title: Elevation of blood glucose level predicts worse outcomes in hospitalized patients with COVID-19: a retrospective cohort study

text: INTRODUCTION: With intense deficiency of medical resources during COVID-19 pandemic, risk stratification is of strategic importance. Blood glucose level is an important risk factor for the prognosis of infection and critically ill patients. We aimed to investigate the prognostic value of blood glucose level in patients with COVID-19. RESEARCH DESIGN AND METHODS: We collected clinical and survival information of 2041 consecutive hospitalized patients with COVID-19 from two medical centers in Wuhan. Patients without available blood glucose level were excluded. We performed multivariable Cox regression to calculate HRs of blood glucose-associated indexes for the risk of progression to critical cases/mortality among non-critical cases, as well as in-hospital mortality in critical cases. Sensitivity analysis were conducted in patient without diabetes. RESULTS: Elevation of admission blood glucose level was an independent risk factor for progression to critical cases/death among non-critical cases (HR=1.30, 95% CI 1.03 to 1.63, p=0.026). Elevation of initial blood glucose level of critical diagnosis was an independent risk factor for in-hospital mortality in critical cases (HR=1.84, 95% CI 1.14 to 2.98, p=0.013). Higher median glucose level during hospital stay or after critical diagnosis (≥6.1 mmol/L) was independently associated with increased risks of progression to critical cases/death among non-critical cases, as well as in-hospital mortality in critical cases. Above results were consistent in the sensitivity analysis in patients without diabetes. CONCLUSIONS: Elevation of blood glucose level predicted worse outcomes in hospitalized patients with COVID-19. Our findings may provide a simple and practical way to risk stratify COVID-19 inpatients for hierarchical management, particularly where medical resources are in severe shortage during the pandemic.


Characteristics and Outcomes of 21 Critically Ill Patients with COVID-19 in Washington State Arentz M, Yim E, Klaff L, et al. JAMA. Published online March 19, 2020. doi:10.1001/jama.2020.4326.


title: Challenges and Opportunities for the Biotechnology Research Community During the Coronavirus Pandemic

text: Abstract The COVID-19 pandemic has presented some significant challenges to the scientific community. However, this conundrum has also offered new opportunities for the pursuit of new scientific activities, and in particular for the field of biotechnology.


Preventing COVID-19-induced pneumonia with anticytokine therapy


title: China's online parrot trade: Generation length and body mass determine sales volume via price

text: Abstract The wildlife trade threatens global biodiversity and animal welfare, where parrots are among the taxa most frequently traded, supplying exotic pets and captive breeders worldwide. Using phylogenetic path analysis, we examine how biological factors interact with price to influence online protected parrot trade volumes in China, using transactions recorded for 46 species (n = 5,862 individuals). Trade was greatest in smaller, faster breeding species that commanded a lower price. This price effect followed the economic law of demand, with Relatively Inelastic Demand (−0.758), outweighing indicators of ‘quality’ such as body coloration, and conservation status. We identify two areas of concern: those larger, slower-breeding, rarer species, even though sold at lower numbers, may be at conservation risk if harvested from the wild. In contrast, the sheer numbers (over 90% of the individuals were under median generation length, body mass and/or price) and ready availability of smaller and more common species comprises a substantial overall animal welfare issue, given that the capture, importation, or captive breeding of many parrot species in China is illegal and thus unregulated. Our investigation highlights the importance of properly understanding the internal relations among drivers of wildlife trade to inform appropriate management.


A case of intrafamilial Human Parechovirus type 3 infections resulting in sepsis-like illness in a neonate but hand, foot and mouth disease in an elder sibling


title: 2.18 Promiscuous Ligands

text: Computational and experimental high-throughput screening are frequently used to discover new leads for drug design. Although novel ligands have been identified by these methods, it has become clear that screening hit lists are plagued by false positives. These nuisance compounds are ultimately found to be developmental dead-ends and are abandoned, often after considerable effort has been invested in them. Much work over the last decade has been devoted to exploring the origins of false-positive screening hits, and ligand promiscuity has emerged as one such cause. Well-known mechanisms of promiscuity include reactive species and privileged substructures. More recently, it has been found that some nonspecific screening hits form aggregates of 30–1000nm in diameter. It has been proposed that these aggregate particles are responsible for the promiscuous behavior of many false positives and that aggregate-forming compounds may be widespread among screening hits. This chapter will review the known mechanisms of ligand promiscuity with an emphasis on the recently described model of aggregation. Experimental and computational methods for identifying promiscuous compounds will be described, and some outstanding questions in the field will be considered.


Covid-19 in Brazil


title: Impact of lockdown on learning status of undergraduate and postgraduate students during COVID-19 pandemic in West Bengal, India

text: To assess the impact of lockdown amidst COVID-19 on undergraduate and postgraduate learners of various colleges and universities of West Bengal. An online survey was conducted from 1 May to 8 May 2020 to collect the information. A structural questionnaire link using ‘Google form’ was sent to students’ through WhatsApp and E-mail. A total of 232 students provided complete information regarding the survey. The simple percentage distribution was used to assess the learning status of the study participants. During the lockdown period, around 70% of learners were involved in e-learning. Most of the learners were used android mobile for attending e-learning. Students have been facing various problems related to depression anxiety, poor internet connectivity, and unfavorable study environment at home. Students from remote areas and marginalized sections mainly face enormous challenges for the study during this pandemic. This study suggests targeted interventions to create a positive space for study among students from the vulnerable section of society. Strategies are urgently needed to build a resilient education system in the state that will ensure to develop the skill for employability and the productivity of the young minds.


title: Post-Translational Protein Deimination Signatures in Serum and Serum-Extracellular Vesicles of Bos taurus Reveal Immune, Anti-Pathogenic, Anti-Viral, Metabolic and Cancer-Related Pathways for Deimination

text: The bovine immune system is known for its unusual traits relating to immunoglobulin and antiviral responses. Peptidylarginine deiminases (PADs) are phylogenetically conserved enzymes that cause post-translational deimination, contributing to protein moonlighting in health and disease. PADs also regulate extracellular vesicle (EV) release, forming a critical part of cellular communication. As PAD-mediated mechanisms in bovine immunology and physiology remain to be investigated, this study profiled deimination signatures in serum and serum-EVs in Bos taurus. Bos EVs were poly-dispersed in a 70–500 nm size range and showed differences in deiminated protein cargo, compared with whole sera. Key immune, metabolic and gene regulatory proteins were identified to be post-translationally deiminated with some overlapping hits in sera and EVs (e.g., immunoglobulins), while some were unique to either serum or serum-EVs (e.g., histones). Protein–protein interaction network analysis of deiminated proteins revealed KEGG pathways common for serum and serum-EVs, including complement and coagulation cascades, viral infection (enveloped viruses), viral myocarditis, bacterial and parasitic infections, autoimmune disease, immunodeficiency intestinal IgA production, B-cell receptor signalling, natural killer cell mediated cytotoxicity, platelet activation and hematopoiesis, alongside metabolic pathways including ferroptosis, vitamin digestion and absorption, cholesterol metabolism and mineral absorption. KEGG pathways specific to EVs related to HIF-1 signalling, oestrogen signalling and biosynthesis of amino acids. KEGG pathways specific for serum only, related to Epstein–Barr virus infection, transcription mis-regulation in cancer, bladder cancer, Rap1 signalling pathway, calcium signalling pathway and ECM-receptor interaction. This indicates differences in physiological and pathological pathways for deiminated proteins in serum-EVs, compared with serum. Our findings may shed light on pathways underlying a number of pathological and anti-pathogenic (viral, bacterial, parasitic) pathways, with putative translatable value to human pathologies, zoonotic diseases and development of therapies for infections, including anti-viral therapies.


title: Chapter 5 Role of risk analysis and risk communication in food safety management

text: Abstract Concept of “risk analysis” in food safety management needs to be understood to assess, manage, and communicate risks for proper implementation of food safety policies, food laws, and standards, in a country. Science-based approaches, which are an integral part of risk analysis to improve modern food safety systems, are intimately linked to processes such as good quality practices. Risk analysis strengthens the ability of traditional food safety systems to meet current challenges. Risk analysis is just one part of an effective food safety system. Other components of food safety system like food safety policies, food legislation, food inspection, laboratory analysis, epidemiological surveillance of food-borne diseases, monitoring systems for chemical and microbiological contamination in foods, and information, education and communication, also need to be improved continuously. “Food safety controls” are now being replaced by “risk-based controls” in all stages of food production.


Virology: Molecular biology of the coronaviruses


title: Genomic RNA sequence of feline coronavirus strain FCoV C1Je

text: This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV). Viral RNA was isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP). A consensus sequence of the jejunum-derived genomic RNA (FCoV C1Je) was determined from overlapping cDNA fragments produced by reverse transcriptase polymerase chain reaction (RT-PCR) amplification. RT-PCR products were sequenced by a reiterative sequencing strategy and the genomic RNA termini were determined using a rapid amplification of cDNA ends PCR strategy. The FCoV C1Je genome was found to be 29,255 nucleotides in length, excluding the poly(A) tail. Comparison of the FCoV C1Je genomic RNA sequence with that of the laboratory strain FCoV FIP virus (FIPV) 79-1146 showed that both viruses have a similar genome organisation and predictions made for the open reading frames and cis-acting elements of the FIPV 79-1146 genome hold true for FCoV C1Je. In addition, the sequence of the 3′-proximal third of the liver derived genomic RNA (FCoV C1Li), which encompasses the structural and accessory protein genes of the virus, was also determined. Comparisons of the enteric (jejunum) and non-enteric (liver) derived viral RNA sequences revealed 100% nucleotide identity, a finding that questions the well accepted ‘internal mutation theory’ of FIPV pathogenicity.


title: Rhabdomyolysis associated with acute renal failure in patients with severe acute respiratory syndrome

text: An outbreak of severe acute respiratory syndrome (SARS) occurred in Taiwan in 2003. SARS complicated with rhabdomyolysis has rarely been reported. This study reported three cases of rhabdomyolysis developing during the clinical course of SARS. Thirty probable SARS patients were admitted to the isolation wards at Linkou Chang Gung Memorial Hospital between 4 April and 4 June 2003. Thirty patients, including four men and 26 women aged from 12 to 87 years (mean age 40). Eleven (36.7%) patients had respiratory failure and required mechanical ventilation with paralytic therapy; three (10%) patients had rhabdomyolysis complicated with acute renal failure and one received haemodialysis; four (13.3%) patients died. Three cases with rhabdomyolysis all received sedative and paralytic therapy for mechanical ventilation. Haemodialysis was performed on one patient. Two patients died from multiple organ failure, and one patient fully recovered from rhabdomyolysis with acute renal failure. SARS is a serious respiratory illness, and its aetiology is a novel coronavirus. Rhabdomyolysis resulting from SARS virus infection was strongly suspected. Immobilisation under paralytic therapy and steroids may also be important in developing rhabdomyolysis.


title: Infectious Hepatopathies in Dogs and Cats

text: This article serves to review the various infectious diseases that affect the liver primarily or as a part of systemic infection. Although bacterial infections are probably the most common cause of infectious hepatitis, the clinician should be aware of other potential organisms and other commonly involved systems. Therefore, this article includes a description of common bacterial, mycobacterial, viral, fungal, protozoal, parasitic, and rickettsial diseases in dogs and cats.


title: COVID-19 and liver transplantation

text: The effect of coronavirus disease 2019 (COVID-19) on liver transplantation programmes and recipients is still not completely understood but overall involves the risk of donor-derived transmission, the reliability of diagnostic tests, health-care resource utilization and the effect of immunosuppression. This Comment reviews the effect of COVID-19 on liver transplantation and summarizes recommendations for donor and recipient management.


title: Thermal Image Scanning for Influenza Border Screening: Results of an Airport Screening Study

text: BACKGROUND: Infrared thermal image scanners (ITIS) appear an attractive option for the mass screening of travellers for influenza, but there are no published data on their performance in airports. METHODS: ITIS was used to measure cutaneous temperature in 1275 airline travellers who had agreed to tympanic temperature measurement and respiratory sampling. The prediction by ITIS of tympanic temperature (37.8°C and 37.5°C) and of influenza infection was assessed using Receiver Operating Characteristic (ROC) curves and estimated sensitivity, specificity and positive predictive value (PPV). FINDINGS: Using front of face ITIS for prediction of tympanic temperature ≥37.8°C, the area under the ROC curve was 0.86 (95%CI 0.75–0.97) and setting sensitivity at 86% gave specificity of 71%. The PPV in this population of travellers, of whom 0.5% were febrile using this definition, was 1.5%. We identified influenza virus infection in 30 travellers (3 Type A and 27 Type B). For ITIS prediction of influenza infection the area under the ROC curve was 0.66 (0.56–0.75), a sensitivity of 87% gave specificity of 39%, and PPV of 2.8%. None of the 30 influenza-positive travellers had tympanic temperature ≥37.8°C at screening (95%CI 0% to 12%); three had no influenza symptoms. CONCLUSION: ITIS performed moderately well in detecting fever but in this study, during a seasonal epidemic of predominantly influenza type B, the proportion of influenza-infected travellers who were febrile was low and ITIS were not much better than chance at identifying travellers likely to be influenza-infected. Although febrile illness is more common in influenza A infections than influenza B infections, many influenza A infections are afebrile. Our findings therefore suggest that ITIS is unlikely to be effective for entry screening of travellers to detect influenza infection with the intention of preventing entry of the virus into a country.


title: From carbohydrate leads to glycomimetic drugs

text: Carbohydrates are the most abundant natural products. Besides their role in metabolism and as structural building blocks, they are fundamental constituents of every cell surface, where they are involved in vital cellular recognition processes. Carbohydrates are a relatively untapped source of new drugs and therefore offer exciting new therapeutic opportunities. Advances in the functional understanding of carbohydrate–protein interactions have enabled the development of a new class of small-molecule drugs, known as glycomimetics. These compounds mimic the bioactive function of carbohydrates and address the drawbacks of carbohydrate leads, namely their low activity and insufficient drug-like properties. Here, we examine examples of approved carbohydrate-derived drugs, discuss the potential of carbohydrate-binding proteins as new drug targets (focusing on the lectin families) and consider ways to overcome the challenges of developing this unique class of novel therapeutics.


title: China as a reserve sink: The evidence from offset and sterilization coefficients

text: China has been stockpiling international reserves at an extremely rapid pace since the late 1990s and has surpassed Japan to become the largest reserve holder in the world. This paper undertakes an empirical investigation to assess the extent of de facto sterilization and capital mobility using monthly data between mid 2000 and late 2008. We find that China has been able to successfully sterilize a large portion of these reserve increases thus making it a reserve sink such as Germany was under the Bretton Wood system.


title: Identification of SARS-CoV-2 Vaccine Epitopes Predicted to Induce Long-term Population-Scale Immunity

text: Summary Here we propose a SARS-CoV-2 vaccine design concept based on identification of highly conserved regions of the viral genome and newly acquired adaptations, both predicted to generate epitopes presented on MHC class I and II across the vast majority of the population. We further prioritize genomic regions that generate highly dissimilar peptides from the human proteome, and are also predicted to produce B cell epitopes. We propose sixty-five 33mer peptide sequences, a subset of which can be tested using DNA or mRNA delivery strategies. These include peptides that are contained within evolutionarily divergent regions of the spike protein reported to increase infectivity through increased binding to the ACE2 receptor and within a newly evolved furin cleavage site thought to increase membrane fusion. Validation and implementation of this vaccine concept could specifically target specific vulnerabilities of SARS-CoV-2 and should engage a robust adaptive immune response in the vast majority of the population.


title: A novel technique for automated concealed face detection in surveillance videos

text: Face detection perceives great importance in surveillance paradigm and security paradigm areas. Face recognition is the technique to identify a person identity after face detection. Extensive research has been done on these topics. Another important research problem is to detect concealed faces, especially in high-security places like airports or crowded places like concerts and shopping centres, for they may prevail security threat. Also, in order to help effectively in preventing the spread of Coronavirus, people should wear masks during the pandemic especially in the entrance to hospitals and medical facilities. Surveillance systems in medical facilities should issue warnings against unmasked people. This paper presents a novel technique for concealed face detection based on complexion detection to challenge a concealed face assumption. The proposed algorithm first determine of the existence of a human being in the surveillance scene. Head and shoulder contour will be detected. The face will be clustered to cluster patches. Then determination of presence or absent of human skin will be determined. We proposed a hybrid approach that combines normalized RGB (rgb) and the YCbCr space color. This technique is tested on two datasets; the first one contains 650 images of skin patches. The second dataset contains 800 face images. The algorithm achieves an average detection rate of 97.51% for concealed faces. Also, it achieved a run time comparable with existing state-of-the-art concealed face detection systems that run in real time.


title: A current review of COVID-19 for the cardiovascular specialist

text: Abstract Although Coronavirus Disease 2019 (COVID-19) predominantly disrupts the respiratory system, there is accumulating experience that the disease, particularly in its more severe manifestations, also affects the cardiovascular system. Cardiovascular risk factors and chronic cardiovascular conditions are prevalent among patients affected by COVID-19 and associated with adverse outcomes. However, whether pre-existing cardiovascular disease is an independent determinant of higher mortality risk with COVID-19 remains uncertain. Acute cardiac injury, manifest by increased blood levels of cardiac troponin, electrocardiographic abnormalities, or myocardial dysfunction, occurs in up to ~60% of hospitalized patients with severe COVID-19. Potential contributors to acute cardiac injury in the setting of COVID-19 include 1) acute changes in myocardial demand and supply due to tachycardia, hypotension, and hypoxemia resulting in type 2 myocardial infarction; 2) acute coronary syndrome due to acute atherothrombosis in a virally-induced thrombotic and inflammatory milieu; 3) microvascular dysfunction due to diffuse microthrombi or vascular injury; 4) stress-related cardiomyopathy (Takotsubo syndrome); 5) non-ischemic myocardial injury due to a hyperinflammatory cytokine storm; or 6) direct viral cardiomyocyte toxicity and myocarditis. Diffuse thrombosis is emerging as an important contributor to adverse outcomes in patients with COVID-19. Practitioners should be vigilant for cardiovascular complications of COVID-19. Monitoring may include serial cardiac troponin and natriuretic peptides, along with fibrinogen, d-dimer, and inflammatory biomarkers. Management decisions should rely on the clinical assessment for the probability of ongoing myocardial ischemia, as well as alternative non-ischemic causes of injury, integrating the level of suspicion for COVID-19.


title: Orthopedic telemedicine encounter during the COVID-19 pandemic: A cautionary tale

text: The COVID-19 pandemic has necessitated increased use of telemedicine for diagnosis and management of musculoskeletal disorders. We describe the initial virtual/telemedicine encounter and management of a patient with knee pain initially diagnosed as gonarthrosis but that actually resulted from an impending pathologic fracture of the femur. Definitive diagnosis and treatment occurred only after completion of the impending fracture. The multiple factors making telemedicine encounters challenging which contributed to this outcome are highlighted. Orthopedists need awareness of these challenges and must take steps to mitigate the risk of complications possible with continued increased utilization of telemedicine during this pandemic and beyond.


title: A novel method for synthetic vaccine construction based on protein assembly

text: In the history of vaccine development, the synthetic vaccine is a milestone that is in stark contrast with traditional vaccines based on live-attenuated or inactivated microorganisms. Synthetic vaccines not only are safer than attenuated or inactivated microorganisms but also provide the opportunity for vaccine design for specific purposes. The first generation of synthetic vaccines has been largely based on DNA recombination technology and genetic manipulation. This de novo generation is occasionally time consuming and costly, especially in the era of genomics and when facing pandemic outbreaks of infectious diseases. To accelerate and simplify the R&D process for vaccines, we developed an improved method of synthetic vaccine construction based on protein assembly. We optimized and employed the recently developed SpyTag/SpyCatcher technique to establish a protein assembly system for vaccine generation from pre-prepared subunit proteins. As proof of principle, we chose a dendritic cell (DC)-targeting molecule and specific model antigens to generate desired vaccines. The results demonstrated that a new vaccine generated in this way does not hamper the individual function of different vaccine components and is efficient in inducing both T and B cell responses. This protein assembly strategy may be especially useful for high-throughput antigen screening or rapid vaccine generation.


title: In vivo and in vitro models of demyelinating disease. XVII. The infectious process in athymic rats inoculated with JHM virus

text: Abstract Wistar Lewis (WL), Long Evans (LE) and other rat strains develop complete resistance to CNS disease when inoculated intracerebrally with murine hepatitis JHM virus (JHMV) after the 10th day of age. 1 1 Sorensen O, Percy D, Dales S. In vivo and in vitro models of demyelinating diseases. III. JHM virus infection of rats. Arch Neurol 1980; 37: 478-84. Two types of studies were conducted to ascertain the involvement of the cellular immune system in development of resistance. Immunosuppression of WL rats with cyclosporin A (CsA) following onset of the age-related resistance demonstrated that this drug was partially able to abrogate resistance. In the other studies nude (rnu/rnu) rats, their heterozygous (rnu/+) litter mates and genetically related LE rats of various ages were challenged with JHMV. The rnu/+ and LE animals became completely resistant before the age of weaning, whereas some rnu/rnu rats, challenged as late as 70 days of age, showed disease symptoms—albeit after a long latent period. These observations indicated that the cellular immune system plays an important role in suppressing the disease process in the CNS. When the infection of nude rats was initiated on or after the 15th day of life, the histological lesions were generally small and present in both grey and white matter but were seldom seen in the spinal cord. Mononuclear infiltrates were evident throughout the CNS. In some nude rats there was massive mononuclear cell infiltration towards the meningies and into ventricular spaces. By contrast in rnu/+, LE and WL rats with late-onset disease symptoms, demyelinating-type lesions were confined to the white matter and only minor infiltration of mononuclear cells was evident. JHMV RNA was detectable by dot-blotting analysis in the CNS of both paralysed and asymptomatic rnu/rnu and rnu/+ rats, but less RNA was usually detected in heterozygous animals. In-situ hybridization with cDNA probes for JHMV RNA showed that neurons in the hippocampus and cerebellum, as well as cells in the white matter, were frequently infected. The present data indicate that in the rat T cells have an important function in maintaining resistance to the JHMV related disease process. However, even without a functional T cell compartment nude rats challenged after 15 days of age did not develop an acute encephalitis, suggesting that an age-dependent, non-immunological mechanism is also involved in restricting the spread of infection. It is possible that resistance in euthymic rats sets in because: (1) at the time of weaning the CNS matures, so that the number of targets available for infection is reduced, (2) T cells prevent the late-onset disease by clearing persistent, low grade infections from the CNS.


title: Proceedings of the fourth National Congress of the Italian Society of Virology

text: The aim of the yearly National Congress of the Italian Society of Virology (SIV) is to promote the discussion between senior and younger researchers to improve the knowledge and scientific collaboration among the various areas of Virology. The invited and selected lecturers of the fourth National Congress of SIV covered the following topics: general Virology and viral Genetics; virus host interactions and pathogenesis; viral immunology and vaccines; emerging and re‐emerging viral diseases; antiviral therapy; innovative diagnostics; viral biotechnologies and gene therapy. As in the previous edition (Salata and Palù, 2004 J Cell Physiol 199:171–173), a specific topic was thoroughly covered in a roundtable. In this edition the overviewed topic was HCV, from epidemiology and genetic variability to immunology and antiviral therapy. The final program can be found at the web site http://www.siv-virologia.it. A summary of the oral presentations of the 2004 meeting is reported. © 2005 Wiley‐Liss, Inc.


title: Influence of FcγRIIA and MBL polymorphisms on severe acute respiratory syndrome

text: Polymorphisms of human Fc γ‐receptor IIA (FcγRIIA) and mannose‐binding lectin (MBL) genes have been associated with susceptibility to or severity of some infectious diseases. In order to investigate whether these genetic factors might influence susceptibility to infection with the severe acute respiratory syndrome‐associated coronavirus (SARS‐Cov) as well as the course and severity of the infection, we evaluated polymorphisms of FcγRIIA and MBL genes in DNA samples from a group of approximately 180 people from Hong Kong who were infected with SARS‐Cov. These included 132 patients who had moderate course of SARS infection (home subgroup), 26 patients with a severe course requiring treatment in an intensive care ward (ICU subgroup) and a subgroup of 22 patients who died from SARS (deceased subgroup). A total of 200 normal blood donors from the same region were used as controls. A significant association was found between the FcγRIIA‐R/R131 genotype and a severe course of SARS, with higher frequency of homozygosity for FcγRIIA‐R/R131 in the ICU subgroup of SARS patients when compared with controls (P = 0.03; odds ratio: 3.2; 95% confidence interval: 1.1–9.1). In comparison with controls, a significant difference in linear trend distribution of FcγRIIA genotypes was seen among the severe SARS patients (ICU and deceased subgroups) without co‐morbidity, and the incidence of FcγRIIA‐H/H131 was lower in these patients as well. There were no significant differences in MBL genotypes and allele frequencies among SARS patients and controls. The study reveals that in addition to age and co‐morbidity, FcγRIIA polymorphism of individuals may also influence outcome after infection with the SARS‐Cov.


title: Corticosteroid treatment of patients with coronavirus disease 2019 (COVID‐19)

text: OBJECTIVES: To assess the efficacy of corticosteroid treatment of patients with coronavirus disease 2019 (COVID‐19). DESIGN, SETTING: Observational study in the two COVID‐19‐designated hospitals in Wuhu, Anhui province, China, 24 January – 24 February 2020. PARTICIPANTS: Thirty‐one patients infected with the severe acute respiratory coronavirus 2 (SARS‐CoV‐2) treated at the two designated hospitals. MAIN OUTCOME MEASURES: Virus clearance time, length of hospital stay, and duration of symptoms, by treatment type (including or not including corticosteroid therapy). RESULTS: Eleven of 31 patients with COVID‐19 received corticosteroid treatment. Cox proportional hazards regression analysis indicated no association between corticosteroid treatment and virus clearance time (hazard ratio [HR], 1.26; 95% CI, 0.58–2.74), hospital length of stay (HR, 0.77; 95% CI, 0.33–1.78), or duration of symptoms (HR, 0.86; 95% CI, 0.40–1.83). Univariate analysis indicated that virus clearance was slower in two patients with chronic hepatitis B infections (mean difference, 10.6 days; 95% CI, 6.2–15.1 days). CONCLUSIONS: Corticosteroids are widely used when treating patients with COVID‐19, but we found no association between therapy and outcomes in patients without acute respiratory distress syndrome. An existing HBV infection may delay SARS‐CoV‐2 clearance, and this association should be further investigated.


Syringe Services Program (SSP) Operational Changes During the COVID-19 Global Outbreak


Étude descriptive et comparative des infections à coronavirus (hors SARS-CoV) chez l'enfant hospitalisé


title: An open call for influenza vaccination pending the new wave of COVID‐19

text: In their study, Yue et al. reported influenza co-infection among COVID-19 patients as 57.3%. The study included a period of January 12-February 21, 2020 in Wuhan, China. We have recently detected this rate as 0.54% in Turkey. This difference between rates of co-infection can be explained by the seasonality of the influenza virus. Our study included the period of March 10-May 10. Another study from Wuhan, including the period of 28 January-29 February 2020, reported the rate of influenza co-infection among critically ill COVID-19 patients as 49.5%. Zhu et al. reported 2.7% influenza co-infections among COVID-19 patients, in their study from January 22-February 2. Two studies from USA reported low rates of 0.08% in March 16-April 20, and 0.9% in March 3-March 25. Therefore, studies from the influenza season reported very high rates of co-infection. When the COVID-19 came to Europe and America, the influenza season was almost over and thus the co-infection rates are low. A recent research found moderate to strong correlation between higher influenza vaccine uptake in the elderly and lower COVID-19 deaths in Italy. This might be explained by the prevention of influenza co-infection. In elderly, both influenza and COVID-19 have higher rates of mortality. The impact of prevention of influenza in this fragile group is higher. Current influenza-COVID-19 co-infection reports suggest that co-infection rates are as high as 57% when influenza is circulating. Pending the new waves of COVID-19, it is reasonable to recommend influenza vaccination especially for elderly, but most probably, to general population. This article is protected by copyright. All rights reserved.


title: Optimal Timing of VT Ablation for Patients with ICD Therapies

text: PURPOSE OF REVIEW: Optimal timing for catheter ablation of ventricular tachycardia is an important yet unresolved subject. While it is clear that it is indicated with relatively advanced disease, it is still uncertain how early it should be recommended. In this review, we will focus on the status of timing of catheter ablation for VT in patients with ICD therapies. RECENT FINDINGS: The latest expert consensus statement added a new timing indication for catheter ablation after the first episode of monomorphic VT, in patients with ischemic heart disease and an ICD. SUMMARY: Early referral for catheter ablation reduces the number of VT recurrences; however, an impact on mortality has not been demonstrated yet. Guidelines and real-world data alike show an increasing trend to refer patients after the first VT episode in ICD patients. Randomized clinical trials powered to assess mortality are essential in order confirm the beneficial effects of an early strategy.


title: Structural Basis of RNA Cap Modification by SARS-CoV-2 Coronavirus

text: The novel severe acute respiratory syndrome coronoavirus-2 (SARS-CoV-2), the causative agent of COVID-19 illness, has caused over 2 million infections worldwide in four months. In SARS coronaviruses, the non-structural protein 16 (nsp16) methylates the 5’-end of virally encoded mRNAs to mimic cellular mRNAs, thus protecting the virus from host innate immune restriction. We report here the high-resolution structure of a ternary complex of full-length nsp16 and nsp10 of SARS-CoV-2 in the presence of cognate RNA substrate and a methyl donor, S-adenosyl methionine. The nsp16/nsp10 heterodimer was captured in the act of 2’-O methylation of the ribose sugar of the first nucleotide of SARS-CoV-2 mRNA. We reveal large conformational changes associated with substrate binding as the enzyme transitions from a binary to a ternary state. This structure provides new mechanistic insights into the 2’-O methylation of the viral mRNA cap. We also discovered a distantly located ligand-binding site unique to SARS-CoV-2 that may serve as an alternative target site for antiviral development.


title: The variability of the serological response to SARS corona virus‐2: Potential resolution of ambiguity through determination of avidity (functional affinity)

text: Data on the serological response towards SARS CoV‐2 in 16 recent reports were analyzed and a high degree of variability was shown. IgM responses were either found earlier than IgG, or together with IgG, later than IgG or were missing. Therefore, clear distinctions between early, intermediate and past infections are obviously not possible merely on the basis of IgM and IgG determinations. The review of publications on the serology of other virus groups shows that variable IgM responses can be found as well and therefore are not specific for SARS CoV‐2 infections. A model to explain this variability is proposed. The inclusion of avidity determination into regular diagnostic procedures has allowed to resolve such “atypical” serological constellations. The potential use of avidity determination for the diagnosis of Covid‐19, for risk assessment, epidemiological studies, analysis of cross reactions, as well as for the control of vaccination programs is suggested and discussed. This article is protected by copyright. All rights reserved.


title: Estimating the cost of vaccine development against epidemic infectious diseases: a cost minimisation study

text: BACKGROUND: The Coalition for Epidemic Preparedness Innovations was established in 2016, to develop vaccines that can contribute to preparedness for outbreaks of epidemic infectious diseases. Evidence on vaccine development costs for such diseases is scarce. Our goal was to estimate the minimum cost for achieving vaccine research and development preparedness targets in a portfolio of 11 epidemic infectious diseases, accounting for vaccine pipeline constraints and uncertainty in research and development preparedness outcomes. METHODS: We assembled a pipeline of 224 vaccine candidates from preclinical through to phase 2 for 11 priority epidemic infectious diseases. We used a linear regression model to identify drivers of development costs from preclinical through to end of phase 2a. Drawing from published estimates of vaccine research and development probabilities of success, we simulated costs for advancing these 224 vaccine candidates through to the end of phase 2a. We combined these findings to determine minimum costs for progressing at least one vaccine through to the end of phase 2a per epidemic infectious disease by means of a stochastic optimisation model. FINDINGS: The cost of developing a single epidemic infectious disease vaccine from preclinical trials through to end of phase 2a is US$31–68 million (US$14–159 million range), assuming no risk of failure. We found that previous licensure experience and indirect costs are upward drivers of research and development costs. Accounting for probability of success, the average cost of successfully advancing at least one epidemic infectious disease vaccine through to the end of phase 2a can vary from US$84–112 million ($23 million–$295 million range) starting from phase 2 to $319–469 million ($137 million–$1·1 billion range) starting from preclinical. This cost includes the cumulative cost of failed vaccine candidates through the research and development process. Assuming these candidates and funding were made available, progressing at least one vaccine through to the end of phase 2a for each of the 11 epidemic infectious diseases would cost a minimum of $2·8–3·7 billion ($1·2 billion–$8·4 billion range). INTERPRETATION: Our analysis provides new evidence on vaccine research and development pipelines and associated costs for 11 epidemic infectious diseases, highlighting both funding needs and research and development gaps for achieving vaccine research and development preparedness targets. FUNDING: This work was partly supported by the Research Council of Norway through the Global Health and Vaccination Programme GLOBVAC.


title: The E3 ligase TRIM56 is a host restriction factor of Zika virus and depends on its RNA-binding activity but not miRNA regulation, for antiviral function

text: Infection by Zika virus (ZIKV) is linked to microcephaly and other neurological disorders, posing a significant health threat. Innate immunity is the first line of defense against invading pathogens, but relatively little is understood regarding host intrinsic mechanisms that guard against ZIKV. Here, we show that host tripartite motif-containing protein 56 (TRIM56) poses a barrier to ZIKV infection in cells of neural, epithelial and fibroblast origins. Overexpression of TRIM56, but not an E3 ligase-dead mutant or one lacking a short C-terminal portion, inhibited ZIKV RNA replication. Conversely, depletion of TRIM56 increased viral RNA levels. Although the C-terminal region of TRIM56 bears sequence homology to NHL repeat of TRIM-NHL proteins that regulate miRNA activity, knockout of Dicer, which abolishes production of miRNAs, had no demonstrable effect on ZIKV restriction imposed by TRIM56. Rather, we found that TRIM56 is an RNA-binding protein that associates with ZIKV RNA in infected cells. Moreover, a recombinant TRIM56 fragment comprising the C-terminal 392 residues captured ZIKV RNA in cell-free reactions, indicative of direct interaction. Remarkably, deletion of a short C-terminal tail portion abrogated the TRIM56-ZIKV RNA interaction, concomitant with a loss in antiviral activity. Altogether, our study reveals TRIM56 is an RNA binding protein that acts as a ZIKV restriction factor and provides new insights into the antiviral mechanism by which this E3 ligase tackles flavivirus infections.


title: Suppression of porcine reproductive and respiratory syndrome virus proliferation by glycyrrhizin

text: Abstract Glycyrrhizin is a natural component extracted from the roots of Glycyrrhiza glabra. In this study, we investigated the antiviral activity of glycyrrhizin against porcine reproductive and respiratory syndrome virus (PRRSV), an Arterivirus that has been devastating the swine industry worldwide since the late 1980s. Our results showed that treatment with glycyrrhizin significantly reduced PRRSV proliferation and PRRSV-encoded protein expression in a dose-dependent manner. Mechanistically, glycyrrhizin mainly inhibits the penetration stage, and has little effect on the steps of adsorption or release of PRRSV in its life cycle. Furthermore, we were able to exclude a direct inhibitory action of glycyrrhizin on PRRSV particles. Given these results, glycyrrhizin may be a candidate component for a novel porcine reproductive and respiratory syndrome (PRRS) control strategy.


title: COVID-19: A Review of Emerging Preventative Vaccines and Treatment Strategies

text: COVID-19, which was first detected in the Hubei province of China, has become a global phenomenon. The effects and devastation on both health and economy have been global. At present, there is a substantial amount of research being done to discover suitable treatment modalities. Efforts have been made on the development of potential efficacious vaccines. The development of a vaccine can be complex, expensive as well as time-consuming. Currently, various ongoing clinical trials are in progress that are investigating either pharmacologic therapies or vaccines against this virus. We, in this brief review have tried to address the process and current development efforts of vaccine in progress.


title: Rat coronavirus (RCV): A prevalent, naturally occurring pneumotropic virus of rats

text: A new virus isolated from the lungs of rats is prevalent in colony reared and wild rats and induces a fatal pneumonitis in newborn rats. The virus, designated as rat coronavirus (RCV), exhibits properties representative of the coronavirus group: characteristic surface structure, particles somewhat variable in size averaging approximately 90 mμ, apparent RNA content, essential lipid, heat sensitivity, and a close serologie relationship with the mouse hepatitis virus complex. RCV grows well in primary rat kidney cell cultures, exhibits a pathognomonic type CPE, and produces a complement fixing antigen which is sensitive for detection of antibody and useful in sero-epidemiologic studies.


Reply to: Psychophysical olfactory testing in COVID‐19: Is smell function really impaired in nearly all patients?


title: A compartmental model for the analysis of SARS transmission patterns and outbreak control measures in China

text: Abstract We propose a compartmental model BloComp(2,7) that mimics the SARS control strategies implemented by the Chinese government after the middle of April 2003: the division of the whole population into two parallel blocks corresponding to the so-called free environment and the isolated environment and the partition of these blocks further into the compartments of susceptible, exposed, infective, possible, diagnosed, removed and the health care workers. We introduce a novel approach to calculate the transfer rate from the free environment to the isolated environment, and we incorporate into the model the fact that many individuals were misdiagnosed as SARS suspected and hence were mistakenly put in the isolated environment due to lack of fast and effective SARS diagnostic tests. We develop some methods for the parameter identification using the daily reported data from the Ministry of Health of China. Simulations based on these parameters agree with the accural data well, thus provide additional validation of the model. We then vary some parameters to assess the effectiveness of different control measures: these new parameters correspond to the situation when the quarantine measures in the free-environment were prematurely relaxed (we thus observe the second outbreak with the maximal number of daily SARS patients much higher than the first outbreak) or when the quarantine time of SARS patients is postponed (we observe delayed peak time but with much higher number of SARS patients at the peak). We also calculate the basic reproductive number and the basic adequate contact rate.


title: Responding to Pandemic Influenza: A Local Perspective

text: OBJECTIVE: To assess, via a tabletop exercise, the ability of a rural health unit to manage an influenza pandemic. PARTICIPANTS: The exercise brought together community stakeholders including representation from public health, hospitals, long-term care, social services, first responders, morticians, local government and the media. SETTING: Leeds, Grenville and Lanark, a rural region of Ontario. p ]Intervention: In June 2002, exercise participants were presented with a scenario involving the local response to pandemic influenza. Facilitators prepared a framework for the mock emergency in advance. However, the scenario was guided by decisions made by participants and the probable consequences of those decisions. Following the exercise, a debriefing session identified recommendations to be included in future plan development. OUTCOMES: The exercise identified critical issues, including communication, emergency decision-making, vaccination priorization, local surge capacity, and disease containment. Both participants and observers deemed the exercise successful. CONCLUSION: Improvements in the local contingency plan for pandemic influenza were identified. The exercise was an opportunity to familiarize participants with the contingency plan, practice working collectively and identify areas for further planning. The principles and lessons generated from the exercise can be used to guide the response to other large-scale infectious disease outbreaks.


title: Psychosocial and coping responses within the community health care setting towards a national outbreak of an infectious disease

text: Abstract Objective The psychological and coping responses of the noninfected community towards infectious disease outbreaks are relatively understudied. This cross-sectional study sought to determine the prevalence of severe acute respiratory syndrome (SARS)-related psychiatric and posttraumatic morbidities and associated coping styles within the general population visiting community health care services. Methods It was conducted on individuals attending community polyclinics in Singapore within the first week of July 2003, 16 weeks after the first national outbreak of SARS. The General Health Questionnaire-28, Impact of Event Scale-Revised, and Brief COPE were used to determine the prevalence rates of psychiatric and posttraumatic morbidities and employed coping strategies respectively. Results The overall response rate was 78.0%. Of the 415 community health care setting respondents, we found significant rates of SARS-related psychiatric (22.9%) and posttraumatic morbidities (25.8%). The presence of psychiatric morbidity was associated with the presence of high level of posttraumatic symptoms [adjusted odds ratio (OR) 2.26, 95% confidence interval (CI) 1.24–4.13, P=.008]. Psychiatric morbidity was further associated with being seen at fever stations (adjusted OR 1.90, 95% CI 1.08–3.34, P=.026), younger age (adjusted OR 0.97, 95% CI 0.94–0.98, P=.021), increased self blame (adjusted OR 1.67, 95% CI 1.22–2.28, P=.001), less substance use (adjusted OR 0.74, 95% CI 0.56–0.98, P=.034) and posttraumatic morbidity was associated with increased use of denial (adjusted OR 1.31, 95% CI 1.04–1.67, P=.024), and planning (adjusted OR 1.51, 95% CI 1.16–1.95, P=.002) as coping measures. Conclusion These findings could potentially inform the development of practical community mental health programs for future infectious disease outbreaks.


title: A data-driven hypothesis on the epigenetic dysregulation of host metabolism by SARS coronaviral infection: potential implications for the SARS-CoV-2 modus operandi

text: COVID-19, the disease caused by the novel SARS-CoV-2, a betacoronavirus structurally similar to SARS-CoV. Based on both structural and syndromic similarities with SARS-CoV, a hypothesis is formed on SARS-CoV-2 potential to affect the host’s metabolism as part of its lifecycle. This hypothesis is evaluated by (a) exploratory analysis of SARS-CoV / human transcriptomic interaction data and gene set enrichment analysis (b) a confirmatory, focused review of the literature based on the findings by (a). A STRING Viruses (available search for human – SARS-CoV (NCBI taxonomy Id: 9606 vs. NCBI taxonomy Id: 694009) genomic interactions reveals ten human proteins, interacting with SARS-CoV: SGTA, FGL2, SPECC1, STAT3, PHB, BCL2L1, PPP1CA, CAV1, JUN, XPO1. Gene set enrichment analyses (GSEA) with STRING on this network revealed their role as a putative protein – protein interaction network (PPI; Enrichment p-value=0.0296) mediating, viral parasitism, interleukin as well as insulin signaling, diabetes and triglyceride catabolism. In the literature, SARS-CoV has been known to cause de novo diabetes by ACE2-dependent uptake on pancreatic isle cells, and furthermore dysregulate lipid autophagy in favor of the viral lifecycle. Conversely, currently there are only non-causative, observational evidence of worse outcomes for COVID-19 patients with comorbid diabetes or hyperglycemia. No study has reported on the lipid profiles of COVID-19 patients; however, lipid-targeting molecules have been proposed as agents against SARS-CoV-2. Future studies, reporting on lipid and glucose metabolism of COVID-19 patients could help elucidate the disease’s seculae and aid drug design.


title: Using an epidemiological framework and bovine spongiform encephalopathy investigation questionnaire to investigate suspect bovine spongiform encephalopathy cases: an example from a bovine spongiform encephalopathy case in Ireland in 2015

text: In several EU member states, bovine spongiform encephalopathy (BSE) cases have been identified in cattle born after the reinforced ban (BARB cases), for reasons that are not entirely clear. Epidemiological investigation of these cases has proved challenging. The European Food Safety Authority recently recommended the collection of a predefined set of epidemiological data from BSE suspects and confirmed BSE cases to aid future investigations. In this study, we present an epidemiological framework and BSE investigation questionnaire to aid the investigation of suspect BSE cases, and illustrate its application during the investigation of a BSE case in Ireland in 2015. It is recommended that the framework and questionnaire are used concurrently: the framework provides structure and focus, whereas the questionnaire (with 135 questions) aids data collection. The framework focuses on confirmation and discrimination, estimating the date and location of exposure, and determining the method/source of exposure. The BSE case in Ireland in 2015 was a BARB case born in 2010. It was identified with classical BSE at an authorised knackery as part of Ireland’s targeted active surveillance programme for BSE. No definitive source of infection with the BSE agent could be attributed in this case.


title: Aviation Medicine: Illness and Limitations for Flying

text: Abstract The world has celebrated over 100 years of powered flight. In December 1903, on a very windy beach in North Carolina, USA, Wilbur and Orville Wright successfully designed, built, and flew the first powered aircraft. In the air for only seconds, it marked the beginning of modern aviation. In just a short time span, aviation has progressed to high-altitude flight, flight at supersonic speeds, and flight to space and back. Aviation is integrated into our modern world and has blurred the boundaries of countries, enhanced business and communication across the world, and become an integral part of military operations. Much has been learned in a century of flight, including the importance of aeromedical factors on the safety of flight.


Entry and Fusion of Emerging Paramyxoviruses


title: Network Meta‐Analysis Comparing the Efficacy of Therapeutic Treatments for Bronchiolitis in Children

text: BACKGROUND: This study aims to compare placebo (PBO) and 7 therapeutic regimens—namely, bronchodilator agents (BAs), hypertonic saline (HS), BA ± HS, corticosteroids (CS), epinephrine (EP), EP ± CS, and EP ± HS—to determine the optimal bronchiolitis treatment. METHODS: We plotted networks using the curative outcome of several studies and specified the relations among the experiments by using mean difference, standardized mean difference, and corresponding 95% credible interval. The surface under the cumulative ranking curve (SUCRA) was used to separately rank each therapy on clinical severity score (CSS) and length of hospital stay (LHS). RESULTS: This network meta‐analysis included 40 articles from 1995 to 2016 concerning the treatment of bronchiolitis in children. All 7 therapeutic regimens displayed no significant difference to PBO with regard to CSS in our study. Among the 7 therapies, BA performed better than CS. As for LHS, EP and EP ± HS had an advantage over PBO. Moreover, EP and EP ± HS were also more efficient than BA. The SUCRA results showed that EP ± CS is most effective, and EP ± HS is second most effective with regard to CSS. With regard to LHS, EP ± HS ranked first, EP ± CS ranked second, and EP ranked third. CONCLUSIONS: We recommend EP ± CS and EP ± HS as the first choice for bronchiolitis treatment in children because of their outstanding performance with regard to CSS and LHS.


title: Successful containment of Covid‐19 outbreak in a large maternity and perinatal center while continuing clinical service

text: With increasing number of SARS‐CoV‐2 infections and COVID‐19 patients to be taken care of by the health system, more and more health workers become affected by the disease. It has been reported that right from the beginning of the outbreak in Lombardy up to 20% of the doctors and nurses became infected. Under these circumstances, the regular operation of health institutions already suffering from a shortage of staff becomes difficult. This has led to complete or partial shutdowns of hospitals, either due to a lack of uninfected personnel or because of uncontrollable chains of infection endangering patients. In one of the largest university perinatal center in Bavaria with more than 3000 births per year, an outbreak of COVID‐19 occurred in March 2020, affecting 36 staff members, including doctors, nurses, and midwives. Here, we describe the outbreak and present the measures contributing to the successful containment of the outbreak within three weeks. At the same time, clinical services could be maintained, however, not without deployment of personnel exposed to employees infected with SARS‐CoV‐2. Apart from massive testing of personnel in pre‐defined phases and increased hygiene measures, including a general obligation to wear surgical face masks, we identified the need to monitor cases of illness across all groups of employees, to ensure social distancing within personnel and to evaluate contacts of clinical personnel outside of the hospital environment, in order to be able to interpret chains of infections and to disrupt them. Overall, only a bundle of measures is needed to contain such an outbreak.


title: Energy performance of independent air dehumidification systems with energy recovery measures

text: Independent air dehumidification provides an attractive alternative to traditional coupled air dehumidification with reduced energy use, better humidity control and indoor air quality. According to this concept, latent load is treated by an independent system and the sensible load is treated by chilled-ceiling panels. In this work, four independent air dehumidification systems with energy recovery strategies are proposed. They are as follows: system 1, mechanical dehumidification with heat pump; system 2, mechanical dehumidification with sensible heat exchanger; system 3, mechanical dehumidification with membrane-based total heat exchanger; and system 4: a heat pump incorporating an active desiccant wheel and evaporative cooler. They are compared with a mechanical dehumidification system with no heat recovery. Hour-by-hour energy analysis is performed on the systems proposed. The results show that the system of mechanical dehumidification with membrane total heat recovery (system 3) consumes the least primary energy. However, since, the systems employ energy recovery measures, the energy savings for the four systems are in the same order, around 4.40×10(6) kJ per person.


title: Epiretinal Membrane Detection at the Ophthalmologist Level using Deep Learning of Optical Coherence Tomography

text: Purpose: Previous deep learning studies on optical coherence tomography (OCT) mainly focused on diabetic retinopathy and age-related macular degeneration. We proposed a deep learning model that can identify epiretinal membrane (ERM) in OCT with ophthalmologist-level performance. Design: Cross-sectional study. Participants: A total of 3,618 central fovea cross section OCT images from 1,475 eyes of 964 patients. Methods: We retrospectively collected 7,652 OCT images from 1,197 patients. From these images, 2,171 were normal and 1,447 were ERM OCT. A total of 3,141 OCT images was used as training dataset and 477 images as testing dataset. DL algorithm was used to train the interpretation model. Diagnostic results by four board-certified non-retinal specialized ophthalmologists on the testing dataset were compared with those generated by the DL model. Main Outcome Measures: We calculated for the derived DL model the following characteristics: sensitivity, specificity, F1 score and area under curve (AUC) of the receiver operating characteristic (ROC) curve. These were calculated according to the gold standard results which were parallel diagnoses of the retinal specialist. Performance of the DL model was finally compared with that of non-retinal specialized ophthalmologists. Results: Regarding the diagnosis of ERM in OCT images, the trained DL model had the following characteristics in performance: sensitivity: 98.7%, specificity: 98.0%, and F1 score: 0.945. The accuracy on the training dataset was 99.7% (95% CI: 99.4 - 99.9%), and for the testing dataset, diagnostic accuracy was 98.1% (95% CI: 96.5 - 99.1%). AUC of the ROC curve was 0.999. The DL model slightly outperformed the average non-retinal specialized ophthalmologists. Conclusions: An ophthalmologist-level DL model was built here to accurately identify ERM in OCT images. The performance of the model was slightly better than the average non-retinal specialized ophthalmologists. The derived model may play a role to assist clinicians to promote the efficiency and safety of healthcare in the future.


title: TNF-α priming effect on polymorphonuclear leukocyte reactive oxygen species generation and adhesion molecule expression in hemodialyzed patients

text: INTRODUCTION: The study aimed to assess reactive oxygen species generation and the expressions of some surface antigens on polymorphonuclear leukocytes (PMNs) in patients on regular hemodialysis (HD) treatment. MATERIALS AND METHODS: The respiratory burst of PMNs was determined with luminol-dependent chemiluminescence (CL) in resting cells and following N-formyl-methionyl-leucyl-phenylalanine (fMLP), phorbol 12-myristate 13-acetate (PMA), or opsonized zymosan (OZ) stimulation and expressed in arbitrary CL units times assay-time (aU × min). The expressions of CD11b/CD18, CD10, and CD13 receptors were determined with flow cytometry. RESULTS: Basal PMN CL was increased in HD patients to up to 1285 ± 129 aU × min compared with 895 ± 88 aU × min in healthy controls (p < 0.05). The CL of unprimed PMNs increased after fMLP stimulation from 3085 ± 746 to 4529 ± 808 aU × min, and after OZ stimulation from 12945 ± 1296 to 14678 ± 1355 aU × min. PMA-stimulated CL of PMNs was similar to control values. The oxidative burst in PMNs from HD patients and healthy controls was similar in response to TNF-α alone. The CL of TNF-α-primed PMNs in HD patients was significantly lower than CL measured in healthy controls (p < 0.05). The expressions of CD10 and CD13 metalloproteinase receptors were also increased (p < 0.05). Although CD11b expression was significantly increased at rest and after fMLP stimulation, the expression of another β-integrin heterodimer compound, CD18, was not increased. CONCLUSIONS: These results provide evidence that TNF-α priming of PMNs is down-regulated in HD patients despite constitutive up-regulation of resting cytotoxicity and enhanced expression of adhesion and metalloproteinase receptors.


title: First report on fatal myocarditis associated with adenovirus infection in Cuba

text: Myocarditis is caused frequently by viral infections of the myocardium. In the past, enteroviruses (EV) were considered the most common cause of myocarditis in all age groups. Other viruses that cause myocarditis are adenovirus and influenza viruses. Parvovirus B19 infection is associated sometimes with myocarditis. Members of the Herpesviridae family, cytomegalovirus (CMV), and human herpesvirus 6 (HHV‐6) have been associated occasionally with myocarditis. During an atypical outbreak of acute febrile syndrome, eight children, with ages from 5 months to 15 years, died in cardiogenic shock due to myocarditis in July–August 2005, in the city of Havana, Cuba. Nested polymerase chain reaction (nPCR) and nested reverse transcription‐PCR (nRT‐PCR) were carried out on fresh heart muscle and lung tissue to analyze the genomic sequences of adenovirus, CMV, HHV‐6, herpes simplex virus, Epstein–Barr virus (EBV), varizella zoster virus, influenza virus A, B, C, respiratory syncytial virus (RSV) A and B, parainfluenza viruses, rhinoviruses, coronavirus, flaviruses and enteroviruses. Evidence was for the presence of the adenovirus genome in 6 (75%) of the children. Phylogenetic analyses of a conserved hexon gene fragment in four cases showed serotype 5 as the causal agent. No others viruses were detected. Histological examination was undertaken to detect myocardial inflammation. After exclusion of other possible causes of death, the results indicated that viral myocarditis was the cause of death in patients with adenovirus infection. J. Med. Virol. 80:1756–1761, 2008. © 2008 Wiley‐Liss, Inc.


title: Best interests versus resource allocation: could COVID-19 cloud decision-making for the cognitively impaired?

text: The COVID-19 pandemic is putting the NHS under unprecedented pressure, requiring clinicians to make uncomfortable decisions they would not ordinarily face. These decisions revolve primarily around intensive care and whether a patient should undergo invasive ventilation. Certain vulnerable populations have featured in the media as falling victim to an increasingly utilitarian response to the pandemic—primarily those of advanced years or with serious existing health conditions. Another vulnerable population potentially at risk is those who lack the capacity to make their own care decisions. Owing to the pandemic, there are increased practical and normative challenges to following the requirements of the Mental Capacity Act 2005. Both capacity assessments and best interests decisions may prove more difficult in the current situation. This may create a more paternalistic situation in decisions about the care of the cognitively impaired which is at risk of taking on a utilitarian focus. We look to these issues and consider whether there is a risk of patients who lack capacity to make their own care decisions being short-changed.


title: Development of a luciferase-based biosensor to assess enterovirus 71 3C protease activity in living cells

text: Enterovirus 71 (EV71) is a major pathogen of hand, foot, and mouth disease (HFMD). To date, no antiviral drug has been approved to treat EV71 infection. Due to the essential role that EV71 3 C protease (3C(pro)) plays in the viral life cycle, it is generally considered as a highly appealing target for antiviral drug development. In this study, we present a transgene-encoded biosensor that can accurately, sensitively and quantitatively report the proteolytic activity of EV71 3C(pro). This biosensor is based on the catalyzed activity of a pro–interleukin (IL)-1β-enterovirus 3C(pro) cleavage site-Gaussia Luciferase (GLuc) fusion protein that we named i-3CS-GLuc. GLuc enzyme is inactive in the fusion protein because of aggregation caused by pro–IL-1β. However, the 3C(pro) of EV71 and other enteroviruses, such as coxsackievirus A9 (CVA9), coxsackievirus B3 (CVB3), and poliovirus can recognize and process the canonical enterovirus 3C(pro) cleavage site between pro–IL-1β and GLuc, thereby releasing and activating GLuc and resulting in increased luciferase activity. The high sensitivity, ease of use, and applicability as a transgene in cell-based assays of i-3CS-GLuc biosensor make it a powerful tool for studying viral protease proteolytic events in living cells and for achieving high-throughput screening of antiviral agents.


Postdigital Feminism and Cultural Visual Regimes: Covid-19 at Women’s Only University in the Gulf


title: Réponse aux maladies à coronavirus 2019 (COVID-19): faits marquants de l’innovation et des percées scientifique et technologique au Ghana

text: Abstract While more attention has been placed on scientific innovativeness and breakthroughs in the advanced countries’ attempt to contain the spread and develop vaccines for the Coronavirus Diseases 2019 (COVID-19), little attention has been paid to the few but significant innovations being achieved in some African countries. This is understandable because the scientific capacity and research infrastructure of most African countries are deficient and weak compared to other regions of the world. Nevertheless, the African country of Ghana, despite its acute healthcare and scientific infrastructure deficit, is achieving some innovational and scientific breakthrough in the COVID-19 fight. Ghanaian scientist was among the first in Africa to successfully sequenced the genome of the novel coronavirus (SARS-CoV-2). The country’s laboratory leading the fight has also introduced some innovative testing methods allowing the country to test a far greater scale per million than the rest of Africa. Besides, drones are being used to deliver samples to the laboratory centers for testing. Local scientists and developers have also developed rapid diagnostic test kits, ventilators, and solar-powered handwashing machines. This paper highlights Ghana’s innovativeness, scientific, and technological breakthroughs achieved so far in the fight against the pandemic.


title: Clinical manifestations and outcomes of respiratory syncytial virus infection in adult hospitalized patients

text: Abstract Background Respiratory syncytial virus (RSV) is an important virus found in adult hospitalized patients. Objectives To study the clinical outcomes of hospitalized patients aged ≥ 15 years and diagnosed with RSV infection. Study design Both retrospective and prospective cohort studies were conducted at a university hospital between May 2014 and December 2015. Results: RSV was detected in 86 of 1562(5.5%) adult hospitalized patients suspected of respiratory viral infection. Sixty-nine patients were included in the study. RSV was detected by RT-PCR (82.6%), IFA (10.1%), and both RT-PCR and IFA (7.3%). Most patients (87.0%) were aged ≥ 50 years. Cardiovascular diseases, pulmonary diseases, immunocompromised hosts, and diabetes were the major comorbidities. The common manifestations were cough (92.8%), dyspnea (91.3%), sputum production (87.0%), tachypnea (75.4%), wheezing (73.9%), and fever (71.0%). Fifty- five patients (79.7%) were diagnosed with pneumonia. Hypoxemia (SpO2 ≤ 92%) was found in 53.6% patients. Twenty-five of 69(36.2%) patients developed respiratory failure and required ventilatory support. Cardiovascular complications were found in 24.6% of patients. Congestive heart failure, acute myocardial infarction (MI), new atrial fibrillation, and supraventricular tachycardia were found in 9(13.0%), 7(10.1%), 4(5.8%), and 3(4.3%) of 69 patients, respectively. Overall mortality was 15.9%. Pneumonia (81.8%) and acute MI (18.2%) were the major causes of death. Conclusions Most adult hospitalized patients with RSV infection were of advanced age and had comorbidities. Cardiopulmonary complications were the major causes of death. Management and prevention of RSV infection in these vulnerable groups are necessary.


title: Polymerase chain reaction for probe synthesis and for direct amplification in detection of bovine coronavirus

text: Abstract The polymerase chain reaction (PCR) was used to synthesize ds and ss probes for the detection of bovine coronavirus (BCV) using recombinant plasmids as template molecules. The ds probes detected a minimum of about 2 × 105 viral genomes after exposure for 1 h, a detection limit similar to nick-translated probes after exposure of the films for 60 h. More than 8 h exposure to blots probed with these ds probes resulted in complete darkening of the film. The ss probes, synthesized by asymmetric PCR on linearized plasmids, permitted the detection of 5 × 104 genomes, which equalled the capacity of random-primed probes. Prolonged exposure did not increase the background as in case of ds PCR-probed blots. Probes, synthesized by asymmetric PCR and random-priming were labeled to similar specific activities and were better in terms of sensitivity and detectability as opposed to nick-translated probes. However, the specificity of detection with ss probes as to random primed probes was increased further. About 10 viral genomes, after fragment-specific amplification by PCR, were detected by agarose-gel analysis. PCR-probe synthesis was simple, highly reproducible, and allowed the synthesis of probes for specific fragments.


title: Positive externalities of an epidemic: The case of the coronavirus (COVID‐19) in China

text: COVID-19 have undisputedly dented global economies as shown by indicators from the various stock markets. However, amidst these woes, China's quest to contain the spread of the pandemic and ultimately find its cure has resulted in some positive spillovers worth discussing. This commentary focuses on the positive effects that emanated from public policies and strategies enacted in China to control and ultimately to eradicate COVID-19. Specifically, these policies gave more room for testing futuristic technologies, reduce the spread of false information and pollution and provided social safety nets for affected individuals and firms. This article is protected by copyright. All rights reserved.


title: Structural insights into the Middle East respiratory syndrome coronavirus 4a protein and its dsRNA binding mechanism

text: Middle East respiratory syndrome coronavirus (MERS-CoV) has evolved to navigate through the sophisticated network of a host’s immune system. The immune evasion mechanism including type 1 interferon and protein kinase R-mediated antiviral stress responses has been recently attributed to the involvement of MERS-CoV protein 4a (p4a) that masks the viral dsRNA. However, the structural mechanism of how p4a recognizes and establishes contacts with dsRNA is not well explained. In this study, we report a dynamic mechanism deployed by p4a to engage the viral dsRNA and make it unavailable to the host immune system. Multiple variants of p4a-dsRNA were created and investigated through extensive molecular dynamics procedures to highlight crucial interfacial residues that may be used as potential pharmacophores for future drug development. The structural analysis revealed that p4a exhibits a typical αβββα fold structure, as found in other dsRNA-binding proteins. The α1 helix and the β1-β2 loop play a crucial role in recognizing and establishing contacts with the minor grooves of dsRNA. Further, mutational and binding free energy analyses suggested that in addition to K63 and K67, two other residues, K27 and W45, might also be crucial for p4a-dsRNA stability.


title: Ebola and Learning Lessons from Moral Failures: Who Cares about Ethics?

text: The exercise of identifying lessons in the aftermath of a major public health emergency is of immense importance for the improvement of global public health emergency preparedness and response. Despite the persistence of the Ebola Virus Disease (EVD) outbreak in West Africa, it seems that the Ebola ‘lessons learned’ exercise is now in full swing. On our assessment, a significant shortcoming plagues recent articulations of lessons learned, particularly among those emerging from organizational reflections. In this article we argue that, despite not being recognized as such, the vast majority of lessons proffered in this literature should be understood as ethical lessons stemming from moral failures, and that any improvements in future global public health emergency preparedness and response are in large part dependent on acknowledging this fact and adjusting priorities, policies and practices accordingly such that they align with values that better ensure these moral failures are not repeated and that new moral failures do not arise. We cannot continue to fiddle at the margins without critically reflecting on our repeated moral failings and committing ourselves to a set of values that engenders an approach to global public health emergencies that embodies a sense of solidarity and global justice.


title: GCN5 inhibits XBP-1S-mediated transcription by antagonizing PCAF action

text: Cellular unfolded protein response (UPR) is induced when endoplasmic reticulum (ER) is under stress. XBP-1S, the active isoform of X-box binding protein 1 (XBP-1), is a key regulator of UPR. Previously, we showed that a histone acetyltransferase (HAT), p300/CBP-associated factor (PCAF), binds to XBP-1S and functions as an activator of XBP-1S. Here, we identify general control nonderepressible 5 (GCN5), a HAT with 73% identity to PCAF, as a novel XBP-1S regulator. Both PCAF and GCN5 bind to the same domain of XBP-1S. Surprisingly, GCN5 potently blocks the XBP-1S-mediated transcription, including cellular UPR genes and latent membrane protein 1 of Epstein-Barr virus. Unlike PCAF, GCN5 acetylates XBP-1S and enhances nuclear retention and protein stability of XBP-1S. However, such GCN5-mediated acetylation of XBP-1S shows no effects on XBP-1S activity. In addition, the HAT activity of GCN5 is not required for repression of XBP-1S target genes. We further demonstrate that GCN5 inhibits XBP-1S-mediated transcription by disrupting the PCAF-XBP-1S interaction and preventing the recruitment of XBP-1S to its target genes. Taken together, our results represent the first work demonstrating that GCN5 and PCAF exhibit different functions and antagonistically regulate the XBP-1S-mediated transcription.


title: The impact of crisis events and macroeconomic activity on Taiwan's international inbound tourism demand

text: The number of inbound tourism arrivals directly impacts the tourism industry and the government agency investments therein. Therefore, policymakers need to improve their understanding of how crisis events affect the demand for inbound tourism. From the first quarter of 1996 to the second quarter of 2006, Taiwan experienced four major disasters at approximately two-year intervals. These disasters included the Asian financial crisis in 1997, the 21st September 1999 earthquake, the 11th September 2001 attacks in the United States, and the outbreak of SARS in 2003. This paper examines the impact of crisis events on the demand for tourism in order to establish a better understanding of changes and trends in the demand for international tourism. This paper uses the auto-regression distributed lag model by Pesaran, Shin, and Smith [Pesaran, M. H., Shin, Y., & Smith, R. J. (2001). Bounds testing approaches to the analysis of long-run relationship. Journal of Applied Econometrics, 16, 289–326] to examine the negative impact of these disasters on the demand for inbound tourism. This paper also explores the influence of variables, such as foreign exchange rates, incomes, relative prices, and transportation costs, on the dynamics of the demand for inbound tourism. This paper finds that a long-term equilibrium exists among all variables, indicating that macroeconomic variables may be used to determine the rise or fall of the number of inbound tourism arrivals. Income and foreign exchange rates are both significant explanatory variables. In terms of incurred losses, the number of inbound tourism arrivals suffered the greatest decline during the outbreak of severe acute respiratory syndrome (SARS), followed by the 21st September 1999 earthquake and the 11th September 2001 attacks. The impact of the Asian financial crisis was relatively mild. This paper finds that any impact on safety, whether domestic or international, negatively affects tourism demand. The impact of financial crises on tourism demand is less significant. Ensuring the safety and health of tourists is the key to maintain demand for inbound tourism.


title: Cellular cholesterol is required for porcine nidovirus infection

text: Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine epidemic diarrhea virus (PEDV) are porcine nidoviruses that are considered emerging and re-emerging viral pathogens of pigs that pose a significant economic threat to the global pork industry. Although cholesterol is known to affect the replication of a broad range of viruses in vitro, its significance and role in porcine nidovirus infection remains to be elucidated. Therefore, the present study was conducted to determine whether cellular or/and viral cholesterol levels play a role in porcine nidovirus infection. Our results showed that depletion of cellular cholesterol by treating cells with methyl-β-cyclodextrin (MβCD) dose-dependently suppressed the replication of both nidoviruses. Conversely, cholesterol depletion from the viral envelope had no inhibitory effect on porcine nidovirus production. The addition of exogenous cholesterol to MβCD-treated cells moderately restored the infectivity of porcine nidoviruses, indicating that the presence of cholesterol in the target cell membrane is critical for viral replication. The antiviral activity of MβCD on porcine nidovirus infection was found to be predominantly exerted when used as a treatment pre-infection or prior to the viral entry process. Furthermore, pharmacological sequestration of cellular cholesterol efficiently blocked both virus attachment and internalization and, accordingly, markedly affected subsequent post-entry steps of the replication cycle, including viral RNA and protein biosynthesis and progeny virus production. Taken together, our data indicate that cell membrane cholesterol is required for porcine nidovirus entry into cells, and pharmacological drugs that hamper cholesterol-dependent virus entry may have antiviral potential against porcine nidoviruses.


Multiplex real time PCRs for detection of influenza A subtypes including H5N1


Some research advances of immune mechanism during infection in China


title: Viruses Associated With Acute Respiratory Infections and Influenza-like Illness Among Outpatients From the Influenza Incidence Surveillance Project, 2010–2011

text: BACKGROUND: The Influenza Incidence Surveillance Project (IISP) monitored outpatient acute respiratory infection (ARI; defined as the presence of ≥2 respiratory symptoms not meeting ILI criteria) and influenza-like illness (ILI) to determine the incidence and contribution of associated viral etiologies. METHODS: From August 2010 through July 2011, 57 outpatient healthcare providers in 12 US sites reported weekly the number of visits for ILI and ARI and collected respiratory specimens on a subset for viral testing. The incidence was estimated using the number of patients in the practice as the denominator, and the virus-specific incidence of clinic visits was extrapolated from the proportion of patients testing positive. RESULTS: The age-adjusted cumulative incidence of outpatient visits for ARI and ILI combined was 95/1000 persons, with a viral etiology identified in 58% of specimens. Most frequently detected were rhinoviruses/enteroviruses (RV/EV) (21%) and influenza viruses (21%); the resulting extrapolated incidence of outpatient visits was 20 and 19/1000 persons respectively. The incidence of influenza virus-associated clinic visits was highest among patients aged 2–17 years, whereas other viruses had varied patterns among age groups. CONCLUSIONS: The IISP provides a unique opportunity to estimate the outpatient respiratory illness burden by etiology. Influenza virus infection and RV/EV infection(s) represent a substantial burden of respiratory disease in the US outpatient setting, particularly among children.


title: Vaccines of the future

text: This report has been prepared by Bear, Stearns & Co. Inc., Bear, Stearns International Limited or Bear Stearns Asia Limited (together with their affiliates, 'Bear Stearns'), as indicated on the cover page hereof. This report has been adopted and approved for distribution in the United States by Bear, Stearns & Co. Inc. If you are a recipient of this publication in the United States, orders in any securities referred to herein should be placed with Bear, Stearns & Co. Inc. This report has been approved for publication in the United Kingdom by Bear, Stearns International Limited, which is regulated by the United Kingdom Financial Services Authority. Private Customers in the U.K. should contact their Bear, Stearns International Limited representatives about the investments concerned. This report is distributed in Hong Kong by Bear Stearns Asia Limited, which is regulated by the Securities and Futures Commission of Hong Kong. Additional information is available upon request. Bear Stearns and its employees, officers, and directors deal as principal in transactions involving the securities referred to herein (or options or other instruments related thereto), including transactions contrary to any recommendations contained herein. Bear Stearns and its employees may also have engaged in transactions with issuers identified herein. This publication does not constitute an offer or solicitation of any transaction in any securities referred to herein. Any recommendation contained herein may not be suitable for all investors. Although the information contained in the subject report has been obtained from sources we believe to be reliable, its accuracy and completeness cannot be guaranteed. This publication and any recommendation contained herein speak only as of the date hereof and are subject to change without notice. Bear Stearns and its affiliated companies and employees shall have no obligation to update or amend any information contained herein. This publication is being furnished to you for informational purposes only and on the condition that it will not form a primary basis for any investment decision. Each investor must make its own determination of the appropriateness of an investment in any securities referred to herein based on the legal, tax, and accounting considerations applicable to such investor and its own investment strategy. By virtue of this publication, none of Bear Stearns or any of its employees shall be responsible for any investment decision. This report may not be reproduced, distributed, or published without the prior consent of Bear Stearns. © 2003. All rights reserved by Bear Stearns. This report may discuss numerous securities, some of which may not be qualified for sale in certain states and may therefore not be offered to investors in such states. NOTE TO ACCOUNT EXECUTIVES: For securities that are not listed on the NYSE, AMEX, or Nasdaq National Market System, check the Compliance page of the Bear Stearns Intranet site for State Blue Sky data prior to soliciting or accepting orders from clients. Outperform (O) - Stock is projected to outperform analyst's industry coverage universe over the next 12 months. Peer Perform (P) - Stock is projected to perform approximately in line with analyst's industry coverage universe over the next 12 months. Underperform (U) - Stock is projected to underperform analyst's industry coverage universe over the next 12 months. Market Overweight (MO) - Expect the industry to perform better than the primary market index for the region over the next 12 months. Market Weight (MW) - Expect the industry to perform approximately in line with the primary market index for the region over the next 12 months. Market Underweight (MU) - Expect the industry to underperform the primary market index for the region over the next 12 months. (%Rated companies / %Banking client in the last 12 months). Outperform (Buy): 34.3 / 19.3. Peer Perform (Neutral): 47.4 / 12.8. Underperform (Sell): 18.2 / 8.2. The costs and expenses of Equity Research, including the compensation of the analyst(s) that prepared this report, are paid out of the Firm's total revenues, a portion of which is generated through investment banking activities. Wyeth WYE Peer Perform $42.85. Merck MRK Underperform $50.32. MedImmune MEDI Outperform $34.70. Aventis (AVE) Peer Perform $49.00. GlaxoSmithkline GSK Peer perform $38.83. GenVec (GNVC) NR $2.35. Avant Immunotherapeutics (AVAN) NR $2.35. VaxGen (VXGN) NR $4.10. Chiron (CHIR) NR $50.81. Acambis (ACAM) NR $56.72. Crucell NV (CRXL) NR $3.70. ID BioMedical (IDBE) NR $13.45. Dor BioPharma (DOR) NR $0.71. Vical (VICL) NR - $5.30. Targeted Genetics (TGEN) NR $1.93. Bavarian Nordic A/S (BAVA.CP) NR. Therion Biologics NR - Private. DynPort Vaccine Company LLC NR - private. AlphaVax NR - private. BioPort Corporation NR - private. Avecia NR - private. Regulation A/C The Research Analyst(s) who prepared the document / email hereby certify that the views expressed in this document / email accurately reflect the analyst(s) personal views about the subject companies and their securities. The Research Analyst(s) also certify that the Analyst(s) have not been, are not, and will not be receiving direct or indirect compensation for expressing the specific recommendation(s) or view(s) in this report.


title: Coronavirus Disease 2019 and Stroke: Clinical Manifestations and Pathophysiological Insights

text: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health threat. Some COVID-19 patients have exhibited widespread neurological manifestations including stroke. Acute ischemic stroke, intracerebral hemorrhage, and cerebral venous sinus thrombosis have been reported in patients with COVID-19. COVID-19-associated coagulopathy is increasingly recognized as a result of acute infection and is likely caused by inflammation, including inflammatory cytokine storm. Recent studies suggest axonal transport of SARS-CoV-2 to the brain can occur via the cribriform plate adjacent to the olfactory bulb that may lead to symptomatic anosmia. The internalization of SARS-CoV-2 is mediated by the binding of the spike glycoprotein of the virus to the angiotensin-converting enzyme 2 (ACE2) on cellular membranes. ACE2 is expressed in several tissues including lung alveolar cells, gastrointestinal tissue, and brain. The aim of this review is to provide insights into the pathophysiological stroke mechanisms in COVID-19 patients. SARS-CoV-2 can down-regulate ACE2 and, in turn, over-activate the classical renin-angiotensin system (RAS) axis and decrease the activation of the alternative RAS pathway in the brain. The consequent imbalance in vasodilation, neuroinflammation, oxidative stress, and thrombotic response may contribute to the pathophysiology of stroke during SARS-CoV-2 infection.


title: ast and current biological factors affecting malaria in the low transmission setting of Botswana: A review

text: Malaria continues to be one of the top infectious agents contributing to morbidity and mortality in sub-Saharan Africa. Annually, Botswana accounts only for a small proportion of cases (<<1%). Despite significantly reduced incidence rate, the country still experiences sporadic outbreaks that hamper the goal of malaria elimination. This review evaluated previous and current biological factors that impact malaria in Botswana, specifically focussing on the vectors, the parasite and the host. This was accomplished via a literature review evaluating these variables in Botswana. Current literature suggests that Anopheles arabiensis is the main malaria vector in the country. Several other potential vectors have been found widely distributed throughout Botswana in high numbers, yet remain largely unstudied with regards to their contribution to the country's malaria burden. We also report the most up to date list of all Anopheles species that have been found in Botswana. Plasmodium falciparum is responsible for the vast majority of symptomatic malaria in the country and some drug resistance markers have been documented for this species. Plasmodium vivax has been reported in asymptomatic subjects, even though a large proportion of the Botswana population appears to be Duffy antigen negative. Very little is known about the true distribution of P. vivax and no point of care testing infrastructure for this species exists in Botswana, making it difficult to tailor treatment to address possible recrudescence or relapse. Due to a genetically diverse population with a substantial Khoisan contribution into the Bantu genetic background, several phenotypes that potentially impact prevalence and severity of malaria exist within the country. These include sickle cell trait, Glucose-6-Phosphate Dehydrogenase deficiency, and Duffy negativity. This review highlights the information that currently exists on malaria in Botswana. It also postulates that a comprehensive understanding of these aforementioned biological factors may help to explain malaria persistence in Botswana.


title: Modification of PCV-2 virulence by substitution of the genogroup motif of the capsid protein

text: Porcine circovirus type 2 (PCV-2) is the causal agent of the post-weaning multisystemic wasting syndrome (PMWS). PCV-2 are small single-stranded circular DNA viruses clustered into two main genogroups: PCV-2a and PCV-2b. Each genogroup present a specific highly-conserved motif of six amino acids (between amino acids 86 and 91) in the PCV-2 capsid protein. The aim of this study was to verify whether the motif located in the capsid protein and specific to each PCV-2 genogroup contributes to virulence. Two parental DNA clones, PCV-2a and PCV-2b, were constructed as well as two mutants DNA clones, PCV-2a/motif 2b and PCV-2b/motif 2a by exchanging the capsid motif of each genogroup. The four DNA clones were characterized in vitro as well as in vivo. Cells transfected by the four DNA clones produced infectious viruses. In specific-pathogen-free piglets transfected by the four infectious DNA clones, PCV-2b/motif 2a virulence was not attenuated while the PCV-2a/motif 2b virulence was drastically reduced compared to their parent virulence. These results suggest that the amino acids between positions 86 and 91 of the capsid protein are determinant for the virulence of isolates. However, the environment of this motif seems also involved.


title: Induction of Th1 type response by DNA vaccinations with N, M, and E genes against SARS-CoV in mice

text: Abstract Vaccination against the SARS-CoV infection is an attractive means to control the spread of viruses in public. In this study, we employed a DNA vaccine technology with the levamisole, our newly discovered chemical adjuvant, to generate Th1 type of response. To avoid the enhancement antibody issue, genes encoding the nucleocapsid, membrane, and envelope protein of SARS-CoV were cloned and their expressions in mammalian cells were determined. After the intramuscular introduction into animals, we observed that the constructs of the E, M, and N genes could induce high levels of specific antibodies, T cell proliferations, IFN-γ, DTH responses, and in vivo cytotoxic T cells activities specifically against SARS-CoV antigens. The highest immune responses were generated by the construct encoding the nucleocapsid protein. The results suggest that the N, M, and E genes could be used as the targets to prevent SARS-CoV infection in the DNA vaccine development.


On the fallibility of simulation models in informing pandemic responses – Authors' reply


title: In vitro inhibition of feline coronavirus replication by small interfering RNAs

text: Abstract Infection with virulent biotypes of feline coronavirus (FCoV) can result in the development of feline infectious peritonitis (FIP), a typically fatal immune mediated disease for which there is currently no effective antiviral treatment. In this study we demonstrate the ability of small interfering RNA (siRNA) mediated RNA interference (RNAi) to inhibit the replication of virulent FCoV strain FIPV WSU 79-1146 in an immortalised feline cell line. A panel of eight synthetic siRNAs targeting four different regions of the FCoV genome were tested for antiviral effects. Efficacy was determined by qRT-PCR of intracellular viral genomic and messenger RNA, TCID50 infectivity assay of extracellular virus, and direct IFA for viral protein expression. All siRNAs demonstrated an inhibitory effect on viral replication in vitro. The two most effective siRNAs, targeting the untranslated 5′ leader sequence (L2) and the nucleocapsid gene (N1), resulted in a >95% reduction in extracellular viral titre. Further characterisation of these two siRNAs demonstrated their efficacy when used at low concentrations and in cells challenged with high viral loads. Taken together these findings provide important information for the potential therapeutic application of RNAi in treating FIP.


Right Ventricular Dilation in Hospitalized Patients with COVID-19 Infection: Authors’ Reply


title: Neurological Impact of Coronavirus Disease (COVID-19): Practical Considerations for the Neuroscience Community

text: Abstract Background The coronavirus disease of 2019 (COVID-19) that is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently been designated a pandemic by the World Health Organization, affecting 2.7 million individuals globally as of April 25, 2020 with over 187,000 deaths. A growing body of evidence supports central nervous system (CNS) involvement. Methods We conducted a review of the literature for articles concerning COVID-19 pathophysiology, neurological manifestations, and neuroscience provider recommendations and guidelines. Results CNS manifestations range from vague non-focal complaints to severe neurologic impairment associated with encephalitis. It is unclear whether neurological dysfunction is due to direct viral injury or systemic disease. The virus may affect brainstem pathways that lead to indirect respiratory dysfunction in addition to direct pulmonary injury. Necessary adaptations in patient management, triage, and diagnosis are evolving in light of ongoing scientific and clinical findings. Conclusions This review consolidates the current body of literature regarding the neurological impact of coronaviruses, discusses the reported neurologic manifestations of COVID-19, and highlights recommendations for patient management. Specific recommendations pertaining to clinical practice for neurologists and neurosurgeons are provided.