DPI in limestone and at 14 DPI in threonine. Supplementary testing of complete feed and SBM indicated viable virus out to 45 and 180 DPI, respectively. All other samples were negative by VI and bioassay. In contrast, treatment with LA inactivated PEDV across all ingredients on 1 DPI and induced RNA reduction over time. CONCLUSIONS: Under the conditions of this study, PEDV viability in feed was influenced by ingredient with extended survival in SBM. Furthermore, LA treatment rendered virus inactive, independent of ingredient type.


title: The effects of e-ridehailing on motorcycle ownership in an emerging-country megacity

text: The impact of app-based e-hailing or ridesourcing services on various transport metrics is an area of active research, and research so far have focused on the car-based (or four-wheeled vehicle based) services only. In many cities in the developing and emerging countries, motorcycle-based passenger e-hailing services have become very popular in the last few years, but the implications of these have not been studied before. This study investigates the effects of motorcycle-hailing apps in Dhaka – a megacity in Bangladesh – on the size of its motorcycle fleet. We employ segmented multiple regression on timeseries data to show that there was a statistically significant increase in motorcycle ownership in Dhaka as a result of the motorcycle-hailing services. The findings were also supported by a visual intervention analysis. By the end of 2018, there were 7.45% more motorcycles in Dhaka than there would have been if these app-based e-hailing services were not available. We conclude with potential implications of these increases in motorcycle numbers and future research directions.


title: Role of Metallic Nanoparticles in Vaccinology: Implications for Infectious Disease Vaccine Development

text: Subunit vaccines are safer but less immunogenic than live-attenuated vaccines or whole cell inactivated vaccines. Adjuvants are used to enhance and modulate antigen (Ag) immunogenicity, aiming to induce a protective and long-lasting immune response. Several molecules and formulations have been studied for their adjuvanticity, but only seven have been approved to formulate human vaccines. Metallic nanoparticles (MeNPs), particularly those containing gold and iron oxides, are widely used in medicine for diagnosis and therapy and have been used as carriers for drugs and vaccines. However, little is known about the immune response elicited by MeNPs or about their importance in the development of new vaccines. There is evidence that these particles display adjuvant characteristics, promoting cell recruitment, antigen-presenting cell activation, cytokine production, and inducing a humoral immune response. This review focuses on the characteristics of MeNPs that could facilitate the induction of a cellular immune response, particularly T-helper 1 and T-helper 17, and their potential functions as adjuvants for subunit vaccines.


title: A new factor influencing pathogen detection by molecular assay in children with both mild and severe hand, foot, and mouth disease

text: Abstract This study aimed to find novel information concerning pathogen detection and some probable coinfection factors in hand, foot, and mouth disease (HFMD). In this study, 1104 clinically diagnosed HFMD patients were included. Enterovirus 71 (EV71), coxsackievirus A16 (CA16), and 14 different respiratory pathogens were examined from nasopharyngeal swabs using polymerase chain reaction (PCR) or reverse transcriptase PCR (RT-PCR). To evaluate the immune activation in HFMD patients, 8 cytokines and IgM antibodies to EV71 and CA16 from mild and severe patients were detected. Our results indicated that the severity of HFMD may affect the pathogen detection. The lower positive rates of enterovirus and respiratory viruses in severe HFMD cases by RT-PCR were probably related to stronger immune response. Therefore, immunological tests such as ELISA are essential supplements to PCR or RT-PCR in order to increase pathogen diagnosis in HFMD, especially in severe cases.


title: Investigation of epidemic spreading process on multiplex networks by incorporating fatal properties

text: Abstract Numerous efforts have been devoted to investigating the network activities and dynamics of isolated networks. Nevertheless, in practice, most complex networks might be interconnected with each other (due to the existence of common components) and exhibit layered properties while the connections on different layers represent various relationships. These types of networks are characterized as multiplex networks. A two-layered multiplex network model (usually composed of a virtual layer sustaining unaware-aware-unaware (UAU) dynamics and a physical one supporting susceptible-infected-recovered-dead (SIRD) process) is presented to investigate the spreading property of fatal epidemics in this manuscript. Due to the incorporation of the virtual layer, the recovered and dead individuals seem to play different roles in affecting the epidemic spreading process. In details, the corresponding nodes on the virtual layer for the recovered individuals are capable of transmitting information to other individuals, while the corresponding nodes for the dead individuals (which are to be eliminated) on the virtual layer should be removed as well. With the coupled UAU-SIRD model, the relationships between the focused variables and parameters of the epidemic are studied thoroughly. As indicated by the results, the range of affected individuals will be reduced by a large amount with the incorporation of virtual layers. Furthermore, the effects of recovery time on the epidemic spreading process are also investigated aiming to consider various physical conditions. Theoretical analyses are also derived for scenarios with and without required time periods for recovery which validates the reducing effects of incorporating virtual layers on the epidemic spreading process.


title: Chapter Four Free Circulating miRNAs Measurement in Clinical Settings The Still Unsolved Issue of the Normalization

text: Abstract Circulating molecules that are released into the circulation in response to specific stimuli are considered potential biomarkers for physiological or pathological processes. Their effective usefulness as biomarkers resides in their stability and high availability in all the biological fluids, combined with the limited invasiveness of intervention. Among the circulating molecules, miRNAs represent a novel class of biomarkers as they possess all the required characteristics such as sensitivity, predictivity, specificity, robustness, translatability, and noninvasiveness. miRNAs are small non-coding RNAs, that act as inhibitors of protein translation, and intervene in the complex network of the post-transcriptional mechanisms finely regulating gene expression. The emerging role of miRNAs as potential biomarkers for clinical applications (e.g., cancer and cardiovascular diseases diagnosis and prediction, musculoskeletal disease diagnosis and bone fracture risk prediction), however, requires the standardization of miRNA processing, from sample collection and sample storage, to RNA isolation, RNA reverse-transcription, and data analyses. Normalization is one of the most controversial issues related to quantitative Real-Time PCR data analysis since no universally accepted normalization strategies and reference genes exist, even more importantly, for circulating miRNA quantification. As it is widely demonstrated that the choice of different normalization strategies influences the results of gene expression analysis, it is important to select the most appropriate normalizers for each experimental set. This review discloses on the different strategies adopted in RT-qPCR miRNA normalization and the concerning issues to highlight on the need of a universally accepted methodology to make comparable the results produced by different studies.


title: Pulmonary embolism during the COVID‐19 pandemic: decline in diagnostic procedures and incidence at a University Hospital

text: BACKGROUND: The COVID‐19 pandemic has focused medical attention on treating affected patients and protecting others from infection. However, concerns have been raised regarding the pandemic´s impact and associated containment measures (e.g. curfew, lockdown) on non‐COVID‐19‐related acute medical diseases. OBJECTIVES: To investigate changes in the incidence of pulmonary embolism (PE) during the COVID‐19 pandemic compared to the period prior to the pandemic and reference periods in previous years. METHODS: In this single‐center study, we explored all diagnostic imaging tests performed for suspected PE between week 1‐17 of the years 2018, 2019, and 2020. Incidence of PE (i.e. primary outcome) was analyzed. Secondary outcomes included number of imaging tests for suspected PE. RESULTS: Compared to week 1‐11, 2020, an abrupt decline in PE diagnosis (mean weekly rate: 5.2 [95%CI: 3.8‐6.6] vs. 1.8 [0.0‐3.6]) and imaging tests (32.5 [27.5‐37.6] vs. 17.3 [11.6‐23.1]) was observed from week 12, with beginning of the containment measures and public lockdown in Austria. Compared to week 12‐17 of 2018 and 2019, PE incidence and imaging tests were similarly decreased from 5.3 [3.6‐7.1] to 1.8 [0.0‐3.6] and 31.5 [27.1‐35.9] to 17.3 [11.6‐23.1]), respectively. The median (IQR) sPESI score of PE patients during the pandemic was higher than in all other PE patients (3 [1‐3] vs. 1 [0‐2]; p=0.002). CONCLUSION: Our study demonstrates that the Covid‐19 pandemic has an impact on non‐COVID‐19‐related acute diseases as shown by the decline in incidence of PE and imaging procedures for diagnostic work‐up. Further studies from other hospitals are needed to confirm our findings.


title: Pediatrician attitudes toward and experiences with telehealth use: Results from a national survey

text: Abstract Background: The American Academy of Pediatrics 2015 policy statement on telehealth proposed that telehealth could increase access to high-quality pediatric care and that pediatricians should work to reduce barriers to telehealth for their patients. However, little is known about pediatricians’ experiences with and attitudes toward telehealth. Methods: Data from a nationally representative survey of AAP post-residency US member pediatricians in 2016, restricted to respondents providing direct patient care (n=744; response rate=48.7%). Survey collected information on experience with telehealth in the previous 12 months, perceived barriers to telehealth incorporation, and conditions under which non-users would consider using telehealth. In addition to descriptive statistics, we used multivariable logistic regression to examine characteristics associated with any telehealth experience in the past 12 months. Results: Fifteen percent of pediatricians reported any telehealth use in the 12 months prior to the survey. The most commonly reported barriers to telehealth adoption were insufficient payment and billing issues. Multivariable regression models indicated that pediatricians in rural areas, the West, and subspecialists were most likely to report telehealth use, and identifying barriers was negatively associated with telehealth use. Among non-users, over half indicated they would consider adopting telehealth if they were paid for the visits. Conclusion: Telehealth is considered an important health care delivery mechanism, but only 15% of pediatricians in 2016 reported having used telehealth. Reducing barriers will be instrumental in promoting future telehealth adoption. Many barriers have been reduced during the response to COVID-19, and the impact of these policy changes will need further study.


title: Chapter 3 Molecular Mimicry and Autoimmunity

text: Abstract The term Molecular mimicry describes the sequence similarity between foreign (microorganism's peptides) and self peptides (the host's antigen). This phenomenon has been recently discovered as a one of the major mechanism in which there is a break-down of self-tolerance of the immune system following autoimmunity. After a short preface, the chapter contains examples of common infectious agents and their role in autoimmune diseases. Later on, it describes the autoimmune diseases in which there was found a relation to infectious agents via molecular mimicry mechanism. The data is summarized in two tables.


Letter to the Editor: Priority considerations of patients with peripheral nerve pathology in the time of COVID-19


title: Round-up of GHSA Steering Group and Action Packages in 2015

text: All Global Health Security Agenda (GHSA) Steering Group Members remain strongly committed to accelerating measurable progress and implementing concrete commitments toward a world safe and secure from infectious disease threats, recognizing the devastation of the Ebola epidemic and the clear interdependence of health in the 21(st) century. All GHSA Steering Group members reinforced that GHSA is supportive of International Health Regulations implementation, as well as components of other global health security frameworks such as the World Organization for Animal Health Performance of Veterinary Services pathway. The GHSA will continue to focus on multilateral engagement. The GHSA Steering Group is committed to engaging non-state actors and agreed to discuss next steps toward engaging the private sector.


title: Deciphering emerging Zika and dengue viral epidemics: Implications for global maternal–child health burden

text: Summary Since its discovery in 1947 in Uganda and control and eradication efforts have aimed at its vectors (Aedes mosquitoes) in Latin America in the 1950s, an absolute neglect of Zika programs and interventions has been documented in Aedes endemic and epidemic-prone countries. The current unprecedented Zika viral epidemics and rapid spread in the Western hemisphere pose a substantial global threat, with associated anxiety and consequences. The lack of safe and effective drugs and vaccines against Zika or dengue epidemics further buttresses the realization from the West Africa Ebola outbreak that most emerging disease-prone countries are still poorly prepared for an emergency response. This paper examines knowledge gaps in both emerging and neglected arthropod-borne flavivirus infectious diseases associated with poverty and their implications for fostering local, national and regional emerging disease preparedness, effective and robust surveillance–response systems, sustained control and eventual elimination. Strengthening the regional and Global Health Flavivirus Surveillance-Response Network (GHFV-SRN) with other models of socio-economic, climatic, environmental and ecological mitigation and adaptation strategies will be necessary to improve evidence-based national and global maternal–child health agenda and action plans.


title: Risk of the Brazilian health care system over 5572 municipalities to exceed health care capacity due to the 2019 novel coronavirus (COVID-19)

text: The spread of the 2019 novel coronavirus (COVID-19) has challenged governments to develop public policies to reduce the load of the COVID-19 on health care systems, which is commonly referred to as “flattening the curve”. This study aims to address this issue by proposing a spatial multicriteria approach to estimate the risk of the Brazilian health care system, by municipality, to exceed the health care capacity because of an influx of patients infected with the COVID-19. We estimated this risk for 5572 municipalities in Brazil using a combination of a multicriteria decision-making approach with spatial analysis to estimate the exceedance risk, and then, we examined the risk variation by designing 5 control intervention scenarios (3 scenarios representing reduction on social contacts, and 2 scenarios representing investment on health care system). For the baseline scenario using an average infection rate across Brazil, we estimated a mean Hospital Bed Capacity (HBC) value of −16.73, indicating that, on average, the Brazilian municipalities will have a deficit of approximately 17 beds. This deficit is projected to occur in 3338 municipalities with the north and northeast regions being at the greatest risk of exceeding health care capacity due to the COVID-19. The intervention scenarios indicate across all of Brazil that they could address the bed shortage, with an average of available beds between 23 and 32. However, when we consider the shortages at a municipal scale, bed exceedances still occur for at least 2119 municipalities in the most effective intervention scenario. Our findings are essential to identify priority areas, to compare populations, and to provide options for government agencies to act. This study can be used to provide support for the creation of effective health public policies for national, regional, and local intervention.


title: Hand Sanitizers: A Review on Formulation Aspects, Adverse Effects, and Regulations

text: Hand hygiene is of utmost importance as it may be contaminated easily from direct contact with airborne microorganism droplets from coughs and sneezes. Particularly in situations like pandemic outbreak, it is crucial to interrupt the transmission chain of the virus by the practice of proper hand sanitization. It can be achieved with contact isolation and strict infection control tool like maintaining good hand hygiene in hospital settings and in public. The success of the hand sanitization solely depends on the use of effective hand disinfecting agents formulated in various types and forms such as antimicrobial soaps, water-based or alcohol-based hand sanitizer, with the latter being widely used in hospital settings. To date, most of the effective hand sanitizer products are alcohol-based formulations containing 62%–95% of alcohol as it can denature the proteins of microbes and the ability to inactivate viruses. This systematic review correlated with the data available in Pubmed, and it will investigate the range of available hand sanitizers and their effectiveness as well as the formulation aspects, adverse effects, and recommendations to enhance the formulation efficiency and safety. Further, this article highlights the efficacy of alcohol-based hand sanitizer against the coronavirus.


title: Positive SARS-Cov-2 test in a woman with COVID-19 at 22 days after hospital discharge: A case report

text: Abstract Background In a few discharged patients with coronavirus disease 2019 (COVID-19), the nucleic acid test shows positive results again. Whether this is due to relapse of the disease, reinfection by the virus, or a false-positive result at hospital discharge is worth exploring. Case presentation A woman with COVID-19 was discharged from the hospital after integrative treatment with traditional Chinese and Western medicine because she met the discharge standards. However, she obtained positive results on a nucleic acid test 22 days later. Conclusion Based on this positive test result in a discharged patient with COVID-19, anal tests and coronavirus antibody tests should be combined with throat swab tests to further develop the diagnosis and discharge standards for patients with COVID-19.


COVID-19 Illness in Native and Immunosuppressed States: A Clinical-Therapeutic Staging Proposal


title: Optimal Decision Model for Sustainable Hospital Building Renovation—A Case Study of a Vacant School Building Converting into a Community Public Hospital

text: Much attention has been paid to hospitals environments since modern pandemics have emerged. The building sector is considered to be the largest world energy consumer, so many global organizations are attempting to create a sustainable environment in building construction by reducing energy consumption. Therefore, maintaining high standards of hygiene while reducing energy consumption has become a major task for hospitals. This study develops a decision model based on genetic algorithms and A* graph search algorithms to evaluate existing hospital environmental conditions and to recommend an optimal scheme of sustainable renovation strategies, considering trade-offs among minimal renovation cost, maximum quality improvement, and low environmental impact. Reusing vacant buildings is a global and sustainable trend. In Taiwan, for example, more and more school space will be unoccupied due to a rapidly declining birth rate. Integrating medical care with local community elder-care efforts becomes important because of the aging population. This research introduces a model that converts a simulated vacant school building into a community public hospital renovation project in order to validate the solutions made by hospital managers and suggested by the system. The result reveals that the system performs well and its solutions are more successful than the actions undertaken by decision-makers. This system can improve traditional hospital building condition assessment while making it more effective and efficient.


title: First Complete Genome Sequence of a French Bovine coronavirus Strain

text: We sequenced the first Bovine coronavirus (BCoV) complete genome sequence from France. This BCoV was directly sequenced from a fecal sample collected from a calf in Normandy in 2014.


The diabetic lung: an easy target for SARS‐CoV‐2?


title: Impacts of Road Traffic Network and Socioeconomic Factors on the Diffusion of 2009 Pandemic Influenza A (H1N1) in Mainland China

text: The 2009 pandemic influenza virus caused the majority of the influenza A virus infections in China in 2009. It arrived in several Chinese cities from imported cases and then spread as people travelled domestically by all means of transportation, among which road traffic was the most commonly used for daily commuting. Spatial variation in socioeconomic status not only accelerates migration across regions but also partly induces the differences in epidemic processes and in responses to epidemics across regions. However, the roles of both road travel and socioeconomic factors have not received the attention they deserve. Here, we constructed a national highway network for and between 333 cities in mainland China and extracted epidemiological variables and socioeconomic factors for each city. We calculated classic centrality measures for each city in the network and proposed two new measures (SumRatio and Multicenter Distance). We evaluated the correlation between the centrality measures and epidemiological features and conducted a spatial autoregression to quantify the impacts of road network and socioeconomic factors during the outbreak. The results showed that epidemics had more significant relationships with both our new measures than the classic ones. Higher population density, higher per person income, larger SumRatio and Multicenter Distance, more hospitals and college students, and lower per person GDP were associated with higher cumulative incidence. Higher population density and number of slaughtered pigs were found to advance epidemic arrival time. Higher population density, more colleges and slaughtered pigs, and lower Multicenter Distance were associated with longer epidemic duration. In conclusion, road transport and socioeconomic status had significant impacts and should be considered for the prevention and control of future pandemics.


title: Exploration of structural and physicochemical requirements and search of virtual hits for aminopeptidase N inhibitors

text: Aminopeptidase N (APN) inhibitors have been reported to be effective in treating of life threatening diseases including cancer. Validated ligand- and structure-based pharmacophore mapping approaches were combined with Bayesian modeling and recursive partitioning to identify structural and physicochemical requirements for highly active APN inhibitors. Based on the assumption that ligand- and structure-based pharmacophore models are complementary, the efficacy of ‘multiple pharmacophore screening’ for filtering true positive virtual hits was investigated. These multiple pharmacophore screening methods were utilized to search novel virtual hits for APN inhibition. The number of hits was refined and reduced by recursive partitioning, drug-likeliness, pharmacokinetic property prediction, and comparative molecular-docking studies. Four compounds were proposed as the potential virtual hits for APN enzyme inhibition. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11030-013-9422-5) contains supplementary material, which is available to authorized users.


COVID-19: Testing the Limits of Human Rights


title: Fragmentation of the Golgi apparatus provides replication membranes for human rhinovirus 1A

text: Abstract All viruses with a positive-stranded RNA genome replicate their genomic RNA in association with membranes from the host cell. Here we demonstrate a novel organelle source of replication membranes for human rhinovirus 1A (HRV-1A). HRV-1A infection induces fragmentation of the Golgi apparatus, and Golgi membranes are rearranged into vesicles of approximately 250–500nm diameter. The newly distributed Golgi membranes co-localize with viral RNA replication templates, strongly suggesting that the observed vesicles are the sites of viral RNA replication. Expression of the HRV-1A 3A protein induces alterations in the Golgi staining pattern similar to those seen during viral infection, and expressed 3A localizes to the Golgi-derived membranes. Taken together, these data show that in HRV-1A infection, the 3A protein plays a role in fragmenting the Golgi complex and generating vesicles that are used as the site of viral RNA replication.


title: First case of Propionibacterium acnes urinary tract infection in a dog

text: BACKGROUND: Propionibacterium acnes has been rarely isolated as a commensal from dogs, but there is little evidence of pathogenicity. Urinary tract infections are common in dogs and are typically caused by various commensal bacteria. Here we present the first case report of a urinary tract infection caused by P. acnes. CASE PRESENTATION: A 6-year-old female Japanese Shiba Inu was hospitalized for polyuria, polydipsia, and severe hematuria. At admission, blood tests revealed leukocytosis, slight anemia, decreased albumin, and slightly elevated blood urea nitrogen. Computerized tomography showed gas accumulation on the inner side of the bladder wall. Urinalysis revealed proteinuria and bilirubinuria without glycosuria. The urine sediment contained large numbers of erythrocytes and leukocytes. Additionally, rod-shaped bacteria were detected by Diff-Quik staining. Enrofloxacin and metronidazole were administered empirically; however, the renal function declined sharply and the patient died 2 days later. Bacteriological examination revealed that the causative agent was Propionibacterium acnes, which was identified as sequence type 53 via multilocus sequence typing. This isolate showed high susceptibility to ampicillin, amoxicillin/clavulanic acid, cefoxitin, imipenem, clindamycin, tetracycline, chloramphenicol, and enrofloxacin, but was resistant to metronidazole. CONCLUSION: To the best of our knowledge, this is the first case report of a dog with urinary tract infection caused by P. acnes.


title: Field Evaluation of the Effect of a Probiotic‐containing Bacillus licheniformis and Bacillus subtilis Spores on the Health Status, Performance, and Carcass Quality of Grower and Finisher Pigs

text: The aim of the study was to assess the efficacy of BioPlus 2B, a probiotic containing Bacillus licheniformis and B. subtilis spores, on the health status and productivity of pigs, during weaning, growing and finishing stages of growth. On a commercial farrow‐to‐finish farm, five experimental groups were formed, each of 54 weaned piglets. The pigs of the first group (double controls) received normal feed with no probiotic and the pigs of the second group (untreated controls) received BioPlus 2B only during the weaning stage. The pigs of the third, the fourth and the fifth group received the same as the second group feed but, at the growing and at a part of the finishing stages, supplemented with three different doses of Bioplus 2B, a low, medium and high dose, respectively. The results have shown that, compared with the double controls, BioPlus 2B‐treated pigs had a lower morbidity and mortality during the whole trial period, compared with the double controls (range from 9.26 to 14.81% versus 25.93% and from 0.00 to 3.70% versus 11.1%, respectively), as a result of the lower incidence of post‐weaning diarrhoea due mainly to Escherichia coli. Weight gain, feed conversion ratio and carcass quality of the BioPlus 2B‐treated pigs were significantly improved compared with the double controls, whilst the beneficial effects of the probiotic were more pronounced when the medium and high doses were used.


Preventing Frailty Progression During the Covid-19 Pandemic


title: Influenza vaccination situation in Middle-East and North Africa countries: Report of the 7th MENA Influenza Stakeholders Network (MENA-ISN)

text: Abstract Background The Middle East and North Africa (MENA) region faces a dual challenge with regard to influenza infection due to severe zoonotic influenza outbreaks episodes and the circulation of Northern Hemisphere human influenza viruses among pilgrims. Methods The MENA Influenza Stakeholder Network (MENA-ISN) was set-up with the aim of increasing seasonal influenza vaccination coverage by (i) enhancing evidence-based exchanges, and (ii) increasing awareness on the safety and benefits of seasonal vaccination. During the 7th MENA-ISN meeting, representatives from 8 countries presented their influenza surveillance, vaccination coverage and actions achieved and provided a list of country objectives for the upcoming 3 years. Results MENA-ISN countries share the goal to reduce influenza related morbidity and mortality. Participants admitted that lack of knowledge about influenza, its consequences in terms of morbidity, mortality and economy are the major barrier to attaining higher influenza vaccination coverage in their countries. The cost of the vaccine is another key barrier that could contribute to low vaccination coverage. Participants drew a list of strategic interventions to bridge gaps in the knowledge of influenza burden in this region. Conclusions Participating countries concluded that despite an increase in vaccine uptake observed during the last few years, influenza vaccination coverage remains relatively low. Priority areas should be identified and action plans tailored to each country situation set-up to investigate the best way to move forward.


Pacientes con carcinoma broncogénico en lista de espera en plena crisis del COVID-19: ¿Y ahora qué hacemos?


title: Fabrication of a lithium chloride solution based composite supported liquid membrane and its moisture permeation analysis

text: Abstract A novel composite supported liquid membrane has been prepared for ventilation air moisture recovery. The membrane is composed of three layers: two hydrophobic protective layers and a sandwiched hydrophilic support layer in which LiCl solution is immobilized to facilitate water vapor transfer. A test is conducted to measure the moisture permeation rate through the composite membrane. Various resistances in the cell and in the composite membrane are clarified. Linear equilibrium relations between humidity, temperature, and LiCl concentration in the liquid solution layer are obtained to aid in the model set-up. It has been found that the mean moisture permeation rate through the composite membrane is around 1.14×10−4 kgm−2 s−1, almost two times higher than that through a solid hydrophilic cellulose acetate membrane with comparative thickness. Further, the supported liquid layer only accounts for 12% of the total moisture transfer resistance in the cell, indicating that there is much potential for further performance improvement.


title: Changes in contact patterns shape the dynamics of the COVID-19 outbreak in China

text: Intense non-pharmaceutical interventions were put in place in China to stop transmission of the novel coronavirus disease (COVID-19). As transmission intensifies in other countries, the interplay between age, contact patterns, social distancing, susceptibility to infection, and COVID-19 dynamics remains unclear. To answer these questions, we analyze contact surveys data for Wuhan and Shanghai before and during the outbreak and contact tracing information from Hunan Province. Daily contacts were reduced 7-8-fold during the COVID-19 social distancing period, with most interactions restricted to the household. We find that children 0-14 years are less susceptible to SARS-CoV-2 infection than adults 15-64 years of age (odd ratio 0.34, 95%CI 0.24-0.49), while in contrast, individuals over 65 years are more susceptible to infection (odd ratio 1.47, 95%CI: 1.12-1.92). Based on these data, we build a transmission model to study the impact of social distancing and school closure on transmission. We find that social distancing alone, as implemented in China during the outbreak, is sufficient to control COVID-19. While proactive school closures cannot interrupt transmission on their own, they can reduce peak incidence by 40-60% and delay the epidemic.


title: A duplex real-time RT-PCR assay for detecting H5N1 avian influenza virus and pandemic H1N1 influenza virus

text: A duplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay was improved for simultaneous detection of highly pathogenic H5N1 avian influenza virus and pandemic H1N1 (2009) influenza virus, which is suitable for early diagnosis of influenza-like patients and for epidemiological surveillance. The sensitivity of this duplex real-time RT-PCR assay was 0.02 TCID(50 )(50% tissue culture infective dose) for H5N1 and 0.2 TCID(50 )for the pandemic H1N1, which was the same as that of each single-target RT-PCR for pandemic H1N1 and even more sensitive for H5N1 with the same primers and probes. No cross reactivity of detecting other subtype influenza viruses or respiratory tract viruses was observed. Two hundred and thirty-six clinical specimens were tested by comparing with single real-time RT-PCR and result from the duplex assay was 100% consistent with the results of single real-time RT-PCR and sequence analysis.


title: Human Bocavirus in French Children

text: Human bocavirus (HBoV), a new member of the genus Bocavirus in the family Parvoviridae, has been recently associated with respiratory tract infections. We report the epidemiologic and clinical features observed from a 1-year retrospective study of HBoV infection in young children hospitalized with a respiratory tract infection.


title: Impaired pulmonary function in discharged patients with COVID-19: More work ahead

text: Impairment of diffusion capacity is the most common abnormality in discharged patients with COVID-19. Both decreased alveolar volume and KCO contribute to the pathogenesis of impaired diffusion capacity. More work ahead for follow-up is needed.


title: Certainty of success: three critical parameters in coronavirus vaccine development

text: Vaccines for 17 viral pathogens have been licensed for use in humans. Previously, two critical biological parameters of the pathogen and the host–pathogen interaction—incubation period and broadly protective, relative immunogenicity—were proposed to account for much of the past successes in vaccine development, and to be useful in estimating the “certainty of success” of developing an effective vaccine for viral pathogens for which a vaccine currently does not exist. In considering the “certainty of success” in development of human coronavirus vaccines, particularly SARS-CoV-2, a third, related critical parameter is proposed—infectious inoculum intensity, at an individual-level, and force of infection, at a population-level. Reducing the infectious inoculum intensity (and force of infection, at a population-level) is predicted to lengthen the incubation period, which in turn is predicted to reduce the severity of illness, and increase the opportunity for an anamnestic response upon exposure to the circulating virus. Similarly, successfully implementing individual- and population-based behaviors that reduce the infectious inoculum intensity and force of infection, respectively, while testing and deploying COVID-19 vaccines is predicted to increase the “certainty of success” of demonstrating vaccine efficacy and controlling SARS-CoV-2 infection, disease, death, and the pandemic itself.


title: Evolution of China's response to HIV/AIDS

text: Summary Four factors have driven China's response to the HIV/AIDS pandemic: (1) existing government structures and networks of relationships; (2) increasing scientific information; (3) external influences that underscored the potential consequences of an HIV/AIDS pandemic and thus accelerated strategic planning; and (4) increasing political commitment at the highest levels. China's response culminated in legislation to control HIV/AIDS—the AIDS Prevention and Control Regulations. Three major initiatives are being scaled up concurrently. First, the government has prioritised interventions to control the epidemic in injection drug users, sex workers, men who have sex with men, and plasma donors. Second, routine HIV testing is being implemented in populations at high risk of infection. Third, the government is providing treatment for infected individuals. These bold programmes have emerged from a process of gradual and prolonged dialogue and collaboration between officials at every level of government, researchers, service providers, policymakers, and politicians, and have led to decisive action.


title: Deoxynivalenol (DON) naturally contaminated feed impairs the immune response induced by porcine reproductive and respiratory syndrome virus (PRRSV) live attenuated vaccine

text: Cereal commodities are frequently contaminated with mycotoxins produced by the secondary metabolism of fungal infection. Among these contaminants, deoxynivalenol (DON), also known as vomitoxin, is the most prevalent type B trichothecene mycotoxin worldwide. Pigs are very sensitive to the toxic effects of DON and are frequently exposed to naturally contaminated feed. Recently, DON naturally contaminated feed has been shown to decrease porcine reproductive and respiratory syndrome virus (PRRSV) specific antibody responses following experimental infection. The objective of this study was to determine the impact of DON naturally contaminated feed on the immune response generated following vaccination with PRRSV live attenuated vaccine. Eighteen pigs were randomly divided into three experimental groups of 6 animals based on DON content of the diets (0, 2.5 and 3.5 mg DON/kg). They were fed these rations one week prior to the vaccination and for all the duration of the immune response evaluation. All pigs were vaccinated intra-muscularly with one dose of Ingelvac(®) PRRSV modified live vaccine (MLV). Blood samples were collected at day −1, 6, 13, 20, 27 and 35 post vaccination (pv) and tested for PRRSV RNA by RT-qPCR and for virus specific antibodies by ELISA. Results showed that ingestion of DON-contaminated diets significantly decreased PRRSV viremia. All pigs fed control diet were viremic while only 1 (17%) and 3 (50%) out of 6 pigs were viremic in the groups receiving 3.5 and 2.5 mg of DON/kg, respectively. Subsequently, all pigs fed control diet developed PRRSV specific antibodies while only viremic pigs that were fed contaminated diets have developed PRRSV specific antibodies. These results suggest that feeding pigs with DON-contaminated diet could inhibit vaccination efficiency of PRRSV MLV by severely impairing viral replication.


title: Rational design of a synthetic mammalian riboswitch as a ligand-responsive -1 ribosomal frame-shifting stimulator

text: Metabolite-responsive RNA pseudoknots derived from prokaryotic riboswitches have been shown to stimulate −1 programmed ribosomal frameshifting (PRF), suggesting −1 PRF as a promising gene expression platform to extend riboswitch applications in higher eukaryotes. However, its general application has been hampered by difficulty in identifying a specific ligand-responsive pseudoknot that also functions as a ligand-dependent -1 PRF stimulator. We addressed this problem by using the −1 PRF stimulation pseudoknot of SARS-CoV (SARS-PK) to build a ligand-dependent −1 PRF stimulator. In particular, the extra stem of SARS-PK was replaced by an RNA aptamer of theophylline and designed to couple theophylline binding with the stimulation of −1 PRF. Conformational and functional analyses indicate that the engineered theophylline-responsive RNA functions as a mammalian riboswitch with robust theophylline-dependent −1 PRF stimulation activity in a stable human 293T cell-line. Thus, RNA–ligand interaction repertoire provided by in vitro selection becomes accessible to ligand-specific −1 PRF stimulator engineering using SARS-PK as the scaffold for synthetic biology application.


title: Influence of different glycoproteins and of the virion core on SERINC5 antiviral activity

text: Host plasma membrane protein SERINC5 is incorporated into budding retrovirus particles where it blocks subsequent entry into susceptible target cells. Three accessory proteins encoded by diverse retroviruses, HIV-1 Nef, EIAV S2, and MLV Glycogag, each independently disrupt SERINC5 antiviral activity, by redirecting SERINC5 from the site of virion assembly on the plasma membrane to an internal RAB7+ endosomal compartment. Pseudotyping retroviruses with particular glycoproteins, e.g., the vesicular stomatitis glycoprotein (VSV G), renders the infectivity of particles resistant to inhibition by virion-associated SERINC5. To better understand viral determinants for SERINC5-sensitivity, the effect of SERINC5 was assessed using HIV-1, MLV, and M-PMV virion cores, pseudotyped with glycoproteins from Arenavirus, Coronavirus, Filovirus, Rhabdovirus, Paramyxovirus, and Orthomyxovirus genera. Infectivity of particles, pseudotyped with HIV-1, amphotropic-MLV, or influenza virus glycoproteins, was decreased by SERINC5, whether the core was provided by HIV-1, MLV, or M-PMV. Particles generated by all three cores, and pseudotyped with glycoproteins from either avian leukosis virus-A, human endogenous retrovirus K (HERV-K), ecotropic-MLV, HTLV-1, Measles morbillivirus, lymphocytic choriomeningitis mammarenavirus (LCMV), Marburg virus, Ebola virus, severe acute respiratory syndrome-related coronavirus (SARS-CoV), or VSV, were insensitive to SERINC5. In contrast, particles pseudotyped with M-PMV, RD114, or rabies virus (RABV) glycoproteins were sensitive to SERINC5, but only with particular retroviral cores. Resistance to SERINC5 by particular glycoproteins did not correlate with reduced SERINC5 incorporation into particles or with the route of viral entry. These findings indicate that some non-retroviruses may be sensitive to SERINC5 and that, in addition to the viral glycoprotein, the retroviral core influences sensitivity to SERINC5. IMPORTANCE The importance of SERINC5 for inhibition of retroviruses is underscored by convergent evolution among three non-monophyletic retroviruses, each of which encodes a structurally unrelated SERINC5 inhibitor. One of these retroviruses causes tumors in mice, a second anemia in horses, and a third causes AIDS. SERINC5 is incorporated into retrovirus particles where it blocks entry into target cells, via a mechanism that is dependent on the viral glycoprotein. Here we demonstrate that retroviruses pseudotyped with glycoproteins from several non-retroviruses are also inhibited by SERINC5, suggesting that enveloped viruses other than retroviruses may also be inhibited by SERINC5. Additionally, we found that sensitivity to SERINC5 is determined by the retrovirus core, as well as by the glycoprotein. By better understanding how SERINC5 inhibits viruses we hope to extend fundamental understanding of virus replication and of the native role of SERINC5 in cells, and perhaps to advance the development of new antiviral strategies.


Genetic Evolution of Human Coronavirus OC43 in Neural Cell Culture


title: A windfall for US biomedical science

text: In December, the US government approved a $2 billion increase in the budget of the US National Institutes of Health (NIH) for the 2016 fiscal year. With that increase comes relief, optimism and the pressure to spend wisely.


title: Kinetics of humoral immune response to the major structural proteins of the porcine reproductive and respiratory syndrome virus

text: The kinetics of appearance of antibodies directed to the major structural proteins N, M and E of porcine reproductive and respiratory syndrome virus (PRRSV) was followed in pigs naturally- and experimentally-exposed to the virus. Specific IgM antibody titers were first detected by indirect immunofluorescence (IIF) at the end of the first week of PRRSV infection, peaked by day 14 to 21 post-inoculation (p.i.), then rapidly decreased to undetectable levels by day 35 to 42 p.i. On the other hand, specific IgG antibody titers peaked by day 21 to 28 p.i. and remained unchanged to the end of the 6- or 9-week observation period; in addition, a persistent viremia was observed. Virus neutralizing (VN) antibody titers >8 were not detected until 3 to 4 weeks p.i. Taken together, the results obtained by Western blotting analyses using purified virus andE. coli-expressed ORFs 5 to 7 gene products, suggested that antibodies directed against the envelope E protein appear by day 7 p.i., whereas antibodies directed against the nucleocapsid N and membrane M proteins can only be detected by the end of the second week p.i. No correlation could be demonstrated between VN and IIF antibody titers, viremia, and viral protein specificities of circulating antibodies at various times p.i.


title: Bat Hunting and Bat-Human Interactions in Bangladeshi Villages: Implications for Zoonotic Disease Transmission and Bat Conservation

text: Bats are an important reservoir for emerging zoonotic diseases. Close human-bat interactions, including the sharing of living spaces and hunting and butchering of bats for food and medicines, may lead to spillover of zoonotic disease into human populations. We used bat exposure and environmental data gathered from 207 Bangladeshi villages to characterize bat exposures and hunting in Bangladesh. Eleven percent of households reported having a bat roost near their homes, 65% reported seeing bats flying over their households at dusk, and 31% reported seeing bats inside their compounds or courtyard areas. Twenty percent of households reported that members had at least daily exposure to bats. Bat hunting occurred in 49% of the villages surveyed and was more likely to occur in households that reported nearby bat roosts (adjusted prevalence ratio [aPR] 2.3, 95% CI 1.1-4.9) and villages located in Northwest (aPR 7.5, 95% CI 2.5-23.0) and Southwest (aPR 6.8, 95% CI 2.1-21.6) regions. Our results suggest high exposure to bats and widespread hunting throughout Bangladesh. This has implications both for zoonotic disease spillover and bat conservation.


Radiology Department Preparedness in the COVID-19 Post-Shutdown Environment


title: Landscape and Selection of Vaccine Epitopes in SARS-CoV-2

text: There is an urgent need for a vaccine with efficacy against SARS-CoV-2. We hypothesize that peptide vaccines containing epitope regions optimized for concurrent B cell, CD4(+) T cell, and CD8(+) T cell stimulation would drive both humoral and cellular immunity with high specificity, potentially avoiding undesired effects such as antibody-dependent enhancement (ADE). Additionally, such vaccines can be rapidly manufactured in a distributed manner. In this study, we combine computational prediction of T cell epitopes, recently published B cell epitope mapping studies, and epitope accessibility to select candidate peptide vaccines for SARS-CoV-2. We begin with an exploration of the space of possible T cell epitopes in SARS-CoV-2 with interrogation of predicted HLA-I and HLA-II ligands, overlap between predicted ligands, protein source, as well as concurrent human/murine coverage. Beyond MHC affinity, T cell vaccine candidates were further refined by predicted immunogenicity, viral source protein abundance, sequence conservation, coverage of high frequency HLA alleles and co-localization of CD4(+) and CD8(+) T cell epitopes. B cell epitope regions were chosen from linear epitope mapping studies of convalescent patient serum, followed by filtering to select regions with surface accessibility, high sequence conservation, spatial localization near functional domains of the spike glycoprotein, and avoidance of glycosylation sites. From 58 initial candidates, three B cell epitope regions were identified. By combining these B cell and T cell analyses, as well as a manufacturability heuristic, we propose a set of SARS-CoV-2 vaccine peptides for use in subsequent murine studies and clinical trials.


title: Interplay between platelets and coagulation

text: Haemostasis stops bleeding at the site of vascular injury and maintains the integrity of blood vessels through clot formation. This regulated physiological process consists of complex interactions between endothelial cells, platelets, von Willebrand factor and coagulation factors. Haemostasis is initiated by a damaged vessel wall, followed with a rapid adhesion, activation and aggregation of platelets to the exposed subendothelial extracellular matrix. At the same time, coagulation factors aggregate on the procoagulant surface of activated platelets to consolidate the platelet plug by forming a mesh of cross-linked fibrin. Platelets and coagulation mutually influence each other and there are strong indications that, thanks to the interplay between platelets and coagulation, haemostasis is far more effective than the two processes separately. Clinically this is relevant because impaired interaction between platelets and coagulation may result in bleeding complications, while excessive platelet-coagulation interaction induces a high thrombotic risk. In this review, platelets, coagulation factors and the complex interaction between them will be discussed in detail.


“Flattening the Curve” of COVID-19 pandemic in Orthopaedics and Trauma: the Greek perspective.


title: Nucleic acid aptamer-based methods for diagnosis of infections

text: Abstract Infectious diseases are a serious global problem, which not only take an enormous human toll but also incur tremendous economic losses. In combating infectious diseases, rapid and accurate diagnostic tests are required for pathogen identification at the point of care (POC). In this review, investigations of diagnostic strategies for infectious diseases that are based on aptamers, especially nucleic acid aptamers, oligonucleotides that have high affinities and specificities toward their targets, are described. Owing to their unique features including low cost of production, easy chemical modification, high chemical stability, reproducibility, and low levels of immunogenicity and toxicity, aptamers have been widely utilized as bio-recognition elements (bio-receptors) for the development of infection diagnostic systems. We discuss nucleic acid aptamer-based methods that have been developed for diagnosis of infections using a format that organizes discussion according to the target pathogenic analytes including toxins or proteins, whole cells and nucleic acids. Also included is, a summary of recent advances made in the sensitive detection of pathogenic bacteria utilizing the isothermal nucleic acid amplification method. Lastly, a nucleic acid aptamer-based POC system is described and future directions of studies in this area are discussed.


title: Permissiveness of human hepatoma cell lines for HCV infection

text: BACKGROUND: Although primary and established human hepatoma cell lines have been evaluated for hepatitis C virus (HCV) infection in vitro, thus far only Huh7 cells have been found to be highly permissive for infectious HCV. Since our understanding of the HCV lifecycle would benefit from the identification of additional permissive cell lines, we assembled a panel of hepatic and non-hepatic cell lines and assessed their ability to support HCV infection. Here we show infection of the human hepatoma cell lines PLC/PRF/5 and Hep3B with cell culture-derived HCV (HCVcc), albeit to lower levels than that achieved in Huh7 cells. To better understand the reduced permissiveness of PLC and Hep3B cells for HCVcc infection, we performed studies to evaluate the ability of each cell line to support specific steps of the viral lifecycle (i.e. entry, replication, egress and spread). RESULTS: We found that while the early events in HCV infection (i.e. entry plus replication initiation) are cumulatively equivalent or only marginally reduced in PLC and Hep3B cells, later steps of the viral life cycle such as steady-state replication, de novo virus production and/or spread are impaired to different degrees in PLC and Hep3B cultures compared to Huh7 cell cultures. Interestingly, we also observed that interferon stimulated gene (i.e. ISG56) expression was significantly and differentially up-regulated in PLC and Hep3B cells following viral infection. CONCLUSIONS: We conclude that the restrictions observed later during HCV infection in these cell lines could in part be attributed to HCV-induced innate signaling. Nevertheless, the identification of two new cell lines capable of supporting authentic HCVcc infection, even at reduced levels, expands the current repertoire of cell lines amendable for the study of HCV in vitro and should aid in further elucidating HCV biology and the cellular determinants that modulate HCV infection.


title: Chimeric Pneumoviridae fusion proteins as immunogens to induce cross‐neutralizing antibody responses

text: Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV), two members of the Pneumoviridae family, account for the majority of severe lower respiratory tract infections worldwide in very young children. They are also a frequent cause of morbidity and mortality in the elderly and immunocompromised adults. High levels of neutralizing antibodies, mostly directed against the viral fusion (F) glycoprotein, correlate with protection against either hRSV or hMPV. However, no cross‐neutralization is observed in polyclonal antibody responses raised after virus infection or immunization with purified F proteins. Based on crystal structures of hRSV F and hMPV F, we designed chimeric F proteins in which certain residues of well‐characterized antigenic sites were swapped between the two antigens. The antigenic changes were monitored by ELISA with virus‐specific monoclonal antibodies. Inoculation of mice with these chimeras induced polyclonal cross‐neutralizing antibody responses, and mice were protected against challenge with the virus used for grafting of the heterologous antigenic site. These results provide a proof of principle for chimeric fusion proteins as single immunogens that can induce cross‐neutralizing antibody and protective responses against more than one human pneumovirus.


title: Time to step up: A call to action for the clinical and quantitative pharmacology community to accelerate therapeutics for COVID‐19

text: The global response to finding therapeutics for COVID‐19 is chaotic even if well intentioned. There is an opportunity, but more importantly, an obligation for the global clinical and quantitative pharmacology community to come together and use our state‐of‐the‐art tools and expertise to help society accelerate therapeutics to fight COVID‐19. This brief commentary is a call to action and highlights how the global pharmacology community should contribute to the COVID‐19 pandemic and prepare for future pandemics.


title: Use of consensus sequences for the design of high density resequencing microarrays: the influenza virus paradigm

text: BACKGROUND: A resequencing microarray called PathogenID v2.0 has been developed and used to explore various strategies of sequence selection for its design. The part dedicated to influenza viruses was based on consensus sequences specific for one gene generated from global alignments of a large number of influenza virus sequences available in databanks. RESULTS: For each HA (H1, H2, H3, H5, H7 and H9) and NA (N1, N2 and N7) molecular type chosen to be tested, 1 to 3 consensus sequences were computed and tiled on the microarray. A total of 12 influenza virus samples from different host origins (humans, pigs, horses and birds) and isolated over a period of about 50 years were used in this study. Influenza viruses were correctly identified, and in most cases with the accurate information of the time of their emergence. CONCLUSIONS: PathogenID v2.0 microarray demonstrated its ability to type and subtype influenza viruses, often to the level of viral variants, with a minimum number of tiled sequences. This validated the strategy of using consensus sequences, which do not exist in nature, for our microarray design. The versatility, rapidity and high discriminatory power of the PathogenID v2.0 microarray could prove critical to detect and identify viral genome reassortment events resulting in a novel virus with epidemic or pandemic potential and therefore assist health authorities to make efficient decisions about patient treatment and outbreak management.


title: History of the World Allergy Organization: Two Decades Leading to World Leadership, 1990-2010

text: Abstract History of the World Allergy Organization: In 1951, the leaders in allergy from all over the world came together to form the International Association of Allergology and Clinical Immunology (IAACI). For the next 60 years, the allergy world converged at the IAACI triennial meetings, which became biennial in 2003. The international meetings, originally named the International Congress of Allergology and Clinical Immunology (ICACI), are now the World Allergy Congress (WAC) hosted by the World Allergy Organization (WAO). Everyone who has aspired to have worldwide recognition has played a part in IAACI-WAO. The History of the World Allergy Organization traces the global arc of the allergy field over the past 60 years. The current officers of WAO elected to focus on this rich history, inviting prominent leaders who are interested in being part of this history project to write about their time with IAACI-WAO. This series will be presented in Cancún, México as part of the XXII World Allergy Congress (December 4-8, 2011). Leading up to the Congress in Cancún, the World Allergy Organization Journal is presenting segments of the History as part of the "Notes of Allergy Watchers Series." Please enjoy. --Michael A. Kaliner, MD Historian and Past President (2006-2007) World Allergy Organization


title: COVID-19 and assisted reproductive technology services: repercussions for patients and proposal for individualized clinical management

text: The prolonged lockdown of health services providing high-complexity fertility treatments –as currently recommended by many reproductive medicine entities– is detrimental for society as a whole, and infertility patients in particular. Globally, approximately 0.3% of all infants born every year are conceived using assisted reproductive technology (ART) treatments. By contrast, the total number of COVID-19 deaths reported so far represents approximately 1.0% of the total deaths expected to occur worldwide over the first three months of the current year. It seems, therefore, that the number of infants expected to be conceived and born –but who will not be so due to the lockdown of infertility services– might be as significant as the total number of deaths attributed to the COVID-19 pandemic. We herein propose remedies that include a prognostic-stratification of more vulnerable infertility cases in order to plan a progressive restart of worldwide fertility treatments. At a time when preventing complications and limiting burdens for national health systems represent relevant issues, our viewpoint might help competent authorities and health care providers to identify patients who should be prioritized for the continuation of fertility care in a safe environment.


title: CT differential diagnosis of COVID-19 and non-COVID-19 in symptomatic suspects: a practical scoring method

text: BACKGROUND: Although typical and atypical CT image findings of COVID-19 are reported in current studies, the CT image features of COVID-19 overlap with those of viral pneumonia and other respiratory diseases. Hence, it is difficult to make an exclusive diagnosis. METHODS: Thirty confirmed cases of COVID-19 and forty-three cases of other aetiology or clinically confirmed non-COVID-19 in a general hospital were included. The clinical data including age, sex, exposure history, laboratory parameters and aetiological diagnosis of all patients were collected. Seven positive signs (posterior part/lower lobe predilection, bilateral involvement, rounded GGO, subpleural bandlike GGO, crazy-paving pattern, peripheral distribution, and GGO +/− consolidation) from significant COVID-19 CT image features and four negative signs (only one lobe involvement, only central distribution, tree-in-bud sign, and bronchial wall thickening) from other non-COVID-19 pneumonia were used. The scoring analysis of CT features was compared between the two groups (COVID-19 and non-COVID-19). RESULTS: Older age, symptoms of diarrhoea, exposure history related to Wuhan, and a lower white blood cell and lymphocyte count were significantly suggestive of COVID-19 rather than non-COVID-19 (p < 0.05). The receiver operating characteristic (ROC) curve of the combined CT image features analysis revealed that the area under the curve (AUC) of the scoring system was 0.854. These cut-off values yielded a sensitivity of 56.67% and a specificity of 95.35% for a score > 4, a sensitivity of 100% and a specificity of 23.26% for a score > 0, and a sensitivity of 86.67% and a specificity of 67.44% for a score > 2. CONCLUSIONS: With a simple and practical scoring system based on CT imaging features, we can make a hierarchical diagnosis of COVID-19 and non-COVID-19 with different management suggestions.


title: Improving early epidemiological assessment of emerging Aedes-transmitted epidemics using historical data

text: Model-based epidemiological assessment is useful to support decision-making at the beginning of an emerging Aedes-transmitted outbreak. However, early forecasts are generally unreliable as little information is available in the first few incidence data points. Here, we show how past Aedes-transmitted epidemics help improve these predictions. The approach was applied to the 2015-2017 Zika virus epidemics in three islands of the French West Indies, with historical data including other Aedes-transmitted diseases (Chikungunya and Zika) in the same and other locations. Hierarchical models were used to build informative a priori distributions on the reproduction ratio and the reporting rates. The accuracy and sharpness of forecasts improved substantially when these a priori distributions were used in models for prediction. For example, early forecasts of final epidemic size obtained without historical information were 3.3 times too high on average (range: 0.2 to 5.8) with respect to the eventual size, but were far closer (1.1 times the real value on average, range: 0.4 to 1.5) using information on past CHIKV epidemics in the same places. Likewise, the 97.5% upper bound for maximal incidence was 15.3 times (range: 2.0 to 63.1) the actual peak incidence, and became much sharper at 2.4 times (range: 1.3 to 3.9) the actual peak incidence with informative a priori distributions. Improvements were more limited for the date of peak incidence and the total duration of the epidemic. The framework can adapt to all forecasting models at the early stages of emerging Aedes-transmitted outbreaks.


title: On pandemics, pandemonium, and possibilities…

text: Abstract We are now over three months into a viral pandemic (COVID 19) that has already left a trail of death and destruction, wreaking social and economic havoc, and disrupting, in most parts of the world, just about every aspect of life?and it is far from over It is therefore a source of some pride that the scientific and medical professions have responded in exemplary fashion and continue to do so Despite the interruptions to their research programs and careers, scientists have pooled resources and expertise, and health care providers have manned the trenches The levels of cooperation and sharing throughout the global community are unprecedented as medicine and science have collectively taken on a common foe, often accompanied by the refocusing of individual work at the expense of established activities


title: Surveillance recommendations based on an exploratory analysis of respiratory syncytial virus reports derived from the European Influenza Surveillance System

text: BACKGROUND: Respiratory syncytial virus (RSV) is an important pathogen that can cause severe illness in infants and young children. In this study, we assessed whether data on RSV collected by the European Influenza Surveillance Scheme (EISS) could be used to build an RSV surveillance system in Europe. METHODS: Influenza and RSV data for the 2002–2003 winter season were analysed for England, France, the Netherlands and Scotland. Data from sentinel physician networks and other sources, mainly hospitals, were collected. Respiratory specimens were tested for influenza and RSV mainly by virus culture and polymerase chain reaction amplification. RESULTS: Data on RSV were entered timely into the EISS database. RSV contributed noticeably to influenza-like illness: in England sentinel RSV detections were common in all age groups, but particularly in young children with 20 (40.8%) of the total number of sentinel swabs testing positive for RSV. Scotland and France also reported the highest percentages of RSV detections in the 0–4 year age group, respectively 10.3% (N = 29) and 12.2% (N = 426). In the Netherlands, RSV was detected in one person aged over 65 years. CONCLUSION: We recommend that respiratory specimens collected in influenza surveillance are also tested systematically for RSV and emphasize the use of both community derived data and data from hospitals for RSV surveillance. RSV data from the EISS have been entered in a timely manner and we consider that the EISS model can be used to develop an RSV surveillance system equivalent to the influenza surveillance in Europe.


title: Lactogenic Immunity to Transmissible Gastroenteritis (TGE) of swine induced by the attenuated nouzilly strain of TGE virus: Passive protection of piglets and detection of serum and milk antibody classes by ELISA

text: Abstract Piglets of eight sows vaccinated by different routes with the attenuated TGE mutant coronavirus, Nouzilly (N) strain, and piglets from two field seropositive sows were challenged with a virulent TGE strain. On the day of challenge and 10 days after challenge, milk and serum samples from sows were analysed for their level of neutralizing antibodies, total immunoglobulin classes and TGE antibody classes by an ELISA. No direct relationship was seen between the level of protection of the litters and the titres of the different antibody classes on the day of challenge. However, an inverse correlation was seen 10 days after challenge between protection and the level of TGE antibodies.


title: A MULTINATIONAL REPORT TO CHARACTERISE SARS-CoV-2 INFECTION IN PEOPLE WITH CYSTIC FIBROSIS

text: Abstract Information is lacking on the clinical impact of the novel coronavirus, SARS-CoV-2 on people with cystic fibrosis (CF). Our aim was to characterize SARS-CoV-2 infection in people with cystic fibrosis. Methods: Anonymised data submitted by each participating country to their National CF Registry was reported using a standardised template, then collated and summarised. Results: 40 cases have been reported across 8 countries. Of the 40 cases, 31 (78%) were symptomatic for SARS-CoV-2 at presentation, with 24 (60%) having a fever. 70% have recovered, 30% remain unresolved at time of reporting, and no deaths have been submitted. Conclusions: This early report shows good recovery from SARS-CoV-2 in this heterogeneous CF cohort. The disease course does not seem to differ from the general population, but the current numbers are too small to draw firm conclusions and people with CF should continue to strictly follow public health advice to protect themselves from infection.


Prone to survive and the priority rule in science


title: How does the COVID-19 pandemic affect the preoperative evaluation and anesthesia applied for urinary stones? EULIS eCORE–IAU multicenter collaborative cohort study

text: Stone disease is a unique condition that requires appropriate management in a timely manner as it can result in both emergent conditions and long term effects on kidney functions. In this study it is aimed to identify the up-to-date practice patterns related to preoperative evaluation and anesthesia for stone disease interventions during COVID-19 pandemic. The data of 473 patients from 11 centers in 5 different countries underwent interventions for urinary stones during the Covid-19 pandemic was collected and analyzed retrospectively. Information on the type of the stone related conditions, management strategies, anesthesiologic evaluation, anesthesia methods, and any alterations related to COVID-19 pandemic was collected. During the preoperative anesthesia evaluation thorax CT was performed in 268 (56.7%) and PCR from nasopharyngeal swab was performed in 31 (6.6%) patients. General anesthesia was applied in 337 (71.2%) patients and alteration in the method of anesthesia was recorded in 45 (9.5%) patients. A cut-off value of 21 days was detected for the hospitals to adapt changes related to COVID-19. Rate of preoperative testing, emergency procedures, conservative approaches and topical/regional anesthesia increased after 21 days. The preoperative evaluation for management of urinary stone disease is significantly affected by COVID-19 pandemic. There is significant alteration in anesthesia methods and interventions. The optimal methods for preoperative evaluation are still unknown and there is discordance between different centers. It takes 21 days for hospitals and surgeons to adapt and develop new strategies for preoperative evaluation and management of stones.


title: Prejudice in Science – the Coronavirus Story

text: In the current pandemic times, medical physicists may not be aware that there is an interesting story on two significant discoveries related to the coronavirus. One is the invention of polymerase chain reaction (PCR) and the other is the first electron microscopic observation and identification of the coronavirus. Both of them were disregarded by the reviewers and major journals declined to publish these discoveries. These days, PCR, for example, is a widespread method for analyzing DNA, having a profound effect on healthcare, especially now during the Covid-19 pandemic. Prejudice or perhaps ignorance prevail in every aspect of our society, and there is no exception in scientific research. We need to, however, learn from these two stories and be open-minded about novel discoveries and findings – as they may be just disruptive in the “right” way to lead to an unexpected breakthrough.


title: Spread of SARS-CoV-2 through Latin America and the Caribbean region: a look from its economic conditions, climate and air pollution indicators

text: We have evaluated the spread of SARS-CoV-2 through Latin America and the Caribbean (LAC) region by means of a correlation between climate and air pollution indicators, namely, average temperature, minimum temperature, maximum temperature, rainfall, average relative humidity, wind speed, and air pollution indicators PM(10), PM(2.5), and NO(2) with the COVID-19 daily new cases and deaths. The study focuses in the following LAC cities: Mexico City (Mexico), Santo Domingo (Dominican Republic), San Juan (Puerto Rico), Bogotá (Colombia), Guayaquil (Ecuador), Manaus (Brazil), Lima (Perú), Santiago (Chile), São Paulo (Brazil) and Buenos Aires (Argentina). The results show that average temperature, minimum temperature, and air quality were significantly associated with the spread of COVID-19 in LAC. Additionally, humidity, wind speed and rainfall showed a significant relationship with daily cases, total cases and mortality for various cities. Income inequality and poverty levels were also considered as a variable for qualitative analysis. Our findings suggest that and income inequality and poverty levels in the cities analyzed were related to the spread of COVID-19 positive and negative, respectively. These results might help decision-makers to design future strategies to tackle the spread of COVID-19 in LAC and around the world.


title: Global reporting of cases of COVID‐19 in psoriasis and atopic dermatitis: an opportunity to inform care during a pandemic

text: We wish to bring your attention to the PsoPROTECT (Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of Covid‐19 infecTion) and SECURE‐AD (Surveillance Epidemiology of Coronavirus Under Research Exclusion‐Atopic Dermatitis) registries; two urgent global initiatives that address an unmet need for delineating the determinants of COVID‐19 outcomes in the common cutaneous immune‐mediated inflammatory diseases (IMIDs) psoriasis and atopic dermatitis.


title: Recombinant infectious bronchitis coronavirus H120 with the spike protein S1 gene of the nephropathogenic IBYZ strain remains attenuated but induces protective immunity

text: Abstract Infectious bronchitis (IB) is a highly infectious viral disease responsible for major economic losses in the poultry industry. A reverse genetic vaccine is a safe, rapid, and effective method of achieving IB prevention and control. In this study, we constructed the recombinant strain, rH120-S1/YZ, using a reverse genetic system, based on the backbone of the H120 vaccine strain, with the S1 gene replaced with that of the QX-like nephropathogenic strain, ck/CH/IBYZ/2011, isolated in China. The results of dwarf chicken embryos, growth kinetics, and viral titration in the embryos demonstrated that the biological characteristics of the recombinant virus remained unchanged. Like the rH120-infected group and in contrast to the rIBYZ-infected group, no mortality, clinical signs, or lesions were observed in the lungs or kidneys of young chickens inoculated with rH120-S1/YZ. The viral loads in various tissues, cloacal, and oral swabs was lower in most types of samples, indicating that the rH120-S1/YZ strain was highly safe in chicks. Compared to rH120 vaccination group, when the efficacy of this strain was evaluated against the QX-like IBV strain, better protection, with 100% survival rate and no disease symptom or gross lesion was observed in the chickens vaccinated with rH120-S1/YZ. Increased levels of IBV-specific antibodies were detected in the serum of the rH120-S1/YZ-vaccinated animals 14 days post-vaccination. Collectively, our results suggest that the recombinant strain, rH120-S1/YZ, may represent a promising vaccine candidate against QX-like IBVs.


title: Destinations, disasters and public relations: Stakeholder engagement in multi-phase disaster management

text: Abstract Research about disasters in tourism has emerged in earnest since the 1990s covering insights for preparedness and response. However, recently, authors have called for more systematic and holistic approaches to tourism disaster management research. To address this gap, this study adopted a public relations perspective to refocus attention to relationships and stakeholder expectations of destination communities across multiple phases of disaster management. The authors used a mixed method approach and developed a battery of disaster management attributes by conducting interviews and analysing industry documents and the extant literature. These attributes formed part of a survey of tourism businesses. Exploratory Factor Analysis resulted in a two factor solution: i) business disaster preparedness, and ii) destination disaster response and recovery. Findings also show that participants reported a gap between the importance and destination performance of these attributes. In particular, tourism businesses perceived destinations did not adequately engage in disaster preparedness activities, which had implications for disaster response and recovery.


title: Synthesis and antiviral activity of a series of 1′-substituted 4-aza-7,9-dideazaadenosine C-nucleosides

text: Abstract A series of 1′-substituted analogs of 4-aza-7,9-dideazaadenosine C-nucleoside were prepared and evaluated for the potential as antiviral agents. These compounds showed a broad range of inhibitory activity against various RNA viruses. In particular, the whole cell potency against HCV when R=CN was attributed to inhibition of HCV NS5B polymerase and intracellular concentration of the corresponding nucleoside triphosphate.


title: Dissecting the ancient rapid radiation of microgastrine wasp genera using additional nuclear genes

text: Abstract Previous estimates of a generic level phylogeny for the ubiquitous parasitoid wasp subfamily Microgastrinae (Hymenoptera) have been problematic due to short internal branches deep in the phylogeny. These short branches might be attributed to a rapid radiation among the taxa, the use of genes that are unsuitable for the levels of divergence being examined, or insufficient quantity of data. We added over 1200 nucleotides from four nuclear genes to a dataset derived from three genes to produce a dataset of over 3000 nucleotides per taxon. While the number of well-supported short branches in the phylogeny increased, we still did not obtain strong bootstrap support for every node. Parametric and nonparametric bootstrap simulations projected that an enormous, and likely unobtainable, amount of data would be required to get bootstrap support greater than 50% for every node. However, a marked increase in the number of well-supported nodes was seen when we conducted a Bayesian analysis of a combined dataset generated from morphological characters added to the seven gene dataset. Our results suggest that, in some cases, combining morphological and genetic characters may be the most practical way to increase support for short branches deep in a phylogeny.


Telemedicine allows quantitative measuring of olfactory dysfunction in COVID‐19


title: Chloroquine dosage regimens in patients with COVID-19: safety risks and optimization using simulations

text: Currently no specific medicinal treatment exists against the new SARS-CoV2 and chloroquine is widely used, since it can decrease the length of hospital stay and improve the evolution of the associated COVID-19 pneumonia. However, several safety concerns have been raised from chloroquine use due to the lack of essential information regarding its dosing. The aim of this study is to provide a critical appraisal of the safety information regarding chloroquine treatment and to apply simulation techniques to unveil relationships between the observed serious adverse events and overdosing, as well as to propose optimized dosage regimens. The dose related adverse events of chloroquine are unveiled and maximum tolerated doses and concentration levels are quoted. Among others, treatment with chloroquine can lead to severe adverse effects like prolongation of the QT interval and cardiomyopathy. In case of chloroquine overdosing, conditions similar to those produced by SARS-CoV2, such as pulmonary oedema with respiratory insufficiency and circulatory collapse, can be observed. Co-administration of chloroquine with other drugs for the treatment of COVID-19 patients, like azithromycin, can further increase the risk of QT prolongation and cardiomyopathy. For elder patients there is a high risk for toxicity and dose reduction should be made. This study unveils the risks of some widely used dosing regimens and binds the observed serious adverse events with dosing. Based on simulations, safer alternative dosage regimens are proposed and recommendations regarding chloroquine dosing are made.