title: Nonstructural protein 6 of porcine epidemic diarrhea virus induces autophagy to promote viral replication via the PI3K/Akt/mTOR axis

text: Abstract Porcine epidemic diarrhea virus (PEDV) has caused, and continues to cause, severe economic losses to the swine industry worldwide. The pathogenic mechanism and immune regulatory interactions between PEDV and the host remain largely unknown. In this study, the interaction between autophagy and PEDV replication in intestinal porcine epithelial (IPEC-J2) cells was investigated. The effects of the structural and nonstructural proteins of PEDV on the autophagy process and the autophagy-related signaling pathways were also examined. The results shown that PEDV replication increased the autophagy flux in IPEC-J2 cells, and that autophagy was beneficial to PEDV replication, which may be one of the reasons for the rapid damage to intestinal epithelial cells and the enhanced virulence of PEDV in both newborn piglets and finishing pigs. When autophagy was pharmacologically induced by rapamycin, PEDV replication increased from 8.5 × 105 TCID50/mL to 8.8 × 106 TCID50/mL in IPEC-J2 cells. When autophagy was pharmacologically suppressed by hydroxychloroquine, PEDV replication decreased from 8.5 × 105 TCID50/mL to 7.9 × 104 TCID50/mL. To identify which PEDV proteins were the key inducers of autophagy, all 4 structural proteins and 17 nonstructural proteins of PEDV were eukaryotic expressed. It was found that the nonstructural protein 6 (nsp6) and ORF3 of PEDV were able to induce significant autophagy in IPEC-J2 cells, but the other proteins were unable to induce autophagy. It was indicated that nsp6-induced autophagy mainly occurred via the PI3K/Akt/mTOR signaling pathway. The results accelerate the understanding of the biology and pathogenesis of PEDV infection and provide new insights into the development of effective therapeutic strategies.


title: The Challenges of COVID-19 for People Living With Diabetes: Considerations for Digital Health

text: The coronavirus disease (COVID-19) is a global pandemic that significantly impacts people living with diabetes. Diabetes-related factors of glycemic control, medication pharmacodynamics, and insulin access can impact the severity of a COVID-19 infection. In this commentary, we explore how digital health can support the diabetes community through the pandemic. For those living with diabetes, digital health presents the opportunity to access care with greater convenience while not having to expose themselves to infection in an in-person clinic. Digital diabetes apps can increase agency in self-care and produce clinically significant improvement in glycemic control through facilitating the capture of diabetes device data. However, the ability to share these data back to the clinic to inform virtual care and enhance diabetes coaching and guidance remains a challenge. In the end, it requires an unnecessarily high level of technical sophistication on the clinic’s part and on those living with diabetes to routinely use their diabetes device data in clinic visits, virtual or otherwise. As the world comes together to fight the COVID-19 pandemic, close collaboration among the global diabetes community is critical to understand and manage the sustained impact of the pandemic on people living with diabetes.


title: Calves are susceptible to infection with the newly emerged porcine deltacoronavirus, but not with the swine enteric alphacoronavirus, porcine epidemic diarrhea virus

text: Fecal virus shedding, seroconversion and histopathology were evaluated in 3-7-year-old gnotobiotic calves orally inoculated with porcine deltacoronavirus (PDCoV) (9.0-9.6 log(10) genomic equivalents [GE] of OH-FD22-P5; n=4) or porcine epidemic diarrhea virus (PEDV) (10.2-12.5 log(10) GE of PC21A; n=3). In PDCoV-inoculated calves, an acute but persisting fecal viral RNA shedding and PDCoV-specific serum IgG antibody responses were observed, but without lesions or clinical disease. However, no fecal shedding, seroconversion, histological lesions, and clinical disease were detected in PEDV-inoculated calves. Our data indicate that calves are susceptible to infection by the newly emerged PDCoV, but not by the swine coronavirus, PEDV.


title: Letter to the Editor: COVID‐19‐Related Liver Injury and Clinical Outcomes: Does It Really Exist?

text: We read with interest the study by Lei and colleagues on the association between markers of liver injury and mortality in coronavirus disease 2019 (COVID‐19) in China. The authors have painstakingly collated data from a large number of COVID‐19 patients from multiple centers across Wuhan. They found that an increase in aspartate aminotransferase (AST) and its dynamicity correlated with COVID‐19‐related liver injury and patient outcomes. They concluded that the dynamic patterns of liver injury indicators, represented by AST, correspond with COVID‐19‐related liver injury.


Quantitative EEG markers to Prognosticate Critically ill Patients with COVID-19: A Retrospective Cohort Study


title: Nanoparticulate systems as drug carriers: the need

text: Development of nanoparticles for drug delivery has progressed by leaps and bounds over the last few decades, facilitating the possibility of an efficacious therapy for some fatal diseases. This development has stemmed from either the unsuitable physicochemical characteristics of the existing drug molecules, such as limited solubility and hence poor bioavailability, or the inadequacy of the conventional delivery systems to provide safe and efficient delivery. This chapter focuses on the precise need for the development of these novel nanoparticulate drug carriers and reasons for their popularity with the drug delivery scientists. The text also discusses the various strategies, including different formulation and targeting approaches, which have been adopted to overcome the challenges presented by the inherent properties of the drug molecules. Examples of nanoparticulate drug delivery systems which have already gained market approval have been cited in the discussion, wherever applicable.


title: Influenza Aerosols in UK Hospitals during the H1N1 (2009) Pandemic – The Risk of Aerosol Generation during Medical Procedures

text: BACKGROUND: Nosocomial infection of health-care workers (HCWs) during outbreaks of respiratory infections (e.g. Influenza A H1N1 (2009)) is a significant concern for public health policy makers. World Health Organization (WHO)-defined ‘aerosol generating procedures’ (AGPs) are thought to increase the risk of aerosol transmission to HCWs, but there are presently insufficient data to quantify risk accurately or establish a hierarchy of risk-prone procedures. METHODOLOGY/PRINCIPAL FINDINGS: This study measured the amount of H1N1 (2009) RNA in aerosols in the vicinity of H1N1 positive patients undergoing AGPs to help quantify the potential risk of transmission to HCWs. There were 99 sampling occasions (windows) producing a total of 198 May stages for analysis in the size ranges 0.86–7.3 µm. Considering stages 2 (4–7.3 µm) and 3 (0.86–4 µm) as comprising one sample, viral RNA was detected in 14 (14.1%) air samples from 10 (25.6%) patients. Twenty three air samples were collected while potential AGPs were being performed of which 6 (26.1%) contained viral RNA; in contrast, 76 May samples were collected when no WHO 2009 defined AGP was being performed of which 8 (10.5%) contained viral RNA (unadjusted OR = 2.84 (95% CI 1.11–7.24) adjusted OR = 4.31 (0.83–22.5)). CONCLUSIONS/SIGNIFICANCE: With our small sample size we found that AGPs do not significantly increase the probability of sampling an H1N1 (2009) positive aerosol (OR (95% CI) = 4.31 (0.83–22.5). Although the probability of detecting positive H1N1 (2009) positive aerosols when performing various AGPs on intensive care patients above the baseline rate (i.e. in the absence of AGPs) did not reach significance, there was a trend towards hierarchy of AGPs, placing bronchoscopy and respiratory and airway suctioning above baseline (background) values. Further, larger studies are required but these preliminary findings may be of benefit to infection control teams.


title: Adaptations de la prise en charge des patients en Nutrition Artificielle à Domicile au cours de l’épidémie virale COVID-19 en France: avis du Comité de Nutrition à Domicile de la Société Francophone de Nutrition Clinique et Métabolisme (SFNCM)

text: Résumé La nutrition artificielle à domicile, entérale ou parentérale, s’adresse à des malades chroniques fragiles. La situation actuelle de pandémie COVID-19 peut compromettre leur prise en charge à plusieurs niveaux : difficultés d’accès aux établissements de santé largement réorientés vers la prise en charge des malades COVID-19, possible pénurie d’infirmières à domicile, forte réduction des visites des prestataires de service à domicile, tensions sur les solutions hydro-alcooliques, les masques et les régulateurs de débit. Le but de ces recommandations établies par le Comité de Nutrition à Domicile de la Société Francophone de Nutrition Clinique et Métabolisme est, d’une part, de préciser la prise en charge minimale de ces patients, tant en termes de suivi que de matériels, mais surtout de s’adapter aux tensions actuelles relatives aux personnes et aux matériels, afin de poursuivre une prise en charge de qualité et de ne pas compromettre l’état de santé des patients en nutrition artificielle à domicile pendant la crise. Abstract Home artificial nutrition, whether enteral or parenteral, is provided to chronic and fragile patients. The current COVID-19 epidemics may compromise their care at several levels: difficulties to access to hospitals mainly focused on treating COVID-19 patients, possible lack of nurses at home, strong reduction of visits by homecare providers, tended flow or lack of hand sanitizers, surgical masks and pumps. The aim of these recommendations put together by the French-speaking Society for Clinical Nutrition and Metabolism (SFNCM)’s Home Artificial Nutrition Committee is to define in terms of healthcare resources the minimum care to provide to these patients. We also aim to help cope with the possible tensions, in order to secure the care we must provide to home artificial nutrition patients during this crisis.


title: Inhibition of Influenza H7 Hemagglutinin-Mediated Entry

text: The recent outbreak of H7N9 influenza in China is of high concern to public health. H7 hemagglutinin (HA) plays a critical role in influenza entry and thus HA presents an attractive target for antivirals. Previous studies have suggested that the small molecule tert-butyl hydroquinone (TBHQ) inhibits the entry of influenza H3 HA by binding to the stem loop of HA and stabilizing the neutral pH conformation of HA, thereby disrupting the membrane fusion step. Based on amino acid sequence, structure and immunogenicity, H7 is a related Group 2 HA. In this work we show, using a pseudovirus entry assay, that TBHQ inhibits H7 HA-mediated entry, as well as H3 HA-mediated entry, with an IC50∼6 µM. Using NMR, we show that TBHQ binds to the H7 stem loop region. STD NMR experiments indicate that the aromatic ring of TBHQ makes extensive contact with the H7 HA surface. Limited proteolysis experiments indicate that TBHQ inhibits influenza entry by stabilizing the H7 HA neutral pH conformation. Together, this work suggests that the stem loop region of H7 HA is an attractive target for therapeutic intervention and that TBHQ, which is a widely used food preservative, is a promising lead compound.


title: Bordetella Pertussis Infection in Hospitalized Infants with Acute Bronchiolitis

text: OBJECTIVE: To assess the frequency of B. pertussis infection among young infants hospitalized with acute bronchiolitis and to determine whether B. pertussis infection affects the clinical course of acute bronchiolitis. METHODS: A total of 172 infants <6 months of age hospitalized with acute bronchiolitis were tested for B. pertussis and respiratory viruses with real-time PCR. Cases were divided into 2 groups according to B. pertussis positive or negative. Clinical parameters, clinical severity scores and laboratory characteristics of the pertussis-positive and pertussis-negative cases were compared. RESULTS: Bordetella pertussis infection was detected in 44 (25.6%) of the 172 infants hospitalized for acute bronchiolitis, and as co-infection with respiratory viral agents in 27 (61.4%) infants. Of the 44 pertussis-positive infants, only 17 (38.6%) experienced a paroxysmal cough, 13 (29.5%) had whooping and 15 (34.1%) had post-tussive vomiting. There was no significant difference between pertussis-positive and pertussis-negative infants according to Wang clinical score at admission (4.9 ± 1.5 vs. 5.2 ± 2.5; p = 0.689). The overall disease severity score was also similar between the two groups (6.5 ± 1.4 vs. 6.9 ± 1.6; p = 0.095). CONCLUSIONS: Bordetella pertussis infection is common in young infants hospitalized for acute bronchiolitis, mostly as co-infection with respiratory viruses. The clinical features of pertussis in the infants are not characteristic. Viral bronchiolitis and pertussis cases could not be differentiated by clinical findings. Co-infection with pertussis did not affect the clinical outcome in infants hospitalized with acute bronchiolitis.


title: Burden of Illness in UK Subjects with Reported Respiratory Infections Vaccinated or Unvaccinated against Influenza: A Retrospective Observational Study

text: OBJECTIVE: Detailed data are lacking on influenza burden in the United Kingdom (UK). The objective of this study was to estimate the disease burden associated with influenza-like illness (ILI) in the United Kingdom stratified by age, risk and influenza vaccination status. METHODS: This retrospective, cross-sectional, exploratory, observational study used linked data from the General Practice Research Database and the Hospital Episode Statistics databases to estimate resource use and cost associated with ILI in the UK. RESULTS: Data were included from 156,193 patients with ≥1 general practitioner visit with ILI. There were 21,518 high-risk patients, of whom 12,514 (58.2%) were vaccinated and 9,004 (41.8%) were not vaccinated, and 134,675 low-risk patients, of whom 17,482 (13.0%) were vaccinated and 117,193 (87.0%) were not vaccinated. High-risk vaccinated patients were older (p<0.001) and had more risk conditions (p<0.001). High-risk (odds ratio [OR] 2.16) or vaccinated (OR 1.19) patients had a higher probability of >1 general practitioner visit compared with low-risk and unvaccinated patients. Patients who were high-risk and vaccinated had a reduced risk of >1 general practitioner visit (OR 0.82; p<0.001). High-risk individuals who were also vaccinated had a lower probability of ILI-related hospitalisation than individuals who were high-risk or vaccinated alone (OR 0.59). In people aged ≥65 years, the mortality rate was lower in vaccinated than unvaccinated individuals (OR 0.75). The cost of ILI-related GP visits and hospital admissions in the UK over the study period in low-risk vaccinated patients was £27,391,142 and £141,932,471, respectively. In low-risk unvaccinated patients the corresponding values were £168,318,709 and £112,534,130, respectively. CONCLUSIONS: Although vaccination rates in target groups have increased, many people are still not receiving influenza vaccination, and the burden of ILI in the United Kingdom remains substantial. Improving influenza vaccination uptake may have the potential to reduce this burden.


title: Direct oral anticoagulant plasma levels’ striking increase in severe COVID‐19 respiratory syndrome patients treated with antiviral agents: The Cremona experience

text: BACKGROUND: Antiviral drugs are administered in patients with severe COVID‐19 respiratory syndrome, including those treated with direct oral anticoagulants (DOACs). Concomitant administration of antiviral agents has the potential to increase their plasma concentration. A series of patients managed in the Cremona Thrombosis Center were admitted at Cremona Hospital for SARS‐CoV‐2 and started antiviral drugs without stopping DOAC therapy. DOAC plasma levels were measured in hospital and results compared with those recorded before hospitalization. METHODS: All consecutive patients on DOACs were candidates for administration of antiviral agents (lopinavir, ritonavir, or darunavir). Plasma samples for DOAC measurement were collected 2to 4 days after starting antiviral treatment, at 12 hours from the last dose intake in patients on dabigatran and apixaban, and at 24 hours in those on rivaroxaban and edoxaban. For each patient, C‐trough DOAC level, expressed as ng/mL, was compared with the one measured before hospitalization. RESULTS: Of the 1039 patients hospitalized between February 22 and March 15, 2020 with COVID‐19 pneumonia and candidates for antiviral therapy, 32 were on treatment with a DOAC. DOAC was stopped in 20 and continued in the remaining 12. On average, C‐trough levels were 6.14 times higher during hospitalization than in the pre‐hospitalization period. CONCLUSION: DOAC patients treated with antiviral drugs show an alarming increase in DOAC plasma levels. In order to prevent bleeding complications, we believe that physicians should consider withholding DOACs from patients with SARS‐CoV‐2 and replacing them with alternative parenteral antithrombotic strategies for as long as antiviral agents are deemed necessary and until discharge.


title: Covid-19 palaver: Ending rights violations of vulnerable groups in Africa

text: This letter amplifies the rising spate of human rights violations exacerbated by the COVID-19 pandemic in Africa. It notes that while governments in the region have declared restrictions on social gathering, in a bid to curtail the deadly disease, violations of human rights of vulnerable groups by State security operatives are on the increase. It argues that the underlying rationale for such abuses emanates from the dearth of a rights-based approach to police-public relations combined with inadequate public health and social care infrastructures for large sections of the populace. Policy implications are drawn out while suggestions are offered to social work professionals given their longstanding commitment to national security and national development.


title: A global-scale ecological niche model to predict SARS-CoV-2 coronavirus infection rate

text: COVID-19 pandemic is a global threat to human health and economy that requires urgent prevention and monitoring strategies. Several models are under study to control the disease spread and infection rate and to detect possible factors that might favour them, with a focus on understanding the correlation between the disease and specific geophysical parameters. However, the pandemic does not present evident environmental hindrances in the infected countries. Nevertheless, a lower rate of infections has been observed in some countries, which might be related to particular population and climatic conditions. In this paper, infection rate of COVID-19 is modelled globally at a 0.5(∘) resolution, using a Maximum Entropy-based Ecological Niche Model that identifies geographical areas potentially subject to a high infection rate. The model identifies locations that could favour infection rate due to their particular geophysical (surface air temperature, precipitation, and elevation) and human-related characteristics (CO(2) and population density). It was trained by facilitating data from Italian provinces that have reported a high infection rate and subsequently tested using datasets from World countries’ reports. Based on this model, a risk index was calculated to identify the potential World countries and regions that have a high risk of disease increment. The distribution outputs foresee a high infection rate in many locations where real-world disease outbreaks have occurred, e.g. the Hubei province in China, and reports a high risk of disease increment in most World countries which have reported significant outbreaks (e.g. Western U.S.A.). Overall, the results suggest that a complex combination of the selected parameters might be of integral importance to understand the propagation of COVID-19 among human populations, particularly in Europe. The model and the data were distributed through Open-science Web services to maximise opportunities for re-usability regarding new data and new diseases, and also to enhance the transparency of the approach and results.


title: Viral disease emergence in shrimp aquaculture: origins, impact and the effectiveness of health management strategies

text: Shrimp aquaculture has grown rapidly over several decades to become a major global industry that serves the increasing consumer demand for seafood and has contributed significantly to socio‐economic development in many poor coastal communities. However, the ecological disturbances and changes in patterns of trade associated with the development of shrimp farming have presented many of the pre‐conditions for the emergence and spread of disease. Shrimp are displaced from their natural environments, provided artificial or alternative feeds, stocked in high density, exposed to stress through changes in water quality and are transported nationally and internationally, either live or as frozen product. These practices have provided opportunities for increased pathogenicity of existing infections, exposure to new pathogens, and the rapid transmission and transboundary spread of disease. Not surprisingly, a succession of new viral diseases has devastated the production and livelihoods of farmers and their sustaining communities. This review examines the major viral pathogens of farmed shrimp, the likely reasons for their emergence and spread, and the consequences for the structure and operation of the shrimp farming industry. In addition, this review discusses the health management strategies that have been introduced to combat the major pathogens and the reasons that disease continues to have an impact, particularly on poor, small‐holder farmers in Asia.


title: Use of Obstetric Practice Web Sites to Distribute Zika Virus Information to Pregnant Women During a Zika Virus Outbreak

text: OBJECTIVE: To describe the current use of obstetric practice Web sites to disseminate Zika virus information to patients. DESIGN: Review of 913 randomly selected practice Web sites and associated social media accounts in January and August 2016. SETTING: Obstetric practice Web sites and associated social media accounts, United States of America. PARTICIPANTS: N/A. MAIN OUTCOME MEASURES: Proportion of obstetric practice Web sites and linked social media accounts providing Zika virus information. RESULTS: Twenty-five percent and 35% of obstetric practice Web sites had information posted about Zika virus in January 2016 and August 2016, respectively. Between the 2 time points, the proportion of practices posting Zika virus content on Facebook and Twitter declined (Facebook: 15% in January, 9% in August; Twitter: 12% in January, 8% in August). In August, the most frequently observed Zika virus–related content themes were the use of insect repellent (14%) and travel advisories (14%). At both time points, practices affiliated with large university hospitals were more likely to have posted information on Zika virus than independent OB/GYN-only practices: January: odds ratio (OR) (95% confidence interval [CI]) = 5.68 (3.50-9.20); August: OR (95% CI) = 8.37 (5.31-13.17). Similarly, practices associated with nonuniversity hospitals were more likely to have posted information than independent OB/GYN-only practices: January: OR (95% CI) = 2.71 (1.88-3.92); August: OR (95% CI) = 6.75 (4.75-9.60). CONCLUSION: Obstetric care practices are not fully utilizing their practice Web sites to relay Zika virus information to their patients. Since practitioner-sponsored Web sites have the capacity to directly reach the populations at greatest risk for Zika virus complications, public health professionals should consider adapting their materials and provider outreach campaigns to more easily accommodate Web site–based information dissemination during this type of public health emergency. There must be greater recognition of the value information gains in the eyes of the patient when it is validated by their own provider, especially when that patient is part of the highest-risk population for a given emergency. Public health organizations should strive to minimize the burden it takes for providers to relay useful resources to patients in order to maximize the impact that those resources can have.


title: Renin-Angiotensin-System (RAS) und COVID-19 – Zur Verordnung von RAS-Blockern

text: Twenty years ago, an enzyme homologous to the previously known angiotensin-converting enzyme (ACE) was identified, and subsequently named ACE2. In the renin-angiotensin system (RAS), ACE2 has counter-regulatory functions against the classical effector peptide angiotensin II, for example in blood pressure regulation and cardiovascular remodeling. However, ACE2 provides an initially unexpected interesting link between virology and cardiovascular medicine. That is, ACE2 represents the binding receptor for the cellular uptake of SARS-CoV and SARS-CoV-2 viruses. Thus, ACE2 is relevant for COVID-19. In this context, it was suspected that therapy with RAS blockers might promote transmission and complications of COVID-19 by upregulation of ACE2 expression. The aim of this short review is, to describe the link between the RAS, particularly ACE2, and COVID-19. Based on our analysis and evaluation of the available findings, we justify our conclusion: important drugs such as ACE inhibitors and angiotensin receptor blockers should continue to be prescribed according to guidelines to stable patients in the context of the COVID-19 pandemic.


Our challenge is to adapt the organization of our system to the six stages of the epidemic to go beyond the COVID‐19 crisis


Giant Retroperitoneal Hematoma during Extracorporeal Membrane Oxygenation in a Patient with 2019-Coronavirus Pneumonia


title: Evolutionary longitudinal network dynamics of global zoonotic research

text: At global and local levels, we are observing an increasing range and rate of disease outbreaks that show evidence of jumping from animals to humans, and from food to humans. Zoonotic infections (i.e. Hendra, swine flu, anthrax) affect animal health and can be deadly to humans. The increasing rate of outbreaks of infectious diseases transferring from animals to humans (i.e. zoonotic diseases) necessitates detailed understanding of the education, research and practice of animal health and its connection to human health. These emerging microbial threats underline the need to exploring the evolutionary dynamics of zoonotic research across public health and animal health. This study investigates the collaboration network of different countries engaged in conducting zoonotic research. We explore the dynamics of this network from 1980 to 2012 based on large scientific data developed from Scopus. In our analyses, we compare several properties of the network including density, clustering coefficient, giant component and centrality measures over time. We also map the network over different time intervals using VOSviewer. We analyzed 5182 publication records. We found United States and United Kingdom as the most collaborative countries working with 110 and 74 other countries in 1048 and 599 cases, respectively. Our results show increasing close collaboration among scientists from the United States, several European countries including United Kingdom, Italy, France, Netherland, Switzerland, China and Australia with scientists from other parts of the world.


title: The close relationship between sudden loss of smell and COVID-19

text: Abstract Introduction The real number of COVID-19 cases may be underestimated since several countries have difficulty offering laboratory tests for all the population. Therefore, finding a symptom with a high predictive value would help in diagnostic and isolation strategies. Objective To correlate the sudden loss of the sense of smell in the context of the COVID-19 pandemic with results of diagnostic tests for COVID-19. Material and methods This is a cross-sectional observational study. An online questionnaire was digitally addressed to 725 outpatients in Brazil who reported partial or total sudden loss of the sense of smell from March to April 2020. Results Total or partial sudden loss of the sense of smell showed high Positive Predictive Value (PPV) for COVID-19 diagnosis, during the COVID-19 pandemic in Brazil (88.8%). There were no differences between groups tested positive and negative in regard to demographic and clinical characteristics such as presence of allergy, rhinitis, neither to olfactory recovery time. Conclusion The identification of sudden loss of the sense of smell during COVID-19 pandemic may serve as a sentinel symptom and may be a warning to establish measures to prevent the transmission of the disease.


title: Human Enterovirus Nonstructural Protein 2C(ATPase) Functions as Both an RNA Helicase and ATP-Independent RNA Chaperone

text: RNA helicases and chaperones are the two major classes of RNA remodeling proteins, which function to remodel RNA structures and/or RNA-protein interactions, and are required for all aspects of RNA metabolism. Although some virus-encoded RNA helicases/chaperones have been predicted or identified, their RNA remodeling activities in vitro and functions in the viral life cycle remain largely elusive. Enteroviruses are a large group of positive-stranded RNA viruses in the Picornaviridae family, which includes numerous important human pathogens. Herein, we report that the nonstructural protein 2C(ATPase) of enterovirus 71 (EV71), which is the major causative pathogen of hand-foot-and-mouth disease and has been regarded as the most important neurotropic enterovirus after poliovirus eradication, functions not only as an RNA helicase that 3′-to-5′ unwinds RNA helices in an adenosine triphosphate (ATP)-dependent manner, but also as an RNA chaperone that destabilizes helices bidirectionally and facilitates strand annealing and complex RNA structure formation independently of ATP. We also determined that the helicase activity is based on the EV71 2C(ATPase) middle domain, whereas the C-terminus is indispensable for its RNA chaperoning activity. By promoting RNA template recycling, 2C(ATPase) facilitated EV71 RNA synthesis in vitro; when 2C(ATPase) helicase activity was impaired, EV71 RNA replication and virion production were mostly abolished in cells, indicating that 2C(ATPase)-mediated RNA remodeling plays a critical role in the enteroviral life cycle. Furthermore, the RNA helicase and chaperoning activities of 2C(ATPase) are also conserved in coxsackie A virus 16 (CAV16), another important enterovirus. Altogether, our findings are the first to demonstrate the RNA helicase and chaperoning activities associated with enterovirus 2C(ATPase), and our study provides both in vitro and cellular evidence for their potential roles during viral RNA replication. These findings increase our understanding of enteroviruses and the two types of RNA remodeling activities.


title: Parasitosis (I). Lesiones cardiacas y pulmonares importadas

text: Imported parasitoses are an uncommon condition in our setting, although recently, the increase of migratory flow has been leading to an increase in the detected cases of these diseases. This fundamentally occurs in immigrants from tropical zones where these conditions are generally endemic. However, imported parasitoses are being increasingly diagnosed in Western persons who have lived in the tropics for different reasons. When examining a subject with cardiovascular syndromes with a possible parasitic origin, it could be useful to classify the possible geographic zone of origin in order to perform disease screening. Then, if the problem is mainly respiratory, it would be well to first rule out the existence of tuberculosis in the case of long stays and to individual the diagnosis according to the geographic area, season of the year, type of exposure and symptoms presented, in the case of shorter stays.


One‐lung ventilation during the COVID‐19 pandemic


Covid-19 in India: Post-Lockdown scenarios and provisioning for healthcare


Preventing Suicide in Rural Communities During the COVID‐19 Pandemic


title: Efficacy of face masks and respirators in preventing upper respiratory tract bacterial colonization and co-infection in hospital healthcare workers

text: Abstract Objective We compared the efficacy of medical masks (MM) and N95 respirators (N95) in preventing bacterial colonization/infection in healthcare workers (HCWs). Methods A cluster randomized clinical trial (RCT) of 1441 hospital HCWs randomized to medical masks or N95 respirators, and compared to 481 control HCWs, was performed in Beijing, China, during the winter season of 2008–2009. Participants were followed for development of clinical respiratory illness (CRI). Symptomatic subjects were tested for Streptococcus pneumoniae, Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae or Haemophilus influenza type B by multiplex polymerase chain reaction (PCR). Results The rate of bacterial colonization was 2.8% in the N95 group (p=0.02), 5.3% among medical mask users (p<0.01) and 7.5% among the controls (p=0.16). N95 respirators were significantly protective (adjusted RR 0.34, 95% CI: 0.21–0.56) against bacterial colonization. Co-infections of two bacteria or a virus and bacteria occurred in up to 3.7% of HCWs, and were significantly lower in the N95 arm. Conclusions N95 respirators were significantly protective against bacterial colonization, co-colonization and viral-bacterial co-infection. We showed that dual respiratory virus or bacterial-viral co-infections can be reduced by the use of N95 respirators. This study has occupational health and safety implications for health workers.


title: Host Single Nucleotide Polymorphisms Modulating Influenza A Virus Disease in Humans

text: A large number of human genes associated with viral infections contain single nucleotide polymorphisms (SNPs), which represent a genetic variation caused by the change of a single nucleotide in the DNA sequence. SNPs are located in coding or non-coding genomic regions and can affect gene expression or protein function by different mechanisms. Furthermore, they have been linked to multiple human diseases, highlighting their medical relevance. Therefore, the identification and analysis of this kind of polymorphisms in the human genome has gained high importance in the research community, and an increasing number of studies have been published during the last years. As a consequence of this exhaustive exploration, an association between the presence of some specific SNPs and the susceptibility or severity of many infectious diseases in some risk population groups has been found. In this review, we discuss the relevance of SNPs that are important to understand the pathology derived from influenza A virus (IAV) infections in humans and the susceptibility of some individuals to suffer more severe symptoms. We also discuss the importance of SNPs for IAV vaccine effectiveness.


title: Imaging of Emerging Infectious Diseases

text: PURPOSE OF REVIEW: Emerging infectious diseases have seen a record increase in prevalence, and understanding their management is critical in an increasingly global community. In this paper, we review current literature detailing the role of radiology in the diagnosis and treatment of the Ebola (EVD), Zika (ZVD), Chikungunya (CHIKF), H1N1, Middle East Respiratory (MERS), and Severe Acute Respiratory Syndrome (SARS) viruses. RECENT FINDINGS: Complex protocols are required to safely use portable imaging in EVD to prevent nosocomial spread of disease. In ZVD, antenatal ultrasound can detect fetal abnormalities early, allowing implementation of care and support to affected families. Imaging is useful in assessing the extent of involvement of chronic CHIKF and monitoring treatment effect. Chest radiography and CT play a more direct role in the diagnosis and monitoring of the viral infections with primarily respiratory manifestations (H1N1, MERS, and SARS). SUMMARY: Radiology plays a variable role in emerging infectious diseases, requiring an understanding of disease transmission and safe imaging practices, as well as imaging features that affect clinical management.


title: Communication Skills in the Age of COVID-19

text: COVID-19 has placed enormous stress on hospitals and health care providers worldwide. Limitations in hospital capacity may result in difficult decisions in how life-sustaining technologies are allocated among patients. The authors of this essay provide guidance on how to communicate with patients who are seriously ill from COVID-19 infection.


title: Can Lower Remittance Costs Improve Human Capital Accumulation in Africa?

text: To evaluate gains in human capital accumulation from reduction in remittance prices, this study constructs a general equilibrium model in which the choices to invest in human capital and to migrate are endogenous. The model is calibrated for a group of eight African economies which offer student loans, and the effect on human capital accumulation of decreasing the remittance price to the level recommended by the United Nations (3%) is numerically derived. It is found that reduction in remittance prices alters the decisions of households, leading in the aggregate to a decrease in interest rates, a curbing of the desire to migrate, and an increase human capital. Hence, the study offers the policy prescription that governments, both in nations where remittances originate and in those to which funds are sent, must continue to lower remittance prices, by, for example, improving access to mobile banking, especially since such policies are relatively immune to economic shocks.


title: Full-length genomic characterization and molecular evolution of canine parvovirus in China

text: Canine parvovirus type 2 (CPV-2) can cause acute haemorrhagic enteritis in dogs and myocarditis in puppies. This disease has become one of the most serious infectious diseases of dogs. During 2014 in China, there were many cases of acute infectious diarrhoea in dogs. Some faecal samples were negative for the CPV-2 antigen based on a colloidal gold test strip but were positive based on PCR, and a viral strain was isolated from one such sample. The cytopathic effect on susceptible cells and the results of the immunoperoxidase monolayer assay, PCR, and sequencing indicated that the pathogen was CPV-2. The strain was named CPV-NY-14, and the full-length genome was sequenced and analysed. A maximum likelihood tree was constructed using the full-length genome and all available CPV-2 genomes. New strains have replaced the original strain in Taiwan and Italy, although the CPV-2a strain is still predominant there. However, CPV-2a still causes many cases of acute infectious diarrhoea in dogs in China.


title: Downstream processing of cell culture-derived virus particles

text: Manufacturing of cell culture-derived virus particles for vaccination and gene therapy is a rapidly growing field in the biopharmaceutical industry. The process involves a number of complex tasks and unit operations ranging from selection of host cells and virus strains for the cultivation in bioreactors to the purification and formulation of the final product. For the majority of cell culture-derived products, efforts focused on maximization of bioreactor yields, whereas design and optimization of downstream processes were often neglected. Owing to this biased focus, downstream procedures today often constitute a bottleneck in various manufacturing processes and account for the majority of the overall production costs. For efficient production methods, particularly in sight of constantly increasing economic pressure within human healthcare systems, highly productive downstream schemes have to be developed. Here, we discuss unit operations and downstream trains to purify virus particles for use as vaccines and vectors for gene therapy.


title: Acute Flaccid Myelitis in Children in Zhejiang Province, China

text: In July–December 2018, an outbreak of polio-like acute flaccid myelitis (AFM) occurred in Zhejiang province, China. Enterovirus (EV)-D68 infection has been reported to be associated with AFM. This study aimed to investigate the clinical presentation, laboratory findings, and outcomes of AFM patients. We investigated the clinical and virologic information regarding the AFM patients, and real-time PCR, sequencing, and phylogenetic analysis were used to investigate the cause of AFM. Eighteen cases met the definition of AFM, with a median age of 4.05 years (range, 0.9–9 years), and nine (50%) were EV-D68 positive. Symptoms included acute flaccid limb weakness and cranial nerve dysfunction. On magnetic resonance imaging, 11 (61.1%) patients had spinal gray matter abnormalities. Electromyography results of 16 out of 17 patients (94.1%) were abnormal. Cerebrospinal fluid (CSF) pleocytosis was common (94.4%), while CSF protein concentration was normal in all patients. There was little improvement after early aggressive therapy. Phylogenetic analysis revealed that EV-D68 subclade B3 was the predominant lineage circulating in Zhejiang province in 2018.


title: Risk Factors for Mortality in 244 Older Adults With COVID‐19 in Wuhan, China: A Retrospective Study

text: BACKGROUND/OBJECTIVES: Previous studies have reported that older patients may experience worse outcome(s) after infection with severe acute respiratory syndrome coronavirus‐2 than younger individuals. This study aimed to identify potential risk factors for mortality in older patients with coronavirus disease 2019 (COVID‐19) on admission, which may help identify those with poor prognosis at an early stage. DESIGN: Retrospective case‐control. SETTING: Fever ward of Sino‐French New City Branch of Tongji Hospital, Wuhan, China. PARTICIPANTS: Patients aged 60 years or older with COVID‐19 (n = 244) were included, of whom 123 were discharged and 121 died in hospital. MEASUREMENTS: Data retrieved from electronic medical records regarding symptoms, signs, and laboratory findings on admission, and final outcomes of all older patients with COVID‐19, were retrospectively reviewed. Univariate and multivariate logistic regression analyses were used to explore risk factors for death. RESULTS: Univariate analysis revealed that several clinical characteristics and laboratory variables were significantly different (ie, P < .05) between discharged and deceased patients. Multivariable logistic regression analysis revealed that lymphocyte (LYM) count (odds ratio [OR] = 0.009; 95% confidence interval [CI] = 0.001‐0.138; P = .001) and older age (OR = 1.122; 95% CI = 1.007‐1.249; P = .037) were independently associated with hospital mortality. White blood cell count was also an important risk factor (P = .052). The area under the receiver operating characteristic curve in the logistic regression model was 0.913. Risk factors for in‐hospital death were similar between older men and women. CONCLUSION: Older age and lower LYM count on admission were associated with death in hospitalized COVID‐19 patients. Stringent monitoring and early intervention are needed to reduce mortality in these patients.


Renewed KIDS SAVE LIVES campaign to further increase awareness and fight sudden cardiac death in the era of Covid-19


title: How to Continue Essential Orthopedic Services during COVID-19 Crisis?

text: The first pandemic of the coronavirus family was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019 As a result of the pandemic critical condition, specialized orthopedic services were obviously affected To respond properly, we initiated a series of strategic measures, aiming at the safety of staff, minimizing the exposure, and prevention of possible disruption in providing services


title: Review of Bats and SARS

text: Bats have been identified as a natural reservoir for an increasing number of emerging zoonotic viruses, including henipaviruses and variants of rabies viruses. Recently, we and another group independently identified several horseshoe bat species (genus Rhinolophus) as the reservoir host for a large number of viruses that have a close genetic relationship with the coronavirus associated with severe acute respiratory syndrome (SARS). Our current research focused on the identification of the reservoir species for the progenitor virus of the SARS coronaviruses responsible for outbreaks during 2002–2003 and 2003–2004. In addition to SARS-like coronaviruses, many other novel bat coronaviruses, which belong to groups 1 and 2 of the 3 existing coronavirus groups, have been detected by PCR. The discovery of bat SARS-like coronaviruses and the great genetic diversity of coronaviruses in bats have shed new light on the origin and transmission of SARS coronaviruses.


title: Megapneumonia Coinfection: pneumococcus, Mycoplasma pneumoniae, and Metapneumovirus

text: We report a young girl who died of Streptococcus pneumoniae 19A pneumonia, septic shock, and hemolytic uremic syndrome despite prior pneumococcal vaccination, appropriate antibiotics, and aggressive intensive care support. Serotype 19A is not covered by the 7- or 10-valent pneumococcal vaccines. Mycoplasma pneumoniae and metapneumovirus were simultaneously detected by PCR in the nasopharyngeal and tracheal aspirates. The pneumococcus is penicillin sensitive. Although infections with each of these pathogens alone are typically mild, this case highlights that co-infection with the triple respiratory pathogens possibly contributed to the fatal outcome of this child. Also, the new policy in Hong Kong to use PCV13 may help prevent further cases of serotype 19A infections.


title: Features discriminating SARS from other severe viral respiratory tract infections

text: This study investigated the discriminatory features of severe acute respiratory syndrome (SARS) and severe non-SARS community-acquired viral respiratory infection (requiring hospitalization) in an emergency department in Hong Kong. In a case-control study, clinical, laboratory and radiological data from 322 patients with laboratory-confirmed SARS from the 2003 SARS outbreak were compared with the data of 253 non-SARS adult patients with confirmed viral respiratory tract infection from 2004 in order to identify discriminatory features. Among the non-SARS patients, 235 (93%) were diagnosed as having influenza infections (primarily H3N2 subtype) and 77 (30%) had radiological evidence of pneumonia. In the early phase of the illness and after adjusting for baseline characteristics, SARS patients were less likely to have lower respiratory symptoms (e.g. sputum production, shortness of breath, chest pain) and more likely to have myalgia (p < 0.001). SARS patients had lower mean leukocyte and neutrophil counts (p < 0.0001) and more commonly had “ground-glass” radiological changes with no pleural effusion. Despite having a younger average age, SARS patients had a more aggressive respiratory course requiring admission to the ICU and a higher mortality rate. The area under the receiver operator characteristic curve for predicting SARS when all variables were considered was 0.983. Using a cutoff score of >99, the sensitivity was 89.1% (95%CI 82.0–94.0) and the specificity was 98.0% (95%CI 95.4–99.3). The area under the receiver operator characteristic curve for predicting SARS when all variables except radiological change were considered was 0.933. Using a cutoff score of >8, the sensitivity was 80.7% (95%CI 72.4–87.3) and the specificity was 94.5% (95%CI 90.9–96.9). Certain clinical manifestations and laboratory changes may help to distinguish SARS from other influenza-like illnesses. Scoring systems may help identify patients who should receive more specific tests for influenza or SARS.


title: Traditional uses of medicinal plants used by Indigenous communities for veterinary practices at Bajaur Agency, Pakistan

text: BACKGROUND: The pastoral lifestyle of Indigenous communities of Bajaur Agency is bringing them close to natural remedies for treating their domestic animals. Several studies have been conducted across the globe describing the importance of traditional knowledge in veterinary care. Therefore, this study was planned with the aim to record knowledge on ethnoveterinary practices from the remote areas and share sit with other communities through published literature. METHODS: Data was gathered from community members through semi-structured interviews and analyzed through informant consensus factor (Fic) to evaluate the consent of current ethnoveterinary practices among the local people. RESULTS: In total, 73 medicinal plants were recorded under the ethnoveterinary practices. Most widely used medicinal plants with maximum use reports (URs) were Visnaga daucoides Gaertn., Foeniculum vulgare Mill., Solanum virginianum L., Withania somnifera (L.) Dunal, Glycyrrhiza glabra L., and Curcuma longa L. New medicinal values were found with confidential level of citations for species including Heracleum candicans and Glycerhiza glabra. Family Apiaceae was the utmost family with high number (7 species) of medicinal plants. Maximum number of medicinal plants (32) was used for gastric problems. High Fic was recorded for dermatological (0.97) followed by reproductive (0.93) and gastrointestinal disorders (0.92). The main route of remedies administration was oral. CONCLUSIONS: Current study revealed that the study area has sufficient knowledge on ethnoveterinary medicinal plants. This knowledge is in the custody of nomadic grazers, herders, and aged community members. Plants with new medicinal uses need to be validated phytochemically and pharmacologically for the development of new alternative drugs for veterinary purposes.


title: Cardiopulmonary resuscitation in COVID-19 patients – To do or not to?

text: • COVID-19 pandemic has changed the risk-benefit balance for cardiopulmonary resuscitation [CPR]. • Amongst many aerosol producing procedures performed on patients, CPR is a highly aerosol-generating procedure. • Available literature is inadequate to direct clinicians towards keeping low or high threshold for performing CPR in COVID-19 patient.


title: Large-scale estimation of random graph models with local dependence

text: A class of random graph models is considered, combining features of exponential-family models and latent structure models, with the goal of retaining the strengths of both of them while reducing the weaknesses of each of them. An open problem is how to estimate such models from large networks. A novel approach to large-scale estimation is proposed, taking advantage of the local structure of such models for the purpose of local computing. The main idea is that random graphs with local dependence can be decomposed into subgraphs, which enables parallel computing on subgraphs and suggests a two-step estimation approach. The first step estimates the local structure underlying random graphs. The second step estimates parameters given the estimated local structure of random graphs. Both steps can be implemented in parallel, which enables large-scale estimation. The advantages of the two-step estimation approach are demonstrated by simulation studies with up to 10,000 nodes and an application to a large Amazon product recommendation network with more than 10,000 products.


title: Influence of atopy on the clinical manifestations of coronavirus infection in adult volunteers

text: In an attempt to understand the relationship between viral upper respiratory tract infection and the underlying virological and immunological mechanisms, thirty‐four volunteers were inoculated intranasally with coronavirus 229E; subsequent virus shedding and/or antibody rises, indicating active infection, were observed in twenty‐nine. There was a greater increase in independently measured scores of clinical severity, e.g. cold symptoms, in those with detectable IgE in nasal secretions (P < 0.01). A similar association was found between clinical scores and serum IgE concentrations 150 IU/ml, but the relationship with systemic atopy, as assessed by skin‐prick tests to common allergens, was less marked. A more detailed study of twelve of the infected volunteers failed to explain these findings on the basis of mast ceil mediator release, as concentrations of leukotriene B(4), the sulphidopeptide leukotriene C(4), and histamine, were not appreciably elevated in the nasal secretions following virus inoculation. Similarly, there was no evidence that circulating coronavirus specific IgE was produced. Thus, this study suggests that atopy may be related to the severity of cold symptoms produced by coronavirus 229E, although the exact connection has yet to be determined.


title: Safety and immunogenicity of a potential checkpoint blockade vaccine for canine melanoma

text: Human immunotherapy with checkpoint blockades has achieved significant breakthroughs in recent years. In this study, a checkpoint blockade vaccine for canine melanoma was tested for safety and immunogenicity. Five healthy adult dogs received a mixture of three replication-defective chimpanzee-derived adenoviral vectors, one expressing mouse fibroblast-associated protein (mFAP) and the others expressing canine melanoma-associated antigens Trp-1 or Trp-2 fused into Herpes Simplex-1 glycoprotein D, a checkpoint inhibitor of herpes virus entry mediator (HVEM) pathways. The vaccine mixture was shown to be well tolerated and increased frequencies of canineTrp-1-specific activated CD8(+) and CD4(+) T cells secreting interferon-(IFN)-γ, tumor necrosis factor (TNF)-α, or interleukin (IL)-2 alone or in combinations in four and five out of five dogs, respectively. To avoid excessive bleeds, responses to cTrp-2 were not analyzed. All dogs responded with increased frequencies of mFAP-specific activated CD8(+) and CD4(+) T cells. The results of this safety/immunogenicity trial invite further testing of this checkpoint blockade vaccine combination in dogs with melanoma. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00262-018-2201-5) contains supplementary material, which is available to authorized users.


title: Intubation of the patient with a suspected or confirmed COVID-19 infection

text: Abstract We propose a set of recommendations from our clinical practice for intubation of the patient with a suspected or confirmed COVID-19 infection, with a goal to safely securing the airway while optimizing infection prevention practices to reduce the risk to healthcare personnel.


Reverse quarantine: Management of COVID‐19 by Kerala with its higher number of aged population


title: Engineered Biological Entities for Drug Delivery and Gene Therapy Protein Nanoparticles

text: The development of genetic engineering techniques has speeded up the growth of the biotechnological industry, resulting in a significant increase in the number of recombinant protein products on the market. The deep knowledge of protein function, structure, biological interactions, and the possibility to design new polypeptides with desired biological activities have been the main factors involved in the increase of intensive research and preclinical and clinical approaches. Consequently, new biological entities with added value for innovative medicines such as increased stability, improved targeting, and reduced toxicity, among others have been obtained. Proteins are complex nanoparticles with sizes ranging from a few nanometers to a few hundred nanometers when complex supramolecular interactions occur, as for example, in viral capsids. However, even though protein production is a delicate process that imposes the use of sophisticated analytical methods and negative secondary effects have been detected in some cases as immune and inflammatory reactions, the great potential of biodegradable and tunable protein nanoparticles indicates that protein-based biotechnological products are expected to increase in the years to come.


title: Impact of coronavirus disease 2019 (COVID‐19) outbreak on outcome of myocardial infarction in Hong Kong, China

text: OBJECTIVE: To determine whether COVID‐19 may adversely affect outcome of myocardial infarction (MI) patients in Hong Kong, China. BACKGROUND: The COVID‐19 pandemic has infected thousands of people and placed enormous stress on healthcare system. Apart from being an infectious disease, it may affect human behavior and healthcare resource allocation which potentially cause treatment delay in MI. METHODS: This was a single center cross‐sectional observational study. From November 1, 2019 to March 31, 2020, we compared outcome of patients admitted for acute ST‐elevation MI (STEMI) and non‐ST elevation MI (NSTEMI) before (group 1) and after (group 2) January 25, 2020 which was the date when Hong Kong hospitals launched emergency response measures to combat COVID‐19. RESULTS: There was a reduction in daily emergency room attendance since January 25, 2020 (group 1,327/day vs. group 2,231/day) and 149 patients with diagnosis of MI were included into analysis (group 1 N = 85 vs. group 2 N = 64). For STEMI, patients in group 2 tended to have longer symptom‐to‐first medical contact time and more presented out of revascularization window (group 1 27.8 vs. group 2 33%). The primary composite outcome of in‐hospital death, cardiogenic shock, sustained ventricular tachycardia or fibrillation (VT/VF) and use of mechanical circulatory support (MCS) was significantly worse in group 2 (14.1 vs. 29.7%, p = .02). CONCLUSIONS: More MI patients during COVID‐19 outbreak had complicated in‐hospital course and worse outcomes. Besides direct infectious complications, cardiology community has to acknowledge the indirect effect of communicable disease on our patients and system of care.


title: Absence of Skin of Colour Images in Publications of COVID‐19 Skin Manifestations

text: There are now over 1 million confirmed cases of COVID‐19 globally with more than 270,000 recorded deaths to date. COVID‐19 has been shown to disproportionately impact people of colour both in the United Kingdom and in the United States where blacks make up 13.4% of the population but 30% of COVID‐19 cases. Mounting evidence shows that COVID‐19 impacts several organ systems, including the skin.


title: Anosmia and Ageusia: Common Findings in COVID‐19 Patients

text: In a not negligible number of patients affected by COVID‐19 (coronavirus disease 2019), especially if paucisymptomatic, anosmia and ageusia can represent the first or only symptomatology present. Laryngoscope, 2020


title: Health and growth of Finnish beef calves and the relation to acute phase response

text: Abstract Healthy, thriving calves are essential for beef calf production. We studied the health status and factors associated with the growth of beef calves in six cow-calf herds during the first month of the calves’ lives and at weaning age (200 days). The six herds were visited three times, when calves were approximately 3 days, 16 days and 30 days of age. On each visit calves (n=37) were clinically examined, weighed or measured, blood samples were collected, faecal samples obtained and deep nasopharyngeal swabs were taken. Each blood sample was analysed for acute phase proteins (haptoglobin, serum amyloid-A, fibrinogen), total proteins and albumin, the faecal sample for intestinal tract pathogens (rotavirus, bovine coronavirus, enterotoxigenic Escherichia coli and Salmonella, oocysts of Eimeria coccidia and Cryptosporidium, and nematode eggs), and the nasopharyngeal swab for respiratory tract pathogens (bovine coronavirus (BCV), respiratory syncytial virus (RSV), bacteria and mycoplasma). Clinical diagnosis of respiratory tract disease, diarrhoea or umbilical disease was set at 15.0% for all the three consecutive examinations combined (n=107), but only few pathogens were detected from the samples. The increased levels of acute phase proteins were neither associated with any of the diseases nor with the pathogens. Random intercept linear models were used to explore factors affecting early (3–30 days) and long-term (3–200 days) growth, showing that calves with elevated serum amyloid-A concentrations at the age of 16 days had lower long-term growth. Increased albumin concentration at 30 days of age and higher parity of the dam increased early-term growth. The lack of association between a disease and the acute phase protein may stem from the low disease prevalence in the beef calves examined. The measurement of acute phase proteins of a young calf can help identify animals with possible future growth deficiencies, although the mechanisms through which the association between acute phase proteins and growth has yet to be explained.


title: Atypical Manifestation of COVID-19-Induced Myocarditis

text: We present a case of a 39-year-old male who presented with chest pain without fever or respiratory symptoms. Troponins were elevated and electrocardiogram (ECG) was inconclusive for ST-elevation myocardial infarction (STEMI). Angiography revealed normal coronaries and the patient was found to be coronavirus disease 2019 (COVID-19) positive; he was diagnosed with COVID-19 myocarditis. With the global pandemic, more cases are emerging regarding myocardial injury induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Although COVID-19 manifests primarily as respiratory disease, few cases of cardiac injury without respiratory involvement or febrile illness have been reported. This case illustrates that COVID-19 can present atypically and affect an isolated non-respiratory organ system.


Commentary: A survey of UK cardiac surgeon opinion during the COVID-19 pandemic: A point and place in time


title: Structure, biosynthesis, and localization of dipeptidyl aminopeptidase B, an integral membrane glycoprotein of the yeast vacuole

text: We have characterized the structure, biogenesis, and localization of dipeptidyl aminopeptidase B (DPAP B), a membrane protein of the yeast vacuole. An antibody specific for DPAP B recognizes a 120-kD glycoprotein in yeast that behaves like an integral membrane protein in that it is not removed from membranes by high pH Na2CO3 treatment. Inspection of the deduced amino acid sequence of DPAP B reveals a hydrophobic domain near the NH2 terminus that could potentially span a lipid bilayer. The in vitro enzymatic activity and apparent molecular weight of DPAP B are unaffected by the allelic state of PEP4, a gene essential for the proteolytic activation of a number of soluble vacuolar hydrolases. DPAP B is synthesized as a glycosylated precursor that is converted to the mature 120-kD species by carbohydrate addition. The precursor form of DPAP B accumulates in sec mutants (Novick, P., C. Field, and R. Schekman. 1980. Cell. 21:205-215) that are blocked at the ER (sec18) or Golgi apparatus (sec7), but not at secretory vesicles (sec1). Immunolocalization of DPAP B in wild-type or sec1 mutant cells shows that the protein resides in the vacuolar membrane. However, it is present in non-vacuolar compartments in sec18 and sec7 cells, confirming that the delivery of DPAP B is blocked in these mutants. Interestingly, DPAP B appears to stain the nuclear envelope in a sec18 mutant, which is consistent with the accumulation of DPAP B in the ER membrane at the restrictive temperature. These results suggest that soluble and membrane-bound vacuolar proteins use the same stages of the secretory pathway for their transport.


title: Use of anakinra in severe COVID-19: a case report

text: Abstract Coronavirus Disease 19 is a global healthcare emergency with high lethality rate. Relevant inflammatory cytokine storm is associated with severity of disease and IL1 inhibition is a cornerstone treatment for hyperinflammatory diseases. We present here the case of a patient with critical COVID-19 successfully treated with IL-1 receptor antagonist (anakinra).


title: Does reduced MHC diversity decrease viability of vertebrate populations?

text: Abstract Loss of genetic variation may render populations more vulnerable to pathogens due to inbreeding depression and depletion of variation in genes responsible for immunity against parasites. Here we review the evidence for the significance of variation in genes of the Major Histocompatibility Complex (MHC) for conservation efforts. MHC molecules present pathogen-derived antigens to the effector cells of the immune system and thus trigger the adaptive immune response. Some MHC genes are the most variable functional genes in the vertebrate genome. Their variation is clearly of adaptive significance and there is considerable evidence that its maintenance is mainly due to balancing selection imposed by pathogens. However, while the evidence for selection shaping MHC variation on the historical timescale is compelling, a correlation between levels of MHC variation and variation at neutral loci is often observed, indicating that on a shorter timescale drift also substantially affects MHC, leading to depletion of MHC diversity. The evidence that the loss of MHC variation negatively affects population survival is so far equivocal and difficult to separate from effects of general inbreeding. Some species with depleted MHC variation seem to be particularly susceptible to infection, but other species thrive and expand following severe bottlenecks that have drastically limited their MHC variation. However, while the latter demonstrate that MHC variation is not always critical for population survival, these species may in fact represent rare examples of survival despite of the loss of MHC variation. There is clearly a compelling need for data that would disclose the possible consequences of MHC diversity for population viability. In particular, we need more data on the impact of MHC allelic richness on the abundance of parasites or prevalence of disease in populations, while controlling for the role of general inbreeding. Before such evidence accumulates, captive breeding programs and other conservation measures aimed at inbreeding avoidance should be favoured over those protecting only MHC variation, especially since inbreeding avoidance programs would usually conserve both types of genetic diversity simultaneously.


title: Livestock Susceptibility to Infection with Middle East Respiratory Syndrome Coronavirus

text: Middle East respiratory syndrome (MERS) cases continue to be reported, predominantly in Saudi Arabia and occasionally other countries. Although dromedaries are the main reservoir, other animal species might be susceptible to MERS coronavirus (MERS-CoV) infection and potentially serve as reservoirs. To determine whether other animals are potential reservoirs, we inoculated MERS-CoV into llamas, pigs, sheep, and horses and collected nasal and rectal swab samples at various times. The presence of MERS-CoV in the nose of pigs and llamas was confirmed by PCR, titration of infectious virus, immunohistochemistry, and in situ hybridization; seroconversion was detected in animals of both species. Conversely, in sheep and horses, virus-specific antibodies did not develop and no evidence of viral replication in the upper respiratory tract was found. These results prove the susceptibility of llamas and pigs to MERS-CoV infection. Thus, the possibility of MERS-CoV circulation in animals other than dromedaries, such as llamas and pigs, is not negligible.


title: COVID-19 and Crosstalk With the Hallmarks of Aging

text: Within the past several decades, the emergence of new viral diseases with severe health complications and mortality is evidence of an age-dependent, compromised bodily response to abrupt stress with concomitantly reduced immunity. The new severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, causes coronavirus disease 2019 (COVID-19). It has increased morbidity and mortality in persons with underlying chronic diseases and those with a compromised immune system regardless of age and in older adults who are more likely to have these conditions. While SARS-CoV-2 is highly virulent, there is variability in the severity of the disease and its complications in humans. Severe pneumonia, acute respiratory distress syndrome, lung fibrosis, cardiovascular events, acute kidney injury, stroke, hospitalization, and mortality have been reported that result from pathogen–host interactions. Hallmarks of aging, interacting with one another, have been proposed to influence health span in older adults, possibly via mechanisms regulating the immune system. Here, we review the potential roles of the hallmarks of aging, coupled with host–coronavirus interactions. Of these hallmarks, we focused on those that directly or indirectly interact with viral infections, including immunosenescence, inflammation and inflammasomes, adaptive immunosenescence, genomic instability, mitochondrial dysfunction, epigenetic alterations, telomere attrition, and impaired autophagy. These hallmarks likely contribute to the increased pathophysiological responses to SARS-CoV-2 among older adults and may play roles as an additive risk of accelerated biological aging even after recovery. We also briefly discuss the role of antiaging drug candidates that require paramount attention in COVID-19 research.


title: The Italian ECMO network experience during the 2009 influenza A(H1N1) pandemic: preparation for severe respiratory emergency outbreaks

text: PURPOSE: In view of the expected 2009 influenza A(H1N1) pandemic, the Italian Health Authorities set up a national referral network of selected intensive care units (ICU) able to provide advanced respiratory care up to extracorporeal membrane oxygenation (ECMO) for patients with acute respiratory distress syndrome (ARDS). We describe the organization and results of the network, known as ECMOnet. METHODS: The network consisted of 14 ICUs with ECMO capability and a national call center. The network was set up to centralize all severe patients to the ECMOnet centers assuring safe transfer. An ad hoc committee defined criteria for both patient transfer and ECMO institutions. RESULTS: Between August 2009 and March 2010, 153 critically ill patients (53% referred from other hospitals) were admitted to the ECMOnet ICU with suspected H1N1. Sixty patients (48 of the referred patients, 49 with confirmed H1N1 diagnosis) received ECMO according to ECMOnet criteria. All referred patients were successfully transferred to the ECMOnet centers; 28 were transferred while on ECMO. Survival to hospital discharge in patients receiving ECMO was 68%. Survival of patients receiving ECMO within 7 days from the onset of mechanical ventilation was 77%. The length of mechanical ventilation prior to ECMO was an independent predictor of mortality. CONCLUSIONS: A network organization based on preemptive patient centralization allowed a high survival rate and provided effective and safe referral of patients with severe H1N1-suspected ARDS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00134-011-2301-6) contains supplementary material, which is available to authorized users.


title: Virus-Specific Immune Memory at Peripheral Sites of Herpes Simplex Virus Type 2 (HSV-2) Infection in Guinea Pigs

text: Despite its importance in modulating HSV-2 pathogenesis, the nature of tissue-resident immune memory to HSV-2 is not completely understood. We used genital HSV-2 infection of guinea pigs to assess the type and location of HSV-specific memory cells at peripheral sites of HSV-2 infection. HSV-specific antibody-secreting cells were readily detected in the spleen, bone marrow, vagina/cervix, lumbosacral sensory ganglia, and spinal cord of previously-infected animals. Memory B cells were detected primarily in the spleen and to a lesser extent in bone marrow but not in the genital tract or neural tissues suggesting that the HSV-specific antibody-secreting cells present at peripheral sites of HSV-2 infection represented persisting populations of plasma cells. The antibody produced by these cells isolated from neural tissues of infected animals was functionally relevant and included antibodies specific for HSV-2 glycoproteins and HSV-2 neutralizing antibodies. A vigorous IFN-γ-secreting T cell response developed in the spleen as well as the sites of HSV-2 infection in the genital tract, lumbosacral ganglia and spinal cord following acute HSV-2 infection. Additionally, populations of HSV-specific tissue-resident memory T cells were maintained at these sites and were readily detected up to 150 days post HSV-2 infection. Unlike the persisting plasma cells, HSV-specific memory T cells were also detected in uterine tissue and cervicothoracic region of the spinal cord and at low levels in the cervicothoracic ganglia. Both HSV-specific CD4(+) and CD8(+) resident memory cell subsets were maintained long-term in the genital tract and sensory ganglia/spinal cord following HSV-2 infection. Together these data demonstrate the long-term maintenance of both humoral and cellular arms of the adaptive immune response at the sites of HSV-2 latency and virus shedding and highlight the utility of the guinea pig infection model to investigate tissue-resident memory in the setting of HSV-2 latency and spontaneous reactivation.


title: Inactivation of Middle East respiratory syndrome‐coronavirus in human plasma using amotosalen and ultraviolet A light

text: BACKGROUND: Middle East respiratory syndrome‐coronavirus (MERS‐CoV) is a novel zoonotic pathogen. Although the potential for MERS‐CoV transmission through blood transfusion is not clear, MERS‐CoV was recognized as a pathogen of concern for the safety of the blood supply especially after its detection in whole blood, serum, and plasma of infected individuals. Here we investigated the efficacy of amotosalen and ultraviolet A light (UVA) to inactivate MERS‐CoV in fresh‐frozen plasma (FFP). STUDY DESIGN AND METHODS: Pooled FFP units were spiked with a recent clinical MERS‐CoV isolate. Infectious and genomic viral titers were determined in plasma before and after inactivation with amotosalen/UVA treatment by plaque assay and reverse transcription–quantitative polymerase chain reaction, respectively. In addition, residual replicating or live virus after inactivation was examined by passaging in the permissive Vero E6 cells. RESULTS: The mean MERS‐CoV infectious titer in pretreatment samples was 4.67 ± 0.25 log plaque‐forming units (pfu)/mL, which was reduced to undetectable levels after inactivation with amotosalen/UVA demonstrating a mean log reduction of more than 4.67 ± 0.25 pfu/mL. Furthermore, inoculation of inactivated plasma on Vero E6 cells did not result in any cytopathic effect (CPE) even after 7 days of incubation and three consecutive passages, nor the detection of MERS RNA compared to pretreatment samples which showed complete CPE within 2 to 3 days postinoculation and log viral RNA titer ranging from 9.48 to 10.22 copies/mL in all three passages. CONCLUSION: Our data show that amotosalen/UVA treatment is a potent and effective way to inactivate MERS‐CoV infectious particles in FFP to undetectable levels and to minimize the risk of any possible transfusion‐related MERS‐CoV transmission.


title: 3 Preparation of antigens

text: Publisher Summary This chapter describes the procedures of purification, concentration, and preservation of antigens. The most general concept to begin with is the most important—the microbiological purity of the starting viral culture. For every virus antigen, there should be a parallel normal antigen to serve as the negative control in the test. Normal antigens are prepared by shaminoculating cell cultures with negative culture material and following these cultures through the entire virus culture and antigen preparation steps in exact parallel fashion. Depending on the test and the day-to-day usage, many antigens are preserved by adding thimerosal to the final product to a final concentration of 1:10,000, or sodium azide to a final concentration of 0.1%. Special preparation of antigens is required for many diagnostic tests, monoclonal or polyclonal antibody production, and many enzyme immunoassays tests. Many viruses and antigens have their own peculiarities based on the specific properties of each virus group. Chromatography is considered to be the most effective means of producing purified preparations of virus proteins, this being achieved by gel filtration, ion exchange, or affinity chromatography.


title: US-Like Strain of Porcine Epidemic Diarrhea Virus Outbreaks in Taiwan, 2013–2014

text: Since late 2013, several outbreaks of porcine epidemic diarrhea virus (PEDV) infection have emerged in Taiwan. Suckling piglets under 2 weeks of age showed severe vomiting and watery yellowish diarrhea with morbidity and mortality ranging from 80 to 100% and 90 to 100%, respectively. A total of 68 samples from 25 pig farms were confirmed as positive for PEDV and negative for rotavirus and transmissible gastroenteritis virus by reverse transcription PCR, and the partial S gene of PEDV was analyzed. Phylogenetic analysis places all 18 Taiwanese PEDV isolates collected during this outbreak in the same clade as the US strains of PEDV. This novel PEDV is prevailing and currently causing severe outbreaks in Taiwan.


title: epiDMS: Data Management and Analytics for Decision-Making From Epidemic Spread Simulation Ensembles

text: BACKGROUND: Carefully calibrated large-scale computational models of epidemic spread represent a powerful tool to support the decision-making process during epidemic emergencies. Epidemic models are being increasingly used for generating forecasts of the spatial-temporal progression of epidemics at different spatial scales and for assessing the likely impact of different intervention strategies. However, the management and analysis of simulation ensembles stemming from large-scale computational models pose challenges, particularly when dealing with multiple interdependent parameters, spanning multiple layers and geospatial frames, affected by complex dynamic processes operating at different resolutions. METHODS: We describe and illustrate with examples a novel epidemic simulation data management system, epiDMS, that was developed to address the challenges that arise from the need to generate, search, visualize, and analyze, in a scalable manner, large volumes of epidemic simulation ensembles and observations during the progression of an epidemic. RESULTS AND CONCLUSIONS: epiDMS is a publicly available system that facilitates management and analysis of large epidemic simulation ensembles. epiDMS aims to fill an important hole in decision-making during healthcare emergencies by enabling critical services with significant economic and health impact.


title: Reflection on SARS precautions in a severe intellectual disabilities hospital in Hong Kong

text: Background Hong Kong went through a battle with a new respiratory disease, severe acute respiratory syndrome (SARS), from March to June 2003. All clinical settings, including rehabilitative and infirmary setting, have actively involved in fighting against the infection. The intent of this paper was to reflect on the SARS precautionary measures that had been taken in a severe intellectual disabilities hospital in Hong Kong. Methods A review on six SARS precautionary measures were conducted. They were assessment of risk, formulation of operational guidelines, implementation of infection control measures, education and training of staff, conducting audits and carrying out environmental improvement work. Results Patients were at risk of getting infected from carers, visitors, volunteers, and staff and patients of general hospitals. A SARS Quarantine Unit, isolation ward, was opened to isolate patients who might have had close contact with SARS patients during a stay in a general hospital or when they returned from home leave. Undoubtedly, both staff and relatives participated in preventing the patients from being infected. No day leave and home leave was reported and the number of hospitalization in general hospital was decreased during the critical period. Three infection control audits were conducted and improvement work was carried out subsequently. Conclusion The practice of grouping within a standard isolation room is recommended to continue in the future. Moreover, intensive infection control training for all staff is of highest importance to safeguard the health of both staff and patient.


title: Transcriptome analysis of responses to bluetongue virus infection in Aedes albopictus cells

text: BACKGROUND: Bluetongue virus (BTV) causes a disease among wild and domesticated ruminants which is not contagious, but which is transmitted by biting midges of the Culicoides species. BTV can induce an intense cytopathic effect (CPE) in mammalian cells after infection, although Culicoides- or mosquito-derived cell cultures cause non-lytic infection with BTV without CPE. However, little is known about the transcriptome changes in Aedes albopictus cells infected with BTV. METHODS: Transcriptome sequencing was used to identify the expression pattern of mRNA transcripts in A. albopictus cells infected with BTV, given the absence of the Culicoides genome sequence. Bioinformatics analyses were performed to examine the biological functions of the differentially expressed genes. Subsequently, quantitative reverse transcription–polymerase chain reaction was utilized to validate the sequencing data. RESULTS: In total, 51,850,205 raw reads were generated from the BTV infection group and 51,852,293 from the control group. A total of 5769 unigenes were common to both groups; only 779 unigenes existed exclusively in the infection group and 607 in the control group. In total, 380 differentially expressed genes were identified, 362 of which were up-regulated and 18 of which were down-regulated. Bioinformatics analyses revealed that the differentially expressed genes mainly participated in endocytosis, FoxO, MAPK, dorso-ventral axis formation, insulin resistance, Hippo, and JAK-STAT signaling pathways. CONCLUSION: This study represents the first attempt to investigate transcriptome-wide dysregulation in A. albopictus cells infected with BTV. The understanding of BTV pathogenesis and virus–vector interaction will be improved by global transcriptome profiling. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12866-019-1498-3) contains supplementary material, which is available to authorized users.


title: Medical Students and COVID-19: Knowledge, Attitudes, and Precautionary Measures. A Descriptive Study From Jordan

text: The recent coronavirus disease (COVID-19) pandemic is associated with increasing morbidity and mortality and has impacted the lives of the global populations. Human behavior and knowledge assessment during the crisis are critical in the overall efforts to contain the outbreak. To assess knowledge, attitude, perceptions, and precautionary measures toward COVID-19 among a sample of medical students in Jordan. This is a cross-sectional descriptive study conducted between the 16th and 19th of March 2020. Participants were students enrolled in different levels of study at the six medical schools in Jordan. An online questionnaire which was posted on online platforms was used. The questionnaire consisted of four main sections: socio-demographics, sources of information, knowledge attitudes, and precautionary measures regarding COVID-19. Medical students used mostly social media (83.4%) and online search engines (84.8%) as their preferred source of information on COVID-19 and relied less on medical search engines (64.1%). Most students believed that hand shaking (93.7%), kissing (94.7%), exposure to contaminated surfaces (97.4%), and droplet inhalation (91.0%) are the primary mode of transmission but were indecisive regarding airborne transmission with only 41.8% in support. Participants also reported that elderly with chronic illnesses are the most susceptible group for the coronavirus infection (95.0%). As a response to the COVID-19 pandemic more than 80.0% of study participants adopted social isolation strategies, regular hand washing, and enhanced personal hygiene measures as their first line of defense against the virus. In conclusion, Jordanian medical students showed expected level of knowledge about the COVID-19 virus and implemented proper strategies to prevent its spread.


title: Pediatric Modification of the Medically Necessary, Time-Sensitive Scoring System for Operating Room Procedure Prioritization During the COVID-19 Pandemic

text: BACKGROUND: The COVID-19 pandemic forced surgeons to reconsider concepts of “elective” surgery. Perceptions regarding the time-sensitivity and medical necessity of a procedure have taken on greater significance during the pandemic. The evolving ethical and clinical environment requires reappraisal of perioperative factors such as personal protective equipment conservation; limiting the risk of exposure to COVID-19 for patients, families, and health care workers; preservation of hospital beds and intensive care unit resources; and minimizing COVID-19 related perioperative risk to patients. STUDY DESIGN: A scaffold for the complex decision-making required for prioritization of Medically Necessary, Time Sensitive (MeNTS) surgeries was developed for adult patients by colleagues at The University of Chicago(i). Although adult MeNTS scoring can be applied across adult surgical specialties, some variables were irrelevant in a pediatric population. Pediatric manifestations of chronic diseases and congenital anomalies were not accounted for. In order to account for the unique challenges children face, we modified the adult MeNTS system for use across pediatric subspecialties. RESULTS: This Pediatric MeNTS (pMeNTS) scoring system was applied to 101 cases both performed and deferred between March 23(rd) and April 19(th), 2020, at The University of Chicago Comer Children’s Hospital. The pMeNTS scores provides a safe, equitable, transparent, and ethical strategy to prioritize children’s surgical procedures. CONCLUSIONS: This process is adaptable to individual institutions, and we project it will be useful during the acute phase of the pandemic (maximal limitations) as well as the anticipated recovery phase.


title: Drug trials under way

text: We'll soon know if covid-19 can be treated with drugs developed for HIV and Ebola, reports Alice Klein


title: The mental health of doctors during the COVID-19 pandemic

text: Doctors experience high levels of work stress even under normal circumstances, but many would be reluctant to disclose mental health difficulties or seek help for them, with stigma an often-cited reason. The coronavirus disease 2019 (COVID-19) crisis places additional pressure on doctors and on the healthcare system in general and research shows that such pressure brings a greater risk of psychological distress for doctors. For this reason, we argue that the authorities and healthcare executives must show strong leadership and support for doctors and their families during the COVID-19 outbreak and call for efforts to reduce mental health stigma in clinical workplaces. This can be facilitated by deliberately adding ‘healthcare staff mental health support process’ as an ongoing agenda item to high-level management planning meetings.


title: Back to Basics: Giant Challenges to Addressing Isaac’s “Geriatric Giants” Post COVID-19 Crisis

text: The COVID-19 pandemic, being the greatest challenge to our healthcare system for over a century, has its greatest impact on older patients. This subgroup has higher morbidity and mortality than younger age groups. Superimposed on this, the major preventative intervention resulting in social isolation has negative consequences. Prof. Bernard Isaacs described the “Geriatric Giant Symptoms” in 1965 and encouraged the development of interventions for immobility, instability, incontinence and impaired intellect/memory with careful management of these symptoms resulting in better outcomes for older patients including reduced admissions to Nursing Homes and mortality. The author’s explore the impact of the current pandemic and, most particularly its aftermath on the provision of such interventions. In the context of a major economic crisis, resources for highly effective interventions such as joint replacement surgery, urological interventions, cataract surgery will be all be limited after this crisis. Moreover delayed access to day patient services with suboptimal access to assessments for conditions such as cognitive decline and falls as well as social care will likewise militate against addressing the “Geriatric Giant Symptoms”. Thus the “Founding Fathers” of Geriatric Medicine including Prof Isaacs would be justifiably concerned regarding our ability to deliver interventions to address the “Geriatric Giant Symptoms”. Current leaders in geriatric medicine, healthcare workers, funders and providers as well as advocacy groups must redouble their efforts to ensure gains made in management of older patients over 2 generations are not lost in the aftermath of this pandemic.


title: Graphical and numerical representations of DNA sequences: statistical aspects of similarity

text: New approaches aiming at a detailed similarity/dissimilarity analysis of DNA sequences are formulated. Several corrections that enrich the information which may be derived from the alignment methods are proposed. The corrections take into account the distributions along the sequences of the aligned bases (neglected in the standard alignment methods). As a consequence, different aspects of similarity, as for example asymmetry of the gene structure, may be studied either using new similarity measures associated with four-component spectral representation of the DNA sequences or using alignment methods with corrections introduced in this paper. The corrections to the alignment methods and the statistical distribution moment-based descriptors derived from the four-component spectral representation of the DNA sequences are applied to similarity/dissimilarity studies of β-globin gene across species. The studies are supplemented by detailed similarity studies for histones H1 and H4 coding sequences. The data are described according to the latest version of the EMBL database. The work is supplemented by a concise review of the state-of-art graphical representations of DNA sequences.


title: Anti–Severe Acute Respiratory Syndrome Coronavirus Immune Responses: The Role Played by Vγ9Vδ2 T Cells

text: Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus (SARS-CoV) strain. Analyses of T cell repertoires in health care workers who survived SARS-CoV infection during the 2003 outbreak revealed that their effector memory Vγ9Vδ2 T cell populations were selectively expanded ∼3 months after the onset of disease. No such expansion of their αβ T cell pools was detected. The expansion of the Vγ9Vδ2 T cell population was associated with higher anti–SARS-CoV immunoglobulin G titers. In addition, in vitro experiments demonstrated that stimulated Vγ9Vδ2 T cells display an interferon-γ–dependent anti–SARS-CoV activity and are able to directly kill SARS-CoV–infected target cells. These findings are compatible with the possibility that Vγ9Vδ2 T cells play a protective role during SARS


The Korean Middle East Respiratory Syndrome Coronavirus Outbreak and Our Responsibility to the Global Scientific Community


title: Emerging viruses and current strategies for vaccine intervention

text: During the past decade several notable viruses have suddenly emerged from obscurity or anonymity to become serious global health threats, provoking concern regarding their sustained epidemic transmission in immunologically naive human populations. With each new threat comes the call for rapid vaccine development. Indeed, vaccines are considered a critical component of disease prevention for emerging viral infections because, in many cases, other medical options are limited or non‐existent, or that infections result in such a rapid clinical deterioration that the effectiveness of therapeutics is limited. While classic approaches to vaccine development are still amenable to emerging viruses, the application of molecular techniques in virology has profoundly influenced our understanding of virus biology, and vaccination methods based on replicating, attenuated and non‐replicating virus vector approaches have become useful vaccine platforms. Together with a growing understanding of viral disease emergence, a range of vaccine strategies and international commitment to underpin development, vaccine intervention for new and emerging viruses may become a possibility.


title: Necrotizing periodontal disease: oral manifestation of COVID‐19

text: We read with interest the series of cases reported by Martín Carreras‐Presas et al. (2020). We believe that the described oral vesiculobullous manifestations were suggestive of coronavirus disease 2019 (COVID‐19) co‐infections, which at present, are overlooked and poorly understood (Cox et al., 2020). Increased disease severity and mortality amongst individuals with respiratory viral infections are often attributed to subsequent bacterial co‐infections, accounting for approximately 95% of deaths during the 1918 Spanish flu pandemic (Morens et al., 2008).


title: Coronavirus disease 2019 (COVID-19) associated coagulopathy and its impact on outcomes in Shenzhen, China: A retrospective cohort study

text: Background: Early detection of suspected critical patients infected with coronavirus disease 2019 (COVID-19) is very important for the treatment of patients. This study aimed to investigate the role of COVID-19 associated coagulopathy (CAC) to preview and triage. Methods and Results: A cohort study was designed from government designated COVID-19 treatment center. CAC was defined as International Society on Thrombosis and Haemostasis (ISTH) score ≥2. Data from 117 patients COVID-19 were reviewed on admission. The primary and secondary outcomes were admission to Intensive Care Unit (ICU), the use of mechanical ventilation, vital organ dysfunction, discharges of days 14, 21 and 28 from admission and hospital mortality. Among them, admission to ICU was increased progressively from 16.1% in patients with non-CAC to 42.6% in patients with CAC (P < 0.01). Likely, invasive ventilation and noninvasive ventilation were increased from 1.8%, 21.4% in patients with non-CAC to 21.3%, 52.5% in patients with CAC, respectively (P < 0.01). The incidences of acute hepatic injury and acute respiratory distress syndrome in non-CAC and CAC were 28.6% vs. 62.3%, 8.9% vs. 27.9%, respectively (P < 0.01). The discharges of days 14, 21 and 28 from admission were more in non-CAC than those of CAC (P < 0.05). Multiple logistic regression results showed that ISTH score ≥2 was obviously associated with the admission to ICU (OR 4.07, 95% CI 1.47–11.25 P = 0.007) and the use of mechanical ventilation (OR 5.54, 95% CI 2.01–15.28 P = 0.001) in patients with COVID-19. Conclusion: All results show ISTH score ≥2 is an important indicator to preview and triage for COVID-19 patients.


Impact of COVID-19 on IR Fellowship


title: Obstetricians on the Coronavirus Disease 2019 (COVID-19) Front Lines and the Confusing World of Personal Protective Equipment

text: As health care systems struggle to maintain adequate supplies of personal protective equipment, there is confusion and anxiety among obstetricians and others about how to best protect themselves, their coworkers, and their patients. Although use of personal protective equipment is a critical strategy to protect health care personnel from coronavirus disease 2019 (COVID-19), other strategies also need to be implemented on labor and delivery units to reduce the risk of health care–associated transmission, including screening of all pregnant women who present for care (case identification), placing a mask on and rapidly isolating ill pregnant women, and minimizing the number of personnel who enter the room of an ill patient (physical distancing). Although the mechanism of transmission of COVID-19 is not known with certainty, current evidence suggests that COVID-19 is transmitted primarily through respiratory droplets. Therefore, strict adherence to hand hygiene and consistent use of recommended personal protective equipment are cornerstones for reducing transmission. In addition, it is critical that health care professionals receive training on and practice correct donning (putting on) and doffing (removing) of personal protective equipment and avoid touching their faces as well as their facial protection to minimize self-contamination.


title: Remdesivir and Tocilizumab: Mix or Match

text: To date, no therapy has demonstrated definite efficacy for patients with COVID‐19. Antiviral, as well as, anti‐inflammatory approaches, as these represented by remdesivir (RDV) and tocilizumab (TCZ) use, have been recently put forward. However, data upon optimal choice of one over the other, or potential need for regimen combination, remains an open question. We hereby report two well‐matched cases of SARS‐CoV‐2 (+) patients, developing respiratory failure, both receiving TCZ following severe inflammatory response, with or without RDV. We argue that, RDV administration is pivotal early in the course of the disease, since TCZ use alone cannot ensure inflammation control. This article is protected by copyright. All rights reserved.


SARS‐CoV2‐related myocarditis‐like syndroms: Shakespeare´s question: What´s in a name?