title: Atypical presentation of SARS-CoV-2 infection in male genitalia

text: Abstract During novel coronavirus 2019 (COVID-19) pandemic, patients usually present with several reports showing symptoms of severe systemic or respiratory illness and, although rare, some genital complaints such as scrotal discomfort can be seen. In the majority of patients, however, genital complaints seem not to be the initial or sole symptoms. In this article, we report an unusual presentation of a male case with severe external genital pain which was suspected to be the first clinical sign of COVID-19.


Staying in a Burning House: Perks and Perils of a Hotline in the Times of COVID‐19


title: Women and occupational lung disease: sex differences and gender influences on research and disease outcomes

text: We have attempted to describe the current state of knowledge regarding occupational lung disease in women. A large section of this article was devoted to describing the methodologic challenges that face researchers when evaluating gender differences in occupational lung disease. The findings of the presented studies are likely limited by many of the methodologic problems that were identified earlier. To accurately identify the true risk of occupational lung disease in women workers, these findings must be replicated in future studies with special attention paid to the various aspects of occupational lung disease research that are susceptible to gender-related bias.


title: 21 Infections and infestations

text: ●. Increasing population mobility means that a wide range of infections is seen globally; ●. Infections are especially common in immunodeficient people.


title: Influencing factors of COVID-19 spreading: a case study of Thailand

text: AIM: A novel corona virus disease 2019 (COVID-19) was declared as pandemic by WHO as global level and local levels in many countries. The movement of people might be one influencing factor, this paper aims to report the situation COVID-19 and spreading in Thailand, including influencing factors of spreading and control. SUBJECT AND METHOD: Infected, confirmed COVID-19 data were obtained from the official website of the Department of Disease Control, Ministry of Public Health. Tourist data was downloaded from Ministry of Tourism and Sports. Researchers analyzed the situation from the first found case in Thailand until 15 April 2020 with the timeline of important influencing factors. Correlation coefficients of tourist data and infected case was calculated by person correlation coefficient. RESULTS: The number of infected cases was significant associated (correlation coefficient > 0.7) with economic factor, namely; number of visitors, generated income from both Thai and foreigner tourist (p value <0.01). The influencing factors of slow increased rate were the enforcement and implementation of both central and local government regulation, the strength of the Thai health care system, the culture and social relation, the partnership among various governmental and private sectors. CONCLUSION: We found that the number of tourist and their activities were significant associated with number of infected, confirmed COVID-19 cases. The public education and social supporting were the key roles for regulation enforcement and implementation.


title: Saikosaponin b2 enhances the hepatotargeting effect of anticancer drugs through inhibition of multidrug resistance-associated drug transporters

text: Abstract Aims: Vinegar-baked Radix Bupleuri (VBRB) potentiates the activity of anticancer drugs in the liver by increasing their hepatic distribution. However, this phenomenon may be associated with drug transporters. We investigated the effect of saikosaponin b2 (SSb2; the main component of VBRB) on the activity and expression of different drug transporters in both normal cells and those that overexpress the transporter. Main methods: The activities of transporters were analyzed by concentration of their cellular substrates. Concentrations of colchicine (substrate of Pgp and MRP1) and cisplatin (substrate of OCT2 and MRP2) were determined by high-performance liquid chromatography (HPLC). The concentration of rhodamine B was determined by flow cytometry. The expression of transporter gene and protein were determined by qRT-PCR and Western blotting analysis. Key findings: SSb2 increased colchicine efflux in HEK293 cells by primarily increasing Mrp1 activity, independent of gene and protein expression. SSb2 enhanced Mrp2 function and increased cisplatin efflux in BRL3A cells by upregulating Mrp2 gene expression, with a marginal effect on Pgp in normal cells. SSb2 increased OCT2 activity in OCT2-HEK293 cells by increasing the expression of OCT2 protein and mRNA; however, SSb2 inhibited MRP2 activity in MRP2-HEK293 cells by decreasing MRP2 protein expression, and decreased Pgp and MRP1 activity in Pgp- and MRP1-HEK293 cells. Significance: SSb2 might potentially be the key active component of VBRB that enhances the hepatotargeting of anticancer drugs through the inhibition of multidrug resistance-associated drug transporters (Pgp, MRP1, and MRP2) in an environment-dependent manner.


title: CC Chemokine Receptor 2 is Protective Against Noise-Induced Hair Cell Death: Studies in CX3CR1(+/GFP) Mice

text: Acoustic trauma was recently shown to induce an inflammatory response in the ear characterized by rapid entry of macrophages in the spiral ligament. The current study seeks to elucidate the mechanisms involved in summoning macrophages to the cochlear lateral wall and the role macrophages play in noise-induced injury or repair. CCL2 and its primary receptor, CCR2, are the most widely validated effectors of monocyte chemotaxis in vivo. CCL2(−/−) and CCR2(−/−) mice have been used extensively in studies of monocyte activation in neuronal injury. However, the function of CCL2 and CCR2 in the cochlea has not been studied. The present study examines the role of CCL2 and CCR2 in acoustic injury. CCL2(−/−) and CCR2(−/−) mice on a CX3CR1(+/GFP) background were exposed to octave band noise (8–16 kHz) for 2 h to determine the effect of CCL2 and CCR2 on monocyte migration into the cochlea, threshold shift, and cell survival. We found that threshold shift was unchanged in the two knockout mouse strains when compared to the background strain (CX3CR1(+/GFP)). Surprisingly, we found that monocyte migration was also unchanged, despite the absence of CCL2 or CCR2. However, there was a dramatic increase in noise-induced hair cell death in the CCR2(−/−) strain. This observation suggests that CCR2, independent of CCL2, plays a protective role in the cochlea after noise, and neither ligand nor receptor is necessary for monocyte migration. Possible mechanisms of neuroprotection by CCR2 are discussed.


title: Building up the “Accountable Ulysses” model. The impact of GDPR and national implementations, ethics, and health-data research: Comparative remarks

text: Abstract The paper illustrates obligations emerging under articles 9 and 89 of the EU Reg. 2016/679 (General Data Protection Regulation, hereinafter “GDPR”) within the health-related data processing for research purposes. Furthermore, through a comparative analysis of the national implementations of the GDPR on the topic, the paper highlights few practical issues that the researcher might deal with while accomplishing the GDPR obligations and the other ethical requirements. The result of the analyses allows to build up a model to achieve an acceptable standard of accountability in health-related data research. The legal remarks are framed within the myth of Ulysses.


title: Modulation of the Host Lipid Landscape to Promote RNA Virus Replication: The Picornavirus Encephalomyocarditis Virus Converges on the Pathway Used by Hepatitis C Virus

text: Cardioviruses, including encephalomyocarditis virus (EMCV) and the human Saffold virus, are small non-enveloped viruses belonging to the Picornaviridae, a large family of positive-sense RNA [(+)RNA] viruses. All (+)RNA viruses remodel intracellular membranes into unique structures for viral genome replication. Accumulating evidence suggests that picornaviruses from different genera use different strategies to generate viral replication organelles (ROs). For instance, enteroviruses (e.g. poliovirus, coxsackievirus, rhinovirus) rely on the Golgi-localized phosphatidylinositol 4-kinase III beta (PI4KB), while cardioviruses replicate independently of the kinase. By which mechanisms cardioviruses develop their ROs is currently unknown. Here we show that cardioviruses manipulate another PI4K, namely the ER-localized phosphatidylinositol 4-kinase III alpha (PI4KA), to generate PI4P-enriched ROs. By siRNA-mediated knockdown and pharmacological inhibition, we demonstrate that PI4KA is an essential host factor for EMCV genome replication. We reveal that the EMCV nonstructural protein 3A interacts with and is responsible for PI4KA recruitment to viral ROs. The ensuing phosphatidylinositol 4-phosphate (PI4P) proved important for the recruitment of oxysterol-binding protein (OSBP), which delivers cholesterol to EMCV ROs in a PI4P-dependent manner. PI4P lipids and cholesterol are shown to be required for the global organization of the ROs and for viral genome replication. Consistently, inhibition of OSBP expression or function efficiently blocked EMCV RNA replication. In conclusion, we describe for the first time a cellular pathway involved in the biogenesis of cardiovirus ROs. Remarkably, the same pathway was reported to promote formation of the replication sites of hepatitis C virus, a member of the Flaviviridae family, but not other picornaviruses or flaviviruses. Thus, our results highlight the convergent recruitment by distantly related (+)RNA viruses of a host lipid-modifying pathway underlying formation of viral replication sites.


title: A new generic real-time reverse transcription polymerase chain reaction assay for vesiviruses; vesiviruses were not detected in human samples

text: Abstract Different viruses belonging to the genus Vesivirus infect a broad range of animals, and cause gastroenteritis, vesicular skin lesions, hemorrhagic disease, respiratory diseases and other conditions. A recent report on Vesivirus viremia, as detected by PCR, in samples from patients with hepatitis of unknown etiology in the USA suggested a zoonotic potential for vesiviruses. These results have not been confirmed by another laboratory. In order to do so, a generic PCR assay on the RNA polymerase region was developed, and validated with RNA from 69 different Vesivirus species. Except SMSV serotype-8, all species tested were detected, including the ones that were suggested to be involved in zoonotic transmission in the USA (SMSV serotype-5). The generic Vesivirus assay was used on RNA extracted from serum samples from patients with hepatitis, stool samples from patients with gastroenteritis, throat-swab specimens of patients with rash illnesses, throat-swab and nose-swabs of patients with acute respiratory diseases, and cell cultures with cytopathologic effect from enterovirus surveillance in which no pathogen was found. None were found positive. In this study a generic Vesivirus assay was developed and it was concluded that vesiviruses are an unlikely cause of common illnesses in humans in the Netherlands.


MERS Countermeasures as One of Global Health Security Agenda


title: LAMP-on-a-chip: Revising microfluidic platforms for loop-mediated DNA amplification

text: Abstract Nucleic acid amplification for the detection of infectious diseases, food pathogens, or assessment of genetic disorders require a laboratory setting with specialized equipment and technical expertise. Isothermal deoxyribonucleic acid amplification methods, such as loop-mediated isothermal amplification (LAMP), exhibit characteristics ideal for point-of-care (POC) applications, since their instrumentation is simpler in comparison with the standard method of polymerase chain reaction. Other key advantages of LAMP are robustness and the production of pyrophosphate in the presence of the target gene, enabling to detect the reaction products using the naked eye. Polymerase inhibitors, presented in clinical samples, do not affect the amplification process, making LAMP suitable for a simple sample-to-answer diagnostic systems with simplified sample preparation. In this review, we discuss the trends in miniaturized LAMP techniques, such as microfluidic, paper-based, and digital with their advantages and disadvantages, especially for POC applications alongside our opinion of the future development of miniaturized LAMP.


Natural Course of Severe Acute Respiratory Syndrome-Associated Coronavirus Immunoglobulin after Infection


title: Comment on “Organ‐protective Effect of Angiotensin‐converting Enzyme 2 and its Effect on the Prognosis of COVID‐19”

text: We read with great interest the article by Cheng H et al. The authors mentioned that angiotensin‐converting enzyme 2 (ACE2) is protective against novel coronavirus disease 2019 (COVID‐19). We would like to explain how cytosolic pH increases the COVID‐19 infection by affecting the ACE2. In addition, we would like to mention that amiloride, which increases the cytosolic pH, can be used in the COVID‐19 treatment. This article is protected by copyright. All rights reserved.


title: Cuidado respiratorio en COVID-19

text: Resumen Antecedentes El COVID-19 forma parte de la familia de los virus conocida como Coronaviridae. El nuevo patógeno β-coronavirus del subgénero Sarbecovirus se denominó inicialmente como el nuevo coronavirus (2019-nCoV); fue identificado en un brote de neumonía en Wuhan. Los pacientes desarrollan alteraciones en el sistema respiratorio, pudiendo llegar a padecer neumonía severa, edema pulmonar o síndrome de dificultad respiratoria aguda. Objetivo Revisar la evidencia científica disponible relacionada con el cuidado del sistema respiratorio, estableciendo pautas generales de tratamiento. Métodos Revisión narrativa de la literatura. Se realizó una búsqueda, selección y revisión de artículos originales y secundarios escritos en inglés o español, en las diferentes bases de datos: NCBI, CENTRAL, MEDLINE y EMBASE, publicados hasta marzo del 2020. Resultados No se ha definido un tratamiento específico ante la nueva enfermedad, teniendo como principal medida terapéutica el control sintomático. Se recomienda utilizar elementos de bioseguridad: gafas, gorros, guantes, bata larga impermeable, tapabocas de alta eficiencia en personal sanitario (FFP2 o N95). En el paciente sintomático, utilizar tapabocas quirúrgico, jabón hospitalario, toallas de papel y alcohol al 70% o isopropílico. Utilizar oxígeno mediante sistemas de bajo flujo. En ventilación mecánica, programar modos VCP o VCV, Vt 4-6ml/kg, Fr≤35, FiO2 para PaO2 de 60mmHg o SpO2 de 92-96%, PEEP 12-17cmH2O, ventilación prono si PAFI≤150 con una relación 16/8 o 18/6, óxido nítrico 5-20ppm. Conclusiones Usar equipos de bioseguridad con el fin de interrumpir la transmisión. En hipoxemia, utilizar sistemas de oxigenoterapia a bajo flujo. Usar estrategias de protección pulmonar, disminución de volúmenes corrientes, presiones de meseta y frecuencias respiratorias, implementación de valores de PEEP elevados, bajos valores de presión de conducción y ventilación en prono, los cuales han demostrado mejoraría en la hipoxemia y la sobrevida en pacientes con síndrome de dificultad respiratoria aguda. Abstract Background COVID-19 is part of the family of viruses known as Coronaviridae. The new pathogen β-coronavirus of the subgenus Sarbecovirus was initially named as a novel coronavirus (2019-nCoV), identified in a pneumonia outbreak in Wuhan. Patients developed alterations in the respiratory system leading to severe pneumonia, pulmonary oedema, and acute respiratory distress syndrome. Objective To review the available scientific evidence related to the care of the respiratory system in order to establish general treatment guidelines. Methods Narrative review of the literature was carried out that included a search, selection, and review of original and secondary articles written in English or Spanish in the different databases: NCBI, CENTRAL, MEDLINE and EMBASE published up to March 2020. Results No specific treatment for the new disease has been defined, with symptomatic control as the main therapeutic measure. The use of biosecurity elements, such as goggles, hats, gloves, long waterproof aprons, high efficiency masks for healthcare personnel (FFP2 or N95) is recommended. In symptomatic patients use surgical masks, hospital soap, paper towels, and 70% alcohol or isopropyl alcohol. Use oxygen through low flow systems. A mechanical ventilation program in VCP or VCV modes, Vt 4-6ml/Kg, Fr≤35, FiO2 for PaO2 =60mmHg or SpO2 92-96%, PEEP 12-17cmH2O, prone ventilation if PAFI≤150 with ratio 16/8 or 18/6, nitric oxide 5-20ppm. Conclusions Use biosecurity equipment in order to prevent transmission. In hypoxaemia use low flow oxygen therapy systems. Use lung protection strategies, decrease in tidal volumes, plateau pressures and respiratory rates, plus implementation of high PEEP values, low conduction pressure values and prone ventilation. These have been shown to improve hypoxaemia and survival in patients with acute respiratory distress syndrome.


title: Who complies with the restrictions to reduce the spread of COVID-19?: Personality and perceptions of the COVID-19 situation()

text: In 2020, many countries around the world created and enforced heavy restrictions geared towards reducing the spread of the coronavirus (i.e., COVID-19). In this study (N = 263), we examined the role of personality traits (i.e., Big Five and Dark Triad) and individual differences in perceptions of the COVID-19 pandemic situation (the situational eight: Duty, Intellect, Adversity, Mating, Positivity, Negativity, Deception, and Sociality) in accounting for individual differences in compliance with the governmental restrictions in Poland. We found that the way people perceived the situation explained more variance in compliance than personality traits which is in accordance with the hypothesis that strong situations, such as the COVID-19 pandemic, leave less room for dispositional tendencies in predicting behaviors than situational cues. Moreover, people scoring low on agreeableness and high on aspects of the Dark Triad traits (i.e., Machiavellianism, psychopathy Factor 1, and narcissistic rivalry) were less likely to comply with the restrictions. Additionally, we replicated and extended what is known about the associations between personality and individual differences in the perception of situations when the latter were assessed in relation to a strong situation and the former were assessed with long and multidimensional measures.


title: The influence of strain due to individual risk factors and social risk factors on depressive symptoms and suicidality-a population-based study in Korean adults: A STROBE-compliant article

text: Suicide is the outcome of the interaction of biological, personal, and social risk factors. The purpose of this study was to verify the effects of strain due to individual risk factors and social risk factors on suicidality, and the mediating effect of depressive symptoms in relationship between strain related to individual risk factors and social risk factors and suicidality. The data from sociopsychological anxiety survey of Korea society conducted by the Korea Institute for Health and Social Affairs in 2015 were used in verifying the model. We analyzed the data of 7000 adults aged 19 to 79 years using Structural Equation Modeling. Strain due to individual risk factors was positively related to depressive symptoms and suicidality. Interestingly, strain induced by social risk factors was positively associated with depressive symptoms and suicidality. Social support is significantly associated with depressive symptoms and suicidality. Depressive symptoms directly affected suicidality. In addition, strain due to individual risk factors and social risk factors indirectly affected suicidality mediating depressive symptoms. These findings suggest that not only individual efforts such as social interaction and depression prevention but also government efforts such as preparation for aging may be needed to decrease suicide rate.


title: Phytochemical Analysis and in vitro Antiviral Activities of the Essential Oils of Seven Lebanon Species

text: The chemical composition of the essential oils of Laurus nobilis, Juniperus oxycedrus ssp. oxycedrus, Thuja orientalis, Cupressus sempervirens ssp. pyramidalis, Pistacia palaestina, Salvia officinalis, and Satureja thymbra was determined by GC/MS analysis. Essential oils have been evaluated for their inhibitory activity against SARS‐CoV and HSV‐1 replication in vitro by visually scoring of the virus‐induced cytopathogenic effect post‐infection. L. nobilis oil exerted an interesting activity against SARS‐CoV with an IC (50) value of 120 μg/ml and a selectivity index (SI) of 4.16. This oil was characterized by the presence of β‐ocimene, 1,8‐cineole, α‐pinene, and β‐pinene as the main constituents. J. oxycedrus ssp. oxycedrus oil, in which α‐pinene and β‐myrcene were the major constituents, revealed antiviral activity against HSV‐1 with an IC (50) value of 200 μg/ml and a SI of 5.


title: Distinct regulation of tonsillar immune response in virus infection

text: BACKGROUND: The relationships between tonsillar immune responses, and viral infection and allergy are incompletely known. OBJECTIVE: To study intratonsillar/nasopharyngeal virus detections and in vivo expressions of T‐cell‐ and innate immune response‐specific cytokines, transcription factors, and type I/II/III interferons in human tonsils. METHODS: Palatine tonsil samples were obtained from 143 elective tonsillectomy patients. Adenovirus, bocavirus‐1, coronavirus, enteroviruses, influenza virus, metapneumovirus, parainfluenza virus, rhinovirus, and respiratory syncytial virus were detected using PCR. The mRNA expression levels of IFN‐α, IFN‐β, IFN‐γ, IL‐10, IL‐13, IL‐17, IL‐28, IL‐29, IL‐37, TGF‐β, FOXP3, GATA3, RORC2, and Tbet were directly analyzed by quantitative RT‐PCR. RESULTS: Fifty percentage of subjects reported allergy, 59% had ≥1 nasopharyngeal viruses, and 24% had ≥1 intratonsillar viruses. Tonsillar virus detection showed a strong negative association with age; especially rhinovirus or parainfluenza virus detection showed positive association with IFN‐γ and Tbet expressions. IL‐37 expression was positively associated with atopic dermatitis, whereas IFN‐α, IL‐13, IL‐28, and Tbet expressions were negatively associated with allergic diseases. Network analyses demonstrated strongly polarized clusters of immune regulatory (IL‐10, IL‐17, TGF‐β, FOXP3, GATA3, RORC2, Tbet) and antiviral (IFN‐α, IFN‐β, IL‐28, IL‐29) genes. These two clusters became more distinctive in the presence of viral infection or allergy. A negative correlation between antiviral cytokines and IL‐10, IL‐17, IL‐37, FOXP3, and RORC2 was observed only in the presence of viruses, and interestingly, IL‐13 strongly correlated with antiviral cytokines. CONCLUSIONS: Tonsillar cytokine expression is closely related to existing viral infections, age, and allergic illnesses and shows distinct clusters between antiviral and immune regulatory genes.


title: Mechanisms of Myocardial Injury in Coronavirus Disease 2019

text: Coronavirus disease 2019 (COVID-19) predominantly presents with symptoms of fever, fatigue, cough and respiratory failure. However, it appears to have a unique interplay with cardiovascular disease (CVD); patients with pre-existing CVD are at highest risk for mortality from COVID-19, along with the elderly. COVID-19 contributes to cardiovascular complications including arrhythmias, myocardial dysfunction and myocardial inflammation. Although the exact mechanism of myocardial inflammation in patients with COVID-19 is not known, several plausible mechanisms have been proposed based on early observational reports. In this article, the authors summarise the available literature on mechanisms of myocardial injury in COVID-19.


title: Proteomic analysis of Chilo iridescent virus

text: Abstract In this first proteomic analysis of an invertebrate iridovirus, 46 viral proteins were detected in the virions of Chilo iridescent virus (CIV) based on the detection of 2 or more distinct peptides; an additional 8 proteins were found based on a single peptide. Thirty-six of the 54 identified proteins have homologs in another invertebrate and/or in one or more vertebrate iridoviruses. The genes for 5 of the identified proteins, 22L (putative helicase), 118L, 142R (putative RNaseIII), 274L (major capsid protein) and 295L, are shared by all iridoviruses for which the complete nucleotide sequence is known and may therefore be considered as iridovirus core genes. Three identified proteins have homologs only in ascoviruses. The remaining 15 identified proteins are so far unique to CIV. In addition to broadening our insight in the structure and assembly of CIV virions, this knowledge is pivotal to unravel the initial steps in the infection process.


title: Type I Interferon Signaling Protects Mice From Lethal Henipavirus Infection

text: Hendra virus (HeV) and Nipah virus (NiV) are closely related, recently emerged paramyxoviruses that form Henipavirus genus and are capable of causing considerable morbidity and mortality in a number of mammalian species, including humans. However, in contrast to many other species and despite expression of functional virus entry receptors, mice are resistant to henipavirus infection. We report here the susceptibility of mice deleted for the type I interferon receptor (IFNAR-KO) to both HeV and NiV. Intraperitoneally infected mice developed fatal encephalitis, with pathology and immunohistochemical features similar to what was found in humans. Viral RNA was found in the majority of analyzed organs, and sublethally infected animals developed virus-specific neutralizing antibodies. Altogether, these results reveal IFNAR-KO mice as a new small animal model to study HeV and NiV pathogenesis, prophylaxis, and treatment and suggest the critical role of type I interferon signaling in the control of henipavirus infection.


Neutralizing antibodies in convalescent patients


title: Herbal bioactivation: The good, the bad and the ugly

text: Abstract It has been well established that the formation of reactive metabolites of drugs is associated with drug toxicity. Similarly, there are accumulating data suggesting the role of the formation of reactive metabolites/intermediates through bioactivation in herbal toxicity and carcinogenicity. It has been hypothesized that the resultant reactive metabolites following herbal bioactivation covalently bind to cellular proteins and DNA, leading to toxicity via multiple mechanisms such as direct cytotoxicity, oncogene activation, and hypersensitivity reactions. This is exemplified by aristolochic acids present in Aristolochia spp, undergoing reduction of the nitro group by hepatic cytochrome P450 (CYP1A1/2) or peroxidases in extrahepatic tissues to reactive cyclic nitrenium ion. The latter was capable of reacting with DNA and proteins, resulting in activation of H-ras oncogene, gene mutation and finally carcinogenesis. Other examples are pulegone present in essential oils from many mint species; and teucrin A, a diterpenoid found in germander (Teuchrium chamaedrys) used as an adjuvant to slimming diets. Extensive pulegone metabolism generated p-cresol that was a glutathione depletory, and the furan ring of the diterpenoids in germander was oxidized by CYP3A4 to reactive epoxide which reacts with proteins such as CYP3A and epoxide hydrolase. On the other hand, some herbal/dietary constituents were shown to form reactive intermediates capable of irreversibly inhibiting various CYPs. The resultant metabolites lead to CYP inactivation by chemical modification of the heme, the apoprotein, or both as a result of covalent binding of modified heme to the apoprotein. Some examples include bergamottin, a furanocoumarin of grapefruit juice; capsaicin from chili peppers; glabridin, an isoflavan from licorice root; isothiocyanates found in all cruciferous vegetables; oleuropein rich in olive oil; dially sulfone found in garlic; and resveratrol, a constituent of red wine. CYPs have been known to metabolize more than 95% therapeutic drugs and activate a number of procarcinogens as well. Therefore, mechanism-based inhibition of CYPs may provide an explanation for some reported herb-drug interactions and chemopreventive activity of herbs. Due to the wide use and easy availability of herbal medicines, there is increasing concern about herbal toxicity. The safety and quality of herbal medicine should be ensured through greater research, pharmacovigilance, greater regulatory control and better communication between patients and health professionals.


MicroRNAs in viral gene regulation


title: Elevated serum aspartate aminotransferase level identifies patients with coronavirus disease 2019 and predicts the length of hospital stay

text: BACKGROUND: Coronavirus disease 2019 (COVID‐19) has become a worldwide public health emergency. This study aimed to investigate the clinical significance of liver blood tests in COVID‐19 patients. METHODS: The analysis included clinical data of 23 patients with suspected COVID‐19 and 66 patients with confirmed COVID‐19 from January 25 to February 20, 2020. The relationship between liver blood test results, liver condition (HBsAb positive, HBcAb positive, and fatty liver disease), and duration of hospital stay among COVID‐19 patients was analyzed. RESULTS: The median hospital stay of COVID‐19 patients was 6 days. Serum albumin (Alb) level was lower in patients with COVID‐19 confirmed on admission than in patients with suspected COVID‐19 (40.08 g/L vs 42.50 g/L, P = .016), while the level of aspartate aminotransferase (AST) was higher (23 U/L vs 18 U/L, P = .005). Abnormal results of liver blood tests in patients with COVID‐19 included increased levels of alanine transaminase (ALT) (21.2%, 14 patients), AST (15.2%, 10 patients), and gamma‐glutamyl transpeptidase (GGT) (22.7%, 15 patients). After 5‐10 days of treatment, levels of Alb and AST in COVID‐19 patients were significantly decreased (P < .001 and P = .027, respectively). Abnormal levels of Alb and AST in patients with COVID‐19 were not associated with the liver condition (all P > .05). In addition, only levels of AST were positively correlated with the duration of hospital stay (r = .334, P = .007). CONCLUSION: Abnormal results of the liver blood test were found in COVID‐19 patients. The COVID‐19 patients on admission with the higher levels of AST might have longer hospital stays.


title: Extracellular: Plasma Membrane Proteases – Serine Proteases

text: Abstract Membrane-anchored serine proteases are a group of extracellular serine proteases tethered directly to plasma membranes, via a C-terminal glycosylphosphatidylinositol linkage (GPI-anchored), a C-terminal transmembrane domain (Type I), or an N-terminal transmembrane domain (Type II). A variety of biochemical, cellular, and in vivo studies have established that these proteases are important pericellular contributors to processes vital for the maintenance of homeostasis, including food digestion, blood pressure regulation, hearing, epithelial permeability, sperm maturation, and iron homeostasis. These enzymes are hijacked by viruses to facilitate infection and propagation, and their misregulation is associated with a wide range of diseases, including cancer malignancy.


title: Knowledge, attitude and practice regarding COVID-19 among health care workers in Henan, China

text: Summary The study analyzed health care workers’ (HCWs) knowledge, practices, and attitudes regarding COVID-19. A cross-sectional survey was conducted from 4th February to 8th February 2020 involving a total of 1357 HCWs across 10 hospitals in Henan, China. Of those surveyed, 89% of HCWs had sufficient knowledge of COVID-19, more than 85% feared self-infection with the virus, and 89.7% followed correct practices regarding COVID-19. In addition to knowledge level, some risk factors including work experience and job category influenced HCWs’ attitudes and practice concerning COVID-19. Measures must be taken to protect HCWs from risks linked to job category, work experience, working hours, educational attainment, and frontline HCWs.


title: Antigen requirements and specificity of a microplate enzyme-linked immunosorbent assay (ELISA) for detecting infectious bronchitis viral antibodies in chicken serum

text: The conditions of a rapid, indirect-enzyme linked immunosorbent assay for Infectious Bronchitis Virus (IBV) antibodies have been established. Optimal sensitivity was obtained using 10 µg/ml protein concentration of the Mass 41 strain purified from infected allantoic fluid. Specificity was demonstrated with Newcastle Disease Virus (NDV) antigen-antibody system. Negligible crossreactions were observed. After bromelain or lipase treatment IBV had an ELISA reactivity similar to untreated particles suggesting that peripheral constituents of IBV play a minor role when whole virus is adsorbed on solid phase. The method offers a simple and specific antibody assay which could be used for the laboratory diagnosis of avian infectious bronchitis.


title: IL-22 suppresses the infection of porcine enteric coronaviruses and rotavirus by activating STAT3 signal pathway

text: Abstract Interleukin-22 (IL-22), a member of the IL-10 superfamily, plays essential roles in fighting against mucosal microbial infection and maintaining mucosal barrier integrity within the intestine. However, little knowledge exists on the ability of porcine IL-22 (pIL-22) to fight against viral infection in the gut. In this study, we found that recombinant mature pIL-22 (mpIL-22) inhibited the infection of multiple diarrhea viruses, including alpha coronavirus, porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), and porcine rotavirus (PoRV), in the intestinal porcine epithelial cell line J2 (IPEC-J2) cells. mpIL-22 up-regulated the expression of the antimicrobial peptide beta-defensin (BD-2), cytokine IL-18 and IFN-λ. Furthermore, we found that mpIL-22 induced phosphorylation of STAT3 on Ser727 and Tyr705 in IPEC-J2 cells. Inhibition of STAT3 phosphorylation by S3I-201 abrogated the antiviral ability of mpIL-22 and the mpIL-22-induced expression of BD-2, IL-18, and IFN-λ. Together, mpIL-22 inhibited the infection of PoRV and enteric coronaviruses, and up-regulated the expression of antimicrobial genes in IPEC-J2, which were mediated by the activation of the STAT3 signal pathway. The significant antiviral activity of IL-22 to curtail multiple enteric diarrhea viruses in vitro suggests that pIL-22 could be a novel therapeutic against devastating viral diarrhea in piglets.


title: Genome Sequence of a Bovine Rhinitis B Virus Identified in Cattle in Sweden

text: A bovine rhinitis B virus, identified in a calf from Sweden, was genetically characterized. The complete polyprotein was recovered, and phylogenetic analysis showed that this virus has the highest similarity to a bovine rhinitis B virus previously identified in Mexico.


title: The clinical impact of the detection of potential etiologic pathogens of community-acquired pneumonia

text: Abstract The etiology of community-acquired pneumonia (CAP) is determined in less than half of the patients based on cultures of sputum and blood plus testing urine for the antigens of Streptococcus pneumoniae and Legionella pneumophila. This study added nasal polymerase chain reaction (PCR) probes for S. pneumoniae, Staphylococcus aureus, and respiratory viruses. Serum procalcitonin (PCT) levels were measured. Pathogens were identified in 78% of the patients. For detection of viruses, patients were randomized to either a 5-virus laboratory-generated PCR bundle or the 17-virus FilmArray PCR platform. The FilmArray PCR platform detected more viruses than the laboratory-generated bundle and did so in less than 2hours. There were fewer days of antibiotic therapy, P =0.003, in CAP patients with viral infections and a low serum PCT levels.


title: Mixing patterns and the spread of close-contact infectious diseases

text: Surprisingly little is known regarding the human mixing patterns relevant to the spread of close-contact infections, such as measles, influenza and meningococcal disease. This study aims to estimate the number of partnerships that individuals make, their stability and the degree to which mixing is assortative with respect to age. We defined four levels of putative at-risk events from casual (physical contact without conversation) to intimate (contact of a sexual nature), and asked university student volunteers to record details on those they contacted at these levels on three separate days. We found that intimate contacts are stable over short time periods whereas there was no evidence of repeat casual contacts with the same individuals. The contacts were increasingly assortative as intimacy increased. Such information will aid the development and parameterisation of models of close contact diseases, and may have direct use in outbreak investigations.


title: Chapter 28 Vaccines for Emerging Viral Diseases

text: Abstract Infectious diseases continue to plague mankind and evolve to keep pace with the efforts to control them. Sir William Osler captured the ongoing fear of infectious pathogens when he said, “Humanity has but three great enemies: fever, famine, and war; of these by far the greatest, by far the most terrible, is fever.” Despite the significant impact of antimicrobials and vaccines on public health, there has only been one major human pathogen eradicated—variola virus, the agent of smallpox. In its place have been a series of new and reemerging microbes responsible for isolated infections, regional outbreaks, and global pandemics. Bacterial, fungal, and parasitic pathogens have the capacity to cause widespread epidemics such as the “Black Death” caused by Yersinia pestis in 14th century Europe. However, bacteria, fungi, and parasites are less likely to cause widespread human pandemics at this point in history and are less amenable to vaccine strategies than viral diseases. Focusing on viruses, a catalog of newly discovered human pathogens from the beginning of the 20th century shows a predictable and nearly linear rate of new agents discovered over time. However, of the more than 100 virus families, only 22 have been associated with human infections, a number that seems to have plateaued. In the chapter we will concentrate on vaccines for emerging viral diseases.


title: The cardenolide ouabain suppresses coronaviral replication via augmenting a Na+/K+-ATPase-dependent PI3K_PDK1 axis signaling

text: Abstract Cardenolides are plant-derived toxic substances. Their cytotoxicity and the underlying mechanistic signaling axes have been extensively documented, but only a few anti-viral activities of cardenolides and the associated signaling pathways have been reported. Previously, we reported that a variety of cardenolides impart anti-transmissible gastroenteritis coronavirus (TGEV) activity in swine testicular (ST) cells, through targeting of the cell membrane sodium/potassium pump, Na+/K+-ATPase. Herein, we further explore the potential signaling cascades associated with this anti-TGEV activity in ST cells. Ouabain, a representative cardenolide, was found to potently diminish TGEV titers and inhibit the TGEV-induced production of IL-6 in a dose dependent manner, with 50% inhibitory concentrations of 37 nM and 23 nM respectively. By pharmacological inhibition and gene silencing, we demonstrated that PI3K_PDK1_RSK2 signaling was induced in TGEV-infected ST cells, and ouabain imparted a degree of anti-TGEV activity via further augmentation of this existing PI3K_PDK1 axis signaling, in a manner dependent upon its association with the Na+/K+-ATPase. Finally, inhibition of PI3K by LY294002 or PDK1 by BX795 antagonized the anti-viral activity of ouabain and restored the TGEV virus titer and yields. This finding is the first report of a PI3K_PDK1 signaling axis further induced by ouabain and implicated in the suppression of TGEV activity and replication; greatly illuminates the underlying mechanism of cardenolide toxicity; and is expected to result in one or more anti-viral applications for the cardenolides in the future.


title: Efficacy of an inactivated genotype 2b porcine epidemic diarrhea virus vaccine in neonatal piglets

text: Abstract Massive outbreaks of porcine epidemic diarrhea virus (PEDV) recurred in South Korea in 2013–2014 and affected approximately 40% of the swine breeding herds across the country, incurring a tremendous financial impact on producers and consumers. Despite the nationwide use of commercially available attenuated and inactivated vaccines in South Korea, PEDV has continued to plague the domestic pork industry, raising concerns regarding their protective efficacies and the need for new vaccine development. In a previous study, we isolated and serially cultivated a Korean PEDV epidemic strain, KOR/KNU-141112/2014, in Vero cells. With the availability of a cell culture-propagated PEDV strain, we are able to explore vaccination and challenge studies on pigs. Therefore, the aim of the present study was to produce an inactivated PEDV vaccine using the KNU-141112 strain and evaluate its effectiveness in neonatal piglets. Pregnant sows were immunized intramuscularly with the inactivated adjuvanted monovalent vaccine at six and three weeks prior to farrowing. Six-day-old piglets born to vaccinated or unvaccinated sows were challenged with the homogeneous KNU-141112 virus. The administration of the inactivated vaccine to sows greatly increased the survival rate of piglets challenged with the virulent strain, from 0% to approximately 92% (22/24), and significantly reduced diarrhea severity including viral shedding in feces. In addition, litters from unvaccinated sows continued to lose body weight throughout the experiment, whereas litters from vaccinated sows started recovering their daily weight gain at 7 days after the challenge. Furthermore, strong neutralizing antibody responses to PEDV were verified in immunized sows and their offspring, but were absent in the unvaccinated controls. Altogether, our data demonstrated that durable lactogenic immunity was present in dams administrated with the inactivated vaccine and subsequently conferred critical passive immune protection to their own litters against virulent PEDV infection.


Home‐based training strategy to maintain muscle function in older adults with diabetes during COVID‐19 confinement


Differences in the seasonality of MERS-CoV and influenza in the Middle East


The effect of COVID‐19 pandemic on oral medicine services in a tertiary referral center


title: VCP/p97 Is a Proviral Host Factor for Replication of Chikungunya Virus and Other Alphaviruses

text: The evolutionarily conserved AAA+ ATPase valosin-containing protein (VCP) was previously shown to be a proviral host factor for several viruses from different viral families such as Flaviviridae, Picornaviridae, and Herpesviridae. VCP was shown to affect trafficking of Sindbis virus receptor and functions as a component of Semliki Forest virus (SFV) replicase compartment. However, the role of this cellular protein was not evaluated during replication of alphaviruses including chikungunya virus (CHIKV). Using siRNA, chemical inhibitors, and trans-replication assays, we show here that VCP is a proviral factor involved in the replication of CHIKV. Immunofluorescence assays confirmed that VCP co-localized with non-structural replicase proteins but not with dsRNA foci possibly due to VCP epitope unavailability. VCP pro-viral role is also observed with other alphaviruses such as o’nyong’nyong virus (ONNV) and SFV in different human cell lines. VCP proviral roles on several viral families now extend to replication of alphaviruses CHIKV and ONNV, emphasizing the pivotal role of VCP in virus–host interaction biology.


title: On the biased nucleotide composition of the human coronavirus RNA genome

text: Abstract We investigated the nucleotide composition of the RNA genome of the six human coronaviruses. Some general coronavirus characteristics were apparent (e.g. high U, low C count), but we also detected species-specific signatures. Most strikingly, the high U and low C proportions are quite variable and act like communicating vessels, C goes down when U goes up and vice versa. U ranges among virus isolates from 30.7% to 40.3%, and C makes the opposite movement from 20.0% to 12.9%, respectively. The nucleotide biases are more pronounced in the unpaired regions of the structured RNA genome, which may suggest a certain biological function for these distinctive sequence signatures. Coronaviruses have an atypical codon usage that has been linked to mutational events operating on the viral RNA genome on an evolutionary time scale. We suggest that the atypical nucleotide bias may serve a distinct biological function and that it is the direct cause of the characteristic codon usage in these viruses. The relevance for evolution of the novel human pathogens MERS and SARS is discussed.


Serological Cross Reactivity between Zika and Dengue Viruses in Experimentally Infected Monkeys


title: From SARS to MERS: evidence and speculation

text: The Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel zoonotic pathogen. In 2012, the infectious outbreak caused by MERS-CoV in Saudi Arabia has spread to more than 1600 patients in 26 countries, resulting in over 600 deaths.Without a travel history, few clinical and radiological features can reliably differentiate MERS from SARS. But in real world, comparing with SARS, MERS presents more vaguely defined epidemiology, more severe symptoms, and higher case fatality rate. In this review, we summarize the recent findings in the field of MERS-CoV, especially its molecular virology, interspecies mechanisms, clinical features, antiviral therapies, and the further investigation into this disease. As a newly emerging virus, many questions are not fully answered, including the exact mode of transmission chain, geographical distribution, and animal origins. Furthermore, a new protocol needs to be launched to rapidly evaluate the effects of unproven antiviral drugs and vaccine to fasten the clinical application of new drugs.


title: Estimating the burden of SARS-CoV-2 in France

text: France has been heavily affected by the SARS-CoV-2 epidemic and went into lockdown on the 17 March 2020. Using models applied to hospital and death data, we estimate the impact of the lockdown and current population immunity. We find 3.6% of infected individuals are hospitalized and 0.7% die, ranging from 0.001% in those <20 years of age (ya) to 10.1% in those >80ya. Across all ages, men are more likely to be hospitalized, enter intensive care, and die than women. The lockdown reduced the reproductive number from 2.90 to 0.67 (77% reduction). By 11 May 2020, when interventions are scheduled to be eased, we project 2.8 million (range: 1.8–4.7) people, or 4.4% (range: 2.8–7.2) of the population, will have been infected. Population immunity appears insufficient to avoid a second wave if all control measures are released at the end of the lockdown.


title: Investigational treatments for COVID-19 may increase ventricular arrhythmia risk through drug interactions

text: Many drugs that have been proposed for treatment of COVID-19 are reported to cause cardiac adverse events, including ventricular arrhythmias. In order to properly weigh risks against potential benefits, particularly when decisions must be made quickly, mathematical modeling of both drug disposition and drug action can be useful for predicting patient response and making informed decisions. Here we explored the potential effects on cardiac electrophysiology of 4 drugs proposed to treat COVID-19: lopinavir, ritonavir, chloroquine, and azithromycin, as well as combination therapy involving these drugs. Our study combined simulations of pharmacokinetics (PK) with quantitative systems pharmacology (QSP) modeling of ventricular myocytes to predict potential cardiac adverse events caused by these treatments. Simulation results predicted that drug combinations can lead to greater cellular action potential prolongation, analogous to QT prolongation, compared with drugs given in isolation. The combination effect can result from both pharmacokinetic and pharmacodynamic drug interactions. Importantly, simulations of different patient groups predicted that females with pre-existing heart disease are especially susceptible to drug-induced arrhythmias, compared males with disease or healthy individuals of either sex. Overall, the results illustrate how PK and QSP modeling may be combined to more precisely predict cardiac risks of COVID-19 therapies.


Nasopharyngeal Detection of Severe Acute Respiratory Syndrome-Associated Coronavirus RNA in Health-Care Workers


Cardiac Troponin-I may be a predictor of complications and mortality in COVID-19 patients.


title: Older Cancer Patients during the COVID-19 Epidemic: Practice Proposal of the International Geriatric Radiotherapy Group

text: The coronavirus disease 19 (COVID-19) pandemic is unprecedented as it reached all countries in the world within a record short period of time. Even though COVID-19 infection may be just severe in any adults, older adults (65-year-old or older) may experience a higher mortality rate. Among those affected, cancer patients may have a worse outcome compared to the general population because of their depressed immune status. As the health resources of most countries are limited, clinicians may face painful decisions about which patients to save if they require artificial ventilation. Cancer patients, especially the older ones, may be denied supportive care because of their shorter life expectancy. Thus, special considerations should be taken to prevent infection of older cancer patients and to provide them with adequate social support during their cancer treatment. The following proposal was reached: (1) Education of health care providers about the special needs of older cancer patients and their risks of infection. (2) Special consideration such as surgical masks and separate scheduling should be made to protect them from being infected. (3) Social services such as patient navigators should be provided to ensure adequate medical supply, food, and daily transportation to cancer centers. (4) Close monitoring through phone calls, telecommunication to ensure social distancing and psychological support from patient family to prevent anxiety and depression. (5) Shorter course of radiotherapy by use of hypofractionation where possible to decrease the needs for daily transportation and exposure to infection. (6) Enrollment of older cancer patients in clinical trials for potential antiviral medications if infection does occur. (7) Home health care telemedicine may be an effective strategy for older cancer patients with COVID-19 infection to avoid hospital admission when health care resources become restricted. (8) For selected patients, immunotherapy and targeted therapy may become the systemic therapy of choice for older cancer patients and need to be tested in clinical trials.


title: Adapting to a new normal? 5 key operational principles for a radiology service facing the COVID-19 pandemic

text: • Radiology services encountering the coronavirus disease-19 pandemic will need to modify their daily operational practices. • Leadership, patient risk stratification, adequate manpower, operational workflow clarity, and workplace/social responsibility will help Radiology services safely and sustainably deal with the current disease outbreak.


title: Contribution of complement activation pathways to neuropathology differs among mouse models of Alzheimer's disease

text: BACKGROUND: Complement proteins and activation products have been found associated with neuropathology in Alzheimer's disease (AD). Recently, a C5a receptor antagonist was shown to suppress neuropathology in two murine models of AD, Tg2576 and 3xTg. Previously, a genetic deficiency of C1q in the Tg2576 mouse model showed an accumulation of fibrillar plaques similar to the complement sufficient Tg2576, but reactive glia were significantly decreased and neuronal integrity was improved suggesting detrimental consequences for complement activation in AD. The goal of this study was to define the role of the classical complement activation pathway in the progression of pathology in the 3xTg mouse that develops tangles in addition to fibrillar plaques (more closely reflecting human AD pathology) and to assess the influence of complement in a model of AD with a higher level of complement hemolytic activity. METHODS: 3xTg mice deficient in C1q (3xTgQ-/-) were generated, and both 3xTg and 3xTgQ-/- were backcrossed to the BUB mouse strain which has higher in vitro hemolytic complement activity. Mice were aged and perfused, and brain sections stained for pathological markers or analyzed for proinflammatory marker expression. RESULTS: 3xTgQ-/- mice showed similar amounts of fibrillar amyloid, reactive glia and hyperphosphorylated tau as the C1q-sufficient 3xTg at the ages analyzed. However, 3xTg and 3xTgQ-/- on the BUB background developed pathology earlier than on the original 3xTg background, although the presence of C1q had no effect on neuropathological and pro-inflammatory markers. In contrast to that seen in other transgenic models of AD, C1q, C4 and C3 immunoreactivity was undetectable on the plaques of 3xTg in any background, although C3 was associated with reactive astrocytes surrounding the plaques. Importantly, properdin a component of the alternative complement pathway was associated with plaques in all models. CONCLUSIONS: In contrast to previously investigated transgenic models of AD, development of neuropathology in 3xTg mice, which progresses much slower than other murine models, may not be influenced by fibrillar amyloid mediated activation of the classical complement pathway, suggesting that the alternative complement pathway activation or a C3-independent cleavage of C5 could account for the detrimental effects in these mice that are prevented by the C5a receptor antagonist. Furthermore, the paucity of complement activation may be a factor in the slower kinetics of progression of pathology in the 3xTg model of this disease.


title: The role of head and neck cancer advocacy organizations during the COVID‐19 pandemic

text: The COVID‐19 pandemic has had a significant impact on many aspects of head and neck cancer (HNC) care. The uncertainty and stress resulting from these changes has led many patients and caregivers to turn to HNC advocacy groups for guidance and support. Here we outline some of the issues being faced by patients with HNC during the current crisis and provide examples of programs being developed by advocacy groups to address them. We also highlight the increased utilization of these organizations that has been observed as well as some of the challenges being faced by these not‐for‐profit groups as they work to serve the head and neck community.


Virus diarrhoea in hospital


title: Characterisation of the RNA binding properties of the coronavirus infectious bronchitis virus nucleocapsid protein amino-terminal region

text: Abstract The coronavirus nucleocapsid (N) protein binds viral RNA to form the ribonucleocapsid and regulate RNA synthesis. The interaction of N protein with viral RNA was investigated using circular dichroism and surface plasmon resonance. N protein underwent a conformational change upon binding viral RNA and the data indicated electrostatic interactions were involved in the binding of the protein to RNA. Kinetic analysis suggested the amino-terminal region facilitates long-range non-specific interactions between N protein and viral RNA, thus bringing the RNA into close proximity to N protein allowing specific contacts to form via a ‘lure’ and ‘lock’ mechanism.


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title: Role of Host Reticulon Proteins in Rearranging Membranes for Positive-strand RNA Virus Replication

text: Positive-strand RNA [(+)RNA] viruses are responsible for numerous human, animal, and plant diseases. Because of the limiting coding capacity of (+)RNA viruses, their replication requires a complex orchestration of interactions between the viral genome, viral proteins and exploited host factors. To replicate their genomic RNAs, (+)RNA viruses induce membrane rearrangements that create membrane-linked RNA replication compartments. Along with substantial advances on the ultrastructure of the membrane-bound RNA replication compartments, recent results have shed light into the role that host factors play in rearranging these membranes. This review focuses on recent insights that have driven a new understanding of the role that the membrane-shaping host reticulon homology domain proteins (RHPs) play in facilitating the replication of various (+)RNA viruses.


title: Triage of Patients with Venous and Lymphatic Diseases during the COVID-19 pandemic- the Venous and Lymphatic Triage and Acuity Scale (VELTAS)

text: The coronavirus disease 2019 (COVID-19) global pandemic has resulted in diversion of healthcare resources to the management of patients infected with SARS-CoV-2 virus. Elective interventions and surgical procedures in most countries have been postponed and operating room resources have been diverted to manage the pandemic. The Venous and Lymphatic Triage and Acuity Scale (VELTAS) was developed to provide an international standard to rationalise and harmonise the management of patients with venous and lymphatic disorders or vascular anomalies. Triage urgency was determined based on clinical assessment of urgency with which a patient would require medical treatment or surgical intervention. Clinical conditions were classified into six categories of: 1) Venous thromboembolism (VTE), 2) Chronic Venous Disease (CVD), 3) Vascular anomalies, 4) Venous trauma 5) Venous compression and 6) Lymphatic disease. Triage urgency was categorised into four groups and individual conditions were allocated to each class of triage. These included 1) Medical Emergencies (requiring immediate attendance), example massive pulmonary embolism; 2) Urgent (to be seen as soon as possible), example deep vein thrombosis ; 3) Semi-urgent (to be attended to within 30-90 days), example highly symptomatic CVD, and 4) Discretionary/Non-urgent- (to be seen within 6-12 months), example chronic lymphoedema. VELTAS aims to standardise the triage of patients with venous and lymphatic disease or vascular anomalies by providing an international consensus-based classification of clinical categories and triage urgency. The scale may be used during pandemics such as the current COVID-19 crisis but may also be used as a general framework to classify urgency of the listed conditions.


Dermatologists’ Role in the Diagnosis and Management of Coronavirus Disease 2019 Coagulopathy


title: A monoclonal antibody binds to threonine 49 in the non-structural 1 protein of influenza A virus and interferes with its ability to modulate viral replication

text: Abstract The emergence of resistant influenza A viruses highlights the continuous requirement of new antiviral drugs that can treat the viral infection. Non-structural 1 (NS1) protein, an indispensable component for efficient virus replication, can be used as a potential target for generating new antiviral agents. Here, we study the interaction of 2H6 monoclonal antibody with NS1 protein and also determine whether influenza virus replication can be inhibited by blocking NS1. The 2H6-antigen binding fragment (Fab) forms a multimeric complex with the NS1 RNA-binding domain (RBD). T49, a residue which forms a direct hydrogen bond with double stranded RNA, in NS1 protein was found to be critical for its interaction with 2H6 antibody. NS1(RBD) has high affinity to 2H6 with KD of 43.5±4.24nM whereas NS1(RBD)-T49A has more than 250 times lower affinity towards 2H6. Interestingly, the intracellular expression of 2H6-single-chain variable fragment (scFv) in mammalian cells caused a reduction in viral growth and the M1 viral protein level was significantly reduced in 2H6-scFv transfected cells in comparison to vector transfected cells at 12h post infection. These results indicate that the tight binding of 2H6 to NS1 could lead to reduction in viral replication and release of progeny virus. In future, 2H6 antibody in combination with other neutralizing antibodies can be used to increase the potency of viral inhibition.


title: Cytoplasmic tail of coronavirus spike protein has intracellular targeting signals

text: Intracellular trafficking and localization studies of spike protein from SARS and OC43 showed that SARS spike protein is localized in the ER or ERGIC compartment and OC43 spike protein is predominantly localized in the lysosome. Differential localization can be explained by signal sequence. The sequence alignment using Clustal W shows that the signal sequence present at the cytoplasmic tail plays an important role in spike protein localization. A unique GYQEL motif is identified at the cytoplasmic terminal of OC43 spike protein which helps in localization in the lysosome, and a novel KLHYT motif is identified in the cytoplasmic tail of SARS spike protein which helps in ER or ERGIC localization. This study sheds some light on the role of cytoplasmic tail of spike protein in cell-to-cell fusion, coronavirus host cell fusion and subsequent pathogenicity.


title: Arbidol: A potential antiviral drug for the treatment of SARS-CoV-2 by blocking the trimerization of viral spike glycoprotein ?

text: Abstract The SARS-CoV-2 pandemic is an urgent global public health emergency and warrants investigating studies on bonafide antivirals for combat. Here we report the drug target and mechanism of action of potential antiviral drug Arbidol for SARS-CoV-2 infections. Our structural and molecular dynamics studies show how Arbidol targets the SARS-CoV-2 spike glycoprotein and impede the trimerization of spike glycoprotein, which is a key for host cell adhesion and hijacking, thus placing Arbidol as a potential drug for repurposing. This study also abets in the development of other new therapeutics for COIVD-19 disease based on Arbidol binding mode and using structure-guided drug designing.


title: Comparison of UV-induced AOPs (UV/Cl(2), UV/NH(2)Cl, UV/ClO(2) and UV/H(2)O(2)) in the degradation of iopamidol: Kinetics, energy requirements and DBPs-related toxicity in sequential disinfection processes

text: The UV-induced advanced oxidation processes (AOPs, including UV/Cl(2), UV/NH(2)Cl, UV/ClO(2) and UV/H(2)O(2)) degradation kinetics and energy requirements of iopamidol as well as DBPs-related toxicity in sequential disinfection were compared in this study. The photodegradation of iopamidol in these processes can be well described by pseudo-first-order model and the removal efficiency ranked in descending order of UV/Cl(2)>UV/H(2)O(2)>UV/NH(2)Cl>UV/ClO(2)>UV. The synergistic effects could be attributed to diverse radical species generated in each system. Influencing factors of oxidant dosage, UV intensity, solution pH and water matrixes (Cl(-), NH(4)(+) and nature organic matter) were evaluated in detail. Higher oxidant dosages and greater UV intensities led to bigger pseudo-first-order rate constants (K(obs)) in these processes, but the pH behaviors exhibited quite differently. The presence of Cl(−), NH(4)(+) and nature organic matter posed different effects on the degradation rate. The parameter of electrical energy per order (EE/O) was adopted to evaluate the energy requirements of the tested systems and it followed the trend of UV/ClO(2)>UV>UV/NH(2)Cl>UV/H(2)O(2)>UV/Cl(2). Pretreatment of iopamidol by UV/Cl(2) and UV/NH(2)Cl clearly enhanced the production of classical disinfection by-products (DBPs) and iodo-trihalomethanes (I-THMs) during subsequent oxidation while UV/ClO(2) and UV/H(2)O(2) exhibited almost elimination effect. From the perspective of weighted water toxicity, the risk ranking was UV/NH(2)Cl>UV/Cl(2)>UV>UV/H(2)O(2)> UV/ClO(2). Among the discussed UV-driven AOPs, UV/Cl(2) was proved to be the most cost-effective one for iopamidol removal while UV/ClO(2) displayed overwhelming advantages in regulating the water toxicity associated with DBPs, especially I-THMs. The present results could provide some insights into the application of UV-activated AOPs technologies in tradeoffs between cost-effectiveness assessment and DBPs- related toxicity control of the disinfected waters containing iopamidol.


title: Partial Derivative Nonlinear Global Pandemic Machine Learning Prediction Of Covid 19

text: The recent worldwide outbreak of the novel coronavirus disease 2019 (COVID-19) opened new challenges for the research community. Machine learning (ML)-guided methods can be useful for feature prediction, involved risk, and the causes of an analogous epidemic. Such predictions can be useful for managing and intercepting the outbreak of such diseases. The foremost advantages of applying ML methods are handling a wide variety of data and easy identification of trends and patterns of an undetermined nature.In this study, we propose a partial derivative regression and nonlinear machine learning (PDR-NML) method for global pandemic prediction of COVID-19. We used a progressive partial derivative linear regression model to search for the best parameters in the dataset in a computationally efficient manner. Next, a nonlinear global pandemic machine learning model was applied to the normalized features for making accurate predictions. The results show that the proposed ML method outperformed state-of-the-art methods in the Indian population and can also be a convenient tool for making predictions for other countries.


The effective use of telemedicine to save lives and maintain structure in a healthcare system: Current response to COVID-1


title: What is known about paediatric nurse burnout: a scoping review

text: Burnout in healthcare providers has impacts at the level of the individual provider, patient, and organization. While there is a substantial body of literature on burnout in healthcare providers, burnout in pediatric nurses has received less attention. This subpopulation may be unique from adult care nurses because of the specialized nature of providing care to children who are typically seen as a vulnerable population, the high potential for empathetic engagement, and the inherent complexities in the relationships with families. Thus, the aim of this scoping review was to investigate, among pediatric nurses, (i) the prevalence and/or degree of burnout, (ii) the factors related to burnout, (iii) the outcomes of burnout, and (iv) the interventions that have been applied to prevent and/or mitigate burnout. This scoping review was performed according to the PRISMA Guidelines Scoping Review Extension. CINAHL, EMBASE, MEDLINE, PsycINFO, ASSIA, and The Cochrane Library were searched on 3 November 2018 to identify relevant quantitative, qualitative, and mixed-method studies on pediatric nurse burnout. Our search identified 78 studies for inclusion in the analysis. Across the included studies, burnout was prevalent in pediatric nurses. A number of factors were identified as impacting burnout including nurse demographics, work environment, and work attitudes. Similarly, a number of outcomes of burnout were identified including nurse retention, nurse well-being, patient safety, and patient-family satisfaction. Unfortunately, there was little evidence of effective interventions to address pediatric nurse burnout. Given the prevalence and impact of burnout on a variety of important outcomes, it is imperative that nursing schools, nursing management, healthcare organizations, and nursing professional associations work to develop and test the interventions to address key attitudinal and environmental factors that are most relevant to pediatric nurses.


title: Antiviral Effects of Plant-Derived Essential Oils and Their Components: An Updated Review

text: The presence of resistance to available antivirals calls for the development of novel therapeutic agents. Plant-derived essential oils may serve as alternative sources of virus-induced disease therapy. Previous studies have demonstrated essential oils to be excellent candidates to treat antiviral-resistant infection associated with their chemical complexity which confers broad-spectrum mechanisms of action and non-specific antiviral properties. However, almost no comprehensive reviews are updated to generalize knowledge in this regard and disclose the interplay between the components and their antiviral activities. This review provides an up-to-date overview of the antiviral efficacy of essential oils from a wide range of plant species and their characteristic components, as well as their overall mechanisms of action, focusing on the last decade. The roles of individual components relative to the overall antiviral efficacy of essential oils, together with the antiviral activity of essential oils in comparison with commercial drugs are also discussed. Lastly, the inadequacies in current research and future research are put forward. This review will provide references in the design of new drug prototypes and improve our understanding of the proper applications of essential oils in the future.


title: COVID‐19 and raising the value of care

text: In this opinion piece, we argue the current pandemic is shining a light on caregiving as critical work that is under‐valued and under‐paid. We call upon national lawmakers to raise the value of care work. Doing so would also make progress in solving another national crisis: closing the gender wage gap. We explore how the gender wage gap is driven primarily by the fact that men and women sort into different work, with women being over‐represented in work where they care for others and in work that allows them to care for their families.


title: Sequence analysis reveals extensive polymorphism and evidence of deletions within the E2 glycoprotein gene of several strains of murine hepatitis virus

text: Abstract Direct RNA sequence analysis of the E2 gene of wild-type MHV-4 and of neutralization resistant, neuroattenuated variants has identified a polymorphic region with respect to deletions. These variants had large deletions of 142 to 159 amino acids mapping to a localized region in the amino-terminal domain of the peplomer glycoprotein. The nucleotide sequence of the E2 gene for wild-type strain MHV-4 was found to be very similar to that of MHV-JHM but had an insertion of 423 nucleotides resulting in the addition of a stretch of 141 unique amino acids in the amino-terminal domain of E2. We propose that deletions reflect a major source of heterogeneity in the E2 protein of MHV.


title: Personal exposure to nitrogen dioxide (NO2) and the severity of virus-induced asthma in children

text: Summary Background A link between exposure to the air pollutant nitrogen dioxide (NO2) and respiratory disease has been suggested. Viral infections are the major cause of asthma exacerbations. We aimed to assess whether there is a relation between NO2 exposure and the severity of asthma exacerbations caused by proven respiratory viral infections in children. Methods A cohort of 114 asthmatic children aged between 8 and 11 years recorded daily upper and lower respiratory-tract symptoms, peak expiratory flow (PEF), and measured personal NO2 exposures every week for up to 13 months. We took nasal aspirates during reported episodes of upper respiratory-tract illness and tested for infection by common respiratory viruses and atypical bacteria with RT-PCR assays. We used generalised estimating equations to assess the relation between low (<7·5 μg/m3), medium (7·5–14 μg/m3), and high (>14 μg/m3) tertiles of NO2 exposure in the week before or after upper respiratory-tract infection and the severity of asthma exacerbation in the week after the start of an infection. Findings One or more viruses were detected in 78% of reported infection episodes, and the medians of NO2 exposure were 5 (IQR 3·6–6·3), 10 (8·7–12·0), and 21 μg/m3 (16·8–42·9) for low, medium, and high tertiles, respectively. There were significant increases in the severity of lower respiratory-tract symptom scores across the three tertiles (0·6 for all viruses [p=0·05] and >2 for respiratory syncytial virus [p=0·01]) and a reduction in PEF of more than 12 L/min for picornavirus (p=0·04) for high compared with low NO2 exposure before the start of the virus-induced exacerbation. Interpretation High exposure to NO2 in the week before the start of a respiratory viral infection, and at levels within current air quality standards, is associated with an increase in the severity of a resulting asthma exacerbation.


title: Cross-sectional prevalence study of MERS-CoV in local and imported dromedary camels in Saudi Arabia, 2016-2018

text: The Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) is an endemic virus in Middle Eastern and African dromedaries. Annually, Saudi Arabia imports thousands of camels from the Horn of Africa, yet the epidemiology of the virus in these animals is largely unknown. Here, MERS-CoV prevalence was compared in imported African camels and their local counterparts. A total of 1399 paired sera and nasal swabs were collected between 2016 and 2018 from camels from Sudan (n = 829), Djibouti (n = 328) and Jeddah (n = 242). Imported animals were sampled on incoming ships at Jeddah Islamic seaport before unloading. Samples were screened for neutralizing antibodies (nAbs) and MERS-CoV viral RNA by RT-PCR. The overall seroprevalence was 92.7% and RNA detection rate was 17.2 %. Imported camels had higher seroprevalence compared to resident herds (93.8% vs 87.6%, p < 0.01) in contrast to RNA detection (13.3% vs 35.5%, p < 0.0001). Seroprevalence significantly increased with age (p < 0.0001) and viral RNA detection rate was ∼2-folds in camels < 2-year-old compared to older camels. RNA detection was higher in males verses females (24.3% vs 12.6%, p < 0.0001) but seroprevalence was similar. Concurrent positivity for viral RNA and nAbs was found in > 87 % of the RNA positive animals, increased with age and was sex-dependent. Importantly, reduced viral RNA load was positively correlated with nAb titers. Our data confirm MERS-CoV widespread in imported and domestic camels in Saudi Arabia and highlight the need for continuous active surveillance and better prevention measures. Further studies are also warranted to understand the correlates of protection in camels for proper vaccine development.


title: Comparison of trends in the quantity and variety of Science Citation Index (SCI) literature on human pathogens between China and the United States

text: The proportion of pathogenic microorganisms in the microbial world is relatively small, while their threat to human health, economic development and social stability is severe. The quantity and variation of Science Citation Index (SCI) literature related to pathogenic microorganisms may reflect the level of relevant research and the degree of attention. Here we compared trends in the quantity and variety of SCI literature relating to certain important pathogenic microorganisms published by scientists from United States and China from 1996 to 2010 by searching the Science Citation Index database. The pathogenic microorganisms in this study comprise two categories of pathogens: Bacillus anthracis, Yersinia pestis, Francisella tularensis, Ebola virus, Burkholderia pseudomallei, which belong to biodefense-associated pathogens (BDAPs) and the human immunodeficiency virus (HIV), SARS coronavirus, hepatitis B virus (HBV), Mycobacterium tuberculosis, influenza virus, which belong to the commonly encountered health-threatening pathogens. Our results showed that the United States (US) published much more SCI literature on these pathogens than China. Furthermore, literature on BDAPs published by scientists from the US has increased sharply since 2002. However, the numbers of literature relating to CEHTPs from China has demonstrated a gradual increase from 1996 to 2010. Research into pathogenic microorganisms requires three balance to be achieved: investment in BDAP and CEHTP studies; basic and applied research; a faster pace of research into pathogens and fulfilling biosafety and biosecurity requirements.


title: What Does Putin Promise Russians? Russia's Authoritarian Social Policy

text: Abstract In his 20 years in power, Vladimir Putin has employed a savvy use of social policy to bolster his popularity, but it is a set of policies not well designed to address Russia's chronic under-provision of healthcare, education, and other social services—particularly in rural areas. The COVID-19 global pandemic will only exacerbate Russia's social policy challenges and could pose a threat to Putin's political survival.


title: Microarrays for Pathogen Detection and Analysis

text: DNA microarrays have emerged as a viable platform for detection of pathogenic organisms in clinical and environmental samples. These microbial detection arrays occupy a middle ground between low cost, narrowly focused assays such as multiplex PCR and more expensive, broad-spectrum technologies like high-throughput sequencing. While pathogen detection arrays have been used primarily in a research context, several groups are aggressively working to develop arrays for clinical diagnostics, food safety testing, environmental monitoring and biodefense. Statistical algorithms that can analyze data from microbial detection arrays and provide easily interpretable results are absolutely required in order for these efforts to succeed. In this article, we will review the most promising array designs and analysis algorithms that have been developed to date, comparing their strengths and weaknesses for pathogen detection and discovery.


Corona and resource resilience—is efficiency still a desirable goal?


Real-Time Remote Surveillance of Doffing During COVID-19 Pandemic: Enhancing Safety of Health Care Workers


title: New muramyl dipeptide (MDP) mimics without the carbohydrate moiety as potential adjuvant candidates for a therapeutic hepatitis B vaccine (HBV)

text: A series of new muramyl dipeptide (MDP) mimics were designed and synthesized via a solid-phase synthetic route. Their adjuvant activities were evaluated ex vivo for investigation of the synergism of the S(28–39) peptide, which is an MHC class I binding epitope of recombinant hepatitis B surface antigen (HBsAg) for both humans and mice. Several compounds without the carbohydrate moiety exerted better adjuvanticity than the MDP-C that has been reported by our laboratory previously. A primary screening test revealed that compounds 6, 14 and 16 exhibited stronger adjuvanticity compared with other MDP mimics.


title: Inactivation of Viruses on Surfaces by Ultraviolet Germicidal Irradiation

text: In many outbreaks caused by viruses, the transmission of the agents can occur through contaminated environmental surfaces. Because of the increasing incidence of viral infections, there is a need to evaluate novel engineering control methods for inactivation of viruses on surfaces. Ultraviolet germicidal irradiation (UVGI) is considered a promising method to inactivate viruses. This study evaluated UVGI effectiveness for viruses on the surface of gelatin-based medium in a UV exposure chamber. The effects of UV dose, viral nucleic acid type (single-stranded RNA, ssRNA; single-stranded DNA, ssDNA; double-stranded RNA, dsRNA; and double-stranded DNA, dsDNA), and relative humidity on the virus survival fraction were investigated. For 90% viral reduction, the UV dose was 1.32 to 3.20 mJ/cm(2) for ssRNA, 2.50 to to 4.47 mJ/cm(2) for ssDNA, 3.80 to 5.36 mJ/cm(2) for dsRNA, and 7.70 to 8.13 mJ/cm(2) for dsDNA. For all four tested viruses, the UV dose for 99% viral reduction was 2 times higher than those for 90% viral reduction. Viruses on a surface with single-stranded nucleic acid (ssRNA and ssDNA) were more susceptible to UV inactivation than viruses with double-stranded nucleic acid (dsRNA and dsDNA). For the same viral reduction, the UV dose at 85% relative humidity (RH) was higher than that at 55% RH. In summary, results showed that UVGI was an effective method for inactivation of viruses on surfaces.


title: ACE2 orthologues in non-mammalian vertebrates (Danio, Gallus, Fugu, Tetraodon and Xenopus)

text: Abstract Angiotensin-converting enzyme 2 (ACE2), a newly identified member in the renin–angiotensin system (RAS), acts as a negative regulator of ACE. It is mainly expressed in cardiac blood vessels and the tubular epithelia of kidneys and abnormal expression has been implicated in diabetes, hypertension and heart failure. The mechanism and physiological function of this zinc metallopeptidase in mammals are not yet fully understood. Non-mammalian vertebrate models offer attractive and simple alternatives that could facilitate the exploration of ACE2 function. In this paper we report the in silico analysis of Ace2 genes from the Gallus (chicken), Xenopus (frog), Fugu and Tetraodon (pufferfish) genome assembly databases, and from the Danio (zebrafish) cDNA library. Exon ambiguities of Danio and Xenopus Ace2s were resolved by RT-PCR and 3′RACE. Analyses of the exon–intron structures, alignment, phylogeny and hydrophilicity plots, together with the conserved synteny among these vertebrates, support the orthologous relationship between mammalian and non-mammalian ACE2s. The putative promoters of Ace2 from human, Tetraodon and Xenopus tropicalis drove the expression of enhanced green fluorescent protein (EGFP) specifically in the heart tissue of transgenic Xenopus thus making it a suitable model for future functional genomic studies. Additionally, the search for conserved cis-elements resulted in the discovery of WGATAR motifs in all the putative Ace2 promoters from 7 different animals, suggesting a possible role of GATA family transcriptional factors in regulating the expression of Ace2.


Ageing out of place in COVID-19 pandemic era: how does the situation look like for older refugees in camps?


title: Photodynamic Antimicrobial Polymers for Infection Control

text: Hospital-acquired infections pose both a major risk to patient wellbeing and an economic burden on global healthcare systems, with the problem compounded by the emergence of multidrug resistant and biocide tolerant bacterial pathogens. Many inanimate surfaces can act as a reservoir for infection, and adequate disinfection is difficult to achieve and requires direct intervention. In this study we demonstrate the preparation and performance of materials with inherent photodynamic, surface-active, persistent antimicrobial properties through the incorporation of photosensitizers into high density poly(ethylene) (HDPE) using hot-melt extrusion, which require no external intervention except a source of visible light. Our aim is to prevent bacterial adherence to these surfaces and eliminate them as reservoirs of nosocomial pathogens, thus presenting a valuable advance in infection control. A two-layer system with one layer comprising photosensitizer-incorporated HDPE, and one layer comprising HDPE alone is also described to demonstrate the versatility of our approach. The photosensitizer-incorporated materials are capable of reducing the adherence of viable bacteria by up to 3.62 Log colony forming units (CFU) per square centimeter of material surface for methicillin resistant Staphylococcus aureus (MRSA), and by up to 1.51 Log CFU/cm(2) for Escherichia coli. Potential applications for the technology are in antimicrobial coatings for, or materials comprising objects, such as tubing, collection bags, handrails, finger-plates on hospital doors, or medical equipment found in the healthcare setting.


title: Role of human metapneumovirus, human coronavirus NL63 and human bocavirus in infants and young children with acute wheezing

text: The role of the novel respiratory viruses, human metapneumovirus (hMPV), human coronavirus NL63 (HCoV NL63) and human bocavirus (HBoV), in wheezing illness in children has not been well studied, especially in Africa. The aim of this study was to investigate the prevalence of hMPV, HCoV NL63 and HBoV in South African children with acute wheezing. A prospective study of consecutive children presenting with acute wheezing to a pediatric hospital from May 2004 to November 2005 was undertaken. A nasal swab was taken for reverse transcription‐polymerase chain reaction (RT‐PCR) and PCR for hMPV, HCoV NL63 and HBoV; when positive, the genes were sequenced. Shell vial culture for RSV, influenza A and B viruses, adenovirus and parainfluenza viruses 1, 2, 3 was performed on every 5th sample. Two hundred and forty two nasal swabs were collected from 238 children (median age 12.4 months). A novel respiratory virus was found in 44/242 (18.2%). hMPV, HBoV, and HCoV NL63 was found in 20 (8.3%), 18 (7.4%), and 6 (2.4%) of samples, respectively. Fifteen of 59 (25%) samples were positive for other respiratory viruses. Viral co‐infections, occurred in 6/242 (2.5%). Phylogenetic analysis showed co‐circulation of hMPV and HCoV NL63 A and B lineages, although only HBoV genotype st2 was found. Viruses are an important cause of wheezing in preschool children; hMPV, HCoV NL63, and HBoV are less common than the usual respiratory pathogens. J. Med. Virol. 80:906–912, 2008. © 2008 Wiley‐Liss, Inc.


title: Characterization of a human monoclonal antibody generated from a B-cell specific for a prefusion-stabilized spike protein of Middle East respiratory syndrome coronavirus

text: Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory infection and continues to infect humans, thereby contributing to a high mortality rate (34.3% in 2019). In the absence of an available licensed vaccine and antiviral agent, therapeutic human antibodies have been suggested as candidates for treatment. In this study, human monoclonal antibodies were isolated by sorting B cells from patient’s PBMC cells with prefusion stabilized spike (S) probes and a direct immunoglobulin cloning strategy. We identified six receptor-binding domain (RBD)-specific and five S1 (non-RBD)-specific antibodies, among which, only the RBD-specific antibodies showed high neutralizing potency (IC(50) 0.006–1.787 μg/ml) as well as high affinity to RBD. Notably, passive immunization using a highly potent antibody (KNIH90-F1) at a relatively low dose (2 mg/kg) completely protected transgenic mice expressing human DPP4 against MERS-CoV lethal challenge. These results suggested that human monoclonal antibodies isolated by using the rationally designed prefusion MERS-CoV S probe could be considered potential candidates for the development of therapeutic and/or prophylactic antiviral agents for MERS-CoV human infection.


title: Considerations for infectious disease research and practice

text: As the 21st century unfolds, strategies to prevent and control infectious diseases remain an area of vital interest and concern. The burden of disease, disability, and death caused by infectious diseases is felt around the world in both developed and developing nations. Moreover, the ability of infectious agents to destabilize populations, economies, and governments is strikingly apparent. To an unprecedented degree, infectious disease-related issues are high on the agendas of world leaders, philanthropists, policymakers, and the public. This enhanced focus, combined with recent scientific and technological advances, creates new opportunities and challenges for infectious disease research and practice. This paper examines these issues in the context of three countries: China, India, and the United States.


title: P115 Pathogenic Influenza A viruses and SARS-Coronaviruses modulate global interferon stimulated gene induction through diverse mechanisms

text: Introduction Successful respiratory viruses have developed means to overcome specific IFN and ISG effector functions. Yet globally, ISGs as a class have broad functions and impede both pathogenesis and viral replication. Therefore, highly successful respiratory viruses including SARS-CoV and Influenza A virus (IAV), likely attempt to short-circuit global ISG induction, potentially through diverse mechanisms. Methods In this work, global RNA (microarray) and proteomics data (mass spectrometry) are utilized to compare and contrast ISG control strategies employed by IAV H5N1, H1N1 2009, and SARS-CoV. Calu-3 cells, a human lung epithelial cell line, are treated with type I IFN to define a consensus list of IFN responsive genes. These genes are then examined in the context of virus infections to evaluate the global ISG response. Results SARS-CoV and IAV H5N1 utilize contrasting approaches to interfere with the global host ISG response. Whereas IAV H5N1 actively manipulates the ISG response with up and down regulation of ISG transcripts, SARS-CoV successfully limits ISG induction until late times during infection. Global proteomic analysis confirms the absence of ISG proteins following H5N1 infection; in contrast, SARS-CoV induces increased abundance of several ISG proteins, but not until after peak viral titers have been achieved. Together, the data illustrate that these two virulent respiratory viruses control the global ISG response. Further examination reveals ISG manipulation is absent in a less virulent IAV strain. H1N1 2009 infection results in robust ISG transcript expression with minimal down regulation. Similarly, proteomics analysis finds increased abundance of ISG proteins absent in H5N1 infection. Transcriptional factor analysis found no direct antagonism; however, truncation of the C-terminal portion of NS1 ablated ISG down regulation in H5N1 infections. Meta-analysis finds a similar ablation is observed in A549 cells infected H1N1 1918 when NS1 is manipulated. Together, the data strongly implicate a role for NS1 in mediating control of the entire global ISG response following virulent IAV infections. For SARS-CoV, the delayed ISG induction is maintained in both mutant and precursor viruses. DORF6, a SARS-CoV mutant lacking a major IFN antagonist, fails to induce ISG induction any earlier. Similarly, Bat-SRBD, a synthetic precursor virus, maintains the ability control the global ISG response, suggesting this trait is maintained in pre-cursors of the epidemic SARS-CoV. Additional work examines the ability of the SARS-CoV to camouflage its viral intermediates as well as replication within double membrane vesicles as mechanisms mediating delayed ISG induction. Conclusion Together, the work highlights the contrasting approaches used by SARS-CoV and IAV strains to limit global ISG induction. In addition, the results imply an important role for controlling ISG response in the context of virulent respiratory virus infection. Further examination of these results will likely produce novel approaches to treat important respiratory virus infection.


title: Differential expression of miRNAs in enterovirus 71-infected cells

text: BACKGROUND: Enterovirus 71 (EV71) is one of the major etiological pathogens of hand, foot and mouth disease (HFMD) and can cause severe cerebral and pulmonary complications and even fatality. MicroRNAs (miRNAs), a class of small non-coding RNA molecules, play an important role in post-transcriptional regulation of gene expression and thereby influencing various physiological and pathological processes. Increasing evidence suggests that miRNAs act as key effector molecules in the complicated pathogen-host interactions. However, the roles of miRNAs in EV71 infection and pathogenesis are not well understood. METHODS: To identify special miRNAs involved in EV71 infection, a microarray assay was performed to study the expression pattern of miRNAs in EV71-infected human rhabdomyosarcoma cells (RD cells) and uninfected RD cells. We further predicted the putative target genes for the dysregulated miRNAs using the online bioinformatic algorithms (TargetScan, miRanda and PicTar) and carried out functional annotation including GO enrichment and KEGG pathway analysis for miRNA predicted targets. Then, the results of microarray were further confirmed by quantitative RT-PCR. RESULTS: Totally, 45 differentially expressed miRNAs ware identified by microarray, among which 36 miRNAs were up-regulated and 9 were down-regulated. 7166 predicted target genes for the dysregulated miRNAs were revealed by using TargetScan in conjunction with miRanda and PicTar. The GO annotation suggested that predicted targets of miRNAs were enriched into the category of signal transduction, regulation of transcription, metabolic process, protein phosphorylation, apoptotic process and immune response. KEGG pathway analysis suggested that these predicted target genes were involved in many important pathways, mainly including endocytosis and focal adhesion, MAPK signaling pathway, hypertrophic cardiomyopathy, melanogenesis and ErbB signaling pathway. The expression levels of 8 most differentially up-regulated miRNAs and 3 most differentially down-regulated miRNAs were confirmed by qRT-PCR. The expressions of hsa-miR-4530, hsa-miR-4492, hsa-miR-6125, hsa-miR-494-3p, hsa-miR-638, hsa-miR-6743-5p, hsa-miR-4459 and hsa-miR-4443 detected by qRT-PCR were consistent with the microarray data. CONCLUSION: These results might extend our understanding to the regulatory mechanism of miRNAs underlying the pathogenesis of EV71 infection, thus strengthening the preventative and therapeutic strategies of HFMD caused by EV71.


title: Anxiety, worry and cognitive risk estimate in relation to protective behaviors during the 2009 influenza A/H1N1 pandemic in Hong Kong: ten cross-sectional surveys

text: BACKGROUND: Few studies have investigated associations between psychological and behavioral indices throughout a major epidemic. This study was aimed to compare the strength of associations between different cognitive and affective measures of risk and self-reported protective behaviors in a series of ten cross-sectional surveys conducted throughout the first wave of influenza A/H1N1 pandemic. METHODS: All surveys were conducted using questionnaire-based telephone interviews, with random digit dialing to recruit adults from the general population. Measures of anxiety and worry (affective) and perceived risk (cognitive) regarding A/H1N1 were made in 10 serial surveys. Multivariate logistic regression models were used to estimate the cognitive/affective-behavioral associations in each survey while multilevel logistic models were conducted to estimate the average effects of each cognitive/affective measure on adoption of protective behaviors throughout the ten surveys. RESULTS: Excepting state anxiety, other affective measures including “anticipated worry”, “experienced worry” and “current worry” specific to A/H1N1 risk were consistently and strongly associated with adoption of protective behaviors across different survey periods. However, the cognitive-behavioral associations were weaker and inconsistent across the ten surveys. Perceived A/H1N1 severity relative to SARS had stronger associations with adoption of protective behaviors in the late epidemic periods than in the early epidemic periods. CONCLUSION: Risk-specific worries appear to be significantly associated with the adoption of protective behaviors at different epidemic stages, whereas cognitive measures may become more important in understanding people’s behavioral responses later in epidemics. Future epidemic-related psycho-behavioral research should include more affective-loaded measures of risk.


More shared urban open spaces: resiliency on demand


title: Viruses associated with Antarctic wildlife: From serology based detection to identification of genomes using high throughput sequencing

text: Abstract The Antarctic, sub-Antarctic islands and surrounding sea-ice provide a unique environment for the existence of organisms. Nonetheless, birds and seals of a variety of species inhabit them, particularly during their breeding seasons. Early research on Antarctic wildlife health, using serology-based assays, showed exposure to viruses in the families Birnaviridae, Flaviviridae, Herpesviridae, Orthomyxoviridae and Paramyxoviridae circulating in seals (Phocidae), penguins (Spheniscidae), petrels (Procellariidae) and skuas (Stercorariidae). It is only during the last decade or so that polymerase chain reaction-based assays have been used to characterize viruses associated with Antarctic animals. Furthermore, it is only during the last five years that full/whole genomes of viruses (adenoviruses, anelloviruses, orthomyxoviruses, a papillomavirus, paramyoviruses, polyomaviruses and a togavirus) have been sequenced using Sanger sequencing or high throughput sequencing (HTS) approaches. This review summaries the knowledge of animal Antarctic virology and discusses potential future directions with the advent of HTS in virus discovery and ecology.


Tabagisme et maladie à coronavirus 2019 (COVID-19)


title: Relationship between rate of infection and markers of inflammation/immunity in Holy Birman cats with feline coronavirus

text: Abstract The aim of this study was to assess whether Holy Birman cats (HB) have a peculiar immune profile and a higher rate of infection by feline coronaviruses (FCoV). Leucocyte and lymphocyte subsets, antibody titers, α1-acid glycoprotein (AGP), globulin fractions, IL-4, IL-12 and IFN-γ in blood and fecal FCoV excretion were determined in HB (n = 75) and in cats from other breeds (n = 94). Significantly higher CD4/CD8 ratio, IFN-γ concentration and IL12/IL4 ratio and significantly lower IL-4 concentration and proportion of shedders were found in HB than in other breeds. No other differences were found. In conclusion, this study did not provide evidence of peculiar immune profiles in HB, except for a prevalent Th1 profile, that may explain why in our caseload the rate of shedders was lower in HB than in other breeds.


title: COVID-19, Health, Conservation, and Shared Wellbeing: Details Matter

text: Abstract Many have stridently recommended banning markets like the one where COVID-19 originally spread. We highlight that millions of people around the world depend on markets for subsistence and the diverse use of animals globally defies uniform bans. We argue that the immediate and fair priority is critical scrutiny of wildlife trade.


Conflicto terapéutico en pacientes con COVID19 y glaucoma