title: Glycogen Synthase Kinase 3β Enhances Hepatitis C Virus Replication by Supporting miR-122

text: Hepatitis C virus (HCV) infection is associated with alterations in host lipid and insulin signaling cascades, which are partially explained by a dependence of the HCV life cycle on key molecules in these metabolic pathways. Yet, little is known on the role in the HCV life cycle of glycogen synthase kinase 3 (GSK3), one of the most important kinases in cellular metabolism. Therefore, the impact of GSK3 on the HCV life cycle was assessed in human hepatoma cell lines harboring subgenomic genotype 1b and 2a replicons or producing cell culture-derived HCV genotype 2a by exposure to synthetic GSK3 inhibitors, GSK3 gene silencing, overexpression of GSK3 constructs and immunofluorescence analyses. In addition, the role of GSK3 in hepatitis E virus (HEV) replication was investigated to assess virus specificity of the observed findings. We found that both inhibition of GSK3 function by synthetic inhibitors as well as silencing of GSK3β gene expression resulted in a decrease of HCV replication and infectious particle production, whereas silencing of the GSK3α isoform had no relevant effect on the HCV life cycle. Conversely, overexpression of GSK3β resulted in enhanced HCV replication. In contrast, GSK3β had no effect on replication of subgenomic HEV replicon. The pro-viral effect of GSK3β on HCV replication was mediated by supporting expression of microRNA-122 (miR-122), a micro-RNA which is mandatory for wild-type HCV replication, as GSK3 inhibitors suppressed miR-122 levels and as inhibitors of GSK3 had no antiviral effect on a miR-122-independent HCV mutant. In conclusion, we have identified GSK3β is a novel host factor supporting HCV replication by maintaining high levels of hepatic miR-122 expression.


COVID-19 and Your Radiology Practice: Case Triage, Staffing Strategies, and Addressing Revenue Concerns


title: World leaders’ usage of Twitter in response to the COVID-19 pandemic: a content analysis

text: BACKGROUND: It is crucial that world leaders mount effective public health measures in response to COVID-19. Twitter may represent a powerful tool to help achieve this. Here, we explore the role of Twitter as used by Group of Seven (G7) world leaders in response to COVID-19. METHODS: This was a qualitative study with content analysis. Inclusion criteria were as follows: viral tweets from G7 world leaders, attracting a minimum of 500 ‘likes’; keywords ‘COVID-19’ or ‘coronavirus’; search dates 17 November 2019 to 17 March 2020. We performed content analysis to categorize tweets into appropriate themes and analyzed associated Twitter data. RESULTS: Eight out of nine (88.9%) G7 world leaders had verified and active Twitter accounts, with a total following of 85.7 million users. Out of a total 203 viral tweets, 166 (82.8%) were classified as ‘Informative’, of which 48 (28.6%) had weblinks to government-based sources, while 19 (9.4%) were ‘Morale-boosting’ and 14 (6.9%) were ‘Political’. Numbers of followers and viral tweets were not strictly related. CONCLUSIONS: Twitter may represent a powerful tool for world leaders to rapidly communicate public health information with citizens. We would urge general caution when using Twitter for health information, with a preference for tweets containing official government-based information sources.


title: Study of knowledge, attitude, anxiety & perceived mental healthcare need in Indian population during COVID-19 pandemic

text: Abstract Novel Corona Virus Disease (COVID-19) originating from China has rapidly crossed borders, infecting people throughout the whole world. This phenomenon has led to a massive public reaction; the media has been reporting continuously across borders to keep all informed about the pandemic situation. All these things are creating a lot of concern for people leading to heightened levels of anxiety. Pandemics can lead to heightened levels of stress; Anxiety is a common response to any stressful situation. This study attempted to assess the knowledge, attitude, anxiety experience, and perceived mental healthcare need among adult Indian population during the COVID-19 pandemic. An online survey was conducted using a semi-structured questionnaire using a non-probability snowball sampling technique. A total of 662 responses were received. The responders had a moderate level of knowledge about the COVID-19 infection and adequate knowledge about its preventive aspects. The attitude towards COVID-19 showed peoples' willingness to follow government guidelines on quarantine and social distancing. The anxiety levels identified in the study were high. More than 80 % of the people were preoccupied with the thoughts of COVID-19 and 72 % reported the need to use gloves, and sanitizers. In this study, sleep difficulties, paranoia about acquiring COVID-19 infection and distress related social media were reported in 12.5 %, 37.8 %, and 36.4 % participants respectively. The perceived mental healthcare need was seen in more than 80 % of participants. There is a need to intensify the awareness and address the mental health issues of people during this COVID-19 pandemic.


title: Analysis of Transmission and Control of Tuberculosis in Mainland China, 2005–2016, Based on the Age-Structure Mathematical Model

text: Tuberculosis (TB), an air-borne infectious disease, is a major public-health problem in China. The reported number of the active tuberculosis cases is about one million each year. The morbidity data for 2005–2012 reflect that the difference in morbidity based on age group is significant, thus the role of age-structure on the transmission of TB needs to be further developed. In this work, based on the reported data and the observed morbidity characteristics, we propose a susceptible-exposed-infectious-recovered (SEIR) epidemic model with age groupings, involving three categories: children, the middle-aged, and senior to investigate the role of age on the transmission of tuberculosis in Mainland China from 2005 to 2016. Then, we evaluated the parameters by the Least Square method and simulated the model and it had good alignment with the reported infected TB data in Mainland China. Furthermore, we estimated the basic reproduction number [Formula: see text] of [Formula: see text] , with an obtained 95% confidence interval for [Formula: see text] of [Formula: see text] by Latin hypercube sampling, and we completed a sensitivity analysis of [Formula: see text] in terms of some parameters. Our study demonstrates that diverse age groups have different effects on TB. Two effective measures were found that would help reach the goals of the World Health Organization (WHO) End TB Strategy: an increase in the recovery rate and the reduction in the infectious rate of the senior age group.


title: Psychiatric hospitalization rates in Italy before and during COVID-19: did they change? An analysis of register data

text: OBJECTIVES. To assess admission rates to seven General Hospital Psychiatric Wards (GHPWs) located in the Lombardy Region in the 40 days after the start of Coronavirus disease 2019 (COVID-19) epidemic, compared to similar periods of 2020 and 2019. METHODS. Anonymized data from the regional psychiatric care register have been obtained and analyzed. The seven GHPWs care for approximately 1.4 million inhabitants and have a total of 119 beds. RESULTS. In the 40-day period (February 21–March 31, 2020) after the start of the COVID-19 epidemic in Italy, compared to a similar 40-day period prior to February 21, and compared to two 40-day periods of 2019, there has been a marked reduction in psychiatric admission rates. The reduction was explained by voluntary admissions, while there was not a noticeable reduction for involuntary admissions. The reduction was visible for all diagnostic groups, except for a group of ‘Other’ diagnoses, which includes anxiety disorders, neurocognitive disorders, etc. CONCLUSIONS. Large-scale pandemics can modify voluntary admission rates to psychiatric facilities in the early phases following pandemic onset. We suggest that the reduction in admission rates may be due to fear of hospitals, seen as possible sites of contagion, as well as to a change in thresholds of behavioral problems acting as a trigger for admission requests from family relatives or referrals from treating clinicians. It is unclear from the study whether the reduction in admissions was contributed to most by the current pandemic or the lockdown imposed due to the pandemic.


title: Population-Based Incidence of Severe Acute Respiratory Virus Infections among Children Aged <5 Years in Rural Bangladesh, June–October 2010

text: BACKGROUND: Better understanding the etiology-specific incidence of severe acute respiratory infections (SARIs) in resource-poor, rural settings will help further develop and prioritize prevention strategies. To address this gap in knowledge, we conducted a longitudinal study to estimate the incidence of SARIs among children in rural Bangladesh. METHODS: During June through October 2010, we followed children aged <5 years in 67 villages to identify those with cough, difficulty breathing, age-specific tachypnea and/or danger signs in the community or admitted to the local hospital. A study physician collected clinical information and obtained nasopharyngeal swabs from all SARI cases and blood for bacterial culture from those hospitalized. We tested swabs for respiratory syncytial virus (RSV), influenza viruses, human metapneumoviruses, adenoviruses and human parainfluenza viruses 1–3 (HPIV) by real-time reverse transcription polymerase chain reaction. We calculated virus-specific SARI incidence by dividing the number of new illnesses by the person-time each child contributed to the study. RESULTS: We followed 12,850 children for 279,029 person-weeks (pw) and identified 141 SARI cases; 76 (54%) at their homes and 65 (46%) at the hospital. RSV was associated with 7.9 SARI hospitalizations per 100,000 pw, HPIV3 2.2 hospitalizations/100,000 pw, and influenza 1.1 hospitalizations/100,000 pw. Among non-hospitalized SARI cases, RSV was associated with 10.8 illnesses/100,000 pw, HPIV3 1.8/100,000 pw, influenza 1.4/100,000 pw, and adenoviruses 0.4/100,000 pw. CONCLUSION: Respiratory viruses, particularly RSV, were commonly associated with SARI among children. It may be useful to explore the value of investing in prevention strategies, such as handwashing and respiratory hygiene, to reduce respiratory infections among young children in such settings.


title: The Mechanism and Clinical Outcome of patients with Corona Virus Disease 2019 Whose Nucleic Acid Test has changed from negative to positive, and the therapeutic efficacy of Favipiravir: A structured summary of a study protocol for a randomised controlled trial

text: OBJECTIVES: A variety of possible mechanisms can make the nucleic acid test of patients who meet the discharge conditions positive again, including reinfection, reactivation of the original virus, lack of strict discharge criteria, new infection, and so on. Different reasons will correspond to different prevention and control measures. We will enroll patients who are discharged after treatment, whose nucleic acid test has changed from negative to positive during the screening visit, regardless of the severity of the symptoms, to investigate the mechanism, clinical outcome and therapeutic efficacy with Favipiravir patients with Corona virus Disease 2019. Favipiravir is an anti-viral agent that selectively and potently inhibits the RNA-dependent RNA polymerase, it has been used for treatment of some life-threatening infections such as Ebola virus, Lassa virus and rabies. Its therapeutic efficacy has been proven in these diseases. TRIAL DESIGN: This is a multi-center, two arm, open label, parallel group, randomized controlled trial. PARTICIPANTS: Eligibility criteria: 1. Adults 18 to 80 years, male or female. 2. After the first diagnosis and treatment of COVID-19, the nucleic acid test of respiratory specimens such as sputum or nasopharyngeal swabs, has been negative for two consecutive times (sampling time interval of at least 24 hours), in accordance with the COVID-19’s diagnosis and treatment Plan (7th Edition), discharged. 3. During screening visit (follow-up after discharge), The nucleic acid test of COVID-19 is positive in any one of the following samples: sputum, throat swabs, blood, feces or other specimens. Regardless of whether or not they had symptoms and the severity of symptoms. 4. Volunteer to participate in the research and sign the Informed Consent Form. 1. Allergic to Favipiravjr; 2. Pregnant or lactating women. 3. Uncontrolled diseases of the blood and cardiovascular system, liver or kidney. 4. History of mental disorders, drug abuse or dependence; 5. Researchers consider it inappropriate for adults to participate; 6. Participating in other clinical studies. Loss to Follow up: Cases that do not complete the clinical trial program will be regarded as lost to follow up. Including the withdrawal of patients by themselves (such as poor compliance, etc.), or the withdrawal of patients ordered by the researcher (those who need other drugs which affect the judgment of the curative effect, and those who need to stop taking drugs for severe adverse events) Study setting: The participating hospitals are some of the designated hospitals that have been or may be admitting patients who meet the eligibility criteria, mainly in Hubei, Shenzhen, Anhui and Beijing. Participants will be recruited from these 15 hospitals: Wuhan Pulmonary Hospital, Hubei; Jinyintan Hospital of Wuhan, Hubei; Ezhou Central Hospital, Hubei; The Second People's Hospital of Fuyang, Anhui; The First Affiliated Hospital of USTC, Anhui; Beijing Youan Hospital, Beijing; Capital Medical University Beijing Institute of Hepatology, Beijing; Ezhou Hospital of Traditional Chinese Medicine, Hubei; Zhongnan Hospital of Wuhan University, Hubei; The Fifth Hospital of ShiJiazhuang, Hebei; Jinan Infectious Diseases Hospital, Shandong; Public Health Clinical Center of Chengdu, Sichuan; Wuxi No.5 People’s Hospital, Jiangsu; The Third People’s Hospital of Shenzhen, Guangdong; The First Affiliated Hospital of Bengfu Medical College, AnHui. INTERVENTION AND COMPARATOR: Favipiravir group (experimental): Favipiravir 1600mg each dose, twice a day on the 1st day; 600mg each dose, twice a day from the 2nd to the 7th day, Oral administration, the maximum number of days taken will be no more than 14 days plus routine treatment for COVID-19. Regular treatment group (control): Treatments other than Antiviral drugs can be given. Routine treatment for patients with the corona virus will be administered, this includes oxygen therapy, drugs that reduced phlegm and relieve cough, including thymosin, proprietary Chinese medicine, etc. MAIN OUTCOMES: Primary Outcome Measures: Viral nucleic acid test negative [Time Frame: 5 months]: Subjects who tested negative for nucleic acid from sputum or nasopharyngeal swabs for two consecutive times (sampling time interval of at least 24 hours). 1. Body temperature returned to normal for more than 3 days; 2. Lung image improved. 3. Clinical manifestation improved; 4. The viral nucleic acid test of respiratory specimens was negative for two consecutive times (sampling time interval of at least 24 hours). RANDOMIZATION: The central randomization system (Interactive Web Response Management System), will be used to randomly divide the subjects into the experimental group and the control group according to the ratio of 2:1. In this study, block randomization will be used, in blocks of 6. BLINDING (MASKING): This is an open label trial. Trial participants, investigators, care givers, outcome assessors, and date analysts are not blinded to group assignment. NUMBERS TO BE RANDOMISED: 210 patients are expected to be enrolled and allocated according to the ratio of 2 (Favipiravir group, n=140): 1(regular treatment group, n=70). TRIAL STATUS: Protocol version number 3.0, 10(th) April 2020 First Patient, first visit 17(th) March 2020; recruitment end date anticipated June 1, 2020. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04333589, April 3, 2020. Registered April 3, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


title: Pulmonary infections

text: This paper reviews the most common imaging findings of pulmonary infection in children. Pneumonia is a leading cause of mortality in children in developing and industrialized countries. While the imaging findings usually are nonspecific, correlation with the patient’s age, immune status and pertinent history can limit the differential diagnoses. The paper will review the common and unique features of pneumonia caused by specific organisms and in specific patient populations.


title: Life beyond PCR: alternative target amplification technologies for the diagnosis of infectious diseases, part I

text: Non-PCR-based target amplification technologies, including transcription-mediated amplification (TMA), nucleic acid sequence-based amplification (NASBA), and strand displacement amplification (SDA), are currently the basis for a broad range of clinical infectious-disease molecular diagnostics. These amplification technologies are very sensitive and specific and can be used in combination with traditional end-point or “real-time” detection formats. For several nucleic acid targets, TMA, NASBA, and SDA have certain advantages over PCR-based applications. This two-part article will review the molecular basis of each technology and how the technology has been applied to clinical diagnostic systems. The articles will describe the current testing platforms available, U.S. Food and Drug Administration (FDA)- and non-FDA-approved assays, and availability of analyte-specific reagents. In addition, an open-platform system is described that utilizes standardized reagents and methods and allows the user to develop in-house protocols. Finally, applications for the future are discussed.


title: Nasopharyngeal isolates and their clinical impact on young children with asthma: a pilot study

text: INTRODUCTION: Respiratory infections have significant effects on childhood asthma. Viral respiratory infections, such as rhinovirus and respiratory syncytial virus are likely to be important in the development and exacerbation of asthma. In this study, we investigated the nasopharyngeal colonization in children with asthma to determine the prevalence of pathogens and their contribution to respiratory symptoms and airway resistance during winter. METHODS: From December 2016 to March 2017, 50 nasopharyngeal specimens were collected from 18 patients (age, 5.0±1.1 years) with asthma and 9 specimens from 9 control children (age, 4.9±1.0 years). Samples were tested for 19 viruses and 7 bacteria, using multiplex real-time PCR. Respiratory disease markers included the Global Asthma Network Questionnaire, the Common-Cold Questionnaire, the Global Initiative for Asthma assessment of asthma control, and the airway resistance at 5 Hz by forced-oscillation technique. RESULTS: The most commonly isolated organisms in both groups (patients and controls) were Streptococcus pneumoniae, Haemophilus influenzae, and rhinovirus. Most patients had multiple isolates (median, 3.5; range, 1–5), which changed during the study period. Types of isolates were 4 bacteria (S. pneumoniae, H. influenzae, Bordetella pertussis, and Bordetella parapertussis) and 6 viruses (rhinovirus, enterovirus, metapneumovirus, adenovirus, coronaviruses, and parainfluenza viruses). Similar isolates, including influenza A-H3 virus and bocavirus, were detected in the controls. Of the 9 patients with “wheezing disturbing sleep ≥1 per week”, 6 had rhinovirus, 2 coronaviruses, and 1 no detectable viruses. Patients with mild common cold symptoms had significantly higher airway resistance at 5 Hz z-score (P=0.025). CONCLUSION: Multiple respiratory pathogens were isolated from many patients with asthma, which appeared to contribute to disease symptoms and airway resistance. Minimizing children’s exposure to respiratory pathogens might be beneficial, especially during winter.


Severe Acute Respiratory Syndrome in children: a clue to better understanding the disease and advancing towards solutions


Unconventional approaches to mechanical ventilation—step-by-step through the COVID-19 crisis


title: Sterilization plan of the used metered dose inhalers (MDI) to avoid wastage amid COVID-19 pandemic drug shortage

text: Background Coronavirus is causing a shortage of critical inhalers needed by patients with Asthma and respiratory illness. Patients with Asthma are at higher risk if they tract the novel Coronavirus. As the coronavirus continues to spread, hospitals are turning to use more salbutamol MDI. Salbutamol MDI has become the line of defence for physicians in the emergency room who are treating patients with Corona Virus Disease 2019 (COVID-19) and have respiratory distress .[Hui et al 2020 ,and Center for Drug Evaluation and Research 2020] During the COVID pandemic, there has been a drastic increase in the use of MDI inhalers; therefore, it led to a decrease in availability and a break in the supply chain. Patients with Asthma are at higher risk if they tract the novel Coronavirus, and an inhaler could be a life or death for them. As the coronavirus continues to spread, hospitals are turning to use more salbutamol Metered Dose inhaler (MDI). Salbutamol MDI is now on short supply as the COVID-19 continues to spread. Salbutamol MDI has become the line of defence for physicians in the emergency room who are treating patients with COVID-19 and have respiratory distress. The current shortage of salbutamol MDI could be a result of stockpiling and hoarding of this life-saving inhaler. That had led to a critical shortage of Salbutamol MDI, and even the case shortage continues with some other alternatives such as Ipratropium MDI and even with long-acting B-agonists such as Salmeterol and Formoterol which also starting to have a limitation on ordering these agents. Coronavirus sparks fear of medication shortage. Coronavirus panic-buying also may have led to a shortage of critical inhalers. We have also got elderly patients with COPD who may need Ventolin MDI and also premature babies who may have caught Respiratory Syncytial Virus (RSV) and need salbutamol MDI to support their lungs have since been compromised, and they rely heavily on Asthma inhalers. Finding a safe and creative strategy is essential during the COVID-19 pandemic.


title: Removal of Hepatitis C Virus-Infected Cells by a Zymogenized Bacterial Toxin

text: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and has become a global health threat. No HCV vaccine is currently available and treatment with antiviral therapy is associated with adverse side effects. Moreover, there is no preventive therapy for recurrent hepatitis C post liver transplantation. The NS3 serine protease is necessary for HCV replication and represents a prime target for developing anti HCV therapies. Recently we described a therapeutic approach for eradication of HCV infected cells that is based on protein delivery of two NS3 protease-activatable recombinant toxins we named “zymoxins”. These toxins were inactivated by fusion to rationally designed inhibitory peptides via NS3-cleavable linkers. Once delivered to cells where NS3 protease is present, the inhibitory peptide is removed resulting in re-activation of cytotoxic activity. The zymoxins we described suffered from two limitations: they required high levels of protease for activation and had basal activities in the un-activated form that resulted in a narrow potential therapeutic window. Here, we present a solution that overcame the major limitations of the “first generation zymoxins” by converting MazF ribonuclease, the toxic component of the E. coli chromosomal MazEF toxin-antitoxin system, into an NS3-activated zymoxin that is introduced to cells by means of gene delivery. We constructed an expression cassette that encodes for a single polypeptide that incorporates both the toxin and a fragment of its potent natural antidote, MazE, linked via an NS3-cleavable linker. While covalently paired to its inhibitor, the ribonuclease is well tolerated when expressed in naïve, healthy cells. In contrast, activating proteolysis that is induced by even low levels of NS3, results in an eradication of NS3 expressing model cells and HCV infected cells. Zymoxins may thus become a valuable tool in eradicating cells infected by intracellular pathogens that express intracellular proteases.


title: 18β-glycyrrhetinic acid inhibits rotavirus replication in culture

text: BACKGROUND: Glycyrrhizin (GA) and primary metabolite 18β-glycyrrhetinic acid (GRA) are pharmacologically active components of the medicinal licorice root, and both have been shown to have antiviral and immunomodulatory properties. Although these properties are well established, the mechanisms of action are not completely understood. In this study, GA and GRA were tested for the ability to inhibit rotavirus replication in cell culture, toward a long term goal of discovering natural compounds that may complement existing vaccines. METHODS: Epithelial cells were treated with GA or GRA various times pre- or post-infection and virus yields were measured by immunofluorescent focus assay. Levels of viral proteins VP2, VP6, and NSP2 in GRA treated cells were measured by immunoblot to determine if there was an effect of GRA treatment on the accumulation of viral protein. RESULTS: GRA treatment reduced rotavirus yields by 99% when added to infected cultures post-- virus adsorption, whereas virus yields in GA treated cultures were similar to mock treated controls. Time of addition experiments indicated that GRA-mediated replication inhibition likely occurs at a step or steps subsequent to virus entry. The amounts of VP2, VP6 and NSP2 were substantially reduced when GRA was added to cultures up to two hours post-entry. CONCLUSIONS: GRA, but not GA, has significant antiviral activity against rotavirus replication in vitro, and studies to determine whether GRA attenuates rotavirus replication in vivo are underway.


title: Validation of an Immunohistochemistry Assay to Detect Turkey Coronavirus: A Rapid and Simple Screening Tool for Limited Resource Settings

text: The objective of the present study was to develop and apply the direct immunohistochemistry (D-IHC) assay to search for turkey coronavirus (TCoV) antigens in formalin-fixed embedded-paraffin tissues by the use of biotin-labeled polyclonal antibody. Twenty-eight-day-old embryonated turkey eggs (n = 50) were inoculated with TCoV-purified virus, and 3 d after inoculation, sections from ileum, ileum-cecal junction, and ceca were harvested, fixed in neutral formalin, and embedded in paraffin blocks and used as positive control. In addition, a total of 100 field samples from ileum, ileum-cecal junction, and ceca, collected from 30 to 45-d-old turkeys poults experiencing an outbreak of acute enteritis, were used to search for TCoV by the same D-IHC. All results were compared with those obtained by conventional RT-PCR and indirect fluorescent antibody assay (IFA) for all tested samples. Turkey coronavirus was detected in experimentally infected embryo tissues and also in field samples in 100% of ileum-cecal junction and ceca by the 3 detection procedures. With IFA as a reference assay, sensitivity and specificity of D-IHC were 98 and 58%, whereas sensitivity and specificity of reverse transcription-PCR were 96 and 66%, calculated from the total of tested samples from experimental infection. Each of the examined procedures was highly specific (D-IHC, 93%; RT-PCR, 90%), sensitive (D-IHC, 85%; RT-PCR, 86%), and agreement of both D-IHC and RT-PCR was 99 and 100%, respectively, compared with IFA results obtained from all the field samples. These findings demonstrated the utility of D-IHC for direct detection of TCoV from field samples and considering the sensitivity and specificity found here, can be used as an alternative technique.


title: Epidemiologic Analysis of Respiratory Viral Infections Mainly in Hospitalized Children and Adults in a Midwest University Medical Center After the Implementation of a 14-Virus Multiplex Nucleic Acid Amplification Test

text: Objectives: To investigate the etiology of viral respiratory tract infections mainly in hospitalized children and adults over a 12-month consecutive period after implementation of a 14-virus multiplex nucleic acid amplification test. Methods: From January 2014 to January 2015, a total of 2,237 respiratory samples were analyzed with the US Food and Drug Administration–cleared eSensor Respiratory Viral Panel (GenMark Diagnostics, Carlsbad, CA). Results: Of the 2,237 specimens tested, 788 specimens were positive for at least one virus, giving a positivity rate of 35.2%, and because of viral codetection, a total of 862 viral targets were identified. The age groups with the highest positivity rates were the 0- to 1-year (73.5%) and 2- to 6-year (78.4%) age groups. The overall viral codetection rate was 9.1%. Human rhinovirus (HRV) was the most prevalent respiratory virus found in children and adults. The peak of HRV seen in September 2014 represented a combination of HRV and enterovirus D68, 2014 epidemic respiratory infections. Conclusion: The ability to detect a wider range of respiratory viruses gave us a better understanding of the etiology of respiratory infections in our population, particularly for HRV and enhanced our ability to detect viral coinfection.


title: The History of Pediatric Infectious Diseases

text: The history of Pediatric Infectious Diseases closely parallels the history of Pediatrics at least until the last century, because historically infections comprised the major causes of childhood morbidity and mortality, as they still do in the developing world. This history reviews developments in the field through the centuries and is writen so that it does not overlap the contribution to this series by Baker and Katz entitled ‘Childhood Vaccine Development in the United States.' Remarkable descriptions of selected pediatric infections existed long before the invention of printing, and early pediatric texts included many chapters devoted to various infections. Coincident with the establishment of pediatric organizations in America in the late 19(th) and early 20(th) Centuries, major attention was focused on diphtheria, infant diarrheal illnesses, tuberculosis, streptococcal infections and their complications, and other pediatric infections, and substantial progress was made. The American Pediatric Society (1888), the American Academy of Pediatrics (1930), the Society for Pediatric Research (1931), and the American Board of Pediatrics (1933) all contributed to the evolution of the discipline of Pediatric Infectious Disease, and numerous leaders of these organizations had significant infectious diseases interests. The establishment of the Pediatric Infectious Diseases Society, the Pediatric Infectious Diseases sub-board, and an accreditation process for training programs, as well as sub-specialty textbooks and journal, further validated the development of this specialty, particularly in North America. The many remaining challenges related to infectious diseases in children (including HIV, emerging infections, antimicrobial resistance, opportunistic infections, and infections in the developing world) insure the future of the specialty. The genomic era of medicine and the tools of molecular biology will lead to new insights into pathogenesis, diagnosis, and treatment of infections. Pediatric Infectious Diseases physicians can celebrate the past triumphs of the discipline and future achievements, all contributing to improved health for children.


title: Lelystad Virus, the Causative Agent of Porcine Epidemic Abortion and Respiratory Syndrome (PEARS), Is Related to LDV and EAV

text: Abstract The genome of Lelystad virus (LV), the causative agent of porcine epidemic abortion and respiratory syndrome (previously known as mystery swine disease), was shown to be a polyadenylated RNA molecule. The nucleotide sequence of the LV genome was determined from a set of overlapping cDNA clones. A consecutive sequence of 15,088 nucleotides was obtained. Eight open reading frames (ORFs) that might encode virus-specific proteins were identified. ORF1a and ORF1b are predicted to encode the vital RNA polymerase because the amino acid sequence contains sequence elements that are conserved in RNA polymerases of the torovirus Berne virus (BEV), equine arteritis virus (EAV), lactate dehydrogenase-elevating virus (LDV), the coronaviruses, and other positive-strand RNA viruses. A heptanucleotide slippery sequence (UUUAAAC) and a putative pseudoknot structure, which are both required for efficient ribosomal frameshifting during translation of the RNA polymerase ORF 1b of BEV, EAV, and the coronaviruses, were identified in the overlapping region of ORF1a and ORF1b of LV. ORFs 2 to 6 probably encode viral membrane-associated proteins, whereas ORF7 is predicted to encode the nucleocapsid protein. Comparison of the amino acid sequences of the ORFs identified in the genome of LV, LDV, and EAV indicated that LV and LDV are more closely related than LV and EAV. A 3′ nested set of six subgenomic RNAs was detected in LV-infected cells. These subgenomic RNAs contain a common leader sequence that is derived from the 5′ end of the genomic RNA and that is joined to the 3′ terminal body sequence. Our results indicate that LV is closely related evolutionarily to LDV and EAV, both members of a recently proposed family of positive-strand RNA viruses, the Arteriviridae.


title: Pneumonia induced by swine-origin influenza A (H1N1) infection: chest computed tomography findings in children

text: PURPOSE: The purpose of this study was to determine the features of chest computed tomography (CT) in children with swine-origin influenza A (H1N1) virus (S-OIV). MATERIALS AND METHODS: The study population consisted of 16 children with laboratory-confirmed S-OIV infection (12 boys, 4 girls), with an age range of 5–10 years (mean 6.3 years). Pneumonia was suspected in these patients based on clinical features or confirmed by radiography. All subjects underwent CT for close evaluation of pneumonia, including characteristics, distribution, extent, and other findings such as pleural effusion, pneumothorax, and pneumomediastinum. RESULTS: The predominant CT finding was consolidation plus ground-grass opacity (GGO) (11/16, 69%). The consolidation-dominant pattern was found in 10 of 16 (66%) patients, and 1 (6%) was GGO-dominant. One (6%) had only GGO. In all, 7 of the 16 patients had segmental or lobar consolidation. Abnormal opacities were primarily distributed in the central lung zone (8/16, 50%) and were multifocal (15/16, 94%). Four showed atelectasis (4/16, 25%). Pneumomediastinum was observed in 4 of 16 (25%). One patient had negative radiographic findings but was positive on CT. CONCLUSION: Multifocal consolidation with central distribution is a common CT finding in children with S-OIV, but there are few GGO-dominant cases. Widespread consolidation (segmental or lobar) is also common.


title: Impact of PRRSV infection and dietary soybean meal on ileal amino acid digestibility and endogenous amino acid losses in growing pigs()

text: Porcine reproductive and respiratory syndrome virus (PRRSV) is a significant disease in the swine industry, and increasing soybean meal (SBM) consumption during this disease challenge may improve performance. Our objectives were to determine the impact of SBM level on apparent total tract (ATTD) and ileal (AID) digestibility during PRRSV infection and to determine ileal basal endogenous losses (BEL) during PRRSV infection. Forty PRRSV negative gilts were fitted with a T-cannula in the distal ileum. Treatments were arranged in a 2 × 2 factorial with high and low SBM (HSBM, 29% vs. LSBM, 10%), with and without PRRSV (n = 6/treatment). The remaining pigs (n = 8/challenge status) were fed a N-free diet. Chromic oxide was used as an indigestible marker. On day post inoculation (dpi) 0, at 47.7 ± 0.57 kg BW, 20 pigs were inoculated with live PRRSV; 20 control pigs were sham inoculated. Infection was confirmed by serum PCR. Feces were collected at dpi 5 to 6 and dpi 16 to 17, and ileal digesta collected at dpi 7 to 8 and dpi 18 to 19. Feed, feces, and digesta were analyzed for DM, N, and GE. Digesta and feed were analyzed for AA. Data were analyzed in a 2 × 2 + 2 factorial design to determine main effects of diet and PRRSV and their interaction. Data from N-free fed pigs were analyzed separately to determine BEL and hindgut disappearance due to PRRSV infection. All control pigs remained PRRSV negative. There were no interactions for AID of AA; however, HSBM reduced DM, GE, Lys, and Met AID and increased Arg and Gly AID during both collection periods (P < 0.05). At dpi 7 to 8 only, PRRSV reduced DM and GE AID (P < 0.05). At 7 to 8 dpi, BEL of Arg, Ala, and Pro were reduced (P < 0.05) due to PRRSV by 64%, 39%, and 94%, respectively. At dpi 18 to 19, BEL of Thr tended (P = 0.06) to be increased in PRRSV-infected pigs; however, no other differences were observed. Pigs fed LSBM had increased Lys, Met, Thr, Trp, and Pro standardized ileal digestibility (SID), primarily at 7 to 8 dpi. At 7 to 8 dpi, PRRSV reduced Arg, Gly, and Pro SID (P < 0.01), and SID Pro continued to be reduced by 17% at dpi 18 to 19. Compared with HSBM pigs, LSBM reduced hindgut disappearance of DM and GE at dpi 5 to 8 and dpi 16 to 19, while N disappearance was reduced at dpi 5 to 8. There were no differences between control and PRRSV N-free fed pigs. Altogether, SBM inclusion impacts SID of AA and hindgut disappearance of nutrients, regardless of PRRSV. In contrast, there is minimal impact of PRRSV on BEL, and therefore, SID of most AA are not different.


title: Methyl-RNA: an evolutionary bridge between RNA and DNA?

text: Abstract Given the apparent limitation of double-stranded RNA (dsRNA) genomes to about 30 kb, together with the complexity of DNA synthesis, it appears difficult for a dsRNA genome to encode all the information required before the transition from an RNA to a DNA genome. Ribonucleotide reductase itself, which synthesises deoxyribonucleotides from ribonucleotides, requires complex protein radical chemistry, and RNA world genomes may have reached their limits of coding capacity well before such complex enzymes had evolved. The transition from RNA to DNA thus appears to require intermediate steps, and we suggest that the naturally occurring 2′-O-methylated RNA, with chemical properties intermediate between RNA and DNA, is a suitable candidate.


title: Blood safety and the choice of anti‐hemophilic factor concentrate

text: Hemophilia is a congenital disorder due to the deficiency of the activity of factor VIII (classical hemophilia A) or IX (Christmas disease or hemophilia B). Bleeding is common and may result in long‐term complications or even death. Bleeding may be treated or prevented by infusion of factor concentrates however these drugs are not without risk. Clinicians often feel ill prepared to provide accurate and impartial information regarding these drugs. This review will provide the reader with an historical yet up to date perspective on blood safety as it relates to the choice of concentrates to treat hemophilia. Pediatr Blood Cancer 2006;47:245–254. © 2006 Wiley‐Liss, Inc.


title: Autopsy: Infectious and Serious Communicable Diseases

text: Abstract The infectious autopsy is the postmortem examination of a decedent who is likely to have a serious infectious disease that can be transmitted at autopsy. Human immunodeficiency virus (HIV), viral hepatitis B and C, and tuberculosis infections are common in forensic autopsy populations. Autopsy and laboratory personnel are at risk for acquiring these postmortem infections. As the autopsy often is essential to determine the cause and manner of death and/or help the living, the use of certain standard precautions can minimize the risk of occupational infections. This chapter reviews frequently encountered occupational infections and provides preventive measures including postexposure management.


Expanding access for COVID-19 patients by transforming a burn unit into a closed-circuit unit for surgical patients: experience from an academic medical center in Jordan


EU‐UK Brexit Negotiations, Covid‐19 and Key Roles for Economists


title: Reprogramming the genetic code: the emerging role of ribosomal frameshifting in regulating cellular gene expression

text: Reading frame maintenance is a critical property of ribosomes. However, a number of genetic elements have been described that can induce ribosomes to shift on mRNAs, the most well understood of which are a class that directs ribosomal slippage by one base in 5′ (-1) direction. This is referred to as programmed -1 ribosomal frameshifting (-1 PRF). Recently, a new -1 PRF promoting element was serendipitously discovered in a study examining the effects of stretches of adenosines in the coding sequences of mRNAs. Here, we discuss this finding, recent studies describing how -1 PRF is used to control gene expression in eukaryotes, and how -1 PRF is itself regulated. The implications of dysregulation of -1 PRF on human health are examined, as are possible new areas in which novel -1 PRF promoting elements might be discovered.


title: The syndrome of inappropriate antidiuresis in COVID-19 pneumonia: report of two cases

text: The emergence of the novel coronavirus or severe acute respiratory syndrome coronavirus 2 leads to a high number of cases of severe pneumonia. So far, little is known about the course of the disease and its symptoms, complications and treatment. We report the first two cases of the syndrome of inappropriate antidiuresis complicating COVID-19 pneumonia.


title: Guía de consenso para el abordaje de la neumonía adquirida en la comunidad en el paciente anciano

text: The incidence of community-acquired pneumonia increases with age and is associated with an elevated morbidity and mortality due to the physiological changes associated with aging and a greater presence of chronic disease. Taking into account the importance of this disease from an epidemiological and prognostic point of view, and the enormous heterogeneity described in the clinical management of the elderly, we believe a specific consensus document regarding this patient profile is necessary. The purpose of the present work was to perform a review of the evidence related to the risk factors for the etiology, the clinical presentation, the management and the treatment of community-acquired pneumonia in elderly patients with the aim of producing a series of specific recommendations based on critical analysis of the literature. This document is the result of the collaboration of different specialists representing the Spanish Society of Emergency Medicine and Emergency Care (SEMES), the Spanish Society of Geriatrics and Gerontology (SEGG), the Spanish Society of Chemotherapy (SEQ), the Spanish Society of Internal Medicine (SEMI), the Spanish Society of Respiratory Medicine and Thoracic Surgery (SEPAR), Spanish Society of Home Hospitalization (SEHAD) and the Spanish Society of Infectious Disease and Clinical Microbiology (SEIMC).


title: Coronavirus IBV: Partial amino terminal sequencing of spike polypeptide S2 identifies the sequence Arg-Arg-Phe-Arg-Arg at the cleavage site of the spike precursor propolypeptide of IBV strains Beaudette and M41

text: Abstract The spike protein of avian infectious bronchitis coronavirus comprises two glycopolypeptides S1 and S2 derived by cleavage of a proglycopolypeptide So, the nucleotide sequence of which has recently been determined for the Beaudette strain (Binns M.M. et al., 1985, J. Gen. Virol. 66, 719–726). The order of the two glycopolypeptides within So is aminoterminus(N)-Sl-S2-carboxyterminus(C). To locate the N-terminus of S2 we have performed partial amino acid sequencing on S2 from IBV-Beaudette labelled with [3H]serine and from the related strain IBV-M41 labelled with [3H]valine, leucine and isoleucine. The residues identified and their positions relative to the N-terminus of S2 were: serine, 13; valine, 6, 12; leucine, none in the first 20 residues; isoleucine, 2, 19. These results identified the N-terminus of S2 of IBV-Beaudette as serine, 520 residues from the N-terminus of S1, excluding the signal sequence. Immediately to the N-terminal side of residue 520 So has the sequence Arg-Arg-Phe-Arg-Arg; similar basic connecting peptides are a feature of several other virus spike glycoproteins. It was deduced that for IBV-Beaudette SI comprises 519 residues (M r 57.0K) or 514 residues (56.2K) if the connecting peptide was to be removed by carboxypeptidase-like activity in vivo while S2 has 625 residues (69.2K). Nucleotide sequencing of the cleavage region of the So gene of IBV-M41 revealed the same connecting peptide as IBV-Beaudette and that the first 20 N-terminal residues of S2 of IBV-M41 were identical to those of the Beaudette strain. IBV-Beaudette grown in Vero cells had some uncleaved So; this was cleavable by 10 μg/ml of trypsin and of chymotrypsin. Partial N-terminal analysis of S1 from IBV-M41 identified leucine and valine residues at positions 2 and 9 respectively from the N-terminus. This confirms the identification made by Binns et al. (1985), of the N-terminus of S1 and the end of the signal sequence of the IBV-Beaudette spike propolypeptide. N-terminal sequencing of [3H]leucine-labelled IBV-Beaudette membrane (M) polypeptide showed leucine residues at positions 8,16 and 22 from the N-terminus; these results confirm the open reading frame identified by M.E.G. Boursnell et al. (1984, Virus Res. 1, 303–313) in the nucleotide sequence of M. The N-terminus of the nucleocapsid (n) polypeptide appeared to be blocked.


title: Dynamics of an SEQIHRS epidemic model with media coverage, quarantine and isolation in a community with pre-existing immunity

text: Abstract An autonomous deterministic non-linear epidemic model SEQIHRS is proposed for the transmission dynamics of an infectious disease with quarantine and isolation control strategies in a community with pre-existing immunity. The model exhibits two equilibria, namely, the disease-free and a unique endemic equilibrium. The existence and local stability of the disease free and endemic equilibria are explored in terms of the effective reproduction number R C . It is observed that media coverage does not affect the effective reproduction number, but it helps to mitigate disease burden by lowering the number of infectious individuals at the endemic steady state and also lowering the infection peak. A new approach is proposed to estimate the coefficient of media coverage. Using the results of central manifold theory, it is established that as R C passes through unity, transcritical bifurcation occurs in the system and the unique endemic equilibrium is asymptotically stable. It is observed that the population level impact of quarantine and isolation depend on the level of transmission by the isolated individuals. Moreover, the higher level of pre-existing immunity in the population decreases the infection peak and causes its early arrival. Theoretical findings are supported by numerical simulation. Sensitivity analysis is performed for R C and state variables at endemic steady state with respect to model parameters.


title: Contact tracing apps and values dilemmas: A privacy paradox in a neo-liberal world

text: Contact tracing apps are presented as a solution, if not the solution, to curb pandemics in the Covid-19 crisis. In France, despite heated public institutional debate on privacy related issues, the app was presented by government as an essential benefit for protecting health and lives, thus avoiding both politicians and citizens to feel morally responsible and looking guilty, and as essential to recover our freedom to move. However we argue that, while detection of cases have still not been reported after 10 days and one million app downloads - a situation comparable to Australia who launched its app a month before -, the adoption of the app generates important risks to our informational privacy, surveillance and habituation to security policies. It also may create discrimination, distrust and generate other health problems such as addiction and others as 5G technology continues to be deployed without prior impact studies. Finally the smartphone app against covid epidemics appears as an extreme case of the privacy paradox where the government plays on the immediate benefits and downplays long-term concerns while inducing a technology of self. Contact tracing apps may become an emblematic case for digital transformation and value changes in the western world.


title: Moving Past the Routine Use of Macrolides—Reviewing the Role of Combination Therapy in Community-Acquired Pneumonia

text: PURPOSE OF REVIEW: Despite advances in diagnostic microbiology and sepsis management, community-acquired pneumonia (CAP) remains a significant cause of morbidity and mortality. Current recommendations regarding the use of beta-lactams in combination with macrolides published in clinical practice guidelines are variable and based on low-quality evidence that is frequently retrospective, observational, and heterogeneous in nature. While population-based studies have historically suggested improved clinical outcomes with the routine use of macrolide combination therapy in hospitalized patients with CAP, emerging evidence from recent randomized controlled trials has challenged this practice. In this article, we discuss the historical rationale and current evidence for combination macrolide therapy in the management of CAP. RECENT FINDINGS: Recent randomized controlled trials have assessed the non-inferiority of beta-lactam monotherapy compared to beta-lactam/macrolide combination therapy in adult patients hospitalized with CAP. Beta-lactam monotherapy was associated with equivalent clinical outcomes in patients with mild to moderate CAP. Patients with severe CAP managed with beta-lactam monotherapy have demonstrated worse clinical outcomes when compared to patients treated with combination therapy. In addition, previous beta-lactam exposure prior to hospitalization has not been shown to negatively impact outcomes in patients managed with beta-lactam monotherapy in the hospital. SUMMARY: Current evidence supports the use of beta-lactam monotherapy in adult patients hospitalized with mild to moderate CAP. While existing evidence supports the use of combination therapy in patients with severe pneumonia, further large-scale randomized controlled trials are urgently needed to clarify the role of combination therapy in this population.


title: Infectious Disease Diagnostic Assays

text: Dogs and cats are commonly exposed to infectious disease agents. The following article is an update on the most common infectious disease assays used in small animal practice. In some situations, results of pathogen-specific molecular diagnostic assays can be used to assist the practicing veterinarian in the management of patients with infectious diseases. However, with some infectious disease agents, the assays are positive in healthy and ill animals and can be falsely negative and so the predictive values of the assays vary.


title: In Vitro and In Vivo Pharmacological Models to Assess Demyelination and Remyelination

text: In making a selection of cellular tools and animal models for generating screening assays in the search for new drugs, one needs to take into consideration the practicality of their use in the drug discovery process. Conducting high-throughput primary screens using libraries of small molecules, close to 1 million members in size, requires the generation of large numbers of cells which are easily acquired, reliably enriched, and reproducibly responsive to standard positive controls. These cells need to be similar in form and function to their counterparts in human disease. In vitro assays that can be mechanized by using robots can therefore save time and costs. In selecting in vivo models, consideration must be given to the species and strain of animal chosen, the appropriateness of the model to human disease, the extent of animal husbandry required during the in-life pharmacological assessment, the technical aspects of generating the model and harvesting the tissues for analyses, the cost of research tools in terms of time and money (demyelinating and remyelinating agents, amount of compound to be generated), and the length of time required for drug testing in the model. A consideration of the translational aspects of the in vivo model compared to those used in the clinic is also important. These themes will be developed with examples for drug discovery in the field of CNS demyelination and repair, specifically as it pertains to multiple sclerosis. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/npp.2008.145) contains supplementary material, which is available to authorized users.


title: COVID-19 and the chemical senses: supporting players take center stage

text: Abstract The main neurological manifestation of COVID-19 is loss of smell or taste. The high incidence of smell loss without significant rhinorrhea or nasal congestion suggests that SARS-CoV-2 targets the chemical senses through mechanisms distinct from those used by endemic coronaviruses or other common cold-causing agents. Here we review recently developed hypotheses about how SARS-CoV-2 might alter the cells and circuits involved in chemosensory processing and thereby change perception. Given our limited understanding of SARS-CoV-2 pathogenesis, we propose future experiments to elucidate disease mechanisms and highlight the relevance of this ongoing work to understanding how the virus might alter brain function more broadly.


title: Structure of Main Protease from Human Coronavirus NL63: Insights for Wide Spectrum Anti-Coronavirus Drug Design

text: First identified in The Netherlands in 2004, human coronavirus NL63 (HCoV-NL63) was found to cause worldwide infections. Patients infected by HCoV-NL63 are typically young children with upper and lower respiratory tract infection, presenting with symptoms including croup, bronchiolitis, and pneumonia. Unfortunately, there are currently no effective antiviral therapy to contain HCoV-NL63 infection. CoV genomes encode an integral viral component, main protease (M(pro)), which is essential for viral replication through proteolytic processing of RNA replicase machinery. Due to the sequence and structural conservation among all CoVs, M(pro) has been recognized as an attractive molecular target for rational anti-CoV drug design. Here we present the crystal structure of HCoV-NL63 M(pro) in complex with a Michael acceptor inhibitor N3. Structural analysis, consistent with biochemical inhibition results, reveals the molecular mechanism of enzyme inhibition at the highly conservative substrate-recognition pocket. We show such molecular target remains unchanged across 30 clinical isolates of HCoV-NL63 strains. Through comparative study with M(pro)s from other human CoVs (including the deadly SARS-CoV and MERS-CoV) and their related zoonotic CoVs, our structure of HCoV-NL63 M(pro) provides critical insight into rational development of wide spectrum antiviral therapeutics to treat infections caused by human CoVs.


title: The Impact of COVID-19 on Cancer Risk and Treatment

text: Millions of people are being infected with COVID-19 around the globe. Though the majority of them will recover, cancer patients remain at a higher risk to SARS-CoV-2 infection and its related severe outcomes. Understanding how viruses contribute to human cancers provides us with new opportunities for preventing or treating virus-associated cancers. However, a limited amount of research has been done to date in the context of how viral infections impact cancer at the cellular level and vice versa. Therefore, in light of the COVID-19 global infection, this review highlights the need for better understanding of the biology of viral infections in cancer patients, to enable novel therapies to co-target viral infections and cancer.


title: Full-length genome sequence and genetic relationship of two paramyxoviruses isolated from bat and pigs in the Americas

text: Mapuera virus (MPRV) was isolated from a fruit bat in Brazil in 1979, but its host range and disease-causing potential are unknown. Porcine rubulavirus (PoRV) was identified as the aetiological agent of disease outbreaks in pigs in Mexico during early 1980s, but the origin of PoRV remains elusive. In this study, the completed genome sequence of MPRV was determined, and the complete genome sequence of PoRV was assembled from previously published protein-coding genes and the non-coding genome regions determined from this study. Comparison of sequence and genome organization indicated that PoRV is more closely related to MPRV than to any other members of the genus Rubulavirus. In the P gene coding region of both viruses, there is an ORF located at the 5′ end of the P gene overlapping with the P protein coding region, similar to the C protein ORF present in most viruses of the subfamily Paramyxovirinae, but absent in other known rubulaviruses. Based on these findings, we hypothesise that PoRV may also originate from bats, and spillover events from bats to pigs, either directly or via an intermediate host, were responsible for the sporadic disease outbreaks observed in Mexico.


title: Efficacy and Safety of Low Dose Recombinant Tissue-Type Plasminogen Activator for the Treatment of Acute Pulmonary Thromboembolism A Randomized, Multicenter, Controlled Trial

text: Background Optimal dosing of the recombinant tissue-type plasminogen activator (rt-PA) is important in treating pulmonary thromboembolism (PTE). The aim of this study was to compare the efficacy and safety of a 50 mg/2 h rt-PA regimen with a 100 mg/2 h rt-PA regimen in patients with acute PTE. Methods A prospective, randomized, multicenter trial was conducted in which 118 patients with acute PTE and either hemodynamic instability or massive pulmonary artery obstruction were randomly assigned to receive a treatment regiment of either rt-PA at 50 mg/2 h (n = 65) or 100 mg/2 h (n = 53). The efficacy was determined by observing the improvements of right ventricular dysfunctions (RVDs) on echocardiograms, lung perfusion defects on ventilation perfusion lung scans, and pulmonary artery obstructions on CT angiograms. The adverse events, including death, bleeding, and PTE recurrence, were also evaluated. Results Progressive improvements in RVDs, lung perfusion defects, and pulmonary artery obstructions were found to be similarly significant in both treatment groups. This is true for patients with either hemodynamic instability or massive pulmonary artery obstruction. Three (6%) patients in the rt-PA 100 mg/2 h group and one (2%) in the rt-PA 50 mg/2 h group died as the result of either PTE or bleeding. Importantly, the 50 mg/2 h rt-PA regimen resulted in less bleeding tendency than the 100 mg/2 h regimen (3% vs 10%), especially in patients with a body weight < 65 kg (14.8% vs 41.2%, P = .049). No fatal recurrent PTE was found in either group. Conclusions Compared with the 100 mg/2 h regimen, the 50 mg/2 h rt-PA regimen exhibits similar efficacy and perhaps better safety in patients with acute PTE. These findings support the notion that optimizing rt-PA dosing is worthwhile when treating patients with PTE. Trial registration clinicaltrials.gov; Identifier: NCT00781378


Coronavirus and the Responsibility of Plastic Surgeons


title: Effects of interleukin 17A (IL-17A) neutralization on murine hepatitis virus (MHV-A59) infection

text: Mice infected with mouse hepatitis virus A59 (MHV-A59) develop hepatitis and autoantibodies (autoAb) to liver and kidney fumarylacetoacetate hydrolase (FAH), a fact closely related to the release of alarmins such as uric acid and/or high-mobility group box protein 1 (HMGB1). We studied the effect of neutralizing monoclonal antibodies (MAb) against IL-17A in our model of mouse MHV-A59-infection. MAb anti-IL-17F and anti-IFNγ were used to complement the study. Results showed that transaminase levels markedly decreased in MHV-A59-infected mice treated with MAb anti-IL-17A whereas plasmatic Ig concentration sharply increased. Conversely, MAb anti-IL-17F enhanced transaminase liberation and did not affect Ig levels. Serum IFNγ was detected in mice infected with MHV-A59 and its concentration increased after MAb anti-IL-17A administration. Besides, MAb anti-IFNγ greatly augmented transaminase plasmatic levels. IL-17A neutralization did not affect MHV-A59-induction of HMGB1 liberation and slightly augmented plasmatic uric acid concentration. However, mice treated with the MAb failed to produce autoAb to FAH. The above results suggest a reciprocal regulation of Th1 and Th17 cells acting on the different MHV-A59 effects. In addition, it is proposed that IL-17A is involved in alarmins adjuvant effects leading to autoAb expression.


title: Stimulation of Dectin-1 and Dectin-2 during Parenteral Immunization, but Not Mincle, Induces Secretory IgA in Intestinal Mucosa

text: Induction of a robust and long-lived mucosal immune response during vaccination is critical to achieve protection against numerous pathogens. However, traditional injected vaccines are generally poor inducers of mucosal immunity. One of the effective strategies to improve vaccine efficacy is incorporation of adjuvant molecules that enhance and polarize adaptive immune reactions. Effects of Syk-coupled lectin receptor agonists as adjuvants to induce mucosal immune reactions during parenteral immunization are not fully studied. We now report that the agonists trehalose-6,6-dibehenate (TDB), curdlan, and furfurman, which stimulate Dectin-1, Dectin-2, and Mincle, respectively, activate transcription factors (NF-κB, NFAT, and AP-1) to various extents in murine RAW 264.7 macrophages, even though similar pathways are activated. The agonists also elicit differential expression of maturation markers in bone marrow-derived dendritic cells, as well as differential cytokine secretion from these cells and from splenic mononuclear cells. In vivo assays also show that agonists of Dectin-1 and Dectin-2, but not Mincle, induce heavy IgA secretion in intestinal mucosa even when delivered parenterally. Strikingly, this effect appears to be formulation-independent. Collectively, the data suggest that adjuvants based on Dectin-1 and Dectin-2 agonists may significantly improve the efficacy of parenteral vaccines by inducing robust local immune reactions in intestinal mucosa.


title: Kaempferol Derivatives as Antiviral Drugs against the 3a Channel Protein of Coronavirus

text: The protein coded by the open-reading-frame 3a of SARS coronavirus has been demonstrated to form a cation-selective channel that may become expressed in the infected cell. The activity of the channel is involved in the mechanism of virus release. Drugs that inhibit the ion channel can, therefore, inhibit virus release, and they could be a source for development of novel therapeutic antiviral agents. Various drugs found in Chinese herbs that are well known as anticancer agents also have an antiviral potency. Here we tested the flavonols kaempferol, kaempferol glycosides, and acylated kaempferol glucoside derivatives with respect to their potency to block the 3a channel. We used the Xenopus oocyte with a heterologously expressed 3a protein as a model system to test the efficacy of the flavonols. Some of these drugs turned out to be potent inhibitors of the 3a channel. The most effective one was the glycoside juglanin (carrying an arabinose residue) with an IC(50) value of 2.3 µM for inhibition of the 3a-mediated current. Kaempferol derivatives with rhamnose residue also seem to be quite effective. We suggest that viral ion channels, in general, may be a good target for the development of antiviral agents, and that, in particular, kaempferol glycosides are good candidates for 3a channel proteins of coronaviruses.


title: Voicing an impact: who does the National Institutes of Health support for voice disorder research?()

text: PURPOSE: Interest in a variety of neoplastic, functional, neurological, and age-related laryngeal disorders has contributed to the development of laryngology as an established subspecialty. Funding support plays a critical role in facilitating scholarship within the field. Our objectives were to evaluate who is receiving funding from the NIH for topics relevant to voice disorders, and further describe temporal trends in grants awarded. METHODS: The NIH RePORTER database was searched for grants relevant to voice disorders. Data were further organized by PI specialty, academic department, and funding totals. Furthermore, PI scholarly impact, as measured by the h-index, was calculated. RESULTS: A total of 830 funded fiscal years (for 232 unique projects) totaling $203 million have supported projects examining voice disorders. A plurality of projects (32.8%) was awarded to PIs in otolaryngology departments, followed by 17.2% to speech pathology/communication sciences departments. Although year-to-year variation was noted, otolaryngology departments received approximately 15% of funding annually. Funded otolaryngologists had similar scholarly impact values to individuals in other specialties. CONCLUSIONS: The study of voice disorders involves an interdisciplinary approach, as PIs in numerous specialties receive NIH funding support. As they receive a considerable proportion of this funding and had similar h-indices compared to other specialties involved, otolaryngologists have just as much scholarly impact despite being a smaller specialty. As speech and language pathologists also comprised a significant proportion of individuals in this analysis, enhanced cooperation and encouragement of interdisciplinary scholarly initiatives may be beneficial.


title: Characterization and immunogenicity of norovirus capsid-derived virus-like particles purified by anion exchange chromatography

text: Recombinant baculovirus (BV) expression systems are widely applied in the production of viral capsid proteins and virus-like particles (VLPs) for use as immunogens and vaccine candidates. Traditional density gradient purification of VLPs does not enable complete elimination of BV-derived impurities, including live viruses, envelope glycoprotein gp64 and baculoviral DNA. We used an additional purification system based on ionic strength to purify norovirus (NoV) GII-4 capsid-derived VLPs. The anion exchange chromatography purification led to highly purified VLPs free from BV impurities with intact morphology. In addition, highly purified VLPs induced strong NoV-specific antibody responses in BALB/c mice. Here, we describe a method for NoV VLP purification and several methods for determining their purity, including quantitative PCR for BV DNA detection.


August 3–9, 2013


title: The Burden of Community-Acquired Pneumonia in Seniors: Results of a Population-Based Study

text: Background. Pneumonia is recognized as a leading cause of morbidity in seniors. However, the overall burden of this disease—and, in particular, the contribution of ambulatory cases to that burden—is not well defined. To estimate rates of community-acquired pneumonia and to identify risk factors for this disease, we conducted a large, population-based cohort study of persons aged ⩾65 years that included both hospitalizations and outpatient visits for pneumonia. Methods. The study population consisted of 46,237 seniors enrolled at Group Health Cooperative who were observed over a 3-year period. Pneumonia episodes presumptively identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes assigned to medical encounters were validated by medical record review. Characteristics of participants were defined by administrative data sources. Results. The overall rate of community-acquired pneumonia ranged from 18.2 cases per 1000 person-years among persons aged 65–69 years to 52.3 cases per 1000 person-years among those aged ⩾85 years. In this population, 59.3% of all pneumonia episodes were treated on an outpatient basis. In multivariate analysis, risk factors for community-acquired pneumonia included age, male sex, chronic obstructive pulmonary disease, asthma, diabetes mellitus, congestive heart failure, and smoking. Conclusions. On the basis of these data, we estimate that roughly 915,900 cases of community-acquired pneumonia occur annually among seniors in the United States and that ∼1 of every 20 persons aged ⩾85 years will have a new episode of community-acquired pneumonia each year.


title: The Involvement of Histone H3 Acetylation in Bovine Herpesvirus 1 Replication in MDBK Cells

text: During bovine herpesvirus 1 (BoHV-1) productive infection in cell cultures, partial of intranuclear viral DNA is present in nucleosomes, and viral protein VP22 associates with histones and decreases histone H4 acetylation, indicating the involvement of histone H4 acetylation in virus replication. In this study, we demonstrated that BoHV-1 infection at the late stage (at 24 h after infection) dramatically decreased histone H3 acetylation [at residues K9 (H3K9ac) and K18 (H3K18ac)], which was supported by the pronounced depletion of histone acetyltransferases (HATs) including CBP/P300 (CREB binding protein and p300), GCN5L2 (general control of amino acid synthesis yeast homolog like 2) and PCAF (P300/CBP-associated factor). The depletion of GCN5L2 promoted by virus infection was partially mediated by ubiquitin-proteasome pathway. Interestingly, the viral replication was enhanced by HAT (histone acetyltransferase) activator CTPB [N-(4-Chloro-3-trifluoromethylphenyl)-2-ethoxy-6-pentadecylbenzamide], and vice versa, inhibited by HAT inhibitor Anacardic acid (AA), suggesting that BoHV-1 may take advantage of histone acetylation for efficient replication. Taken together, we proposed that the HAT-dependent histone H3 acetylation plays an important role in BoHV-1 replication in MDBK (Madin-Darby bovine kidney) cells.


title: Covid‐19 diffusion and its impact on dental practice in distant countries with similar ethnic background

text: Epidemiology of Covid‐19 and diffusion patterns of the novel coronavirus (SARS – CoV – 2) are still poorly understood, as they differ substantially among countries and even in neighboring regions within the same country. It is not clear if differences in viral spreading depends on population age, genetic influences, specific environmental factors (e.g. season of the year), socioeconomic conditions or a combination of these. Some Authors hypothesized that differences in models of SARS – CoV – 2 diffusion may be explained also on the basis of ethnic influences (Pareek, Bangash, Pareek, Pan, Sze, Minhas, Hanif, Khunti, 2020). Under such perspective, it seems rational to compare the Italian experience to that of Uruguay.


title: Immune and bioinformatics identification of T cell and B cell epitopes in the protein structure of SARS-CoV-2: A Systematic Review

text: The beginning of 2020 was marked as the emergence of a COVID-19 outbreak caused by a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, there is no vaccine or approved treatment for this infectious virus so the invention of an efficient vaccine is certainly a high priority. Some studies have employed several techniques to facilitate the combination of the immunoinformatics approach and comparative genomic approach in order to determine the potential peptides for designing the T-cell epitope-based peptide vaccine using the 2019-nCoV envelope protein as a target. Via screening the bioimmunoinformatic SARS-CoV2 derived B-cell and T-cell epitopes within the basic immunogenic of SARS-CoV2 proteins, we presented a set of inferred B-cell and T-cell epitopes from the spike (S) and nucleocapsid (N) proteins with high antigenicity and without allergenic property or toxic effects. Our findings provide a screened set of epitopes that can be introduced as potential targets for developing peptide vaccines against the SARS-CoV-2 virus.


title: Successful Treatment of Disseminated Nocardiosis Caused by Nocardia veterana in a Dog

text: A 5‐year‐old male castrated Lhasa Apso cross was evaluated for a 1‐month history of inappetence, lethargy, gagging, and progressive right thoracic limb lameness. Synovial fluid analysis revealed nonseptic suppurative inflammation, and a diagnosis of immune‐mediated polyarthritis (IMPA) was made. After 3 months of treatment with prednisone and later cyclosporine, the dog developed multiple firm cutaneous and subcutaneous masses and a focal mass within the jejunum. Cultures of blood, urine, skin lesions, and the jejunal mass identified Nocardia veterana by matrix‐absorption laser desorption ionization‐time‐of‐flight mass spectrometry (MALDI‐TOF MS) and allowed for earlier identification of the organism compared to more traditional secA1 gene sequencing. Immunosuppressive drug treatment was discontinued, and the dog was treated for 3 months by administration of trimethoprim‐sulfamethoxazole (TMS). No recurrence of clinical signs was reported 1 year later. This case report highlights the clinical utility of MALDI‐TOF MS, particularly for the rapid identification of slow‐growing, fastidious organisms.


title: Targeting the NLRP3 Inflammasome in Severe COVID-19

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the genus Betacoronavirus within the family Coronaviridae. It is an enveloped single-stranded positive-sense RNA virus. Since December of 2019, a global expansion of the infection has occurred with widespread dissemination of coronavirus disease 2019 (COVID-19). COVID-19 often manifests as only mild cold-like symptomatology, but severe disease with complications occurs in 15% of cases. Respiratory failure occurs in severe disease that can be accompanied by a systemic inflammatory reaction characterized by inflammatory cytokine release. In severe cases, fatality is caused by the rapid development of severe lung injury characteristic of acute respiratory distress syndrome (ARDS). Although ARDS is a complication of SARS-CoV-2 infection, it is not viral replication or infection that causes tissue injury; rather, it is the result of dysregulated hyperinflammation in response to viral infection. This pathology is characterized by intense, rapid stimulation of the innate immune response that triggers activation of the Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome pathway and release of its products including the proinflammatory cytokines IL-6 and IL-1β. Here we review the literature that describes the pathogenesis of severe COVID-19 and NLRP3 activation and describe an important role in targeting this pathway for the treatment of severe COVID-19.


Therapeutic antibodies for infectious diseases


title: Molecular detection and phylogenetic properties of isolated infectious bronchitis viruses from broilers in Ahvaz, southwest Iran, based on partial sequences of spike gene

text: Infectious bronchitis (IB) is a highly contagious disease involving mostly upper respiratory tract in chickens, leading to significant economic losses in the poultry industry worldwide. One of the major concerns regarding to IB is the emergence of new types of infectious bronchitis viruses (IBVs). The purpose of this study was to identify the IBVs isolated from Iranian broiler chickens with respiratory symptoms. Twenty-five broiler flocks around Ahwaz (southwest of Iran) were examined for IBV. The specimens including trachea, lung, liver, kidney, and ceacal tonsil, were collected from diseased birds and inoculated into chicken embryonated eggs. Harvested allantoic fluids were subjected to reverse transcription polymerase chain reaction (RT-PCR) using primers in order to amplify spike 1 (S1) gene of IBV. The RT-PCR products of four IBV isolates were sequenced. The results showed that from 25 examined flocks with respiratory disease, 12 flocks (48.00%) were positive for IBV. In phylogenetic analysis, our isolates were closely related to the QX-like viruses such as PCRLab/06/2012 (Iran), QX, HC9, HC10, CK/CH/GX/NN11-1, CK/CH/JS/YC11-1, CK/CH/JS/2010/13, CK/CH/JS/2011/2 (China), QX/SGK-21, QX/SGK-11 (Iraq) with nucleotide homology up to 99.00%. This study indicates the role of IBVs in the respiratory disorders of broiler flocks located in southwest Iran, and also the existence of a variant of IBV, which is distinguishable from the other Iranian variants.


title: Are RNA Viruses Adapting or Merely Changing?

text: RNA viruses and retroviruses fix substitutions approximately 1 million-fold faster than their hosts. This diversification could represent an inevitable drift under purifying selection, the majority of substitutions being phenotypically neutral. The alternative is to suppose that most fixed mutations are beneficial to the virus, allowing it to keep ahead of the host and/or host population. Here, relative sequence diversification of different proteins encoded by viral genomes is found to be linear. The examples encompass a wide variety of retroviruses and RNA viruses. The smoothness of relative divergence spans quasispeciation following clonal infection, to variation among different isolates of the same virus, to viruses from different species or those associated with different diseases, indicating that the majority of fixed mutations likely reflects drift. This held for both mammalian and plant viruses, indicating that adaptive immunity doesn't necessarily shape the relative accumulation of amino acid substitutions. When compared to their hosts RNA viruses evolution appears conservative.


title: Hospitalized adult patients with 2009 influenza A(H1N1) in Beijing, China: risk factors for hospital mortality

text: BACKGROUND: In April 2009, the pandemic influenza A(H1N1) virus emerged and spread globally. The objective of this study was to describe the independent risk factors for hospital mortality and the treatment effect of corticosteroids among patients with 2009 influenza A(H1N1) infection. METHODS: We retrospectively obtained clinical data of 155 adult patients with confirmed infection of 2009 influenza A(H1N1) in 23 hospitals in Beijing, China from October 1 to December 23, 2009. Risk factors for hospital mortality were identified with multivariate logistic regression analysis. RESULTS: Among the 155 patients, 90 (58.1%) were male, and mean age was 43.0 ± 18.6 years, and comorbidities were present in 81 (52.3%) patients. The most common organ dysfunctions included acute respiratory failure, altered mental status, septic shock, and acute renal failure. Oseltamivir was initiated in 125 patients (80.6%), only 16 patients received antiviral therapy within 48 hours after symptom onset. Fifty-two patients (33.5%) were treated with systemic corticosteroids, with a median daily dose of 80 mg. Twenty-seven patients (17.4%) died during hospital stay. Diabetes [odds ratio (OR) 8.830, 95% confidence interval [CI] 2.041 to 38.201, p = 0.004) and lactate dehydrogenase (LDH) level (OR 1.240, 95% CI 1.025 to 1.500, p = 0.027) were independent risk factors of hospital death, as were septic shock and altered mental status. Corticosteroids use was associated with a trend toward higher hospital mortality (OR 3.668, 95% CI 0.987 to 13.640, p = 0.052). CONCLUSIONS: Hospitalized patients with 2009 H1N1 influenza had relative poor outcome. The risk factors at hospitalization may help clinicians to identify the high-risk patients. In addition, corticosteroids use should not be regarded as routine pharmacologic therapy.


title: Age‐specific prevalence of complement‐fixing antibodies to sixteen viral antigens: A computer analysis of 58,500 patients covering a period of eight years

text: The age‐specific prevalence of CF antibodies against 16 viral antigens was determined by using the computerized data registry of the routine diagnostic laboratory of the authors' department. The material consisted of data based on serum specimens from about 58,500 patients. All ages from newborn infants to 90‐year‐olds were represented. The sera had been collected and tested with a CF screening test over a period of 8 years (1971–1978). Several different antibody prevalence patterns were distinguished in regard to the rapidity and timing of the initial increase of the prevalence, as well as to the mode of later changes in prevalence. For most respiratory viruses a rapid increase of the prevalence was seen through the childhood continuing, for some of them, up to the 30s (influenza A and coronavirus), while rather variable patterns were found in the older age groups. Herpes simplex and cytomegaloviruses showed, interestingly, another type of pattern: a slow increase of prevalence continuing through the whole age range. The frequency of herpes simplex antibodies reached 90% by the age of 80 years. Antibody levels against any antigen in infants less than one‐month‐old were equal to those in 20‐ to 40‐year‐old adults, and the expected rapid decrease of antibodies took place within the first 6 months of life. Possible influences of epidemics and repeated exposures to different viruses (external boosting), and of latent or chronic infections (internal boosting), as wells as of technical variations, on the observed prevalence patterns are discussed.


Guest editorial: Building COVID‐19 resilient insolvency frameworks


title: Implications for the use of telehealth in surgical patients during the COVID-19 pandemic

text: Abstract The COVID-19 pandemic has brought rapid changes to the way care must be delivered to keep patients and providers safe while simultaneously managing limited resources. Multiple fields have used telemedicine to continue care while maintaining social distancing and quarantine practices in the pandemic. Presented in this paper is a review describing the application of telemedicine in caring for surgical patients, and methods for potential implications of telehealthcare for surgical patients during the COVID-19 pandemic. A review of the PubMed Central and Medline provides articles examining the role of telemedicine for preoperative, postoperative, and follow up evaluation of surgical patients encompassing the past two decades. Additionally, articles examining the financial and legal considerations of telemedicine, and the effect COVID-19 has had on the current legislature were included. We report the summarized findings of these studies, the financial and HIPAA considerations of using telemedicine, potential benefits, pitfalls and strategies for the utilization of telemedicine into the clinical practice of general surgery and its subspecialties during the COVID-19 pandemic.


title: Chapter 2 Why Do We Produce Anti-Gal Evolutionary Appearance of Anti-Gal in Old World Primates

text: Abstract The natural anti-Gal antibody is one of the multiple natural anti-carbohydrate antibodies produced in humans against a wide range of carbohydrate antigens on GI bacteria. The antibody is unique to humans, apes, and Old World monkeys, and it binds specifically to a mammalian carbohydrate antigen called the α-gal epitope that is synthesized in nonprimate mammals, lemurs (prosimians) and New World monkeys by the glycosylation enzyme α1,3GT. The α1,3GT gene (GGTA1) appeared in mammals >100 million years ago, prior to the split between marsupial and placental mammals. This gene has been conserved in its active form, in all mammals, except for Old World monkeys, apes, and humans. Inactivation of the α1,3GT gene in ancestral Old World primates occurred 20–30 million years ago and could have been associated with epidemics of enveloped viruses in the Eurasia-Africa continent. It is suggested that prior to such epidemics, few ancestral Old World primates acquired deletion point mutations that inactivated the α1,3GT gene and eliminated α-gal epitopes. This resulted in loss of immune tolerance to the α-gal epitope and thus, in production of the anti-Gal antibody against antigens on bacteria colonizing the GI tract. This accidental inactivation of the α1,3GT gene in very small populations is analogous to the highly rare blood type “Bombay” individuals who do not synthesize blood group H (O antigen) because of inactivation of the α1,2-fucosyltransferase gene. The loss of immune tolerance to blood group H antigen has resulted in production of natural anti-blood group H antibodies in the blood group Bombay individuals. It is suggested that anti-Gal protected against infections by enveloped viruses presenting α-gal epitopes, which were lethal to the parental primate populations that conserved active α1,3GT and thus, synthesized α-gal epitopes. Alternative causes for the elimination of Old World primates synthesizing α-gal epitopes could be bacteria or protozoa parasites presenting α-gal or α-gal-like epitopes, and bacterial toxins, or detrimental viruses that used α-gal epitopes in these primates as “docking receptors.” Ultimately, any of these proposed selective processes could result in extinction of Old World primates synthesizing α-gal epitopes on their cells. These ancestral primates were replaced by offspring populations lacking α-gal epitopes and producing the anti-Gal antibody, which continues to be produced by Old World monkeys, apes, and humans. New World monkeys and lemurs were protected from pathogens of the Old World by oceanic barriers, thus they continue to synthesize α-gal epitopes and lack the ability to produce the anti-Gal antibody. This scenario of few individuals in a large population having a mutation(s) that inactivates a glycosyltransferase gene thus, resulting in production of evolutionary advantageous natural antibodies against the eliminated carbohydrate antigen, may reflect one of the mechanisms inducing changes in the carbohydrate profile of various mammalian populations.


title: First Complete Genome Sequence of a Feline Alphacoronavirus 1 Strain from Brazil

text: We identified a strain of Alphacoronavirus 1, FCoV-SB22, from a pool of fecal samples from domestic cats from a rural settlement in the municipality of Santa Bárbara, Pará, Brazil. The nucleotide identity with feline coronavirus was 91.5%. The present study reports the first complete genome sequence of a feline coronavirus from Brazil.


title: COVID-19 and addiction

text: BACKGROUND AND AIMS: 2019-coronavirus disease (COVID-19) is causing insurmountable psychosocial impact on the whole mankind. Marginalized community, particularly those with substance use disorders (SUD), are particularly vulnerable to contract the infection and also likely to suffer from greater psychosocial burden. This article analyses the intricate bi-directional relationship between COVID-19 and addiction. METHODS: Pubmed and Google Scholar are searched with the following key terms- “COVID-19”, “SARS-CoV2”, “Pandemic”, “Addiction”, “Opioid”, “Alcohol”, “Smoking”, “Addiction Psychiatry”, “Deaddiction”, “Substance use disorders”, “Behavioral addiction”. Few newspaper reports related to COVID-19 and addiction have also been added as per context. RESULTS: People with SUD are at greater risk of worse COVID-19 outcome. There is surge of addictive behaviors (both new and relapse) including behavioral addiction in this period. Withdrawal emergencies and death are also being increasingly reported. Addicted people are especially facing difficulties in accessing the healthcare services which are making them prone to procure drugs in illegal means. CONCLUSION: COVID-19 and addiction are the two pandemics which are on the verge of collision causing major public health threat. While every effort must be taken to make the public aware of deleterious effects of SUD on COVID-19 prognosis, the resumption of deaddiction services and easier accessibility of prescription drugs are needs of the hour.


title: Detection of WU polyomavirus DNA by real-time PCR in nasopharyngeal aspirates, serum, and stool samples

text: Abstract Background The human WU polyomavirus (WUPyV) has been recently described as a novel virus in respiratory tract samples. Objective To investigate the viral load of WUPyV in nasopharyngeal aspirates (NPAs), stool, and serum samples of pediatric patients with acute respiratory tract diseases. Study design We established a real-time PCR for WUPyV DNA and tested NPA obtained between 2002 and 2007 from pediatric in-patients with acute respiratory tract diseases. In addition, 14 stool and 14 serum samples of children with WUPyV DNA positive NPA were analysed. Results WUPyV DNA was found in 5.2% of 1232 NPA. The median viral load in the NPA was 950copies/ml (maximum 3.4E10copies/ml). The WUPyV load in NPA was neither associated with the coinfection status nor with the clinical diagnoses. WUPyV DNA was found in 3 of 14 serum samples and in 2 of 14 stool samples. The WUPyV load in NPA tended to be higher in viremic children. Conclusion WUPyV DNA was found in NPA, serum, and stool of hospitalised children with acute respiratory tract diseases. Further studies are necessary to determine whether WUPyV is a human pathogen.


title: COVID-19-associated shortage of alcohol-based hand rubs, face masks, medical gloves and gowns – proposal for a risk-adapted approach to ensure patient and healthcare worker safety

text: Summary The COVID-19 pandemic has caused a huge demand of alcohol-based hand rubs, medical gloves, face masks and gowns in healthcare and from the public. More and more hospitals face a serious shortage of these articles. We propose a risk-adapted approach to ensure adequate patient and healthcare worker safety for as long as possible.


title: Rational improvement of gp41-targeting HIV-1 fusion inhibitors: an innovatively designed Ile-Asp-Leu tail with alternative conformations

text: Peptides derived from the C-terminal heptad repeat (CHR) of HIV gp41 have been developed as effective fusion inhibitors against HIV-1, but facing the challenges of enhancing potency and stability. Here, we report a rationally designed novel HIV-1 fusion inhibitor derived from CHR-derived peptide (Trp628~Gln653, named CP), but with an innovative Ile-Asp-Leu tail (IDL) that dramatically increased the inhibitory activity by up to 100 folds. We also determined the crystal structures of artificial fusion peptides N36- and N43-L6-CP-IDL. Although the overall structures of both fusion peptides share the canonical six-helix bundle (6-HB) configuration, their IDL tails adopt two different conformations: a one-turn helix with the N36, and a hook-like structure with the longer N43. Structural comparison showed that the hook-like IDL tail possesses a larger interaction interface with NHR than the helical one. Further molecular dynamics simulations of the two 6-HBs and isolated CP-IDL peptides suggested that hook-like form of IDL tail can be stabilized by its binding to NHR trimer. Therefore, CP-IDL has potential for further development as a new HIV fusion inhibitor, and this strategy could be widely used in developing artificial fusion inhibitors against HIV and other enveloped viruses.


title: Sialic Acid Receptors of Viruses

text: Sialic acid linked to glycoproteins and gangliosides is used by many viruses as a receptor for cell entry. These viruses include important human and animal pathogens, such as influenza, parainfluenza, mumps, corona, noro, rota, and DNA tumor viruses. Attachment to sialic acid is mediated by receptor binding proteins that are constituents of viral envelopes or exposed at the surface of non-enveloped viruses. Some of these viruses are also equipped with a neuraminidase or a sialyl-O-acetyl-esterase. These receptor-destroying enzymes promote virus release from infected cells and neutralize sialic acid-containing soluble proteins interfering with cell surface binding of the virus. Variations in the receptor specificity are important determinants for host range, tissue tropism, pathogenicity, and transmissibility of these viruses.


title: Orchitis in a Cat Associated with Coronavirus Infection

text: Abstract A case of severe, pyogranulomatous and necrotizing orchitis in a cat, which later succumbed to systemic feline infectious peritonitis (FIP), is described. The 3·5-year-old cat, positive for feline immunodeficiency virus infection, presented with a left testicular enlargement. A few months after castration the animal was humanely destroyed due to declining health. Post-mortem examination revealed inflammatory lesions in abdominal organs and in the brain compatible with FIP. Infection was confirmed with a reverse transcriptase–polymerase chain reaction test and by immunohistochemical demonstration of coronavirus antigen in the affected tissues, including the left testicle. FIP is usually a systemic disease. However, lesions and presenting clinical signs in a single organ system such as the brain are not uncommon. The results of this case study indicate that orchitis, although rare, should be on the list of lesions of FIP.


title: β(2)-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study

text: BACKGROUND: Despite the significant interest in β(2)-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. METHODS: To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. RESULTS: There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95 % confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. CONCLUSIONS: ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0229-3) contains supplementary material, which is available to authorized users.


Chest tube with air leaks is a potential “super spreader” of COVID-19


title: Decontamination of Surgical Face Masks and N95 Respirators by Dry Heat Pasteurization for One Hour at 70°C

text: BACKGROUND: The need for protective masks greatly exceeds their global supply during the current COVID-19 pandemic. METHODS: We optimized the temperature used in the dry heat pasteurization method to destroy pathogens and decontaminate masks while retaining their filtering capacity. RESULTS: The current study showed that dry heat at both 60°C and 70°C for one hour could successfully kill six species of respiratory bacteria and one fungi species, and inactivate the H1N1 indicator virus. After being heated at 70°C for 1 h, 2 h, and 3 h, the N95 respirators and surgical face masks showed no changes in their shape and components. The filtering efficiency of bacterial aerosol for N95 respirators were 98%, 98%, and 97% after being heated for 1 h, 2 h, and 3 h, respectively, all of which were over the 95% efficiency required and similar to the value before being heated (99%). The filtering efficiency for surgical face masks was 97%, 97%, and 96% for 1 h, 2 h, and 3 h of heating, respectively, all of which were also similar to the value before being heated (97%). CONCLUSIONS: This method can be used at home and can resolve the current shortage of masks.


title: Tumor necrosis factor and interferon: cytokines in harmony

text: Individually, tumor necrosis factor (TNF) and the various interferons frequently display strong antiviral activities. Certain combinations of these cytokines, however, induce a synergistic antiviral state which is distinct from that induced by either one alone. This novel synergistic antiviral state likely occurs through several possible mechanisms, involves multiple signaling pathways, and inhibits a wider range of viruses than the individual cytokines alone. While underappreciated when first discovered, this synergistic phenomenon is proving to be of a much broader scope than initially thought. More work is needed to refine our understanding of this observation and its physiological implications for anti-pathogen responses.