title: Estimating the nationwide transmission risk of measles in US schools and impacts of vaccination and supplemental infection control strategies

text: BACKGROUND: The spread of airborne infectious diseases such as measles is a critical public health concern. The U.S. was certified measles-free in 2000, but the number of measles cases has increased in recent years breaking the record of the nationwide annual number of cases since 1992. Although the characteristics of schools have made them one of the most vulnerable environments during infection outbreaks, the transmission risk of measles among students is not completely understood. We aimed to evaluate how three factors influence measles transmission in schools: personal (vaccination), social (compartmentalizing), and building systems (ventilation, purification, and filtration). METHODS: We used a combination of a newly developed multi-zone transient Wells-Riley approach, a nationwide representative School Building Archetype (SBA) model, and a Monte-Carlo simulation to estimate measles risk among U.S. students. We compared our risk results with the range of reported transmission rates of measles in school outbreaks to validate the risk model. We also investigated the effectiveness of vaccination and ten supplemental infection control scenarios for reducing the risk of measles transmission among students. RESULTS: Our best nationwide estimate of measles transmission risk in U.S. schools were 3.5 and 32% among all (both unvaccinated and immunized) and unvaccinated students, respectively. The results showed the transmission risk of measles among unvaccinated students is > 70 times higher than properly immunized ones. We also demonstrated that the transmission risk of measles in primary schools (assuming teacher self-contained classrooms) is less than secondary schools (assuming departmentalized systems). For building-level interventions, schools with ductless-with-air-filter and ductless-without-air-filter systems have the lowest and highest transmission risks of measles, respectively. Finally, our simulation showed that infection control strategies could cut the average number of infected cases among all students in half when a combination of advanced air filtration, ventilation, and purification was adopted in the modeled schools. CONCLUSIONS: Our results highlight the primary importance of vaccination for reducing the risk of measles transmission among students. Yet, additional and significant risk reduction can be achieved through compartmentalizing students and enhancing building ventilation and filtration systems.


title: Revisitation of autoimmune hypophysitis: knowledge and uncertainties on pathophysiological and clinical aspects

text: PURPOSE: This publication reviews the accepted knowledges and the findings still discussed on several features of autoimmune hypophysitis, including the most recently described forms, such as IgG4 and cancer immunotherapy- related hypophysitis. METHODS: The most characteristic findings and the pending controversies were derived from a literature review and previous personal experiences. A single paragraph focused on some atypical examples of the disease presenting under confounding pretences. RESULTS: Headache, visual field alterations and impaired pituitary secretion are the most frequent clinical findings of the disease. Pituitary biopsy, still considered the gold diagnostic standard, does not always receive consent from the patients. The role of magnetic resonance imaging is limited, as this disease may generate images similar to those of other diseases. The role of antipituitary and antihypothalamus antibodies is still discussed owing to methodological difficulties and also because the findings on the true pituitary antigen(s) are still debated. However, the low sensitivity and specificity of immunofluorescence, one of the more widely employed methods to detect these antibodies, may be improved, considering a predetermined cut-off titre and a particular kind of immunostaining. CONCLUSION: Autoimmune hypophysitis is a multifaceted disease, which may certainly be diagnosed by pituitary biopsy. However, the possible different clinical, laboratory and imaging features must be considered by the physician to avoid a misdiagnosis when examining a possibly affected patient. Therapeutic choice has to be made taking into account the clinical conditions and the degree of hypothalamic-pituitary involvement, but also considering that spontaneous remissions can occur.


docid: eymqlbix

title: Society of Cardiovascular Computed Tomography Guidance for Use of Cardiac Computed Tomography Amidst the COVID-19 Pandemic

text: Abstract The world is currently suffering through a pandemic outbreak of severe respiratory syndrome coronavirus 2 (SARS-CoV-2) known as Coronavirus Disease 2019 (COVID-19). The United States (US) Centers for Disease Control and Prevention (CDC) currently advises medical facilities to “reschedule non-urgent outpatient visits as necessary” (1). The European Centre for Disease Prevention and Control, the United Kingdom National Health Service and several other international agencies covering Asia, North America and most regions of the world have recommended similar “social distancing” measures(2, 3). The Society of Cardiovascular Computed Tomography (SCCT) offers guidance for cardiac CT (CCT) practitioners to help implement these international recommendations in order to decrease the risk of COVID-19 transmission in their facilities while deciding on the timing of outpatient and inpatient CCT exams. This document also emphasizes SCCT’s commitment to the health and well-being of CCT technologists, imagers, trainees, and research community, as well as the patients served by CCT.


title: Localization of ribophorin II to the endoplasmic reticulum involves both its transmembrane and cytoplasmic domains

text: Summary Proteins that are concentrated in specific compartments of the endomembrane system in order to exert their organelle-specific function must possess specific localization signals that prevent their transport to distal regions of the exocytic pathway. Some resident proteins of the endoplasmic reticulum (ER) that are known to escape with low efficiency from this organelle to a post ER compartment are recognized by a recycling receptor and brought back to their site of residence. Other ER proteins, however, appear to be retained in the ER by mechanisms that operate in the organelle itself. The mammalian oligosaccharyltransferase (OST) is a protein complex that effects the cotranslational N-glycosylation of newly synthesized polypeptides, and is composed of at least four rough ER-specific membrane proteins: ribophorins I and II (RI and RII), OST48, and Dad1. The mechanism(s) by which the subunits of this complex are retained in the ER are not well understood. In an effort to identify the domains within RII responsible for its ER localization we have studied the fate of chimeric proteins in which one or more RII domains were replaced by the corresponding ones of the Tac antigen, the latter being a well characterized plasma membrane protein that lacks intrinsic ER retention signals and serves to provide a neutral framework for the identification of retention signals in other proteins. We found that the luminal domain of RII by itself does not contain retention information, while the cytoplasmic and transmembrane domains contain independent ER localization signals. We also show that the retention function of the transmembrane domain is strengthened by the presence of a flanking luminal region consisting of 15 amino acids.


title: Formation of stable homodimer via the C-terminal α-helical domain of coronavirus nonstructural protein 9 is critical for its function in viral replication

text: Abstract Coronaviruses devote more than three quarters of their coding capacity to encode two large polyproteins (1a and 1ab polyproteins), which are proteolytically processed into 15–16 mature, nonstructural replicase proteins (nsp1 to 16). These cleavage products are believed to play essential roles in replication of the giant RNA genome of ∼30 kb and transcription of a nested set of 5 to 9 subgenomic RNA species by a unique discontinuous transcription mechanism. In this report, one of these replicase proteins, nsp9 of the coronavirus infectious bronchitis virus (IBV) is systematically studied using both biochemical and reverse genetic approaches. The results showed that substitution mutation of a conserved Gly (G98) residue in the C-terminal α-helix domain with an Asp greatly destabilized the IBV nsp9 homodimer and abolished its RNA-binding activity. Introduction of the same mutation into an infectious IBV clone system showed that the mutation totally abolishes the transcription of subgenomic RNA and no infectious virus could be recovered. Mutation of a semi-conserved Ile (I95) residue in the same region showed moderately destabilizing effect on the IBV nsp9 homodimer but minimal effect on its RNA-binding activity. Introduction of the mutation into the IBV infectious clone system showed recovery of a mutant virus with severe growth defects, supporting that dimerization is critical for the function of this replicase protein. Meanwhile, mutations of some positively charged residues in the β-barrel regions of the IBV nsp9 protein significantly reduced its RNA-binding activity, but with no obvious effect on dimerization of the protein. Introduction of these mutations into the viral genome showed only mild to moderate effects on the growth and infectivity of the rescued mutant viruses.


title: Are health care workers protected? An observational study of selection and removal of personal protective equipment in Canadian acute care hospitals

text: BACKGROUND: The proper use of personal protective equipment (PPE) by health care workers (HCWs) is vital in preventing the spread of infection and has implications for HCW safety. METHODS: An observational study was performed in 11 hospitals participating in the Canadian Nosocomial Infection Surveillance Program between January 7 and March 30, 2011. Using a standardized data collection tool, observers recorded HCWs selecting and removing PPE and performing hand hygiene on entry into the rooms of febrile respiratory illness patients. RESULTS: The majority of HCWs put on gloves (88%, n = 390), gown (83%, n = 368), and mask (88%, n = 386). Only 37% (n = 163) were observed to have put on eye protection. Working in a pediatric unit was significantly associated with not wearing eye protection (7%), gown (70%), gloves (77%), or mask (79%). Half of the observed HCWs (54%, n = 206) removed their PPE in the correct sequence. Twenty-six percent performed hand hygiene after removing their gloves, 46% after removing their gown, and 57% after removing their mask and/or eye protection. CONCLUSION: Overall adherence with appropriate PPE use in health care settings involving febrile respiratory illness patients was modest, particularly on pediatric units. Interventions to improve PPE use should be targeted toward the use of recommended precautions (eg, eye protection), HCWs working in pediatric units, the correct sequence of PPE removal, and performing hand hygiene.


title: Integrating spatial support tools into strategic planning—SEA of the GMS North–South Economic Corridor Strategy and Action Plan

text: Abstract The GMS countries, supported by the Asian Development Bank, have adopted a holistic, multidimensional approach to strengthen infrastructural linkages and facilitate cross border trade through (i) the establishment of a trans-boundary road connecting two economic nodes across marginalised areas, followed by 2) facilitation of environmentally and socially sound investments in these newly connected areas as a means to develop livelihoods. The North–South Economic Corridor is currently in its second phase of development, with investment opportunities to be laid out in the NSEC Strategy and Action Plan (SAP). It targets the ecologically and culturally sensitive border area between PR China's Yunnan Province, Northern Lao PDR, and Thailand. A trans-boundary, cross-sectoral Strategic Environmental Assessment was conducted to support the respective governments in assessing potential environmental and social impacts, developing alternatives and mitigation options, and feeding the findings back into the SAP writing process. Given the spatial dimension of corridor development—both with regard to opportunities and risks—particular emphasis was put in the application of spatial modelling tools to help geographically locate and quantify impacts as a means to guide interventions and set priorities.


Philanthropy and Humanity in the Face of a Pandemic – A letter to the editor on “World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19)” (Int J Surg 2020; 76:71-6)


title: The Vietnam Initiative on Zoonotic Infections (VIZIONS): A Strategic Approach to Studying Emerging Zoonotic Infectious Diseases

text: The effect of newly emerging or re-emerging infectious diseases of zoonotic origin in human populations can be potentially catastrophic, and large-scale investigations of such diseases are highly challenging. The monitoring of emergence events is subject to ascertainment bias, whether at the level of species discovery, emerging disease events, or disease outbreaks in human populations. Disease surveillance is generally performed post hoc, driven by a response to recent events and by the availability of detection and identification technologies. Additionally, the inventory of pathogens that exist in mammalian and other reservoirs is incomplete, and identifying those with the potential to cause disease in humans is rarely possible in advance. A major step in understanding the burden and diversity of zoonotic infections, the local behavioral and demographic risks of infection, and the risk of emergence of these pathogens in human populations is to establish surveillance networks in populations that maintain regular contact with diverse animal populations, and to simultaneously characterize pathogen diversity in human and animal populations. Vietnam has been an epicenter of disease emergence over the last decade, and practices at the human/animal interface may facilitate the likelihood of spillover of zoonotic pathogens into humans. To tackle the scientific issues surrounding the origins and emergence of zoonotic infections in Vietnam, we have established The Vietnam Initiative on Zoonotic Infections (VIZIONS). This countrywide project, in which several international institutions collaborate with Vietnamese organizations, is combining clinical data, epidemiology, high-throughput sequencing, and social sciences to address relevant one-health questions. Here, we describe the primary aims of the project, the infrastructure established to address our scientific questions, and the current status of the project. Our principal objective is to develop an integrated approach to the surveillance of pathogens circulating in both human and animal populations and assess how frequently they are exchanged. This infrastructure will facilitate systematic investigations of pathogen ecology and evolution, enhance understanding of viral cross-species transmission events, and identify relevant risk factors and drivers of zoonotic disease emergence.


title: Computational and Experimental Studies of ADP-Ribosylation

text: The macrodomains are a multifunctional protein family that function as receptors and enzymes acting on poly(ADP-ribose), ADP-ribosylated proteins, and other metabolites of nicotinamide adenine dinucleotide (NAD(+)). Several new functions for macrodomains, such as nucleic acid binding and protein/protein interaction, have recently been identified in this family. Here, we discuss methods for the identification of new macrodomains in viruses and the prediction of their function. This is followed by the expression and purification of these proteins following overexpression in bacterial cells and confirmation of folding and function using biophysical methods.


title: Education, the science of learning, and the COVID-19 crisis

text: In the COVID-19 crisis, the science of learning has two different responsibilities: first, to offer guidance about how best to deal with the impact of the current situation, including lockdown and home-schooling; and second, to consider bigger questions about what this large-scale educational experiment might mean for the future. The first part of this Viewpoint summarises advice for parents on mental health, and on becoming stand-in-teachers. The second part, taking the longer view, considers the potential negative impact of the COVID-19 crisis in increasing inequality in education; but also the potential positive impact of driving innovations in technology use for educating children.


Feasibility of controlling COVID-19 – Authors' reply


title: Safety Profile of Musculoskeletal Contrast-Enhanced Ultrasound with Sulfur Hexafluoride Contrast Agent

text: PURPOSE: Muscle, bone and tendon regeneration depend on the microperfusion of the corresponding tissue which can be quantified with contrast-enhanced ultrasound (CEUS) using sulfur hexafluoride contrast agent (SonoVue(®)). This study investigated the incidence of adverse events (AEs) in musculoskeletal patients and gives an overview of musculoskeletal CEUS applications. PATIENTS AND METHODS: Based on 13 studies in a standardized monocentric setting, a total of 2268 CEUS examinations in 764 patients were performed and AEs due to the administration of sulfur hexafluoride contrast agent were classified as either mild, moderate or severe. RESULTS: No fatal events occurred. AEs were reported in three cases, of which only one was classified as severe and two as mild. The total rate of all AEs was 0.13% and 0.04% for severe AEs. CONCLUSION: The present analysis confirms the safety of musculoskeletal CEUS using sulfur hexafluoride contrast agent with a lower rate of AEs than that reported for other contrast agents even in elderly patients with concomitant diseases.


title: Competition in Public Procurement in the Czech and Slovak Public Health Care Sectors

text: Sustainability of health financing is a critical issue for all countries, especially now in the COVID-19 period The final level of achievements of critical public health goals is connected not only with the efforts of the people involved, but also with the availability of funding to cover the costs of the actions needed One of the "internal sources" providing more resources to cover public health care costs is effective public procurement in the health care sector According to existing scientific literature, a low rate of competition represents one important factor that has a direct negative impact on the efficiency of public procurement The aim of our article is to examine the degree of competitiveness of public procurement in the Czech and Slovak health care systems and its impact on the final price of a contract The research fully attested the findings of those studies carried out so far - the higher the number of tenderers, the lower the final price, even in the Czech and Slovak health sectors However, the average number of tenderers is only around two and in the Czech Republic for more than half of the tenders only one bid was submitted


title: C-reactive protein: a promising biomarker for poor prognosis in COVID-19 infection

text: BACKGROUND: The novel coronavirus disease 2019 (COVID-19) break out from Wuhan, China, spread over 227 countries and caused approximately 0.3 million death worldwide. Several biomolecules have been explored for possible biomarkers for prognosis outcome. Although increased C reactive protein (CRP) has been associated with death due to COVID-19 infections, results from different populations remain inconsistent. For a conclusive result, the present meta-analysis was performed. METHODS: We conducted a literature survey in PubMed and Scopus database for the association of CRP concentration with COVID-19 disease outcomes. A total of 16 eligible studies were enrolled in the present analysis comprising of 1896 survivors and 849 non-survivors cases. Concentrations of CRP were compared and analyzed by a meta-analysis. RESULTS: Egger’s regression analysis (intercept=0.04, P=0.98, 95%CI=-5.48 to 5.58) and funnel plot revealed an absence of publication bias in the included studies. Due to the presence of significant heterogeneity across the studies (Q=252.03, P(heterogeneity)= 0.000, I(2)=93.65) random model was used for the analysis of the present study. The results of the meta-analysis demonstrated a significant role of CRP in COVID-19 infection outcome (Standard difference in means= 1.371, P=0.000). CONCLUSIONS: Concentrations of CRP remained increased in patients who died in COVID-19 infection and could be a promising biomarker for accessing disease lethality.


docid: cwfujgya

title: Pathogenesis of severe acute respiratory syndrome

text: Severe acute respiratory syndrome (SARS) is a zoonotic infectious disease caused by a novel coronavirus (CoV). The tissue tropism of SARS-CoV includes not only the lung, but also the gastrointestinal tract, kidney and liver. Angiotensin-converting enzyme 2 (ACE2), the C-type lectin CD209L (also known L-SIGN), and DC-SIGN bind SARS-CoV, but ACE2 appears to be the key functional receptor for the virus. There is a prominent innate immune response to SARS-CoV infection, including acute-phase proteins, chemokines, inflammatory cytokines and C-type lectins such as mannose-binding lectin, which plays a protective role against SARS. By contrast there may be a lack of type 1 interferon response. Moreover, lymphopenia with decreased numbers of CD4+ and CD8+ T cells is common during the acute phase. Convalescent patients have IgG-class neutralizing antibodies that recognize amino acids 441–700 of the spike protein (S protein) as the major epitope.


docid: tqhntbau

title: Spatial associations of dockless shared e-scooter usage

text: In this study, we explore the usage of e-scooter sharing services in Austin, Texas over about a six-month period. The study is based on trip records of all the shared e-scooter operators in Austin and includes trip start and end locations. We use both analysis of trip patterns and spatial regression techniques to examine how the built environment, land use, and demographics affect e-scooter trip generation. Our findings show that people use e-scooters almost exclusively in central Austin. Commuting does not seem to be the main trip purpose, and usage of e-scooters is associated with areas with high employment rates, and in areas with bicycle infrastructure. People use e-scooter sharing regardless of the affluence of the neighborhood, although less affluent areas with high usage rates have large student populations, suggesting that students use this mode of travel. Implications for planners suggest that better bicycle infrastructure will facilitate e-scooter usage, college towns are a ready market for e-scooter sharing services, and e-scooters may be a substitute for some short non-work trips, reducing car usage, and benefiting the environment.


title: Using cellular automata to generate image representation for biological sequences

text: A novel approach to visualize biological sequences is developed based on cellular automata (Wolfram, S. Nature 1984, 311, 419–424), a set of discrete dynamical systems in which space and time are discrete. By transforming the symbolic sequence codes into the digital codes, and using some optimal space-time evolvement rules of cellular automata, a biological sequence can be represented by a unique image, the so-called cellular automata image. Many important features, which are originally hidden in a long and complicated biological sequence, can be clearly revealed thru its cellular automata image. With biological sequences entering into databanks rapidly increasing in the post-genomic era, it is anticipated that the cellular automata image will become a very useful vehicle for investigation into their key features, identification of their function, as well as revelation of their “fingerprint”. It is anticipated that by using the concept of the pseudo amino acid composition (Chou, K.C. Proteins: Structure, Function, and Genetics, 2001, 43, 246–255), the cellular automata image approach can also be used to improve the quality of predicting protein attributes, such as structural class and subcellular location.


A Long Journey Back to Normal Life


Protocol against coronavirus diseases in patients on renal replacement therapy: Dialysis and kidney transplant


Dengue et Covid-19, une association à haut risque


title: Massive use of disinfectants against COVID-19 poses potential risks to urban wildlife

text: • Globally, massive disinfectants are used to contain the rapid spread of COVID-19. • Applying massive disinfectants pose a significant threat to urban environment and wildlife. • Policies are required to minimize the adverse effects on wildlife due to overuse of disinfectants.


title: A numerical study of ventilation strategies for infection risk mitigation in general inpatient wards

text: Aerial dispersion of human exhaled microbial contaminants and subsequent contamination of surfaces is a potential route for infection transmission in hospitals. Most general hospital wards have ventilation systems that drive air and thus contaminants from the patient areas towards the corridors. This study investigates the transport mechanism and deposition patterns of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) within a typical six bedded general inpatient ward cubicle through numerical simulation. It demonstrates that both air change and exhaust airflow rates have significant effects on not only the airflow but also the particle distribution within a mechanically ventilated space. Moreover, the location of an infected patient within the ward cubicle is crucial in determining the extent of infection risk to other ward occupants. Hence, it is recommended to provide exhaust grilles in close proximity to a patient, preferably above each patient’s bed. To achieve infection prevention and control, high exhaust airflow rate is also suggested. Regardless of the ventilation design, all patients and any surfaces within a ward cubicle should be regularly and thoroughly cleaned and disinfected to remove microbial contamination. The outcome of this study can serve as a source of reference for hospital management to better ventilation design strategies for mitigating the risk of infection.


title: Nucleic acid detection using G-quadruplex amplification methodologies

text: Abstract In the last decade, there has been an explosion in the use of G-quadruplex labels to detect various analytes, including DNA/RNA, proteins, metals and other metabolites. In this review, we focus on strategies for the detection of nucleic acids, using G-quadruplexes as detection labels or as enzyme labels that amplify detection signals. Methods to detect other analytes are briefly mentioned. We highlight various strategies, including split G-quadruplex, hemin–G-quadruplex conjugates, molecular beacon G-quadruplex or inhibited G-quadruplex probes. The tandem use of G-quadruplex labels with various DNA-modifying enzymes, such as polymerases (used for rolling circle amplification), exonucleases and endonucleases, is also discussed. Some of the detection modalities that are discussed in this review include fluorescence, colorimetric, chemiluminescence, and electrochemical methods.


title: SARS-CoV-2 Infection and the Newborn

text: Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) affects people at all ages and it may be encountered in pregnant women and newborns also. The information about its clinical features, laboratory findings and prognosis in children and newborns is scarce. All the reported cases in pregnant women were in the 2nd or 3rd trimester and only 1% of them developed severe disease. Miscarriages are rare. Materno-fetal transmission of the disease is controversial. Definitive diagnosis can be made by a history of contact with a proven case, fever, pneumonia and gastrointestinal disorder and a Polymerase chain reaction (PCR) test of nasopharyngeal swabs. Lymphopenia as well as liver and renal dysfunctions may be seen. Suspected or proven cases of newborns with symptoms should be quarantined in the neonatal intensive care unit for at least 14 days with standart and droplet isolation precautions. Asymptomatic infants may be quaratined at home. Transport of the neonates should be performed in a dedicated transport incubator and ambulance with isolation precautions. There is no specific treatment for the disease, but hemodynamic stabilization of the infant, respiratory management and other daily care are essential. Drugs against cytokine storm syndrome such as corticosteroids or tocilizumab are under investigation. Routine antibiotics are not recommended. No deaths have been reported so far in the neonatal population. Families and healthcare staff should receive pyschological support. Since the infection is quite new and knowledge is constantly accumulating, following developments and continuous updates are crucial.


title: Swine Influenza (H1N1) Pneumonia: Clinical Considerations

text: Influenza is a viral zoonosis of birds and mammals that has probably existed since antiquity. Attack rates of influenza are relatively high but mortality is relatively low. Influenza mortality is highest in the very young, the very old, and the immunosuppressed. Influenza has the potential for rapid spread and may involve large populations. This article examines the swine influenza (H1N1) strain of recent origin, and compares the microbiology, epidemiology, clinical presentation, differential, clinical, and laboratory diagnosis, therapy, complications, and prognosis with previous recorded outbreaks of avian and human seasonal influenza pneumonias.


title: Etiology of Pulmonary Infections in Human Immunodeficiency Virus–infected Inpatients Using Sputum Multiplex Real-time Polymerase Chain Reaction

text: BACKGROUND: There are limited data on the etiology of respiratory infections in human immunodeficiency virus (HIV)–infected patients in resource-limited settings. METHODS: We performed quantitative multiplex real-time polymerase chain reaction (PCR) for Pneumocystis jirovecii and common bacterial and viral respiratory pathogens on sputum samples (spontaneous or induced) from a prospective cohort study of HIV-infected inpatients with World Health Organization danger signs and cough. Mycobacterial culture was done on 2 sputum samples, blood cultures, and relevant extrapulmonary samples. RESULTS: We enrolled 284 participants from 2 secondary-level hospitals in Cape Town, South Africa: median CD4 count was 97 cells/μL, 64% were women, and 38% were on antiretroviral therapy. One hundred forty-eight had culture-positive tuberculosis, 100 had community-acquired pneumonia (CAP), 26 had P. jirovecii pneumonia (PJP), and 64 had other diagnoses. Probable bacterial infection (>10(5) copies/mL) was detected in 133 participants; the prevalence was highest in those with CAP (52%). Haemophilus influenzae and Streptococcus pneumoniae were the commonest bacterial pathogens detected; atypical bacteria were uncommon. Viruses were detected in 203 participants; the prevalence was highest in those with PJP (85%). Human metapneumovirus was the commonest virus detected. Multiple coinfections were commonly detected. CONCLUSIONS: Sputum multiplex PCR could become a useful diagnostic tool for bacterial respiratory infections in HIV-infected inpatients, but its value is limited as quantitative cutoffs have only been established for a few bacterial pathogens and validation has not been done in this patient population. We found a high prevalence of respiratory viruses, but it is unclear whether these viruses were causing infection as there are no accepted quantitative PCR cutoffs for diagnosing respiratory viral infections.


title: Methicillin-Resistant Staphylococcus aureus (MRSA) Contamination in Bedside Surfaces of a Hospital Ward and the Potential Effectiveness of Enhanced Disinfection with an Antimicrobial Polymer Surfactant

text: The aim in this study was to assess the effectiveness of a quaternary ammonium chloride (QAC) surfactant in reducing surface staphylococcal contamination in a routinely operating medical ward occupied by patients who had tested positive for methicillin-resistant Staphylococcus aureus (MRSA). The QAC being tested is an antibacterial film that is sprayed onto a surface and can remain active for up to 8 h. A field experimental study was designed with the QAC plus daily hypochlorite cleaning as the experimental group and hypochlorite cleaning alone as the control group. The method of swabbing on moistened surfaces was used for sampling. It was found that 83% and 77% of the bedside surfaces of MRSA-positive and MRSA-negative patients respectively were contaminated with staphylococci at 08:00 hours, and that the staphylococcal concentrations increased by 80% at 1200 h over a 4-hour period with routine ward and clinical activities. Irrespective of the MRSA status of the patients, high-touch surfaces around the bed-units within the studied medical ward were heavily contaminated (ranged 1 to 276 cfu/cm(2) amongst the sites with positive culture) with staphylococcal bacteria including MRSA, despite the implementation of daily hypochlorite wiping. However, the contamination rate dropped significantly from 78% to 11% after the application of the QAC polymer. In the experimental group, the mean staphylococcal concentration of bedside surfaces was significantly (p < 0.0001) reduced from 4.4 ± 8.7 cfu/cm(2) at 08:00 hours to 0.07 ± 0.26 cfu/cm(2) at 12:00 hours by the QAC polymer. The results of this study support the view that, in addition to hypochlorite wiping, the tested QAC surfactant is a potential environmental decontamination strategy for preventing the transmission of clinically important pathogens in medical wards.


title: Severe acute respiratory syndrome (SARS) in Hong Kong: patients' experiences

text: Abstract Background This past year there was an outbreak of Severe Acute Respiratory Syndrome (SARS) in Hong Kong. During that time we investigated the clinical features, treatment, and nursing care of 36 patients and reported on 12 of these patients' perceptions of their illness experience. Purpose The purpose of this article is to describe the clinical features, treatment, nursing care and perceptions of the illness experience of patients with SARS in Hong Kong in order to better inform nurses caring for patients with this highly contagious and potentially lethal disease. Method We abstracted data from the medical and nursing records on the clinical features, treatment and nursing care of 36 patients (21 women, 15 men) in whom SARS was diagnosed and who were admitted to the Queen Mary Hospital in Hong Kong between March 15 and April 15, 2003. A review of the hospital's policy and procedures on infection control was also undertaken. Semi-structured interviews were conducted with 12 of the patients to elicit their perceptions of the illness experience. Findings The most common symptoms were cough (83%), dyspnea (80.6%), malaise (69.4%) and fever (61%). Less common symptoms included headache (38.9%), diarrhea (38.9%), dizziness (30.6%), myalgia (25%), chills (19.4%), nausea and vomiting (19.4%) and rigor (the occurrence of a sensation of hot-and-cold and shivering in addition to teeth chattering and bed shaking) (8.3%). All 36 patients received a combination of corticosteroids and ribavirin. The patients were at risk of drug-related adverse reactions and deterioration of respiratory function, and nursing vigilance was required. Conclusion Nursing patients with SARS was challenging as the disease was highly contagious and potentially lethal, and not much was known about this disease. In addition to the use of frontline treatment, infection control and sensitivity to individual responses to sudden and catastrophic illness were required to support these patients. From this outbreak of SARS, we have learned the importance of infection control in containing and controlling the disease. Other lessons included the need to strengthen the surge capacity in our hospitals and support health care workers during the crisis.


COVID-19: TIMING IS IMPORTANT


How and why rheumatologists are relevant to COVID-19?


title: Mitral valve prolapse in adolescent female with hyperthyroidism

text: Mitral valve prolapse is prevalent in about 6% of young healthy females yet two to three times as prevalent in patients with hyperthyroidism [1, 8]. Hyperthyroidism is often missed as an underlying diagnosis when mitral valve prolapse is visualized by echocardiogram. There are many cardiac findings reported in the literature associated with hyperthyroidism. However, hyperthyroidism may be difficult to diagnose in the early stages of the disease process without other classic signs and symptoms. We report a case of an adolescent female who presented to our cardiology clinic with palpitations and chest pain diagnosed with hyperthyroidism after subtle findings of mitral valve prolapse and trivial mitral regurgitation. This case report will review the classic cardiac changes which may be observed on echocardiography in patients with hyperthyroidism.


Javier Padilla Bernáldez. ¿A quién vamos a dejar morir? Sanidad pública, crisis y la importancia de lo político. Madrid: Capitán Swing; 2019. 176 p. ISBN: 9788412064421


title: Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population-level observational study

text: Summary Background As the outbreak of coronavirus disease 2019 (COVID-19) progresses, epidemiological data are needed to guide situational awareness and intervention strategies. Here we describe efforts to compile and disseminate epidemiological information on COVID-19 from news media and social networks. Methods In this population-level observational study, we searched DXY.cn, a health-care-oriented social network that is currently streaming news reports on COVID-19 from local and national Chinese health agencies. We compiled a list of individual patients with COVID-19 and daily province-level case counts between Jan 13 and Jan 31, 2020, in China. We also compiled a list of internationally exported cases of COVID-19 from global news media sources (Kyodo News, The Straits Times, and CNN), national governments, and health authorities. We assessed trends in the epidemiology of COVID-19 and studied the outbreak progression across China, assessing delays between symptom onset, seeking care at a hospital or clinic, and reporting, before and after Jan 18, 2020, as awareness of the outbreak increased. All data were made publicly available in real time. Findings We collected data for 507 patients with COVID-19 reported between Jan 13 and Jan 31, 2020, including 364 from mainland China and 143 from outside of China. 281 (55%) patients were male and the median age was 46 years (IQR 35–60). Few patients (13 [3%]) were younger than 15 years and the age profile of Chinese patients adjusted for baseline demographics confirmed a deficit of infections among children. Across the analysed period, delays between symptom onset and seeking care at a hospital or clinic were longer in Hubei province than in other provinces in mainland China and internationally. In mainland China, these delays decreased from 5 days before Jan 18, 2020, to 2 days thereafter until Jan 31, 2020 (p=0·0009). Although our sample captures only 507 (5·2%) of 9826 patients with COVID-19 reported by official sources during the analysed period, our data align with an official report published by Chinese authorities on Jan 28, 2020. Interpretation News reports and social media can help reconstruct the progression of an outbreak and provide detailed patient-level data in the context of a health emergency. The availability of a central physician-oriented social network facilitated the compilation of publicly available COVID-19 data in China. As the outbreak progresses, social media and news reports will probably capture a diminishing fraction of COVID-19 cases globally due to reporting fatigue and overwhelmed health-care systems. In the early stages of an outbreak, availability of public datasets is important to encourage analytical efforts by independent teams and provide robust evidence to guide interventions. Funding Fogarty International Center, US National Institutes of Health.


Chapter 1 Mechanisms and Morphology of Cellular Injury, Adaptation, and Death 1 1 For a glossary of abbreviations and terms used in this chapter see E-Glossary 1-1.


title: Secondary Household Transmission of SARS, Singapore

text: Secondary household transmission of severe acute respiratory syndrome (SARS) was studied in 114 households involving 417 contacts. The attack rate was low (6.2%). Occupation of the index case was the factor that most influenced household transmission (adjusted hazard ratio for healthcare workers 0.157; 95% confidence interval 0.042 to 0.588).


Incidence of Anxiety in Parkinson's Disease During the Coronavirus Disease (COVID‐19) Pandemic


title: Rapid molecular diagnosis of infectious viruses in microfluidics using DNA hydrogel formation

text: There has been an urgent need to quickly screen and isolate patients with viral infections from patients with similar symptoms at point-of-care. In this study, we introduce a new microfluidic method for detection of various viruses using rolling circle amplification (RCA) of pathogens on the surface of thousands of microbeads packed in microchannels. When a targeted pathogen meets the corresponding particular template, the DNAs are rapidly amplified into a specific dumbbell shape through the RCA process, forming a DNA hydrogel and blocking the flow path formed between the beads. Due to the significant increase in reaction surface area, the detection time was shortened to less than 15 min and the detection limit of various pathogens has been reached to 0.1 pM. By injecting the stained liquid, the existence of the target pathogens in a sample fluid can be determined with the naked eye. Furthermore, by integrating multi-channel design, simultaneous phenotyping of various infective pathogens (i.e., Ebola, Middle East respiratory syndrome (MERS), and others) in biological specimens can be performed at a point-of-care.


title: Toxic proteins in plants

text: Abstract Plants have evolved to synthesize a variety of noxious compounds to cope with unfavorable circumstances, among which a large group of toxic proteins that play a critical role in plant defense against predators and microbes. Up to now, a wide range of harmful proteins have been discovered in different plants, including lectins, ribosome-inactivating proteins, protease inhibitors, ureases, arcelins, antimicrobial peptides and pore-forming toxins. To fulfill their role in plant defense, these proteins exhibit various degrees of toxicity towards animals, insects, bacteria or fungi. Numerous studies have been carried out to investigate the toxic effects and mode of action of these plant proteins in order to explore their possible applications. Indeed, because of their biological activities, toxic plant proteins are also considered as potentially useful tools in crop protection and in biomedical applications, such as cancer treatment. Genes encoding toxic plant proteins have been introduced into crop genomes using genetic engineering technology in order to increase the plant’s resistance against pathogens and diseases. Despite the availability of ample information on toxic plant proteins, very few publications have attempted to summarize the research progress made during the last decades. This review focuses on the diversity of toxic plant proteins in view of their toxicity as well as their mode of action. Furthermore, an outlook towards the biological role(s) of these proteins and their potential applications is discussed.


title: A framework for identifying and mitigating the equity harms of COVID-19 policy interventions

text: Abstract: Introduction Coronavirus disease 2019 (COVID-19) is a global pandemic. Governments have implemented combinations of ‘lockdown’ measures of various stringencies, including school and workplace closures, cancellations of public events, and restrictions on internal and external movements. These policy interventions are an attempt to shield high risk individuals and to prevent overwhelming countries’ healthcare systems, or, colloquially, ‘flatten the curve’. However, these policy interventions may come with physical and psychological health harms, group and social harms, and opportunity costs. These policies may particularly affect vulnerable populations and not only exacerbate pre-existing inequities, but also generate new ones. Methods We developed a conceptual framework to identify and categorise adverse effects of COVID-19 lockdown measures. We based our framework on Lorenc and Oliver’s framework for the adverse effects of public health interventions and the PROGRESS-Plus equity framework. To test its application we purposively sampled COVID-19 policy examples from around the world and evaluated them for the potential physical, psychological, and social harms, as well as opportunity costs, in each of the PROGRESS-Plus equity domains: Place of residence, Race/ethnicity, Occupation, Gender/sex, Religion, Education, Socioeconomic status, Social capital, Plus (age, and disability). Results We found examples of inequitably distributed adverse effects for each COVID-19 lockdown policy example, stratified by LMIC and HIC, in every PROGRESS-Plus equity domain. We identified known policy interventions intended to mitigate some of these adverse effects. The same harms (anxiety; depression; food insecurity; loneliness; stigma; violence) appear to be repeated across many groups, and are exacerbated by several COVID-19 policy interventions. Conclusion Our conceptual framework highlights the fact that COVID-19 policy interventions can generate or exacerbate interactive and multiplicative equity harms. Applying this framework can help in three ways: (1) identifying areas where a policy intervention may generate inequitable adverse effects; (2) mitigating policy and practice interventions by facilitating the systematic examination of relevant evidence; and (3) planning for lifting COVID-19 lockdowns and policy interventions around the world.


title: Clinical and epidemiological features of COVID-19 family clusters in Beijing, China

text: ABSTRACT Background Since its discovery, SARS-CoV-2 has been spread throughout China before becoming a global pandemic. In Beijing, family clusters are the main mode of human-human transmission accounting for 57.6% of the total confirmed cases. Method We present the epidemiological and clinical features of the clusters of three large and one small families. Result Our results revealed that SARS-CoV-2 is transmitted quickly through contact with index case, and a total of 22/24 infections were observed. Among those infected, 20/22 had mild symptoms and only two had moderate to severe clinical manifestations. Children in the families generally showed milder symptoms. The incubation period varied from 2 to 13 days, and the shedding of virus from the upper respiratory tract lasted from 5 to over 30 days. A prolonged period of virus shedding (>30 days) in upper respiratory tract was observed in 6/24 cases. Conclusion SARS-CoV-2 is transmitted quickly in the form of family clusters. While the infection rate is high within the cluster, the disease manifestations, latent period, and virus shedding period varied greatly. We therefore recommend rigorously testing contacts even during the no-symptom phase and consider whether viral shedding has ceased before stopping isolation measures for an individual.


title: Strategies to control PRRS: A summary of field and research experiences

text: Abstract Various methods for the control of PRRS virus have been published. The technology of nursery depopulation (ND) appears to effectively control the spread of virus between members of endemically infected populations. ND consists of a strategic adjustment in pigflow based on the presence of specific serologic patterns as detected by the indirect fluorescent antibody test. This pattern indicates a low seroprevalence of antibodies detected in the breeding herd and recently weaned piglets (≤ 10%), in contrast to a high (> 50%) seroprevalence in 8 to 10 week old piglets. ND has been carried out on swine farms in the US and results indicate improvements in nursery piglet growth rate and mortality levels. Three examples are provided in the following text. Recently a modified live virus vaccine (RespPRRS, NOBL Laboratories/Boerhinger Ingleheim) has become commercially available. It is currently approved for use in piglets from 3 to 18 weeks of age; however, potential for the use in adult animals is currently under investigation.


title: Genetic polymorphisms and risk of recurrent wheezing in pediatric age

text: BACKGROUND: Wheezing during early life is a very common disorder, but the reasons underlying the different wheezing phenotypes are still unclear. The aims of this study were to analyse the potential correlations between the risk of developing recurrent wheezing and the presence of specific polymorphisms of some genes regulating immune system function, and to study the relative importance of the associations of different viruses and genetic polymorphisms in causing recurrent episodes. METHODS: The study involved 119 otherwise healthy infants admitted to hospital for a first episode of wheezing (74 of whom subsequently experienced recurrent episodes) and 119 age- and sex-matched subjects without any history of respiratory problem randomly selected from those attending our outpatient clinic during the study period. All of the study subjects were followed up for two years, and 47 single nucleotide polymorphisms (SNPs) in 33 candidate genes were genotyped on whole blood using an ABI PRISM 7900 HT Fast Real-time instrument. RESULTS: IL8-rs4073AT, VEGFA-rs833058CT, MBL2-rs1800450CT and IKBKB-rs3747811AT were associated with a significantly increased risk of developing wheezing (p = 0.02, p = 0.03, p = 0.05 and p = 0.0018), whereas CTLA4-rs3087243AG and NFKBIB-rs3136641TT were associated with a significantly reduced risk (p = 0.05 and p = 0.04). IL8-rs4073AT, VEGFA-rs2146323AA and NFKBIA-rs2233419AG were associated with a significantly increased risk of developing recurrent wheezing (p = 0.04, p = 0.04 and p = 0.03), whereas TLR3-rs3775291TC was associated with a significantly reduced risk (p = 0.03). Interestingly, the study of gene-environment interactions showed that rhinovirus was significantly associated with recurrent wheezing in the presence of IL4Ra-rs1801275GG and G (odds ratio [OR] 6.03, 95% confidence interval [CI]: 1.21-30.10, p = 0.03) and MAP3K1-rs702689AA (OR 4.09, 95% CI: 1.14-14.61, p = 0.03). CONCLUSIONS: This study shows a clear relationship between the risk of wheezing and polymorphisms of some genes involved in the immune response. Although further studies are needed to confirm the results, these findings may be useful for the early identification of children at the highest risk of developing recurrent episodes and possibly subsequent asthma.


title: Soluble HLA Class I and Class II Molecule Levels in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients

text: Increased concentrations of soluble HLA class I and class II molecules (sHLA-I and sHLA-II) have been observed in infectious, inflammatory, and autoimmune diseases. Because autoimmune mechanisms are considered to play a role in the pathogenesis of multiple sclerosis (MS), we decided to dose sHLA-I and sHLA-II in serum and cerebrospinal fluid (CSF) of MS patients comparing their concentrations with those observed in serum and CSF of patients with other neurologic diseases (OND) without evidence of neuroradiologic involvement of central nervous system (CNS) and in serum of healthy donors. The serum concentrations of sHLA-I were higher in both MS and OND patients than in healthy donors (P < 0.05) whereas sHLA-II serum concentrations were lower in MS patients than in both OND patients and healthy donors (P < 0.01). Detectable amounts of sHLA-II were observed in the CSF of 45% of MS patients and in CSF of only 6% of OND patients (P < 0.001). In MS patients a significant correlation between sHLA-I serum and CSF concentrations was observed (P < 0.01), whereas sHLA-II serum and CSF levels did not correlate. In conclusion, alterations of sHLA-I and sHLA-II serum and CSF concentrations are present in MS patients and could be involved in the induction of enhanced susceptibility to develop MS or in MS pathogenesis.


title: The viral capping enzyme nsP1: a novel target for the inhibition of chikungunya virus infection

text: The chikungunya virus (CHIKV) has become a substantial global health threat due to its massive re-emergence, the considerable disease burden and the lack of vaccines or therapeutics. We discovered a novel class of small molecules ([1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones) with potent in vitro activity against CHIKV isolates from different geographical regions. Drug-resistant variants were selected and these carried a P34S substitution in non-structural protein 1 (nsP1), the main enzyme involved in alphavirus RNA capping. Biochemical assays using nsP1 of the related Venezuelan equine encephalitis virus revealed that the compounds specifically inhibit the guanylylation of nsP1. This is, to the best of our knowledge, the first report demonstrating that the alphavirus capping machinery is an excellent antiviral drug target. Considering the lack of options to treat CHIKV infections, this series of compounds with their unique (alphavirus-specific) target offers promise for the development of therapy for CHIKV infections.


title: The Impact of the COVID-19 Pandemic on Bariatric Surgery: Results from a Worldwide Survey

text: BACKGROUND: The ongoing “coronavirus disease 19” (COVID-19) pandemic has had a strong effect on the delivery of surgical care worldwide. Elective surgeries have been canceled or delayed in order to reallocate resources to the treatment of COVID-19 patients. Currently, the impact of the COVID-19 pandemic on bariatric and metabolic surgical practice remains unclear. METHODS: An internet-based online survey was performed among bariatric surgeons worldwide. The survey was sent to bariatric surgeons via the International Bariatric Club Facebook group and by electronic mail via the International Federation for the Surgery of Obesity and metabolic disorders (IFSO) secretariat to members of the associated national IFSO societies. RESULTS: One hundred sixty-nine (n = 169) bariatric surgeons participated in the survey. The majority of the respondents postponed preoperative upper gastrointestinal tract endoscopies, appointments in the outpatient clinic and bariatric operations. Most surgeons performed video calls for follow-up appointments instead of meeting the patients in the outpatient clinics. Laparoscopy was still the preferred treatment for surgical emergencies, but a trend towards conservative treatment of acute appendicitis and acute cholecystitis was shown. Rapid preoperative COVID-19 testing availability was poor; therefore, routine screening of emergency bariatric cases was not widely provided. A wide variance occurred regarding precautions and personal protection equipment among the participants. CONCLUSION: The COVID-19 pandemic showed a strong impact on bariatric surgical practice regarding surgical and outpatient planning as well as personnel management. Coordinated effort from the national bariatric societies should focus on strict implementation of the current recommendations regarding precaution measures and personal protection equipment. Further studies should evaluate how this impact will evolve in the near future.


title: New Class of Monoclonal Antibodies against Severe Influenza: Prophylactic and Therapeutic Efficacy in Ferrets

text: BACKGROUND: The urgent medical need for innovative approaches to control influenza is emphasized by the widespread resistance of circulating subtype H1N1 viruses to the leading antiviral drug oseltamivir, the pandemic threat posed by the occurrences of human infections with highly pathogenic avian H5N1 viruses, and indeed the evolving swine-origin H1N1 influenza pandemic. A recently discovered class of human monoclonal antibodies with the ability to neutralize a broad spectrum of influenza viruses (including H1, H2, H5, H6 and H9 subtypes) has the potential to prevent and treat influenza in humans. Here we report the latest efficacy data for a representative antibody of this novel class. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the prophylactic and therapeutic efficacy of the human monoclonal antibody CR6261 against lethal challenge with the highly pathogenic avian H5N1 virus in ferrets, the optimal model of human influenza infection. Survival rates, clinically relevant disease signs such as changes in body weight and temperature, virus replication in lungs and upper respiratory tract, as well as macro- and microscopic pathology were investigated. Prophylactic administration of 30 and 10 mg/kg CR6261 prior to viral challenge completely prevented mortality, weight loss and reduced the amount of infectious virus in the lungs by more than 99.9%, abolished shedding of virus in pharyngeal secretions and largely prevented H5N1-induced lung pathology. When administered therapeutically 1 day after challenge, 30 mg/kg CR6261 prevented death in all animals and blunted disease, as evidenced by decreased weight loss and temperature rise, reduced lung viral loads and shedding, and less lung damage. CONCLUSIONS/SIGNIFICANCE: These data demonstrate the prophylactic and therapeutic efficacy of this new class of human monoclonal antibodies in a highly stringent and clinically relevant animal model of influenza and justify clinical development of this approach as intervention for both seasonal and pandemic influenza.


title: Investing in Our First Line of Defense: Environmental Services Workers

text: Environmental services personnel are a critical first line of defense against the spread of COVID-19. This commentary discusses the importance of environmental cleaning during the pandemic and the essential role of environmental services personnel in patient safety.


title: A new player in a deadly game: influenza viruses and the PI3K/Akt signalling pathway

text: Upon influenza A virus infection of cells, a wide variety of antiviral and virus‐supportive signalling pathways are induced. Phosphatidylinositol‐3‐kinase (PI3K) is a recent addition to the growing list of signalling mediators that are activated by these viruses. Several studies have addressed the role of PI3K and the downstream effector protein kinase Akt in influenza A virus‐infected cells. PI3K/Akt signalling is activated by diverse mechanisms in a biphasic manner and is required for multiple functions during infection. While the kinase supports activation of the interferon regulatory factor‐3 during antiviral interferon induction, it also exhibits virus supportive functions. In fact, PI3K not only regulates a very early step during viral entry but also results in suppression of premature apoptosis at later stages of infection. The latter function is dependent on the expression of the viral non‐structural protein‐1 (A/NS1). It has been shown that PI3K activation occurs by direct interaction of A/NS1 with the p85 regulatory subunit and interaction sites of A/NS1 and p85 have now been mapped in detail. Here, we summarize the current knowledge on influenza virus‐induced PI3K signalling and how this pathway supports viral propagation.


title: COVID‐19 and the heart: An update for clinicians

text: SARS‐CoV‐2, the cause of the COVID‐19 pandemic has significantly impacted cardiovascular healthcare. Patients with pre‐existing cardiovascular disease are at higher risk of morbidity and mortality. The virus may affect the heart directly and indirectly with clinical syndromes of acute myocardial injury, myocarditis, acute coronary syndromes, heart failure, arrhythmias, and venous thromboembolism. Some therapeutics under investigation for COVID‐19 may also have adverse cardiac effects. The involvement of the RAAS system in viral entry makes it pertinent to consider the effects of medications that modulate the system. Comprehensive knowledge of peculiar cardiovascular manifestations of COVID‐19 and the role of RAAS in the prognosis of COVID‐19 disease is needed for optimal patient management.


title: Contact with Domestic Dogs Increases Pathogen Exposure in Endangered African Wild Dogs (Lycaon pictus)

text: BACKGROUND: Infectious diseases have contributed to the decline and local extinction of several wildlife species, including African wild dogs (Lycaon pictus). Mitigating such disease threats is challenging, partly because uncertainty about disease dynamics makes it difficult to identify the best management approaches. Serious impacts on susceptible populations most frequently occur when generalist pathogens are maintained within populations of abundant (often domestic) “reservoir” hosts, and spill over into less abundant host species. If this is the case, disease control directed at the reservoir host might be most appropriate. However, pathogen transmission within threatened host populations may also be important, and may not be controllable by managing another host species. METHODOLOGY/PRINCIPAL FINDINGS: We investigated interspecific and intraspecific transmission routes, by comparing African wild dogs' exposure to six canine pathogens with behavioural measures of their opportunities for contact with domestic dogs and with other wild dogs. Domestic dog contact was associated with exposure to canine parvovirus, Ehrlichia canis, Neospora caninum and perhaps rabies virus, but not with exposure to canine distemper virus or canine coronavirus. Contact with other wild dogs appeared not to increase the risk of exposure to any of the pathogens. CONCLUSIONS/SIGNIFICANCE: These findings, combined with other data, suggest that management directed at domestic dogs might help to protect wild dog populations from rabies virus, but not from canine distemper virus. However, further analyses are needed to determine the management approaches – including no intervention – which are most appropriate for each pathogen.


title: Intracellular antibodies for proteomics

text: Abstract The intracellular antibody technology has many applications for proteomics studies. The potential of intracellular antibodies for the systematic study of the proteome has been made possible by the development of new experimental strategies that allow the selection of antibodies under conditions of intracellular expression. The Intracellular Antibody Capture Technology (IACT) is an in vivo two-hybrid-based method originally developed for the selection of antibodies readily folded for ectopic expression. IACT has been used for the rapid and effective identification of novel antigen–antibody pairs in intracellular compartments and for the in vivo identification of epitopes recognized by selected intracellular antibodies. IACT opens the way to the use of intracellular antibody technology for large-scale applications in proteomics. In its present format, its use is however somewhat limited by the need of a preselection of the input phage antibody libraries on protein antigens or by the construction of an antibody library from mice immunized against the target protein(s), to provide an enriched input library to compensate for the suboptimal efficiency of transformation of the yeast cells. These enrichment steps require expressing the corresponding proteins, which represents a severe bottleneck for the scaling up of the technology. We describe here the construction of a single pot library of intracellular antibodies (SPLINT), a naı̈ve library of scFv fragments expressed directly in the yeast cytoplasm in a format such that antigen-specific intrabodies can be isolated directly from gene sequences, with no manipulation whatsoever of the corresponding proteins. We describe also the isolation from SPLINT of a panel of intrabodies against a number of different proteins. The application of SPLINT on a genome-wide scale should help the systematic study of the functional organization of cell proteome.


title: Organ‐protective effect of angiotensin‐converting enzyme 2 and its effect on the prognosis of COVID‐19

text: This article reviews the correlation between angiotensin‐converting enzyme 2 (ACE2) and severe risk factors for coronavirus disease 2019 (COVID‐19) and the possible mechanisms. ACE2 is a crucial component of the renin‐angiotensin system (RAS). The classical RAS ACE‐Ang II‐AT1R regulatory axis and the ACE2‐Ang 1‐7‐MasR counter‐regulatory axis play an essential role in maintaining homeostasis in humans. ACE2 is widely distributed in the heart, kidneys, lungs, and testes. ACE2 antagonizes the activation of the classical RAS system and protects against organ damage, protecting against hypertension, diabetes, and cardiovascular disease. Similar to SARS‐CoV, SARS‐CoV‐2 also uses the ACE2 receptor to invade human alveolar epithelial cells. Acute respiratory distress syndrome (ARDS) is a clinical high‐mortality disease, and ACE2 has a protective effect on this type of acute lung injury. Current research shows that the poor prognosis of patients with COVID‐19 is related to factors such as sex (male), age (>60 years), underlying diseases (hypertension, diabetes, and cardiovascular disease), secondary ARDS, and other relevant factors. Because of these protective effects of ACE2 on chronic underlying diseases and ARDS, the development of spike protein‐based vaccine and drugs enhancing ACE2 activity may become one of the most promising approaches for the treatment of COVID‐19 in the future.


title: Identification and characterization of a mouse mammary tumor virus protein uniquely expressed on the surface of BALB/cV mammary tumor cells

text: Abstract A unique subline of BALB/c mice, designated BALB/cV, exhibits an intermediate mammary tumor incidence (47%) and harbors a distinct milk-transmitted mouse mammary tumor virus (MMTV). The BALB/cV subline was used to study the molecular basis of potential virus-host interactions involving cell surface-expressed MMTV proteins. Cell surface iodination identified virus-specific proteins expressed on BALB/cv primary mammary tumor cells grown in culture. In contrast to (C3H)MMTV-producing cell lines which expressed MMTV gp52, BALB/cV tumor cells lacked gp52 and expressed instead a 68K, env-related protein. The 68K env protein was also detected on the surface of metabolically labeled BALB/cV tumor cells by an external immunoprecipitation technique. The expression of 68K env was restricted to mammary tissues of BALB/cV mice that also expressed other MMTV proteins. Biochemical analysis established that 68K env was not modified by N-linked glycosylation. 125I-labeled 68K env was rapidly released into the media of tumor cell cultures and was recovered both in the form of a soluble protein and in a 100,000 g pellet. The biologic function of this cell surface-expressed viral protein remains unknown.


title: COVID-19–We urgently need to start developing an exit strategy

text: Abstract Aim The purpose of this perspective is to review the options countries have to exit the draconian “lock downs” in a carefully staged manner. Methods Experts from different countries experiencing Corona Virus Infectious Disease 2019 (COVID-19) review evidence and country specific approaches and results of their interventions. Results Three key factors are important: 1. Reintroduction from countries with ongoing community transmission; 2. The need for extensive testing capacity and widespread community testing, and 3. Adequate supply of personal protective equipment, PPE, to protect health care workers. Lifting social distancing is discussed at length. How to open manufacturing, construction and logistics. The opening og higher educational institutions and schools. The use of electronic surveillance is discussed. Conclusion Each country has to decide what is the best path forward. However, we can learn from each other and the approach is in reality very similar.


title: Confirmation of electron microscopy results by direct testing of viruses adhered to grids using nucleic acid amplification techniques

text: Abstract It is possible to visualize rapidly viral particles by electron microscopy (EM) in patient samples and in cell cultures, and characterize the particles on the basis of their size and morphology. In many instances, EM has contributed to the diagnosis of specific infectious agents. Four different types of viruses with different characteristics of particle size, capsid structure, the presence or absence of an envelope, genomic content and stability outside the host were screened and diagnosed by EM at the level of family/genus. The results were confirmed at the species level by elution of the sample material from the grids used for EM examination and nucleic acid amplification. This approach could be valuable in situations where the immediate diagnosis is unclear, or when new infectious agents appear.


title: Viral pathogen discovery

text: Viral pathogen discovery is of critical importance to clinical microbiology, infectious diseases, and public health. Genomic approaches for pathogen discovery, including consensus polymerase chain reaction (PCR), microarrays, and unbiased next-generation sequencing (NGS), have the capacity to comprehensively identify novel microbes present in clinical samples. Although numerous challenges remain to be addressed, including the bioinformatics analysis and interpretation of large datasets, these technologies have been successful in rapidly identifying emerging outbreak threats, screening vaccines and other biological products for microbial contamination, and discovering novel viruses associated with both acute and chronic illnesses. Downstream studies such as genome assembly, epidemiologic screening, and a culture system or animal model of infection are necessary to establish an association of a candidate pathogen with disease.


Enemy at the Gate


title: Biowarfare and Bioterrorism

text: Bioterrorism is not only a reality of the times in which we live but bioweapons have been used for centuries. Critical care physicians play a major role in the recognition of and response to a bioterrorism attack. Critical care clinicians must be familiar with the diagnosis and management of the most likely bioterrorism agents, and also be adequately prepared to manage a mass casualty situation. This article reviews the epidemiology, diagnosis, and treatment of the most likely agents of biowarfare and bioterrorism.


title: Principles of Virus Structural Organization

text: Viruses, the molecular nanomachines infecting hosts ranging from prokaryotes to eukaryotes, come in different sizes, shapes and symmetries. Questions such as what principles govern their structural organization, what factors guide their assembly, how these viruses integrate multifarious functions into one unique structure have enamored researchers for years. In the last five decades, following Caspar and Klug's elegant conceptualization of how viruses are constructed, high resolution structural studies using X-ray crystallography and more recently cryo-EM techniques have provided a wealth of information on structures of variety of viruses. These studies have significantly furthered our understanding of the principles that underlie structural organization in viruses. Such an understanding has practical impact in providing a rational basis for the design and development of antiviral strategies. In this chapter, we review principles underlying capsid formation in a variety of viruses, emphasizing the recent developments along with some historical perspective.


title: The D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivity

text: SARS coronavirus 2 (SARS-CoV-2) isolates encoding a D614G mutation in the viral spike (S) protein predominate over time in locales where it is found, implying that this change enhances viral transmission. We therefore compared the functional properties of the S proteins with aspartic acid (S(D614)) and glycine (S(G614)) at residue 614. We observed that retroviruses pseudotyped with S(G614) infected ACE2-expressing cells markedly more efficiently than those with S(D614). This greater infectivity was correlated with less S1 shedding and greater incorporation of the S protein into the pseudovirion. Similar results were obtained using the virus-like particles produced with SARS-CoV-2 M, N, E, and S proteins. However, S(G614) did not bind ACE2 more efficiently than S(D614), and the pseudoviruses containing these S proteins were neutralized with comparable efficiencies by convalescent plasma. These results show S(G614) is more stable than S(D614), consistent with epidemiological data suggesting that viruses with S(G614) transmit more efficiently.


title: DNA vaccination of poultry: The current status in 2015

text: Abstract DNA vaccination is a promising alternative strategy for developing new human and animal vaccines. The massive efforts made these past 25 years to increase the immunizing potential of this kind of vaccine are still ongoing. A relatively small number of studies concerning poultry have been published. Even though there is a need for new poultry vaccines, five parameters must nevertheless be taken into account for their development: the vaccine has to be very effective, safe, inexpensive, suitable for mass vaccination and able to induce immune responses in the presence of maternal antibodies (when appropriate). DNA vaccination should meet these requirements. This review describes studies in this field performed exclusively on birds (chickens, ducks and turkeys). No evaluations of avian DNA vaccine efficacy performed on mice as preliminary tests have been taken into consideration. The review first describes the state of the art for DNA vaccination in poultry: pathogens targeted, plasmids used and different routes of vaccine administration. Second, it presents strategies designed to improve DNA vaccine efficacy: influence of the route of administration, plasmid dose and age of birds on their first inoculation; increasing plasmid uptake by host cells; addition of immunomodulators; optimization of plasmid backbones and codon usage; association of vaccine antigens and finally, heterologous prime-boost regimens. The final part will indicate additional properties of DNA vaccines in poultry: fate of the plasmids upon inoculation, immunological considerations and the use of DNA vaccines for purposes other than preventing infectious diseases.


docid: hnryfbdd

title: Healthcare-Associated Pneumonia: Don't Forget About Respiratory Viruses!

text: Introduction: Healthcare-associated infections are an important cause of morbidity and mortality, are among the most common adverse events in healthcare, and of them, pneumonia is the most commonly reported. Our objective was to evaluate the incidence and clinical outcome of respiratory viruses in hospital-acquired pneumonia (HAP). Methods: This was a prospective cohort study, include patients aged between 0 and 18 who fulfilled Centers for Diseases Control and Prevention (CDC) criteria for HAP. Demographic and clinical data were obtained, and a nasopharyngeal swab specimen was taken for the detection of respiratory viruses. All included patients were monitored until discharge to collect data on the need for mechanical ventilation, intensive care unit (ICU) admission, and mortality. All-cause 30-day mortality was also ascertained. Results: Four thousand three hundred twenty-seven patients were followed for 42,658 patient-days and 5,150 ventilator-days. Eighty-eight patients (2.03%) met the CDC criteria for HAP, 63 patients were included, and clinical and epidemiological characteristics showed no statistically significant differences between patients with virus associated healthcare-associated pneumonia (VAHAP) and those with non-viral healthcare-associated pneumonia (NVHAP). At least one respiratory virus was detected in 65% [95% CI (53–77)] of episodes of HAP, with a single viral pathogen observed in 53.9% and coinfection with 2 viruses in 11.1% of cases. The outcome in terms of ICU admission, mechanical ventilation and the 30-day mortality did not show a significant difference between groups. Conclusions: In two-thirds of the patients a respiratory virus was identified. There was no difference in mortality or the rest of the clinical outcome variables. About half of the patients required mechanical ventilation and 10% died, which emphasizes the importance of considering these pathogens in nosocomial infections, since their identification can influence the decrease in hospital costs and be taken into account in infection control policies.


A 2010 working formulation for the standardization of definitions of infections in cardiothoracic transplant recipients


Rwanda – Uganda: Expulsions Over Coronavirus


title: Utilization of Teleconsultation: Mitigation in Handling Mental Disorders in the COVID-19 Era

text: The COVID-19 pandemic has caused many undesirable effects, including death. The COVID-19 outbreak occurred suddenly, and many countries were ill prepared to face it. Community behaviour has been altered due to the pandemic. Uncertainty surrounding the disease triggered panic buying; public panic caused additional worry about limited food supplies, and thus demand increased. World economies have also felt the impacts of the COVID-19 outbreak. Owing to the measures put in place to address the spread of COVID-19, many service providers and industries were closed, resulting in financial losses, and the risk of unemployment was elevated, which inevitably increased negative emotions in individuals. A psychosocial consequence of the COVID-19 pandemic is worldwide fear. Because psychological defence is a supporting factor for the recovery of COVID-19 patients, it is important to encourage prevention of mental stress. Psychotherapy is able to provide counselling services to the community through teleconsultation. Strengthening psychological defences can help countries fight against this disease.


docid: wicgztpr

title: Proteinuria in Covid-19 pregnant women: preeclampsia or severe infection?


title: From the Similarity Analysis of Protein Cavities to the Functional Classification of Protein Families Using Cavbase

text: In this contribution, the classification of protein binding sites using the physicochemical properties exposed to their pockets is presented. We recently introduced Cavbase, a method for describing and comparing protein binding pockets on the basis of the geometrical and physicochemical properties of their active sites. Here, we present algorithmic and methodological enhancements in the Cavbase property description and in the cavity comparison step. We give examples of the Cavbase similarity analysis detecting pronounced similarities in the binding sites of proteins unrelated in sequence. A similarity search using SARS Mpro protease subpockets as queries retrieved ligands and ligand fragments accommodated in a physicochemical environment similar to that of the query. This allowed the characterization of the protease recognition pockets and the identification of molecular building blocks that can be incorporated into novel antiviral compounds. A cluster analysis procedure for the functional classification of binding pockets was implemented and calibrated using a diverse set of enzyme binding sites. Two relevant protein families, the α-carbonic anhydrases and the protein kinases, are used to demonstrate the scope of our cluster approach. We propose a relevant classification of both protein families, on the basis of the binding motifs in their active sites. The classification provides a new perspective on functional properties across a protein family and is able to highlight features important for potency and selectivity. Furthermore, this information can be used to identify possible cross-reactivities among proteins due to similarities in their binding sites.


Abstract Influenza A(H1N1)pdm09 virus infection was associated with significant morbidity, mainly among children and young adults. The majority of patients had self-limited mild-to-moderate uncomplicated disease. However, some patients developed severe illness and some died. In addition to respiratory complications, several complications due to direct and indirect effects on other body systems were associated with influenza A(H1N1)pdm09 virus infection. The main complications reported in hospitalized adults with influenza A(H1N1)pdm09 were pneumonia (primary influenza pneumonia and concomitant/secondary bacterial pneumonia), exacerbations of chronic pulmonary diseases (mainly chronic obstructive pulmonary disease and asthma), the need for intensive unit care admission (including mechanical ventilation, acute respiratory distress syndrome and septic shock), nosocomial infections and acute cardiac events. In experimentally infected animals, the level of pulmonary replication of the influenza A(H1N1)pdm09 virus was higher than that of seasonal influenza viruses. Pathological studies in autopsy specimens indicated that the influenza A(H1N1)pdm09 virus mainly targeted the lower respiratory tract, resulting in diffuse alveolar damage (edema, hyaline membranes, inflammation, and fibrosis), manifested clinically by severe acute respiratory distress syndrome with refractory hypoxemia. Influenza A(H1N1)pdm09-related pneumonia and other complications were associated with increased morbidity and mortality among hospitalized patients.


title: HMGB1: un lien entre inflammation septique et non septique

text: Résumé La protéine HMGB1 (high mobility group box 1) a été originalement identifiée comme une protéine nucléaire capable de se fixer à l’ADN. Elle est considérée comme un facteur architectural de la chromatine. Des travaux récents ont pu montrer qu’HMGB1 pouvait être également présente dans le milieu extracellulaire et ont permis de caractériser les processus cellulaires qui conduisent à la libération de la protéine. HMGB1 peut se retrouver dans le milieu extracellulaire de deux façons : (1) lors d’une sécrétion active par les cellules de l’inflammation ; (2) lors d’une libération passive et rapide lorsque les cellules meurent par nécrose. Dans ces conditions, la protéine HMGB1 est capable d’agir comme un médiateur soluble impliqué dans la coordination de divers mécanismes cellulaires. HMGB1 joue un rôle crucial dans l’amplification de la réponse inflammatoire, dans l’établissement de la réponse immunitaire et dans la réparation tissulaire. Cependant, la protéine HMGB1 dans le milieu extracellulaire serait également capable d’agir comme une cytokine pro-inflammatoire et contribuerait ainsi à la pathogenèse de différentes maladies qu’elles soient d’origine inflammatoire ou infectieuse. Summary HMGB1 (High Mobility group box 1) protein was originally identified as a DNA-binding protein that functions as a structural co-factor. Recent works demonstrated that HMGB1 can be released outside the cell, upon immune activation or primary cell necrosis. In the extracellular space, HMGB1 acts as a potent soluble factor that coordinates cellular events that are crucial for the amplification of inflammation, establishment of early immune responses and tissue repair. However, extracellular HMGB1 also acts as a potent pro-inflammatory cytokine that contributes to the pathogenesis of diverse inflammatory and infectious disorders.


La Sociedad Colombiana de Cardiología y Cirugía Cardiovascular y la pandemia COVID-19


title: Interference of ribosomal frameshifting by antisense peptide nucleic acids suppresses SARS coronavirus replication

text: The programmed −1 ribosomal frameshifting (−1 PRF) utilized by eukaryotic RNA viruses plays a crucial role for the controlled, limited synthesis of viral RNA replicase polyproteins required for genome replication. The viral RNA replicase polyproteins of severe acute respiratory syndrome coronavirus (SARS-CoV) are encoded by the two overlapping open reading frames 1a and 1b, which are connected by a −1 PRF signal. We evaluated the antiviral effects of antisense peptide nucleic acids (PNAs) targeting a highly conserved RNA sequence on the – PRF signal. The ribosomal frameshifting was inhibited by the PNA, which bound sequence-specifically a pseudoknot structure in the −1 PRF signal, in cell lines as assessed using a dual luciferase-based reporter plasmid containing the −1 PRF signal. Treatment of cells, which were transfected with a SARS-CoV-replicon expressing firefly luciferase, with the PNA fused to a cell-penetrating peptide (CPP) resulted in suppression of the replication of the SARS-CoV replicon, with a 50% inhibitory concentration of 4.4 μM. There was no induction of type I interferon responses by PNA treatment, suggesting that the effect of PNA is not due to innate immune responses. Our results demonstrate that −1 PRF, critical for SARS-CoV viral replication, can be inhibited by CPP-PNA, providing an effective antisense strategy for blocking −1 PRF signals.


title: The Impact of Media on the Control of Infectious Diseases

text: We develop a three dimensional compartmental model to investigate the impact of media coverage to the spread and control of infectious diseases (such as SARS) in a given region/area. Stability analysis of the model shows that the disease-free equilibrium is globally-asymptotically stable if a certain threshold quantity, the basic reproduction number ([Formula: see text]), is less than unity. On the other hand, if [Formula: see text] , it is shown that a unique endemic equilibrium appears and a Hopf bifurcation can occur which causes oscillatory phenomena. The model may have up to three positive equilibria. Numerical simulations suggest that when [Formula: see text] and the media impact is stronger enough, the model exhibits multiple positive equilibria which poses challenge to the prediction and control of the outbreaks of infectious diseases.


title: Psychological Outcomes Associated with Stay-at-Home Orders and the Perceived Impact of COVID-19 on Daily Life

text: The COVID-19 pandemic has resulted in the widespread implementation of extraordinary physical distancing interventions (e.g., stay-at-home orders) to slow the spread of the virus. Although vital, these interventions may be socially and economically disruptive, contributing to adverse psychological outcomes. This study examined relations of both stay-at-home orders and the perceived impact of COVID-19 on daily life to psychological outcomes (depression, health anxiety, financial worry, social support, and loneliness) in a nationwide U.S. community adult sample (N = 500; 47% women, mean age = 40). Participants completed questionnaires assessing psychological outcomes, stay-at-home order status, and COVID-19’s impact on their daily life. Being under a stay-at-home order was associated with greater health anxiety, financial worry, and loneliness. Moreover, the perceived impact of COVID-19 on daily life was positively associated with health anxiety, financial worry, and social support, but negatively associated with loneliness. Findings highlight the importance of social connection to mitigate negative psychological consequences of the COVID-19 pandemic.


title: Serum levels of mannan-binding lectin in chickens prior to and during experimental infection with avian infectious bronchitis virus

text: ABSTRACT Mannan-binding lectin (MBL) is a glycoprotein and a member of the C-type lectin super family, the collectin family, and the acute phase protein family. The MBL exerts its function by directly binding to microbial surfaces through its carbohydrate recognition domains, followed by direct opsonization or complement activation via MBL-associated serine proteases (MASP)-1 and -2. Thus, MBL plays a major role in the first-line innate defense against pathogens. We investigated the MBL concentrations in serum during experimental infectious bronchitis virus (IBV) infections in chickens. The results showed that the acute phase MBL response to infection with IBV was, to a degree (P < 0.0068), dependent on whether the chickens were inoculated after 12 h of rest (dark) or after 12 h of activity (light). The acute phase response in chickens challenged after 12 h of activity peaked after 4.6 d with an increase of 24%, whereas the acute phase response in chickens challenged after 12 h of rest peaked after 3.1 d with an increase of 51%. The specific antibody titer against IBV was also tested, and a difference (P < 0.0091) between the two experimental groups was found with peak titer values of 6,816 and 4,349. However, the highest value was found in chickens inoculated after 12 h of activity. Thus, an inverse relation exists between the MBL response and the IBV specific antibody response. The ability of MBL to activate the complement cascade was tested in a heterologous system by deposition of human C4 on the chicken MBL/MASP complex. The complement activation was directly associated with the concentration of MBL in serum, indicating neutralization of the virus before the humoral antibody response took over.


title: Antiviral activity of quercetin 7-rhamnoside against porcine epidemic diarrhea virus

text: Abstract Porcine epidemic diarrhea virus (PEDV) is the predominant cause of severe entero-pathogenic diarrhea in swine. The lack of effective therapeutical treatment underlines the importance of research for new antivirals. In this study, we identified Q7R, which actively inhibited PEDV replication with a 50% inhibitory concentration (IC50) of 0.014μg/mL. The 50% cytotoxicity concentration (CC50) of Q7R was over 100μg/mL and the derived therapeutic index was 7142. Several structural analogues of Q7R, quercetin, apigenin, luteolin and catechin, also showed moderate anti-PEDV activity. Antiviral drugs and natural compounds revealed ribavirin, interferon-α, coumarin and tannic acid have relative weaker efficacy compared to Q7R. Q7R did not directly interact with or inactivate PEDV particles and affect the initial stage of PEDV infection by interfering of PEDV replication. Also, the effectiveness of Q7R against the other two viruses (TGEV, PRCV) was lower compared to PEDV. Q7R could be considered as a lead compound for development of anti-PEDV drugs to may be used to during the early stage of PEDV replication and the structure-activity data of Q7R may usefully guideline to design other related antiviral agents.


title: Lopinavir-Ritonavir in the Treatment of COVID-19: A Dynamic Systematic Benefit-Risk Assessment

text: INTRODUCTION AND OBJECTIVE: COVID-19 is an ongoing, global public health crisis for which safe and effective treatments need to be identified. The benefit-risk balance for the use of lopinavir-ritonavir in COVID-19 needs to be monitored on an ongoing basis, therefore a systematic benefit-risk assessment was designed and conducted. A key objective of this study was to provide a platform for a dynamic systematic benefit-risk evaluation; although initially this evaluation is likely to contain limited information, it is required because of the urgent unmet public need. Importantly, it allows additional data to be incorporated as they become available, and re-evaluation of the benefit-risk profile. METHODS: A systematic benefit-risk assessment was conducted using the Benefit-Risk Action Team (BRAT) framework. The exposure of interest was lopinavir-ritonavir treatment in severe COVID-19 compared to standard of care, placebo or other treatments. A literature search was conducted in PubMed and Embase to identify peer-reviewed papers reporting clinical outcomes. Two clinicians constructed a value tree and ranked key benefits and risks in order of considered clinical importance. RESULTS: We screened 143 papers from PubMed and 264 papers from Embase for lopinavir-ritonavir; seven papers were included in the final benefit-risk assessment. In comparison to standard of care, data for several key benefits and risks were identified for lopinavir-ritonavir. Time to clinical improvement was not significantly different for lopinavir-ritonavir in comparison to standard of care (hazard ratio 1.31, 95% confidence interval 0.95–1.80). From one study, there were fewer cases of acute respiratory distress syndrome with lopinavir-ritonavir compared with standard of care (13% vs 27%). There also appeared to be fewer serious adverse events with lopinavir-ritonavir (20%) vs standard of care (32%). Limited data were available for comparison of lopinavir-ritonavir to other treatments. CONCLUSIONS: Based on currently available data, there was no clear benefit for the use of lopinavir-ritonavir compared to standard of care in severe COVID-19. Risk data suggested a possible decrease in serious adverse events. There was a reduction in acute respiratory distress syndrome with lopinavir-ritonavir in one study. Overall, the benefit-risk profile for lopinavir-ritonavir in severe COVID-19 cannot be considered positive until further efficacy and effectiveness data become available.


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title: Rethinking the Gendered Dimensions in the Impacts and Response to COVID-19 Pandemic

text: Abstract The outbreak of the novel coronavirus disease 2019 (COVID-19) has demonstrated the urgency to rethink the health system quality to efficiently support and improve global health. Whilst efforts are now gathering pace in response to the deleterious impacts of COVID-19, gendered analysis of these impacts and response to the pandemic has been far too little. A critical consideration of gendered lenses and the respective brunt of health crises of the pandemic on men and women can improve our understanding and direction of efforts toward building robust and equitable public health response. Strategic plans for preparedness must be fully grounded in strong gender analysis in the remit of gender roles and norms, and strengthen the leadership and resourceful participation of women in the decision-making process toward addressing COVID-19 outbreak.


title: Extent of pulmonary thromboembolic disease in patients with COVID-19 on CT: relationship with pulmonary parenchymal disease

text: Abstract Aim To report the severity and extent of pulmonary thromboembolic disease (PTD) in COVID-19 patients undergoing computed tomography pulmonary angiography (CTPA) in a tertiary centre. Materials and methods This is a retrospective analysis of COVID-19 patients undergoing CTPA over a period of 27 days. The presence, extent, and severity of PTD were documented. Two observers scored the pattern and extent of lung parenchymal disease including potential fibrotic features, as well as lymph node enlargement and pleural effusions. Consensus was achieved via a third observer. Interobserver agreement was assessed using kappa statistics. Student’s t-test, chi-squared, and Mann–Whitney U-tests were used to compare imaging features between PTD and non-PTD sub-groups. Results During the study period, 100 patients with confirmed COVID-19 underwent CTPA imaging. Ninety-three studies were analysed, excluding indeterminate CTPA examinations. Overall incidence of PTD was 41/93 (44%) with 28/93 patients showing small vessel PTD (30%). D-dimer was elevated in 90/93 (96.8%) cases. A high Wells’ score did not differentiate between PTD and non-PTD groups (p=0.801). The interobserver agreement was fair (kappa=0.659) for parenchymal patterns and excellent (kappa=0.816) for severity. Thirty-four of the 93 cases (36.6%) had lymph node enlargement; 29/34 (85.3%) showed no additional source of infection. Sixteen of the 93 (17.2%) cases had potential fibrotic features. Conclusion There is a high incidence of PTD in COVID-19 patients undergoing CTPA and lack of a risk stratification tool. The present data indicate a higher suspicion of PTD is needed in severe COVID-19 patients. The concomitant presence of possible fibrotic features on CT indicates the need for follow-up.


title: A FTA-based method for risk decision-making in emergency response

text: Abstract Decision-making problems in emergency response are usually risky and uncertain due to the limited decision data and possible evolvement of emergency scenarios. This paper focuses on a risk decision-making problem in emergency response with several distinct characteristics including dynamic evolvement process of emergency, multiple scenarios, and impact of response actions on the emergency scenarios. A method based on Fault Tree Analysis (FTA) is proposed to solve the problem. By analyzing the evolvement process of emergency, the Fault Tree (FT) is constructed to describe the logical relations among conditions and factors resulting in the evolvement of emergency. Given different feasible response actions, the probabilities of emergency scenarios are estimated by FTA. Furthermore, the overall ranking value of each action is calculated, and a ranking of feasible response actions is determined. Finally, a case study on H1N1 infectious diseases is given to illustrate the feasibility and validity of the proposed method.