title: Designed DNA molecules: principles and applications of molecular nanotechnology

text: Long admired for its informational role in the cell, DNA is now emerging as an ideal molecule for molecular nanotechnology. Biologists and biochemists have discovered DNA sequences and structures with new functional properties, which are able to prevent the expression of harmful genes or detect macromolecules at low concentrations. Physical and computational scientists can design rigid DNA structures that serve as scaffolds for the organization of matter at the molecular scale, and can build simple DNA-computing devices, diagnostic machines and DNA motors. The integration of biological and engineering advances offers great potential for therapeutic and diagnostic applications, and for nanoscale electronic engineering.


title: ciliaFA: a research tool for automated, high-throughput measurement of ciliary beat frequency using freely available software

text: BACKGROUND: Analysis of ciliary function for assessment of patients suspected of primary ciliary dyskinesia (PCD) and for research studies of respiratory and ependymal cilia requires assessment of both ciliary beat pattern and beat frequency. While direct measurement of beat frequency from high-speed video recordings is the most accurate and reproducible technique it is extremely time consuming. The aim of this study was to develop a freely available automated method of ciliary beat frequency analysis from digital video (AVI) files that runs on open-source software (ImageJ) coupled to Microsoft Excel, and to validate this by comparison to the direct measuring high-speed video recordings of respiratory and ependymal cilia. These models allowed comparison to cilia beating between 3 and 52 Hz. METHODS: Digital video files of motile ciliated ependymal (frequency range 34 to 52 Hz) and respiratory epithelial cells (frequency 3 to 18 Hz) were captured using a high-speed digital video recorder. To cover the range above between 18 and 37 Hz the frequency of ependymal cilia were slowed by the addition of the pneumococcal toxin pneumolysin. Measurements made directly by timing a given number of individual ciliary beat cycles were compared with those obtained using the automated ciliaFA system. RESULTS: The overall mean difference (± SD) between the ciliaFA and direct measurement high-speed digital imaging methods was −0.05 ± 1.25 Hz, the correlation coefficient was shown to be 0.991 and the Bland-Altman limits of agreement were from −1.99 to 1.49 Hz for respiratory and from −2.55 to 3.25 Hz for ependymal cilia. CONCLUSIONS: A plugin for ImageJ was developed that extracts pixel intensities and performs fast Fourier transformation (FFT) using Microsoft Excel. The ciliaFA software allowed automated, high throughput measurement of respiratory and ependymal ciliary beat frequency (range 3 to 52 Hz) and avoids operator error due to selection bias. We have included free access to the ciliaFA plugin and installation instructions in Additional file 1 accompanying this manuscript that other researchers may use.


title: Post-Discharge Cardiac Care in the Era of Coronavirus 2019: How Should We Prepare?

text: Abstract The novel coronavirus 2019 (COVID-19) pandemic has placed intense pressure on healthcare organizations around the world. Amongst others, there has been an increasing recognition of common and deleterious cardiovascular effects of COVID-19 based on preliminary studies. Furthermore, patients with pre-existing cardiac disease are likely to experience a more severe disease course with COVID-19. As case numbers continue to increase exponentially, a surge in the number of patients with new or comorbid cardiovascular disease will translate into more frequent, and in some cases, prolonged rehabilitation needs following acute hospitalization. This manuscript describes the current status of post-discharge cardiac care in Canada and provides suggestions with regards to steps that policymakers and healthcare organizations can take to prepare for the COVID-19 pandemic.


title: Studies on the interactions of Ti-containing polyoxometalates (POMs) with SARS-CoV 3CLpro by molecular modeling

text: Abstract Ti-containing α-Keggin polyoxometalates (POMs) have been proved with properties of both anti-tumor and anti-HIV (human immunodeficiency virus). The potential anti-SARS (severe acute respiratory syndrome) activity of the POMs [α-PTi2W10O40]7− isomers was investigated in this paper by molecular modeling method. The SARS 3c like protease, namely the SARS 3CLpro is the key function protease for virus replication as well as transcription and thus can be taken as one of the key targets for anti-SARS drug design. Affinity/Insight II was used to explore possible binding locations for POMs/3CLpro interaction. Charges in the POMs were obtained from density-functional theory (DFT) method. The results show that POMs bind with 3CLpro in the active site region with high affinity; POMs are more prone to bind with 3CLpro than with some organic compounds; for the POMs/3CLprocomplex, the OTi2 in POMs is the vital element for electrostatic interaction, and the electrostatic binding energy is strong enough to keep the complex stable.


title: High proportion of MERS-CoV shedding dromedaries at slaughterhouse with a potential epidemiological link to human cases, Qatar 2014

text: Two of the earliest Middle East respiratory syndrome (MERS) cases were men who had visited the Doha central animal market and adjoining slaughterhouse in Qatar. We show that a high proportion of camels presenting for slaughter in Qatar show evidence for nasal MERS-CoV shedding (62/105). Sequence analysis showed the circulation of at least five different virus strains at these premises, suggesting that this location is a driver of MERS-CoV circulation and a high-risk area for human exposure. No correlation between RNA loads and levels of neutralizing antibodies was observed, suggesting limited immune protection and potential for reinfection despite previous exposure.


title: Policy-driven ecosystems for new vaccine development

text: Abstract This paper examines the relationship between biomedical policies and entrepreneurial R&D strategies. Public health programs have been unable to provide effective and affordable treatment of infectious diseases for the poor. While governments have become more open to private sector contributions to policy objectives, it is rare to find new ventures commercializing healthcare innovations for neglected diseases. Two case studies of entrepreneurial ventures, in the UK and China, provide evidence on how resource-constrained firms mobilize participants in policy-specific ecosystems to achieve their goals of new vaccine development for tuberculosis. Ecosystem analysis reveals how the innovators’ business models can align their strategies with national policy objectives.


title: Screening for consequences of trauma – an update on the global collaboration on traumatic stress

text: This letter provides an update on the activities of “The Global Collaboration on Traumatic Stress” (GC-TS) as first described by Schnyder et al. in 2017. It presents in further detail the projects of the first theme, in particular the development of and initial data on the Global Psychotrauma Screen (GPS), a brief instrument designed to screen for the wide range of potential outcomes of trauma. English language data and ongoing studies in several languages provide a first indication that the GPS is a feasible, reliable and valid tool, a tool that may be very useful in the current pandemic of the coronavirus disease 2019 (COVID-19). Further multi-language and cross-cultural validation is needed. Since the start of the GC-TS, new themes have been introduced to focus on in the coming years: a) Forcibly displaced persons, b) Global prevalence of stress and trauma related disorders, c) Socio-emotional development across cultures, and d) Collaborating to make traumatic stress research data “FAIR”. The most recent theme added is that of Global crises, currently focusing on COVID-19-related projects.


title: Measles virus gene expression in subacute sclerosing panencephalitis

text: Abstract RNA was extracted from the diseased brain of a case of human subacute sclerosing panencephalitis (SSPE) and analysed for the expression of measles-specific RNA. Measles virus-specific mRNAs were present, but the amount of matrix (M) protein mRNA was greatly reduced in comparison to lytically infected cells and phospho- (P) protein mRNA was hardly detectable whereas the level of the corresponding intermediate-sized (is-) RNA was greatly increased. RNA obtained from the human brain was also translated in vitro and measles virus nucleocapsid and P protein was produced. However, in marked contrast to control reactions M protein was not detected in the products formed by translation in vitro. These results indicate an impaired measles virus M protein mRNA synthesis in infected brain tissue.


title: Environmental and Regulatory Concerns During the COVID-19 Pandemic: Results from the Pandemic Food and Stigma Survey

text: In this article, we present data from the monthly Pandemic Food and Stigma Survey (PFSS), a nationwide representative sample of adults in the United States designed to identify how the pandemic is affecting concerns about food and the environment. Two surveys were conducted in May and June 2020. Our analysis suggests that the public’s concern about contracting COVID-19 has been high; however, infection with COVID-19 was not the only concern. A majority of respondents remained strongly concerned about environmental issues, such as climate change, while responses to sudden relaxations of environmental and food safety policies varied. We analyze the PFSS data to identify factors associated with concerns about pandemic and environmental regulatory changes. In general, we find that people whose food security has been threatened by COVID-19 remain concerned about relaxation of environmental regulations, and those most inclined to take steps to reduce spread of the virus, such as wearing masks and social distancing, are more concerned about relaxed regulations than those less willing to take mitigating actions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10640-020-00438-9) contains supplementary material, which is available to authorized users.


title: Collision of the COVID-19 and Addiction Epidemics

text: People with substance use disorder may be especially susceptible to COVID-19, and compromised lung function from COVID-19 could also put at risk those who have opioid use disorder and methamphetamine use disorder. This commentary describes the risks of the collision of the COVID-19 and addiction epidemics.


title: Burden of lower respiratory infections in the Eastern Mediterranean Region between 1990 and 2015: findings from the Global Burden of Disease 2015 study

text: OBJECTIVES: We used data from the Global Burden of Disease 2015 study (GBD) to calculate the burden of lower respiratory infections (LRIs) in the 22 countries of the Eastern Mediterranean Region (EMR) from 1990 to 2015. METHODS: We conducted a systematic analysis of mortality and morbidity data for LRI and its specific etiologic factors, including pneumococcus, Haemophilus influenzae type b, Respiratory syncytial virus, and influenza virus. We used modeling methods to estimate incidence, deaths, and disability-adjusted life-years (DALYs). We calculated burden attributable to known risk factors for LRI. RESULTS: In 2015, LRIs were the fourth-leading cause of DALYs, causing 11,098,243 (95% UI 9,857,095–12,396,566) DALYs and 191,114 (95% UI 170,934–210,705) deaths. The LRI DALY rates were higher than global estimates in 2015. The highest and lowest age-standardized rates of DALYs were observed in Somalia and Lebanon, respectively. Undernutrition in childhood and ambient particulate matter air pollution in the elderly were the main risk factors. CONCLUSIONS: Our findings call for public health strategies to reduce the level of risk factors in each age group, especially vulnerable child and elderly populations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00038-017-1007-0) contains supplementary material, which is available to authorized users.


COVID-19: handicaps, perte d’autonomie et aides humaines


title: Surveillance of acute respiratory infections among outpatients: A pilot study in Isfahan city

text: BACKGROUND: Considering that there was not any regional survey in Isfahan, Iran regarding the epidemiology of acute respiratory tract infections (ARTI) in different age groups of general population, the aim of this study was to determine the epidemiologic feature of ARTIs in Isfahan using multiplex polymerase chain reaction (PCR) method. MATERIALS AND METHODS: In this cross-sectional study, patients aged <80 years with symptoms of ARTI were studied, during 2009-2010 Nasopharyngeal and dry throat swab specimens were collected and pathogens of ARTI was determined using multiplex real-time PCR. RESULTS: In this study, 455 cases with ARTI were studied. Mean age of studied population was 29.9 ± 18.5 (range: 0.2-80). Symptoms such as sore throat (86.3%), coryza (68.0%) and dry cough (54.3%) were the most common symptoms in all studied groups, whereas fever was the most clinical presentation of younger patients (<15 years old) and headache and skeletal pain were the most common symptoms of older patients (>15 years old). Rhinovirus was the most common cause of ARTI in patients aged <5 years and those aged >50 years. Influenza virus B was the most common cause of ARTI in patients aged 5-50 years. CONCLUSION: Our study provides baseline information on the epidemiologic and clinical feature of outpatients with ARTIs in Isfahan city. Though our findings in this pilot study could be helpful in diagnosis, treatment, and prevention of ARTI, planning preventive interventional.


title: Fundamental protective mechanisms of face masks against droplet infections

text: Many governments have instructed the population to wear simple mouth-and-nose covers or surgical face masks to protect themselves from droplet infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in public. However, the basic protection mechanisms and benefits of these masks remain controversial. Therefore, the aim of this work is to show from a fluid physics point of view under which circumstances these masks can protect against droplet infection. First of all, we show that the masks protect people in the surrounding area quite well, since the flow resistance of the face masks effectively prevents the spread of exhaled air, e.g. when breathing, speaking, singing, coughing and sneezing. Secondly, we provide visual evidence that typical household materials used by the population to make masks do not provide highly efficient protection against respirable particles and droplets with a diameter of 0.3–2 μm as they pass through the materials largely unfiltered. According to our tests, only vacuum cleaner bags with fine dust filters show a comparable or even better filtering effect than commercial particle filtering FFP2/N95/KN95 half masks. Thirdly, we show that even simple mouth-and-nose covers made of good filter material cannot reliably protect against droplet infection in contaminated ambient air, since most of the air flows through gaps at the edge of the masks. Only a close-fitting, particle-filtering respirator without an outlet valve offers good self-protection and protection against droplet infection. Nevertheless, wearing simple homemade or surgical face masks in public is highly recommended if no particle filtrating respiratory mask is available. Firstly, because they protect against habitual contact of the face with the hands and thus serve as self-protection against contact infection. Secondly, because the flow resistance of the masks ensures that the air stays close to the head when breathing, speaking, singing, coughing and sneezing, thus protecting other people if they have sufficient distance from each other. However, if the distance rules cannot be observed and the risk of inhalation-based infection becomes high because many people in the vicinity are infectious and the air exchange rate is small, improved filtration efficiency masks are needed, to take full advantage of the three fundamental protective mechanisms these masks provide.


title: Coronavirus Disease‐2019 with Dermatologic Manifestations and Implications: An Unfolding Conundrum

text: The novel coronavirus SARS‐CoV‐2 has caused Coronavirus Disease‐2019, widely known as COVID‐19, now a pandemic with extraordinary infectivity, mortality, and fomite adhesiveness. As a nosocomial infection for hospital and nursing home patients and health care workers, it represents an extraordinary challenge. The cutaneous markers of this pandemic are being elucidated with preliminary experiences being shared and rapidly communicated. We will review COVID‐19 from both a dermatologic and public health perspective. This article is protected by copyright. All rights reserved.


title: Infectious Diseases Subspecialty: Declining Demand Challenges and Opportunities

text: Recent match results from the National Resident Matching Program for the subspecialty of infectious diseases show an ongoing decline in the number of fellowship positions filled, and, more important, in the number of applicants, particularly from the pool of international medical graduates. The main reasons for this declining application rate are unclear; in the absence of hard data, we present our viewpoint on this issue. Difficulties in securing visas for permanent residency in the United States, perception of a limited job market, and the explosive growth in the number of hospitalist positions may be important contributing factors. Infectious Diseases Society of America members need to focus on medical students and medical residents in their formative years. We present potential solutions to this problem of declining interest in the field of infectious diseases.


title: Impact of Trust and Privacy Concerns on Technology Acceptance in Healthcare: An Indian Perspective

text: This paper augments the technology acceptance model (TAM) by empirically investigating the influence of behavioral traits (privacy concerns and trust) and cognitive beliefs (perceived usefulness and perceived ease of use) on patients’ behavioral intention to accept technology in healthcare service delivery. Despite increased emphasis on healthcare service delivery, there has been limited studies as to how various behavioral constructs are related to adoption of new technology in healthcare sector. To this end, and to develop meaningful insights, a conceptual model integrating behavioral constructs with constructs related to technology acceptance model is devised. The aim here is essentially to understand relationships that predict patients’ acceptance of technology in healthcare services. The devised model is tested on responses obtained from survey of 416 patients availing healthcare service at various primary health centers in New Delhi, India. Structural equation modeling (SEM) is employed to conceptualize the model and validate nine hypotheses entailing key constructs. The results indicate that perceived usefulness, perceived ease of use, trust and privacy concern are direct predictors of patients’ behavior to accept technology in availing healthcare services. In summary, this research provides an empirical contribution to the literature on effect of trust and privacy concerns on acceptance of technology in healthcare.


title: Chapter 14 The Human Microbiome and Personalized Medicine

text: As the group of organisms living most closely with humans, the relationship between microbes and humans is a very tight and intimate one. They live in nearly every possible ecological niche in or on the human body and play diverse and important roles in human health; some microbes influence our ability to digest food, some help protect the human body against pathogens, and some may become the cause of disease. As disease states caused by diverse members of various microbial communities have been identified, microbial genomes have been paid a lot of attention, and scientists have uncovered a notably high individual level of microbial diversity that promises increasing relevance to personalized medicine. Keywords disease, gut microbe, human microbiome, nasal microbe, oral microbe, personalized medicine, skin microbe, vaginal microbe


title: Echocardiographic Characteristics of Subjects With COVID-19: A Case Series

text: Although coronavirus disease 2019 (COVID-19) manifests in most cases with respiratory symptoms, other presentations can occur. Direct damage to the cardiovascular system has been reported and recently, acute myocardial injury has been identified as a risk factor for mortality. Transthoracic echocardiography is a non-invasive tool that allows the detection of myocardial damage with validated markers (left ventricular ejection fraction and global longitudinal strain). Herein, we present the echocardiographic findings in four patients with COVID-19. All cases had acute respiratory distress syndrome (100%). Three out of four had elevated levels of creatine kinase and creatine kinase myocardial band. One case had ventricular concentric remodeling (25%). All cases (100%) had altered ventricular function: two had a reduced ejection fraction (50%) and, of those available for global longitudinal strain analysis, all had abnormal global longitudinal strain (100%). One case was found to have a tricuspid vegetation of 12 × 10 mm with no other manifestation of endocarditis. All of our cases had left ventricular dysfunction as assessed by echocardiography. One of our patients had a vegetation in the tricuspid valve. Two of our cases had a reduced ejection fraction. The importance of acute cardiac injury in COVID-19 has recently been established. A recent study found it to be an independent risk factor for mortality in patients with this disease. Information regarding echocardiographic characteristics of this population is scarce. Further research to elucidate the impact of these characteristics on morbidity and mortality is urgently needed.


title: Hydroxychloroquine augments early virological response to pegylated interferon plus ribavirin in genotype‐4 chronic hepatitis C patients

text: The therapeutic effect of pegylated interferon (peg‐IFN) alfa‐2a combined with ribavirin (RBV) on chronic hepatitis C Egyptian patients is low and further efforts are required to optimize this therapy for achievement of higher rates of virological response. This study aimed to evaluate the safety and efficacy of hydroxychloroquine (HCQ) in combination with pegylated interferon plus ribavirin on early virological response (EVR) in chronic hepatitis C Egyptian patients. Naïve 120 Egyptian patients with chronic hepatitis C virus infection were divided into two groups. Group 1 have administered the standard of care therapy (pegylated interferon alfa‐2a plus ribavirin) for 12 weeks, (n = 60). Group 2 have administered hydroxychloroquine plus standard of care therapy for 12 weeks, (n = 60). Therapeutics included hydroxychloroquine (200 mg) oral twice daily, peginterferon alfa‐2a (160 μg) subcutaneous once weekly and oral weight‐based ribavirin (1000–1200 mg/day). Baseline characteristics were similar in the two groups. The percentage of early virological response was significantly more in patients given the triple therapy than in patients given the standard of care [54/60 (90%) vs. 43/60 (71.7%); P = 0.011; respectively]. Biochemical response at week 12 was also significantly higher in patients given the triple therapy compared with the standard of care [58/60 (96.7%) vs. 42/60 (70%); P < 0.001; respectively]. Along the study, the observed adverse events were mild and similar across treatment groups. Addition of hydroxychloroquine to pegylated interferon plus ribavirin improves the rate of early virological and biochemical responses in chronic hepatitis C Egyptian patients without an increase in adverse events. J. Med. Virol. 88:2170–2178, 2016. © 2016 Wiley Periodicals, Inc.


title: Acute Kidney Injury in Hospitalized Patients with COVID-19

text: Importance: Preliminary reports indicate that acute kidney injury (AKI) is common in coronavirus disease (COVID)-19 patients and is associated with worse outcomes. AKI in hospitalized COVID-19 patients in the United States is not well-described. Objective: To provide information about frequency, outcomes and recovery associated with AKI and dialysis in hospitalized COVID-19 patients. Design: Observational, retrospective study. Setting: Admitted to hospital between February 27 and April 15, 2020. Participants: Patients aged [≥]18 years with laboratory confirmed COVID-19 Exposures: AKI (peak serum creatinine increase of 0.3 mg/dL or 50% above baseline). Main Outcomes and Measures: Frequency of AKI and dialysis requirement, AKI recovery, and adjusted odds ratios (aOR) with mortality. We also trained and tested a machine learning model for predicting dialysis requirement with independent validation. Results: A total of 3,235 hospitalized patients were diagnosed with COVID-19. AKI occurred in 1406 (46%) patients overall and 280 (20%) with AKI required renal replacement therapy. The incidence of AKI (admission plus new cases) in patients admitted to the intensive care unit was 68% (553 of 815). In the entire cohort, the proportion with stages 1, 2, and 3 AKI were 35%, 20%, 45%, respectively. In those needing intensive care, the respective proportions were 20%, 17%, 63%, and 34% received acute renal replacement therapy. Independent predictors of severe AKI were chronic kidney disease, systolic blood pressure, and potassium at baseline. In-hospital mortality in patients with AKI was 41% overall and 52% in intensive care. The aOR for mortality associated with AKI was 9.6 (95% CI 7.4-12.3) overall and 20.9 (95% CI 11.7-37.3) in patients receiving intensive care. 56% of patients with AKI who were discharged alive recovered kidney function back to baseline. The area under the curve (AUC) for the machine learned predictive model using baseline features for dialysis requirement was 0.79 in a validation test. Conclusions and Relevance: AKI is common in patients hospitalized with COVID-19, associated with worse mortality, and the majority of patients that survive do not recover kidney function. A machine-learned model using admission features had good performance for dialysis prediction and could be used for resource allocation.


title: Portable sequencer in the fight against infectious disease

text: Infectious disease is still a major threat in the world today. Five decades ago, it was considered soon to be eradicated, but the adaptation of pathogens to environmental pressure, such as antimicrobials, encouraged the emergence and reemergence of infectious disease. The fight with infectious disease starts with prevention, diagnosis, and treatment. Diagnosis can be upheld by observing the cause of disease under the microscope or detecting the presence of nucleic acid and proteins of the pathogens. The molecular techniques span from classical polymerase chain reaction (PCR) to sequencing the nucleic acid composition. Here, we are reviewing the works have been undertaken to utilize a portable sequencer, MinION, in various aspects of infectious disease management.


title: Relational Cities Disrupted: Reflections on the Particular Geographies of COVID‐19 For Small But Global Urbanisation in Dublin, Ireland, and Luxembourg City, Luxembourg

text: This paper looks at the particular geographies associated with the COVID‐19 outbreak through the lens of cities that are products of relational urbanisation. This includes small but highly globalised cities, such as financial centres or hot spots of politics and diplomacy, which are usually situated between different political, economic or cultural systems and their boundaries. These cities experienced strong growth due to internationalisation and a dedicated politics of extraversion. Our argument is that such places are unusually affected by the current lock‐down, illustrated by two empirical cases, the cities of Dublin, Ireland, and Luxembourg City, Luxembourg. Both have experienced striking growth rates recently, but now suffer from disruption. Their development trajectories remain unclear, since a return to the ‘old normal’ seems unlikely, and the emergent ‘new normal’ calls for adaptation towards more state involvement in areas hitherto governed by the market. The paper addresses possible alternative geographies for both cases.


Applications and future directions in invertebrate and fish cell culture


title: Ramping up Delivery of Cardiac Surgery During the COVID-19 Pandemic: A Guidance Statement from The Society of Thoracic Surgeons COVID-19 Task Force

text: Abstract The COVID-19 pandemic has had a profound global impact. Its rapid transmissibility has transformed healthcare delivery and forced countries to adopt strict measures to contain its spread. The vast majority of U.S. cardiac surgical programs have deferred all but truly emergent/urgent operative procedures in an effort to reduce the burden on the healthcare system and to mobilize resources to combat the pandemic surge. While the number of COVID-19 cases continues to increase worldwide, the incidence of new cases has begun to decline in many North American cities. This “flattening of the curve” has prompted interest in re-opening the economy, relaxing public health restrictions, and resuming non-urgent health care delivery.


title: The dependence of viral RNA replication on co-opted host factors

text: Positive-sense RNA ((+)RNA) viruses such as hepatitis C virus exploit host cells by subverting host proteins, remodelling subcellular membranes, co-opting and modulating protein and ribonucleoprotein complexes, and altering cellular metabolic pathways during infection. To facilitate RNA replication, (+)RNA viruses interact with numerous host molecules through protein–protein, RNA–protein and protein–lipid interactions. These interactions lead to the formation of viral replication complexes, which produce new viral RNA progeny in host cells. This Review presents the recent progress that has been made in understanding the role of co-opted host proteins and membranes during (+)RNA virus replication, and discusses common themes employed by different viruses.


title: Severe acute respiratory syndrome

text: Severe acute respiratory syndrome (SARS) was caused by a previously unrecognized animal coronavirus that exploited opportunities provided by 'wet markets' in southern China to adapt to become a virus readily transmissible between humans. Hospitals and international travel proved to be 'amplifiers' that permitted a local outbreak to achieve global dimensions. In this review we will discuss the substantial scientific progress that has been made towards understanding the virus—SARS coronavirus (SARS-CoV)—and the disease. We will also highlight the progress that has been made towards developing vaccines and therapies The concerted and coordinated response that contained SARS is a triumph for global public health and provides a new paradigm for the detection and control of future emerging infectious disease threats.


title: DRREP: deep ridge regressed epitope predictor

text: INTRODUCTION: The ability to predict epitopes plays an enormous role in vaccine development in terms of our ability to zero in on where to do a more thorough in-vivo analysis of the protein in question. Though for the past decade there have been numerous advancements and improvements in epitope prediction, on average the best benchmark prediction accuracies are still only around 60%. New machine learning algorithms have arisen within the domain of deep learning, text mining, and convolutional networks. This paper presents a novel analytically trained and string kernel using deep neural network, which is tailored for continuous epitope prediction, called: Deep Ridge Regressed Epitope Predictor (DRREP). RESULTS: DRREP was tested on long protein sequences from the following datasets: SARS, Pellequer, HIV, AntiJen, and SEQ194. DRREP was compared to numerous state of the art epitope predictors, including the most recently published predictors called LBtope and DMNLBE. Using area under ROC curve (AUC), DRREP achieved a performance improvement over the best performing predictors on SARS (13.7%), HIV (8.9%), Pellequer (1.5%), and SEQ194 (3.1%), with its performance being matched only on the AntiJen dataset, by the LBtope predictor, where both DRREP and LBtope achieved an AUC of 0.702. CONCLUSION: DRREP is an analytically trained deep neural network, thus capable of learning in a single step through regression. By combining the features of deep learning, string kernels, and convolutional networks, the system is able to perform residue-by-residue prediction of continues epitopes with higher accuracy than the current state of the art predictors.


Middle East Respiratory Syndrome Coronavirus (MERS-CoV)


title: Photodynamic Inactivation of Herpes Simplex Viruses

text: Herpes simplex virus (HSV) infections can be treated with direct acting antivirals like acyclovir and foscarnet, but long-term use can lead to drug resistance, which motivates research into broadly-acting antivirals that can provide a greater genetic barrier to resistance. Photodynamic inactivation (PDI) employs a photosensitizer, light, and oxygen to create a local burst of reactive oxygen species that inactivate microorganisms. The botanical plant extract Orthoquin(TM) is a powerful photosensitizer with antimicrobial properties. Here we report that Orthoquin also has antiviral properties. Photoactivated Orthoquin inhibited herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) infection of target cells in a dose-dependent manner across a broad range of sub-cytotoxic concentrations. HSV inactivation required direct contact between Orthoquin and the inoculum, whereas pre-treatment of target cells had no effect. Orthoquin did not cause appreciable damage to viral capsids or premature release of viral genomes, as measured by qPCR for the HSV-1 genome. By contrast, immunoblotting for HSV-1 antigens in purified virion preparations suggested that higher doses of Orthoquin had a physical impact on certain HSV-1 proteins that altered protein mobility or antigen detection. Orthoquin PDI also inhibited the non-enveloped adenovirus (AdV) in a dose-dependent manner, whereas Orthoquin-mediated inhibition of the enveloped vesicular stomatitis virus (VSV) was light-independent. Together, these findings suggest that the broad antiviral effects of Orthoquin-mediated PDI may stem from damage to viral attachment proteins.


title: Bronchiolitis obliterans syndrome after allogeneic hematopoietic SCT: phenotypes and prognosis

text: Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic SCT (HSCT) is recognized as a new-onset obstructive lung defect (OLD) in pulmonary function testing and is related to pulmonary chronic GVHD. Little is known about the different phenotypes of patients with BOS and their outcomes. We reviewed the data of all allogeneic HSCT recipients referred to our pulmonary department for a non-infectious bronchial disease between 1999 and 2010. We identified 103 patients (BOS (n=77), asthma (n=11) and chronic bronchitis (n=15)). In patients with BOS, we identified two functional phenotypes: a typical OLD, that is, forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7 (n=53), and an atypical OLD with a concomitant decrease in the FEV1 <80% and FVC <80% predicted with a normal total lung capacity (n=24). The typical OLD was characterized by more severe FEV1 and fewer centrilobular nodules on the computed tomography scan. The FEV1 was not significantly affected during the follow-up, regardless of the phenotype. In addition to acute and extensive chronic GVHD, only the occurrence of BOS soon after transplantation and the intentional treatment of BOS with steroids were associated with a poor survival. The determination of patient subgroups should be explored to improve the management of this condition.


title: COVID-19 wastewater surveillance: An African perspective

text: Abstract The COVID-19 pandemic has once again highlighted the importance of access to sufficient quantities of safe water and sanitation in public health. In the current COVID-19 pandemic, an early warning wastewater system has been proposed as a platform for SARS-CoV-2 surveillance, and a potentially important public health strategy to combat the disease. This short communication on wastewater surveillance in sub-Saharan Africa highlights challenges, opportunities and alternatives taken into account the local context.


title: Surgeons, plague, and leadership: A historical mantle to carry forward

text: COVID-19 has sickened millions, killed hundreds of thousands, and disrupted daily life for citizens around the world. Utterly devastating, COVID-19 is but the most recent pandemic to sweep the globe. Throughout history, surgeons like Guy de Chauliac, James Lind, John Hunter, John Snow, and Walter Reed have led scientific campaigns to understand, prevent, and treat epidemics like the bubonic plague, scurvy, syphilis, cholera, and yellow fever. We as a surgical community should herald their examples and re-focus our efforts to pioneer investigations into the coronavirus, helping elucidate the biology, understand its social effects, and provide effective treatment regimens for the disease.


title: Early administration of ritonavir-boosted lopinavir could prevent severe COVID-19

text: No specific treatment against SARS-CoV-2 is available after 6 months of COVID-19 worldwide outbreak Antivirals could decrease the viral load and reduce direct and indirect damages of SARSCoV-2 infection Ritonavir-bosted lopinavir is effective against SARS-CoV-2 in vitro Sequential virological and pharmacological monitoring helped to understand the efficacy of ritonavir-boosted lopinavir in a SARS-CoV-2 infected patient Ritonavir-boosted lopinavir could be proposed as early treatment for SARS-CoV-2 infection


title: The influenza A(H1N1) epidemic in Mexico. Lessons learned

text: Several influenza pandemics have taken place throughout history and it was assumed that the pandemic would emerge from a new human virus resulting from the adaptation of an avian virus strain. Mexico, since 2003 had developed a National Preparedness and Response Plan for an Influenza Pandemic focused in risk communication, health promotion, healthcare, epidemiological surveillance, strategic stockpile, research and development. This plan was challenged on April 2009, when a new influenza A(H1N1) strain of swine origen was detected in Mexico. The situation faced, the decisions and actions taken, allowed to control the first epidemic wave in the country. This document describes the critical moments faced and explicitly point out the lessons learned focused on the decided support by the government, the National Pandemic Influenza Plan, the coordination among all the government levels, the presence and solidarity of international organizations with timely and daily information, diagnosis and the positive effect on the population following the preventive hygienic measures recommended by the health authorities. The international community will be able to use the Mexican experience in the interest of global health.


title: AGA Institute Rapid Review of the GI and Liver Manifestations of COVID-19, Meta-Analysis of International Data, and Recommendations for the Consultative Management of Patients with COVID-19

text: Abstract Background Multiple gastrointestinal (GI) symptoms including diarrhea, nausea/vomiting, and abdominal pain, as well liver enzyme abnormalities have been variably reported in patients with COVID-19. The AGA) Institute Clinical Guideline Committee and Clinical Practice Updates Committee performed a systematic review and meta-analysis of international data on GI and liver manifestations of COVID-19. Methods We performed a systematic literature search to identify published and unpublished studies using OVID Medline and pre-print servers (medRxiv, LitCovid, and SSRN) up until April 5 2020; major journal sites were monitored for US publications until April 19 2020. We analyzed the prevalence of diarrhea, nausea, vomiting, and abdominal pain as well as LFT abnormalities using a fixed effect model and assessed the certainty of evidence using GRADE. Results We identified 118 studies and used a hierarchal study selection process to identify unique cohorts. We performed a meta-analysis of 47 studies including 10,890 unique patients. Pooled prevalence estimates of GI symptoms was diarrhea 7.7% (95% CI 7.2-8.2), nausea/vomiting 7.8% (95% CI 7.1-8.5), abdominal pain 2.7% (95% CI 2.0-3.4). Most studies reported on hospitalized patients. The pooled prevalence of elevated liver abnormalities was: AST 15.0% (13.6 to 16.5) and ALT 15.0% (13.6 to 16.4). When analyzed comparing data from China to studies from countries other than China, diarrhea, nausea/vomiting, liver abnormalities were more prevalent outside of China with diarrhea reported in 18.3% (16.6 to 20.1). Isolated GI symptoms were rarely reported. We also summarized of the Gl and liver adverse effects of the most commonly utilized medications for COVID19 Conclusions GI symptoms are associated with COVID-19 in less than 10% of patients. In studies outside of China, estimates are higher. Further studies are needed with standardized GI symptoms questionnaires and LFT checks on admission to better quantify and qualify the association of these symptoms with COVID-19. Based on findings from our meta-anlaysis, we make several Best Practice Statements for the consultative management of COVID-19.


title: COVSACK: an innovative portable isolated and safe COVID-19 sample collection kiosk with automatic disinfection

text: The Corona VIrus Disease 2019 (COVID-19) is one of the significant medical disaster that changed the life of humankind in the 21st century. The deadly virus is transmittable from infected person, through his nasal droplets, to surrounding people among whom, the healthcare personnel are the utmost affected. The present article brings out an innovative chamber, which is used for collection of throat, or nasal swabs/samples for diagnosis of COVID-19 suspected persons. The chamber, called COVid SAmple Collection Kiosk (COVSACK), eliminates the transmission of the deadly virus to the health care personnel while collecting the sample. The kiosk is designed based on CFD simulations for effective spread of disinfectant in fine droplet form, built with a lightweight composite that is sustainable in extreme weather conditions and the kiosk can be easily sanitized within 3 min after sample collection. The chamber is first positioned in ESI Hospital, Hyderabad, and other hospitals and diagnostics centres across India, extensively being used for testing the COVID-19 patients at a faster rate, with a drastic reduction in use of personal protection equipment (PPE). This technological innovation, to certain extent, has changed the way the testing of COVID-19 patients carried out in the country.


title: Apoptosis transcriptional mechanism of feline infectious peritonitis virus infected cells

text: Apoptosis has been postulated to play an important role during feline infectious peritonitis virus (FIPV) infection; however, its mechanism is not well characterized. This study is focused on apoptosis and transcriptional profiling of FIPV-infected cells following in vitro infection of CRFK cells with FIPV 79-1146 WSU. Flow cytometry was used to determine mode of cell death in first 42 h post infection (hpi). FIPV infected cells underwent early apoptosis at 9 hpi (p < 0.05) followed by late apoptosis at 12 hpi (p < 0.05) and necrosis from 24 hpi (p < 0.05). Then, next generation sequencing was performed on 9 hpi and control uninfected cells by Illumina analyzer. An aggregate of 4546 genes (2229 down-regulated and 2317 up-regulated) from 17 cellular process, 11 molecular functions and 130 possible biological pathways were affected by FIPV. 131 genes from apoptosis cluster (80 down-regulated and 51 up-regulated) along with increase of apoptosis, p53, p38 MAPK, VEGF and chemokines/cytokines signaling pathways were probably involved in apoptosis process. Six of the de-regulated genes expression (RASSF1, BATF2, MAGEB16, PDCD5, TNFα and TRAF2) and TNFα protein concentration were analyzed by RT-qPCR and ELISA, respectively, at different time-points. Up-regulations of both pro-apoptotic (i.e. PDCD5) and anti-apoptotic (i.e. TRAF2) were detected from first hpi and continuing to deregulate during apoptosis process in the infected cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10495-015-1172-7) contains supplementary material, which is available to authorized users.


title: Human metapneumovirus infection after allogeneic hematopoietic stem cell transplantation

text: BACKGROUND: The clinical characteristics of human metapneumovirus (hMPV)-associated lower respiratory tract infection (LRTI) after allogeneic hematopoietic stem cell transplantation (HSCT) is not well described. We describe the clinical course in eight HSCT recipients suffering from hMPV infection. METHODS: We prospectively included all patients with hMPV-associated LRTI after allogeneic HSCT during a period of 1 year. hMPV was diagnosed by multiplex polymerase chain reaction (PCR) from bronchoalveolar lavage (BAL). RESULTS: Eight patients with hMPV-associated LRTI were identified from 93 BAL samples. Three of the eight patients had co-infections with other pathogens. The median age of the patients was 45 years [interquartile range (IQR) 36.8–53.5], the median time posttransplant was 473 days (IQR 251–1,165), 5/8 patients had chronic graft-versus-host disease (cGvHD), and 6/8 patients received immunosuppression. Chest computed tomography (CT) scanning showed a ground-glass pattern in 7/8 patients. Seven of eight patients required hospitalization due to severe symptoms and hypoxemia. All were treated with intravenous immunoglobulin (IVIG), which was combined with oral ribavirin in six patients. The mortality rate was 12.5 % (1/8). CONCLUSIONS: hMPV-associated LRTI in allogeneic HSCT recipients are not uncommon and present with unspecific respiratory symptoms, ground-glass pattern in CT scanning, and co-infection.


title: Relationship Between the Prevalence of Blood Groups and Severity of Leptospirosis: A Case-Control Study

text: INTRODUCTION: The correlation between the prevalence and severity of leptospirosis with blood groups has not been investigated so far, but several studies have been conducted to link the infectious diseases with blood groups. The aim of this study was to investigate the prevalence of blood type in patients with leptospirosis and its association with disease severity. METHODS: This is a case-control study performed on hospitalized patients with the diagnosis of leptospirosis in Mazandaran province, Iran, in 2018. The control group was selected from among the families of patients. Blood groups (ABO and Rh) and severity of the disease were assessed. Data were analyzed by SPSS 22. RESULTS: A total of 300 people (150 in the case and 150 in the control) enrolled in the study. The mean age was 44.35 ± 15.39 years and 81.3% were men. The highest frequency of blood type in both groups was O+, A+, and B+, respectively. There was a statistically significant difference in the frequency of blood groups (P = .037). Comparison between severity of disease and blood types (ABO, Rh) showed no significant difference (P > .05). CONCLUSIONS: According to our study, O+ was the most common among patients with leptospirosis. The frequency of O in patients was significantly higher than in the control group, but there was no significant relationship between leptospirosis and Rh. The prevalence of this blood type was higher in people with a severe form of the disease. Finally, there is no statistically significant difference between the severity of the disease and ABO and Rh.


title: Rhinovirus-Induced Oxidative Stress and Interleukin-8 Elaboration Involves p47-phox but Is Independent of Attachment to Intercellular Adhesion Molecule-1 and Viral Replication

text: Virus-induced elaboration of proinflammatory cytokines is mediated by virus-induced oxidative stress. The purpose of these studies was to determine the source of the virus-induced oxidative stress. Inhibition of viral replication with antibody to intercellular adhesion molecule-1 had no effect on virus-induced oxidative stress or interleukin-8 (IL-8) response (597 ± 88 vs. 668 ± 78 pg/mL in control cells). Treatment of cells with diphenylene iodonium inhibited virus-induced oxidative stress and IL-8 elaboration, but allopurinol, ibuprofen, and rotenone had no effect. Studies in cell lines produced from a patient with gp91-phox deficiency revealed normal responses. In contrast, the oxidative response was decreased and the IL-8 concentration was 227 ± 36 pg/mL in cells from a patient with p47-phox deficiency, compared with 664 ± 48 pg/mL in control cells. These studies suggest that the stimulation of reactive oxygen species by viral challenge occurs at the cell surface even in the absence of viral replication and involves a flavoprotein that may act in concert with p47-phox.


Novel coronavirus (2019-nCoV) cases in Hong Kong and implications for further spread


title: Trends in Incident and Recurrent Rates of First-Ever Ischemic Stroke in Taiwan between 2000 and 2011

text: BACKGROUND AND PURPOSE: The burden of stroke is comparatively greater in Asian countries than in the Western world. While there has been a documented recent decline in the incidence of stroke in several Western nations due to better risk factor management, much less is known about the nature and trajectory of stroke in Asia over the last decade. The objective of this study was to explore risk factors, medication use, incidence, and one-year recurrence of stroke in Taiwan. METHODS: We conducted a nationwide cohort study by reviewing all hospitalized patients (≥ 18 years) with a primary diagnosis of ischemic stroke between 2001 and 2011 from Taiwan National Health Insurance Research Database. RESULTS: A total of 291,381 first-ever ischemic stroke patients were enrolled between 2000 and 2011. The average age was about 70 years and approximately 58.6% of them were men. While prevalence of diabetes mellitus and hyperlipidemia, as well as use of statins, antiplatelet agents, and oral anticoagulant agents for atrial fibrillation significantly increased; incidence (142.3 vs. 129.5 per 100,000 in 2000 and 2011, respectively) and one-year recurrence (9.6% vs. 7.8% in 2000 and 2011, respectively) of stroke declined during this period of time. CONCLUSIONS: Over the last decade in Taiwan, rates of primary ischemic stroke and one-year recurrent stroke decreased by 9% and 18% respectively.


Potential neurological symptoms of COVID-19


title: Topological Indices of Some Chemical Structures Applied for the Treatment of COVID-19 Patients

text: The novel coronavirus disease 2019 (COVID-19) emerged in Wuhan, China, and has spread rapidly to nearly every part of the world. Unfortunately, no drug or vaccine has been accepted for the treatment of this pandemic. Researchers have established the efficacy of some existing antiviral drugs to control COVID-19 in vitro. Some of them are remdesivir (GS-5734), chloroquine, hydroxychloroquine, theaflavin. Topological indices are mathematical interpretations of a molecule generated by an algorithm implemented to a given molecular representation. Topological indices are used to model different physicochemical properties and biological activities of chemical compounds. In this work, some degree-based and neighborhood degree sum-based topological indices are investigated for the aforesaid antiviral drugs using polynomial approach. The results obtained can aid in the design of new medicine for the treatment of COVID-19.


title: Epidemiology

text: This chapter provides an overview of the global epidemiology of rabies, focusing on major changes over the past half-century and highlighting recent discoveries. This chapter also describes the natural and iatrogenic routes of transmission, as well as the risk and necessary actions for the prevention of rabies following an exposure. It reviews the methods for rabies diagnosis and the biologics for prevention, in addition to differences in rabies prophylaxis recommendations among advisory committees. The chapter also considers epidemiology and trends in global human rabies and the dynamics of the corresponding mammalian reservoir hosts for each area. Furthermore, it considers the phylogenetics of rabies virus, other lyssaviruses, and specific rabies virus variants in the context of regional rabies and the potential for novel emergences. Special attention is paid to developed countries, where existing surveillance and diagnostic infrastructure have provided detailed insights into the nature changing patterns in rabies epidemiology-patterns expected to be increasingly relevant to other less-developed nations based on current trends. Special attention is afforded to canine rabies, as dogs remain responsible for over 99% of all human exposures to the virus, including the methods and problems associated with intentional and unintentional movement of dogs at national and international levels. Finally, the chapter discusses the economic burden of rabies in terms of human and infrastructure support.


title: Fidelity Variants of RNA Dependent RNA Polymerases Uncover an Indirect, Mutagenic Activity of Amiloride Compounds

text: In a screen for RNA mutagen resistance, we isolated a high fidelity RNA dependent RNA polymerase (RdRp) variant of Coxsackie virus B3 (CVB3). Curiously, this variant A372V is also resistant to amiloride. We hypothesize that amiloride has a previously undescribed mutagenic activity. Indeed, amiloride compounds increase the mutation frequencies of CVB3 and poliovirus and high fidelity variants of both viruses are more resistant to this effect. We hypothesize that this mutagenic activity is mediated through alterations in intracellular ions such as Mg(2+) and Mn(2+), which in turn increase virus mutation frequency by affecting RdRp fidelity. Furthermore, we show that another amiloride-resistant RdRp variant, S299T, is completely resistant to this mutagenic activity and unaffected by changes in ion concentrations. We show that RdRp variants resist the mutagenic activity of amiloride via two different mechanisms: 1) increased fidelity that generates virus populations presenting lower basal mutation frequencies or 2) resisting changes in divalent cation concentrations that affect polymerase fidelity. Our results uncover a new antiviral approach based on mutagenesis.


COVID‐19 disease in New York City pediatric hematology and oncology patients


title: How digital tools can advance quality and equity in genomic medicine

text: Now more than ever, digital applications are essential to accessing genetics services and optimizing their delivery. At this watershed moment, digital solutions must be balanced with the merits of human interaction, without compromising quality or exacerbating existing genomic and technological disparities.


title: Comparison of ePlex Respiratory Pathogen Panel with Laboratory-Developed Real-Time PCR Assays for Detection of Respiratory Pathogens

text: Infections of the respiratory tract can be caused by a diversity of pathogens, both viral and bacterial. Rapid microbiological diagnosis ensures appropriate antimicrobial therapy as well as effective implementation of isolation precautions. The ePlex respiratory pathogen panel (RP panel) is a novel molecular biology-based assay, developed by GenMark Diagnostics, Inc. (Carlsbad, CA), to be performed within a single cartridge for the diagnosis of 25 respiratory pathogens (viral and bacterial). The objective of this study was to compare the performance of the RP panel with those of laboratory-developed real-time PCR assays, using a variety of previously collected clinical respiratory specimens. A total of 343 clinical specimens as well as 29 external quality assessment (EQA) specimens and 2 different Middle East respiratory syndrome coronavirus isolates have been assessed in this study. The RP panel showed an agreement of 97.4% with the real-time PCR assay regarding 464 pathogens found in the clinical specimens. All pathogens present in clinical samples and EQA samples with a threshold cycle (C(T)) value of <30 were detected correctly using the RP panel. The RP panel detected 17 additional pathogens, 7 of which could be confirmed by discrepant testing. In conclusion, this study shows excellent performance of the RP panel in comparison to real-time PCR assays for the detection of respiratory pathogens. The ePlex system provided a large amount of useful diagnostic data within a short time frame, with minimal hands-on time, and can therefore potentially be used for rapid diagnostic sample-to-answer testing, in either a laboratory or a decentralized setting.


title: RNA Virus Fidelity Mutants: A Useful Tool for Evolutionary Biology or a Complex Challenge?

text: RNA viruses replicate with low fidelity due to the error-prone nature of the RNA-dependent RNA polymerase, which generates approximately one mutation per round of genome replication. Due to the large population sizes produced by RNA viruses during replication, this results in a cloud of closely related virus variants during host infection, of which small increases or decreases in replication fidelity have been shown to result in virus attenuation in vivo, but not typically in vitro. Since the discovery of the first RNA virus fidelity mutants during the mid-aughts, the field has exploded with the identification of over 50 virus fidelity mutants distributed amongst 7 RNA virus families. This review summarizes the current RNA virus fidelity mutant literature, with a focus upon the definition of a fidelity mutant as well as methods to confirm any mutational changes associated with the fidelity mutant. Due to the complexity of such a definition, in addition to reports of unstable virus fidelity phenotypes, the future translational utility of these mutants and applications for basic science are examined.


title: Multiplex RT‐PCR and Automated Microarray for Detection of Eight Bovine Viruses

text: Microarrays can be a useful tool for pathogen detection as it allow for simultaneous interrogation of the presence of a large number of genetic sequences in a sample. However, conventional microarrays require extensive manual handling and multiple pieces of equipment for printing probes, hybridization, washing and signal detection. In this study, a reverse transcription (RT)–PCR with an accompanying novel automated microarray for simultaneous detection of eight viruses that affect cattle [vesicular stomatitis virus (VSV), bovine viral diarrhoea virus type 1 and type 2, bovine herpesvirus 1, bluetongue virus, malignant catarrhal fever virus, rinderpest virus (RPV) and parapox viruses] is described. The assay accurately identified a panel of 37 strains of the target viruses and identified a mixed infection. No non‐specific reactions were observed with a panel of 23 non‐target viruses associated with livestock. Vesicular stomatitis virus was detected as early as 2 days post‐inoculation in oral swabs from experimentally infected animals. The limit of detection of the microarray assay was as low as 1 TCID (50)/ml for RPV. The novel microarray platform automates the entire post‐PCR steps of the assay and integrates electrophoretic‐driven capture probe printing in a single user‐friendly instrument that allows array layout and assay configuration to be user‐customized on‐site.


title: Viral infections of the respiratory tract in patients with cystic fibrosis

text: Abstract The role of viruses and bacteria in the development of respiratory tract infections causing acute deteriorations in lung function in patients with cystic fibrosis (CF) was investigated. Over a period of 30 months, 29 viral respiratory diseases were proven serologically by testing 275 sporadically collected sera from 75 patients with cystic fibrosis. The influenza A virus was the most frequent responsible viral pathogen (11 × ), followed by adenovirus (8 × ), influenza B virus (5 × ), parainfluenza virus type 3 (3 × ), parainfluenza virus type 1 and respiratory syncytial virus (RSV) (each of 1 × ). There was no serological evidence for infections with parainfluenza virus type 2, Mycoplasma pneumoniae or Coxiella burnetii. Deterioration of the clinical condition was found in 78% of the viral infections leading in 70% to hospital admission. Patients with cystic fibrosis and viral respiratory illnesses showed significantly more admissions to the hospital (3·2 ± 2·7) with a longer stay (90·6 ± 99·6 days). Nearly all viral episodes (93%) were accompanied or followed by a significant change of the microbial flora in the sputum especially by colonisation with Pseudomonas aeruginosa, Staphylococcus aureus and Haemophilus influenzae. Seventy-two per cent of the viral infections occurred at home and 28% seemed to be hospital acquired. Our study emphasises the importance of improving antibacterial therapy at home to reduce the number of hospital admissions. Efforts for prophylaxis by vaccination or the use of chemotherapeutic agents should be made for the patients with cystic fibrosis.


title: Bioinformatics in Design of Antiviral Vaccines

text: Abstract Viral diseases and epidemics are occurring across the world with increasing frequency and with incidences of new and old viruses with renewed vigor. Traditional drugs and vaccines with their long developmental times, incidences of allergenic reactions, growth of resistant strains and other issues are proving inadequate to curb the menace. Advancements in computer science and technology, in genetics and immunology and the growth of the new science of bioinformatics are leading to a more focused approach in a new paradigm of vaccine design that challenges the traditional approach and promises to be more effective; lead times should get much shorter, preselection of peptide antivirals will be designed to preclude allergenic reactions, stability against mutational changes to viral strains will be much more assured, and coverage of immunological status will enable community-specific vaccines development. We outline in this article the basics of viruses, immune responses, and traditional vaccines and move on to describe the bioinformatics methods and development of new vaccines.


title: Protein science research in China

text: Proteins are major executors of life processes, carrying out essential and nonessential functions inside and outside of the cell, in species ranging from simple unicellular organisms to mammals. Thus, not surprisingly, studies of structure and function of proteins span the entire spectrum of molecular biology and modern biomedical sciences in general. Due to historical reasons, protein science research in China was isolated and limited in scope until late 1970s. In the last two decades, China has seen an outburst of research activities, government initiatives, and aggregation of human talents in protein science research. This article provides an overview of major initiatives in research funding, investment in infrastructures, and research forces for protein science research in China.


title: Cross‐species transfer of viruses: implications for the use of viral vectors in biomedical research, gene therapy and as live‐virus vaccines

text: Summary All living organisms are continuously exposed to a plethora of viruses. In general, viruses tend to be restricted to the natural host species which they infect. From time to time viruses cross the host‐range barrier expanding their host range. However, in very rare cases cross‐species transfer is followed by the establishment and persistence of a virus in the new host species, which may result in disease. Recent examples of viruses that have crossed the species barrier from animal reservoirs to humans are hantavirus, haemorrhagic fever viruses, arboviruses, Nipah and Hendra viruses, avian influenza virus (AI), monkeypox virus, and the SARS‐associated coronavirus (SARS‐CoV). The opportunities for cross‐species transfer of mammalian viruses have increased in recent years due to increased contact between humans and animal reservoirs. However, it is difficult to predict when such events will take place since the viral adaptation that is needed to accomplish this is multifactorial and stochastic. Against this background the intensified use of viruses and their genetically modified variants as viral gene transfer vectors for biomedical research, experimental gene therapy and for live‐vector vaccines is a cause for concern. This review addresses a number of potential risk factors and their implications for activities with viral vectors from the perspective of cross‐species transfer of viruses in nature, with emphasis on the occurrence of host‐range mutants resulting from either cell culture or tropism engineering. The issues are raised with the intention to assist in risk assessments for activities with vector viruses. Copyright © 2005 John Wiley & Sons, Ltd.


title: Unusual presentations of COVID-19 pneumonia on CT scans with spontaneous pneumomediastinum and loculated pneumothorax: a report of two cases and a review of the literature.

text: Spontaneous pneumomediastinum (SPM) and Loculated pneumothorax (LPNX) are both generally rare clinical and radiological conditions associated with Coronavirus Disease 2019 (COVID-19). We report for the first time clinical data and radiological chest CT imaging of two patients affected by COVID-pneumonia associated with early radiological findings of SPM and LPNX.


Consensus is needed at a global level concerning dual‐use research


title: Regulation, risk and safety of Faecal Microbiota Transplant

text: Summary From its origins as a left-field, experimental, and even “maverick” intervention, faecal microbiota transplantation (FMT) is now a well-recognised, accepted, and potentially life-saving therapeutic strategy, for the management of recurrent Clostridiodes difficile infection (rCDI). It is being investigated as a treatment for a growing number of diseases including hepatic encephalopathy and eradication of antimicrobial resistant organisms, and the list of indications will likely expand in the future. There is no universally accepted definition of what FMT is, and its mechanism of action remains incompletely understood; this has likely contributed to the breadth of approaches to regulation depending on interpretation. In the UK FMT is considered a medicinal product, in North America, a biological product, whereas in parts of Europe, it is considered a human cell/ tissue product. Regulation seeks to improve quality and safety, however, lack of standardisation creates confusion, and overly restrictive regulation may hamper widespread access and discourage research using FMT. FMT is generally considered safe, especially if rigorous donor screening and testing is conducted. Most short-term risks are associated with the delivery method (e.g. colonoscopy). Longer term risks are less well described but longitudinal follow-up of treated cohorts is in place to assess for this, and no signal towards harm has been found to date. Rarely it has been associated with adverse outcomes including the transmission of antibiotic resistant bacteria, and even death. It is vital patients undergoing FMT are well informed to the currently appreciated risks and benefits before proceeding.


title: Tuberculosis among Foreign-born Persons, Singapore, 2000–2009

text: We determined the proportion of foreign-born persons with tuberculosis (TB) in Singapore. This proportion increased from 25.5% in 2004 to 37.6% in 2009. Unskilled workers from countries with high incidences of TB accounted for the highest number of and greatest increase in foreign-born TB case-patients.


title: Use of Aptamers as Diagnostics Tools and Antiviral Agents for Human Viruses

text: Appropriate diagnosis is the key factor for treatment of viral diseases. Time is the most important factor in rapidly developing and epidemiologically dangerous diseases, such as influenza, Ebola and SARS. Chronic viral diseases such as HIV-1 or HCV are asymptomatic or oligosymptomatic and the therapeutic success mainly depends on early detection of the infective agent. Over the last years, aptamer technology has been used in a wide range of diagnostic and therapeutic applications and, concretely, several strategies are currently being explored using aptamers against virus proteins. From a diagnostics point of view, aptamers are being designed as a bio-recognition element in diagnostic systems to detect viral proteins either in the blood (serum or plasma) or into infected cells. Another potential use of aptamers is for therapeutics of viral infections, interfering in the interaction between the virus and the host using aptamers targeting host-cell matrix receptors, or attacking the virus intracellularly, targeting proteins implicated in the viral replication cycle. In this paper, we review how aptamers working against viral proteins are discovered, with a focus on recent advances that improve the aptamers’ properties as a real tool for viral infection detection and treatment.


title: Chapter Four Coronavirus cis-Acting RNA Elements

text: Abstract Coronaviruses have exceptionally large RNA genomes of approximately 30 kilobases. Genome replication and transcription is mediated by a multisubunit protein complex comprised of more than a dozen virus-encoded proteins. The protein complex is thought to bind specific cis-acting RNA elements primarily located in the 5′- and 3′-terminal genome regions and upstream of the open reading frames located in the 3′-proximal one-third of the genome. Here, we review our current understanding of coronavirus cis-acting RNA elements, focusing on elements required for genome replication and packaging. Recent bioinformatic, biochemical, and genetic studies suggest a previously unknown level of conservation of cis-acting RNA structures among different coronavirus genera and, in some cases, even beyond genus boundaries. Also, there is increasing evidence to suggest that individual cis-acting elements may be part of higher-order RNA structures involving long-range and dynamic RNA–RNA interactions between RNA structural elements separated by thousands of nucleotides in the viral genome. We discuss the structural and functional features of these cis-acting RNA elements and their specific functions in coronavirus RNA synthesis.


title: Structure and Dynamics of the HIV-1 Frameshift Element RNA

text: [Image: see text] The HIV-1 ribosomal frameshift element is highly structured, regulates translation of all virally encoded enzymes, and is a promising therapeutic target. The prior model for this motif contains two helices separated by a three-nucleotide bulge. Modifications to this model were suggested by SHAPE chemical probing of an entire HIV-1 RNA genome. Novel features of the SHAPE-directed model include alternate helical conformations and a larger, more complex structure. These structural elements also support the presence of a secondary frameshift site within the frameshift domain. Here, we use oligonucleotide-directed structure perturbation, probing in the presence of formamide, and in-virion experiments to examine these models. Our data support a model in which the frameshift domain is anchored by a stable helix outside the conventional domain. Less stable helices within the domain can switch from the SHAPE-predicted to the two-helix conformation. Translational frameshifting assays with frameshift domain mutants support a functional role for the interactions predicted by and specific to the SHAPE-directed model. These results reveal that the HIV-1 frameshift domain is a complex, dynamic structure and underscore the importance of analyzing folding in the context of full-length RNAs.


title: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)

text: In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named “2019 novel coronavirus (2019-nCoV)” by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.


Is There a Role for Lung Ultrasound During the COVID‐19 Pandemic?


title: SARS-CoV-2 in the ocular surface of COVID-19 patients

text: The 2019 novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, while the routes of transmission of this virus are still controversial. We enrolled 33 patients, without any ocular manifestation, with their ocular surface swabs collected for virus detection. RNA was detected strong positive in samples of both eyes from two patients. Therefore, SARS-CoV-2 may exist in the normal ocular surface of COVID-19 patients, suggesting that this virus might be spread through conjunctival contact.


title: The synergistic effect of IFN-α and IFN-γ against HSV-2 replication in Vero cells is not interfered by the plant antiviral 1-cinnamoyl-3, 11-dihydroxymeliacarpin

text: BACKGROUND: Recent studies have shown that gamma interferon (IFN-γ) synergizes with IFN-α/β to inhibit herpes simplex virus type 1 (HSV-1) replication in vitro. Since IFN response represents an early host defense event against viral infection and the fact that treatment with meliacine, a plant antiviral, ameliorate the severity of the herpetic infection in female mice infected intravaginally with HSV-2, we wanted to investigate whether the administration of meliacine to HSV-2 infected mice could altered the homoestasis of IFNs host response. For this purpose we studied the effect of the compound 1-cinnamoyl-3,11-dihydroxymeliacarpin (CDM), which is the responsible for meliacine antiviral action, on the HSV-2 inhibition exerted by IFN α, IFN-γ or their combination. RESULTS: We have found that like HSV-1, IFN-γ synergizes with IFN-α to inhibit HSV-2 replication in Vero cells. While treatment with IFN-α or IFN-γ alone has weak antiviral action, HSV-2 plaque formation, viral replication and the onset of viral CPE in Vero cells are synergistically inhibited by interferon combination. In addition, CDM treatment contributes to protect cells from virus cytopathic effect and causes a strong inhibition of HSV-2 titer. Moreover, the presence of CDM for 2 h before IFN induction, during the 16 h induction period, only for 24 h after infection or during the complete IFN treatment period, reduces virus yields in an additive way without affecting IFN antiviral action. CONCLUSION: The results reported here indicated that the presence of CDM did not alter the antiviral activity of IFN-α, IFN-γ or the synergism exerted by their combination. As a result we can envision that the administration of CDM in vivo could not affect the biological activity of IFNs, which are so important mediators of the innate resistance to HSV-2 infection.


title: Chapter 22 Environmentally Transmitted Pathogens

text: Publisher Summary Pathogenic microorganisms usually originate from an infected host or directly from the environment; however, only a small proportion of these microbes cause infection. This chapter discusses the pathogens that are transmitted through the environment such as bacteria, viruses, and protozoa. Many human pathogens can be transmitted only by direct or close contact with an infected person or animal such as herpesvirus. Virus transmission by the airborne route may be both direct and indirect inhalation of infectious droplets or through contact with contaminated fomites. Water-borne diseases—such as yellow fever, dengue, filariasis, malaria, onchocerciasis, and sleeping sicknessare transmitted by insects that breed in water or live near water. The common bacterial pathogens transmitted through water include Salmonella, Escherichia coli, Shigella, Campylobacter, Yersinia, Vibrio, Helicobacter, and Legionella. Opportunistic pathogens are also numerous in the environment, and the most important opportunistic pathogen is Pseudomonas aeruginosa. Viruses are a leading cause of gastroenteritis and water-borne outbreaks may be caused by norovirus, hepatitis A virus, Coxsackie virus, echovirus, and adenoviruses. Respiratory diseases are also associated with a large number of viruses such as rhinoviruses, coronaviruses, parainfluenza viruses, respiratory syncytial virus (RSV), influenza virus, and adenovirus. Generally, viral and protozoan pathogens survive longer in the environment than enteric bacterial pathogens.


title: Occupational Risks and Exposures Among Wildlife Health Professionals

text: Most emerging infectious diseases are zoonotic in origin, with wildlife a frequent source of zoonotic disease events. Although individuals with extensive wildlife contact may be at the greatest risk of contracting novel infectious agents, the occupational risk of those working closely with wildlife has not been well studied. This study assessed the occupational exposures among wildlife health professionals working in multiple countries worldwide. An occupational risk survey of past and present exposures was developed and administered online in a confidential manner to wildlife workers recruited through an ongoing international wildlife pathogen surveillance project. Surveys were completed by 71 participants in 14 countries. Significant lifetime exposures reported included bites from bats and rodents and touching dead animals. Completion of training in occupational safety was reported by 75% of respondents. While gloves were used for most tasks, use of N95 respirators and other personal protective equipment varied by task. Eighty percent of workers reported rabies vaccination. Some respondents indicated interest in enhanced occupational health services targeting their unique needs. Wildlife workers represent an occupational population at risk of zoonotic infection and injury. Enhanced occupational health services targeting wildlife workers could reduce the risk and sequelae of zoonotic exposure and infection.


title: Surveillance for Febrile Respiratory Infections during Cobra Gold 2003

text: The Naval Health Research Center conducted laboratory-based surveillance for febrile respiratory infections at the 2003 Cobra Gold Exercise in Thailand. Seventeen individuals met the case definition for febrile respiratory illness, and diagnostic specimens were obtained from 16. Laboratory testing identified influenza A for 44%; sequence analysis demonstrated that these were Fujian-like influenza strains, which represented the predominant strain found globally in 2003/2004. Other pathogens identified included coronavirus OC43, respiratory syncytial virus, and rhinovirus. Logistical challenges were overcome as laboratory-supported febrile respiratory illness surveillance was conducted during a military training exercise. With heightened concern over the potential for another global influenza pandemic, such surveillance could prove critical for the detection of emerging influenza and respiratory pathogen strains with potential for importation to the United States.


title: Chapter 18 Mineral Adjuvants ∗ ∗ The present chapter is an updated version of the chapter “Mineral Adjuvants,” published in Immunopotentiators in Modern Vaccines, p. 217–233. Ed. Virgil Schijns & Derek O'Hagan, Elsevier Science Publishers (2005).

text: Abstract Mineral adjuvants comprise aluminum hydroxide and phosphate adjuvants as well as calcium phosphate adjuvants. In particular, the aluminum salts have achieved an undisputed status as the most commonly used adjuvants in human and veterinary vaccines. Calcium phosphate adjuvant, later discovered by Edgar Relyveld, constitutes a very interesting alternative and has also been applied both in human and veterinary vaccines. New analytical tools applied in adjuvant research are about to take us to the next level of understanding mineral adjuvants. These tools have been used to characterize mineral adjuvants, but so far, in particular, aluminum-based adjuvants in terms of surface marker expression profiles, isotypic profiles, and cytokine profiles. In the past 10years, the discovery of adjuvant-mediated induction of the NALP3 inflammasome and its impact on the secretion of interleukin (IL)-1β and IL-18 as proinflammatory mediators in the early phases of immune response has been described as an important mechanism for the function of these adjuvants.


title: Immunostimulants in respiratory diseases: focus on Pidotimod

text: Usefulness of Pidotimod and its role as immunostimulant, has been discussed, we know, for several decades. Nevertheless, there is still much to know. Understanding its mechanisms and its potential usefulness in airway infections and its prevention, asthma both Th2 and non Th2 type, bronchiectasis, as adjuvant in vaccination and in allergen immunotherapy still remains to clearly unveil. The aim of this paper was to provide a useful updated review of the role of the main available immunostimulants, giving particular focus on Pidotimod use and its potentials utility in respiratory diseases. Pidotimod showed its usefulness in reducing need for antibiotics in airway infections, increasing the level of immunoglobulins (IgA, IgM, IgG) and T-lymphocyte subsets (CD3+, CD4+) endowed with immunomodulatory activity that affect both innate and adaptive immune responses. Higher expression of TLR2 and of HLA-DR molecules, induction of dendritic cell maturation and release of pro-inflammatory molecules, stimulation of T lymphocyte proliferation and differentiation toward a Th1 phenotype, as well as an increase of the phagocytosis have been demonstrated to be associated with Pidotimod in in vitro studies. All these activities are potentially useful for several respiratory conditions such as asthma, COPD, and recurrent respiratory tract infections.


AVTRW abstracts


title: Acute pulmonary embolism in COVID-19 disease: Preliminary report on seven patients

text: There is some evidence that Covid 19 pneumonia is associated with prothrombotic status and increased risk of venous thromboembolic events (deep venous thrombosis and pulmonary embolism). Over a two-week period we admitted in our Unit 25 patients with Covid-19 pneumonia, of these pulmonary embolism was diagnosed using computed tomography angiography in 7. We report on clinical and biochemical features of these patients. They were all males, with a mean age of 70.3 years (range 58–84); traditional risk factors for venous thromboembolism were identified in the majority of patients with pulmonary embolism, however not differently from those without pulmonary embolism. Clinical presentation of pulmonary embolism patients was usually characterized by persistence or worsening of respiratory symptoms, with increasing oxygen requirement. D-dimer levels were several fold higher than the upper threshold of normal; in patients in whom PE was recognized during hospital stay, a rapid and relevant increase of D-dimer levels was observed. Computed tomographic findings ranged from massive acute pulmonary embolism to a segmental or sub-segmental pattern; furthermore, thrombosis of sub-segmental pulmonary arteries within lung infiltrates were occasionally seen, suggesting local mechanisms. Six out of 7 patients were treated with unfractionated or low molecular weight heparin with clinical benefit within few days; one patient needed systemic thrombolysis (death from hemorrhagic complication).


title: Transmission potential of the novel coronavirus (COVID-19) onboard the diamond Princess Cruises Ship, 2020

text: An outbreak of COVID-19 developed aboard the Princess Cruises Ship during January–February 2020. Using mathematical modeling and time-series incidence data describing the trajectory of the outbreak among passengers and crew members, we characterize how the transmission potential varied over the course of the outbreak. Our estimate of the mean reproduction number in the confined setting reached values as high as ~11, which is higher than mean estimates reported from community-level transmission dynamics in China and Singapore (approximate range: 1.1–7). Our findings suggest that R(t) decreased substantially compared to values during the early phase after the Japanese government implemented an enhanced quarantine control. Most recent estimates of R(t) reached values largely below the epidemic threshold, indicating that a secondary outbreak of the novel coronavirus was unlikely to occur aboard the Diamond Princess Ship.


title: Development of Medical Countermeasures to Middle East Respiratory Syndrome Coronavirus

text: Preclinical development of and research on potential Middle East respiratory syndrome coronavirus (MERS-CoV) medical countermeasures remain preliminary; advancements are needed before most countermeasures are ready to be tested in human clinical trials. Research priorities include standardization of animal models and virus stocks for studying disease pathogenesis and efficacy of medical countermeasures; development of MERS-CoV diagnostics; improved access to nonhuman primates to support preclinical research; studies to better understand and control MERS-CoV disease, including vaccination studies in camels; and development of a standardized clinical trial protocol. Partnering with clinical trial networks in affected countries to evaluate safety and efficacy of investigational therapeutics will strengthen efforts to identify successful medical countermeasures.


title: Management of dysphagia in the patient with head and neck cancer during COVID‐19 pandemic: Practical strategy

text: The global pandemic of 2019 novel coronavirus disease (COVID‐19) has tremendously altered routine medical service provision and imposed unprecedented challenges to the health care system. This impacts patients with dysphagia complications caused by head and neck cancers. As this pandemic of COVID‐19 may last longer than severe acute respiratory syndrome (SARS) in 2003, a practical workflow for managing dysphagia is crucial to ensure a safe and efficient practice to patients and health care personnel. This document provides clinical practice guidelines based on available evidence to date to balance the risks of SARS‐CoV‐2 exposure with the risks associated with dysphagia. Critical considerations include reserving instrumental assessments for urgent cases only, optimizing the noninstrumental swallowing evaluation, appropriate use of personal protective equipment (PPE), and use of telehealth when appropriate. Despite significant limitations in clinical service provision during the pandemic of COVID‐19, a safe and reasonable dysphagia care pathway can still be implemented with modifications of setup and application of newer technologies.


title: Microbiota modulating nutritional approaches to countering the effects of viral respiratory infections including SARS-CoV-2 through promoting metabolic and immune fitness with probiotics and plant bioactives

text: Viral respiratory infections (VRIs) can spread quickly and cause enormous morbidity and mortality worldwide. These events pose serious threats to public health due to time lags in developing vaccines to activate the acquired immune system. The high variability of people’s symptomatic responses to viral infections, as illustrated in the current COVID-19 pandemic, indicates the potential to moderate the severity of morbidity from VRIs. Growing evidence supports roles for probiotic bacteria (PB) and prebiotic dietary fiber (DF) and other plant nutritional bioactives in modulating immune functions. While human studies help to understand the epidemiology and immunopathology of VRIs, the chaotic nature of viral transmissions makes it difficult to undertake mechanistic study where the pre-conditioning of the metabolic and immune system could be beneficial. However, recent experimental studies have significantly enhanced our understanding of how PB and DF, along with plant bioactives, can significantly modulate innate and acquired immunity responses to VRIs. Synbiotic combinations of PB and DF potentiate increased benefits primarily through augmenting the production of short-chain fatty acids (SCFAs) such as butyrate. These and specific plant polyphenolics help to regulate immune responses to both restrain VRIs and temper the neutrophil response that can lead to acute respiratory distress syndrome (ARDS). This review highlights the current understanding of the potential impact of targeted nutritional strategies in setting a balanced immune tone for viral clearance and reinforcing homeostasis. This knowledge may guide the development of public health tactics and the application of functional foods with PB and DF components as a nutritional approach to support countering VRI morbidity.


COVID-2019.2 Reboot: Returning a GI Fellowship to Pre-pandemic Practices


title: COVID-19 severity and mortality in patients with chronic lymphocytic leukemia: a joint study by ERIC, the European Research Initiative on CLL, and CLL Campus

text: Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency. Hence, patients with CLL might be considered more susceptible to severe complications from COVID-19. We undertook this retrospective international multicenter study to characterize the course of COVID-19 in patients with CLL and identify potential predictors of outcome. Of 190 patients with CLL and confirmed COVID-19 diagnosed between 28/03/2020 and 22/05/2020, 151 (79%) presented with severe COVID-19 (need of oxygen and/or intensive care admission). Severe COVID-19 was associated with more advanced age (≥65 years) (odds ratio 3.72 [95% CI 1.79–7.71]). Only 60 patients (39.7%) with severe COVID-19 were receiving or had recent (≤12 months) treatment for CLL at the time of COVID-19 versus 30/39 (76.9%) patients with mild disease. Hospitalization rate for severe COVID-19 was lower (p < 0.05) for patients on ibrutinib versus those on other regimens or off treatment. Of 151 patients with severe disease, 55 (36.4%) succumbed versus only 1/38 (2.6%) with mild disease; age and comorbidities did not impact on mortality. In CLL, (1) COVID-19 severity increases with age; (2) antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; (3) age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.


title: Detection of viral respiratory pathogens in mild and severe acute respiratory infections in Singapore

text: To investigate the performance of laboratory methods and clinical case definitions in detecting the viral pathogens for acute respiratory infections (ARIs) from a prospective community cohort and hospital inpatients, nasopharyngeal swabs from cohort members reporting ARIs (community-ARI) and inpatients admitted with ARIs (inpatient-ARI) were tested by Singleplex Real Time-Polymerase Chain Reaction (SRT-PCR), multiplex RT-PCR (MRT-PCR) and pathogen-chip system (PathChip) between April 2012 and December 2013. Community-ARI and inpatient-ARI was also combined with mild and severe cases of influenza from a historical prospective study as mild-ARI and severe-ARI respectively to evaluate the performance of clinical case definitions. We analysed 130 community-ARI and 140 inpatient-ARI episodes (5 inpatient-ARI excluded because multiple pathogens were detected), involving 138 and 207 samples respectively. Detection by PCR declined with days post-onset for influenza virus; decrease was faster for community-ARI than for inpatient-ARI. No such patterns were observed for non-influenza respiratory virus infections. PathChip added substantially to viruses detected for community-ARI only. Clinical case definitions discriminated influenza from other mild-ARI but performed poorly for severe-ARI and for older participants. Rational strategies for diagnosis and surveillance of influenza and other respiratory virus must acknowledge the differences between ARIs presenting in community and hospital settings.


title: Long-term Results with the Modified Sugiura Procedure for the Management of Variceal Bleeding: Standing the Test of Time in the Treatment of Bleeding Esophageal Varices

text: BACKGROUND: The surgical approaches to the treatment of bleeding esophageal varices in cirrhotic patients have been reduced since the clinical development of endoscopic sclerotherapy, transjugular intrahepatic portosystemic shunt (TIPS), and liver transplantation. However, when acute sclerotherapy fails, and in cases where no further treatment is accessible, emergency surgery may be life saving. In the present study we retrospectively analyzed the results of the modified Sugiura procedure, performed as emergency and semi-elective treatment in the patient with bleeding esophageal varices. METHODS: Ninety patients with cirrhosis and portal hypertension were managed in our department for variceal esophageal bleeding between January 1985 and December 1992. The modified Sugiura procedure was performed in 46 patients on an emergency (25 patients) or semi-elective (21 patients) basis. Liver cirrhosis stage according to Child classification was A in 4 patients, B in 16 patients, and C in 26 patients. RESULTS: Acute bleeding was controlled in all patients. Postoperative mortality was 23.9% (11 of 46 patients). The mortality rate was 34.6% in Child class C patients (9 of 26 patients), and 12.5% in Child class B patients (2 of 16 patients). Twenty-four patients had long-term follow-up extending from 14 months to 22 years (mean 83.1 months). Ten of 24 patients (41.6%) did not develop rebleeding for 5–22 years (mean 10.3 years). Overall 5-year survival in these 24 patients was 62.5%. CONCLUSIONS: The modified Sugiura procedure remains an effective rescue therapy for patients with bleeding esophageal varices when alternative treatments fail or are not indicated. Moreover, it can be a life-saving procedure in patients with anatomy unsuitable for shunt surgery or for patients treated in nonspecialized centers where surgical expertise for a shunt operation is not available.


Response to ‘Multimorbidity and SARS-CoV-2 infection in UK Biobank’


title: Full genome sequence of guinea fowl coronavirus associated with fulminating disease

text: Guinea fowl coronavirus (GfCoV), a recently characterized avian coronavirus, was identified from outbreaks of fulminating disease (peracute enteritis) in guinea fowl in France. The full-length genomic sequence was determined to better understand its genetic relationship with avian coronaviruses. The full-length coding genome sequence was 26,985 nucleotides long with 11 open reading frames and no hemagglutinin–esterase gene: a genome organization identical to that of turkey coronavirus [5′ untranslated region (UTR)—replicase (ORFs 1a, 1ab)—spike (S) protein—ORF3 (ORFs 3a, 3b)—small envelop (E or 3c) protein—membrane (M) protein—ORF5 (ORFs 4b, 4c, 5a, 5b)—nucleocapsid (N) protein (ORFs N and 6b)—3′ UTR]. This is the first complete genome sequence of a GfCoV and confirms that the new virus belongs to group gammacoronaviruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11262-015-1183-z) contains supplementary material, which is available to authorized users.


Hypertension and diabetes mellitus in patients with COVID 19: a viewpoint on mortality


title: Human IgG neutralizing monoclonal antibodies block SARS-CoV-2 infection

text: Summary COVID-19 has become a worldwide threat to humans, and neutralizing antibodies have therapeutic potential. We have purified more than one thousand memory B cells specific to SARS-CoV-2 S1 or RBD (receptor binding domain), and obtain 729 paired heavy and light chain fragments. Among these, 178 antibodies test positive for antigen binding, and the majority of the top 17 binders with EC50 below 1 nM are RBD binders. Furthermore, we identify 11 neutralizing antibodies, 8 of which show an IC50 within 10 nM, and the best one, 414-1, with IC50 of 1.75 nM. Through epitope mapping, we find 3 main epitopes in RBD recognized by these antibodies, and epitope B antibody 553-15 could substantially enhance the neutralizing abilities of most of the other antibodies. We also find that 515-5 could cross-neutralize the SARS-CoV pseudovirus. Altogether, our study provides 11 potent human neutralizing antibodies for COVID-19 as therapeutic candidates.


title: Patient Isolation Precautions: Are They Worth It?

text: Isolation precautions are intended to minimize pathogen transmission and reduce hospital-acquired infections. More recently, the effectiveness of isolation precautions has been questioned because of increasing evidence of risks. These putative downsides are divided into a quantifiable monetary cost (i.e., a literal cost to the system) and clinically important but less easily quantifiable costs (i.e., “costs” to the patient). The authors also briefly review deisolation and alternatives to isolation. The present review is not arguing against appropriate isolation or precautions, simply that the authors consider both risks and benefits and disseminate up-to-date information. Their patient-focused goal is to mitigate risks for those who truly need isolating and to end isolation as soon as it is safe and appropriate to do so.


Extracorporeal membrane oxygenation in patients with acute respiratory distress syndrome caused by COVID-19