title: Reflections of the Angiotensin Receptor Blocker Recall by the FDA and Repercussions on Healthcare

text: PURPOSE: Beginning in July of 2018, the FDA issued a voluntary recall regarding the presence of a contaminant found in the manufacturing of valsartan. What would ensue has become a largely unprecedented sequence of alarming events since the FDA began reporting public recalls, withdrawals and safety alerts on their website in 2016. Since then, the United States has been significantly impacted by drug recalls affecting angiotensin receptor blockers. This report arms clinicians with additional guidance and provides a framework for responding appropriately to future similar incidents and includes an overview of the angiotensin receptor blockers, and their effects and safety profiles. METHODS: This report includes a review of data from all pertinent clinical and scientific sources including information from the FDA’s inspection documents and recall website. Additional information is provided on the specific bottles including all lot numbers, expiration dates, etc. RESULTS: The recalls/withdrawals are attributable to the presence of cancer-causing contaminants identified during the manufacturing process from drug manufacturers abroad. The root causes behind the recalls and subsequent shortage appear multifactorial, and stem to a certain extent from the outsourcing of medication manufacturing overseas and lack of quality checks and appropriate oversight. CONCLUSIONS: This inherent issue is not likely to resolve soon and has eroded the public trust of/in the healthcare system and the pharmaceutical industry. Patients and healthcare providers are significantly affected and should have a full understanding of the matter in order to guide appropriate response and actions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10557-020-06976-0) contains supplementary material, which is available to authorized users.


docid: gissdksr

title: The positive impact of lockdown in Wuhan on containing the COVID-19 outbreak in China

text: BACKGROUND: With its epicenter in Wuhan, China, the COVID-19 outbreak was declared a public health emergency of international concern (PHEIC) by the World Health Organization (WHO). Consequently, many countries have implemented flight restrictions to China. China itself has imposed a lockdown of the population of Wuhan as well as the entire Hubei province. However, whether these two enormous measures have led to significant changes in the spread of COVID-19 cases remains unclear. METHODS: We analyzed available data on the development of confirmed domestic and international COVID-19 cases before and after lockdown measures. We evaluated the correlation of domestic air traffic to the number of confirmed COVID-19 cases and determined the growth curves of COVID-19 cases within China before and after lockdown as well as after changes in COVID-19 diagnostic criteria. RESULTS: Our findings indicate a significant increase in doubling time from 2 days (95% Confidence Interval, CI): 1.9–2.6), to 4 days (95% CI: 3.5–4.3), after imposing lockdown. A further increase is detected after changing diagnostic and testing methodology to 19.3 (95% CI: 15.1–26.3), respectively. Moreover, the correlation between domestic air traffic and COVID-19 spread became weaker following lockdown (before lockdown: r = 0.98, p < 0.05 vs. after lockdown: r = 0.91, p = NS). CONCLUSIONS: A significantly decreased growth rate and increased doubling time of cases was observed, which is most likely due to Chinese lockdown measures. A more stringent confinement of people in high risk areas seem to have a potential to slow down the spread of COVID-19.


title: The role of evolution in the emergence of infectious diseases

text: It is unclear when, where and how novel pathogens such as human immunodeficiency virus (HIV), monkeypox and severe acute respiratory syndrome (SARS) will cross the barriers that separate their natural reservoirs from human populations and ignite the epidemic spread of novel infectious diseases. New pathogens are believed to emerge from animal reservoirs when ecological changes increase the pathogen's opportunities to enter the human population(1) and to generate subsequent human-to-human transmission(2). Effective human-to-human transmission requires that the pathogen's basic reproductive number, R(0), should exceed one, where R(0) is the average number of secondary infections arising from one infected individual in a completely susceptible population(3). However, an increase in R(0), even when insufficient to generate an epidemic, nonetheless increases the number of subsequently infected individuals. Here we show that, as a consequence of this, the probability of pathogen evolution to R(0) > 1 and subsequent disease emergence can increase markedly. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature02104) contains supplementary material, which is available to authorized users.


title: Stellungnahme der Österreichischen Gesellschaft für Pneumologie (ÖGP): Management von Patienten mit SARS-CoV-2-Infektionen und von Patienten mit chronischen Lungenerkrankungen während der COVID-19-Pandemie (Stand 27.04.2020)

text: The COVID-19 pandemic is currently a challenge worldwide. In Austria, a crisis within the health care system has so far been avoided. The treatment of patients with community-acquired pneumonia (CAP), including SARS-CoV‑2 infections, should continue to be based on evidence-based CAP guidelines during the pandemic. However, COVID-19-specific adjustments are useful. The treatment of patients with chronic lung diseases must be adapted during the pandemic, but must still be guaranteed.


title: Membrane Composition Modulates Fusion by Altering Membrane Properties and Fusion Peptide Structure

text: Membrane fusion, one of the most essential processes in the life of eukaryotes, occurs when two separate lipid bilayers merge into a continuous bilayer and internal contents of two separated membranes mingle. There is a certain class of proteins that assist the binding of the viral envelope to the target host cell and catalyzing fusion. All class I viral fusion proteins contain a highly conserved 20–25 amino-acid amphipathic peptide at the N-terminus, which is essential for fusion activity and is termed as the ‘fusion peptide’. It has been shown that insertion of fusion peptides into the host membrane and the perturbation in the membrane generated thereby is crucial for membrane fusion. Significant efforts have been given in the last couple of decades to understand the lipid-dependence of structure and function of the fusion peptide in membranes to understand the role of lipid compositions in membrane fusion. In addition, the lipid compositions further change the membrane physical properties and alter the mechanism and extent of membrane fusion. Therefore, lipid compositions modulate membrane fusion by changing membrane physical properties and altering structure of the fusion peptide.


docid: bvoogkdu

title: Evaluation of percutaneous dilatational tracheostomy under laryngosuspension

text: PURPOSE: To describe the technique and outcomes of percutaneous tracheostomy under laryngosuspension. METHODS: A consecutive series of patients who underwent percutaneous tracheostomy under laryngosuspension were reviewed for outcomes. The procedure is performed under general anesthesia and laryngosuspension. An 8.5 oral endotracheal tube is inserted and the cuff is inflated in the supraglottis, allowing access to the whole trachea and subglottis. The tube is taped to the laryngoscope. A rigid endoscope is inserted in the endotracheal tube through a swivel connector connected to the tube and the ventilation circuit. Percutaneous tracheostomy kit is used to perform dilatational tracheostomy at the desired level of the trachea under direct visual endoscopic control. RESULTS: Forty-eight patients underwent percutaneous tracheostomy under laryngosuspension. Thirty-two cases were performed in an emergency after securing the airway with endotracheal intubation. In all other cases, tracheostomy was performed as a part of an elective procedure affecting the airway or in patients requiring prolonged ventilation. More than half of patients were considered high risk by virtue of one or more of the following: morbid obesity, prior neck surgery, prior neck radiotherapy, progressive head and neck cancer, or laryngotracheal stenosis. Complications occurred in seven cases. CONCLUSION: Percutaneous tracheostomy under laryngosuspension has the advantage of optimal control of patient ventilation and hemostasis throughout the procedure. High-quality endoscopic vision and easy access to the airway under laryngosuspension allow tracheostomy to be performed with maximum safety.


title: Telemedicine: Potential applications in epidemic situations

text: Summary Background Telemedicine has several applications regarding different medical specialties or clinical situations. However, telemedicine as a potential tool during epidemics is not as well considered. Methods In this paper, the application of telemedicine is conceptualised using five possible evidence-based epidemic situations. Results The first situation corresponds to asymptomatic individuals, mainly home-based, living in an epidemic-affected location. The application of telemedicine would be through the use of teleconsultation for emergency medical dispatching and would occur when suspicious symptoms are detected by an individual. The second situation for the application of telemedicine is principally home-based and corresponds to the follow-up telemonitoring of asymptomatic individuals identified as case contacts. Concrete applications of these concepts were used during the Ebola virus disease outbreak in Africa since 2014. The third situation links to symptomatic cases in need of isolation. Examples include patients isolated in Taiwan during SARS epidemic in 2003 and H1N1 pandemic influenza in 2009, as well as H7N9 influenza infected patients in 2013 in China. The fourth situation involves tele-expertise when local medical resources do not have the technical expertise for the diagnosis or treatment of a patient and support is required from reference centres. The fifth situation corresponds to a healthcare facility under quarantine that would use telemedicine to keep taking care of patients that cannot access the facility, as it was the case in June 2015 in Seoul during the Middle East Respiratory Syndrome Coronavirus epidemic. Conclusion The use of telemedicine in epidemic situations has a high potential in improving epidemiological investigations, disease control, and clinical case management. However, since it is a recent application, further research would be needed to gain an improved understanding of how telemedicine could be applied in epidemic situations.


Evidence-based ED Disaster Planning


docid: dkdsjbix

title: Antiviral activity of Isatidis Radix derived glucosinolate isomers and their breakdown products against influenza A in vitro/ovo and mechanism of action

text: Abstract Ethnopharmacological relevance Isatidis Radix, the sun-dried roots of Isatis indigotica Fortune ex Lindl., is one of the most usually used traditional Chinese medicines. For centuries, the herb has been employed in clinical practice for treatment of virus infection and inflammation. However, its active ingredients remain unclear. Aim of the study In the present study, the anti-influenza virus activity of epiprogoitrin, progoitrin, epigoitrin and goitrin, the Isatidis Radix derived glucosinolate isomers and their breakdown products, was firstly evaluated in vitro and in ovo and their mechanism of action was investigated. Materials and methods Epiprogoitrin, progoitrin, epigoitrin and goitrin were isolated from Isatidis Radix by chiral separation. In vitro and in ovo evaluations were performed on Madin-Darby canine kidney (MDCK) cells and embryonated eggs respectively, both using protocols including prevention, treatment and virus neutralization. Hemagglutination (HA) and neuraminidase (NA) inhibition assays were performed for further understanding of the antiviral mechanism. Results Isatidis Radix derived glucosinolate isomers and their breakdown products all exhibited dose-dependent inhibition effect against influenza A virus (H1N1) without toxicity. The antiviral potency of the components was in the order of progoitrin > goitrin > epigoitrin > epiprogoitrin. The attachment of the constituents to the viral envelope conduced to the mechanism of their antiviral action without disturbing viral adsorption or budding. Conclusion Taken together, these results are promising for further development of Isatidis Radix and may contribute an adjunct to pharmacotherapy for influenza virus infection.


title: Photochemical treatment of plasma with amotosalen and long‐wavelength ultraviolet light inactivates pathogens while retaining coagulation function

text: BACKGROUND: The INTERCEPT Blood System, a photochemical treatment (PCT) process, has been developed to inactivate pathogens in platelet concen‐trates. These studies evaluated the efficacy of PCT to inactivate pathogens in plasma and the effect of PCT on plasma function. STUDY DESIGN AND METHODS: Jumbo (600 mL) plasma units were inoculated with high titers of test pathogens and treated with 150 µmol per L amotosalen and 3 J per cm(2) long‐wavelength ultraviolet light. The viability of each pathogen before and after treatment was measured with biological assays. Plasma function was evaluated through measurement of coagulation factors and antithrombotic protein activities. RESULTS: The levels of inactivation expressed as log‐reduction were as follows: cell‐free human immunodeficiency virus‐1 (HIV‐1), greater than 6.8; cell‐associated HIV‐1, greater than 6.4; human T‐lymphotropic virus‐I (HTLV‐I), 4.5; HTLV‐II, greater than 5.7; hepatitis B virus (HBV) and hepatitis C virus, greater than 4.5; duck HBV, 4.4 to 4.5; bovine viral diarrhea virus, 6.0; severe acute respiratory syndrome coronavirus, 5.5; West Nile virus, 6.8; bluetongue virus, 5.1; human adenovirus 5, 6.8; Klebsiella pneumoniae, greater than 7.4; Staphylococcus epidermidis and Yersinia enterocolitica, greater than 7.3; Treponema pallidum, greater than 5.9; Borrelia burgdorferi, greater than 10.6; Plasmodium falciparum, 6.9; Trypanosoma cruzi, greater than 5.0; and Babesia microti, greater than 5.3. Retention of coagulation factor activity after PCT was expressed as the proportion of pretreatment (baseline) activity. Retention was 72 to 73 percent of baseline fibrinogen and Factor (F)VIII activity and 78 to 98 percent for FII, FV, FVII, F IX, FX, FXI, FXIII, protein C, protein S, antithrombin, and α2‐antiplasmin. CONCLUSION: PCT of plasma inactivated high levels of a wide range of pathogens while maintaining adequate coagulation function. PCT has the potential to reduce the risk of transfusion‐transmitted diseases in patients requiring plasma transfusion support.


title: Type I IFN Exhaustion is a Host Defence Protecting Against Secondary Bacterial Infections

text: Type I interferons (IFN‐I) have been known for decades for their indispensable role in curtailing viral infections. It is, however, now also increasingly recognized that IFN‐I is detrimental to the host in combating a number of bacterial infections. We have previously reported that viral infections induce partial lymphocyte activation, characterized by significant increases in the cell surface expression of CD69 and CD86, but not CD25. This systemic partial activation of lymphocytes, mediated by IFN‐I, is rapid and is followed by a period of IFN‐I unresponsiveness. Here we propose that IFN‐I exhaustion that occurs soon after a primary viral infection may be a host response protecting it from secondary bacterial infections.


title: An Extended Signal Involved in Eukaryotic −1 Frameshifting Operates through Modification of the E Site tRNA

text: Abstract By using a sensitive search program based on hidden Markov models (HMM), we identified 74 viruses carrying frameshift sites among 1500 fully sequenced virus genomes. These viruses are clustered in specific families or genera. Sequence analysis of the frameshift sites identified here, along with previously characterized sites, identified a strong bias toward the two nucleotides 5′ of the shifty heptamer signal. Functional analysis in the yeast Saccharomyces cerevisiae demonstrated that high frameshifting efficiency is correlated with the presence of a Ψ39 modification in the tRNA present in the E site of the ribosome at the time of frameshifting. These results demonstrate that an extended signal is involved in eukaryotic frameshifting and suggest additional interactions between tRNAs and the ribosome during decoding.


title: A placebo-controlled trial of Korean red ginseng extract for preventing Influenza-like illness in healthy adults

text: ABSTRACTS: BACKGROUND: Standardized Korean red ginseng extract has become the best-selling influenza-like illness (ILI) remedy in Korea, yet much controversy regarding the efficacy of the Korean red ginseng (KRG) in reducing ILI incidence remains. The aim of the study is to assess the efficacy of the KRG extract on the ILI incidence in healthy adults. METHODS/DESIGN: We will conduct a randomized, double-blind, placebo-controlled study at the onset of the influenza seasons. A total of 100 subjects 30-70 years of age will be recruited from the general populations. The subjects will be instructed to take 9 capsules per day of either the KRG extract or a placebo for a period of 3 months. The primary outcome measure is to assess the frequency of ILI onset in participated subjects. Secondary variable measures will be included severity and duration of ILI symptoms. The ILI symptoms will be scored by subjects using a 4-point scale. DISCUSSION: This study is a randomized placebo controlled trial to evaluate the efficacy of the KRG extract compared to placebo and will be provided valuable new information about the clinical and physiological effects of the KRG extract on reduction of ILI incidence including flu and upper respiratory tract infections. The study has been pragmatically designed to ensure that the study findings can be implemented into clinical practice if KRG extract can be shown to be an effective reduction strategy in ILI incidence. TRIAL REGISTRATION: NCT01478009.


title: Artificial infectious disease optimization: A SEIQR epidemic dynamic model-based function optimization algorithm

text: Abstract To solve some complicated function optimization problems, an artificial infectious disease optimization algorithm based on the SEIQR epidemic model is constructed, it is called as the SEIQR algorithm, or SEIQRA in short. The algorithm supposes that some human individuals exist in an ecosystem; each individual is characterized by a number of features; an infectious disease (SARS) exists in the ecosystem and spreads among individuals, the disease attacks only a part of features of an individual. Each infected individual may pass through such states as susceptibility (S), exposure (E), infection (I), quarantine (Q) and recovery (R). State S, E, I, Q and R can automatically and dynamically divide all people in the ecosystem into five classes, it provides the diversity for SEIQRA; that people can be attacked by the infectious disease and then transfer it to other people can cause information exchange among people, information exchange can make a person to transit from one state to another; state transitions can be transformed into operators of SEIQRA; the algorithm has 13 legal state transitions, which corresponds to 13 operators; the transmission rules of the infectious disease among people is just the logic to control state transitions of individuals among S, E, I, Q and R, it is just the synergy of SEIQRA, the synergy can be transformed into the logic structure of the algorithm. The 13 operators in the algorithm provide a native opportunity to integrate many operations with different purposes; these operations include average, differential, expansion, chevy, reflection and crossover. The 13 operators are executed equi-probably; a stable heart rhythm of the algorithm is realized. Because the infectious disease can only attack a small part of organs of a person when it spreads among people, the part variables iteration strategy (PVI) can be ingeniously applied, thus enabling the algorithm to possess of high performance of computation, high suitability for solving some kinds of complicated optimization problems, especially high dimensional optimization problems. Results show that SEIQRA has characteristics of strong search capability and global convergence, and has a high convergence speed for some complicated functions optimization problems.


Active smoking and severity of coronavirus disease 2019 (COVID-19): the use of significance testing leads to an erroneous conclusion


title: Expression of SARS-coronavirus nucleocapsid protein in Escherichia coli and Lactococcus lactis for serodiagnosis and mucosal vaccination

text: The nucleocapsid (N) protein of the severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) is an important antigen for the early diagnosis of SARS and the development of vaccines. It was expressed in Escherichia coli as a fusion with human glutathione S-transferase (hGST) and was confirmed by Western blotting analysis. This recombinant N protein (hGST-N) was purified and used to measure the SARS-CoV N-specific antibody in the sera of eight SARS patients by enzyme-linked immunosorbent assay. Specific antibody response to this purified recombinant N protein was 100% positive in the SARS patients’ sera, while none of the control sera from 30 healthy people gave a positive reaction in the same assay. The SARS-CoV N protein was also expressed in Lactococcus lactis in the cytoplasm or secreted into the medium. The N-producing strain MG1363/pSECN and the purified hGST-N protein were respectively administered to mice, either orally or intranasally. Results indicated that orally delivered MG1363/pSECN induced significant N-specific IgG in the sera. In conclusion, our work provides a novel strategy to produce the SARS-CoV N protein for serodiagnosis and for L. lactis-based mucosal vaccines.


title: Use of COVID‐19 convalescent plasma in low‐ and middle‐income countries: a call for ethical principles and the assurance of quality and safety

text: Most high‐income countries are aggressively engaged in the collection and research evaluation of convalescent plasma as a specific passive immunotherapy for treatment of COVID‐19. Preliminary clinical data fully support such initiatives. Outbreaks of COVID‐19 are now dramatically affecting LMIC, which have restricted capability for ensuring organized and controlled collection of safe blood and plasma collection due to fragmented blood systems with limited oversight, infrastructure, equipment, and trained personnel. Nevertheless, there is an urgent effort in LMIC to provide COVID‐19 convalescent plasma as a potentially effective therapy that can be produced locally. The Working Party on Global Blood Safety of the International Society of Blood Transfusion has published “Points to consider in the preparation and transfusion of COVID‐19 convalescent plasma in low‐ and middle‐ income countries”. The purpose of this commentary is to provide an urgent general frame of ethical and technical recommendations on the use of convalescent plasma to treat patients affected by the SARS‐CoV‐2 virus in LMIC. Key ethical, quality, and safety guidance for the selection of donors, the collection and processing of blood, and the transfusion of COVID‐19 convalescent plasma should be followed. Governments should be reminded that an adequate supply of quality and safe blood components for transfusion is essential to meet the primary healthcare needs of the population. The response to the COVID‐19 epidemic highlights the importance of capacity building for an organized and sustainable national blood system while steps are taken to provide appropriately collected, tested and processed COVID‐19 convalescent plasma for investigational clinical use.


IS TEICOPLANIN A COMPLEMENTARY TREATMENT OPTION FOR COVID-19? THE QUESTION REMAINS


title: Smoking is Associated with COVID-19 Progression: A Meta-Analysis

text: Objective: To determine the association between smoking and progression of COVID-19. Design: A meta-analysis of 12 published papers. Data Source: PubMed database was searched on April 6, 2020. Eligibility criteria and data analysis: We included studies reporting smoking behavior of COVID-19 patients and progression of disease. Search terms included smoking, smoker*, characteristics, risk factors, outcomes, and COVID-19, COVID, coronavirus, sar cov-2, sar cov 2. There were no language limitations. One author extracted information for each study, screened the abstract or the full text, with questions resolved through discussion among both authors. A random effects meta-analysis was applied. Main Outcome Measures: The study outcome was progression of COVID-19 among people who already had the disease. Results: We identified 12 papers with a total of 9,025 COVID-19 patients, 878 (9.7%) with severe disease and 495 with a history of smoking (5.5%). The meta-analysis showed a significant association between smoking and progression of COVID-19 (OR 2.25, 95% CI 1.49-3.39, p=0.001). Limitations in the 12 papers suggest that the actual risk of smoking may be higher. Conclusions: Smoking is a risk factor for progression of COVID-19, with smokers having higher odds of COVID-19 progression than never smokers. Physicians and public health professionals should collect data on smoking as part of clinical management and add smoking cessation to the list of practices to blunt the COVID-19 pandemic.


title: Vaccines for respiratory disease in cattle

text: Abstract Respiratory disease is one of the most serious disease complexes affecting beef cattle production. For example, it is claimed to cost the UK industry about £70 million per year. It is usually associated with young cattle and can occur in a variety of situations. It is a good example of multifactorial disease in that its aetiology involves both infection by a variety of microorganisms and a number of environmental factors. Several distinct syndromes occur and a number of microorganisms are thought to be important including the bacteria Pasteurella haemolytica type A1, P. multocida, Haemophilus somnus, Corynebacterium pyogenes, Mycoplasma bovis and M. dispar. Of the viruses, bovine herpes virus 1 (BHV1) and respiratory syncytial virus (RSV) are known to be important, the former also causing the specific syndrome, infectious bovine rhinotracheitis (IBR) in addition to its involvement in the pneumonia complex. Other viruses of possible importance include para-influenza 3 (Pi3), adenoviruses, bovine viral diarrhoea (BVD) virus, coronavirus and rhinovirus.


title: Epidemiology of viral respiratory infections

text: Abstract Acute respiratory tract infections are the most common illnesses in all individuals, regardless of age or gender. Epidemiologic surveys and community-based studies conducted since the beginning of the 20th century have determined the rates of illness and the pathogens involved in such infections. These studies have shown that rhinoviruses cause the great majority of these respiratory illnesses, and their findings have examined the means of transmission of respiratory illness. More recently, advances in diagnostic techniques have enabled more complete identification of the viruses involved in respiratory infections, which has aided in the ability to direct specific therapeutic agents at the causative pathogens.


title: Why is active travel more satisfying than motorized travel? Evidence from Dublin

text: Abstract Some trips are better than others, and more and more studies find that active travel (walking and cycling) is more satisfying than motorized forms of travel (using the car or public transport). Why is this the case? Using data on travel satisfaction from 4134 commutes to a large University campus in Dublin, Ireland, this paper replicates the differences in travel satisfaction between active and motorized travel. We attribute these differences in large part to the duration of the trip. Subjective trip characteristics, such as safety and convenience, also play important roles. The trip duration explains rush-hour effects as well as why people starting from less affluent and more difficult-to-reach places are less satisfied with their trips. Longer-term policy options suggested by these results include infrastructure developments and spatial development strategies. A shorter-term initiative would be to delay university schedules in the morning to avoid low travel satisfaction during the slow rush-hour period and simultaneously ease pressure on the transport network at peak times.


title: Study on the 2‐Phenylchroman‐4‐One Derivatives and their anti‐MERS‐CoV Activities

text: Study on the 2‐phenylchroman‐4‐one derivatives and their anti‐MERS‐CoVactivities. [Image: see text]


COVID‐19 diffusion capability is its worst, unpredictable chracateristic. How to visit a patient from a distance


Returning to Sport during the Covid-19 pandemic: The sports physicians’ role


title: COVID‐19 chilblain‐like lesion: immunohistochemical demonstration of SARS‐CoV‐2 spike protein in blood vessel endothelium and sweat gland epithelium in a PCR‐negative patient

text: A 35‐year‐old woman with no significant previous medical history presented at the Emergency Department of Fundación Jiménez Díaz Hospital (Madrid, Spain) on April 14(th) with acral purpuric lesions of three weeks duration. These had started as oedematous, erythematous areas and had appeared coincidentally with fever and coughing, which lasted only two days. There was no history of diarrhoea, ageusia, hyposmia or dyspnea. The patient stated that the skin of her feet acquired a bluish discoloration after standing for some time.


title: The effect of natural feline coronavirus infection on the host immune response: A whole-transcriptome analysis of the mesenteric lymph nodes in cats with and without feline infectious peritonitis

text: Feline infectious peritonitis (FIP) is a coronavirus-induced disease of cats, in which the immune system is known to play a crucial, but complex, role in the pathogenesis. This role is still incompletely understood, with involvement of both host and viral factors. To evaluate differential gene expression and pathway involvement in feline coronavirus (FCoV) infection and FIP, we applied next-generation RNA-sequencing of the mesenteric lymph nodes from cats with naturally-acquired FIP, as well as those with systemic FCoV infection without FIP, and those with neither. Viral infection was associated with upregulation of viral defenses regardless of the disease state, but to a greater degree in FIP. FIP was associated with higher pro-inflammatory pathway enrichment, whilst non-FIP FCoV-positive cats showed lower enrichment of humoral immunity pathways, below that of uninfected cats in the case of immunoglobulin production pathways. This host response is presumed to be protective. In FIP, downregulation of T cell-related processes was observed, which did not occur in non-FIP FCoV-positive cats. These results emphasize the importance of the host’s immune balance in determining the outcome of the FCoV infection.


title: Evidence for ribosomal frameshifting and a novel overlapping gene in the genomes of insect-specific flaviviruses

text: Flaviviruses have a positive-sense, single-stranded RNA genome of ∼11 kb, encoding a large polyprotein that is cleaved to produce ∼10 mature proteins. Cell fusing agent virus, Kamiti River virus, Culex flavivirus and several recently discovered flaviviruses have no known vertebrate host and apparently infect only insects. We present compelling bioinformatic evidence for a 253-295 codon overlapping gene (designated fifo) conserved throughout these insect-specific flaviviruses, and immunofluorescent detection of its product. Fifo overlaps the NS2A/NS2B coding sequence in the -1/+2 reading frame and is most likely expressed as a trans-frame fusion protein via ribosomal frameshifting at a conserved GGAUUUY slippery heptanucleotide with 3′-adjacent RNA secondary structure (which stimulates efficient frameshifting in vitro). The discovery bears striking parallels to the recently discovered ribosomal frameshifting site in the NS2A coding sequence of the Japanese encephalitis serogroup of flaviviruses, and suggests that programmed ribosomal frameshifting may be more widespread in flaviviruses than currently realized.


title: Estimates and determinants of economic impacts from influenza‐like illnesses caused by respiratory viruses in Australian children attending childcare: a cohort study

text: BACKGROUND: Influenza and other respiratory infections cause excess winter morbidity in children. This study assessed the economic impact of influenza‐like illness (ILI) on families with children attending childcare using a societal perspective. METHODS: We conducted a prospective cohort study in 90 childcare centres and one general practitioner clinics in Sydney, Australia, during 2010. Healthy children aged ≥6 months to <3 years were enrolled. Economic impacts of ILI (temperature ≥37·8°C or parental report of fever, plus ≥1 respiratory symptoms) were collected at 2 and 4 weeks after ILI onset by telephone interview. Parent‐collected respiratory specimens were tested for respiratory viruses using real‐time PCR (RT‐PCR). Costs associated with healthcare visits, medication usage, carer time lost (work or recreation) and home care and/or additional childcare were collected. Influenza‐like illness costs were described and further analysed using a Tobit model. Zero‐inflated Poisson regression was employed to compare the numbers of healthcare visits for each ILI. RESULTS: Of 381 children enrolled and analysed, 105 developed 124 ILIs. Specimens were available for 117 ILIs: five were positive by RT‐PCR for A(H1N1)pdm09, 39 for adenovirus, 39 for rhinovirus, 15 for a coronavirus and 27 for a polyomavirus. The mean cost of all ILIs was AU$626 (95% confidence interval: AU$484–768) per ILI with no significant differences observed between viruses. Carers lost on average 13 hours of work and 3 hours of leisure time per ILI. Independent drivers of ILI costs were having both parents in employed work and longer duration of ILI. In multivariate analyses, four variables were significantly associated with an increased number of healthcare visits per ILI: non‐Caucasian child, living in a detached house, both parents in employed work and having an ILI with one or more viruses identified. CONCLUSIONS: For families with a child attending childcare, ILIs cause a substantial economic burden. An ILI in a child with working parents and/or with longer duration appears to cost more in monetary terms. Healthcare visits were increased if the child was non‐Caucasian, lived in a detached house, had working parents or had a virus‐positive ILI. Our findings on the estimates and determinants of economic impacts from respiratory virus infection highlight the importance and feasibility of an interdisciplinary (epidemiology/health economics) approach to such research.


title: Development of a polyclonal antibody-based AC-ELISA and its comparison with PCR for diagnosis of canine parvovirus infection

text: A polyclonal antibody-based antigen-capture ELISA (AC-ELISA) has been developed for detection of Canine parvovirus (CPV) antigens in faecal samples of dogs. The assay uses rabbit anti-CPV polyclonal antibody as the capture antibody, guinea pig anti-CPV polyclonal antibody as tracing antibody and anti-guinea pig HRPO conjugate as the detection system. The optimum dilution of the capture antibody and the tracing antibody capable of detecting the CPV-2 antigens was found to be 1:1 600 and 1:400, respectively, in the check-board titration. In this study, a total of 152 samples (129 faecal samples and 23 cell culture supernatant) were tested both by AC-ELISA and by polymerase chain reaction (PCR). Of the samples tested, 69 and 78 samples were found positive by AC-ELISA and PCR, respectively. The AC-ELISA had relative sensitivity, relative specificity and accuracy of 88.4%, 100.0% and 91.4% respectively. The analytical sensitivity of AC-ELISA was estimated to be 10(2.8) TCID(50)/mL whereas PCR sensitivity was 10(0.8) TCID(50)/mL. The AC-ELISA is a simple, quick and reliable method for screening large numbers of faecal samples of dogs suspected of CPV infection.


title: Where do pets fit into human quarantines?

text: Currently, there are over 400 viral zoonoses in the world. In addition, there are numerous bacterial zoonoses. Of the emerging diseases, <75% are zoonoses. The potential for household transmission through pets is now being considered in any new disease when information is incomplete regarding potential hosts, and the risk for interspecies transmission is unknown. The possible role of household pets in disease transmission in community-based quarantines has previously been overlooked.


title: Short- and long-term exposure to methamidophos impairs spermatogenesis in mice

text: Methamidophos (MET) is a pesticide that has toxic properties, including effects on fertility. This study aimed to assess the joint action of treatment time and exposure to methamidophos on the male reproductive system. MET was orally administered to adult male Swiss mice at a dose of 0.004 mg.kg(−1) for 15 and 50 consecutive days. The following parameters were evaluated: weight of reproductive organs, spermatogenesis, sperm and Sertoli cell count, daily sperm production and sperm transit time. Short-term exposure to methamidophos induced a decrease in epididymal weight. The frequency of stages V–VI of spermatogenesis increased and the frequency of stage IX decreased. In the epididymis, sperm transit time (caput/corpus) was reduced and the relative sperm number (cauda) increased. Long-term exposure induced an increase in the frequencies of stages I–IV and V-VI and decreased the stages VII-VIII and IX. The number of Sertoli cells with evident nucleoli was reduced in both exposures. These results confirm the reproductive toxicity of MET.


Rethinking COVID-19 in children: Lessons learned from pediatric viral and inflammatory cardiovascular diseases


SARS-CoV-2 (COVID-19): INTERFERON-EPSILON MAY BE RESPONSIBLE OF DECREASED MORTALITY IN FEMALES


title: Disease outcome and cytokine responses in cats immunized with an avirulent feline infectious peritonitis virus (FIPV)-UCD1 and challenge-exposed with virulent FIPV-UCD8

text: Abstract Eight cats were immunized with an avirulent strain of feline infectious peritonitis virus (FIPV)-UCD1, then challenge-exposed to a highly virulent cat passaged strain (FIPV-UCD8). Th1 and Th2 cytokine profiles in the peripheral blood mononuclear cells (PBMCs) were measured throughout in the experiment. No clinical signs of FIP were evident in the experimental cats after immunization. After challenge, the immunized cats demonstrated one of four clinical outcomes: (1) classical effusive FIP; (2) accelerated FIP; (3) non-effusive FIP, or (4) resistance to challenge. Only minor cytokine changes were observed following immunization, however, several cytokine changes occurred following challenge-exposure. The most noteworthy changes were in tumor necrosis factor-alpha (TNF-α) and interferon gamma (IFN-γ) levels. Our preliminary findings suggest that immunity against FIP is associated with TNF-α and IFN-γ response imbalance, with high TNF-α/low IFN-γ mRNA responses favouring disease and low TNF-α/high IFN-γ mRNA responses being indicative of immunity.


There are two types of the new coronavirus What does that mean? Jessica Hamzelou explains


title: APA stress report amid COVID‐19 points to parental challenges

text: COVID‐19 is undoubtedly placing a considerable toll on parents, according to the American Psychological Association's (APA's) annual Stress in America report, with many saying that working from home while coordinating their children's online learning is causing a significant amount of stress. To better understand how individuals are coping with the extreme stress of this crisis, the APA has adapted its annual stress poll into a monthly analysis of stressors and stress levels, officials stated.


Digital Learning During the COVID‐19 Pandemic


title: Identifying key papers within a journal via network centrality measures

text: This article examines the extent to which existing network centrality measures can be used (1) as filters to identify a set of papers to start reading within a journal and (2) as article-level metrics to identify the relative importance of a paper within a journal. We represent a dataset of published papers in the Public Library of Science (PLOS) via a co-citation network and compute three established centrality metrics for each paper in the network: closeness, betweenness, and eigenvector. Our results show that the network of papers in a journal is scale-free and that eigenvector centrality (1) is an effective filter and article-level metric and (2) correlates well with citation counts within a given journal. However, closeness centrality is a poor filter because articles fit within a small range of citations. We also show that betweenness centrality is a poor filter for journals with a narrow focus and a good filter for multidisciplinary journals where communities of papers can be identified.


title: Respiratory viruses in children admitted to hospital intensive care units: Evaluating the CLART® Pneumovir DNA array, ,

text: Viruses play a significant part in children's respiratory infections, sometimes leading to hospitalization in cases of severe respiratory distress. The aim of this study was to investigate respiratory infections in children treated in a hospital intensive care unit (ICU). Assays were performed using the CLART® Pneumovir DNA array assay (Genomica, Coslada, Madrid, Spain), which makes it possible to detect 11 genus of respiratory viruses simultaneously. During the winter of 2008–2009, 73 respiratory specimens collected from 53 children under 2 years of age and admitted to an ICU were tested. At least one virus was detected in 78% (57/73) of the samples. The virological diagnosis was based on single infections in 65% (37/57) and on multiple infections in 35% (20/57) of cases. The array assay revealed respiratory syncytial virus (RSV) in 73.6% (42/57) of the samples and rhinovirus in 24.6% (14/57), either on their own or in co‐infections. All viruses identified in single and multiple infections were tested, taking into account clinical features, risk factors, and severity criteria. Children with no risk factors presented more multiple infections, up to 42% of cases, than children with at least one risk factor. RSV seemed to induce severe symptoms by itself as no difference in intubation needs was observed when RSV was detected on its own or in co‐infection. The CLART® Pneumovir DNA array was useful for examining severe viral respiratory infections, when other viruses than those detected by conventional methods could be involved, particularly in an ICU. J. Med. Virol. 83:150–155, 2011. © 2010 Wiley‐Liss, Inc.


title: Renin–angiotensin system in human coronavirus pathogenesis

text: Although initially considered relatively harmless pathogens, human coronaviruses (HCoVs) are nowadays known to be associated with more severe clinical complications. Still, their precise pathogenic potential is largely unknown, particularly regarding the most recently identified species HCoV-NL63 and HCoV-HKU1. HCoVs need host cell proteins to successively establish infections. Proteases of the renin–angiotensin system serve as receptors needed for entry into target cells; this article describes the current knowledge on the involvement of this system in HCoV pathogenesis.


title: Hospital course and discharge criteria for children hospitalized with bronchiolitis

text: BACKGROUND: For children hospitalized with bronchiolitis, there is uncertainty about the expected inpatient clinical course and when children are safe for discharge. OBJECTIVES: Examine the time to clinical improvement, risk of clinical worsening after improvement, and develop discharge criteria. DESIGN: Prospective multiyear cohort study. SETTING: Sixteen US hospitals. PARTICIPANTS: Consecutive hospitalized children age <2 years with bronchiolitis. MEASUREMENT: We defined clinical improvement using: (1) retraction severity, (2) respiratory rate, (3) room air oxygen saturation, and (4) hydration status. After meeting improvement criteria, children were considered clinically worse based on the inverse of ≥1 of these criteria or need for intensive care. RESULTS: Among 1916 children, the median number of days from onset of difficulty breathing until clinical improvement was 4 (interquartile range, 3–7.5 days). Of the total, 1702 (88%) met clinical improvement criteria, with 4% worsening (3% required intensive care). Children who worsened were age <2 months (adjusted odds ratio [AOR]: 3.51; 95% confidence interval [CI]: 2.07‐5.94), gestational age <37 weeks (AOR: 1.94; 95% CI: 1.13‐3.32), and presented with severe retractions (AOR: 5.55; 95% CI: 2.12‐14.50), inadequate oral intake (AOR: 2.54; 95% CI: 1.39‐4.62), or apnea (AOR: 2.87; 95% CI: 1.45‐5.68). Readmissions were similar for children who did and did not worsen. CONCLUSIONS: Although children hospitalized with bronchiolitis had wide‐ranging recovery times, only 4% worsened after initial improvement. Children who worsened were more likely to be younger, premature infants presenting in more severe distress. For children hospitalized with bronchiolitis, these data may help establish more evidence‐based discharge criteria, reduce practice variability, and safely shorten hospital length‐of‐stay. Journal of Hospital Medicine 2015;10:205–211. © 2015 Society of Hospital Medicine


docid: xfptlkuc

title: C‐reactive protein correlates with computed tomographic findings and predicts severe COVID‐19 early

text: COVID‐19 has developed into a worldwide pandemic; early identification of severe illness is critical for controlling it and improving the prognosis of patients with limited medical resources. The present study aimed to analyze the characteristics of severe COVID‐19 and identify biomarkers for differential diagnosis and prognosis prediction. In total, 27 consecutive patients with COVID‐19 and 75 patients with flu were retrospectively enrolled. Clinical parameters were collected from electronic medical records. The disease course was divided into four stages: initial, progression, peak, and recovery stages, according to computed tomography (CT) progress. to mild COVID‐19, the lymphocytes in the severe COVID‐19 progressively decreased at the progression and the peak stages, but rebound in the recovery stage. The levels of C‐reactive protein (CRP) in the severe group at the initial and progression stages were higher than those in the mild group. Correlation analysis showed that CRP (R = .62; P < .01), erythrocyte sedimentation rate (R = .55; P < .01) and granulocyte/lymphocyte ratio (R = .49; P < .01) were positively associated with the CT severity scores. In contrast, the number of lymphocytes (R = −.37; P < .01) was negatively correlated with the CT severity scores. The receiver‐operating characteristic analysis demonstrated that area under the curve of CRP on the first visit for predicting severe COVID‐19 was 0.87 (95% CI 0.10–1.00) at 20.42 mg/L cut‐off, with sensitivity and specificity 83% and 91%, respectively. CRP in severe COVID‐19 patients increased significantly at the initial stage, before CT findings. Importantly, CRP, which was associated with disease development, predicted early severe COVID‐19.


title: Antiviral activities of whey proteins

text: Milk contains an array of proteins with useful bioactivities. Many milk proteins encompassing native or chemically modified casein, lactoferrin, alpha-lactalbumin, and beta-lactoglobulin demonstrated antiviral activities. Casein and alpha-lactalbumin gained anti-HIV activity after modification with 3-hydroxyphthalic anhydride. Many milk proteins inhibited HIV reverse transcriptase. Bovine glycolactin, angiogenin-1, lactogenin, casein, alpha-lactalbumin, beta-lactoglobulin, bovine lactoferrampin, and human lactoferrampin inhibited HIV-1 protease and integrase. Several mammalian lactoferrins prevented hepatitis C infection. Lactoferrin, methylated alpha-lactalbumin and methylated beta-lactoglobulin inhibited human cytomegalovirus. Chemically modified alpha-lactalbumin, beta-lactoglobulin and lysozyme, lactoferrin and lactoferricin, methylated alpha-lactalbumin, methylated and ethylated beta-lactoglobulins inhibited HSV. Chemically modified bovine beta-lactoglobulin had antihuman papillomavirus activity. Beta-lactoglobulin, lactoferrin, esterified beta-lactoglobulin, and esterified lactoferrindisplayed anti-avian influenza A (H5N1) activity. Lactoferrin inhibited respiratory syncytial virus, hepatitis B virus, adenovirus, poliovirus, hantavirus, sindbis virus, semliki forest virus, echovirus, and enterovirus. Milk mucin, apolactoferrin, Fe(3+)-lactoferrin, beta-lactoglobulin, human lactadherin, bovine IgG, and bovine kappa-casein demonstrated antihuman rotavirus activity.


Role of the Replicase Gene of Murine Coronavirus JHM Strain in Hepatitis


title: DNA-programming multicolor silver nanoclusters for sensitively simultaneous detection of two HIV DNAs

text: Abstract A novel DNA-stabilized silver nanoclusters (AgNCs)-based label-free fluorescent platform for simultaneously detecting two human immunodeficiency virus oligonucleotides (HIV DNAs) was developed. The sensing platform was established based on fluorescence enhancement of guanine (G)-rich and the phenomenon in the process of two silver nanoclusters (AgNCs) forming a nanoclusters dimer. The probe (AgNCs/G) utilized for HIV-1 detection adopted an effective conformation based on enhancement effect of G-rich sequence (at 500 nm ex / 565 nm em) while the probe (AgNCs/AgNCs) for HIV-2 generated fluorescence signals (at 580 nm ex / 630 nm em) with bright fluorescence only in nanoclusters dimer. The nanoprobe shows high selectivity for multiplexed analysis of target DNA with a detection limit of 11 pM, respectively. Moreover, this is the first time to use the affectivity of fluorescent AgNCs and two HIV DNAs simultaneous detection integrated into a novel method, which shows a great promise in biomedical research and early clinical diagnosis.


title: Integrated, multi-cohort analysis identifies conserved transcriptional signatures across multiple respiratory viruses

text: Respiratory viral infections are a significant burden to healthcare worldwide. Many whole genome expression profiles have identified different respiratory viral infection signatures, but these have not translated to clinical practice. Here, we performed two integrated, multi-cohort analyses of publicly available transcriptional data of viral infections. First, we identified a common host signature across different respiratory viral infections that could distinguish (a) individuals with viral infections from healthy controls and from those with bacterial infections, and (b) symptomatic from asymptomatic subjects prior to symptom onset in challenge studies. Second, we identified an influenza-specific host response signature that (a) could distinguish influenza-infected samples from those with bacterial and other respiratory viral infections, (b) was a diagnostic and prognostic marker in influenza-pneumonia patients and influenza challenge studies, and (c) was predictive of response to influenza vaccine. Our results have applications in the diagnosis, prognosis, and identification of drug targets in viral infections.


title: Host and Viral Proteins Modulating Ebola and Marburg Virus Egress

text: The filoviruses Ebolavirus and Marburgvirus are among the deadliest viral pathogens known to infect humans, causing emerging diseases with fatality rates of up to 90% during some outbreaks. The replication cycles of these viruses are comprised of numerous complex molecular processes and interactions with their human host, with one key feature being the means by which nascent virions exit host cells to spread to new cells and ultimately to a new host. This review focuses on our current knowledge of filovirus egress and the viral and host factors and processes that are involved. Within the virus, these factors consist of the major matrix protein, viral protein 40 (VP40), which is necessary and sufficient for viral particle release, and nucleocapsid and glycoprotein that interact with VP40 to promote egress. In the host cell, some proteins are hijacked by filoviruses in order to enhance virion budding capacity that include members of the family of E3 ubiquitin ligase and the endosomal sorting complexes required for transport (ESCRT) pathway, while others such as tetherin inhibit viral egress. An understanding of these molecular interactions that modulate viral particle egress provides an important opportunity to identify new targets for the development of antivirals to prevent and treat filovirus infections.


The general practitioner facing the COVID-19


title: Ultrastructural Characterization of SARS Coronavirus

text: Severe acute respiratory syndrome (SARS) was first described during a 2002–2003 global outbreak of severe pneumonia associated with human deaths and person-to-person disease transmission. The etiologic agent was initially identified as a coronavirus by thin-section electron microscopic examination of a virus isolate. Virions were spherical, 78 nm in mean diameter, and composed of a helical nucleocapsid within an envelope with surface projections. Herein, we show that infection with the SARS-associated coronavirus resulted in distinct ultrastructural features: double-membrane vesicles, nucleocapsid inclusions, and large granular areas of cytoplasm. These three structures and the coronavirus particles were shown to be positive for viral proteins and RNA by using ultrastructural immunogold and in situ hybridization assays. In addition, ultrastructural examination of a bronchiolar lavage specimen from a SARS patient showed numerous coronavirus-infected cells with features similar to those in infected culture cells. Electron microscopic studies were critical in identifying the etiologic agent of the SARS outbreak and in guiding subsequent laboratory and epidemiologic investigations.


title: Patterns of Human Respiratory Viruses and Lack of MERS-Coronavirus in Patients with Acute Upper Respiratory Tract Infections in Southwestern Province of Saudi Arabia

text: We undertook enhanced surveillance of those presenting with respiratory symptoms at five healthcare centers by testing all symptomatic outpatients between November 2013 and January 2014 (winter time). Nasal swabs were collected from 182 patients and screened for MERS-CoV as well as other respiratory viruses using RT-PCR and multiplex microarray. A total of 75 (41.2%) of these patients had positive viral infection. MERS-CoV was not detected in any of the samples. Human rhinovirus (hRV) was the most detected pathogen (40.9%) followed by non-MERS-CoV human coronaviruses (19.3%), influenza (Flu) viruses (15.9%), and human respiratory syncytial virus (hRSV) (13.6%). Viruses differed markedly depending on age in which hRV, Flu A, and hCoV-OC43 were more prevalent in adults and RSV, hCoV-HKU1, and hCoV-NL63 were mostly restricted to children under the age of 15. Moreover, coinfection was not uncommon in this study, in which 17.3% of the infected patients had dual infections due to several combinations of viruses. Dual infections decreased with age and completely disappeared in people older than 45 years. Our study confirms that MERS-CoV is not common in the southwestern region of Saudi Arabia and shows high diversity and prevalence of other common respiratory viruses. This study also highlights the importance and contribution of enhanced surveillance systems for better infection control.


Screening all pregnant women admitted to Labor and Delivery for the virus responsible for COVID-19


Evidence-Based Medicine in China


title: Cutaneous small‐vessel vasculitis associated with novel 2019 coronavirus SARS‐CoV‐2 infection (COVID‐19)

text: The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has rapidly become a global health issue. Although it is known to produce diverse cutaneous manifestations, some of them have yet to be described. This letter reports new dermatologic findings associated with a confirmed COVID‐19 case.


title: Metaphyseal osteopathy in three Australian Kelpie siblings

text: CASE REPORT: Metaphyseal osteopathy (MO) was diagnosed in three Australian Kelpie puppies that were presented for veterinary assessment of lameness. The three puppies were siblings. Each was from a different litter by the same breeding pair. The puppy in case one was seen by the authors, and the puppies in cases two and three were patients at other veterinary hospitals. However, the medical records and radiographs were examined and reviewed for this report. Radiographic investigation of the lameness revealed pathognomonic appearance of MO affecting the metaphyseal region of the long bones in all three puppies. The diagnosis was confirmed on histopathology in one patient. CONCLUSION: MO is considered a disease of large and giant‐breed dogs, being rarely reported in non‐large‐breed dogs, and has not been reported in the Australian Kelpie, which is considered a medium‐breed dog. This case series suggests a previously unreported breed predisposition to MO in the Australian Kelpie.


title: Technologies to Optimize the Care of Severe Coronavirus Disease 2019 Patients for Health Care Providers Challenged by Limited Resources

text: Health care systems are belligerently responding to the new Coronavirus Disease 2019 (COVID-19). The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a specific condition, whose distinctive features are severe hypoxemia associated with (>50% of cases) normal respiratory system compliance.(1) When a patient requires intubation and invasive ventilation, the outcome is poor,(2–4) and the length of stay in the intensive care unit (ICU) is usually 2or 3 weeks.(2) In this article, theauthors review several technological devices, which could support health care providers at the bedside to optimizethe care for COVID-19 patients who are sedated, paralyzed, and ventilated. Particular attention is provided to the use of videolaryngoscopes (VL) because these can assist anesthetists to perform a successful intubation outside the ICU while protecting health care providers from this viral infection. Authors will also review processed electroencephalographic (EEG) monitors which are used to better titrate sedation and the train-of-four monitors which are utilizedto better titrate neuromuscular blocking agents in the view of sparing limited pharmacological resources. COVID-19 can rapidly exhaust human and technological resources too within the ICU. This review features a series of technological advancements that can significantly improve the care of patients requiring isolation. The working conditions in isolation could cause gaps or barriers in communication, fatigue, and poor documentation of provided care. The available technology has several advantages including (a) facilitating appropriate paperless documentation and communication between all health care givers working in isolation rooms or large isolation areas; (b) testing patients and staff at the bedside using smart point-of-care diagnostics (SPOCD) to confirm COVID-19 infection; (c) allowing diagnostics and treatment at the bedside through point-of-care ultrasound (POCUS) and thromboelastography(TEG); (d) adapting the use of anesthetic machines and the use of volatile anesthetics. Implementing technologies for safeguarding health care providers as well as monitoring the limited pharmacological resources are paramount. Only by leveraging new technologies, it will be possible to sustain and support health care systems during the expected long course of this pandemic.


title: Pandemic Palliative Care Consultations Spanning State and Institutional Borders

text: Many critically ill patients with COVID‐19 need specialty level palliative care to manage symptoms, conduct goals of care conversations, and facilitate medical decision making in ethically and emotionally charged situations. During the apex of the COVID‐19 crisis in New York, the Adult Palliative Care Service at Columbia University Irving Medical Center (CUIMC)/NewYork‐Presbyterian (NYP) received a 7‐fold increase in consultation requests. This unprecedented increase in demand outpaced the palliative care team's ability to respond. We describe the rapid development and implementation of a scalable virtual consultation model staffed by out‐of‐state palliative care specialist volunteers. This article is protected by copyright. All rights reserved.


COVID‐19 collateral damage: delayed presentation of a perforated rectal cancer presenting as Fournier's gangrene


title: Respiratory virology and microbiology in intensive care units: a prospective cohort study

text: Our aim was to determine the frequency of 12 common respiratory viruses in patients admitted to intensive care units with respiratory symptoms, evaluate the clinical characteristics and to compare the results to routine microbiological diagnostics. Throat swabs from 122 intensive care‐patients >18 years with acute respiratory symptoms were collected upon admission and analysed with multiplex real‐time polymerase chain reaction, for 12 community respiratory viruses. Blood and respiratory tract specimens were analysed for bacteria and fungi upon clinicians' request. Clinical and paraclinical data were collected. Viruses were detected in 19 (16%) of the 122 study patients. Five virus‐positive patients (26%) had possible clinically relevant bacteria or fungi co‐detected. Patients with exacerbation in COPD were associated with a viral infection (p = 0.02). Other comorbidities, clinical and paraclinical parameters, and death were independent of a viral infection or co‐detection of bacteria/fungi. In conclusion, respiratory viruses were frequently detected in the patients. The investigated clinical and paraclinical parameters were not different in viral infections compared to other agents, thus respiratory viruses likely have similar impact on the clinical course as other agents. In 25% of the virus‐positive patients, polymicrobial aetiology was identified. Comprehensive and sensitive diagnostic methods should be emphasized to enhance respiratory diagnostics.


title: Urbanization and International Trade and Investment Policies as Determinants of Noncommunicable Diseases in Sub-Saharan Africa

text: There are three dominant globalization pathways affecting noncommunicable diseases in Sub-Saharan Africa (SSA): urbanization, trade liberalization, and investment liberalization. Urbanization carries potential health benefits due to improved access to an increased variety of food imports, although for the growing number of urban poor, this has often meant increased reliance on cheap, highly processed food commodities. Reduced barriers to trade have eased the importation of such commodities, while investment liberalization has increased corporate consolidation over global and domestic food chains. Higher profit margins on processed foods have promoted the creation of ‘obesogenic’ environments, which through progressively integrated global food systems have been increasingly ‘exported’ to developing nations. This article explores globalization processes, the food environment, and dietary health outcomes in SSA through the use of trend analyses and structural equation modelling. The findings are considered in the context of global barriers and facilitators for healthy public policy.


docid: yapqrthp

title: Shifting the paradigm: using disease outbreaks to build resilient health systems


Pediatric hematology oncology during SARS‐CoV‐2: A brief communication of 28 patients and changes in clinical practice from a single institute in Pakistan


Aspectos médico-legales de la pandemia por COVID-19


Lung tissue distribution of drugs as a key factor for COVID‐19 treatment


title: The R0 package: a toolbox to estimate reproduction numbers for epidemic outbreaks

text: BACKGROUND: Several generic methods have been proposed to estimate transmission parameters during an outbreak, especially the reproduction number. However, as of today, no dedicated software exists that implements these methods and allow comparisons. RESULTS: A review of generic methods used to estimate transmissibility parameters during outbreaks was carried out. Most methods used the epidemic curve and the generation time distribution. Two categories of methods were available: those estimating the initial reproduction number, and those estimating a time dependent reproduction number. We implemented five methods as an R library, developed sensitivity analysis tools for each method and provided numerical illustrations of their use. A comparison of the performance of the different methods on simulated datasets is reported. CONCLUSIONS: This software package allows a standardized and extensible approach to the estimation of the reproduction number and generation interval distribution from epidemic curves.


title: Keratoconjunctivitis as the initial medical presentation of the novel coronavirus disease 2019 (COVID-19)

text: Abstract We present a case of coronavirus disease 2019 (COVID-19) with an initial medical presentation of keratoconjunctivitis, the first such reported case in North America. The patient's primary symptom was a red eye with watery discharge, though she did have mild respiratory symptoms, without fever. She was diagnosed with keratoconjunctivitis; evolving corneal findings were characterized through repeat visits to ophthalmology. A conjunctival swab of the affected eye was positive for the SAR-CoV-2 virus. This case emphasizes the importance of ensuring that first-line health care providers, including ophthalmologists, optometrists, emergency physicians, and family physicians, consider COVID-19 on the differential for any patient with recent travel who presents with acute conjunctivitis. Having a high index of suspicion with this presentation would allow for appropriate precautions to be taken to prevent further spread of COVID-19.


title: When SARS‐CoV‐2 comes knocking on your lab door: Individual scientists’ experiences during the pandemic

text: A snapshot of how scientists are personally affected by the global Covid‐19 pandemic.[Image: see text]


title: Enzymatic activity of the SARS coronavirus main proteinase dimer

text: The enzymatic activity of the SARS coronavirus main proteinase dimer was characterized by a sensitive, quantitative assay. The new, fluorogenic substrate, (Ala-Arg-Leu-Gln-NH)(2)-Rhodamine, contained a severe acute respiratory syndrome coronavirus (SARS CoV) main proteinase consensus cleavage sequence and Rhodamine 110, one of the most detectable compounds known, as the reporter group. The gene for the enzyme was cloned in the absence of purification tags, expressed in Escherichia coli and the enzyme purified. Enzyme activity from the SARS CoV main proteinase dimer could readily be detected at low pM concentrations. The enzyme exhibited a high K(m), and is unusually sensitive to ionic strength and reducing agents.


Summary of the 21st United States-Japan Joint Cholera Conference


title: The Importance Of Naturally Attenuated Sars‐Cov‐2 In The Fight Against Covid‐19

text: The current SARS‐CoV‐2 pandemic is wreaking havoc throughout the world and has rapidly become a global health emergency. A central question concerning COVID‐19 is why some individuals become sick and others not. Many have pointed already at variation in risk factors between individuals. However, the variable outcome of SARS‐CoV‐2 infections may, at least in part, be due also to differences between the viral subspecies with which individuals are infected. A more pertinent question is how we are to overcome the current pandemic. A vaccine against SARS‐CoV‐2 would offer significant relief, although vaccine developers have warned that design, testing, and production of vaccines may take a year if not longer. Vaccines are based on a handful of different designs (1), but the earliest vaccines were based on live, attenuated virus. As has been the case for other viruses during earlier pandemics, SARS‐CoV‐2 will mutate and may naturally attenuate over time (2). What makes the current pandemic unique is that, thanks to state‐of‐the‐art nucleic acid sequencing technologies, we can follow in detail how SARS‐CoV‐2 evolves while it spreads. We argue that knowledge of naturally emerging attenuated SARS‐CoV‐2 variants across the globe should be of key interest in our fight against the pandemic. This article is protected by copyright. All rights reserved.


COVID‐19 in rural non‐resort town: Observation from Thailand


title: Enteric viruses in turkey enteritis

text: Gut health is very important to get maximum returns in terms of weight gain and egg production. Enteric diseases such as poult enteritis complex (PEC) in turkeys do not allow their production potential to be achieved to its maximum. A number of viruses, bacteria, and protozoa have been implicated but the primary etiology has not been definitively established. Previously, electron microscopy was used to detect the presence of enteric viruses, which were identified solely on the basis of their morphology. With the advent of rapid molecular diagnostic methods and next generation nucleic acid sequencing, researchers have made long strides in identification and characterization of viruses associated with PEC. The molecular techniques have also helped us in identification of pathogens which were previously not known. Regional and national surveys have revealed the presence of several different enteric viruses in PEC including rotavirus, astrovirus, reovirus and coronavirus either alone or in combination. There may still be unknown pathogens that may directly or indirectly play a role in enteritis in turkeys. This review will focus on the role of turkey coronavirus, rotavirus, reovirus, and astrovirus in turkey enteritis.


title: Aminopeptidase N is not required for porcine epidemic diarrhea virus cell entry

text: Abstract Porcine epidemic diarrhea virus (PEDV) is an emerging pathogenic coronavirus that causes a significant economic burden to the swine industry. The virus infects the intestinal epithelium and causes villous atrophy, resulting in diarrhea and dehydration. Interaction of the viral spike (S) surface glycoprotein − through its S1 subunit − with the host cell receptor is the first step in infection and the main determinant for virus tropism. As for several other alphacoronaviruses including the porcine transmissible gastroenteritis virus (TGEV) and the human coronavirus 229E (HCoV-229E), the aminopeptidase N (APN) protein was reported to be a functional receptor for PEDV. In this study we examined the role of APN as a receptor. We show that overexpression of porcine APN renders MDCK cells susceptible to TGEV, but not to PEDV. Consistently, unlike TGEV-S1, PEDV-S1 exhibited no binding to cell-surface expressed APN or to a soluble version of APN. Moreover, preincubation of these viruses with soluble APN or pretreatment of APN expressing ST cells with soluble TGEV-S1 blocked TGEV infection, but had no effect on infection by PEDV. The combined observations indicated that APN is not required for PEDV infection. To definitively prove this conclusion, we applied CRISPR/Cas9 genome engineering to knock out APN expression in PEDV-susceptible porcine (ST) and human cell lines (Huh7 and HeLa). As a consequence these cells no longer bound TGEV-S1 and HCoV-229E-S1 at their surface and were resistant to infection by the corresponding viruses. However, genetic ablation of APN expression had no effect on their infectability by PEDV, demonstrating that APN is not essential for PEDV cell entry.


title: Molecular characterization and phylogenetic analyses of virulent infectious bronchitis viruses isolated from chickens in Eastern Saudi Arabia

text: Infectious bronchitis virus (IBV) is one of the major respiratory viral threats for chickens. Despite the intensive application of IBV vaccines, several outbreaks have been reported worldwide. Here, we report several IBV outbreaks in thirteen poultry farms in Eastern Saudi Arabia (ESA) from 2013 to 2014. The main goals of the current study were as follows: (1) isolation and molecular characterization of the currently circulating strains in ESA (Al-Hasa, Dammam, and Buqayq) and (2) evaluation of the immune status of these birds to IBV. To achieve our goals, tissue specimens (trachea, lungs, liver, kidney and cecal tonsils) and sera were collected. High morbidity up to 100% and mortality ranging from 18 to 90% were reported. Severe infection was observed in the trachea, bronchi, and kidneys of the infected birds. IBV strains were isolated using embryonated chicken eggs. The isolated viruses induced hemorrhage, dwarfing and death of the inoculated embryos 3–5 days post-infection. The circulating IBV strains were identified by sequencing the partial IBV-N and IBV-S1 genes. These viruses showed 95% sequence identity to Indian, Italian, Egyptian and Chinese strains and were quite distinct from the locally used vaccines on the genomic level. Interestingly, high antibody titers against IBV were reported in some of these farms, suggesting the presence of new virulent strains in ESA. The seroconversion of infected birds was reported among the affected flocks. In conclusion, very virulent IBV strains are currently circulating in ESA. Further studies are currently in progress to molecularly characterize these IBV strains. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13337-017-0375-7) contains supplementary material, which is available to authorized users.


docid: yruyfazb

title: Limited awareness of animal influenza prevention and control among Dai Lue smallholder farmers in Southwest China

text: Awareness of animal influenza and its prevention and control is important for ensuring livestock health, production and welfare. In China, a country stereotyped as a major source of emerging zoonotic infectious diseases, research on the public understanding of animal influenza is limited to the Han, the main ethnic group. The present qualitative study in Southwest China investigated awareness of animal influenza among the Dai, an ethnic minority. The participants (15 men and 10 women, ages 18–83) were smallholder farmers of pigs and poultry in rural areas of Jinghong, Xishuangbanna, Yunnan Province. A mixture of interviews and group discussions took place in homes and villages. The participants were asked about their knowledge of avian influenza (H7N9), swine influenza (H1N1), precautions taken to protect against influenza, procedures when animals were sick and perceived risk of animal influenza. The data were analysed following coding and thematic analysis. The findings demonstrated a limited understanding of animal health and welfare among participants. Specifically, they were largely unaware of animal influenza (H7N9, H1N1) including its causes, symptoms, prevention and treatment. The farmers were also uninformed of the risks they faced and unknowingly engaged in behaviours which increased direct or indirect exposure to infected animals, a risk factor for human infection. They also reported poor usage of veterinary services. In order to guarantee the health, welfare and production of their livestock, immediate action is needed to enable Dai smallholder farmers to prevent and respond to animal influenza effectively and timely.


docid: ttfukeue

title: Prediction for Progression Risk in Patients with COVID-19 Pneumonia: the CALL Score

text: BACKGROUND: We aimed to clarify the high-risk factors with multivariate analysis and establish a prediction of disease progression, so as to help clinicians to better choose therapeutic strategy. METHODS: All the consecutive patients with COVID-19 admitted to Fuyang second people’s hospital or the fifth medical center of Chinese PLA general hospital between January 20 and February 22, 2020, were enrolled and their clinical data were retrospectively collected. Multivariate COX regression was used to identify the risk factors associated with progression, and then were incorporated into the nomogram to establish a novel prediction scoring model. ROC was used to assess the performance of the novel model. RESULTS: Overall, 208 patients were divided into stable group (n=168, 80.8%) and progressive group (n=40,19.2%) based on whether their conditions worsened during the hospitalization Univariate and multivariate analysis showed that comorbidity, older age, lower lymphocyte and higher lactate dehydrogenase at presentation were independent high-risk factors for COVID-19 progression. Incorporating these 4 factors, the nomogram achieved good concordance indexes of 0.86 (95%CI 0.81 - 0.91), and had well-fitted calibration curves. A novel scoring model, named as CALL, was established, and its area under ROC was 0.91 (95% CI 0.86 to 0.94). Using a cutoff value of 6 points, the positive and negative predictive values were 50.7% (38.9% - 62.4%) and 98.5% (94.7% - 99.8%), respectively. CONCLUSION: Using the CALL score model, clinicians can improve the therapeutic effect and reduce the mortality of COVID-19 with more accurate and reasonable resolutions on medical resources.


Eating disorders in the time of COVID-19


docid: nbmawmqi

title: Obesidad Y Sars-Cov-2: Consideraciones Sobre La Cirugía Bariátrica Y Recomendaciones Para El Inicio De La Actividad Quirúrgica

text: ABSTRACT The SARS-Cov-2 pandemic has a great impact worldwide, being Spain one of the most affected countries. The delay in bariatric surgery can have fatal consequences since up to 50% of the patients who are on the waiting list develop a new comorbidity during the time they remain on it and 1.5% of patients die while waiting for the intervention. That is why bariatric surgery should not be delayed, if the occupation of the hospital by COVID-19 + patients decreases significantly, and sufficient resources and safety are available to restart surgery in patients with benign pathology. This document contains the main recommendations for the bariatric surgery programs in our country from the point of view of safety, bariatric patient preparation and follow up during the SARS-Cov-2 pandemia.


title: Evolutionary and genetic analysis of the VP2 gene of canine parvovirus

text: BACKGROUND: Canine parvovirus (CPV) type 2 emerged in 1978 in the USA and quickly spread among dog populations all over the world with high morbidity. Although CPV is a DNA virus, its genomic substitution rate is similar to some RNA viruses. Therefore, it is important to trace the evolution of CPV to monitor the appearance of mutations that might affect vaccine effectiveness. RESULTS: Our analysis shows that the VP2 genes of CPV isolated from 1979 to 2016 are divided into six groups: GI, GII, GIII, GIV, GV, and GVI. Amino acid mutation analysis revealed several undiscovered important mutation sites: F267Y, Y324I, and T440A. Of note, the evolutionary rate of the CPV VP2 gene from Asia and Europe decreased. Codon usage analysis showed that the VP2 gene of CPV exhibits high bias with an ENC ranging from 34.93 to 36.7. Furthermore, we demonstrate that natural selection plays a major role compared to mutation pressure driving CPV evolution. CONCLUSIONS: There are few studies on the codon usage of CPV. Here, we comprehensively studied the genetic evolution, codon usage pattern, and evolutionary characterization of the VP2 gene of CPV. The novel findings revealing the evolutionary process of CPV will greatly serve future CPV research. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-3935-8) contains supplementary material, which is available to authorized users.


Pain Medicine Goes Digital: A Lamentation on COVID-19, the Printing Press, and the 21(st) Century


COVID-19 and Orthodontics in Brazil: What should we do?


title: The underlying changes and predicting role of peripheral blood inflammatory cells in severe COVID-19 patients: a sentinel?

text: BACKGROUND: The underlying changes of peripheral blood inflammatory cells (PBICs) in COVID-19 patients are little known. Moreover, the risk factors for the underlying changes of PBICs and their predicting role in severe COVID-19 patients remain uncertain. MATERIAL AND METHODS: This retrospective study including two cohorts: the main cohort enrolling 45 patients of severe type serving as study group, and the secondary cohort enrolling 12 patients of no-severe type serving as control group. The PBICs analysis was based on blood routine and lymphocyte subsets. The inflammatory cell levels were compared among patients according to clinical classifications, disease-associated phases, as well as one-month outcomes. RESULTS: Compared with patients of non-severe type, the patients of severe type suffered from significantly decreased counts of lymphocytes, eosinophils, basophils, but increased counts of neutrophils. These PBICs alterations got improved in recovery phase, but persisted or got worse in aggravated phase. Compared with patients in discharged group, the patients in un-discharged/died group suffered from decreased counts of total T lymphocytes, CD4+T lymphocytes, CD8+T lymphocytes, as well as NK cells at 2 weeks after treatment. Clinical classification-critically severe was the independently risk factor for lymphopenia (OR=7.701, 95%CI:1.265-46.893, P=0.027), eosinopenia (OR=5.595, 95%CI:1.008-31.054, P=0.049) and worse one-month outcome (OR=8.984; 95%CI:1.021-79.061, P=0.048). CONCLUSION: Lymphopenia and eosinopenia may serve as predictors of disease severity and disease progression in COVID-19 patients, and enhancing the cellular immunity may contribute to COVID-19 treatment. Thus, PBICs might become a sentinel of COVID-19, and it deserves attention during COVID-19 treatment.


docid: llxqcikz

title: Coronavirus and paramyxovirus in bats from Northwest Italy

text: BACKGROUND: Bat-borne virus surveillance is necessary for determining inter-species transmission risks and is important due to the wide-range of bat species which may harbour potential pathogens. This study aimed to monitor coronaviruses (CoVs) and paramyxoviruses (PMVs) in bats roosting in northwest Italian regions. Our investigation was focused on CoVs and PMVs due to their proven ability to switch host and their zoonotic potential. Here we provide the phylogenetic characterization of the highly conserved polymerase gene fragments. RESULTS: Family-wide PCR screenings were used to test 302 bats belonging to 19 different bat species. Thirty-eight animals from 12 locations were confirmed as PCR positive, with an overall detection rate of 12.6% [95% CI: 9.3–16.8]. CoV RNA was found in 36 bats belonging to eight species, while PMV RNA in three Pipistrellus spp. Phylogenetic characterization have been obtained for 15 alpha- CoVs, 5 beta-CoVs and three PMVs; moreover one P. pipistrellus resulted co-infected with both CoV and PMV. A divergent alpha-CoV clade from Myotis nattereri SpA is also described. The compact cluster of beta-CoVs from R. ferrumequinum roosts expands the current viral sequence database, specifically for this species in Europe. To our knowledge this is the first report of CoVs in Plecotus auritus and M. oxygnathus, and of PMVs in P. kuhlii. CONCLUSIONS: This study identified alpha and beta-CoVs in new bat species and in previously unsurveyed Italian regions. To our knowledge this represents the first and unique report of PMVs in Italy. The 23 new bat genetic sequences presented will expand the current molecular bat-borne virus databases. Considering the amount of novel bat-borne PMVs associated with the emergence of zoonotic infections in animals and humans in the last years, the definition of viral diversity within European bat species is needed. Performing surveillance studies within a specific geographic area can provide awareness of viral burden where bats roost in close proximity to spillover hosts, and form the basis for the appropriate control measures against potential threats for public health and optimal management of bats and their habitats.


COVID-19 and TB co-infection - 'Finishing touch'' in perfect recipe to 'severity’ or ‘death'


title: Viral Etiology of Influenza-Like Illnesses in Antananarivo, Madagascar, July 2008 to June 2009

text: BACKGROUND: In Madagascar, despite an influenza surveillance established since 1978, little is known about the etiology and prevalence of viruses other than influenza causing influenza-like illnesses (ILIs). METHODOLOGY/PRINCIPAL FINDINGS: From July 2008 to June 2009, we collected respiratory specimens from patients who presented ILIs symptoms in public and private clinics in Antananarivo (the capital city of Madagascar). ILIs were defined as body temperature ≥38°C and cough and at least two of the following symptoms: sore throat, rhinorrhea, headache and muscular pain, for a maximum duration of 3 days. We screened these specimens using five multiplex real time Reverse Transcription and/or Polymerase Chain Reaction assays for detection of 14 respiratory viruses. We detected respiratory viruses in 235/313 (75.1%) samples. Overall influenza virus A (27.3%) was the most common virus followed by rhinovirus (24.8%), RSV (21.2%), adenovirus (6.1%), coronavirus OC43 (6.1%), influenza virus B (3.9%), parainfluenza virus-3 (2.9%), and parainfluenza virus-1 (2.3%). Co-infections occurred in 29.4% (69/235) of infected patients and rhinovirus was the most detected virus (27.5%). Children under 5 years were more likely to have one or more detectable virus associated with their ILI. In this age group, compared to those ≥5 years, the risk of detecting more than one virus was higher (OR = 1.9), as was the risk of detecting of RSV (OR = 10.1) and adenovirus (OR = 4.7). While rhinovirus and adenovirus infections occurred year round, RSV, influenza virus A and coronavirus OC43 had defined period of circulation. CONCLUSIONS: In our study, we found that respiratory viruses play an important role in ILIs in the Malagasy community, particularly in children under 5 years old. These data provide a better understanding of the viral etiology of outpatients with ILI and describe for the first time importance of these viruses in different age group and their period of circulation.


title: Discovery of potential multi-target-directed ligands by targeting host-specific SARS-CoV-2 structurally conserved main protease

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in the current COVID-19 pandemic. Worldwide this disease has infected over 2.5 million individuals with a mortality rate ranging from 5 to 10%. There are several efforts going on in the drug discovery to control the SARS-CoV-2 viral infection. The main protease (M(Pro)) plays a critical role in viral replication and maturation, thus can serve as the primary drug target. To understand the structural evolution of M(Pro), we have performed phylogenetic and Sequence Similarity Network analysis, that depicted divergence of Coronaviridae M(Pro) in five clusters specific to viral hosts. This clustering was corroborated with the comparison of M(Pro) structures. Furthermore, it has been observed that backbone and binding site conformations are conserved despite variation in some of the residues. These attributes can be exploited to repurpose available viral protease inhibitors against SARS-CoV-2 M(Pro). In agreement with this, we performed screening of ∼7100 molecules including active ingredients present in the Ayurvedic anti-tussive medicines, anti-viral phytochemicals and synthetic anti-virals against SARS-CoV-2 M(Pro) as the primary target. We identified several natural molecules like δ-viniferin, myricitrin, taiwanhomoflavone A, lactucopicrin 15-oxalate, nympholide A, afzelin, biorobin, hesperidin and phyllaemblicin B that strongly binds to SARS-CoV-2 M(Pro). Intrestingly, these molecules also showed strong binding with other potential targets of SARS-CoV-2 infection like viral receptor human angiotensin-converting enzyme 2 (hACE-2) and RNA dependent RNA polymerase (RdRp). We anticipate that our approach for identification of multi-target-directed ligand will provide new avenues for drug discovery against SARS-CoV-2 infection. Communicated by Ramaswamy H. Sarma


title: Turkish Society of Cardiovascular Surgery (TSCVS) Proposal for use of ECMO in respiratory and circulatory failure in COVID-19 pandemic era.

text: The document is prepared to guide the members of the The Turkish Society of Cardiovascular Surgery (TSCVS) and other extracorporeal membrane oxygenation (ECMO) centers worldwide to share experiences in using ECMO in COVID-19 pandemic.


title: Health promotion, risk stratification, and treatment options to decrease hospitalization rates for community‐acquired pneumonia in adults

text: PURPOSE: Community‐acquired pneumonia (CAP) is a serious illness and hospitalization for this illness is expensive. There is much the nurse practitioner (NP) can do to prevent and manage this illness. DATA SOURCES: Review of current literature, medical/nursing references, and data from the healthcare utilization project (HCUP). CONCLUSIONS: The use of health promotion, risk stratification, and current evidence‐based treatment guidelines can help to decrease hospitalization rates for CAP for adults. IMPLICATIONS FOR PRACTICE: NPs are experts at health promotion and evidence‐based practice. Adhering to these practices and using risk stratification, NPs can help to further decrease hospitalization rates for CAP lowering healthcare costs related to this serious illness.


title: The role of acute and chronic respiratory colonization and infections in the pathogenesis of COPD

text: COPD is a major global concern, increasingly so in the context of ageing populations. The role of infections in disease pathogenesis and progression is known to be important, yet the mechanisms involved remain to be fully elucidated. While COPD pathogens such as Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae are strongly associated with acute exacerbations of COPD (AECOPD), the clinical relevance of these pathogens in stable COPD patients remains unclear. Immune responses in stable and colonized COPD patients are comparable to those detected in AECOPD, supporting a role for chronic colonization in COPD pathogenesis through perpetuation of deleterious immune responses. Advances in molecular diagnostics and metagenomics now allow the assessment of microbe–COPD interactions with unprecedented personalization and precision, revealing changes in microbiota associated with the COPD disease state. As microbial changes associated with AECOPD, disease severity and therapeutic intervention become apparent, a renewed focus has been placed on the microbiology of COPD and the characterization of the lung microbiome in both its acute and chronic states. Characterization of bacterial, viral and fungal microbiota as part of the lung microbiome has the potential to reveal previously unrecognized prognostic markers of COPD that predict disease outcome or infection susceptibility. Addressing such knowledge gaps will ultimately lead to a more complete understanding of the microbe–host interplay in COPD. This will permit clearer distinctions between acute and chronic infections and more granular patient stratification that will enable better management of these features and of COPD.


Nutritional Considerations in Frail Older Patients with COVID-19


title: Identification of encoding proteins related to SARS-CoV

text: By sampling 100 encoding proteins from SARS-coronavirus (SARS-CoV, NC 004718) and other six coronaviruses and selecting 23 variables through stepwise multiple regression (SMR) from 172 variables, the multiple linear regression (MLR) model was established with good results of the quantitative modelling correlation coefficient R (2) = 0.645 and the cross-validation correlation coefficient R (CV)(2) = 0.375. After removing 4 outliers, the quantitative modelling and cross-validation correlation coefficients were R (2)= 0.743 and R (CV)(2) = 0.543, respectively.


Cytokine Storm: is it the only major death factor in COVID-19 patients? Coagulation role


title: Evaluation of an Immunochromatographic Assay for the Rapid and Simultaneous Detection of Rotavirus and Adenovirus in Stool Samples

text: BACKGROUND: We evaluated the analytical and clinical performances of the SD BIOLINE Rota/Adeno Rapid kit (SD Rota/Adeno Rapid; Standard Diagnostics, Inc., Korea), an immunochromatographic assay (ICA), for the simultaneous detection of rotaviruses and adenoviruses in human stool samples. METHODS: We tested 400 clinical stool samples from patients with acute gastroenteritis and compared the ICA results with the results obtained by using ELISA, enzyme-linked fluorescent assays (ELFA), PCR, and multiplex reverse transcription-PCR (mRT-PCR). To assess the analytical performance of the SD BIOLINE Rota/Adeno Rapid kit, we determined its detection limit, reproducibility, cross-reactivity, and analytical reactivity for adenovirus subtypes, and performed interference studies. RESULTS: The overall agreement rates among the tested methods were 91.5% for rotavirus and 85.5% for adenovirus. On the basis of mRT-PCR, the overall agreement, positive agreement, and negative agreement rates of the ICA were 95.6%, 100%, and 94.9% for rotavirus, and 94.0%, 71.4%, and 94.8% for adenovirus, respectively. Using the ICA, we detected all the subtypes of adenovirus tested, but the analytical reactivities for adenovirus subtypes were different between the 4 adenovirus detection methods. The high reproducibility was confirmed, and no cross-reactivity or interference was detected. CONCLUSIONS: The SD BIOLINE Rota/Adeno Rapid kit showed acceptable analytical and clinical performances. However, interpretation of adenovirus positive/negative result should be cautious because of different detectability for adenovirus subtypes among adenovirus detection methods.


title: Origin and dispersal of Hepatitis E virus

text: Hepatitis E virus (HEV, genus Orthohepevirus) is a common cause of hepatitis worldwide. Human-infecting HEV strains (Orthohepevirus A) include human-restricted and enzootic genotypes. Viruses in the Orthohepevirus A species also infect rabbits (HEV-3ra), camels, and swine. Using a selection-informed method, we dated the origin of the Orthohepevirus genus at least 21 million years ago, whereas the Orthohepevirus A species originated in Asia, most likely from a human-infecting ancestor that existed ~4500 to 6800 years ago. In this period, the appearance of large human settlements probably facilitated HEV emergence and spread. The earliest events in Orthohepevirus A evolutionary history involved the separation of the enzootic and human-restricted genotypes, as well as the split of the camel-infecting genotypes, which occurred during the time-frame of camel domestication. The place and timing of HEV-3ra divergence also correspond to the circumstances of rabbit domestication. This study clarifies the origin and historical events underlying HEV dispersal.


title: Convergence of carbon intensity in the Yangtze River Delta, China

text: As China's industrialization and urbanization have grown rapidly in recent years, China's CO(2) emissions rose from 3405.1799 Mt to 10,249.4630 Mt from 2000 to 2013, and it has reached the highest levels in the word since 2006. Chinese government has emphasized the importance of reducing carbon emissions and set the target of reducing carbon intensity to 60–65% of 2005 levels by 2030. Investigating the convergence of carbon intensity can identify the convergence rate, which is helpful in guiding allocations of carbon intensity reduction. The Yangtze River Delta is one of the key carbon emission regions in China, with higher urbanization levels and larger carbon emissions; thus, we employed prefecture-level panel data derived from grid data between 2000 and 2010 to examine whether the convergence of carbon intensity exists across prefecture-level cities in the Yangtze River Delta. Spatial panel data models were utilized to investigate β-convergence of carbon intensity. The results indicated that carbon intensity showed divergence during 2002–2004 and σ-convergence over other periods (2000–2002 and 2004–2010). Carbon intensity exhibited stochastic convergence, indicating that the shocks to carbon intensity relative to the average level of carbon intensity are only transitory. There was a spatial spillover effect and β-convergence of carbon intensity, suggesting that prefecture-level cities with higher carbon intensity would decrease rapidly in the Yangtze River Delta. Our results highlight the importance of considering the present state of carbon intensity, spatial factors, and socioeconomic factors such as industrial structure and economic levels during allocation planning for reducing carbon intensity.


title: BVDV Npro protein mediates the BVDV induced immunosuppression through interaction with cellular S100A9 protein

text: Abstract The innate immune response is a vital part of the body's antiviral defense system. The innate immune response is initiated by various receptor interactions, including danger associated molecular patterns (DAMPs). The S100A9 is a member of the DAMPs protein family and, is released by activated phagocytic cells such as neutrophils, monocytes, macrophages or endothelial cells, and S100A9 induces its effect through TLR4/MyD88 pathway. Bovine viral diarrhea virus (BVDV) is one of the major devastating disease in the cattle industry worldwide. It shows its effect through immunosuppression and develops persistent infection in calves born from infected cows. The current study revealed that BVDV potentially induced immunosuppression by the interaction of BVDV Npro protein with cellular S100A9 protein. The Inhibition of S100A9 protein expression by small interfering RNA (siRNA) enhanced the virus replication in infected cells. Overexpression of bovine S100A9 enhanced the ncpBVDV2a 1373 mediated Type-I interferon production. A co-immunoprecipitation experiment demonstrated a strong interaction between ncp BVDV2a 1373 Npro protein and cellular S100A9 protein. This suggested that BVDV Npro reduced the S100A9 protein availability/activity in infected cells, resulting in reduced Type-I interferon production. A further study of S100A9-BVDV interaction will be need for better understanding of BVDV pathophysiology.