title: Reflections on the COVID-19 Pandemic in the USA: Will We Better Prepared Next Time?

text: Abstract The United States (US) spends more on healthcare than any other country with little evidence of better, or even comparable, outcomes. We reflect on the US and the COVID-19 pandemic and focus on cultural, economic and structural barriers that threaten both current and future responses to infectious diseases emergencies. These include the US healthcare delivery model, the defunding of public health, a scarcity of infectious diseases physicians, the market failure of vaccines and anti-infectives and the concept of American exceptionalism. Without institutionalizing the lessons learned, the US will be positioned to repeat the missteps of COVID-19 with the next pandemic.


title: Structure and Function of Angiotensin Converting Enzyme and Its Inhibitors

text: Abstract Angiotensin converting enzyme (ACE, EC 3.4.15.1) is a membrane-bound, zinc dependent dipeptidase that catalyzes the conversion of the decapeptide angiotensin I to the potent vasopressor octapeptide angiotensin II by removing the two C-terminal amino acids. ACE is well known to be a key part of the rennin-angiotensin system that regulates blood pressure. The inhibitors of ACE have the potency of treating hypertension. This article reviews the structure-function relationship of ACE as well as its gene polymorphism and inhibitor development. In particular, it has been found that the catalytic mechanisms of the two active sites of somatic ACE in the cleavage of angiotensin I and bradykin are different. Therefore, by specifically targeting the individual active sites of somatic ACE, it will likely offer a new way to develop novel ACE inhibitors with fewer side effects.


title: Functional Role of Dietary Intervention to Improve the Outcome of COVID-19: A Hypothesis of Work

text: Background: On the 31 December 2019, the World Health Organization (WHO) was informed of a cluster of cases of pneumonia of unknown origin detected in Wuhan City, Hubei Province, China. The infection spread first in China and then in the rest of the world, and on the 11th of March, the WHO declared that COVID-19 was a pandemic. Taking into consideration the mortality rate of COVID-19, about 5–7%, and the percentage of positive patients admitted to intensive care units being 9–11%, it should be mandatory to consider and take all necessary measures to contain the COVID-19 infection. Moreover, given the recent evidence in different hospitals suggesting IL-6 and TNF-α inhibitor drugs as a possible therapy for COVID-19, we aimed to highlight that a dietary intervention could be useful to prevent the infection and/or to ameliorate the outcomes during therapy. Considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a dietary regimen modification in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of patients, improving their outcomes.


title: Removal of carbon constituents from hospital solid waste incinerator fly ash by column flotation

text: Abstract Hospital solid waste incinerator (HSWI) fly ash contains a large number of carbon constituents including powder activated carbon and unburned carbon, which are the major source of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in fly ash. Therefore, the removal of carbon constituents could reduce PCDD/Fs in fly ash greatly. In this study, the effects of the main flotation parameters on the removal of carbon constituents were investigated, and the characteristics of the final product were evaluated. The results showed that loss on ignition (LOI) of fly ash increased from 11.1% to 31.6% during conditioning process. By optimizing the flotation parameters at slurry concentration 0.05kg/l, kerosene dosage 12kg/t, frother dosage 3kg/t and air flow rate 0.06m3/h, 92.7% of the carbon constituents were removed from the raw fly ash. Under these conditions, the froth product has LOI of 56.35% and calorific values of 12.5MJ/kg, LOI in the tailings was below 5%, and the total toxic equivalent (TEQ) of PCDD/Fs decreased from 5.61ng-TEQ/g in the raw fly ash to 1.47ng-TEQ/g in the tailings. The results show that column flotation is a potential technology for simultaneous separation of carbon constituents and PCDD/Fs from HSWI fly ash.


title: Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients

text: The discovery of angiotensin converting enzyme-2 (ACE-2) as the receptor for SARS- CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) has implicated the renin-angiotensin-aldosterone system in acute respiratory distress syndrome (ARDS) and respiratory failure in patients with coronavirus disease-19 (COVID-19). The angiotensin converting enzyme-1–angiotensin II–angiotensin AT(1) receptor pathway contributes to the pathophysiology of ARDS, whereas activation of the ACE-2–angiotensin(1-7)-angiotensin AT(2) receptor and the ACE-2–angiotensin(1-7)–Mas receptor pathways have been shown to be protective. Here we propose and discuss therapeutic considerations how to increase soluble ACE-2 in plasma in order for ACE-2 to capture and thereby inactivate SARS-CoV-2. This could be achieved by administering recombinant soluble ACE-2. We also discuss why and how ACEIs and ARBs provide cardiovascular, renal and also pulmonary protection in SARS-CoV-2- associated ARDS. Discontinuing these medications in COVID-19 patients may therefore potentially be harmful.


title: Confidence in managing human monkeypox cases in Asia: A cross-sectional survey among general practitioners in Indonesia

text: Abstract The current re-emergence of human monkeypox (HMPX) is a global concern for endemic and non-endemic countries, but healthcare workers in some regions, like Asia, have less experience with identifying and treating HMPX cases. This study aimed to assess the confidence and its predictors in HMPX case management among general practitioners (GPs), the frontline doctors in Indonesia, and to explore their perspectives on HMPX. Between May and July 2019, GPs in Indonesia completed an online-based survey. The questionnaire collected information on GPs’ confidence, perspective, sociodemographic, workplace and professional characteristics, exposure to HMPX information and knowledge on HMPX. A logistic regression analysis was employed to explore the explanatory variables influencing the confidence and the perspective. We included 395 GPs in our analysis (77.4% out of 510 responses received) of which 10.1% and 34.9% were classified having good confidence using an 80% and 70% cut-off for confidence score, respectively. In the adjusted analysis, receiving information about HMPX during medical training was the only variable significantly associated with good confidence (adjusted odds ratio 2.74, 95% confidence interval 1.57 to 4.78 and p < 0.001). Approximately 73.6% and 77.9% of GPs agreed that HMPX is an important infectious disease and it has potential to detrimentally impact the Indonesian economy, respectively. In addition, 88.8% of GPs suggested that the disease should be incorporated into the National Medical Curriculum of Indonesia. In conclusion, in case of HMPX outbreak, majority of the GPs in Indonesia seem to be less confident in diagnosing and treating cases, using their current knowledge, skills and their workplace facilities. Therefore, a systematic strategy to improve their confidence in managing HMPX is required.


title: Efficacy of various disinfectants against SARS coronavirus

text: Summary The recent severe acute respiratory syndrome (SARS) epidemic in Asia and Northern America led to broad use of various types of disinfectant in order to control the public spread of the highly contagious virus. However, only limited data were available to demonstrate their efficacy against SARS coronavirus (SARS-CoV). We therefore investigated eight disinfectants for their activity against SARS-CoV according to prEN 14476. Four hand rubs were tested at 30s (Sterillium, based on 45% iso-propanol, 30% n-propanol and 0.2% mecetronium etilsulphate; Sterillium Rub, based on 80% ethanol; Sterillium Gel, based on 85% ethanol; Sterillium Virugard, based on 95% ethanol). Three surface disinfectants were investigated at 0.5% for 30min and 60min (Mikrobac forte, based on benzalkonium chloride and laurylamine; Kohrsolin FF, based on benzalkonium chloride, glutaraldehyde and didecyldimonium chloride; Dismozon pur, based on magnesium monoperphthalate), and one instrument disinfectant was investigated at 4% for 15min, 3% for 30min and 2% for 60min [Korsolex basic, based on glutaraldehyde and (ethylenedioxy)dimethanol]. Three types of organic load were used: 0.3% albumin, 10% fetal calf serum, and 0.3% albumin with 0.3% sheep erythrocytes. Virus titres were determined by a quantitative test (endpoint titration) in 96-well microtitre plates. With all tested preparations, SARS-CoV was inactivated to below the limit of detection (reduction factor mostly ≥4), regardless of the type of organic load. In summary, SARS-CoV can be inactivated quite easily with many commonly used disinfectants.


title: Comparative transcriptome analysis reveals the role of p53 signalling pathway during red‐spotted grouper nervous necrosis virus infection in Lateolabrax japonicus brain cells

text: Nervous necrosis virus (NNV) is one of the fish pathogens that have caused mass mortalities of many marine and freshwater fishes in the world. To better comprehend the molecular immune mechanism of sea perch (Lateolabrax japonicus) against NNV infection, the comparative transcriptome analysis of red‐spotted grouper nervous necrosis virus (RGNNV)‐infected or mock‐infected L. japonicus brain (LJB) cells was performed via RNA sequencing technology. Here, 1,969 up‐regulated genes and 9,858 down‐regulated genes, which were widely implicated in immune response pathways, were identified. Furthermore, we confirmed that p53 signalling pathway was repressed at 48 hr post‐RGNNV infection, as indicated by up‐regulation of Mdm2 and down‐regulation of p53 and its downstream target genes, including Bax, Casp8 and CytC. Overexpression of L. japonicus p53 (Ljp53) significantly inhibited RGNNV replication and up‐regulated the expression of apoptosis‐related genes, whereas the down‐regulation caused by pifithrin‐α led to the opposite effect, suggesting Ljp53 might promote cell apoptosis to repress virus replication. Luciferase assay indicated that Ljp53 could enhance the promoter activities of zebrafish interferon (IFN)1, indicating that Ljp53 could exert its anti‐RGNNV activities by enforcing the type I IFN response. This study revealed the potential antiviral role of p53 during NNV infection.


title: The psychological distress and coping styles in the early stages of the 2019 coronavirus disease (COVID-19) epidemic in the general mainland Chinese population: A web-based survey

text: As the epidemic outbreak of 2019 coronavirus disease (COVID-19), general population may experience psychological distress. Evidence has suggested that negative coping styles may be related to subsequent mental illness. Therefore, we investigate the general population’s psychological distress and coping styles in the early stages of the COVID-19 outbreak. A cross-sectional battery of surveys was conducted from February 1–4, 2020. The Kessler 6 psychological distress scale, the simplified coping style questionnaire and a general information questionnaire were administered on-line to a convenience sample of 1599 in China. A multiple linear regression analysis was performed to identify the influence factors of psychological distress. General population’s psychological distress were significant differences based on age, marriage, epidemic contact characteristics, concern with media reports, and perceived impacts of the epidemic outbreak (all p <0.001) except gender (p = 0.316). The population with younger age (F = 102.04), unmarried (t = 15.28), with history of visiting Wuhan in the past month (t = -40.86), with history of epidemics occurring in the community (t = -10.25), more concern with media reports (F = 21.84), perceived more impacts of the epidemic outbreak (changes over living situations, F = 331.71; emotional control, F = 1863.07; epidemic-related dreams, F = 1642.78) and negative coping style (t = 37.41) had higher level of psychological distress. Multivariate analysis found that marriage, epidemic contact characteristics, perceived impacts of the epidemic and coping style were the influence factors of psychological distress (all p <0.001). Epidemic of COVID-19 caused high level of psychological distress. The general mainland Chinese population with unmarried, history of visiting Wuhan in the past month, perceived more impacts of the epidemic and negative coping style had higher level of psychological distress in the early stages of COVID-19 epidemic. Psychological interventions should be implemented early, especially for those general population with such characteristics.


title: Genomic analysis of codon usage shows influence of mutation pressure, natural selection, and host features on Senecavirus A evolution

text: Abstract Senecavirus A (SVA) infection was recently confirmed in pigs in Brazil, United States of America and Canada. To better understand the molecular characteristics of isolated SVA genomes, we first reported genome-wide comprehensive analyses of codon usage and various factors that have contribute to the molecular evolution in SVA. The effective number of codons (ENC) ranged from 54.51 to 55.54 with an average of 54.87 ± 0.285, which reveals a relatively stable nucleotide composition. We found that codon usage bias of the SVA was low. Mutational pressure acted as an increasingly dominant factor for the evolution of the virus compared with the natural selection. Notably, codon usage bias was also affected by the geographic distribution and isolated time. The first systemic analysis on the codon usage bias of the SVA provides important information for the understanding of the evolution of the SVA and has fundamental and theoretical benefits.


docid: eavcabvf

title: Implications of near-term mitigation on China's long-term energy transitions for aligning with the Paris goals

text: In the international community, there are many appeals to ratcheting up the current nationally determined contributions (NDCs), in order to narrow the 2030 global emissions gap with the Paris goals. Near-term mitigation has a direct impact on the required efforts beyond 2030 to control warming within 2 °C or 1.5 °C successfully. In this study, implications of near-term mitigation on China's long-term energy transitions until 2100 for aligning with the Paris goals, are quantified using a refined Global Change Assessment Model (GCAM) with six mitigation scenarios. Results show that intensifying near-term mitigation will alleviate China's transitional challenges during 2030–2050 and long-term reliance on carbon dioxide removal technologies (CDR). Each five-year earlier peaking of CO(2) allows almost a five-year later carbon neutrality of China's energy system. To align with 2 °C (1.5 °C), peaking in 2025 instead of 2030 reduces the requirement of CDR over the century by 17% (13%). Intensifying near-term mitigation also tends to have economic benefits to China's Paris-aligned energy transitions. Under 2 °C (1.5 °C), peaking in 2025 instead of 2030, with larger near-term mitigation costs by 1.3 (1.6) times, has the potential to reduce China's aggregate mitigation costs throughout the century by 4% (6%). Although in what way China's NDC is to be updated is determined by decision-makers, transitional and economic benefits suggest China to try its best to pursue more ambitious near-term mitigation in accordance with its latest national circumstances and development needs.


Fear of disease progression and psychological stress in cancer patients under the outbreak of COVID‐19


Understanding the "Scope" of the Problem: Why Laparoscopy is Considered Safe During the COVID-19 Pandemic


title: Comparative analysis of rodent and small mammal viromes to better understand the wildlife origin of emerging infectious diseases

text: BACKGROUND: Rodents represent around 43% of all mammalian species, are widely distributed, and are the natural reservoirs of a diverse group of zoonotic viruses, including hantaviruses, Lassa viruses, and tick-borne encephalitis viruses. Thus, analyzing the viral diversity harbored by rodents could assist efforts to predict and reduce the risk of future emergence of zoonotic viral diseases. RESULTS: We used next-generation sequencing metagenomic analysis to survey for a range of mammalian viral families in rodents and other small animals of the orders Rodentia, Lagomorpha, and Soricomorpha in China. We sampled 3,055 small animals from 20 provinces and then outlined the spectra of mammalian viruses within these individuals and the basic ecological and genetic characteristics of novel rodent and shrew viruses among the viral spectra. Further analysis revealed that host taxonomy plays a primary role and geographical location plays a secondary role in determining viral diversity. Many viruses were reported for the first time with distinct evolutionary lineages, and viruses related to known human or animal pathogens were identified. Phylogram comparison between viruses and hosts indicated that host shifts commonly happened in many different species during viral evolutionary history. CONCLUSIONS: These results expand our understanding of the viromes of rodents and insectivores in China and suggest that there is high diversity of viruses awaiting discovery in these species in Asia. These findings, combined with our previous bat virome data, greatly increase our knowledge of the viral community in wildlife in a densely populated country in an emerging disease hotspot. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40168-018-0554-9) contains supplementary material, which is available to authorized users.


title: Airborne bioaerosols and their impact on human health

text: Abstract Bioaerosols consist of aerosols originated biologically such as metabolites, toxins, or fragments of microorganisms that are present ubiquitously in the environment. International interests in bioaerosols have increased rapidly to broaden the pool of knowledge on their identification, quantification, distribution, and health impacts (e.g., infectious and respiratory diseases, allergies, and cancer). However, risk assessment of bioaerosols based on conventional culture methods has been hampered further by several factors such as: (1) the complexity of microorganisms or derivatives to be investigated; (2) the purpose, techniques, and locations of sampling; and (3) the lack of valid quantitative criteria (e.g., exposure standards and dose/effect relationships). Although exposure to some microbes is considered to be beneficial for health, more research is needed to properly assess their potential health hazards including inter-individual susceptibility, interactions with non-biological agents, and many proven/unproven health effects (e.g., atopy and atopic diseases).


title: Glycyrrhizin inhibits the manifestations of anti-inflammatory responses that appear in association with systemic inflammatory response syndrome (SIRS)-like reactions

text: Abstract In association with the systemic inflammatory response syndrome (SIRS), anti-inflammatory response syndrome is commonly manifested in patients with trauma, burn injury, and after major surgery. These patients are increasingly susceptible to infection with various pathogens due to the excessive release of anti-inflammatory cytokines from anti-inflammatory effector cells. Recently, CC-chemokine ligand 2 (CCL2) found in the sera of mice with pancreatitis was identified as an active molecule for SIRS-associated anti-inflammatory response manifestation. Also, the inhibitory activity of glycyrrhizin (GL) on CCL2 production was reported. Therefore, the effect of GL on SIRS-associated anti-inflammatory response manifestation was investigated in a murine SIRS model. Without any stimulation, splenic T cells from mice 5 days after SIRS induction produced cytokines associated with anti-inflammatory response manifestation. However, these cytokines were not produced by splenic T cells from SIRS mice previously treated with GL. In dual-chamber transwells, IL-4-producing cells were generated from normal T cells cultured with peripheral blood polymorphonuclear neutrophils (PMN) from SIRS mice. However, IL-4-producing cells were not generated from normal T cells in transwell cultures performed with PMN from GL-treated SIRS mice. CCL2 was produced by PMN from SIRS mice, while this chemokine was not demonstrated in cultures of PMN from SIRS mice treated with GL. These results indicate that GL has the capacity to suppress SIRS-associated anti-inflammatory response manifestation through the inhibition of CCL2 production by PMN.


title: Repertoire of Intensive Care Unit Pneumonia Microbiota

text: Despite the considerable number of studies reported to date, the causative agents of pneumonia are not completely identified. We comprehensively applied modern and traditional laboratory diagnostic techniques to identify microbiota in patients who were admitted to or developed pneumonia in intensive care units (ICUs). During a three-year period, we tested the bronchoalveolar lavage (BAL) of patients with ventilator-associated pneumonia, community-acquired pneumonia, non-ventilator ICU pneumonia and aspiration pneumonia, and compared the results with those from patients without pneumonia (controls). Samples were tested by amplification of 16S rDNA, 18S rDNA genes followed by cloning and sequencing and by PCR to target specific pathogens. We also included culture, amoeba co-culture, detection of antibodies to selected agents and urinary antigen tests. Based on molecular testing, we identified a wide repertoire of 160 bacterial species of which 73 have not been previously reported in pneumonia. Moreover, we found 37 putative new bacterial phylotypes with a 16S rDNA gene divergence ≥98% from known phylotypes. We also identified 24 fungal species of which 6 have not been previously reported in pneumonia and 7 viruses. Patients can present up to 16 different microorganisms in a single BAL (mean ± SD; 3.77±2.93). Some pathogens considered to be typical for ICU pneumonia such as Pseudomonas aeruginosa and Streptococcus species can be detected as commonly in controls as in pneumonia patients which strikingly highlights the existence of a core pulmonary microbiota. Differences in the microbiota of different forms of pneumonia were documented.


title: Projecting the impact of COVID-19 pandemic on childhood obesity in the U.S.: A microsimulation model

text: OBJECTIVE: The COVID-19 pandemic in the U.S. led to nationwide stay-at-home orders and school closures. Declines in energy expenditure resulting from canceled physical education classes and reduced physical activity (PA) may elevate childhood obesity risk. This study estimated the impact of COVID-19 on childhood obesity. METHODS: A microsimulation model simulated the trajectory of a nationally representative kindergarten cohort's body mass index z-scores (BMIz) and childhood obesity prevalence from April 2020 to March 2021 under the control scenario without COVID-19 and under the 4 alternative scenarios with COVID-19—Scenario 1: 2-month nationwide school closure in April and May 2020; Scenario 2: Scenario 1 followed by a 10% reduction in daily PA in summer from June to August; Scenario 3: Scenario 2 followed by 2-month school closure in September and October; and Scenario 4: Scenario 3 followed by an additional 2-month school closure in November and December. RESULTS: Relative to the control scenario without COVID-19, Scenarios 1, 2, 3, and 4 were associated with an increase in the mean BMIz by 0.056 (95% confidence interval (95%CI): 0.055–0.056), 0.084 (95%CI: 0.084–0.085), 0.141 (95%CI: 0.140–0.142), and 0.198 (95%CI: 0.197–0.199), respectively, and an increase in childhood obesity prevalence by 0.640 (95%CI: 0.515–0.765), 0.972 (95%CI: 0.819–1.126), 1.676 (95%CI: 1.475–1.877), and 2.373 (95%CI: 2.135–2.612) percentage points, respectively. Compared to girls and non-Hispanic whites and Asians, the impact of COVID-19 on childhood obesity was modestly larger among boys and non-Hispanic blacks and Hispanics, respectively. CONCLUSION: Public health interventions are urgently called to promote an active lifestyle and engagement in PA among children to mitigate the adverse impact of COVID-19 on unhealthy weight gains and childhood obesity.


title: Smallpox containment updated: considerations for the 21st century

text: Summary The emergence and re-emergence of infectious diseases since the eradication of smallpox has had a direct impact on preparedness for a deliberately-caused smallpox outbreak, should one occur. The emergence of HIV has placed restrictions on the safe and effective use of smallpox vaccines and made the need for vaccinia immune globulin important for outbreak control. At the same time, the threat of international spread of emerging and re-emerging infections has prompted global investments in surveillance and response mechanisms such as the Global Outbreak Alert and Response Network (GOARN), a mechanism that would enhance the world's collaboration in smallpox containment as it did during the recent outbreak of SARS. Though global preparedness for a deliberately-caused smallpox outbreak has increased with the creation of GOARN, it does not replace the need for increased national public health investment to expand surge capacity for the management of patients and their contacts and to strengthen emergency communication networks to ensure effective response.


title: Impact of bacteremia prediction rule in CAP: Before and after study

text: Abstract Objective In cases of community acquired pneumonia (CAP), it has been known that blood cultures have low yields and rarely affect clinical outcomes. Despite many studies predicting the likelihood of bacteremia in CAP patients, those results have been rarely implemented in clinical practice, and use of blood culture in CAP is still increasing. This study evaluated impact of implementing a previously derived and validated bacteremia prediction rule. Methods In this registry-based before and after study, we used piecewise regression analysis to compare the blood culture rate before and after implementation of the prediction rule. We also compared 30-day mortality, emergency department (ED) length of stay, time-interval to initial antibiotics after ED arrival, and any changes to the antibiotics regimen as results of the blood cultures. In subgroup analysis, we compared two groups (with or without the use of the prediction rule) after implementation period, using propensity score matching. Results Following the implementation, the blood culture rate declined from 85.5% to 78.1% (P =0.003) without significant changes in 30-day mortality and antibiotics regimen. The interval to initial antibiotics (231min vs. 221min, P =0.362) and length of stay (1019min vs. 954min, P =0.354) were not significantly changed. In subgroup analysis, the group that use the prediction rule showed 25min faster antibiotics initiation (P =0.002) and 48min shorter length of stay (P =0.007) than the group that did not use the rule. Conclusion Implementation of the bacteremia prediction rule in CAP patients reduced the blood culture rate without affecting the 30-day mortality and antibiotics regimen.


title: Canine coronavirus infection in the dog following oronasal inoculation

text: Abstract The pathogenesis of canine coronavirus (CCV) infection in 10-week-old puppies was studied up to 14 days after oronasal inoculation. Mild diarrhoea was seen from three to 11 days after inoculation, approximately coincident with faecal virus shedding. Virus was initially isolated from the tonsils on day 3, and then from both small and large intestinal tissues up to 14 days after inoculation. Virus was also isolated from liver and lung. Histological changes were not seen in any tissues, but CCV antigen was detected, using a peroxidase antiperoxidase staining technique, mainly in epithelium overlying gut-associated lymphoid tissue. Virus neutralising antibody was first detected on day 10. Specific anti-CCV IgM was first detected in plasma three days after inoculation and IgG on days 4 to 7. Small amounts of anti-CCV IgG, IgM and IgA were detected in duodenal secretion, but none in bile.


title: Lack of Antiviral Activity of Darunavir against SARS-CoV-2

text: Abstract Objectives Given the high need and the absence of specific antivirals for treatment of COVID-19 (the disease caused by severe acute respiratory syndrome-associated coronavirus-2 [SARS-CoV-2]), human immunodeficiency virus (HIV) protease inhibitors are being considered as therapeutic alternatives. Methods Prezcobix/Rezolsta is a fixed-dose combination of 800mg of the HIV protease inhibitor darunavir (DRV) and 150mg cobicistat, a CYP3A4 inhibitor, which is indicated in combination with other antiretroviral agents for the treatment of HIV infection. There are currently no definitive data on the safety and efficacy of DRV/cobicistat for treatment of COVID-19. The in vitro antiviral activity of darunavir against a clinical isolate from a patient infected with SARS-CoV-2 was assessed. Results DRV showed no activity against SARS-CoV-2 at clinically relevant concentrations (EC50 >100μM). Remdesivir, used as a positive control, showed potent antiviral activity (EC50 =0.38μM). Conclusions Overall, the data do not support the use of DRV for treatment of COVID-19.


title: Divergent bufavirus harboured in megabats represents a new lineage of parvoviruses

text: Bufavirus is a recently recognized member of the genus Protoparvovirus in the subfamily Parvovirinae. It has been reported that human bufavirus was detected predominantly in patients with diarrhoea in several countries. However, little is known about bufavirus or its close relatives in nonhuman mammals. In this study, we performed nested-PCR screening and identified bufavirus from 12 megabats of Pteropus spp. in Indonesia. Furthermore, we determined nearly the full genome sequence of a novel megabat-borne bufavirus, tentatively named megabat bufavirus 1. Phylogenetic analyses showed that megabat bufavirus 1 clustered with known protoparvoviruses, including human bufavirus but represented a distinct lineage of bufavirus. Our analyses also inferred phylogenetic relationships among animal-borne bufaviruses recently reported by other studies. Recombination analyses suggested that the most common recent ancestor of megabat bufavirus 1 might have arisen from multiple genetic recombination events. These results characterized megabat bufavirus 1 as the first protoparvovirus discovered from megabats and indicates the high genetic divergence of bufavirus.


title: Inflammatory monocytes and the pathogenesis of viral encephalitis

text: Monocytes are a heterogeneous population of bone marrow-derived cells that are recruited to sites of infection and inflammation in many models of human diseases, including those of the central nervous system (CNS). Ly6C(hi)/CCR2(hi) inflammatory monocytes have been identified as the circulating precursors of brain macrophages, dendritic cells and arguably microglia in experimental autoimmune encephalomyelitis; Alzheimer’s disease; stroke; and more recently in CNS infection caused by Herpes simplex virus, murine hepatitis virus, Theiler’s murine encephalomyelitis virus, Japanese encephalitis virus and West Nile virus. The precise differentiation pathways and functions of inflammatory monocyte-derived populations in the inflamed CNS remains a contentious issue, especially in regard to the existence of monocyte-derived microglia. Furthermore, the contributions of monocyte-derived subsets to viral clearance and immunopathology are not well-defined. Thus, understanding the pathways through which inflammatory monocytes migrate to the brain and their functional capacity within the CNS is critical to inform future therapeutic strategies. This review discusses some of the key aspects of inflammatory monocyte trafficking to the brain and addresses the role of these cells in viral encephalitis.


title: SURGICAL RESECTIONS OF SUPERINFECTED PNEUMATOCELES IN A COVID-19 PATIENT

text: ABSTRACT Emerging studies on radiological findings in COVID-19 patients report a high incidence of bilateral lung involvement, with GGOs imaging being the most common pattern on CT. Cystic lesions, such as pneumatoceles, are rare, although they may occur in 10% of cases. Cyst formation may be explained by a focal pulmonary trauma due to mechanical ventilation and/or infection-related damage to the alveolar walls leading to pneumatoceles. The superinfection of pneumatoceles is a potential life-threating condition for which no standardized therapeutic algorithm has been accepted. We report a case of a COVID-19 patient successfully treated by lung resections for infected pneumatoceles.


title: Genotype-specific differences in structural features of hepatitis C virus (HCV) p7 membrane protein

text: Abstract The 63 amino acid polytopic membrane protein, p7, encoded by hepatitis C virus (HCV) is involved in the modulation of electrochemical gradients across membranes within infected cells. Structural information relating to p7 from multiple genotypes has been generated in silico (e.g. genotype (GT) 1a), as well as obtained from experiments in form of monomeric and hexameric structures (GTs 1b and 5a, respectively). However, sequence diversity and structural differences mean that comparison of their channel gating behaviour has not thus far been simulated. Here, a molecular model of the monomeric GT 1a protein is optimized and assembled into a hexameric bundle for comparison with both the 5a hexamer structure and another hexameric bundle generated using the GT 1b monomer structure. All bundles tend to turn into a compact structure during molecular dynamics (MD) simulations (Gromos96 (ffG45a3)) in hydrated lipid bilayers, as well as when simulated at ‘low pH’, which may trigger channel opening according to some functional studies. Both GT 1a and 1b channel models are gated via movement of the parallel aligned helices, yet the scenario for the GT 5a protein is more complex, with a short N-terminal helix being involved. However, all bundles display pulsatile dynamics identified by monitoring water dynamics within the pore.


title: miR-142-5p Disrupts Neuronal Morphogenesis Underlying Porcine Hemagglutinating Encephalomyelitis Virus Infection by Targeting Ulk1

text: Porcine hemagglutinating encephalomyelitis virus (PHEV) invades the central nervous system (CNS) and causes neurodegenerative disease in suckling piglets, but the understanding of its neuropathogenicity for neurological dysfunction remains limited. Here, we report that miR-142-5p is localized to neurons and negatively regulates neuronal morphogenesis in porcine hemagglutinating encephalomyelitis (PHE). This phenotype was mediated by miR-142-5p inhibition of an mRNA encoding unc-51-like-kinase1 (Ulk1), which controls axon outgrowth and dendrite formation. Modulating miR-142-5p activity by microRNA mimics or inhibitors induced neurodegeneration, including stunted axon elongation, unstable dendritic spine formation, and irregular swelling and disconnection in neurites. Relieving Ulk1 mRNA repression in primary cortical neurons by miR-142-5p antagomirs or replication-deficient adenoviruses encoding Ulk1 (Ad5-Ulk1), which improved rescue of nerve injury, restricted viral replication, and increased survival rate in mice underlying PHEV infection. In contrast, disrupting Ulk1 in RNAi-expressing neurons mostly led to significantly shortened axon elongation and/or an abnormally large number of branched dendrites. Taken together, we demonstrated that the abnormal neuronal morphogenesis underlying PHEV infection was mainly caused by functional mRNA repression of the miR-142-5p target Ulk1. Our data revealed that PHEV adapted to use spatiotemporal control of host microRNAs to invade CNS, and provided new insights into the virus-associated neurological dysfunction microenvironment.


docid: emtrrwpv

title: Paediatric pandemic planning: children’s perspectives and recommendations

text: Children, as major stakeholders in paediatric hospitals, have remained absent from discussions on important healthcare issues. One critical area where children’s voices have been minimised is in the planning for future pandemics. This paper presents a subset of data from a programme of research which examined various stakeholder experiences of the severe acute respiratory syndrome (SARS) outbreaks of 2003. These data also generated recommendations for future pandemic planning. Specifically, this paper will examine the perspectives and recommendations of children hospitalised during SARS in a large paediatric hospital in Canada. Twenty‐one (n = 21) child and adolescent participants were interviewed from a variety of medical areas including cardiac (n = 2), critical care (n = 2), organ transplant (n = 4), respiratory medicine (n = 8) and infectious diseases (patients diagnosed with suspected or probable SARS; n = 5). Data analyses exposed a range of children’s experiences associated with the outbreaks as well as recommendations for future pandemic planning. Key recommendations included specific policies and guidelines concerning psychosocial care, infection control, communication strategies and the management of various resources. This paper is guided by a conceptual framework comprised of theories from child development and literature on children’s rights. The authors call for greater youth participation in healthcare decision‐making and pandemic planning.


title: Rabies elimination research: juxtaposing optimism, pragmatism and realism

text: More than 100 years of research has now been conducted into the prevention, control and elimination of rabies with safe and highly efficacious vaccines developed for use in human and animal populations. Domestic dogs are a major reservoir for rabies, and although considerable advances have been made towards the elimination and control of canine rabies in many parts of the world, the disease continues to kill tens of thousands of people every year in Africa and Asia. Policy efforts are now being directed towards a global target of zero human deaths from dog-mediated rabies by 2030 and the global elimination of canine rabies. Here we demonstrate how research provides a cause for optimism as to the feasibility of these goals through strategies based around mass dog vaccination. We summarize some of the pragmatic insights generated from rabies epidemiology and dog ecology research that can improve the design of dog vaccination strategies in low- and middle-income countries and which should encourage implementation without further delay. We also highlight the need for realism in reaching the feasible, although technically more difficult and longer-term goal of global elimination of canine rabies. Finally, we discuss how research on rabies has broader relevance to the control and elimination of a suite of diseases of current concern to human and animal health, providing an exemplar of the value of a ‘One Health’ approach.


title: Managing multi-lateral, intergovernmental projects and programmes: the case of the UNEP/GEF South China Sea project

text: Abstract The management of comprehensive and extensive, multi-lateral and multi-national programmes and projects in the field of coastal and ocean management poses numerous organisational problems encompassing co-ordination between: the actions of individual participating countries at the regional level; the national level actions of institutions from different sectors; and actions that are designed to address issues as diverse as: biological diversity conservation and sustainable use; fisheries management; maritime transport; and the control of land based pollution. Most large multi-lateral projects focus on sound scientific knowledge and information, and pay less attention to the design of a management structure that will ensure coherence and co-ordination of the interventions once the programme or project is under implementation. The project entitled “Reversing Environmental Degradation Trends in the South China Sea and Gulf of Thailand” was complex since it addressed three priority areas of concern namely the loss and degradation of coastal habitats, over-exploitation of fisheries in the Gulf of Thailand, and land-based pollution. It is suggested that the success of the management framework reflects the following key design elements: • The framework permitted and encouraged both “horizontal” (inter-country) and “vertical” (intra-country) interactions and networking between individuals at all levels of project implementation and execution; • Inclusion of a body (the Regional Scientific and Technical Committee) that served as a forum for reconciling both sectorial and national interests and priorities; • The clear separation between discussions of scientific and technical matters from discussions dealing with policy and principles at both the national and regional levels; • The framework facilitated the incorporation of sound scientific and technical advice and information into politically based decision-making; • The use of regional experts and consultants from the participating countries fostered “ownership” of the activities and outputs; • Restriction of the membership of the Project Steering Committee to government representatives only, and exclusion of observers from regional and international agencies and institutions other than UNEP; and, • The framework allowed for adaptive management and was not a rigid unchanging structure.


title: Herpesviruses—a rationale for antiviral treatment in multiple sclerosis

text: Abstract In multiple sclerosis (MS), the extensive and long lasting search for viruses or other pathogens has hitherto failed to identify a common etiological agent. However, the beneficial effects by interferon-β treatment in MS, although suggested to depend mainly on immunomodulation, might lend support to a viral involvement in the pathogenesis. The human herpesviruses have attracted interest since their recurrent modes of infection share some similarity with the relapsing-remitting course of MS, most members are readily detected within the brain, and several of these viruses may induce demyelination within the central nervous system in human hosts as well as in animal models. Accumulated diagnostic and epidemiological data are compatible with a role for the herpesviruses as possible cofactors rather than etiological agents, and recent studies showing early neuronal damage in MS patients focus attention on the neurotropic α-herpesviruses. Antiviral treatment trials with safe and effective drugs such as valaciclovir offer a possibility of testing the hypotheses concerning herpesviral involvement in MS.


Objective Determination of End of MERS Outbreak, South Korea, 2015


title: Lujo viral hemorrhagic fever: considering diagnostic capacity and preparedness in the wake of recent Ebola and Zika virus outbreaks

text: Lujo virus is a novel Old World arenavirus identified in Southern Africa in 2008 as the cause of a viral hemorrhagic fever (VHF) characterized by nosocomial transmission with a high case fatality rate of 80% (4/5 cases). Whereas this outbreak was limited, the unprecedented Ebola virus disease outbreak in West Africa, and recent Zika virus disease epidemic in the Americas, has brought into acute focus the need for preparedness to respond to rare but potentially highly pathogenic outbreaks of zoonotic or arthropod‐borne viral infections. A key determinant for effective control of a VHF outbreak is the time between primary infection and diagnosis of the index case. Here, we review the Lujo VHF outbreak of 2008 and discuss how preparatory measures with respect to developing diagnostic capacity might be effectively embedded into existing national disease control networks, such as those for human immunodeficiency virus, tuberculosis, and malaria.


title: Temporal radiographic changes in COVID-19 patients: relationship to disease severity and viral clearance

text: COVID-19 is “public enemy number one” and has placed an enormous burden on health authorities across the world. Given the wide clinical spectrum of COVID-19, understanding the factors that can predict disease severity will be essential since this will help frontline clinical staff to stratify patients with increased confidence. To investigate the diagnostic value of the temporal radiographic changes, and the relationship to disease severity and viral clearance in COVID-19 patients. In this retrospective cohort study, we included 99 patients admitted to the Renmin Hospital of Wuhan University, with laboratory confirmed moderate or severe COVID-19. Temporal radiographic changes and viral clearance were explored using appropriate statistical methods. Radiographic features from HRCT scans included ground-glass opacity, consolidation, air bronchogram, nodular opacities and pleural effusion. The HRCT scores (peak) during disease course in COVID-19 patients with severe pneumonia (median: 24.5) were higher compared to those with pneumonia (median: 10) (p = 3.56 × 10 (−12)), with more frequency of consolidation (p = 0.025) and air bronchogram (p = 7.50 × 10(−6)). The median values of days when the peak HRCT scores were reached in pneumonia or severe pneumonia patients were 12 vs. 14, respectively (p = 0.048). Log-rank test and Spearman’s Rank-Order correlation suggested temporal radiographic changes as a valuable predictor for viral clearance. In addition, follow up CT scans from 11 pneumonia patients showed full recovery. Given the values of HRCT scores for both disease severity and viral clearance, a standardised HRCT score system for COVID-19 is highly demanded.


title: Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicenter) and outside Hubei (non-epicenter): A Nationwide Analysis of China

text: BACKGROUND: During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China has been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences. METHODS: Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients in and outside of Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicenter as well the administrative center of Hubei province) and the duration between symptom onset and admission on prognosis were also determined. RESULTS: Upon data cut-off (Jan 31st, 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597/647, 92.3%) were older (mean: 49.7 versus 44.9 years), had more cases with comorbidity (32.9% versus 19.7%), higher symptomatic burden, abnormal radiologic manifestations, and, especially, a longer waiting time between symptom onset and admission (5.7 versus 4.5 days) compared with patients outside Hubei. Patients in Hubei [severe event rate 23.0% versus 11.1%, death rate 7.3% versus 0.3%, hazards ratio (HR) for critical illness 1.59, 95%CI 1.05–2.41] have a poorer prognosis compared with patients outside of Hubei after adjusting for age and comorbidity. However, among patients outside of Hubei, the duration from symptom onset to hospitalisation (mean: 4.4 versus 4.7 days) and prognosis (HR 0.84, 95%CI 0.40–1.80) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR 1.05, 1.01–1.08). CONCLUSION: There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicenter. Future studies to determine the reason for delaying hospitalisation are warranted.


Palliative care in the emergency department during a COVID-19 pandemic


title: Molecular epidemiology and viremia of porcine astrovirus in pigs from Guangxi province of China

text: BACKGROUND: Porcine astroviruses (PAstVs) are common in pigs worldwide. There are five distinct lineages with each lineage representing a different ancestral origin. Recently, multiple reports have demonstrated the evidence of extra-intestinal infection of PAstVs, but little is known about viremia. RESULTS: In this study, a total of 532 fecal samples and 120 serum samples from healthy pigs were collected and tested from 2013 to 2015 in Guangxi province, China; of these 300/532 (56.4%) and 7/120 (5.8%) of fecal samples tested positive for PAstVs, respectively. Our study revealed that there was wide genetic diversity and high prevalence of the virus in the pig population. All five of the known PAstVs genotypes (1–5) prevailed in the pig population of Guangxi province and were distributed in all age groups of pigs, from suckling piglets to sows, with PAstV2 (47.7%), PAstV1 (26.2%) and PAstV5 (21.5%) seen predominantly. Phylogenetic analysis of partial ORF1b and partial capsid sequences from fecal and serum samples revealed that they were divided into the five lineages. Among these genotypes, based on partial ORF2 genes sequencing 23 strains were grouped as PAstV1, including 6 serum-derived strains, and were regarded as the causative agents of viremia in pigs. CONCLUSIONS: Due to the information regarding the types of PAstV in blood is limit. This is the first report for the presence of PAstV1 in blood and PAstV3 in the feces of nursery pigs of China. This study provides a reference for understanding the prevalence and genetic evolution of PAstVs in pigs in Guangxi province, China. It also provides a new perspective for understanding of the extra-intestinal infection of PAstVs in pigs.


title: KnotInFrame: prediction of −1 ribosomal frameshift events

text: Programmed −1 ribosomal frameshift (−1 PRF) allows for alternative reading frames within one mRNA. First found in several viruses, it is now believed to exist in all kingdoms of life. Strong stimulators for −1 PRF are a heptameric slippery site and an RNA pseudoknot. Here, we present a new algorithm KnotInFrame, for the automatic detection of −1 PRF signals from genomic sequences. It finds the frameshifting stimulators by means of a specialized RNA-pseudoknot folding program, fast enough for genome-wide analyses. Evaluations on known −1 PRF signals demonstrate a high sensitivity.


title: Genome-wide analysis of differentially expressed genes and the modulation of PEDV infection in Vero E6 cells

text: Abstract PEDV remains one of the most important swine diseases that infects pigs of all ages. It causes devastating viral enteric disease in piglets with a high mortality rate, leading to significant threats and huge economic loss to the pork industry. In this study, a transcriptomic shotgun sequencing (RNA-Seq) procedure was used to study gene responses against PEDV infection. Genome-wide analysis of differentially expressed genes (DEGs) was performed in Vero E6 cells post-PEDV infection. mTOR signaling pathway activator-MHY1485, and inhibitor-PP242 were used to study the antiviral function. Results revealed that the IRF3 was significantly up-regulated post-PEDV infection. Although most of the IFN-regulatory and –related genes evaluated in this study were either down-regulated or remained unchanged, IL11 behaved significantly up-regulated, with the peak at 16 hpi. Nearly 90% of PEDV infections were suppressed in the PP242 pretreated cells whereas the reverse effect was observed in the MYH1485 pretreated cells. Results indicated that the mTOR signaling pathway played a vital role in the PEDV antiviral regulation in the Vero E6 cells. Future studies will contribute to better understand the cellular antiviral mechanism against PEDV.


title: Disciplines Associated with Food Safety: Food Virology

text: Abstract Food virology is a relatively young but important field in food safety. Viruses in general and human noroviruses in particular, are the leading cause of foodborne disease of known etiology in developed countries. Hepatitis A virus is also important, as are a number of emerging viruses. This article identifies the relevant viruses, describes their structural characteristics and the diseases they cause, and what is known about their epidemiological significance. It also describes why their transmission is so difficult to control, their detection difficult to achieve, and future research needs that will facilitate their study by food safety scientists.


title: COVID-19 pandemic and non invasive respiratory management: every Goliath needs a David. An evidence based evaluation of problems.

text: Abstract Background and aim The war against Covid-19 is far from won. This narrative review attempts to describe some problems with the management of Covid-19 induced acute respiratory failure (ARF) by pulmonologists. Methods We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and reviewed the references of retrieved articles for additional studies. The search was limited to the terms: Covid-19 AND: acute respiratory distress syndrome (ARDS), SARS, MERS, non invasive ventilation (NIV), high flow nasal cannula (HFNC), pronation (PP), health care workers (HCW). Results Protection of Health care workers should be paramount, so full Personal Protective Equipment and Negative pressure rooms are warranted. HFNC alone or with PP could be offered for mild cases (PaO2/FiO2 between 200-300); NIV alone or with PP may work in moderate cases (PaO2/FiO2 between 100-200). Rotation and coupled (HFNC/NIV) strategy can be beneficial. A window of opportunity of 1-2hours is advised. If PaO2/FIO2 significantly increases, Respiratory Rate decreases with a relatively low Exhaled Tidal Volume, the non-invasive strategy could be working and intubation delayed. Conclusion Although there is a role for non-invasive respiratory therapies in the context of COVID-19 ARF, more research is still needed to define the balance of benefits and risks to patients and HCW. Indirectly, non invasive respiratory therapies may be of particular benefit in reducing the risks to healthcare workers by obviating the need for intubation, a potentially highly infectious procedure.


title: COVID-19: a primer for healthcare providers

text: According to the World Health Organization (WHO) the China office was first notified of cases of atypical pneumonia in Wuhan City on 31 December 2019. A viral genome sequence of a novel coronavirus, currently termed SARS-CoV‑2, with a disease process called COVID-19 was released 1 week later via online resources to obtain public health support in control of spread. Since then, the virus rapidly evolved into a global pandemic. Therefore, healthcare providers need to be familiar with the clinical presentation of infected patients and measures to quickly isolate them. The prevention of nosocomial spread is paramount to proper control of COVID-19 and is reviewed. Currently, treatment is supportive. Researchers are working to develop vaccines and identify effective antiviral interventions. Those recently discussed in the literature are briefly reviewed.


title: Retrocyclins and their activity against HIV-1

text: Primate theta-defensins are physically distinguished as the only known fully-cyclic peptides of animal origin. Humans do not produce theta-defensin peptides due to a premature stop codon present in the signal sequence of all six theta-defensin pseudogenes. Instead, since the putative coding regions of human theta-defensin pseudogenes have remained remarkably intact, their corresponding peptides, called “retrocyclins”, have been recreated using solid-phase synthetic approaches. Retrocyclins exhibit an exceptional therapeutic index both as inhibitors of HIV-1 entry and as bactericidal agents, which makes retrocyclins promising candidates for further development as topical microbicides to prevent sexually transmitted diseases. This review presents the evolution, antiretroviral mechanism of action, and potential clinical applications of retrocyclins to prevent sexual transmission of HIV-1.


title: Carbohydrate biomarkers for future disease detection and treatment

text: Carbohydrates are considered as one of the most important classes of biomarkers for cell types, disease states, protein functions, and developmental states. Carbohydrate “binders” that can specifically recognize a carbohydrate biomarker can be used for developing novel types of site specific delivery methods and imaging agents. In this review, we present selected examples of important carbohydrate biomarkers and how they can be targeted for the development of therapeutic and diagnostic agents. Examples are arranged based on disease categories including (1) infectious diseases, (2) cancer, (3) inflammation and immune responses, (4) signal transduction, (5) stem cell transformation, (6) embryo development, and (7) cardiovascular diseases, though some issues cross therapeutic boundaries.


title: Biochemical characterization of recombinant Avihepatovirus 3C protease and its localization

text: BACKGROUND: The picornaviral 3C protease mediates viral polyprotein maturation and multiple cleavages of host proteins to modulate viral translation and transcription. The 3C protease has been regarded as a valid target due to its structural similarity among different picornaviruses and minimal sequence similarity with host proteins; therefore, the development of potent inhibitors against the 3C protease as an antiviral drug is ongoing. Duck hepatitis A virus (DHAV) belongs to the Picornavidea family and is a major threat to the poultry industry. To date, little is known about the roles of the DHAV 3C protease plays during infection. METHODS: In this study, we compared the full-length DHAV 3C protein sequence with other 3C sequences to obtain an alignment for the construction of a phylogenetic tree. Then, we expressed and purified recombinant DHAV 3C protease in the BL21 expression system using nickel-NTA affinity chromatography. The optimization of the cleavage assay conditions and the kinetic analysis for DHAV 3C protease were done by in vitro cleavage assays with a fluorogenic peptide respectively. The inhibitory activity of rupintrivir against the DHAV 3C protease was further evaluated. The localization of the 3C protease in infected and transfected cells was determined using immunofluorescence and confocal microscopy. RESULTS: Under different expression conditions, the 3C protease was found to be highly expressed after induction with 1 mM IPTG at 16 °C for 10 h. We synthesized a fluorogenic peptide derived from the cleavage site of the DHAV polyprotein and evaluated the protease activity of the DHAV 3C protease for the first time. We used fluorimetric based kinetic analysis to determine kinetic parameters, and V(max) and K(m) values were determined to be 16.52 nmol/min and 50.78 μM, respectively. Rupintrivir was found to exhibit inhibitory activity against the DHAV 3C protease. Using polyclonal antibody and an indirect immunofluorescence microscopy assay (IFA), it was determined that the DHAV 3C protease was found in the nucleus during infection. In addition, the DHAV 3C protease can enter into the nucleus without the cooperation of viral proteins. CONCLUSIONS: This is the first study to examine the activity of the DHAV 3C protease, and the activity of the DHAV 3C protease is temperature-, pH- and NaCl concentration- dependent. The DHAV 3C protease localizes throughout DHAV-infected cells and can enter into the nucleus in the absence of other viral proteins. The kinetic analysis was calculated, and the V(max) and K(m) values were 16.52 nmol/min and 50.78 μM, respectively, using the Lineweaver–Burk plot.


Pneumomediastinum in critically ill adult with COVID-19


title: Tackling two crises at once

text: We can't lose sight of the climate emergency when dealing with the covid-19 pandemic, say Christiana Figueres and Tom Rivett-Carnac


MERS-COV


title: Evolutionary Medicine IV. Evolution and Emergence of Novel Pathogens

text: Abstract This article discusses how evolutionary and ecological factors interact to affect the epidemiology of emerging infectious diseases. It further explains how the nascent field of phylodynamics constructs mathematical models, which link evolution and epidemiology, to study pathogen transmission. To illustrate the importance of considering both evolution and ecology – along with the utility of the phylodynamic approach – when studying novel pathogens, the author considers examples from HIV, influenza, and Ebola.


title: Clinical Management of Avian Renal Disease

text: Treatment of avian renal disease relies on supportive care, such as fluid therapy and nutritional support. Analgesia and adaptations of the environment are indicated in cases of renal disease associated with painful joints. Other treatments vary with the underlying etiology and may include systemic antibiotics, antifungal therapy, vitamin A supplementation, or chelation therapy.


docid: kmamrknk

title: Cross-sectional surveillance of Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels and other mammals in Egypt, August 2015 to January 2016

text: A cross-sectional study was conducted in Egypt to determine the prevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) in imported and resident camels and bats, as well as to assess possible transmission of the virus to domestic ruminants and equines. A total of 1,031 sera, 1,078 nasal swabs, 13 rectal swabs, and 38 milk samples were collected from 1,078 camels in different types of sites. In addition, 145 domestic animals and 109 bats were sampled. Overall, of 1,031 serologically-tested camels, 871 (84.5%) had MERS-CoV neutralising antibodies. Seroprevalence was significantly higher in imported (614/692; 88.7%) than resident camels (257/339; 5.8%) (p < 0.05). Camels from Sudan (543/594; 91.4%) had a higher seroprevalence than those from East Africa (71/98; 72.4%) (p < 0.05). Sampling site and age were also associated with MERS-CoV seroprevalence (p < 0.05). All tested samples from domestic animals and bats were negative for MERS-CoV antibodies except one sheep sample which showed a 1:640 titre. Of 1,078 camels, 41 (3.8%) were positive for MERS-CoV genetic material. Sequences obtained were not found to cluster with clade A or B MERS-CoV sequences and were genetically diverse. The presence of neutralising antibodies in one sheep apparently in contact with seropositive camels calls for further studies on domestic animals in contact with camels.


title: Development of human antibody fragments using antibody phage display for the detection and diagnosis of Venezuelan equine encephalitis virus (VEEV)

text: BACKGROUND: Venezuelan equine encephalitis virus (VEEV) belongs to the Alphavirus group. Several species of this family are also pathogenic to humans and are recognized as potential agents of biological warfare and terrorism. The objective of this work was the generation of recombinant antibodies for the detection of VEEV after a potential bioterrorism assault or an natural outbreak of VEEV. RESULTS: In this work, human anti-VEEV single chain Fragments variable (scFv) were isolated for the first time from a human naïve antibody gene library using optimized selection processes. In total eleven different scFvs were identified and their immunological specificity was assessed. The specific detection of the VEEV strains TC83, H12/93 and 230 by the selected antibody fragments was proved. Active as well as formalin inactivated virus particles were recognized by the selected antibody fragments which could be also used for Western blot analysis of VEEV proteins and immunohistochemistry of VEEV infected cells. The anti-VEEV scFv phage clones did not show any cross-reactivity with Alphavirus species of the Western equine encephalitis virus (WEEV) and Eastern equine encephalitis virus (EEEV) antigenic complex, nor did they react with Chikungunya virus (CHIKV), if they were used as detection reagent. CONCLUSION: For the first time, this study describes the selection of antibodies against a human pathogenic virus from a human naïve scFv antibody gene library using complete, active virus particles as antigen. The broad and sensitive applicability of scFv-presenting phage for the immunological detection and diagnosis of Alphavirus species was demonstrated. The selected antibody fragments will improve the fast identification of VEEV in case of a biological warfare or terroristic attack or a natural outbreak.


title: Gene expression analyses in Atlantic salmon challenged with infectious salmon anemia virus reveal differences between individuals with early, intermediate and late mortality

text: BACKGROUND: Infectious salmon anemia virus (ISAV) causes a multisystemic disease responsible for severe losses in salmon aquaculture. Better understanding of factors that explain variations in resistance between individuals and families is essential for development of strategies for disease control. To approach this, we compared global gene expression using microarrays in fish dying early and late in the time course following infection from a highly pathogenic ISAV. RESULTS: Tissues (gill, heart, liver and spleen) from infected Atlantic salmon (cohabitation, ISAV Glesvaer 2/90 isolate) were collected from three stages over the time course of the experiment; early (EM, 0–10% cumulative mortality (CM), 21–25 days post-infection (DPI)), intermediate (IM, 35–55% CM, 28–31 DPI) and late (LM, 75–85% CM, 37–48 DPI) mortality. Viral loads were equal in EM and IM but dropped markedly in LM fish. Gene expression analyses using a 1.8 K salmonid fish cDNA microarray (SFA2.0) and real-time qPCR revealed a large group of genes highly up-regulated across tissues in EM, which were mainly implicated in innate antiviral responses and cellular stress. Despite equal levels of MHC class I in EM and LM, increase of splenic and cardiac expression of immunoglobulin-like genes was found only in LM while a suite of adaptive immunity markers were activated already in IM. The hepatic responses to ISAV were characterized by difference between EM and LM in expression of chaperones and genes involved in eicosanoid metabolism. To develop classification of high and low resistance phenotypes based on a small number of genes, we processed results from qPCR analyses of liver using a linear discriminant analysis. Four genes (5-lipoxygenase activating protein, cytochrome P450 2K4-1, galectin-9 and annexin A1) were sufficient for correct assignment of individuals to EM, LM and uninfected groups, while IM was inseparable from EM. Three of four prognostic markers are involved in metabolism of inflammatory regulators. CONCLUSION: This study adds to the understanding of molecular determinants for resistance to acute ISAV infection. The most susceptible individuals were characterized by high viral replication and dramatic activation of innate immune responses, which did not provide protection. The ability to endure high levels of infection for sustained periods could be associated with lower inflammatory responses while subsequent protection and viral clearance was most likely conferred by activation of adaptive immunity.


title: IV Magnesium Sulfate for Bronchiolitis A Randomized Trial

text: Background The goal of this study was to determine if IV magnesium, useful for severe pediatric asthma, reduces time to medical readiness for discharge in patients with bronchiolitis when added to supportive care. Methods We compared a single dose of 100 mg/kg of IV magnesium sulfate vs placebo for acute bronchiolitis. Patients received bronchodilator therapy, nebulized hypertonic saline, and 5 days of dexamethasone if there was eczema and/or a family history of asthma. Time to medical readiness for discharge was the primary efficacy outcome. Bronchiolitis severity scores and need for infirmary or hospital admission and for clinic revisits within 2 weeks were secondary outcomes. Cardiorespiratory instability onset was the safety outcome. Results A total of 162 previously healthy infants diagnosed with bronchiolitis aged 22 days to 17.6 months (median, 3.7 months) were enrolled. Approximately one-half of patients had eczema and/or a family history of asthma; 86.4% had positive findings on nasopharyngeal virus swabs. Geometric mean time until medical readiness for discharge was 24.1 h (95% CI, 20.0-29.1) for the 78 magnesium-treated patients and 25.3 h (95% CI, 20.3-31.5) for the 82 patients receiving placebo (ratio, 0.95 [95% CI, 0.52-1.80]; P = .91). Mean bronchiolitis severity scores over time were similar for the two groups. The frequency of clinic visits in the subsequent 2 weeks (33.8% and 27.2%, respectively) was also similar. Fifteen magnesium recipients (19.5%) vs five placebo recipients (6.2%) were readmitted to the infirmary or hospital within 2 weeks (P = .016). No acute cardiorespiratory side effects were reported. Conclusions IV magnesium did not provide benefit for patients with acute bronchiolitis and may be harmful. Trial Registry ClinicalTrials.gov; No.: NCT02145520; URL: www.clinicaltrials.gov.


title: Porcine Circovirus Type 2 ORF5 Protein Induces Autophagy to Promote Viral Replication via the PERK-eIF2α-ATF4 and mTOR-ERK1/2-AMPK Signaling Pathways in PK-15 Cells

text: Porcine circovirus type 2 (PCV2) is the primary causative agent that causing porcine circovirus-associated disease (PCVAD). The open reading frame 5 (ORF5) protein is a newly discovered non-structural protein in PCV2, which the function in viral pathogenesis remains unknown. The aim of this study was to investigate the mechanism of PCV2 ORF5 protein on autophagy and viral replication. The pEGFP-tagged ORF5 gene was ectopic expressed in PK-15 cells and an ORF5-deficient PCV2 mutant strain (PCV2(ΔORF5)) were used to infected PK-15 cells. This study demonstrated that the ORF5 is essential for the of PCV2-induced autophagy. The ORF5 protein triggers the phosphorylation of PERK, eIF2α and the expression of downstream transcription factor ATF4. In addition, ORF5 protein activated the AMPK-ERK1/2-mTOR signaling pathways. These findings suggest that ORF5 play essential roles in the induction of autophagy by PCV2. We further revealed that PCV2 ORF5 promotes viral replication through PERK-eIF2α-ATF4 and AMPK-ERK1/2-mTOR pathways. In conclusion, we showed that PCV2 ORF5 induces autophagy to promote virus replication in PK-15 cells.


Biologists seek to head off future sources of infection


title: Higher plasma levels of chemokine CCL19 are associated with poor SARS-CoV-2 acute respiratory distress syndrome (ARDS) outcomes.

text: COVID19 pandemic has so far caused over three hundred thousand deaths worldwide, primarily due to complications from SARS-CoV-2-associated acute respiratory distress syndrome (ARDS). While an ARDS-driven hyperinflammatory phenotype is associated with higher mortality in non-COVID patients, there is little information on how cytokines and chemokines expressions correlate with clinical outcomes in COVID19 patients. We prospectively enrolled a cohort of 41 patients with acute respiratory distress syndrome on mechanical ventilation. Patients’ blood was obtained at enrollment and outcome measures were liberation from mechanical ventilation and hospital-free days. We determined the expression levels of 44 circulating cytokines/chemokines and found 13 of them associated with worse outcomes. After correcting for multiple comparisons/false discovery rate, only one chemokine (CCL19) remained significantly associated with outcomes (p=0.009). Although not described in association with COVID19, this chemokine was previously found elevated in an animal model of SARS-CoV. Moreover, CCL19 seems to be relevant for bronchus-associated lymphoid tissue (BALT) maintenance and for lung immunity to influenza virus. While this finding requires corroboration, CCL19 determination could facilitate early identification of COVID19-ARDS patients at higher risk of death and be novel target for immunotherapy in this setting.


title: Proteomics Computational Analyses Suggest that the Antennavirus Glycoprotein Complex Includes a Class I Viral Fusion Protein (α-Penetrene) with an Internal Zinc-Binding Domain and a Stable Signal Peptide

text: A metatranscriptomic study of RNA viruses in cold-blooded vertebrates identified two related viruses from frogfish (Antennarius striatus) that represent a new genus Antennavirus in the family Arenaviridae (Order: Bunyavirales). Computational analyses were used to identify features common to class I viral fusion proteins (VFPs) in antennavirus glycoproteins, including an N-terminal fusion peptide, two extended alpha-helices, an intrahelical loop, and a carboxyl terminal transmembrane domain. Like mammarenavirus and hartmanivirus glycoproteins, the antennavirus glycoproteins have an intracellular zinc-binding domain and a long virion-associated stable signal peptide (SSP). The glycoproteins of reptarenaviruses are also class I VFPs, but do not contain zinc-binding domains nor do they encode SSPs. Divergent evolution from a common progenitor potentially explains similarities of antennavirus, mammarenavirus, and hartmanivirus glycoproteins, with an ancient recombination event resulting in a divergent reptarenavirus glycoprotein.


title: Taiwan's Public Health National Laboratory System: Success in Influenza Diagnosis and Surveillance

text: Taiwan's National Laboratory System is one of the action packages of the Global Health Security Agenda, which was launched by the World Health Organization (WHO) to promote health security as an international priority and to encourage progress toward full implementation of the WHO International Health Regulations (IHR) 2005. The mission of each national laboratory system is to conduct real-time biosurveillance and effective laboratory-based diagnostics, as measured by a nationwide laboratory system able to reliably conduct diagnoses on specimens transported properly to designated laboratories from at least 80% of the regions in the country. In Taiwan, the national laboratory system for public health is well-established and coordinated by the Taiwan Centers for Disease Control (CDC), which is the government authority in charge of infectious disease prevention and intervention. Through the national laboratory system, Taiwan CDC effectively detects and characterizes pathogens that cause communicable diseases across the entire country, including both known and novel threats, and also conducts epidemiologic analyses of infectious diseases. In this article, we describe the national laboratory system for public health in Taiwan. We provide additional information on the national influenza laboratory surveillance network to demonstrate how our national laboratory systems work in practice, including descriptions of long-term seasonal influenza characterization and successful experiences identifying novel H7N9 and H6N1 influenza viruses.


title: Resequencing microarray for detection of human adenoviruses in patients with conjunctivitis

text: Abstract Background Although high-density resequencing microarray is useful for detection and tracking the evolution of viruses associated with respiratory tract infections, no report on using this technology for the detection of viruses in patients with conjunctivitis is available. Objectives To test if high-density resequencing microarray can be applied to detection of viruses in conjunctival swabs for patients with conjunctivitis. Study design In this prospective proof-of-concept study, every 4 or 5 bacterial culture-negative conjunctival swab samples were pooled and subject to viral detection using TessArray™ Resequencing Pathogen Microarrays-Flu 3.1 (RPM-Flu-3.1). Results were compared with human adenovirus (HAdV) hexon gene PCR sequencing and viral culture. Results Thirty-two of the 38 conjunctival swab samples were bacterial culture-negative. Four of the 7 pooled samples were positive for HAdV using RPM-Flu-3.1. Hexon gene PCR sequencing on the 38 original individual samples showed that 3 and 4 samples contained HAdVs species D and B respectively. All the 6 samples that were positive for hexon gene PCR but negative for bacterial culture were also positive by the resequencing microarray. Viral culture was positive for HAdV type 3 in 1 sample, which was also positive by PCR and resequencing microarray. Conclusions Resequencing microarray is as sensitive as PCR for detection of HAdV in conjunctival swabs. Unlike viral culture and hexon gene PCR sequencing, resequencing microarray was not able to differentiate the type and species of HAdV. Development of microarrays for conjunctivitis can be performed for rapid diagnosis of the viral cause of conjunctivitis.


title: L’usage récréatif du cannabis: des effets aux méfaits Données épidémiologiques*

text: RÉSUMÉ À l’heure où l’usage médical de la plante « cannabis dit thérapeutique » est pratiquement acté dans notre pays, l’ouverture à son usage récréatif constitue la suite logique, à l’image de la chronologie toujours suivie dans tous les pays. En effet, ceux qui ont légalisé la drogue - le végétal - ont auparavant approuvé son emploi en thérapeutique, étape de « justification » qui semble incontournable. Il nous a donc paru opportun de rappeler les effets et les méfaits de la drogue dans le cadre de son usage récréatif. Les enquêtes en population générale réalisées en France depuis 25 ans par Santé publique France et l’Observatoire français des drogues et toxicomanies, permettent de suivre l’évolution de la consommation de substances psychoactives. Une attention toute particulière est portée aux usages de cannabis qui, dans un contexte de large diffusion depuis un quart de siècle n’ont cessé de progresser parmi les jeunes générations, mais également parmi les adultes plus âgés. La France est le pays européen dont la prévalence de consommation de cannabis est la plus élevée chez les jeunes et les adultes. En 25 ans, sa diffusion n’a cessé de s’étendre et le taux d’expérimentation a été pratiquement multiplié par 4. Estimé à 12,7 % en 1992, il atteint 44,8 % en 2017. De surcroît, en 2017, ce sont 25 % des usagers dans l’année de 18 à 64 ans qui présentent un risque élevé d’usage problématique ou de dépendance. Ce chiffre est inquiétant car il est en progression constante, il affecte 3 % des 18-64 ans, soit un peu plus d’un million de personnes. SUMMARY As the medical use of so called “therapeutic cannabis" is in the process of being approved in France, the opening to its recreational use is the next logical step, as it has been always the chronology followed in all countries. Indeed, those who have legalized the drug have previously approved its therapeutic use. This 'justifying a project phase' stage seems unavoidable. Therefore, it is appropriate to recall the effects and misdeeds of the drug during its recreational use. The general population surveys carried out in France for 25 years by public health France and the French Observatory of Drugs and Drug Addiction, have followed the evolution of psychoactive substances consumption. Particular attention was focused on cannabis use, which, in a context of wide dissemination for a quarter of a century, rose steadily higher among younger generations, but also among older adults. France is the European country with the highest prevalence of cannabis use among young people and adults. Last 25 years, its diffusion has continued to expand, and the experimentation rate multiplied by near 4. Estimated at 12.7% in 1992, it reached 44.8% in 2017. Moreover, 25% of users in the year aged from 18 to 64 years old were at high risk of problematic use or dependence in 2017. This figure is worrying because it is constantly increasing; it affects 3% of 18-64-year-old, just over a million people.


title: A mouse model of SARS-CoV-2 infection and pathogenesis

text: Summary Since December 2019, a novel coronavirus SARS-CoV-2 has emerged and rapidly spread throughout the world, resulting in a global public health emergency. The lack of vaccine and antivirals has brought an urgent need for animal model. Human Angiotensin converting enzyme II (ACE2) has been identified as a functional receptor for SARS-CoV-2. In this study, we generated a mouse model expressing human ACE2 (hACE2) using CRISPR/Cas9 knock-in technology. Compared with wild-type C57BL/6 mice, both young and aged hACE2 mice sustained high viral loads in lung, trachea and brain upon intranasal infection. Although fatalities were not observed, interstitial pneumonia and elevated cytokines were seen in SARS-CoV-2 infected- aged hACE2 mice. Interestingly, intragastric inoculation of SARS-CoV-2 was evidenced to cause productive infection and lead to pulmonary pathological changes in hACE2 mice. Overall, this animal model described here provides a useful tool for studying SARS-CoV-2 transmission and pathogenesis, and evaluating COVID-19 vaccines and therapeutics.


title: Acquired but reversible loss of erythrocyte complement receptor 1 (CR1, CD35) and its longitudinal alteration in patients with severe acute respiratory syndrome

text: This longitudinal study investigates the change of erythrocyte complement receptor (E-CR1) expression in patients with severe acute respiratory syndrome (SARS). Circulating E-CR1 expression was semiquantified by flow cytometric analyses in 54 SARS patients and in 212 healthy individuals as a control. Since E-CR1 expression is influenced by the genetic polymorphisms in the CR1 gene, a major genetic polymorphism located within intron 27 of the CR1 gene was simultaneously analysed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The results showed that the expression level of E-CR1 (referred to as net fluorescence intensity values, NFI) was statistically correlated with the relevant genetic genotypes among the Chinese population including the healthy individuals (NFI: 5·14 ± 0·82, 3·57 ± 0·66 and 2·67 ± 0·32 for HH, HL and LL genotypes, respectively) and SARS patients (NFI: 3·52 ± 0·91 and 2·63 ± 0·70 for HH and HL genotypes, respectively). Interestingly, the expression density of E-CR1 was found to fall significantly during the initiation and progressive phases (weeks 1 and 2 after the disease onset) and gradually returned close to normal through their whole convalescent phase (beginning from weeks 2 or 3 to weeks 7 or 8) in SARS patients irrespective CR1 genotype. In conclusion, our findings, at least, suggest that E-CR1 is likely involved in immune pathogenesis of SARS disease.


title: De Novo Assembly and Comparative Transcriptome Analysis Provide Insight into Lysine Biosynthesis in Toona sinensis Roem

text: Toona sinensis Roem is a popular leafy vegetable in Chinese cuisine and is also used as a traditional Chinese medicine. In this study, leaf samples were collected from the same plant on two development stages and then used for high-throughput Illumina RNA-sequencing (RNA-Seq). 125,884 transcripts and 54,628 unigenes were obtained through de novo assembly. A total of 25,570 could be annotated with known biological functions, which indicated that the T. sinensis leaves and shoots were undergoing multiple developmental processes especially for active metabolic processes. Analysis of differentially expressed unigenes between the two libraries showed that the lysine biosynthesis was an enriched KEGG pathway, and candidate genes involved in the lysine biosynthesis pathway in T. sinensis leaves and shoots were identified. Our results provide a primary analysis of the gene expression files of T. sinensis leaf and shoot on different development stages and afford a valuable resource for genetic and genomic research on plant lysine biosynthesis.


Substance 'disuse' during crisis


docid: gbyyehbu

title: Detection of human coronavirus 229E-specific antibodies using recombinant fusion proteins

text: Abstract Human coronaviruses are known to be a common cause of respiratory infections in man. However, the diagnosis of human coronavirus infections is not carried out routinely, primarily because the isolation and propagation of these viruses in tissue culture is difficult and time consuming. The aim of this study was to evaluate the use of recombinant, bacterial expressed proteins in the serodiagnosis of coronavirus infections. Two proteins were examined: the human coronavirus 229E nucleocapsid protein (N), expressed as a fusion protein in the vector pUR and the coronavirus 229E surface glycoprotein (S), expressed as a fusion protein in the vector pROS. The recombinant proteins were used as antigens in Western blot (WB) assays to detect the 229E-specific IgG antibodies and the results were compared with a standard serological method, indirect immunofluorescence. Serum samples of 51 paediatric patients, suffering from acute respiratory illness, and 10 adults, voluntarily infected with human coronavirus, were tested. The serum samples of the adult group had coronavirus-specific IgG antibodies in both test systems. In contrast, only 8 51 sera of the paediatric group were positive for coronavirus-specific IgG by both WB and IF and 20 51 sera were positive by WB, but not by IF. The overall incidence of human coronavirus infections in the paediatric age group was 55% evaluated by WB analysis and 16% evaluated by IF. This study shows that recombinant human coronavirus 229E proteins are suitable reagents for the epidemiological screening of coronavirus 229E infections.


Genomic Characterization of a Novel Hepatovirus from Great Roundleaf Bats in China


title: Molecular identification and transcriptional regulation of porcine IFIT2 gene

text: IFN-induced protein with tetratricopeptide repeats 2 (IFIT2) plays important roles in host defense against viral infection as revealed by studies in humans and mice. However, little is known on porcine IFIT2 (pIFIT2). Here, we performed molecular cloning, expression profile, and transcriptional regulation analysis of pIFIT2. pIFIT2 gene, located on chromosome 14, is composed of two exons and have a complete coding sequence of 1407 bp. The encoded polypeptide, 468 aa in length, has three tetratricopeptide repeat motifs. pIFIT2 gene was unevenly distributed in all eleven tissues studied with the most abundance in spleen. Poly(I:C) treatment notably strongly upregulated the mRNA level and promoter activity of pIFIT2 gene. Upstream sequence of 1759 bp from the start codon which was assigned +1 here has promoter activity, and deltaEF1 acts as transcription repressor through binding to sequences at position − 1774 to − 1764. Minimal promoter region exists within nucleotide position − 162 and − 126. Two adjacent interferon-stimulated response elements (ISREs) and two nuclear factor (NF)-κB binding sites were identified within position − 310 and − 126. The ISRE elements act alone and in synergy with the one closer to start codon having more strength, so do the NF-κB binding sites. Synergistic effect was also found between the ISRE and NF-κB binding sites. Additionally, a third ISRE element was identified within position − 1661 to − 1579. These findings will contribute to clarifying the antiviral effect and underlying mechanisms of pIFIT2.


title: Data-driven modelling and prediction of COVID-19 infection in India and correlation analysis of the virus transmission with socio-economic factors

text: AIMS: The current study attempts to model the COVID-19 outbreak in India, USA, China, Japan, Italy, Iran, Canada and Germany. The interactions of coronavirus transmission with socio-economic factors in India using the multivariate approach were also investigated. METHODS: Actual cumulative infected population data from 15 February to May 15, 2020 was used for determination of parameters of a nested exponential statistical model, which were further employed for the prediction of infection. Correlation and Principal component analysis provided the relationships of coronavirus spread with socio-economic factors of different states of India using the Rstudio software. RESULTS: Cumulative infection and spreadability rate predicted by the model was in good agreement with the actual observed data for all countries (R(2) = 0.985121 to 0.999635, and MD = 1.2–7.76%) except Iran (R(2) = 0.996316, and MD = 18.38%). Currently, the infection rate in India follows an upward trajectory, while other countries show a downward trend. The model claims that India is likely to witness an increased spreading rate of COVID-19 in June and July. Moreover, the flattening of the cumulative infected population is expected to be obtained in October infecting more than 12 lakhs people. Indian states with higher population were more susceptible to virus infection. CONCLUSIONS: A long-term prediction of cumulative cases, spreadability rate, pandemic peak of COVID-19 was made for India. Prediction provided by the model considering most recent data is useful for making appropriate interventions to deal with the rapidly emerging pandemic.


Therapeutic Use of Immunoglobulins


docid: wcpdiykp

title: Ocular Examination and Corneal Surface Disease in the Ferret

text: This article provides a brief, clinically relevant review of corneal surface disease in the ferret. A description of the ophthalmic examination of the ferret is provided. Stepwise descriptions of the most common ophthalmic abnormalities are provided, along with common rule-outs.


title: Transcriptome-wide shift from photosynthesis and energy metabolism upon endogenous fluid protein depletion in young Nepenthes ampullaria pitchers

text: Carnivorous pitcher plants produce specialised pitcher organs containing secretory glands, which secrete acidic fluids with hydrolytic enzymes for prey digestion and nutrient absorption. The content of pitcher fluids has been the focus of many fluid protein profiling studies. These studies suggest an evolutionary convergence of a conserved group of similar enzymes in diverse families of pitcher plants. A recent study showed that endogenous proteins were replenished in the pitcher fluid, which indicates a feedback mechanism in protein secretion. This poses an interesting question on the physiological effect of plant protein loss. However, there is no study to date that describes the pitcher response to endogenous protein depletion. To address this gap of knowledge, we previously performed a comparative RNA-sequencing experiment of newly opened pitchers (D0) against pitchers after 3 days of opening (D3C) and pitchers with filtered endogenous proteins (>10 kDa) upon pitcher opening (D3L). Nepenthes ampullaria was chosen as a model study species due to their abundance and unique feeding behaviour on leaf litters. The analysis of unigenes with top 1% abundance found protein translation and stress response to be overrepresented in D0, compared to cell wall related, transport, and signalling for D3L. Differentially expressed gene (DEG) analysis identified DEGs with functional enrichment in protein regulation, secondary metabolism, intracellular trafficking, secretion, and vesicular transport. The transcriptomic landscape of the pitcher dramatically shifted towards intracellular transport and defence response at the expense of energy metabolism and photosynthesis upon endogenous protein depletion. This is supported by secretome, transportome, and transcription factor analysis with RT-qPCR validation based on independent samples. This study provides the first glimpse into the molecular responses of pitchers to protein loss with implications to future cost/benefit analysis of carnivorous pitcher plant energetics and resource allocation for adaptation in stochastic environments.


title: Serological survey of SARS‐CoV‐2 for experimental, domestic, companion and wild animals excludes intermediate hosts of 35 different species of animals

text: The pandemic SARS‐CoV‐2 has been reported in 123 countries with more than 5,000 patients died from it. However, the original and intermediate hosts of the virus remain unknown. In this study, 1,914 serum samples from 35 animal species were used for detection of SARS‐CoV‐2‐specific antibodies using double‐antigen sandwich ELISA after validating its specificity and sensitivity. The results showed that no SARS‐CoV‐2‐specific antibodies were detected in above samples which excluded the possibility of 35 animal species as intermediate host for SARS‐CoV‐2. More importantly, companion animals including pet dogs (including one dog the SARS‐CoV‐2 patient kept and two dogs which had close contact with it) and cats, street dogs and cats also showed serological negative to SARS‐CoV‐2, which relieved the public concerns for the pets as SARS‐CoV‐2 carriers.


title: The growth pattern and fuel life cycle analysis of the electricity consumption of Hong Kong

text: As the consumption of electricity increases, air pollutants from power generation increase. In metropolitans such as Hong Kong and other Asian cities, the surge of electricity consumption has been phenomenal over the past decades. This paper presents a historical review about electricity consumption, population, and change in economic structure in Hong Kong. It is hypothesized that the growth of electricity consumption and change in gross domestic product can be modeled by 4-parameter logistic functions. The accuracy of the functions was assessed by Pearson's correlation coefficient, mean absolute percent error, and root mean squared percent error. The paper also applies the life cycle approach to determine carbon dioxide, methane, nitrous oxide, sulfur dioxide, and nitrogen oxide emissions for the electricity consumption of Hong Kong. Monte Carlo simulations were applied to determine the confidence intervals of pollutant emissions. The implications of importing more nuclear power are discussed.


title: Opening up while locking down: how an Irish independent sector mental health service is responding to the COVID-19 crisis

text: The COVID-19 pandemic poses a particular set of challenges for health services. Some of these are common across all services (e.g. strategies to minimise infections; timely testing for patients and staff; and sourcing appropriate personal protective equipment (PPE)) and some are specific to mental health services (e.g. how to access general medical services quickly; how to safely deliver a service that traditionally depends on intensive face to face contact; how to isolate someone who does not wish to do so; and how to source sufficient PPE in the face of competing demands for such equipment). This paper describes how St Patrick’s Mental Health Services (SPMHS) chose to address this unfolding and ever-changing crisis, how it developed its strategy early based on a clear set of objectives and how it adapted (and continues to adapt) to the constantly evolving COVID-19 landscape.


docid: dwfwwdbn

title: International Adoption: Issues in Infectious Diseases

text: International adoptions have become increasingly common in the United States. Children awaiting international adoption and families traveling to adopt these children can be exposed to a variety of infectious diseases. Compared with the United States, foreign countries often have different immunization practices and methods of diagnosing, treating, and monitoring disease. Reporting of medical conditions can also differ from that of the United States. The prevalence of infectious diseases varies from country to country and may or may not be common among adopted children. The transmission of tuberculosis, hepatitis B, and measles from adopted children to family members has been documented. Furthermore, infectious organisms (e.g., intestinal parasites), bacterial pathogens (e.g., Bordetella pertussis and Treponema pallidum), and viruses (e.g., human immunodeficiency virus and hepatitis viruses) may cause clinically significant morbidity and mortality among infected children. Diseases such as severe acute respiratory syndrome or avian influenza have not been reported among international adoptees, but transmission is possible if infection is present. Family members may be infected by others during travel or by their adopted child after returning home. Families preparing to adopt a child from abroad should pay special attention to the infectious diseases they may encounter and to the precautions they should take on returning home.


title: In-hospital evaluation of orthophthalaldehyde as a high level disinfectant for flexible endoscopes

text: Abstract One hundred endoscopes used for bronchoscopy (30), gastroscopy (35) or colonoscopy (35) were studied to determine the efficiency of a new high level disinfectant, orthophthalaldehyde (OPA). Manual cleaning was the method studied since this would be the least effective and thereby provide the greatest challenge to the 0·5% ( w v ) OPA solution. The OPA was convenient and easy to use since it did not have irritating vapours and as it is used directly, does not require dilution. Our study demonstrated that the OPA was stable for up to 14 days despite repeated re-use. The cleaning/ disinfection procedure could achieve a ⩾5 LOG10 reduction in bacterial load. This in-hospital evaluation supports the conclusion that OPA is an effective choice as a high level disinfectant for flexible endoscopes.