title: SARS-CoV-2 Entry Genes Are Most Highly Expressed in Nasal Goblet and Ciliated Cells within Human Airways

text: The SARS-CoV-2 coronavirus, the etiologic agent responsible for COVID-19 coronavirus disease, is a global threat. To better understand viral tropism, we assessed the RNA expression of the coronavirus receptor, ACE2, as well as the viral S protein priming protease TMPRSS2 thought to govern viral entry in single-cell RNA-sequencing (scRNA-seq) datasets from healthy individuals generated by the Human Cell Atlas consortium. We found that ACE2, as well as the protease TMPRSS2, are differentially expressed in respiratory and gut epithelial cells. In-depth analysis of epithelial cells in the respiratory tree reveals that nasal epithelial cells, specifically goblet/secretory cells and ciliated cells, display the highest ACE2 expression of all the epithelial cells analyzed. The skewed expression of viral receptors/entry-associated proteins towards the upper airway may be correlated with enhanced transmissivity. Finally, we showed that many of the top genes associated with ACE2 airway epithelial expression are innate immune-associated, antiviral genes, highly enriched in the nasal epithelial cells. This association with immune pathways might have clinical implications for the course of infection and viral pathology, and highlights the specific significance of nasal epithelia in viral infection. Our findings underscore the importance of the availability of the Human Cell Atlas as a reference dataset. In this instance, analysis of the compendium of data points to a particularly relevant role for nasal goblet and ciliated cells as early viral targets and potential reservoirs of SARS-CoV-2 infection. This, in turn, serves as a biological framework for dissecting viral transmission and developing clinical strategies for prevention and therapy.


title: Emerging and reemerging respiratory viral infections up to Covid-19

text: Infectious diseases remain as the significant causes of human and animal morbidity and mortality, leading to extensive outbreaks and epidemics. Acute respiratory viral diseases claim over 4 million deaths and cause millions of hospitalizations in developing countries every year. Emerging viruses, especially the RNA viruses, are more pathogenic since most people have no herd immunity. The RNA viruses can adapt to the rapidly changing global and local environment due to the high error rate of their polymerases that replicate their genomes. Currently, coronavirus disease 2019 (COVID-19) is determined as an u28a9 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first identified in 2019 in u28ac. Herein we discuss emerging and reemerging respiratory viral infections till to SARS-CoV-2.


title: First Things First: Parent Psychological Flexibility and Self-Compassion During COVID-19

text: The COVID-19 pandemic has brought about significant stress and anxiety for many parents around the world. Psychological flexibility and self-care are fundamental aspects of psychological health. For parents, shaping these processes may help promote family nurturance, support children’s prosocial behavior, and provide effective and consistent use of evidence-based parenting “kernels.” The goal of this article is to provide practitioners with evidence-based tools that will support psychological flexibility, self-care, and positive parenting behaviors in caregivers during COVID-19 and beyond.


title: Seasonal evaluation of bioaerosols from indoor air of residential apartments within the metropolitan area in South Korea

text: The aims of the present study were to determine the levels of bioaerosols including airborne culturable bacteria (total suspended bacteria, Gram-positive bacteria, Staphylococcus, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and Gram-negative bacteria), fungi, endotoxin, and viruses (influenza A, influenza B, respiratory syncytial virus types A/B, parainfluenza virus types 1/2/3, metapnemovirus, and adenovirus) and their seasonal variations in indoor air of residential apartments. Of the total suspended bacteria cultured in an indoor environment, Staphylococcus was dominant and occupied 49.0 to 61.3 % of indoor air. Among Staphylococcus, S. aureus were detected in 100 % of households' indoor air ranging from 4 to 140 CFU/m(3), and 66 % of households were positive for MRSA ranging from 2 to 80 CFU/m(3). Staphylococcus and S. aureus concentrations correlated with indoor temperature (adjusted β: 0.4440 and 0.403, p < 0.0001). Among respiratory viruses, adenovirus was detected in 14 (14 %) samples and influenza A virus was detected in 3 (3 %) samples regarding the indoor air of apartments. Adenovirus concentrations were generally higher in winter (mean concentration was 2,106 copies/m(3)) than in spring (mean concentration was 173 copies/m(3)), with concentrations ranging between 12 and 560 copies/m(3). Also, a strong negative correlation between adenovirus concentrations and relative humidity in indoor air was observed (r = −0.808, p < 0.01). Furthermore, temperature also negatively correlated with adenovirus concentrations (r = −0.559, p < 0.05).


title: Conferencia de Consenso sobre bronquiolitis aguda (II): epidemiología de la bronquiolitis aguda. Revisión de la evidencia científica

text: Resumen Presentamos una revisión de la evidencia sobre epidemiología, factores de riesgo, etiología y perfil clínico-etiológico de la bronquiolitis aguda. Las estimaciones de frecuencia son muy heterogéneas; para población menor de 2 años la frecuencia de ingreso por bronquiolitis se sitúa entre 1 y 3,5%, la de consultas en Atención Primaria entre 4 y 20% y la de Urgencias entre 1 y 2%. Para población de riesgo la frecuencia de ingresos por infección respiratoria por virus respiratorio sincitial es en prematuros de ≤32 semanas de gestación entre 4,4 y 18%, en niños con displasia broncopulmonar entre 7,3 y 42%, y en cardiópatas entre 1,6 y 9,8%. Los principales factores de riesgo son: prematuridad, enfermedad pulmonar o displasia broncopulmonar, las cardiopatías congénitas y la edad al inicio de la epidemia inferior a 3–6 meses. Otros factores son: hermanos mayores o asistencia a guardería, sexo masculino, exposición a tabaco, lactancia materna durante menos de 1–2 meses y variables asociadas a bajo nivel socioeconómico. El virus respiratorio sincitial es el agente etiológico dominante, constituyendo algo más de la mitad de los casos (mediana 56%; intervalo 27–73%). Otros virus implicados por orden descendente de frecuencia son los rinovirus, adenovirus, metapneumovirus, virus de la gripe, parainfluenza, enterovirus y bocavirus. En estudios que recurren a técnicas de detección genómica, el virus implicado no es identificado en un 20–25% de los casos; entre el 9% y el 27% de los casos presentan coinfección viral. Aunque las bronquiolitis por virus respiratorio sincitial tienen más sibilantes y trabajo respiratorio, mayor duración de síntomas y oxigenoterapia y se asocian a menor uso de antibióticos, estos datos están asociados a la menor edad de los pacientes y no permiten predecir la etiología. En general, la identificación etiológica no resulta útil de cara al manejo de los pacientes; no obstante, en lactantes pequeños (<3 meses) con bronquiolitis febriles en el medio hospitalario, podría facilitar el manejo conservador de dichos pacientes y ahorrar procedimientos diagnóstico y terapéuticos. Abstract A review of the evidence on epidemiology, risk factors, etiology and clinical-etiological profile of acute bronchiolitis is presented. The frequency estimates are very heterogeneous; in the population under two years the frequency of admission for bronchiolitis is between 1 and 3.5%, primary care consultations between 4 and 20% and emergency visits between 1 and 2%. The frequency of admissions for respiratory infection by respiratory syncytial virus in the risk population is: in premature infants ≤32 weeks of gestation between 4.4 and 18%, in patients with bronchopulmonary dysplasia between 7.3 and 42%, and in infants with congenital heart disease between 1.6 and 9.8%. The main risk factors are: prematurity, chronic lung disease or bronchopulmonary dysplasia, congenital heart disease and age less than 3–6 months at onset of the epidemic. Other factors are: older siblings or day care attendance, male gender, exposure to smoking, breastfeeding for less than 1–2 months and variables associated with lower socioeconomic status. Respiratory syncytial virus is the dominant etiological agent, constituting just over half the cases (median 56%; interval 27% to 73%). Other viruses implicated, in descending order of frequency, are rhinovirus, adenovirus, metapneumovirus, influenza viruses, parainfluenza, enterovirus and bocavirus. In studies with genomic detection techniques, between 20 and 25% of cases the virus involved is not identified and between 9% and 27% of cases have viral co-infection. Although respiratory syncytial virus bronchiolitis shows more wheezing and retractions, longer duration of respiratory symptoms and oxygen therapy and are associated with lower use of antibiotics. This pattern is associated with the younger age of the patients and does not help us to predict the etiology. In general, the etiological identification is not useful for the management of patients. However, in young infants (<3 months) with febrile bronchiolitis in the hospital environment, conservative management may help these patients and avoid diagnostic and therapeutic procedures.


title: A systematic review of neurological manifestations of SARS‐CoV‐2 infection: the devil is hidden in the details

text: BACKGROUND: We systematically reviewed available evidence for reports of neurological signs and symptoms in Coronavirus disease (COVID)‐19 patients to identify cases with severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection or immune‐mediated reaction in the nervous system. METHODS: We followed PRISMA guidelines and used the MEDLINE, EMBASE, Google Scholar, MedRxiv and ChinaXiv databases to search for papers on COVID‐19 and nervous system involvement which were published from January 1(st) to April 24(th) 2020. Data on design, sample size, neurologic assessment and related work‐up were extracted. Biases were assessed with the Newcastle‐Ottawa scale. RESULTS: We analysed 27 publications on potential neuroinvasive or parainfectious neurological complications of COVID‐19. The reports focused on smell and taste (n=5) and evaluation of neurological symptoms and signs in cohorts (n=5). There were cases of Guillain‐Barré syndrome/Miller‐Fisher syndrome/cranial neuropathy (7 cases), meningitis/encephalitis (9 cases) and various other conditions (5 cases). Patients with cerebrospinal fluid (CSF) examination and in particular SARS‐CoV‐2 PCR was negligible. Amongst, two had a positive SARS‐CoV‐2 PCR exam of CSF specimen. The study of potential parenchymal involvement with magnetic resonance imaging was rare. Only 4 reports received a rating for the highest quality standards. CONCLUSION: This systematic review failed to establish comprehensive insights to nervous system manifestations of COVID‐19 beyond immune‐mediated complications as aftermath of respiratory symptoms. The authors therefore provide guidance for more careful clinical, diagnostic and epidemiological studies to characterize the manifestations and burden of neurological disease caused by SARS‐CoV‐2 on behalf of the Infectious Disease Panel of the European Academy of Neurology.


Chloroquine and COVID-19: A Western Medical and Scientific Drift?


Potential changes to the hikikimori phenomenon in the wake of the Covid-19 pandemic


title: COVID-19 and surface water quality: Improved lake water quality during the lockdown

text: Abstract Human life comes to a standstill as many countries shut themselves off from the work due to the novel coronavirus disease pandemic (COVID-19) that hit the world severely in the first quarter of 2020. All types of industries, vehicle movement, and people's activity suddenly halted, perhaps for the first time in modern history. For a long time, it has been stated in various literature that the increased industrialization and anthropogenic activities in the last two decades polluted the atmosphere, hydrosphere, and biosphere. Since the industries and people's activities have been shut off for a month or more in many parts of the world, it is expected to show some improvement in the prevailing conditions in the aforementioned spheres of environment. Here, with the help of remote sensing images, this work quantitatively demonstrated the improvement in surface water quality in terms of suspended particulate matter (SPM) in the Vembanad Lake, the longest freshwater lake in India. The SPM estimated based on established turbidity algorithm from Landsat-8 OLI images showed that the SPM concentration during the lockdown period decreased by 15.9% on average (range: −10.3% to 36.4%, up to 8 mg/l decrease) compared with the pre-lockdown period. Time series analysis of satellite image collections (April 2013 – April 2020) showed that the SPM quantified for April 2020 is the lowest for 11 out of 20 zones of the Vembanad lake. When compared with preceding years, the percentage decrease in SPM for April 2020 is up to 34% from the previous minima.


title: COVID-19: The forgotten priorities of the pandemic

text: Abstract The zoonotic virus now named SARS-CoV-2 first infected humans in China, and COVID-19 has rapidly become pandemic. To mitigate its impact on societies, health systems and economies, countries have adopted non-pharmacological preventive practices such as ‘spatial’ or ‘social’ distancing, the use of protective masks, and handwashing; these have been widely implemented. However, measures aimed at protecting physical health and healthcare systems have side-effects that might have a big impact on individuals’ wellbeing. As the pandemic reaches low- and middle-income countries, weaker health systems, limited resources and the lower socioeconomic status of their populations make halting the pandemic more challenging. In this article, we explore the impact of COVID-19 and its prevention measures on the wellbeing of vulnerable populations. Special attention must be given to homeless, indigenous, migrant and imprisoned populations, as well as people living with disabilities and the elderly. More than just resolute governmental action will be required to overcome the pandemic. Links between science and political actions have to be strengthened. Fighting COVID-19 is a collective endeavour and community action, on a global scale, is of paramount importance.


title: Persistent Seoul virus infection in Lewis rats

text: Mechanistic studies of hantavirus persistence in rodent reservoirs have been limited by the lack of a versatile animal model. This report describes findings from experimental infection of inbred Lewis rats with Seoul virus strain 80–39. Rats inoculated with virus intraperitoneally at 6 days of age became persistently infected without clinical signs. Tissues from Seoul virus-inoculated 6-day-old rats were assessed at 6, 9, and 12 weeks post-inoculation for viral RNA by RT-PCR and in situ hybridization (ISH) and for infectious virus by inoculation of Vero E6 cells. Virus was isolated from lung and kidney of infected rats at 6 weeks and viral RNA was detected in lung, kidney, pancreas, salivary gland, brain, spleen, liver and skin at 6, 9 and 12 weeks. Rats inoculated with Seoul virus intraperitoneally at 10 or 21 days of age became infected without clinical signs but had low to undetectable levels of viral RNA in tissues at 6 weeks post-inoculation. ISH identified vascular smooth muscle and endothelial cells as common sites of persistent infection. Cultured rat smooth muscle cells and to a lesser extent cultured endothelial cells also were susceptible to Seoul virus infection. Pancreatic infection resulted in insulitis with associated hyperglycemia. These studies demonstrate that infant Lewis rats are uniformly susceptible to asymptomatic persistent Seoul virus infection. Additionally, they offer opportunities for correlative in vivo and in vitro study of Seoul virus interactions in host cell types that support persistent infection.


title: Interferons at age 50: past, current and future impact on biomedicine

text: The family of interferon (IFN) proteins has now more than reached the potential envisioned by early discovering virologists: IFNs are not only antivirals with a spectrum of clinical effectiveness against both RNA and DNA viruses, but are also the prototypic biological response modifiers for oncology, and show effectiveness in suppressing manifestations of multiple sclerosis. Studies of IFNs have resulted in fundamental insights into cellular signalling mechanisms, gene transcription and innate and acquired immunity. Further elucidation of the multitude of IFN-induced genes, as well as drug development strategies targeting IFN production via the activation of the Toll-like receptors (TLRs), will almost certainly lead to newer and more efficacious therapeutics. Our goal is to offer a molecular and clinical perspective that will enable IFNs or their TLR agonist inducers to reach their full clinical potential.


title: Dampened NLRP3-mediated inflammation in bats and implications for a special viral reservoir host

text: Bats are special in their ability to host emerging viruses. As the only flying mammal, bats endure high metabolic rates yet exhibit elongated lifespans. It is currently unclear whether these unique features are interlinked. The important inflammasome sensor, NLR family pyrin domain containing 3 (NLRP3), has been linked to both viral-induced and age-related inflammation. Here, we report significantly dampened activation of the NLRP3 inflammasome in bat primary immune cells compared to human or mouse counterparts. Lower induction of apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and secretion of interleukin-1β in response to both ‘sterile’ stimuli and infection with multiple zoonotic viruses including influenza A virus (−single-stranded (ss) RNA), Melaka virus (PRV3M, double-stranded RNA) and Middle East respiratory syndrome coronavirus (+ssRNA) was observed. Importantly, this reduction of inflammation had no impact on the overall viral loads. We identified dampened transcriptional priming, a novel splice variant and an altered leucine-rich repeat domain of bat NLRP3 as the cause. Our results elucidate an important mechanism through which bats dampen inflammation with implications for longevity and unique viral reservoir status.


title: Community-based programs to tackle environmental education and COVID-19: A case study from Millburn, New Jersey

text: Contextual and social realities must be built into any educational program for activism to take place. This case study examines an education and environment program which has adapted to the social distancing measures of COVID-19, resulting in an even more community-reliant and community-driven program than the program designers initially intended. The Eco Ambassador Program uses environmental activism within a space that supports mental health during COVID-19 social isolation. While community engagement and action have been elements of the program, the program has transformed to utilize new levels of social capital in the program’s network, to overcome the obstacles presented in regular programming. Many aspects of the critical pedagogy of space are utilized to conceptualize this educational program during the pandemic. The limitations of in-person interactions in defined learning spaces led to more technology-reliant programming, hence broadening the space of place-based learning, while enabling personal spaces and personal environments to become new learning spaces.


title: A Deep Learning System to Screen Novel Coronavirus Disease 2019 Pneumonia

text: The real-time reverse transcription-polymerase chain reaction (RT-PCR) detection of viral RNA from sputum or nasopharyngeal swab had a relatively low positive rate in the early stage of coronavirus disease 2019 (COVID-19). Meanwhile, the manifestations of COVID-19 as seen through computed tomography (CT) imaging show individual characteristics that differ from those of other types of viral pneumonia such as Influenza-A viral pneumonia (IAVP). This study aimed to establish an early screening model to distinguish COVID-19 pneumonia from IAVP and healthy cases through pulmonary CT images using deep learning techniques. A total of 618 CT samples were collected: 219 samples from 110 patients with COVID-19 (mean age 50 years; 63 (57.3%) male patients); 224 samples from 224 patients with IAVP (mean age 61 years; 156 (69.6%) male patients); and 175 samples from 175 healthy cases (mean age 39 years; 97 (55.4%) male patients). All CT samples were contributed from three COVID-19-designated hospitals in Zhejiang Province, China. First, the candidate infection regions were segmented out from the pulmonary CT image set using a 3D deep learning model. These separated images were then categorized into the COVID-19, IAVP, and irrelevant to infection (ITI) groups, together with the corresponding confidence scores, using a location-attention classification model. Finally, the infection type and overall confidence score for each CT case were calculated using the Noisy-or Bayesian function. The experimental result of the benchmark dataset showed that the overall accuracy rate was 86.7% in terms of all the CT cases taken together. The deep learning models established in this study were effective for the early screening of COVID-19 patients and were demonstrated to be a promising supplementary diagnostic method for frontline clinical doctors.


title: Vaccine Development for Nipah Virus Infection in Pigs

text: Nipah virus (NiV) causes a severe and often fatal neurological disease in humans. Whilst fruit bats are considered the natural reservoir, NiV also infects pigs and may cause an unapparent or mild disease. Direct pig-to-human transmission was responsible for the first and still most devastating NiV outbreaks in Malaysia and Singapore in 1998–99, with nearly 300 human cases and over 100 fatalities. Pigs can therefore play a key role in the epidemiology of NiV by acting as an “amplifying” host. The outbreak in Singapore ended with the prohibition of pig imports from Malaysia and the Malaysian outbreak was ended by culling 45% of the country's pig population with costs exceeding US$500 million. Despite the importance of NiV as an emerging disease with the potential for pandemic, no vaccines, or therapeutics are currently approved for human or livestock use. In this mini-review, we will discuss current knowledge of NiV infection in pigs; our ongoing work to develop a NiV vaccine for use in pigs; and the pig as a model to support human vaccine development.


title: Microbiota and probiotics in canine and feline welfare

text: Abstract Dogs and cats have been cohabiting with us for thousands of years. They are the major human companions. Today, dogs and cats live in urban areas. Cats and most dogs are on high carbohydrate diets and face similar life-style challenges as the human beings. The health and well-being of companion animals, just as their owners, depends on the gut microbes. Providing a proper care and nutritionally balanced diet to companion animals is recognised as a part of our responsibility to maintain the health and well being of our pet. However, as microbiota differences may facilitate exposure to pathogens and harmful environmental influences, it is prudent to search for novel tools to protect dogs and cats and at the same time the human owners from pathogens. Specific probiotic strains and/or their defined combinations may be useful in the canine and feline nutrition, therapy, and care. Probiotic supplementations have been successful in the prevention and treatment of acute gastroenteritis, treatment of IBD, and prevention of allergy in companion animals. New challenges for probiotic applications include maintenance of obesity and overweight, urogenital tract infections, Helicobacter gastritis and parasitic infections. The probiotics of human origin appear to be among the new promising tools for the maintenance of pets' health. However, the host-derived microorganisms might be the most appropriate probiotic source. Therefore, more controlled trials are needed to characterise new and safe probiotic preparations with an impact on general health and well being as well as health maintenance in dogs and cats.


title: An Opportunistic Pathogen Afforded Ample Opportunities: Middle East Respiratory Syndrome Coronavirus

text: The human coronaviruses (CoV) include HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1, some of which have been known for decades. The severe acute respiratory syndrome (SARS) CoV briefly emerged into the human population but was controlled. In 2012, another novel severely human pathogenic CoV—the Middle East Respiratory Syndrome (MERS)-CoV—was identified in the Kingdom of Saudi Arabia; 80% of over 2000 human cases have been recorded over five years. Targeted research remains key to developing control strategies for MERS-CoV, a cause of mild illness in its camel reservoir. A new therapeutic toolbox being developed in response to MERS is also teaching us more about how CoVs cause disease. Travel-related cases continue to challenge the world’s surveillance and response capabilities, and more data are needed to understand unexplained primary transmission. Signs of genetic change have been recorded, but it remains unclear whether there is any impact on clinical disease. How camels came to carry the virus remains academic to the control of MERS. To date, human-to-human transmission has been inefficient, but virus surveillance, characterisation, and reporting are key to responding to any future change. MERS-CoV is not currently a pandemic threat; it is spread mainly with the aid of human habit and error.


title: The COVID‐19 epidemic

text: The current outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; previously 2019-nCoV), epi-centered in Hubei Province of the People's Republic of China, has spread to many other countries. On January 30, 2020, the WHO Emergency Committee declared a global health emergency based on growing case notification rates at Chinese and international locations. The case detection rate is changing hourly and daily and can be tracked in almost real time on website provided by Johns Hopkins University [1] and other websites. As of early February 2020, China bears the large burden of morbidity and mortality, whereas the incidence in other Asian countries, in Europe and North America remains low so far.


title: Development of a degenerated TaqMan real‐time Q‐PCR for detection of bacteria‐free DNA in dialysis fluid

text: Bacterial‐derived DNA fragments (BDNAs) have been shown to be present in a dialysis fluid, to pass through dialyzer membranes, and to induce interleukin 6 (IL‐6) in mononuclear cells. DNA fragments are thought to be derived from microorganisms inhabiting hemodialysis water and fluid. The primary aim of the present study was to develop two degenerated TaqMan real‐time quantitative‐PCR (Q‐PCR) for detection of a broad range of bacterial DNA that specifically detect 16S ribosomal DNA (rDNA) (862 and 241 bp) and evaluate the efficiency of the Bellco Selecta resin to capture the BDNAs in the dialysis fluid. For this purpose, we decided to compare measurements of unfragmented samples (9.8 × 10(5) Escherichia coli genome) with artificially fragmented DNA samples. We assessed two broad‐range real‐time PCR targeting bacterial 16S rRNA genes for detection of fragmented and unfragmented bacterial DNA in the dialytic fluid and demonstrated that Bellco Selecta resin is capable of retaining these types of bacterial DNA.


title: DDESC: Dragon database for exploration of sodium channels in human

text: BACKGROUND: Sodium channels are heteromultimeric, integral membrane proteins that belong to a superfamily of ion channels. The mutations in genes encoding for sodium channel proteins have been linked with several inherited genetic disorders such as febrile epilepsy, Brugada syndrome, ventricular fibrillation, long QT syndrome, or channelopathy associated insensitivity to pain. In spite of these significant effects that sodium channel proteins/genes could have on human health, there is no publicly available resource focused on sodium channels that would support exploration of the sodium channel related information. RESULTS: We report here Dragon Database for Exploration of Sodium Channels in Human (DDESC), which provides comprehensive information related to sodium channels regarding different entities, such as "genes and proteins", "metabolites and enzymes", "toxins", "chemicals with pharmacological effects", "disease concepts", "human anatomy", "pathways and pathway reactions" and their potential links. DDESC is compiled based on text- and data-mining. It allows users to explore potential associations between different entities related to sodium channels in human, as well as to automatically generate novel hypotheses. CONCLUSION: DDESC is first publicly available resource where the information related to sodium channels in human can be explored at different levels. This database is freely accessible for academic and non-profit users via the worldwide web .


title: Quantifying SARS-CoV-2 transmission suggests epidemic control with digital contact tracing

text: The newly emergent human virus SARS-CoV-2 is resulting in high fatality rates and incapacitated health systems. Preventing further transmission is a priority. We analyzed key parameters of epidemic spread to estimate the contribution of different transmission routes and determine requirements for case isolation and contact-tracing needed to stop the epidemic. We conclude that viral spread is too fast to be contained by manual contact tracing, but could be controlled if this process was faster, more efficient and happened at scale. A contact-tracing App which builds a memory of proximity contacts and immediately notifies contacts of positive cases can achieve epidemic control if used by enough people. By targeting recommendations to only those at risk, epidemics could be contained without need for mass quarantines (‘lock-downs’) that are harmful to society. We discuss the ethical requirements for an intervention of this kind.


title: COVID‐19: Nasal and oropharyngeal swab

text: Performing a proper nasal and oropharyngeal swab procedure is essential in the screening of COVID‐19 infection. The video illustration of nasal and oropharyngeal swab is presented (Video S1). To correctly perform the nasopharyngeal swab, the patient must be seated comfortably with the back of their head against the headrest. The swab is inserted in the nose horizontally, along an imaginary line between the nostril and the ear. Oropharyngeal sampling is easier to perform. The swab is directed toward the rear wall of the oropharynx and it is rotated a few times before removal. After taking the sample, it is necessary to insert both swabs in the same tube, breaking the rod with one swift and controlled movement. Finally, carefully reset the cap. It appears to be extremely important to properly collect nasopharyngeal and oropharyngeal swabs in order to minimize the false negative rate among COVID‐19 positive patients.


title: A Survey Exploring Personalized Medicine among of Radiography Academics within the United Kingdom

text: INTRODUCTION: This article explores the application of personalized medicine (PM) within the academic environment in the United Kingdom. There is a growing acceptance of the utility of PM in health care and the role medical imaging can play. In response, this article explored the views and opinions of diagnostic and therapeutic academics and the utilization of PM in education. METHODS: This study primarily adopted a quantitative approach using an online survey. However, participants were also encouraged to provide qualitative comments in response to open-ended questions. The survey was distributed to radiography and radiotherapy academic departments, which received a response rate of 29%. RESULTS: The findings identify some important considerations. On the one hand some participants reported teaching PM on their programmes (24%, n = 16), whereas 30% (n = 20) did not. Importantly, the remaining academics (46%) were either unsure or did not know what PM was. This finding, coincided with qualitative commentary, highlights some discrepancies linked to knowledge and understanding of PM within higher education and highlights areas where academics may need additional support. CONCLUSION: This article concludes by recognizing the challenges of delivering PM by some academics. It is noted that although the findings cannot be fully generalized, it does highlight fragmented understanding of PM among academic staff. This is important to reflect upon following the increasing requirements for radiography to become “more personalized.”


title: Phosphonooxymethyl Prodrug of Triptolide: Synthesis, Physicochemical Characterization, and Efficacy in Human Colon Adenocarcinoma and Ovarian Cancer Xenografts

text: [Image: see text] A disodium phosphonooxymethyl prodrug of the antitumor agent triptolide was prepared from the natural product in three steps (39% yield) and displayed excellent aqueous solubility at pH 7.4 (61 mg/mL) compared to the natural product (17 μg/mL). The estimated shelf life (t(90)) for hydrolysis of the prodrug at 4 °C and pH 7.4 was found to be two years. In a mouse model of human colon adenocarcinoma (HT-29), the prodrug administered intraperitoneally was effective in reducing or eliminating xenograft tumors at dose levels as low as 0.3 mg/kg when given daily and at 0.9 mg/kg when given less frequently. When given via intraperitoneal and oral routes at daily doses of 0.6 and 0.9 mg/kg, the prodrug was also effective and well tolerated in a mouse model of human ovarian cancer (A2780).


title: Der erste COVID-19-Hotspot in einer Hamburger Senioreneinrichtung: Präventionskonzept, Letalität und Obduktionsbefunde

text: BACKGROUND: Coronavirus disease 2019 (COVID-19), a disease caused by the new coronavirus (SARS-CoV-2), is a particular threat to old people. At the end of March 2020, the first and so far largest outbreak of the disease occurred in a retirement home in Hamburg. METHODS: Analysis of procedures in dealing with a residential unit affected by SARS-CoV‑2, accommodating a risk group of 60 seniors with dementia is presented as well as a detailed presentation of post-mortem examination results of all 8 deceased tested positive for SARS-CoV‑2. RESULTS: Out of 60 residents, 39 were infected by SARS-CoV‑2. Due to preventive procedures it was possible to stop further spreading of the infection to other residential areas. In all 8 fatal cases, the autopsy diagnosis was death due to COVID-19. Autopsies revealed all COVID-19 patients to have a fatal (broncho)pneumonia and signs of relevant pre-existing cardiac, renal and pulmonary conditions in all cases. In 75% (n = 6) of the cases a fresh venous thrombosis was found. In 66.7% (n = 4) of the cases thrombotic events were combined with peripheral pulmonary artery thromboembolisms. CONCLUSION: The cohort of SARS-CoV‑2 infected residents of a nursing home is characteristic for clinical and epidemiological features of the new coronavirus disease. Due to a centralized evaluation of all fatalities at the Institute of Legal Medicine in Hamburg, a detailed examination of all deceased positive for SARS-CoV‑2 was possible. Thereby, increased case fatality rates of approximately 20% could in all cases be assigned to a relevant number of pre-existing comorbidities of multiple organ systems, which was consistent with the clinical data available.


Luminescence literature


title: The ProTide Prodrug Technology: From the Concept to the Clinic: Miniperspective

text: [Image: see text] The ProTide technology is a prodrug approach developed for the efficient intracellular delivery of nucleoside analogue monophosphates and monophosphonates. In this approach, the hydroxyls of the monophosphate or monophosphonate groups are masked by an aromatic group and an amino acid ester moiety, which are enzymatically cleaved-off inside cells to release the free nucleoside monophosphate and monophosphonate species. Structurally, this represents the current end-point of an extensive medicinal chemistry endeavor that spans almost three decades. It started from the masking of nucleoside monophosphate and monophosphonate groups by simple alkyl groups and evolved into the sophisticated ProTide system as known today. This technology has been extensively employed in drug discovery, and it has already led to the discovery of two FDA-approved (antiviral) ProTides. In this work, we will review the development of the ProTide technology, its application in drug discovery, and its role in the improvement of drug delivery and efficacy.


title: A Taxonomy Proposal for the Assessment of the Changes in Soundscape Resulting from the COVID-19 Lockdown

text: Many countries around the world have chosen lockdown and restrictions on people’s mobility as the main strategies to combat the COVID-19 pandemic. These actions have significantly affected environmental noise and modified urban soundscapes, opening up an unprecedented opportunity for research in the field. In order to enable these investigations to be carried out in a more harmonized and consistent manner, this paper makes a proposal for a set of indicators that will enable to address the challenge from a number of different approaches. It proposes a minimum set of basic energetic indicators, and the taxonomy that will allow their communication and reporting. In addition, an extended set of descriptors is outlined which better enables the application of more novel approaches to the evaluation of the effect of this new soundscape on people’s subjective perception.


title: Recommendations from the CSO-HNS taskforce on performance of tracheotomy during the COVID-19 pandemic

text: INTRODUCTION: The performance of tracheotomy is a common procedural request by critical care departments to the surgical services of general surgery, thoracic surgery and otolaryngology - head & neck surgery. A Canadian Society of Otolaryngology – Head & Neck Surgery (CSO-HNS) task force was convened with multi-specialty involvement from otolaryngology-head & neck surgery, general surgery, critical care and anesthesiology to develop a set of recommendations for the performance of tracheotomies during the COVID-19 pandemic. MAIN BODY: The tracheotomy procedure is highly aerosol generating and directly exposes the entire surgical team to the viral aerosol plume and secretions, thereby increasing the risk of transmission to healthcare providers. As such, we believe extended endotracheal intubation should be the standard of care for the entire duration of ventilation in the vast majority of patients. Pre-operative COVID-19 testing is highly recommended for any non-emergent procedure. CONCLUSION: The set of recommendations in this document highlight the importance of avoiding tracheotomy procedures in patients who are COVID-19 positive if at all possible. Recommendations for appropriate PPE and environment are made for COVID-19 positive, negative and unknown patients requiring consideration of tracheotomy. The safety of healthcare professionals who care for ill patients and who keep critical infrastructure operating is paramount.


Rates of symptomatic SARS-CoV-2 infection in patients with autoimmune liver diseases in Northern Italy: a telemedicine study


title: Design, synthesis and activity evaluation of mannose-based DC-SIGN antagonists

text: In this article, we describe the design, synthesis and activity evaluation of glycomimetic DC-SIGN antagonists, that use a mannose residue to anchor to the protein carbohydrate recognition domain (CRD). The molecules were designed from the structure of the known pseudo-mannobioside antagonist 1, by including additional hydrophobic groups, which were expected to engage lipophilic areas of DC-SIGN CRD. The results demonstrate that the synthesized compounds potently inhibit DC-SIGN-mediated adhesion to mannan coated plates. Additionally, in silico docking studies were performed to rationalize the results and to suggest further optimization. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11030-010-9285-y) contains supplementary material, which is available to authorized users.


title: Regulation of influenza virus replication by Wnt/β-catenin signaling

text: Wnt/β-catenin signaling is an essential pathway in cell cycle control. Dysregulation of the Wnt/β-catenin signaling pathway during viral infection has been reported. In this study, we examined the effect of modulating Wnt/β-catenin signaling during influenza virus infection. The activation of the Wnt/β-catenin pathway by Wnt3a increased influenza virus mRNA and virus production in in vitro in mouse lung epithelial E10 cells and mRNA expresson of influenza virus genes in vivo in the lungs of mice infected with influenza virus A/Puerto Rico/8/34. However, the inhibition of Wnt/β-catenin signaling by iCRT14 reduced virus titer and viral gene expression in human lung epithelial A549 cells and viral replication in primary mouse alveolar epithelial cells infected with different influenza virus strains. Knockdown of β-catenin also reduced viral protein expression and virus production. iCRT14 acts at the early stage of virus replication. Treatment with iCRT14 inhibited the expression of the viral genes (vRNA, cRNA and mRNA) evaluated in this study. The intraperitoneal administration of iCRT14 reduced viral load, improved clinical signs, and partially protected mice from influenza virus infection.


The “crisis after the crisis”: the time is now to prepare your radiology department


docid: gmznmdgh

title: Sex- and age-dependent association of SLC11A1 polymorphisms with tuberculosis in Chinese: a case control study

text: BACKGROUND: Host genetic factors are important determinants in tuberculosis (TB). The SLC11A1 (or NRAMP1) gene has been studied extensively for genetic association with TB, but with inconsistent findings. In addition, no study has yet looked into the effect of sex and age on the relationship between SLC11A1 polymorphisms and TB. METHODS: A case-control study was conducted. In total, 278 pulmonary TB patients and 282 sex- and age-matched controls without TB were recruited. All subjects were ethnic Chinese. On the basis of linkage disequilibrium pattern, three genetic markers from SLC11A1 and one from the nearby IL8RB locus were selected and examined for association with TB susceptibility. These markers were genotyped using single strand conformation polymorphism analysis or fragment analysis of amplified products. RESULTS: Statistically significant differences in allele (P = 0.0165, OR = 1.51) and genotype (P = 0.0163, OR = 1.59) frequencies of the linked markers SLC6a/b (classically called D543N and 3'UTR) of the SLC11A1 locus were found between patients and controls. With stratification by sex, positive associations were identified in the female group for both allele (P = 0.0049, OR = 2.54) and genotype (P = 0.0075, OR = 2.74) frequencies. With stratification by age, positive associations were demonstrated in the young age group (age ≤65 years) for both allele (P = 0.0047, OR = 2.52) and genotype (P = 0.0031, OR = 2.92) frequencies. All positive findings remained significant even after correction for multiple comparisons. No significant differences were noted in either the male group or the older age group. No significant differences were found for the other markers (one SLC11A1 marker and one IL8RB marker) either. CONCLUSION: This study confirmed the association between SLC11A1 and TB susceptibility and demonstrated for the first time that the association was restricted to females and the young age group.


title: In silico approach to screen compounds active against parasitic nematodes of major socio-economic importance

text: BACKGROUND: Infections due to parasitic nematodes are common causes of morbidity and fatality around the world especially in developing nations. At present however, there are only three major classes of drugs for treating human nematode infections. Additionally the scientific knowledge on the mechanism of action and the reason for the resistance to these drugs is poorly understood. Commercial incentives to design drugs that are endemic to developing countries are limited therefore, virtual screening in academic settings can play a vital role is discovering novel drugs useful against neglected diseases. In this study we propose to build robust machine learning model to classify and screen compounds active against parasitic nematodes. RESULTS: A set of compounds active against parasitic nematodes were collated from various literature sources including PubChem while the inactive set was derived from DrugBank database. The support vector machine (SVM) algorithm was used for model development, and stratified ten-fold cross validation was used to evaluate the performance of each classifier. The best results were obtained using the radial basis function kernel. The SVM method achieved an accuracy of 81.79% on an independent test set. Using the model developed above, we were able to indentify novel compounds with potential anthelmintic activity. CONCLUSION: In this study, we successfully present the SVM approach for predicting compounds active against parasitic nematodes which suggests the effectiveness of computational approaches for antiparasitic drug discovery. Although, the accuracy obtained is lower than the previously reported in a similar study but we believe that our model is more robust because we intentionally employed stringent criteria to select inactive dataset thus making it difficult for the model to classify compounds. The method presents an alternative approach to the existing traditional methods and may be useful for predicting hitherto novel anthelmintic compounds.


docid: fxlqxmci

title: Stewardship opportunities in viral pneumonia: Why not the immunocompromised?

text: Antimicrobial management of viral pneumonia has proven to be a challenge in hospitalized immunocompromised patients. A host of factors contribute to the dilemma, such as diagnostic uncertainty, lack of organism identification, and clinical status of the patient. Respiratory virus panel (RVP) use was compared between 131 immunocompromised patients who received send‐out (n = 56) vs in‐house (n = 75) testing. Antimicrobial optimization interventions consisted of antiviral addition/discontinuation, antibiotic discontinuation/de‐escalation, or modification of immunosuppressive regimen. After implementation of an in‐house test with audit and feedback, turnaround time of the RVP was reduced from 46.7 to 5.5 hours (P < .001) and time to intervention was reduced from 52.1 to 13.9 hours (P < .001), yet the frequency of antimicrobial optimization interventions was unchanged (30.7% vs 35.7%). Differences were not observed in duration of empiric antibiotic therapy or length of stay. The overall discontinuation rate for patients tested with a RVP was low (4.6%), and those with positive RVP (n = 43) had antibiotics stopped in 14% of cases. Bacterial pneumonia coinfection was confirmed in 2 patients. Further systematic efforts should be taken to reduce antibiotic use in viral pneumonia and identify the major barriers in the immunocompromised population.


title: Inhibitors of SARS-CoV-2 Entry: Current and Future Opportunities

text: [Image: see text] Recently, a novel coronavirus initially designated 2019-nCoV but now termed SARS-CoV-2 has emerged and raised global concerns due to its virulence. SARS-CoV-2 is the etiological agent of “coronavirus disease 2019”, abbreviated to COVID-19, which despite only being identified at the very end of 2019, has now been classified as a pandemic by the World Health Organization (WHO). At this time, no specific prophylactic or postexposure therapy for COVID-19 are currently available. Viral entry is the first step in the SARS-CoV-2 lifecycle and is mediated by the trimeric spike protein. Being the first stage in infection, entry of SARS-CoV-2 into host cells is an extremely attractive therapeutic intervention point. Within this review, we highlight therapeutic intervention strategies for anti-SARS-CoV, MERS-CoV, and other coronaviruses and speculate upon future directions for SARS-CoV-2 entry inhibitor designs.


title: Anxiety and public responses to covid-19: Early data from Thailand

text: Any new pandemic has the potential to arouse considerable anxiety, with this anxiety associated in previous work with economic disruption and societal disruption. We examined anxiety, symptom awareness, trust and associated behavioural responses in the first three weeks of the SARS-CoV-2 (covid-19) outbreak in Thailand. We collected data on-street at randomly selected locations in Bangkok. Of 274 potential respondents, 203 (74.7%) responded. A four-item measure assessed anxiety, with open-ended questions assessing knowledge of symptoms, trusted information sources and measures taken to avoid infection. Respondents reported good awareness of the prime symptoms of the Coronovirus. Binary logistic regressions controlling for sex and age found the more anxious avoided the Chinese, people who were coughing, crowded places and public transport or flying. Younger respondents reported greater trust in foreign media and older populations information from national government. Trust in doctors online was positively associated with handwashing, avoidance of coughing people and keeping fit; trust in national government with avoiding coughing people, keeping fit, avoiding public transport and avoiding Chinese people. We conclude that anxiety can motivate both desirable and undesirable behaviours during pandemic outbreaks. Effective and targeted communication by trusted sources is needed to motivate preventive actions but also limit unnecessary or disruptive behaviours.


COVID-19, Ethics and Equity—What Is Our Role as Surgeons?


docid: owoksyol

title: Standardization of enzyme-linked immunosorbent assays for serosurveys of the SARS-CoV-2 pandemic using clinical and at-home blood sampling

text: The extent of SARS-CoV-2 infection throughout the United States population is currently unknown. High quality serology is a key tool to understanding the spread of infection, immunity against the virus, and correlates of protection. Limited validation and testing of serology assays used for serosurveys can lead to unreliable or misleading data, and clinical testing using such unvalidated assays can lead to medically costly diagnostic errors and improperly informed public health decisions. Estimating prevalence and clinical decision making is highly dependent on specificity. Here, we present an optimized ELISA-based serology protocol from antigen production to data analysis. This protocol defines thresholds for IgG and IgM for determination of seropositivity with estimated specificity well above 99%. Validation was performed using both traditionally collected serum and dried blood on mail-in blood sampling kits, using archival (pre-2019) negative controls and known PCR-diagnosed positive patient controls. Minimal cross-reactivity was observed for the spike proteins of MERS, SARS1, OC43 and HKU1 viruses and no cross reactivity was observed with anti-influenza A H1N1 HAI titer during validation. This strategy is highly specific and is designed to provide good estimates of seroprevalence of SARS-CoV-2 seropositivity in a population, providing specific and reliable data from serosurveys and clinical testing which can be used to better evaluate and understand SARS-CoV-2 immunity and correlates of protection.


title: The first report of Hepatozoon canis infection of a dog in Iran

text: An 11-year-old male dog was presented with a 1-week history of inappetence, weight loss and hind limb paralysis. Physical examination revealed weakness, depression, incoordination of the posterior limbs, peripheral lymphadenopathy and pale mucous membranes. Laboratory analysis of blood samples revealed anaemia, thrombocytopenia and low serum albumin concentration. The diagnosis was confirmed microscopically, by demonstrating the presence of Hepatozoon canis gametocytes within neutrophils in Giemsa-stained peripheral blood smears and bone marrow smear. Also, schizonts of H. canis were seen in tissue sections of muscles, lymph nodes, spleen and liver. To the best of authors’ knowledge, this is the first description of H. canis infection in a dog in Iran.


title: Evidence of a Novel Human Coronavirus That Is Associated with Respiratory Tract Disease in Infants and Young Children

text: Background. The etiological agents responsible for a substantial proportion of respiratory tract diseases have not been identified. We sought to determine whether novel human coronaviruses (HCoVs) are circulating in New Haven, Connecticut, and, if so, whether they are associated with respiratory tract disease in infants and young children. Methods. We developed a polymerase chain reaction (PCR)-based approach for screening specimens from the respiratory tracts of symptomatic children. PCR probes that target regions of the replicase 1a gene that are conserved among genetically diverse animal CoVs and HCoVs were designed. Using these probes, we identified genomic sequences of a novel HCoV, designated “New Haven coronavirus” (HCoV-NH). Thereafter, we designed specific probes to screen respiratory specimens from children <5 years old for this novel HCoV. Clinical features associated with HCoV-NH infection were identified. Results. Seventy-nine (8.8%) of 895 children tested positive for HCoV-NH. Cough, rhinorrhea, tachypnea, fever, abnormal breath sounds, and hypoxia were the most common findings associated with HCoV-NH infection. Sequence analysis revealed that HCoV-NH is closely related to a novel HCoV recently reported in The Netherlands. Conclusions. The novel HCoVs identified in New Haven and The Netherlands are similar and likely represent the same species. This newly discovered virus may have worldwide distribution and may account for a significant proportion of respiratory tract disease in infants and young children.


docid: uxewsyli

title: Further Studies on Aminopeptidase-M in Blood in Children with Cholestatic Liver Diseases and Viral Hepatitis

text: Aim of this study was to determine and furthercharacterize the serum aminopeptidase-M in children withliver diseases. Based on our new assay, we have showntwo fractions of the enzyme. Activity of the first fraction is expressed in undiluted serumat pH adjusted from 8.5 (pH of storaged serum) to 7.4.Activity of the second fraction (cryptic activity)appears in the serum (pH 7.4) as a result of dilution and/or addition of aniline naphthalene sulfonicacid. In children with Alagille syndrome, extrahepaticbiliary duct atresia, Byler's disease, and acutehepatitis due to hepatitis B virus infection, activities of both fractions are highly elevated ascompared to healthy children or those with chronic viralhepatitis. Moreover, serum aminopeptidase-M seems toreflect other aspects of the pathological process than those reflected by the alanine aminotransferaseand gamma-glutamyltranspeptidase. Due to increasedactivity and broad substrate specificity, the enzymeseems to be also a cofactor of cholestasis andhepatitis.


docid: dvfeosgt

title: Imaging and clinical features of patients with 2019 novel coronavirus SARS‐CoV‐2: A systematic review and meta‐analysis

text: BACKGROUND: Currently, the epidemic of coronavirus disease 2019 (COVID‐19) has begun to spread worldwide. We aim to explore reliable evidence for the diagnosis and treatment of the COVID‐19 by analyzing all the published studies by Chinese scholars on the clinical and imaging features in novel coronavirus pneumonia caused by SARS‐CoV‐2. METHODS: We searched five medical databases including two Chinese and three English databases for all published articles on COVID‐19 since the outbreak. A random‐effects model was designed, and the imaging and clinical data from all studies were collected for meta‐analysis. RESULTS: Overall, 31 articles and 46 959 patients were included, including 10 English articles and 21 Chinese articles. The results of meta‐analysis showed that the most common clinical manifestations were fever (87.3%; 0.838‐0.909), cough (58.1%; 0.502‐0.660), dyspnea (38.3%; 0.246‐0.520), muscle soreness or fatigue (35.5%; 0.253‐0.456), and chest distress (31.2%; −0.024 to 0.648). The main imaging findings were bilateral pneumonia (75.7%; 0.639‐0.871) and ground‐glass opacification (69.9%; 0.602‐0.796). Among the patients, the incidence that required intensive care unit (ICU) was (29.3%; 0.190‐0.395), the incidence with acute respiratory distress syndrome was (28.8%; 0.147‐0.429), the incidence with multiple organ dysfunction syndrome was (8.5%; −0.008 to 0.179), and the case fatality rate of patients with COVID‐19 was (6.8%; 0.044‐0.093). CONCLUSION: COVID‐19 is a new clinical infectious disease that mainly causes bilateral pneumonia and lung function deteriorates rapidly. Nearly a third of patients need to be admitted to the ICU, and patients are likely to present respiratory failure or even death.


title: Letter to the Editor: Are severe COVID‐19 patients more susceptible to conjunctivitis?

text: We read with interest the article by Lorenzo et al On Conjunctivitis and COVID-19: a meta analysis. We appreciate the article's suggestions on protection in ophthalmic diagnosis and treatment, but believe that the data and conclusions in meta-analysis need further study. This article is protected by copyright. All rights reserved.


title: Chapter 12. Antiviral Agents

text: Publisher Summary This chapter discusses the agents with activity primarily against RNA viruses. The communicable diseases of the respiratory tract are probably the most common cause of symptomatic human infections. The viruses that are causative agents for human respiratory disease comprise the five taxonomically distinct families: orthomyxoviridae, paramyxoviridae, picornaviridae, coronaviridae, and adenoviridae. The influenza viruses, which consist of types A, B, and C, belong to the family orthomyxoviridae. Types A and B have been associated with significant increases in mortality during epidemics. The disease may be asymptomatic or cause symptoms ranging from the common cold to fatal pneumonia. Immunization against influenza has been recommended for high-risk groups and antiviral chemotherapy (amantadine) is available for the treatment and prophylaxis of all influenza A infections. There is both a great need for and interest in developing a chemotherapeutic agent for the treatment of these two viral, respiratory tract pathogens. The family picornaviridae contains the genus Rhinovirus that is composed of over a hundred distinct serotypes. Amantadine and rimantadine are specifically active against influenza A virus infections. The amantadine recipients reported a higher incidence of side effects largely attributed to the central nervous system (CNS) symptoms. This difference in side effects may be a pharmacokinetic phenomenon that results in higher plasma concentrations of amantadine. Significant progress continues to be made in the clinical use and development of agents active against DNA viruses. Acyclovir (9-(2-h droxyethoxymethyl)guanine) has been the subject of several reviews and of a syrnposium. Considerable progress has been made in evaluating the clinical promise of acyclovir; however, there remains much to be learned concerning the best use of this drug in clinical practice. Significant strides have been made in the development of clinically useful antiviral agents, especially against the DNA viruses of the herpes family. Most of these agents are directed against viral nucleic acid synthesis and require activation by a virus-induced thymidine kinase. Researchers have begun to focus on other strategies that may produce broader spectrum anti-viral agents with different mechanisms of action.


title: Elevated levels of plasma cytokines in COVID-19 reflect viral load and lung injury

text: This article was published early due to publisher error and has been temporarily removed. The publisher apologizes for the error.


title: COVID-19 outbreak on the Diamond Princess cruise ship: estimating the epidemic potential and effectiveness of public health countermeasures

text: BACKGROUND: Cruise ships carry a large number of people in confined spaces with relative homogeneous mixing. On 3 February, 2020, an outbreak of COVID-19 on cruise ship Diamond Princess was reported with 10 initial cases, following an index case on board around 21-25(th) January. By 4(th) February, public health measures such as removal and isolation of ill passengers and quarantine of non-ill passengers were implemented. By 20(th) February, 619 of 3,700 passengers and crew (17%) were tested positive. METHODS: We estimated the basic reproduction number from the initial period of the outbreak using SEIR models. We calibrated the models with transient functions of countermeasures to incidence data. We additionally estimated a counterfactual scenario in absence of countermeasures, and established a model stratified by crew and guests to study the impact of differential contact rates among the groups. We also compared scenarios of an earlier versus later evacuation of the ship. RESULTS: The basic reproduction rate was initially 4 times higher on-board compared to the [Formula: see text] in the epicentre in Wuhan, but the countermeasures lowered it substantially. Based on the modeled initial [Formula: see text] of 14.8, we estimated that without any interventions within the time period of 21 January to 19 February, 2920 out of the 3700 (79%) would have been infected. Isolation and quarantine therefore prevented 2307 cases, and lowered the [Formula: see text] to 1.78. We showed that an early evacuation of all passengers on 3 February would have been associated with 76 infected persons in their incubation time. CONCLUSIONS: Conclusions: The cruise ship conditions clearly amplified an already highly transmissible disease. The public health measures prevented more than 2000 additional cases compared to no interventions. However, evacuating all passengers and crew early on in the outbreak would have prevented many more passengers and crew from infection.


title: Adipogenesis in ducks interfered by small interfering ribonucleic acids of peroxisome proliferator-activated receptor γ gene

text: ABSTRACT Peroxisome proliferator-activated receptor γ (PPARγ) participates in adipocyte differentiation and maintenance, including the promotion of lipid storage in mammals. In the present study, 3 duck PPARγ small interfering RNA (siRNA) expression plasmids were constructed to investigate the effect of downregulating the expression of PPARγ on adipogenesis and fat accumulation in ducks. The results indicate that the 3 siRNA specific for conserved regions of PPARγ can effectively inhibit expression of PPARγ. It was demonstrated that the expression of lipoprotein lipase and adipocyte fatty acid-binding protein in duck adipose tissue is repressed when the expression of PPARγ is downregulated by siRNA. At the same time, the weight of abdominal fat at 21 and 35 d of age is decreased significantly (P < 0.05) compared with the control. However, the triglyceride levels in serum and muscle are not affected when the mRNA of PPARγ is repressed. The current study indicates that the suppression of PPARγ reduces abdominal fat deposition and regulates adipogenesis in ducks.


title: Using Artificial Intelligence in Infection Prevention

text: PURPOSE OF REVIEW: Artificial intelligence (AI) offers huge potential in infection prevention and control (IPC). We explore its potential IPC benefits in epidemiology, laboratory infection diagnosis, and hand hygiene. RECENT FINDINGS: AI has the potential to detect transmission events during outbreaks or predict high-risk patients, enabling development of tailored IPC interventions. AI offers opportunities to enhance diagnostics with objective pattern recognition, standardize the diagnosis of infections with IPC implications, and facilitate the dissemination of IPC expertise. AI hand hygiene applications can deliver behavior change, though it requires further evaluation in different clinical settings. However, staff can become dependent on automatic reminders, and performance returns to baseline if feedback is removed. SUMMARY: Advantages for IPC include speed, consistency, and capability of handling infinitely large datasets. However, many challenges remain; improving the availability of high-quality representative datasets and consideration of biases within preexisting databases are important challenges for future developments. AI in itself will not improve IPC; this requires culture and behavior change. Most studies to date assess performance retrospectively so there is a need for prospective evaluation in the real-life, often chaotic, clinical setting. Close collaboration with IPC experts to interpret outputs and ensure clinical relevance is essential.


SARS-Cov-2 outbreak-imposed medical isolation increased sleep problems


docid: wloahziy

title: IL‐1 blockade with anakinra in acute leukaemia patients with severe COVID‐19 pneumonia appears safe and may result in clinical improvement

text: As of 17th May, 2020 the number of patients infected by coronavirus disease 2019 (COVID‐19) worldwide has exceeded 4.5 million (WHO 2020). A subgroup of patients with COVID‐19 pneumonia develop a hyperinflammatory syndrome which has a similar cytokine release profile to secondary haemophagocytic lymphohistiocytosis (HLH) (Huang, et al 2020). Immunomodulatory drugs are hypothesised to abrogate the dysfunctional immune response in hyperinflammatory COVID‐19 and are currently being investigated in clinical trials. IL‐1 blockage with anakinra has been shown to be safe and is associated with clinical improvement in patients with hyperinflammatory COVID‐19 (Cavalli, et al 2020).


title: Constructing and transient expression of a gene cassette containing edible vaccine elements and shigellosis, anthrax and cholera recombinant antigens in tomato

text: Shigella dysenteriae causing shigellosis is one of the diseases that threaten the health of human society in the developing countries. In Shigella, IpaD gene is one of the key pathogenic genes causing strong mucosal immune system reactions. Anthrax disease is caused by Bacillus anthracis. PA protective antigen is one of the subunits in anthrax toxin complex responsible for the transfer of other subunits into the cytosol of host cells. The 20 kDa subunit of PA (PA20) has the property of immunogenicity. CTxB or B subunit of Vibrio cholerae toxin (CT) is a non-toxic protein and has the function to transfer toxic subunit into cytosol of the host cells by binding to GM1 receptor. The aim of this study was to fuse PA20, ipaD and CTxB and transform tomato plants by this cassette in order to produce an oral vaccine against shigellosis, anthrax and cholera. CTxB was used for these two antigens as an immune adjuvant. IpaD and PA20 genes were cloned in pBI121 containing the CTxB gene and Extensin signal peptide. In order to evaluate the transient expression of Shigellosis, Anthrax and Cholera antigens, agro-infiltrated tomato tissues were inoculated with Agrobacterium tumefaciens containing the gene cassette. Cloning was confirmed by PCR, enzymatic digestion and sequencing techniques. Expression of the antigens was examined by SDS-PAGE, dot blot and ELISA. Maturate green fruits demonstrated the highest expression of the recombinant proteins. The first phase of this study was carried out for cloning and expressing of CtxB, ipaD and PA20 antigens in tomato. In the next phase, we aim to analyze the immunogenicity of this vaccine candidate in laboratory animals.


title: Highly Conserved Homotrimer Cavity Formed by the SARS-CoV-2 Spike Glycoprotein: A Novel Binding Site

text: An important stage in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) life cycle is the binding of the spike (S) protein to the angiotensin converting enzyme-2 (ACE2) host cell receptor. Therefore, to explore conserved features in spike protein dynamics and to identify potentially novel regions for drugging, we measured spike protein variability derived from 791 viral genomes and studied its properties by molecular dynamics (MD) simulation. The findings indicated that S2 subunit (heptad-repeat 1 (HR1), central helix (CH), and connector domain (CD) domains) showed low variability, low fluctuations in MD, and displayed a trimer cavity. By contrast, the receptor binding domain (RBD) domain, which is typically targeted in drug discovery programs, exhibits more sequence variability and flexibility. Interpretations from MD simulations suggest that the monomer form of spike protein is in constant motion showing transitions between an “up” and “down” state. In addition, the trimer cavity may function as a “bouncing spring” that may facilitate the homotrimer spike protein interactions with the ACE2 receptor. The feasibility of the trimer cavity as a potential drug target was examined by structure based virtual screening. Several hits were identified that have already been validated or suggested to inhibit the SARS-CoV-2 virus in published cell models. In particular, the data suggest an action mechanism for molecules including Chitosan and macrolides such as the mTOR (mammalian target of Rapamycin) pathway inhibitor Rapamycin. These findings identify a novel small molecule binding-site formed by the spike protein oligomer, that might assist in future drug discovery programs aimed at targeting the coronavirus (CoV) family of viruses.


Duty of care and health worker protections in the age of Ebola: lessons from Médecins Sans Frontières


title: Sequence analysis of the nucleoprotein genes of three enterotropic strains of murine coronavirus

text: The nucleotide sequences of the nucleoprotein genes of three enterotropic strains of the murine coronavirus mouse hepatitis virus (MHV-Y, MHV-RI and DVIM) were determined and compared with previously reported sequences of three polytropic (respiratory) strains (MHV-A59, MHV-JHM and MHV-S). Greater than 92% homology was found among the six strains by pair-wise comparison at the nucleotide level. The genes encoded proteins of 451 to 455 residues and the deduced amino acid sequences were more than 91% homologous. A unique deletion of twelve nucleotides was found at the carboxy terminus of MHV-Y and a three nucleotide deletion was found in MHV-RI, which corresponded to the one previously reported in MHV-A59 and MHV-S. Two internal open reading frames were found within the coding region of the nucleoprotein, the smaller one was specific for the enterotropic strains. It could potentially encode a truncated version of the hypothetical protein described for MHV-A59 and MHV-S. Sequence relationship of the N gene showed no correlation with tissue tropism and no sequence or even single amino acid change unique to either tropism group was found. This indicates that the nucleoprotein of MHV probably has no part in the determination of the primary tissue tropism of an MHV strain. The role of the potential internal protein warrants further investigation.


title: A Crimean-Congo hemorrhagic fever (CCHF) viral vaccine expressing nucleoprotein is immunogenic but fails to confer protection against lethal disease

text: Crimean-Congo Hemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in many countries in Africa, the Middle East, Eastern Europe and Asia. Between 15–70% of reported cases are fatal with no approved vaccine available. In the present study, the attenuated poxvirus vector, Modified Vaccinia virus Ankara, was used to develop a recombinant candidate vaccine expressing the CCHF virus nucleoprotein. Cellular and humoral immunogenicity was confirmed in 2 mouse strains, including type I interferon receptor knockout mice, which are susceptible to CCHF disease. Despite the immune responses generated post-immunisation, the vaccine failed to protect animals from lethal disease in a challenge model.


title: Community‐acquired respiratory viruses and co‐infection among patients of Ontario sentinel practices, April 2009 to February 2010

text: Please cite this paper as: Peci et al. (2012) Community‐acquired respiratory viruses and co‐infection among patients of Ontario Sentinel practices, April 2009 to February 2010. Influenza and Other Respiratory Viruses 7(4), 559–566. Background Respiratory viruses are known to cocirculate but this has not been described in detail during an influenza pandemic. Objectives To describe respiratory viruses, including co‐infection and associated attributes such as age, sex or comorbidity, in patients presenting with influenza‐like illness to a community sentinel network, during the pandemic A(H1N1)pdm09 in Ontario, Canada. Methods Respiratory samples and epidemiologic details were collected from 1018 patients with influenza‐like illness as part of respiratory virus surveillance and a multiprovincial case–control study of influenza vaccine effectiveness. Results At least one virus was detected in 668 (65·6%) of 1018 samples; 512 (50·3%) had single infections and 156 (15·3%) co‐infections. Of single infections, the most common viruses were influenza A in 304 (59·4%) samples of which 275 (90·5%) were influenza A(H1N1)pdm09, and enterovirus/rhinovirus in 149 (29·1%) samples. The most common co‐infections were influenza A and respiratory syncytial virus B, and influenza A and enterovirus/rhinovirus. In multinomial logistic regression analyses adjusted for age, sex, comorbidity, and timeliness of sample collection, single infection was less often detected in the elderly and co‐infection more often in patients <30 years of age. Co‐infection, but not single infection, was more likely detected in patients who had a sample collected within 2 days of symptom onset as compared to 3–7 days. Conclusions Respiratory viral co‐infections are commonly detected when using molecular techniques. Early sample collection increases likelihood of detection of co‐infection. Further studies are needed to better understand the clinical significance of viral co‐infection.


title: Hematopoietic cellular aging is not accelerated during the first 2 years of life in children born preterm

text: BACKGROUND: Prematurity in itself and exposure to neonatal intensive care triggers inflammatory processes and oxidative stress, leading to risk for disease later in life. The effects on cellular aging processes are incompletely understood. METHODS: Relative telomere length (RTL) was measured by qPCR in this longitudinal cohort study with blood samples taken at birth and at 2 years of age from 60 children (16 preterm and 44 term). Viral respiratory infections the first year were evaluated. Epigenetic biological DNA methylation (DNAm) age was predicted based on methylation array data in 23 children (11 preterm and 12 term). RTL change/year and DNAm age change/year was compared in preterm and term during the 2 first years of life. RESULTS: Preterm infants had longer telomeres than term born at birth and at 2 years of age, but no difference in telomere attrition rate could be detected. Predicted epigenetic DNAm age was younger in preterm infants, but rate of DNAm aging was similar in both groups. CONCLUSIONS: Despite early exposure to risk factors for accelerated cellular aging, children born preterm exhibited preserved telomeres. Stress during the neonatal intensive care period did not reflect accelerated epigenetic DNAm aging. Early-life aging was not explained by preterm birth. IMPACT: Preterm birth is associated with elevated disease risk later in life. Preterm children often suffer from inflammation early in life. Stress-related telomere erosion during neonatal intensive care has been proposed. Inflammation-accelerated biological aging in preterm is unknown. We find no accelerated aging due to prematurity or infections during the first 2 years of life.


docid: gneuzgts

title: Education as the path to a sustainable recovery from COVID-19

text: COVID-19 has disrupted education for millions of children across the globe. The education community is re-imagining and re-designing to build back better. This Viewpoint takes the principles behind UNESCO’s Futures of Education initiative to highlight their importance in post-COVID-19 recovery. The pandemic has shown how communities can come together to educate children. The article argues that, post-COVID-19, education systems should recognize community-driven support systems, use technology to overcome the digital divide in learning, and focus more on SDG 4.7 and its links to climate crises.


title: One Health concept for strengthening public health surveillance and response through Field Epidemiology and Laboratory Training in Ghana

text: The lack of highly trained field epidemiologists in the public health system in Ghana has been known since the 1970s when the Planning Unit was established in the Ghana Ministry of Health. When the Public Health School was started in 1994, the decision was taken to develop a 1 academic-year general MPH course. The persisting need for well-trained epidemiologists to support the public health surveillance, outbreak investigation and response system made the development of the Field Epidemiology and Laboratory Training Programme (FELTP) a national priority. The School of Public health and the Ministry of Health therefore requested the technical and financial assistance of the United States Centers for Disease Control and Prevention (CDC) in organizing the Programme. The collaboration started by organizing short courses in disease outbreak investigations and response for serving Ghana Health Service staff. The success of the short courses led to development of the FELTP. By October 2007, the new FELTP curriculum for the award of a Masters of Philosophy in Applied Epidemiology and Disease Control was approved by the Academic Board of the University of Ghana and the programme started that academic year. Since then five cohorts of 37 residents have been enrolled in the two tracks of the programme. They consist of 12 physicians, 12 veterinarians and 13 laboratory scientists. The first two cohorts of 13 residents have graduated. The third cohort of seven has submitted dissertations and is awaiting the results. The fourth cohort has started the second year of field placement while the fifth cohort has just started the first semester. The field activities of the graduates have included disease outbreak investigations and response, evaluation of disease surveillance systems at the national level and analysis of datasets on diseases at the regional level. The residents have made a total of 25 oral presentations and 39 poster presentations at various regional and global scientific conferences. The Ghana FELTP (GFELTP) has promoted the introduction of the One Health concept into FELTP. It hosted the first USAID–supported workshop in West Africa to further integrate and strengthen collaboration of the animal and human health sectors in the FETP model. GFELTP has also taken the lead in hosting the first AFENET Center for Training in Public Health Leadership and Management, through which the short course on Management for Improving Public Health Interventions was developed for AFENET member countries. The GFELTP pre-tested the Integrated Avian Influenza Outbreak and Pandemic Influenza course in preparation for introducing the materials into the curriculum of other FELTP in the network. The leadership positions to which the graduates of the program have been appointed in the human and animal Public Health Services, improvement in disease surveillance, outbreak investigation and response along with the testimony of the health authorities about their appreciation of the outputs of the graduates at various fora, is a strong indication that the GFELTP is meeting its objectives.


title: Knocking Out Angiotensin II in the Heart

text: Despite ongoing medical advances, cardiovascular disease continues to be a leading health concern. The renin-angiotensin system (RAS) plays an important role in regulating cardiovascular function, and is, therefore, the subject of extensive study. Several drugs currently used to treat hypertension and heart failure are designed to target angiotensin II synthesis and function, but thus far, none have been able to completely block the effects of RAS signaling. This review discusses current and emerging approaches towards inhibiting cardiac RAS function in order to further improve cardiovascular disease outcomes.


docid: nomfciyu

title: Middle East respiratory syndrome: pathogenesis and therapeutic developments

text: The first case of Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in the year 2012, which spread rapidly and increased to more than 2200 in 2018. This highly pathogenic virus with high mortality rate is among one of the major public health concerns. Saudi Arabia remains to be the most affected region with the majority of MERS-CoV cases, and currently, no effective drugs and vaccines are available for prevention and treatment. A large amount of information is now available regarding the virus, its structure, route of transmission and its pathophysiology. Therefore, this review summarizes the current understanding of MERS-CoV's pathogenesis, treatment options and recent scientific advancements in vaccine and other therapeutic developments, and the major steps taken for MERS prevention control.


title: Gut Brain Axis and Its Microbiota Regulation in Mammals and Birds

text: This article provides a brief overview of the advances made in microbiota research in parrots and pet birds. It describes this complex ecosystem and the contribution of the intestinal microbiota to host health and disease, including the nervous system.


title: Inpatient Dermatology Consultations during Covid 19 Pandemic in a Tertiary Referral Center

text: Since the COVID‐19 infection first appeared in December 2019, patient profile of outpatient and inpatient clinics have changed. Various cutaneous findings associated with COVID‐19 have been reported in the literature. The main objective of this study was to describe and analyze the profile of the consultations requested from dermatology department during the COVID pandemic. Retrospective, cohort study In this study we observed the dermatology consultations of the hospitalized patients over a period of 2 months, corresponding to the peak of COVID outbreak in a tertiary care hospital in Turkey. We reviewed the inpatient dermatology consult database retrospectively. Both pediatric and adult dermatology inpatient consultations were evaluated. A total of 166 inpatient dermatology consultations were requested from dermatology department during March‐May, 2020. The mean age of the patients was 53,12 (1‐89) years. Almost 32,5% (n = 54) of dermatology consultations were requested from the COVID wards and the COVID intensive care unit. The second most common consultations were requested from internal medicine departments (n = 46, 27,7%). The most common indications for the consultations were cutaneous infections (36%), followed by inflammatory disorders (32%), and urticaria (11%). Dermatology consultations have an essential role on the management of hospitalized patients, especially at that pandemic time. Careful dermatological examination improves diagnostic accuracy in skin disorders and skin manifestations of COVID‐19 infection that provides an early diagnosis and treatment, helps to improve the quality of the patient care and management. This article is protected by copyright. All rights reserved.


title: AKT1 polymorphisms are associated with tuberculosis in the Chinese population

text: AKT1, a serine/threonine kinase, plays a critical role in the controlling of intracellular growth of Mycobacterium tuberculosis. In this study, we investigated whether polymorphisms in AKT1 affect susceptibility to tuberculosis (TB). Two single nucleotide polymorphisms of AKT1, IVS3+18C>T and +726G>A were genotyped in Chinese patients with pulmonary TB by polymerase chain reaction‐restriction fragment length polymorphism. Patients with pulmonary TB had significantly lower IVS3+18 C/C genotype and higher C/T genotype compared with age‐, gender‐ and ethnically matched controls (P < 0.05). The T–A haplotype frequency was significantly higher in patients than in controls (P < 0.05). In conclusion, our result indicates that AKT1 polymorphisms are associated with susceptibility to pulmonary TB.


title: Schistosomiasis control and the health system in P.R. China

text: Over the last sixty years advances have been made in the control of schistosomiasis in P.R. China. There are, however, difficult challenges still to be met. This paper looks at the extent to which the health system offers a positive environment for the control of the disease. It starts by tracing three phases in schistosomiasis control: disease elimination strategy through snail control (1950s-early 1980s); morbidity control strategy based on chemotherapy (mid 1980s to 2003); integrated control strategy (2004+). Each one of these phases took place in distinct policy-making environments. The paper partly draws on these phases to set out five issues of disease control and discusses them in the context of the health system and its recent trends. These cover the policy-making process, intersectoral action for health, equity and access to health services, funding for public goods and externalities, and strengthening resource management and planning. These issues form the basis of an agenda for integrating research and capacity strengthening in the Chinese health system with a view to creating a more positive enabling environment for schistosomiasis control. In so doing it is important to emphasize the role and integrity of the public sector against its commercialization, the underlying value of equity, a systems wide perspective, and the role of advocacy.


title: Level of colorectal cancer awareness: a cross sectional exploratory study among multi-ethnic rural population in Malaysia

text: BACKGROUND: This paper presents the level of colorectal cancer awareness among multi-ethnic rural population in Malaysia. METHODS: A rural-based cross sectional survey was carried out in Perak state in Peninsular Malaysia in March 2011. The survey recruited a population-representative sample using multistage sampling. Altogether 2379 participants were included in this study. Validated bowel/colorectal cancer awareness measure questionnaire was used to assess the level of colorectal cancer awareness among study population. Analysis of variance (ANOVA) was done to identify socio-demographic variance of knowledge score on warning signs and risk factors of colorectal cancer. RESULTS: Among respondents, 38% and 32% had zero knowledge score for warning signs and risk factors respectively. Mean knowledge score for warning signs and risk factors were 2.89 (SD 2.96) and 3.49 (SD 3.17) respectively. There was a significant positive correlation between the knowledge score of warning signs and level of confidence in detecting a warning sign. Socio-demographic characteristics and having cancer in family and friends play important role in level of awareness. CONCLUSIONS: Level of awareness on colorectal cancer warning signs and risk factors in the rural population of Malaysia is very low. Therefore, it warrants an extensive health education campaign on colorectal cancer awareness as it is one of the commonest cancer in Malaysia. Health education campaign is urgently needed because respondents would seek medical attention sooner if they are aware of this problem.


title: Bacteria and viruses in the nasopharynx immediately prior to onset of acute lower respiratory infections in Indigenous Australian children

text: Acute lower respiratory infection (ALRI) is a major cause of hospitalization for Indigenous children in remote regions of Australia. The associated microbiology remains unclear. Our aim was to determine whether the microbes present in the nasopharynx before an ALRI were associated with its onset. A retrospective case-control/crossover study among Indigenous children aged up to 2 years. ALRI cases identified by medical note review were eligible where nasopharyngeal swabs were available: (1) 0–21 days before ALRI onset (case); (2) 90–180 days before ALRI onset (same child controls); and (3) from time and age-matched children without ALRI (different child controls). PCR assays determined the presence and/or load of selected respiratory pathogens. Among 104 children (182 recorded ALRI episodes), 120 case-same child control and 170 case-different child control swab pairs were identified. Human adenoviruses (HAdV) were more prevalent in cases compared to same child controls (18 vs 7%; OR = 3.08, 95% CI 1.22–7.76, p = 0.017), but this association was not significant in cases versus different child controls (15 vs 10%; OR = 1.93, 95% CI 0.97–3.87 (p = 0.063). No other microbes were more prevalent in cases compared to controls. Streptococcus pneumoniae (74%), Haemophilus influenzae (75%) and Moraxella catarrhalis (88%) were commonly identified across all swabs. In a pediatric population with a high detection rate of nasopharyngeal microbes, HAdV was the only pathogen detected in the period before illness presentation that was significantly associated with ALRI onset. Detection of other potential ALRI pathogens was similar between cases and controls. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-018-3314-7) contains supplementary material, which is available to authorized users.


docid: apgimmhp

title: Sign‐on letter requests more flexibility in methadone treatment during COVID‐19

text: A sign‐on letter spearheaded by the National Alliance for Medication Assisted Recovery (NAMA), and harm reduction groups, including the Urban Survivors Union (USU) and the Drug Policy Alliance (DPA) is calling for reducing restrictions on methadone and opioid treatment programs (OTPs), so that patients don't have to go to the clinics so often. Included in the over 100 signatories are Patty McCarthy Metcalf of Faces & Voices of Recovery, Ben Levenson of the Levenson Foundation (and former founder of Origins) and many addiction physicians, as well as drug user organizations. Many of the signers have said for months that OTPs should be eliminated entirely.


title: A multiplex quantitative real-time polymerase chain reaction panel for detecting neurologic pathogens in dogs with meningoencephalitis

text: Meningoencephalitis (ME) is a common inflammatory disorder of the central nervous system in dogs. Clinically, ME has both infectious and non-infectious causes. In the present study, a multiplex quantitative real-time polymerase chain reaction (mqPCR) panel was optimized for the detection of eight canine neurologic pathogens (Blastomyces dermatitidis, Cryptococcus spp., Neospora caninum, Borrelia burgdorferi, Bartonella spp., Toxoplasma gondii, Ehrlichia canis, and canine distemper virus [CDV]). The mqPCR panel was subsequently applied to 53 cerebrospinal fluid (CSF) samples collected from dogs with ME. The analytic sensitivity (i.e., limit of detection, expressed as molecules per 1 µL of recombinant vector) was 3.8 for CDV, 3.7 for Ehrlichia canis, 3.7 for Bartonella spp., 3.8 for Borrelia burgdorferi, 3.7 for Blastomyces dermatitidis, 3.7 for Cryptococcus spp., 38 for Neospora caninum, and 3.7 for Toxoplasma gondii. Among the tested CSF samples, seven (15%) were positive for the following pathogens in decreasing order of frequency: Cryptococcus spp. (3/7), Blastomyces dermatitidis (2/7), and Borrelia burgdorferi (2/7). In summary, use of an mqPCR panel with high analytic sensitivity as an initial screen for infectious agents in dogs with ME could facilitate the selection of early treatment strategies and improve outcomes.


title: Social Network Analysis for Coronavirus (COVID‐19) in the United States

text: OBJECTIVES: This study explores how public key players play an important role in social networks for coronavirus (COVID‐19). METHODS: This study employs social network analyses based on 2,864 Twitter users and 2,775 communications of Twitter. RESULTS: This study finds that President Trump plays the most important role in social networks among the top 20 key players for both in‐degree centrality and content in tweets. Second, Donald Trump and Barak Obama show the opposite result for the in‐degree centrality and follower analysis. The result shows that the topic‐based networks and the person‐based networks play a different role in social networks. This study demonstrates that the presidents, the World Health Organization (WHO) and its regional offices, the Centers for Disease Control, and news channels play a crucial role in the news of COVID‐19 for people. Key players, such as Donald Trump, Barack Obama, and BBC, are located in the central networks. In contrast, U.S. news channels and WHO and its regional offices have independent channels. CONCLUSIONS: Governments should understand the characteristics of public key players to provide information for COVID‐19 in a timely manner.


title: SARS-Cov-2 infection: response of human immune system and possible implications for the rapid test and treatment

text: Abstract The new coronavirus outbreak is an ongoing pandemic that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The new coronavirus SARS-Cov-2 belongs to the subfamily of β−coronaviruses and shares 79.5% of the genetic sequence of SARS-CoV, the causative agent of the epidemic that started in 2002 and ended in 2004. Considering the clinical impact of the new outbreak, it is highly important to study the potential responses of the human immune system during the SARS-CoV-2 infection as well as the role of virus-specific T cells and by B-lymphocytes. Moreover, specific data on the production of IgG and IgM is crucial to allow the rapid identification of the infection. In this paper we also described the importance of sensitive and specific rapid test for SARS-CoV-2. Indeed, this test represents an important immunological tool aimed at identifying the precise phase of the infection in order to undertake a more appropriate pharmacological treatment. Lastly, we provided an overview of pharmacological treatments aimed to reduce inflammatory processes underlying the infection and the need for the discovery of a new vaccine against SARS-CoV-2.


title: Henipavirus RNA in African Bats

text: BACKGROUND: Henipaviruses (Hendra and Nipah virus) are highly pathogenic members of the family Paramyxoviridae. Fruit-eating bats of the Pteropus genus have been suggested as their natural reservoir. Human Henipavirus infections have been reported in a region extending from Australia via Malaysia into Bangladesh, compatible with the geographic range of Pteropus. These bats do not occur in continental Africa, but a whole range of other fruit bats is encountered. One of the most abundant is Eidolon helvum, the African Straw-coloured fruit bat. METHODOLOGY/PRINCIPAL FINDINGS: Feces from E. helvum roosting in an urban setting in Kumasi/Ghana were tested for Henipavirus RNA. Sequences of three novel viruses in phylogenetic relationship to known Henipaviruses were detected. Virus RNA concentrations in feces were low. CONCLUSIONS/SIGNIFICANCE: The finding of novel putative Henipaviruses outside Australia and Asia contributes a significant extension of the region of potential endemicity of one of the most pathogenic virus genera known in humans.


title: Interferon-Independent Innate Responses to Cytomegalovirus

text: The critical role of interferons (IFNs) in mediating the innate immune response to cytomegalovirus (CMV) infection is well established. However, in recent years the functional importance of the IFN-independent antiviral response has become clearer. IFN-independent, IFN regulatory factor 3 (IRF3)-dependent interferon-stimulated gene (ISG) regulation in the context of CMV infection was first documented 20 years ago. Since then several IFN-independent, IRF3-dependent ISGs have been characterized and found to be among the most influential in the innate response to CMV. These include virus inhibitory protein, endoplasmic reticulum-associated IFN-inducible (viperin), ISG15, members of the interferon inducible protein with tetratricopeptide repeats (IFIT) family, interferon-inducible transmembrane (IFITM) proteins and myxovirus resistance proteins A and B (MxA, MxB). IRF3-independent, IFN-independent activation of canonically IFN-dependent signaling pathways has also been documented, such as IFN-independent biphasic activation of signal transducer and activator of transcription 1 (STAT1) during infection of monocytes, differential roles of mitochondrial and peroxisomal mitochondrial antiviral-signaling protein (MAVS), and the ability of human CMV (HCMV) immediate early protein 1 (IE1) protein to reroute IL-6 signaling and activation of STAT1 and its associated ISGs. This review examines the role of identified IFN-independent ISGs in the antiviral response to CMV and describes pathways of IFN-independent innate immune response induction by CMV.


title: Waiting for COVID‐19

text: I wrote this as a narrative piece for school, but it is a very honest description of how I'm feeling at this time. I just wanted to reassure people that I am ok. For anyone else who is feeling the same as I am, it's ok. I think it is good for us to be honest about how we are feeling, and it is perfectly reasonable for us to feel confusion during this time. I also think it is good for us to not let any anxiety overwhelm us. So let it out. Talk to someone. Write it down. And breathe. For me, watching the sunrise this morning was a good way to focus on something other than the chaos, other than my feelings.