title: Discovery and Genomic Characterization of Noroviruses from a Gastroenteritis Outbreak in Domestic Cats in the US

text: Norovirus (NoV) RNA was detected in the stools of 6 out 14 (42.8%) 8–12-week-old cats with enteritis from a feline shelter, in New York State. Upon sequence analysis of the complete capsid, the six NoVs were found to be identical, suggesting the spread of a unique NoV strain in the shelter. The full-length genomic sequence (7839 nt) of one feline NoV, CU081210E/2010/US, was determined. In the capsid protein VP1 region, the virus displayed the highest amino acid identity to animal genogroup IV genotype 2 (GIV.2) NoVs: lion/Pistoia-387/06/IT (97.9%) and dog/Bari-170/07/IT (90.4%). These findings document the discovery of a novel feline calicivirus, different from vesiviruses, and extend the spectrum of NoV host range. Epidemiological studies using feline NoV-specific diagnostic tools and experimental infection of cats are required to understand whether NoVs have a pathogenic role in this species.


In Response: "Perioperative COVID-19 Defense: An Evidence-Based Approach for Optimization of Infection Control and Operating Room Management"


A Meta-Analysis of the Relationship Between Renin-Angiotensin-Aldosterone System Inhibitors and COVID-19


docid: avvxppzm

title: Agent-based simulation for weekend-extension strategies to mitigate influenza outbreaks

text: BACKGROUND: Non-pharmaceutical strategies are vital in curtailing impacts of influenza and have been intensively studied in public health. However, few strategies have explicitly utilized the weekend effect, which has been widely reported to be capable of reducing influenza infections. This study aims to explore six weekend-extension strategies against seasonal and pandemic flu outbreaks. METHODS: The weekend-extension strategies were designed to extend regular two-day weekend by one, two and three days, respectively, and in combination with either a continuous or discontinuous pattern. Their effectiveness was evaluated using an established agent-based spatially explicit simulation model in the urbanized area of Buffalo, NY, US. RESULTS: If the extensions last more than two days, the weekend-extension strategies can remarkably reduce the overall disease attack rate of seasonal flu. Particularly, a three-day continuous extension is sufficient to suppress the epidemic and confine the spread of disease. For the pandemic flu, the weekend-extension strategies only produce a few mitigation effects until the extensions exceed three days. Sensitivity analysis indicated that a compliance level above 75% is necessary for the weekend-extension strategies to take effects. CONCLUSION: This research is the first attempt to incorporate the weekend effect into influenza mitigation strategies. The results suggest that appropriate extensions of the regular two-day weekend can be a potential measure to fight against influenza outbreaks, while minimizing interruptions on normal rhythms of socio-economy. The concept of weekend extension would be particularly useful if there were a lack of vaccine stockpiles, e.g., in countries with limited health resources, or in the case of unknown emerging infectious diseases.


title: Sex-specific clinical characteristics and prognosis of coronavirus disease-19 infection in Wuhan, China: A retrospective study of 168 severe patients

text: To confirm the relationship between sex and the progression of Coronavirus Disease-19 (COVID-19), and its potential mechanism, among severe patients. For this retrospective study, we included 168 consecutive severe patients with pathogen-confirmed COVID-19 who were hospitalized between January 16th and February 4th, 2020, at Tongji Hospital in Wuhan, China. Clinical characteristics, laboratory parameters, and outcomes were compared and analyzed between males and females. In the present study, we analyzed 168 severe patients with COVID-19, including 86 males and 82 females, and 48 patients (28.6%) were diagnosed as critically ill. Of 86 male patients, 12.8% (11/86) died and 75.6% (65/86) were discharged; of 82 female patients, 7.3% (6/82) died and 86.6% (71/82) were discharged. Eleven laboratory parameters showed significant differences between male and female patients, and six of them were higher during the whole clinical course in patients who died than in patients who were discharged. In adjusted logistic regression analysis, males with comorbidities presented a higher risk of being critically ill than males without comorbidities (OR = 3.824, 95% CI = 1.279–11.435). However, this association attenuated to null in female patients (OR = 2.992, 95% CI = 0.937–9.558). A similar sex-specific trend was observed in the relation between age and critically ill conditions. We highlighted sex-specific differences in clinical characteristics and prognosis. Male patients appeared to be more susceptible to age and comorbidities. Sex is an important biological variable that should be considered in the prevention and treatment of COVID-19.


title: In vitro biochemical and thermodynamic characterization of nucleocapsid protein of SARS

text: Abstract The major biochemical and thermodynamic features of nucelocapsid protein of SARS coronavirus (SARS_NP) were characterized by use of non-denatured gel electrophoresis, size-exclusion chromatographic and surface plasmon resonance (SPR) techniques. The results showed that SARS_NP existed in vitro as oligomer, more probably dimer, as the basic functional unit. This protein shows its maximum conformational stability near pH 9.0, and it seems that its oligomer dissociation and protein unfolding occur simultaneously. Thermal-induced unfolding for SARS_NP was totally irreversible. Both the thermal and chemical denaturant-induced denaturation analyses showed that oligomeric SARS_NP unfolds and refolds through a two-state model, and the electrostatic interactions among the charge groups of SARS_NP made a significant contribution to its conformational stability.


title: The impact of the interferon-lambda family on the innate and adaptive immune response to viral infections

text: Type-III interferons (IFN-λ, IFNL) are the most recently described family of IFNs. This family of innate cytokines are increasingly being ascribed pivotal roles in host–pathogen interactions. Herein, we will review the accumulating evidence detailing the immune biology of IFNL during viral infection, and the implications of this novel information on means to advance the development of therapies and vaccines against existing and emerging pathogens. IFNLs exert antiviral effects via induction of IFN-stimulated genes. Common single nucleotide polymorphisms (SNPs) in the IFNL3, IFNL4 and the IFNL receptor α-subunit genes have been strongly associated with IFN-α-based treatment of chronic hepatitis C virus infection. The clinical impact of these SNPs may be dependent on the status of viral infection (acute or chronic) and the potential to develop viral resistance. Another important function of IFNLs is macrophage and dendritic cell polarization, which prime helper T-cell activation and proliferation. It has been demonstrated that IFNL increase Th1- and reduce Th2-cytokines. Therefore, can such SNPs affect the IFNL signaling and thereby modulate the Th1/Th2 balance during infection? In turn, this may influence the subsequent priming of cytotoxic T cells versus antibody-secreting B cells, with implications for the breadth and durability of the host response.


Africa CDC: Establishing Integrated Surveillance and Laboratory Networks for Rapid Disease Detection and Response, Control, Prevention, and Clinical Care in Africa


1 Tropical Lung Diseases


PARV4: An Emerging Tetraparvovirus


title: The influenza virus, SARS-CoV-2, and the airways: clarification for the otorhinolaryngologist

text: Abstract The influenza virus and SARS-CoV-2 cause trivial upper and severe lower respiratory infections (Influenza virus 290,000 to 650,000 deaths/year). These viruses come into contact with the airways either by direct projection, by secondary inhalation of airborne droplets, or by handling (fomites). The objective of this article is to clarify the mechanisms of production and penetration of droplets of secretions emitted during all expiratory phenomena likely to transport these viruses and come into contact with the respiratory mucosa. The droplets > 5 µm follow the laws of ballistics, those < 5 µm follow Brownian motion and remain suspended in the air. The aerosols of droplets are very heterogeneous whether the subject is healthy or sick. During an infectious period, not all droplets contain viral RNA. If these RNAs are detectable around patients, on surfaces, and in the ambient air at variable distances according to the studies (from 0.5 m to beyond the patient’s room), this is without prejudice to the infectious nature (viability) of the virus and the minimum infectious dose. There is a time lag between the patient’s infectious period and that of RNA detection for both viruses. Subsequently, the inhaled particles must meet the laws of fluid dynamics (filtration) to settle in the respiratory tree. All of this partly explains the contagiousness and the clinical expression of these two viruses from the olfactory cleft to the alveoli.


title: Detoxifying PCDD/Fs and heavy metals in fly ash from medical waste incinerators with a DC double arc plasma torch

text: Abstract Medical waste incinerator (MWI) fly ash is regarded as a highly toxic waste because it contains high concentrations of heavy metals and dioxins, including polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). Therefore fly ash from MWI must be appropriately treated before being discharged into the environment. A melting process based on a direct current thermal plasma torch has been developed to convert MWI fly ash into harmless slag. The leaching characteristics of heavy metals in fly ash and vitrified slag were investigated using the toxicity characteristic leaching procedure, while the content of PCDD/Fs in the fly ashes and slags was measured using method 1613 of the US EPA. The experimental results show that the decomposition rate of PCDD/Fs is over 99% in toxic equivalent quantity value and the leaching of heavy metals in the slag significantly decreases after the plasma melting process. The produced slag has a compact and homogeneous microstructure with density of up to 2.8 g/cm3.


title: First description of sarcoptic mange in the endangered Iberian lynx (Lynx pardinus): clinical and epidemiological features

text: A 6-month-old female Iberian lynx (Lynx pardinus) cub that was severely affected by mange died in September 2016 in the Montes de Toledo (Spain) with crusts and fissures on its face, outer ears, nipples and footpads. The body condition of the cub was very poor, and it also had a mandibular abscess and a severely ankylosed luxation on its left knee. After confirming that the origin of the deceased cub’s dermal lesions was Sarcoptes scabiei, the subsequent search for ectoparasites and a comparison of histopathological and immunohistochemical findings in all sympatric lynxes handled (n = 30) and submitted for necropsy (n = 4) during 2016 and 2017 revealed the presence of S. scabiei mites and/or milder mange compatible lesions in five members of her family group, which was treated against mange together with two exposed contiguous family groups. An ELISA developed by the authors showed the presence of antibodies against S. scabiei in the deceased female cub and one brother. The presence of concomitant immunosuppressive factors in the dead female cub and the results obtained for the other sympatric lynxes studied since 2016 suggest that S. scabiei had a limited effect on immune-competent Iberian lynxes in the local population of the Montes de Toledo. However, a different evolution and relevance of sarcoptic mange in different populations—or even in the same one in the presence of immunosuppressive factors—cannot be ruled out, thus confirming the need for further research in order to attain a complete comprehension of the epidemiology and the real threat that this ectoparasitic disease may imply for L. pardinus.


title: What would sérgio ferreira say to your physician in this war against COVID-19: How about kallikrein/kinin system?

text: Coronavirus disease 2019 (COVID-19) is an infectious disease with fast spreading all over the world caused by the SARS-CoV-2 virus which can culminate in a severe acute respiratory syndrome by the injury caused in the lungs. However, other organs can be also damaged. SARS-CoV-2 enter into the host cells using the angiotensin-converting enzyme 2 (ACE2) as receptor, like its ancestor SARS-CoV. ACE2 is then downregulated in lung tissues with augmented serum levels of ACE2 in SARS-CoV-2 patients. Interestingly, ACE2(+) organs reveal the symptomatic repercussions, which are signals of the infection such as dry cough, shortness of breath, heart failure, liver and kidney damage, anosmia or hyposmia, and diarrhea. ACE2 exerts a chief role in the renin-angiotensin system (RAS) by converting angiotensin II to angiotensin-(1-7) that activates Mas receptor, inhibits ACE1, and modulates bradykinin (BK) receptor sensitivity, especially the BK type 2 receptor (BKB2R). ACE2 also hydrolizes des-Arg(9)-bradykinin (DABK), an active BK metabolite, agonist at BK type 1 receptors (BKB1R), which is upregulated by inflammation. In this opinion article, we conjecture a dialogue by the figure of Sérgio Ferreira which brought together basic science of classical pharmacology and clinical repercussions in COVID-19, then we propose that in the course of SARS-CoV-2 infection: i) downregulation of ACE2 impairs the angiotensin II and DABK inactivation; ii) BK and its metabolite DABK seems to be in elevated levels in tissues by interferences in kallikrein/kinin system; iii) BK1 receptor contributes to the outbreak and maintenance of the inflammatory response; iv) kallikrein/kinin system crosstalks to RAS and coagulation system, linking inflammation to thrombosis and organ injury. We hypothesize that targeting the kallikrein/kinin system and BKB1R pathway may be beneficial in SARS-CoV-2 infection, especially on early stages. This route of inference should be experimentally verified by SARS-CoV-2 infected mice.


title: Chapter 16 Eye and Associated Glands

text: Abstract The eye is susceptible to adverse toxic effects by direct application, inadvertent ocular contact, or systemic exposure to chemicals or their metabolites. Although the albino rat is a less than ideal model for ocular toxicity studies, it has gained popularity for specific applications and may be the first species in which the ocular toxicity of a systemically administered xenobiotic becomes evident. This chapter reviews the embryology, anatomy, and physiology of the eye and associated glands and describes common nonneoplastic and neoplastic lesions encountered in laboratory rats.


title: Development of a Potent and Protective Germline-Like Antibody Lineage Against Zika Virus in a Convalescent Human

text: Zika virus (ZIKV) specific neutralizing antibodies hold great promise for antibody-based interventions and vaccine design against ZIKV infection. However, their development in infected patients remains unclear. Here, we applied next-generation sequencing (NGS) to probe the dynamic development of a potent and protective ZIKV E DIII-specific antibody ZK2B10 isolated from a ZIKV convalescent individual. The unbiased repertoire analysis showed dramatic changes in the usage of antibody variable region germline genes. However, lineage tracing of ZK2B10 revealed limited somatic hypermutation and transient expansion during the 12 months following the onset of symptoms. The NGS-derived, germline-like ZK2B10 somatic variants neutralized ZIKV potently and protected mice from lethal challenge of ZIKV without detectable cross-reactivity with Dengue virus (DENV). Site-directed mutagenesis identified two residues within the λ chain, N31 and S91, that are essential to the functional maturation of ZK2B10. The repertoire and lineage features unveiled here will help elucidate the developmental process and protective potential of E DIII-directed antibodies against ZIKV infection.


Role of human coronavirus in Brazilian hospitalized children with respiratory lower infection


title: Congestive heart failure in two pet rabbits

text: This case report describes congestive heart failure with pleural effusion in two middle‐aged, pet house rabbits. Both had a history of acute onset dyspnoea, weakness and weight loss. Bi‐atrial enlargement was seen on echocardiography in both rabbits. One rabbit had atrial fibrillation and ventricular premature complexes identified on electrocardiography. There was a radiographically evident pleural effusion in both rabbits and thoracocentesis was undertaken in one rabbit. These findings were confirmed on post‐mortem examination. The aetiology for the underlying heart disease was not found, but the potential types of cardiomyopathies are discussed.


title: CEPI: Driving Progress Toward Epidemic Preparedness and Response

text: The Coalition for Epidemic Preparedness Innovations (CEPI) was formed in the aftermath of the 2014–2015 Ebola outbreak in west Africa to support the development of vaccines that could improve the world’s preparedness against outbreaks of epidemic infectious diseases. Since its launch in 2017, CEPI has mobilized more than US$750 million to support its mission to develop vaccines against agents such as Lassa virus, Middle East respiratory syndrome coronavirus, and Nipah virus, as well as several rapid-response vaccine platforms to accelerate response times to unexpected epidemic threats. CEPI has also played a leading role in fostering institutional partnerships between public- and private-sector organizations to optimize allocation of resources for vaccine development against its priority pathogens. CEPI’s priorities include diversification of its current vaccine research and development investment portfolio to include additional pathogens, such as Rift Valley fever and chikungunya; establishment of technical and regulatory pathways for vaccine development across CEPI’s portfolio; development of sustainable manufacturing solutions for vaccine candidates nearing completion of safety and immunogenicity testing in humans; and creation of investigational stockpiles of its vaccine candidates for use in emergency situations. This commentary provides an overview of the global health challenges CEPI was established to address and its achievements to date, and indicates priorities for funding and coordination in the coming years.


title: High resolution two-dimensional gel electrophoresis of structural proteins of baculoviruses of Autographa californica and Porthetria (lymantria) dispar

text: Abstract The structural polypeptides of baculoviruses of Autographa californica (AcMNPV) and Porthetria dispar (PdMNPV) were analyzed by two-dimensional (2-D) gel electrophoresis. Purified proteins were solubilized in urea-NP40 mix and separated by isoelectric focusing in the first dimension; electrophoresis in the presence of sodium dodecyl sulfate (SDS) separated proteins by molecular weight in the second dimension. Eighty-one acidic polypeptides ranging in molecular weight from 13,500 to 86,000 Da were resolved in AcMNPV enveloped virions. The predominant polypeptide had a molecular weight of 41,500 and was considered to be the major capsid protein. Nucleocapsids from AcMNPV were resolved into 64 polypeptides. At least 11 of the polypeptides, including most of the high molecular weight proteins, that were not resolved in nucleocapsids were considered to be envelope proteins. For PdMNPV enveloped virions, there were 95 acidic polypeptides ranging in molecular weight from 13,500 to 85,500. The predominant polypeptide had a molecular weight of 46,500 Da. Polyhedral proteins (polyhedrin) isolated from protease-inactivated polyhedra and separable into a single major polypeptide (approx. 31,000) on one-dimensional SDS-polyacrylamide gel electrophoresis were resolved into six polypeptides for both viruses. All six polyhedrin polypeptides had the same molecular weight, but their isoelectric points ranged from pH 5.3 to 5.9 for AcMNPV and from pH 5.7 to 6.2 for PdMNPV. These six polypeptides were also detected when protease-inactivated or noninactivated whole polyhedra were analyzed directly by 2-D electrophoresis. It is assumed that not all the observed baculovirus polypeptides were unique species. Some proteins, especially the polyhedrin polypeptides, appeared to be related and had altered mobilities as a consequence of post-translational modifications.


title: In-cell infection: a novel pathway for Epstein-Barr virus infection mediated by cell-in-cell structures

text: Epstein-Barr virus (EBV) can infect both susceptible B lymphocytes and non-susceptible epithelial cells (ECs). Viral tropism analyses have revealed two intriguing means of EBV infection, either by a receptor-mediated infection of B cells or by a cell-to-cell contact-mediated infection of non-susceptible ECs. Herein, we report a novel “in-cell infection” mechanism for EBV infection of non-susceptible ECs through the formation of cell-in-cell structures. Epithelial CNE-2 cells were invaded by EBV-infected Akata B cells to form cell-in-cell structures in vitro. Such unique cellular structures could be readily observed in the specimens of nasopharyngeal carcinoma. Importantly, the formation of cell-in-cell structures led to the autonomous activation of EBV within Akata cells and subsequent viral transmission to CNE-2 cells, as evidenced by the expression of viral genes and the presence of virion particles in CNE-2 cells. Significantly, EBV generated from in-cell infected ECs displayed altered tropism with higher infection efficacy to both B cells and ECs. In addition to CNE-2 tumor cells, cell-in-cell structure formation could also mediate EBV infection of NPEC1-Bmi1 cells, an immortalized nasopharyngeal epithelial cell line. Furthermore, efficient infection by this mechanism involved the activation of the PI3K/AKT signaling pathway. Thus, our study identified “in-cell infection” as a novel mechanism for EBV infection. Given the diversity of virus-infected cells and the prevalence of cell-in-cell structures during chronic infection, we speculate that “in-cell infection” is likely a general mechanism for EBV and other viruses to infect non-susceptible ECs.


title: Predicting Illness Severity and Short-Term Outcomes of COVID-19: A Retrospective Cohort Study in China

text: Among 417 COVID-19 patients in Shenzhen, demographic characteristics, clinical manifestations and baseline laboratory tests showed significant differences between mild-moderate cohort and severe-critical cohort.Based on these differences, a convenient mathematical model was established to predict the illness severity of COVID-19. The model includes four parameters: age, BMI, CD4(+) lymphocytes and IL-6 levels. The AUC of the model is 0.911.The high risk factors for developing to severe COVID-19 are: age ≥ 55 years, BMI > 27 kg / m(2), IL-6 ≥ 20 pg / ml, CD4(+) T cell ≤ 400 count / μ L.Among 249 discharged COVID-19 patients, those who recovered after 20 days had a lower count of platelet, a higher level of estimated glomerular filtration rate, and higher level of interleukin-6 and myoglobin than those who recovered within 20 days.


title: A process for daily checks when using anaesthetic machines to ventilate the lungs of COVID‐19 patients: the ‘domino switch’ technique

text: The COVID-19 pandemic has increased demand for ventilators. Anaesthetic machines offer an alternative, but these are not designed to run continuously. Our department uses Dräger Primus anaesthetic machines which require daily checks. Dräger company representatives have indicated that checks can be deferred for up to 72 h [1], but this might increase the risk of malfunctions. Checks take several minutes, so an alternative means of ventilation is required to cover this period, necessitating two circuit disconnections per patient. Each disconnection potentially generates an infectious aerosol, and risks tracheal tube displacement and lung derecruitment, even with precautions such as tracheal tube clamping. We concluded that multiple circuit disconnections were unsatisfactory and devised a process for daily checks with a single disconnection per patient. We call this process 'domino switching'.


title: Deliberate release: Plague – A review

text: Yersinia pestis is the causative agent of plague and is considered one of the most likely pathogens to be used as a bioweapon. In humans, plague is a severe clinical infection that can rapidly progress with a high mortality despite antibiotic therapy. Therefore, early treatment of Y. pestis infection is crucial. This review provides an overview of its clinical manifestations, diagnosis, treatment, prophylaxis, and protection requirements for the use of clinicians. We discuss the likelihood of a deliberate release of plague and the feasibility of obtaining, isolating, culturing, transporting and dispersing plague in the context of an attack aimed at a westernized country. The current threat status and the medical and public health responses are reviewed. We also provide a brief review of the potential prehospital treatment strategy and vaccination against Y. pestis. Further, we discuss the plausibility of antibiotic resistant plague bacterium, F1-negative Y. pestis, and also the possibility of a plague mimic along with potential strategies of defense against these. An extensive literature search on the MEDLINE, EMBASE, and Web of Science databases was conducted to collate papers relevant to plague and its deliberate release. Our review concluded that the deliberate release of plague is feasible but unlikely to occur, and that a robust public health response and early treatment would rapidly halt the transmission of plague in the population. Front-line clinicians should be aware of the potential of a deliberate release of plague and prepared to instigate early isolation of patients. Moreover, front-line clinicians should be weary of the possibility of suicide attackers and mindful of the early escalation to public health organizations.


title: Optimal control for SIRC epidemic outbreak

text: Abstract In this paper the mathematical SIRC epidemic model is considered. It efficiently describes diseases in which a cross immune class (C) is present, along with the susceptible (S), the infected (I) and the removed (R) ones. Controlling epidemic diseases corresponds to the introduction of vaccination, quarantine and treatment strategies; generally only one of these actions is considered. In this paper the possibility of optimal controls both over the susceptible and the infected subjects is assumed, taking into account also limitations of resources. A suitable cost index is introduced and via the Pontryagin's Minimum Principle the optimal control strategy is determined and the existence of the optimal solution is assessed. Numerical results are developed analyzing the effects of different control strategies.


title: Carbon emissions reductions in last mile and grocery deliveries utilizing air and ground autonomous vehicles

text: The rapid growth of e-commerce and package deliveries across the globe is demanding new solutions to meet customers’ desire for more and faster deliveries. New driverless air and ground vehicles are being launched and tested to deliver products or services in the areas of retail, groceries, and healthcare. This research focuses on the efficiency of autonomous (driverless) air and ground delivery vehicles in terms of vehicle-miles, energy consumption, and CO(2) emissions. Three types of autonomous vehicle are analyzed: drones or unmanned aerial vehicles (UAVs), sidewalk autonomous delivery robots (SADRs), and road autonomous delivery robots (RADRs). The CO(2) emissions of these autonomous vehicles are compared against emissions from an electric van (e-van), a conventional internal combustion engine van, and driving to a store utilizing electric and conventional vehicles. The impacts of vehicle capacity, range, and time constraints are analyzed as well as the impacts of number of deliveries, service time, area of service, and depot-service area distance. Novel results are found regarding the efficiency of each vehicle type and tradeoffs between driving to a store and store delivery as a function of order size and type of vehicle driven by consumers.


Hantavirus Pulmonary Syndrome: The Sound of a Mouse Roaring


title: Antimicrobial potential of macro and microalgae against pathogenic and spoilage microorganisms in food

text: Algae are a valuable and never-failing source of bioactive compounds. The increasing efforts to use ingredients that are as natural as possible in the formulation of innovative products has given rise to the introduction of macro and microalgae in food industry. To date, scarce information has been published about algae ingredients as antimicrobials in food. The antimicrobial potential of algae is highly dependent on: (i) type, brown algae being the most effective against foodborne bacteria; (ii) the solvent used in the extraction of bioactive compounds, ethanolic and methanolic extracts being highly effective against Gram-positive and Gram-negative bacteria; and (iii) the concentration of the extract. The present paper reviews the main antimicrobial potential of algal species and their bioactive compounds in reference and real food matrices. The validation of the algae antimicrobial potential in real food matrices is still a research niche, being meat and bakery products the most studied substrates.


title: Modelling input-output flows of severe acute respiratory syndrome in mainland China

text: BACKGROUND: Severe acute respiratory syndrome (SARS) originated in China in 2002, and it spread to 26 provinces in mainland China and 32 countries across five continents in a matter of months. This outbreak resulted in 774 deaths. However, the spatial features and potential determinants of SARS input-output flows remain unclear. METHODS: We used an adjusted spatial interaction model to examine the spatial effects and potential factors associated with SARS input-output flows. RESULTS: The presence of origin-based spatial dependence positively affected SARS input-output flows from the neighbours of the origin regions. Two components of the input-output flows, migrant and hospitalization flows, exhibited distinctive features. The origin-based and destination-based spatial dependence positively affected migrant flows (i.e., due to those seeking jobs) from the neighbours of origin and destination locations. Similarly, the destination-based spatial dependence also positively affected hospitalization flows (i.e., due to those seeking treatment) from the neighbours of destination regions. However, the origin-to-destination based spatial dependence negatively affected hospitalisation flows from the neighbours of origin-to-destination regions. The direct effects accounted for 78 % of the SARS input-output flows, which was 3.56-fold greater than the indirect effects. Differences in regional income drove the SARS input-output flows. Therefore, urban income had a positive effect, whereas rural income had a negative effect. Total interregional flows increased by 3.54 % with a 1 % increase in urban income, and intraregional flows increased by 8.35 %. In contrast, the total interregional flows decreased by 3.38 % with a 1 % increase in rural income, and intraregional flows declined by 2.29 %. Railway capacity, per person gross domestic product (PGDP), urban rate and the law of distance decay also affected the input-output flows. CONCLUSIONS: Our results confirm that the SARS input-output flows presented significant geographic spatial heterogeneity and spatial effects. Income differences were the major cause of the flows between pairs of regions. Railway capacity, PGDP, and urban rate also played important roles. These findings provide valuable information for the Chinese government to control the future spread of nationwide epidemics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-016-2867-6) contains supplementary material, which is available to authorized users.


title: Lack of transparency during the COVID-19 pandemic: Nurturing a future and more devastating crisis

text: CoI: I am an unpaid member of the Haut Conseil de la Santé Publique (High Council of Public Health), the expert body of the Ministry of Health for the French government.


title: Perceived Impact of Urologic Surgery Training Program Modifications due to COVID-19 in the United States

text: OBJECTIVE: Significant healthcare disruption due to pandemic coronavirus disease 2019 (COVID-19) has implications across all aspects of clinical care in the United States (US). In this study, we aim to assess urology residency program modifications in the context of COVID-19, and perceptions of the impact on urology trainees. METHODS: A cross-sectional survey of program leadership and residents at accredited US urology residencies was administered between April 28, 2020 – March 11, 2020. Total cohort responses are reported, and sub-analyses were preformed comparing responses between those in in high vs low COVID-19 geographic regions, and between program leaders vs residents. RESULTS: Program leaders from 43% of programs and residents from 18% of programs responded. Respondents reported decreased surgical volume (83%-100% varying by subspecialty), increased use of telehealth (99%), a transition to virtual educational platforms (95%) and decreased size of inpatient resident teams (90%). Most residents are participating in care of COVID-19 patients (83%) and 20% endorsed that urology residents have been re-deployed. 79% of respondents perceive a negative impact of recent events on urology surgery training and anxiety regarding competency upon completion of residency training was more pronounced among respondents in high COVID-19 regions. CONCLUSION: Major modifications to urology training programs were implemented in response to COVID-19. Attention must be paid to the downstream effects of the training disruption on urology residents.


title: Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus

text: Spike (S) proteins of coronaviruses, including the coronavirus that causes severe acute respiratory syndrome (SARS), associate with cellular receptors to mediate infection of their target cells(1,2). Here we identify a metallopeptidase, angiotensin-converting enzyme 2 (ACE2)(3,4), isolated from SARS coronavirus (SARS-CoV)-permissive Vero E6 cells, that efficiently binds the S1 domain of the SARS-CoV S protein. We found that a soluble form of ACE2, but not of the related enzyme ACE1, blocked association of the S1 domain with Vero E6 cells. 293T cells transfected with ACE2, but not those transfected with human immunodeficiency virus-1 receptors, formed multinucleated syncytia with cells expressing S protein. Furthermore, SARS-CoV replicated efficiently on ACE2-transfected but not mock-transfected 293T cells. Finally, anti-ACE2 but not anti-ACE1 antibody blocked viral replication on Vero E6 cells. Together our data indicate that ACE2 is a functional receptor for SARS-CoV. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature02145) contains supplementary material, which is available to authorized users.


title: Global Strategies for the Prevention and Control of Infectious Diseases and Non-Communicable Diseases

text: This article on global health reviews the environment surrounding health strategies and plans, as well as lessons learned from the first 15 years of the 21st century, followed by a discussion on the quest for a new paradigm for disease control efforts and challenges and opportunities for Japan.


title: Correlation between dissociation and catalysis of SARS-CoV main protease

text: Abstract The dimeric interface of severe acute respiratory syndrome coronavirus main protease is a potential target for the anti-SARS drug development. We have generated C-terminal truncated mutants by serial truncations. The quaternary structure of the enzyme was analyzed using both sedimentation velocity and sedimentation equilibrium analytical ultracentrifugation. Global analysis of the combined results showed that truncation of C-terminus from 306 to 300 had no appreciable effect on the quaternary structure, and the enzyme remained catalytically active. However, further deletion of Gln-299 or Arg-298 drastically decreased the enzyme activity to 1–2% of wild type (WT), and the major form was a monomeric one. Detailed analysis of the point mutants of these two amino acid residues and their nearby hydrogen bond partner Ser-123 and Ser-139 revealed a strong correlation between the enzyme activity loss and dimer dissociation.


title: Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2

text: Severe Acute Respiratory Syndrome Coronavirus 2 is rapidly spreading around the world. There is no existing vaccine or proven drug to prevent infections and stop virus proliferation. Although this virus is similar to human and animal SARS- and MERS-CoVs the detailed information about SARS-CoV-2 proteins structures and functions is urgently needed to rapidly develop effective vaccines, antibodies and antivirals. We applied high-throughput protein production and structure determination pipeline at the Center for Structural Genomics of Infectious Diseases to produce SARS-CoV-2 proteins and structures. Here we report the high-resolution crystal structure of endoribonuclease Nsp15/NendoU from SARS-CoV-2 – a virus causing current world-wide epidemics. We compare this structure with previously reported models of Nsp15 from SARS and MERS coronaviruses.


title: Polyglutamine Repeats in Viruses

text: This review explores the presence and functions of polyglutamine (polyQ) in viral proteins. In mammals, mutations in polyQ segments (and CAG repeats at the nucleotide level) have been linked to neural disorders and ataxias. PolyQ regions in normal human proteins have documented functional roles, in transcription factors and, more recently, in regulating autophagy. Despite the high frequency of polyQ repeats in eukaryotic genomes, little attention has been given to the presence or possible role of polyQ sequences in virus genomes. A survey described here revealed that polyQ repeats occur rarely in RNA viruses, suggesting that they have detrimental effects on virus replication at the nucleotide or protein level. However, there have been sporadic reports of polyQ segments in potyviruses and in reptilian nidoviruses (among the largest RNA viruses known). Conserved polyQ segments are found in the regulatory control proteins of many DNA viruses. Variable length polyQ tracts are found in proteins that contribute to transmissibility (cowpox A-type inclusion protein (ATI)) and control of latency (herpes viruses). New longer-read sequencing methods, using original biological samples, should reveal more details on the presence and functional role of polyQ in viruses, as well as the nucleotide regions that encode them. Given the known toxic effects of polyQ repeats, the role of these segments in neurovirulent and tumorigenic viruses should be further explored. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12035-018-1269-4) contains supplementary material, which is available to authorized users.


title: Minireview of progress in the structural study of SARS-CoV-2 proteins

text: Abstract A severe form of pneumonia, named coronavirus disease 2019 (COVID-19) by the World Health Organization, broke out in China and rapidly developed into a global pandemic, with millions of cases and hundreds of thousands of deaths reported globally. The novel coronavirus, which was designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified as the etiological agent of COVID-19. On the basis of experience accumulated following previous SARS-CoV and MERS-CoV outbreaks and research, a series of studies have been conducted rapidly, and major progress has been achieved with regard to the understanding of the phylogeny and genomic organization of SARS-CoV-2 in addition its molecular mechanisms of infection and replication. In the present review, we summarized crucial developments in the elucidation of the structure and function of key SARS-CoV-2 proteins, especially the main protease, RNA-dependent RNA polymerase, spike glycoprotein, and nucleocapsid protein. Results of studies on their associated inhibitors and drugs have also been highlighted.


title: Disidratazione acuta da gastroenterite nei lattanti

text: Il bambino sotto 1 anno e, soprattutto, di meno di 6 mesi è ad alto rischio di disidratazione, la cui causa principale è una gastroenterite acuta, soprattutto di origine virale. La gestione di una disidratazione da gastroenterite ha due componenti: la sua correzione e il rapido ripristino della normale perfusione tissutale e il mantenimento dei fabbisogni di acqua e di nutrienti, per limitare al massimo il deficit energetico. La valutazione della gravità della disidratazione è l’elemento chiave che guiderà la terapia. La perdita di peso, espressa in percentuale di peso corporeo prima dell’episodio di disidratazione, è il metodo di riferimento, ma è spesso difficile o impossibile da ottenere. Inoltre, i segni clinici, come l’alterazione dell’aspetto generale, l’allungamento del tempo di riempimento capillare, il riconoscimento di una plica cutanea persistente, gli occhi infossati, una secchezza delle mucose e la mancanza di lacrime, sono i principali elementi che permettono di valutare la gravità della disidratazione. Il trattamento si basa sulla rapida correzione del deficit del settore extracellulare. Un’espansione volemica di 20 ml/kg di una soluzione isotonica somministrata per via endovenosa o intraossea può essere necessaria nella fase iniziale nei casi più gravi (disidratazione > 10%). In tutti gli altri casi, la reidratazione per via orale per correggere il deficit di acqua in 4-6 ore è la tecnica di scelta, che si è dimostrata efficace, sicura e veloce. Essa utilizza delle soluzioni di reidratazione adattate che soddisfano criteri specifici. Il loro utilizzo precoce è la prevenzione più efficace delle forme gravi. L’allattamento al seno non deve essere interrotto e l’alimentazione artificiale deve essere ripresa da 4 a 6 ore dopo l’inizio della reidratazione. La vaccinazione contro i rotavirus prima dei 6 mesi è fortemente raccomandata.


title: Impact of dietary spray-dried bovine plasma addition on pigs infected with porcine epidemic diarrhea virus

text: Experimental data suggest that the addition of spray-dried plasma (SDP) to pig feed may enhance antibody responses against certain pathogens and negatively impact virus survival. The benefit of SDP on Escherichia coli infection is well documented. The aim of this study was to determine the effect of bovine SDP (BovSDP) in the pig diet on acute porcine epidemic diarrhea virus (PEDV) infection. A total of 16 3-wk-old conventional crossbred pigs were used and divided into three groups. Treatments included 1) a negative control group fed a commercial diet and sham inoculated with commercial liquid porcine plasma (n = 3), 2) a positive control group fed a commercial diet and inoculated with PEDV-spiked porcine plasma (PEDV; n = 8), and 3) a third group of pigs fed the commercial diet with inclusion of 5% spray-dried bovine plasma and inoculated with PEDV-spiked porcine plasma (BovSDP; n = 5). Although clinical signs associated with PEDV infection were mild in the BovSDP group, two of eight pigs in the PEDV group developed moderate clinical disease and had to be euthanized. The PEDV IgG and IgA antibody levels and prevalence rates were significantly (P < 0.05) higher in the PEDV–BovSDP group compared with the PEDV group at 7 d postinoculation. The average fecal PEDV RNA shedding time was 7.2 ± 1.0 d for the PEDV–BovSDP group and 9.3 ± 1.1 d for the PEDV group with an overall time to clearance of PEDV shedding of 11 d for PEDV–BovSDP pigs and at least 14 d for PEDV pigs, which was not different (P = 0.215). The results indicate that addition of BovSDP induced an earlier anti-PEDV antibody response in pigs experimentally infected with PEDV thereby reducing clinical disease and the amount and duration of viral shedding during acute PEDV infection.


title: Super-spreaders and the rate of transmission of the SARS virus

text: Abstract We describe a stochastic small-world network model of transmission of the SARS virus. Unlike the standard Susceptible-Infected-Removed models of disease transmission, our model exhibits both geographically localised outbreaks and “super-spreaders”. Moreover, the combination of localised and long range links allows for more accurate modelling of partial isolation and various public health policies. From this model, we derive an expression for the probability of a widespread outbreak and a condition to ensure that the epidemic is controlled. Moreover, multiple simulations are used to make predictions of the likelihood of various eventual scenarios for fixed initial conditions. The main conclusions of this study are: (i) “super-spreaders” may occur even if the infectiousness of all infected individuals is constant; (ii) consistent with previous reports, extended exposure time beyond 3–5 days (i.e. significant nosocomial transmission) was the key factor in the severity of the SARS outbreak in Hong Kong; and, (iii) the spread of SARS can be effectively controlled by either limiting long range links (imposing a partial quarantine) or enforcing rapid hospitalisation and isolation of symptomatic individuals.


title: Community-acquired pneumonia in children — a changing spectrum of disease

text: Pneumonia remains the leading cause of death in children outside the neonatal period, despite advances in prevention and management. Over the last 20 years, there has been a substantial decrease in the incidence of childhood pneumonia and pneumonia-associated mortality. New conjugate vaccines against Haemophilus influenzae type b and Streptococcus pneumoniae have contributed to decreases in radiologic, clinical and complicated pneumonia cases and have reduced hospitalization and mortality. The importance of co-infections with multiple pathogens and the predominance of viral-associated disease are emerging. Better access to effective preventative and management strategies is needed in low- and middle-income countries, while new strategies are needed to address the residual burden of disease once these have been implemented.


title: Insulin Resistance in Osteoarthritis: Similar Mechanisms to Type 2 Diabetes Mellitus

text: Osteoarthritis (OA) and type 2 diabetes mellitus (T2D) are two of the most widespread chronic diseases. OA and T2D have common epidemiologic traits, are considered heterogenic multifactorial pathologies that develop through the interaction of genetic and environmental factors, and have common risk factors. In addition, both of these diseases often manifest in a single patient. Despite differences in clinical manifestations, both diseases are characterized by disturbances in cellular metabolism and by an insulin-resistant state primarily associated with the production and utilization of energy. However, currently, the primary cause of OA development and progression is not clear. In addition, although OA is manifested as a joint disease, evidence has accumulated that it affects the whole body. As pathological insulin resistance is viewed as a driving force of T2D development, now, we present evidence that the molecular and cellular metabolic disturbances associated with OA are linked to an insulin-resistant state similar to T2D. Moreover, the alterations in cellular energy requirements associated with insulin resistance could affect many metabolic changes in the body that eventually result in pathology and could serve as a unified mechanism that also functions in many metabolic diseases. However, these issues have not been comprehensively described. Therefore, here, we discuss the basic molecular mechanisms underlying the pathological processes associated with the development of insulin resistance; the major inducers, regulators, and metabolic consequences of insulin resistance; and instruments for controlling insulin resistance as a new approach to therapy.


title: Virus respiratorios: viejos y nuevos virus. Revisión de métodos diagnósticos

text: Las infecciones respiratorias agudas de etiología viral se encuentran entre las principales causas de morbimortalidad infecciosa en el mundo. Junto a los virus tradicionalmente reconocidos, como los de la gripe, virus respiratorio sincitial, rinovirus, parainfluenza 1 a 4 y adenovirus, se han incorporado otros virus, como metaneumovirus, nuevos coronavirus (coronavirus humanos NL63 y HKU1 y coronavirus causante del síndrome respiratorio agudo grave [SRAG]) y, recientemente, los bocavirus. Aunque la mayoría de estas viriasis son clínicamente benignas y autolimitadas cuando afectan a adultos sanos, sus repercusiones sanitarias se incrementan cuando afectan a niños, ancianos o personas inmunodeprimidas o con enfermedades crónicas de base. Son una importante causa de hospitalización y defunción, fundamentalmente en los meses fríos y, desde el punto de vista sociosanitario, suponen un gran consumo de recursos económicos y una frecuente causa de absentismo laboral. Ocasionalmente, algunos de estos virus dan lugar a problemas sanitarios emergentes en todo el mundo, como sucede con las cepas pandémicas de gripe o el coronavirus asociado al SRAG. Si bien para los virus respiratorios tradicionales los métodos de diagnóstico clásicos, basados en el cultivo y la detección de antígenos, siguen siendo útiles, para los virus recientemente descritos el diagnóstico se realiza fundamentalmente por técnicas de amplificación genómica. Acute respiratory infections (ARI) of viral origin are one of the main causes of morbidity and mortality worldwide. In addition to traditional viruses, such as the influenza virus, respiratory syncytial virus, rhinovirus, parainfluenza viruses 1 to 4, and adenovirus, other viruses such as metapneumovirus, new coronaviruses (human coronavirus NL63 and HKU1 and severe acute respiratory syndrome [SARS]-coronavirus), and recently bocaviruses, have been identified as causal agents of ARI. Although most of these viral infections follow a benign and selflimiting course in healthy adults, the consequences for the health care systems increase when they involve children, the elderly, immunosuppressed individuals, or those with chronic underlying diseases. These viral infections are an important cause of hospitalization and death, mainly during the cold months of the year, and, from a social-health perspective, ARI are a drain on economic resources and a frequent cause of work absenteeism. Occasionally, some of these viruses may cause emergent world health problems, as has occurred with the influenza virus pandemic strain and SARScoronavirus. While classical diagnostic methods based on culture and antigen detection remain useful for traditional respiratory viruses, recently described viruses are diagnosed mainly by molecular amplification techniques.


title: Drug Repurposing to Fight Colistin and Carbapenem-Resistant Bacteria

text: The emergence of new resistance mechanisms, the failure of classical antibiotics in clinic, the decrease in the development of antibiotics in the industry are all challenges that lead us to consider new strategies for the treatment of infectious diseases. Indeed, in recent years controversy has intensified over strains resistant to carbapenem and/or colistin. Various therapeutic solutions are used to overcome administration of last line antibiotics. In this context, drug repurposing, which consists of using a non-antibiotic compound to treat multi-drug resistant bacteria (MDR), is encouraged. In this review, we first report what may have led to drug repurposing. Main definitions, advantages and drawbacks are summarized. Three major methods are described: phenotypic, computational and serendipity. In a second time we will focus on the current knowledge in drug repurposing for carbapenem and colistin-resistant bacteria with different studies describing repurposed compounds tested on Gram-negative bacteria. Furthermore, we show that drug combination therapies can increase successful by drug repurposing strategy. In conclusion, we discuss the pharmaceutical industries that have little interest in reprofiling drugs due to lack of profits. We also consider what a clinician might think of the indications of these uncommon biologists to treat MDR bacterial infections and avoid therapeutic impasses.


Ethique et recherche biomédicale durant l’épidémie du COVID-19 : ne confondons pas vitesse et précipitation !


title: Convalescent plasma: A possible treatment protocol for COVID- 19 patients suffering from diabetes or underlying liver diseases

text: BACKGROUND & AIM: As on date, no specific treatment is available for devastating COVID-19 (SARS-CoV-2) infection. This pandemic viral infection has affected over 200 countries within a very short time and created a calamitous situationacross the globe. As per WHO guidelines, the treatment is mainly symptomatic andsupportive. This clinical protocol has not proven sufficient to save the lives of COVID-19 patients suffering from diabetes or having underlying liver diseases; hence there isutmost need to tackle this situation by other means such as Convalescent Plasma (CP)therapy. METHODS: A comprehensive literature survey was carriedout using Elsevier, PubMed, Taylor & Francis, Springer, Nature and Google searchengines. RESULTS: The patients suffering from diabetes or liverdysfunction or any other underlying diseases are at greatest risk of SARS-CoV-2infection. From the study, it is proved that plasma collected from the recovered patientsof viral infection has considerable potential to treat the viral disease without theoccurrence of adverse effects. CONCLUSION: The CP therapy can bea possible life saving alternative to treat critical COVID-19 patients having diabetes orunderlying liver dysfunction. Hence, randomised clinical trials are recommended at theearliest to save the lives of infected individuals of COVID-19.


title: Psychological status and fatigue of frontline staff two months after the COVID-19 pandemic outbreak in China: A cross-sectional study

text: OBJECTIVE: Assessing the psychological status and fatigue of frontline staff exposed to COVID-19 in China. MEASURES: A cross-sectional survey via online questionnaires was conducted to evaluate frontline staff's psychological status and fatigue. Occurrence of depression, anxiety, and fatigue were measured with the Patient Health Questionnaire-9 (PHQ-9), the Self-Rating Anxiety Scale (SAS), and The Fatigue Self-Assessment Scale (FSAS), respectively. RESULTS: The study included 2614 participants and found that anxiety (23.4%), depression (50.0%), and fatigue (73.7%) were common in frontline workers. Participants were divided into five groups (community workers, health care workers, volunteers, market administration, and others). Analysis showed that levels of depression, anxiety, and fatigue were much higher in community workers than others (P < 0.01). Binary logistic regression indicated that being a woman, young age, sleeping difficulty, having lower income or family support, and physical or mental diseases, were associated with bad mood and proneness to fatigue. Spearman analysis showed fatigue to be highly correlated with depression and anxiety. CONCLUSION: In this study of frontline staff fighting COVID-19 in China, a high incidence of depression, anxiety, insomnia, and fatigue was reported. Effective strategies need to be provided immediately to improve the mental health of staff in the COVID-19 frontline, with community workers, women, the young, and those with physical and mental diseases requiring particular attention.


title: Healthcare Worker Perceptions of Mask Use during a Nosocomial Pertussis Outbreak—Pennsylvania, 2003

text: Abstract BACKGROUND: Recent experiences with severe acute respiratory syndrome (SARS) and influenza have led to new Respiratory Hygiene and Cough Etiquette (RHCE) recommendations that include use of surgical masks by healthcare workers (HCWs) who come within 3 feet of all patients with symptoms of respiratory infection. In September 2003, prior to these recommendations, eight HCWs at a Pennsylvania tertiary-care hospital developed respiratory symptoms after exposure to an infant with pertussis. We observed that HCWs did not routinely wear masks while caring for patients with cough illness. Anticipating the new recommendations and in an effort to understand potential barriers for implementation, we evaluated perceptions of mask use among HCWs in this hospital. METHODS: We conducted focus group discussions (FGDs) with two groups of nurses and one group of physicians (n1=4, n2=6, n3=9). Based on the discussions, we developed a structured, self-administered questionnaire for distribution to all HCWs present during two consecutive hospital shifts. RESULTS: Overall, 96 of 120 (80%) HCWs responded. Forty-nine (51%) respondents viewed coughing patients as potentially contagious to other patients and HCWs, and 67 (70%) believed that they and their patients would be protected against droplet infections by masks. Forty-three (45%) HCWs perceived obstacles to using mask. Masks were considered a barrier to a trusting provider-patient relationship: 20 HCWs felt that a provider in a mask increased worries among patients, and 26 thought that the mask was a barrier to communicating with patients. Thirty respondents indicated that wearing a mask was uncomfortable and/or a burden. HCWs were less likely to perceive obstacles if they recognized a risk for patient-to-patient transmission (27/35 versus 31/61; P=0.0095). CONCLUSIONS: Our findings suggest several potential barriers among HCWs to mask use, despite a recent pertussis outbreak in the hospital. HCWs may benefit from education regarding the risk of nosocomial transmission of respiratory pathogens such as SARS, influenza, and pertussis. Patients should be educated on the benefits of HCW mask use and its association with quality medical care.


title: A Review of Current Interventions for COVID-19 Prevention

text: Abstract The recent outbreak of CoVID-19 is declared as a global public health emergency of international concern by the World Health Organization (WHO). A fresh figure of 2268011 positive cases and 155185 death records (till April 18th 2020) across the worldwide signify the severity of this viral infection. CoVID-19 infection is a pandemic, surface to surface communicable disease with a case fatality rate of 3.4% as estimated by WHO up to March 3rd 2020. Unfortunately, the current unavailability of an effective antiviral drug and approved vaccine, worsen the situation more critical. Implementation of an effective preventive measure is the only option left to counteract CoVID-19. Further, a retrospective analysis provides evidence that contemplates the decisive role of preventive measures in controlling severe acute respiratory syndrome (SARS) outbreak in 2003. A statistical surveillance report of WHO reflects, maintaining a coherent infection, prevention and control guideline resulted in a 30% reduction in healthcare-associated infections. The effectiveness of preventive measures completely relies on the strength of surface disinfectants, the composition of hand sanitizer, appropriate material for the manufacture of personal protective equipment (PPE). This review enlightens the various preventive measures such as a suitable selection of surface disinfectants, appropriate hand sanitization, and empowering the PPE that could be a potential intervention to fight against CoVID-19.


title: Late Recognition of SARS in Nosocomial Outbreak, Toronto

text: Late recognition of severe acute respiratory syndrome (SARS) was associated with no known SARS contact, hospitalization before the nosocomial outbreak was recognized, symptom onset while hospitalized, wards with SARS clusters, and postoperative status. SARS is difficult to recognize in hospitalized patients with a variety of underlying conditions in the absence of epidemiologic links.


Age is just a number – and so is frailty: Strategies to inform resource allocation during the COVID-19 pandemic


title: Mitochondrial Dynamics in Basal and Stressful Conditions

text: The historical role of mitochondria resides in converting the energy released during the oxidation of macromolecules (carbohydrates, lipids and proteins) into adenosine tri-phosphate, a major form of chemically stored energy which sustains cell growth and homeostasis. Beyond this role in bioenergetics regulation, mitochondria play a role in several other cellular processes including lipid metabolism, cellular calcium homeostasis, autophagy and immune responses. Furthermore, mitochondria are highly dynamic organelles: as all other cellular endomembranes, they are continuously moving along cytoskeleton, and, most importantly, they constantly interact one with each other by membrane tethering, fusion and fission. This review aims to highlight the tight correlation between the morphodynamics of mitochondria and their biological function(s), in physiological as well as stress conditions, in particular nutrient deprivation, pathogen attack and some human diseases. Finally, we emphasize some crosstalk between the fusion/fission machinery and the autophagy pathway to ending on some speculative hypothesis to inspire future research in the field.


docid: bxyzhsfs

title: Anatomic evidence shows that lymphatic drainage exists in the pituitary to loop the cerebral lymphatic circulation

text: Respiratory infections can result in intracranial infections and unknown neurological symptoms. The central nervous system lacks classical meningeal lymphatic (circulation) drainage, and the exact underlying mechanisms of how immune cells from the peripheral lymphatic system enter the central nervous system (CNS) remain unknown. To determine whether the perinasal lymphatic system or lymphatic vessels are involved in cerebral immune defence and play a role in causing CNS infections (especially respiratory tract-related infections), we performed an anatomic study to investigate the drainage differences between the perinasal and intracerebral lymphatic systems by using injection of Evans blue and anatomic surgery, together with immunohistochemistry and immunofluorescence assays. Surprisingly, we found that (1) the pituitary (adenohypophysis) is involved and is rich in lymphatic vessels and (2) perinasal tissue could communicate with central pituitary lymphatic vessels in a specific and unidirectional manner. Taken together, our study may be the first to anatomically demonstrate the existence of novel lymphatic vessel structures in the pituitary, as well as their communication with the perinasal (lymphatic) tissue. Our findings suggest the existence of an ultimate loop for “classical” meningeal lymphatic drainage and are relevant to cerebral infection and immune defence.


title: Barriers to and new approaches for gene therapy and gene delivery in cystic fibrosis

text: Abstract Clinical trials of gene therapy for cystic fibrosis suggest that current levels of gene transfer efficiency are probably too low to result in clinical benefit, largely as a result of the barriers faced by gene transfer vectors within the airways. The respiratory epithelium has evolved a complex series of extracellular barriers (mucus, lack of receptors, immune surveillance, etc.) aimed at preventing penetration of lumenally delivered materials, including gene therapy vectors. In addition, once in the cell, further hurdles have to be overcome, including DNA degradation, nuclear import and the ability to maintain long-term transgene expression. Strategies to overcome these barriers will be addressed in this review and include the use of: (i) clinically relevant adjuncts to overcome the extra- and intracellular barriers; (ii) less-conventional delivery routes, such as intravenous or in utero administration; (iii) more efficient non-viral vectors and ‘stealth’ viruses which can be re-administered; and (iv) new approaches to prolong transgene expression by means of alternative promoters or integrating vectors. These advances have the potential to improve the efficiency of gene delivery to the airway epithelium, thus making gene therapy a more realistic option for cystic fibrosis.


title: Cynomolgus Macaque as an Animal Model for Severe Acute Respiratory Syndrome

text: BACKGROUND: The emergence of severe acute respiratory syndrome (SARS) in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV) infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs) infected with SARS-CoV. METHODS AND FINDINGS: In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain. CONCLUSIONS: SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children.


docid: ryychtqa

title: Attenuated Measles Virus as a Vaccine Vector

text: Live attenuated measles virus (MV) vaccines have an impressive record of safety, efficacy and ability to induce life-long immunity against measles infection. Using reverse genetics technology, such negative-strand RNA viruses can now be rescued from cloned DNA. This technology allows the insertion of exogenous genes encoding foreign antigens into the MV genome in such a way that they can be expressed by the MV vaccine strain, without affecting virus structure, propagation and cell targeting. Recombinant viruses rescued from cloned cDNA induce immune responses against both measles virus and the cloned antigens. The tolerability of MV to gene(s) insertion makes it an attractive flexible vector system, especially if broad immune responses are required. The fact that measles replication strictly occurs in the cytoplasm of infected cells without DNA intermediate has important biosafety implications and adds to the attractiveness of MV as a vector. In this article we report the characteristics of reporter gene expression (GFP, LacZ and CAT) and the biochemical, biophysical and immunological properties of recombinant MV expressing heterologous antigens of simian immunogeficiency virus (SIV).


Air Travel and Respiratory Disease


title: Acute phase proteins as local biomarkers of respiratory infection in calves

text: BACKGROUND: Cumulating reports suggest that acute phase proteins (APPs) do not only play a role as systemic inflammatory mediators, but are also expressed in different tissues as local reaction to inflammatory stimuli. The present study aimed to evaluate presence and changes in luminal lung concentrations of the APPs haptoglobin (Hp), lipopolysaccharide binding protein (LBP), C-reactive protein (CRP), and lactoferrin (Lf) in calves with an acute respiratory disease experimentally induced by Chlamydia (C.) psittaci. RESULTS: Intra-bronchial inoculation of the pathogen resulted in a consistent respiratory illness. In venous blood of the infected calves (n = 13), concentrations of plasma proteins and serum LBP were assessed (i) before exposure and (ii) 8 times within 14 days after inoculation (dpi). Increasing clinical illness correlated significantly with increasing LBP—and decreasing albumin concentrations in blood, both verifying a systemic acute phase response. Broncho-alveolar lavage fluid (BALF) was obtained from all 13 calves experimentally infected with C. psittaci at 4, 9 and 14 dpi, and from 6 uninfected healthy calves. Concentrations of bovine serum albumin (BSA), Hp, LBP, CRP and Lf in BALF were determined by ELISA. In infected animals, absolute concentrations of LBP and Hp in BALF correlated significantly with the respiratory score. The quotient [LBP]/[BSA] in BALF peaked significantly in acutely infected animals (4 dpi), showed a time-dependent decrease during the recovery phase (9-14 dpi), and was significantly higher compared to healthy controls. Concentrations of Hp and Lf in BALF as well as [Hp]/[BSA]—and [Lf]/[BSA]-quotients decreased during the study in infected animals, but were never higher than in healthy controls. CRP concentrations and [CRP]/[BSA]-quotient did not express significant differences between infected and healthy animals or during the course of infection. CONCLUSION: In conclusion, absolute concentrations of LBP in blood and BALF as well as the quotient [LBP]/[BSA] in BALF perfectly paralleled the clinical course of respiratory illness after infection. Beside LBP, the suitability of Hp and Lf as local biomarkers of respiratory infections in cattle and their role in the local response to pathogens is worth further investigation, while CRP does not seem to play a role in local defense mechanisms of the bovine lung.


title: Pan-cancer analysis of transmembrane protease serine 2 and cathepsin L that mediate cellular SARS-CoV-2 infection leading to COVID-19

text: Severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV2) is the cause of a new disease (COVID-19) which has evolved into a pandemic during the first half of 2020. Older age, male sex and certain underlying diseases, including cancer, appear to significantly increase the risk for severe COVID-19. SARS-CoV-2 infection of host cells is facilitated by the angiotensin-converting enzyme 2 (ACE-2), and by transmembrane protease serine 2 (TMPRSS2) and other host cell proteases such as cathepsin L (CTSL). With the exception of ACE-2, a systematic analysis of these two other SARS-CoV2 infection mediators in malignancies is lacking. Here, we analysed genetic alteration, RNA expression, and DNA methylation of TMPRSS2 and CTSL across a wide spectrum of tumors and controls. TMPRSS2 was overexpressed in cervical squamous cell carcinoma and endocervical adenocarcinoma, colon adenocarcinoma, prostate adenocarcinoma (PRAD), rectum adenocarcinoma (READ), uterine corpus endometrial carcinoma and uterine carcinosarcoma, with PRAD and READ exhibiting the highest expression of all cancers. CTSL was upregulated in lymphoid neoplasm diffuse large B-cell lymphoma, oesophageal carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, lower grade glioma, pancreatic adenocarcinoma, skin cutaneous melanoma, stomach adenocarcinoma, and thymoma. Hypo-methylation of both genes was evident in most cases where they have been highly upregulated. We have expanded on our observations by including data relating to mutations and copy number alterations at pan-cancer level. The novel hypotheses that are stemming out of these data need to be further investigated and validated in large clinical studies.


Wound Healing Center: Analysis of preventive measures and new indications in a teaching hospital in central Italy during the Covid‐19 emergency


Saturation of critical care capacity and mortality in patients with the novel coronavirus (COVID-19) in Italy


docid: gnrnsxej

title: SARS-CoV2 envelope protein: Non-synonymous mutations and its consequences

text: Abstract In the NCBI database, as on June 6, 2020, total number of available complete genome sequences of SARS-CoV2 across the world is 3617. The envelope protein of SARS-CoV2 possesses several non-synonymous mutations over the transmembrane domain and (C)-terminus in 15 (0.414%) genomes among 3617 available SARS-CoV2 genomes. More precisely, it is to be mentioned that 10(0.386%) out of 2588 genomes from the USA, 3(0.806%) from Asia, 1 (0.348%) from Europe and 1 (0.274%) from Oceania contain the missense mutations over the envelope proteins of SARS-CoV2 genomes. The C-terminus motif DLLV has been changed to DFLV and YLLV in the proteins QJR88103 (Australia: Victoria) and QKI36831 (China: Guangzhou) respectively, which might affect the binding of this motif with the host protein PALS1.


title: Assessing the Exacerbations Risk of Influenza‐Associated Chronic Occupational Asthma

text: The purpose of this article was to conduct a risk‐based study based on a linkage of experimental human influenza infections and fluctuation analysis of airway function to assess whether influenza viral infection was risk factor for exacerbations of chronic occupational asthma. Here we provided a comprehensive probabilistic analysis aimed at quantifying influenza‐associated exacerbations risk for occupational asthmatics, based on a combination of published distributions of viral shedding and symptoms scores and lung respiratory system properties characterized by long‐range peak expiratory flow (PEF) dynamics. Using a coupled detrended fluctuation analysis‐experimental human influenza approach, we estimated the conditional probability of moderate or severe lung airway obstruction and hence the exacerbations risk of influenza‐associated occupational asthma in individuals. The long‐range correlation exponent (α) was used as a predictor of future exacerbations risk of influenza‐associated asthma. For our illustrative distribution of PEF fluctuations and influenza‐induced asthma exacerbations risk relations, we found that the probability of exacerbations risk can be limited to below 50% by keeping α to below 0.53. This study also found that limiting wheeze scores to 0.56 yields a 75% probability of influenza‐associated asthma exacerbations risk and a limit of 0.34 yields a 50% probability that may give a representative estimate of the distribution of chronic respiratory system properties. This study implicates that influenza viral infection is an important risk factor for exacerbations of chronic occupational asthma.


title: Forests in a warming world

text: Summary As the climate catastrophe unfolds, forests are an important part of nature’s carbon sequestration and storage and thus planet-wide damage limitation. But will they still be able to play that role in a warmer world? As some forest ecosystems already suffer from rising temperatures, a comprehensive study of forest resilience identifies a new tipping point. Michael Gross reports.


COVID-19 containment measures adopted by AIEOP centres to prevent the virus spread among healthcare providers


docid: cyudxipf

title: Emerging coronavirus diseases and future perspectives

text: Coronavirus related infectious diseases seems to be biggest challenge of 21 century that have been constantly emerging and threating public health around the globe. Coronavirus disease-19 (COVID-19) that was detected as cause of respiratory tract infection in China by end the December 2019 impelled World Health Organization to declare in January 2020 public health emergency of international concern and consequently pandemic in March 2020. Over a past six months COVID-19 pandemic has wrapped up all continents except Antarctica. Scientists around the globe are finding way to tackle and reduce the ultimate risk and size of pandemic with lower morbidity and mortality rates. In this context, technologies such as sequencing, Crispr and artificial intelligence are playing vital role in diagnosis and management of infectious disease in contrast to conventional methods. Despite of this, there is a need to have rapid and early diagnostic tools and systems that recognize infectious disease in asymptotic condition. Here we provide an overview on the recent CoV outbreak and contribution of technologies with the emphasis on the future management for detection of such infectious diseases.


title: Differential transcription of matrix-metalloproteinase genes in primary mouse astrocytes and microglia infected with Theiler’s murine encephalomyelitis virus

text: The BeAn strain of Theiler’s murine encephalomyelitis virus (TMEV) induces demyelinating disease in susceptible mice comparable to human multiple sclerosis. Recent in vivo studies showed that matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of MMPs, TIMPs) are associated with demyelination in Theiler’s murine encephalomyelitis. The present study was performed to evaluate the in vitro MMP and TIMP expression in astrocytes and microglia following TMEV infection. Brain cell cultures from SJL/J mice were infected with the BeAn strain of TMEV and the expressions of 11 MMPs and 4 TIMPs were evaluated by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) at different time points post infection (p.i.). In control astrocytes and microglia, a constitutive expression of MMP-2, -3, -9, -10, -12, -13,-14, -15, -24 and TIMP-2 to -4 was detected. In addition, TIMP-1 and MMP-11 was found in astrocytes only, and MMP-7 was absent in both cells cultures. RT-qPCR demonstrated high virus RNA copy numbers in astrocytes and a low amount in microglia. In accordance, TMEV antigen was detected in astrocytes, whereas it was below the limit of detection in microglia. MMP-3, -9, -10, -12, and -13 as well as TIMP-1 were the enzymes most prominently up-regulated in TMEV-infected astrocytes. In contrast, TMEV infection was associated with a down-regulation of MMPs and TIMPs in microglia. Conclusively, in addition to inflammatory infiltrates, TMEV-induced astrocytic MMPs might trigger a proteolysis cascade leading to an opening of the blood-brain barrier and demyelination in vivo.


docid: mvqoyror

title: Spectrum of Viral Infections Among Primary Immunodeficient Children: Report From a National Registry

text: Objective: To present the frequency and spectrum of viral infections in primary immunodeficient children. Methods: The data was obtained from the Kuwait National Primary Immunodeficiency Disorders (PIDs) Registry during the period of 2004-2018. Results: A total of 274 PID children were registered in KNPIDR during the study period with predominance of immunodeficiencies affecting cellular and humoral immunity, followed by combined immunodeficiencies with associated syndromic features and diseases of immune dysregulation. Overall infectious complications affected 82.4% of the patients, and viral infections affected 31.7% of the registered patients. Forty-five patients (16.4%) developed viral infections caused by at least 2 organisms, among those 20 patients were affected by three or more viral infections. There was a statistically significant association between viral infections and PID category. However, there was no statistically significant association between viral infections and gender or the patients' onset age. There was a total of 170 viral infections during the study period and the causes of these infections were predominated by CMV (22.2%), adenovirus (11.7%), EBV (11.1%), and enteroviruses (7.4%). CMV and parainfluenza infections were more common in the group of immunodeficiencies affecting cellular and humoral immunity while EBV and human papilloma virus (HPV) were more common in the immune dysregulation group and combined immunodeficiencies with associated syndromic features, respectively. The most common presentation was viremia (28.8%) followed by pneumonia (28.2%) and skin infections (17.6%). The most common causes of viremia were CMV followed by adenovirus and EBV, while the most common organisms causing pneumonia were CMV followed by rhinovirus and parainfluenza. There were 80 deaths among the registered patients, 10% were caused by viral infections. Conclusions: Viral infections are common in PIDs and result into a wide-range of clinical manifestations causing significant morbidity and mortality.


title: COVID‐19 Vulnerability Among People Who Use Drugs: Recommendations for Global Public Health Programs and Policies

text: As cases of COVID‐19, the disease caused by the novel coronavirus (SARS‐CoV‐2), continue to spread globally, public health experts have warned about the devastating impact this pandemic may have on society's most vulnerable(1). Meanwhile, another public health crisis, the opioid epidemic, rages on throughout the U.S. (2, 3). In other parts of the world, the use of opiates and opioids has remained relatively stable; however, in Eastern Europe, Russia and Central Asia opiate use has increased(4).


title: Use of Sensitive, Broad-Spectrum Molecular Assays and Human Airway Epithelium Cultures for Detection of Respiratory Pathogens

text: Rapid and accurate detection and identification of viruses causing respiratory tract infections is important for patient care and disease control. Despite the fact that several assays are available, identification of an etiological agent is not possible in ∼30% of patients suffering from respiratory tract diseases. Therefore, the aim of the current study was to develop a diagnostic set for the detection of respiratory viruses with sensitivity as low as 1–10 copies per reaction. Evaluation of the assay using a training clinical sample set showed that viral nucleic acids were identified in ∼76% of cases. To improve assay performance and facilitate the identification of novel species or emerging strains, cultures of fully differentiated human airway epithelium were used to pre-amplify infectious viruses. This additional step resulted in the detection of pathogens in all samples tested. Based on these results it can be hypothesized that the lack of an etiological agent in some clinical samples, both reported previously and observed in the present study, may result not only from the presence of unknown viral species, but also from imperfections in the detection methods used.


title: Role of Pharmacists in COVID-19 Disease: A Jordanian Perspective

text: OBJECTIVES: The novel 2019 coronavirus outbreak that first appeared in Wuhan has quickly gained global attention, due to its high transmissibility and devastating clinical and economic outcomes. The aim of this study was to assess the possible roles of Jordanian pharmacists in minimizing the stage of community transmission. METHODS: A cross-sectional survey using Google forms targeting Jordanian pharmacists was conducted during March 2020 and distributed electronically by means of social media. Using the survey tool, we measured the pharmacists’ knowledge, the educative activities they perform, and their perceptions regarding undertaking traditional and untraditional roles during the COVID-19 outbreak, as specified by the International Pharmaceutical Federation (FIP). Collected data were analyzed using SPSS version-19. RESULTS: Jordanian pharmacists (n = 449) reported performing various educative activities, and in general, they were knowledgeable about various aspects of the COVID-19 disease (median knowledge score: 20 [range, 13-25]), but certain gaps in knowledge were detected that must be addressed. Pharmacists had positive perceptions about both their traditional and untraditional roles specified by the FIP, the median perceptions score was 4 (range, 1-5). CONCLUSIONS: Jordanian pharmacists can be used to reduce community transmission of the outbreak. However, more actions are required to keep pharmacists knowledgeable with recent disease updates to enable them to perform their tasks effectively during times of crisis.


title: CLEC2 and CLEC5A: Pathogenic Host Factors in Acute Viral Infections

text: The protective roles of endosomal toll-like receptors (TLRs) and cytosolic nucleic acid sensors are well elucidated, but the pathogenic host factors during viral infections remain unclear. Spleen tyrosine kinase (Syk)-coupled C-type lectins (CLECs) CLEC2 and CLEC5A are highly expressed on platelets and myeloid cells, respectively. CLEC2 has been shown to recognize snake venom aggretin and the endogenous ligand podoplanin and acts as a critical regulator in the development and immunothrombosis. Although CLEC2 has been reported to interact with type I immunodeficiency virus (HIV-1), its role in viral infections is still unclear. CLEC5A binds to fucose and mannose moieties of dengue virus membrane glycans, as well as to N-acetylglucosamine (GlcNAc)/N-acetylmuramic acid (MurNAc) disaccharides that form the backbone of L. monocytogenes peptidoglycans. Recently, we demonstrated that both CLEC2 and CLEC5A are critical in microbe-induced “neutrophil extracellular trap” (NET) formation and proinflammatory cytokine production. Moreover, activation of CLEC2 by dengue virus (DV) and H5N1 influenza virus (IAV) induces the release of extracellular vesicles (EVs), which further enhance NETosis and proinflammatory cytokine production via CLEC5A and Toll-like receptor 2 (TLR2). These findings not only illustrate the immunomodulatory effects of EVs during platelet-leukocyte interactions, but also demonstrate the critical roles of CLEC2 and CLEC5A in acute viral infections.


title: CRISPR-based surveillance for COVID-19 using genomically-comprehensive machine learning design

text: The emergence and outbreak of SARS-CoV-2, the causative agent of COVID-19, has rapidly become a global concern and has highlighted the need for fast, sensitive, and specific tools to surveil circulating viruses. Here we provide assay designs and experimental resources, for use with CRISPR-based nucleic acid detection, that could be valuable for ongoing surveillance. We provide assay designs for detection of 67 viral species and subspecies, including: SARS-CoV-2, phylogenetically-related viruses, and viruses with similar clinical presentation. The designs are outputs of algorithms that we are developing for rapidly designing nucleic acid detection assays that are comprehensive across genomic diversity and predicted to be highly sensitive and specific. Of our design set, we experimentally screened 4 SARS-CoV-2 designs with a CRISPR-Cas13 detection system and then extensively tested the highest-performing SARS-CoV-2 assay. We demonstrate the sensitivity and speed of this assay using synthetic targets with fluorescent and lateral flow detection. Moreover, our provided protocol can be extended for testing the other 66 provided designs. Assay designs are available at https://adapt.sabetilab.org/.


title: RNA regulatory processes in RNA virus biology

text: Numerous post‐transcriptional RNA processes play a major role in regulating the quantity, quality and diversity of gene expression in the cell. These include RNA processing events such as capping, splicing, polyadenylation and modification, but also aspects such as RNA localization, decay, translation, and non‐coding RNA‐associated regulation. The interface between the transcripts of RNA viruses and the various RNA regulatory processes in the cell, therefore, has high potential to significantly impact virus gene expression, regulation, cytopathology and pathogenesis. Furthermore, understanding RNA biology from the perspective of an RNA virus can shed considerable light on the broad impact of these post‐transcriptional processes in cell biology. Thus the goal of this article is to provide an overview of the richness of cellular RNA biology and how RNA viruses use, usurp and/or avoid the associated machinery to impact the outcome of infection. This article is categorized under: RNA in Disease and Development > RNA in Disease.


docid: awtfagku

title: Identification of previously unknown antigenic epitopes on the S and N proteins of avian infectious bronchitis virus

text: This paper describes mapping of antigenic and host-protective epitopes of infectious bronchitis virus proteins by assessing the ability of defined peptide regions within the S1, S2 and N proteins to elicit humoral, cell-mediated and protective immune responses. Peptides corresponding to six regions in the S1 (Sp1–Sp6), one in the S2 (Sp7) and four in the N protein (Np1–Np4) were synthesized and coupled to either diphtheria toxoid (dt) or biotin (bt). Bt-peptides were used to assess if selected regions were antigenic and contained B- or T-cell epitopes and dt-peptides if regions induced an antibody response and protection against virulent challenge. All S1 and S2 peptides were antigenic, being recognised by IBV immune sera and also induced an antibody response following inoculation into chicks. Three S1-and one S2-bt peptides also induced a delayed type hypersensitivity response indicating the presence of T-cell epitopes. The S2 peptide Sp7 (amino acid position 566–584) previously identified as an immundominant region, was the most antigenic of all peptides used in this study. Two S1 (Sp4 and Sp6) and one S2 peptide (Sp7), protected kidney tissue against virulent challenge. From four N peptides located in the amino-terminal part of the N protein, only one, Np2 (amino acid position 72–86), was antigenic and also induced a delayed type hypersensitivity response. None of the N peptides induced protection against virulent challenge. The results suggest that the S1 glycoprotein carries additional antigenic regions to those previously identified and that two regions located in the S1 and one in the S2 at amino acid positions 294–316 (Sp4), 532–537 (Sp6) and 566–584 (Sp7) may have a role in protection.


JAID/JSC Guidelines for the Treatment of Respiratory Infectious Diseases: The Japanese Association for Infectious Diseases/Japanese Society of Chemotherapy – The JAID/JSC Guide to Clinical Management of Infectious Disease/Guideline-preparing Committee Respiratory Infectious Disease WG


title: Cutaneous manifestations in hospitalized patients diagnosed as COVID‐19

text: BACKGROUND: Cutaneous manifestations of COVID‐19 disease have not yet been fully described. OBJECTIVES: To describe cutaneous manifestations of COVID‐19 disease in hospitalized patients. METHODS: We examined the cutaneous manifestations of 210 hospitalized patients. RESULTS: Cutaneous findings were observed during COVID‐19 infection in 52 of the patients. Lesions may be classified as erythematous scaly rash (32.7%), maculopapular rash (23%), urticarial lesions (13.5%), petechial purpuric rash (7.7%), necrosis (7.7%), enanthema and apthous stomatitis (5.8%), vesicular rash (5.8%), pernio (1.9%) and pruritus (1.9%). Cutaneous manifestations were observed statistically significantly more in certain age groups: patients of 55 to 64 and 65 to 74 years of age complained of more cutaneous manifestations than the other age groups. As for gender, there was no significant difference between male and female patients in terms of cutaneus findings. The relationship between comorbidity and dermatological finding status was statistically significant. The relationship increases linearly according to the comorbidities. According the statistical results the patients who were hospitalized in the intensive care unit had a higher risk of having cutaneous findings due to COVID‐19 infection. CONCLUSIONS: With this study we may highlight the importance of overlooked dermatological findings in patients that are hospitalized. This article is protected by copyright. All rights reserved.


Fluid colour sign on chest ultrasonography in a cat with exudate pleural effusion and pleuropneumonia


title: Traditional Chinese herbal medicine as a source of molecules with antiviral activity

text: Abstract Traditional Chinese herbal medicine (TCHM) is widely used in the prevention and treatment of viral infectious diseases. However, the operative mechanisms of TCHM remain largely obscure, mainly because of its complicated nature and the fragmented nature of research. In recent years, systematic methodologies have been developed to discover the active compounds in TCHM and to elucidate its underlying mechanisms. In this review, we summarize recent progress in TCHM-based antiviral research in China and other Asian countries. In particular, this review focuses on progress in targeting key steps in the viral replication cycle and key cellular components of the host defense system. Recent developments in centralized and standardized TCHM screening and databases are also summarized.


docid: nbwfjats

title: Matrix Protein 2 Vaccination and Protection against Influenza Viruses, Including Subtype H5N1

text: Changes in influenza viruses require regular reformulation of strain-specific influenza vaccines. Vaccines based on conserved antigens provide broader protection. Influenza matrix protein 2 (M2) is highly conserved across influenza A subtypes. To evaluate its efficacy as a vaccine candidate, we vaccinated mice with M2 peptide of a widely shared consensus sequence. This vaccination induced antibodies that cross-reacted with divergent M2 peptide from an H5N1 subtype. A DNA vaccine expressing full-length consensus-sequence M2 (M2-DNA) induced M2-specific antibody responses and protected against challenge with lethal influenza. Mice primed with M2-DNA and then boosted with recombinant adenovirus expressing M2 (M2-Ad) had enhanced antibody responses that cross-reacted with human and avian M2 sequences and induced T-cell responses. This M2 prime-boost vaccination conferred broad protection against challenge with lethal influenza A, including an H5N1 strain. Vaccination with M2, with key sequences represented, may provide broad protection against influenza A.


title: Inclusion of Oat in Feeding Can Increase the Potential Probiotic Bifidobacteria in Sow Milk

text: SIMPLE SUMMARY: In this study we isolated and characterized potential probiotic bifidobacteria from sow milk. The bifidobacterial population in milk has been attributed to the existence of prebiotic oat in feeding systems. Since breast feeding protects the newborns against several infectious diseases, milk from sows fed with oat could improve the health of piglets. ABSTRACT: The objectives of this study were to (i) investigate the impact of feeding oat on the population of bifidobacteria and (ii) evaluate their probiotic potential. In this study, we investigated the effects of supplementing sows’ gestation and lactation feed with 15% oat (prebiotic source) on the levels of probiotic population in milk. We found that dietary inclusion of oat during lactation and gestation resulted in increased levels of bifidobacteria compared to lactobacilli in sow milk. Furthermore bifidobacteria within the sow milk samples were further evaluated for probiotic potential based on aggregating properties, and acid- and bile-tolerance after exposure to hydrochloric acid (pH 2.5) and bile salts (0%, 0.25%, 0.50%, 1.0% and 2.0%). All isolates survived under the condition of low pH and bile 2.0%. Autoaggregation ability ranged from 17.5% to 73%. These isolates also showed antimicrobial activity against E. coli O157:H7. Together our results suggest that inclusion of oat in feeding systems could have the potential to improve the intestinal health of piglets by increasing the population of bifidobacteria.


docid: xlpzmgkf

title: Coxsackievirus A6 Induces Cell Cycle Arrest in G0/G1 Phase for Viral Production

text: Recent epidemiological data indicate that outbreaks of hand, foot, and mouth disease (HFMD), which can be categorized according to its clinical symptoms as typical or atypical, have markedly increased worldwide. A primary causative agent for typical HFMD outbreaks, enterovirus 71 (EV71), has been shown to manipulate the cell cycle in S phase for own replication; however, it is not clear whether coxsackievirus (CVA6), the main agent for atypical HFMD, also regulates the host cell cycle. In this study, we demonstrate for the first time that CVA6 infection arrests the host cell cycle in G0/G1-phase. Furthermore, synchronization in G0/G1 phase, but not S phase or G2/M phase, promotes viral production. To investigate the mechanism of cell cycle arrest induced by CVA6 infection, we analyzed cell cycle progression after cell cycle synchronization at G0/G1 or G2/M. Our results demonstrate that CVA6 infection promotes G0/G1 phase entry from G2/M phase, and inhibits G0/G1 exit into S phase. In line with its role to arrest cells in G0/G1 phase, the expression of cyclinD1, CDK4, cyclinE1, CDK2, cyclinB1, CDK1, P53, P21, and P16 is regulated by CVA6. Finally, the non-structural proteins of CVA6, RNA-dependent RNA polymerase 3D and protease 3C , are demonstrated to be responsible for the G0/G1-phase arrest. These findings suggest that CVA6 infection arrested cell cycle in G0/G1-phase via non-structural proteins 3D and 3C, which may provide favorable environments for virus production.


title: COVID‐19: Consider IL6 receptor antagonist for the therapy of cytokine storm syndrome in SARS‐CoV‐2 infected patients

text: COVID‐19 leads to mortality of several patients and the cytokine storm is reportedly critical in the patients. In order to reduce the cytokine storm, we would like to propose the IL6 receptor antagonist therapy for the COVID‐19 patients. Two humanized monoclonal antibodies are in clinical trial following IL6R antagonist therapies namely tocilizumab and sarilumab. However, researchers and physicians should look for more IL6 receptor antagonists for the therapy of cytokine storm syndrome SARS‐CoV‐2 infected persons to enhance the therapeutic options for cytokine storm. This article is protected by copyright. All rights reserved.